A glucose tolerance test in medical practice is the administration of glucose to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, and sometimes reactive hypoglycemia. The glucose is most often given orally so the common test is technically an oral glucose tolerance test (OGTT). The test may be performed as part of a panel of tests, such as the comprehensive metabolic panel.
Indications for OGTT:
In non pregnant adults an OGTT is recommended,
• For all patients with impaired fasting glucose.
• When results of the recommended diagnostic tests (FPG and RPG) fail to determine the diagnosis in an individual patient (E.g. equivocal or borderline results).
Protocol for the OGTT
1. Preparation of the patient:
• Three days unrestricted, carbohydrate rich diet and activity.
• No medication on the day of the test.
• 8 to 14 h fasting
• for paediatric patients: Children > 6 years: 8 -10 hr fast,Children <> 6.1 & <7.0>7.8 >7.0 >11.1
(mg/dl) <110>110 & <126>140 >126 >200
Variations
A standard 2 hour OGTT is sufficient to diagnose or exclude all forms of diabetes mellitus at all but the earliest stages of development. Longer tests have been used for a variety of other purposes, such as detecting reactive hypoglycemia or defining subsets of hypothalamic obesity. Insulin levels are sometimes measured to detect insulin resistance or deficiency.
The OGTT is of limited value in the diagnosis of reactive hypoglycemia, since (1) normal levels do not preclude the diagnosis, (2) abnormal levels do not prove that the patient's other symptoms are related to a demonstrated atypical OGTT, and (3) many people without symptoms of reactive hypoglycemia may have the late low glucoses that are said to be characteristic. Using a glucose tolerance in this context resembles use of a Rorschach test in that it is often used to support a diagnosis that the patient and doctor are already reaching agreement on based on other evidence, but it is inadequate by itself to confirm or refute the diagnosis (unlike its use for diabetes).
When the glucose is given intravenously it is termed an intravenous glucose tolerance test (IVGTT). This has been used in the investigation of early insulin secretion abnormalities in prediabetic states.
Saturday, January 31, 2009
Glycosylated Hemoglobin (HbA1C)
Introduction
Glycosylated hemoglobin is the combination of hemoglobin and glucose. When the blood sugar level is higher than normal for long period, hemoglobin is glycosylated. Glycosylation of hemoglobin occurs as a two-step reaction, resulting in the formation of a covalent bond between the glucose molecule and the terminal valine of the β chain of the hemoglobin molecule. The rate at which this reaction occurs is related to the prevailing glucose concentration.
Glycosylated haemoglobin is expressed as a percentage of the normal haemoglobin (standardized range 4-6.5%). This test provides an index of the average blood glucose concentration over the life of the haemoglobin molecule (approximately 6 weeks). The figure will be misleading if the life-span of the red cell is reduced or if an abnormal haemoglobin or thalassaemia is present. There are considerable inter-individual variations in HbA1c levels, even in normal people. Although the glycosylated haemoglobin test provides a rapid assessment of the level of glycaemic control in a given patient, blood glucose testing is needed before the clinician can know what to do about it.
Important HbA1C values are;
HbA1c <6.5% Good glycemic control
HbA1C 6.5-8.5% Moderate glycemic control
HbA1C >8.5% Bad glycemic control
Assessment of Long-Term Glycemic Control
Measurement of glycated hemoglobin is the standard method for assessing long-term glycemic control. When plasma glucose is consistently elevated, there is an increase in nonenzymatic glycation of hemoglobin; this alteration reflects the glycemic history over the previous 2 to 3 months, since erythrocytes have an average life span of 120 days.
Glycated hemoglobin or A1C should be measured in all individuals with DM during their initial evaluation and as part of their comprehensive diabetes care. As the primary predictor of long-term complications of DM, the A1C should mirror, to a certain extent, the short term measurements.
In standardized assays, the A1C approximates the following mean plasma glucose values:
1. HbA1C of 6% is 7.5 mmol/L (135 mg/ dL),
2. HbA1C of 7% is 9.5 mmol/L (170 mg/dL),
3. HbA1C of 8% is 11.5 mmol/L (205 mg/dL),
4. A 1% rise in the A1C translates into a 2.0-mmol/L (35 mg/dL) increase in the mean glucose
ESTABLISHMENT OF A TARGET LEVEL OF GLYCEMIC CONTROL
Because the complications of DM are related to glycemic control, normoglycemia or near normoglycemia is the desired, but often elusive, goal for most patients. However, normalization of the plasma glucose for long periods of time is extremely difficult. Regardless of the level of hyperglycemia, improvement in glycemiccontrol will lower the risk of diabetes complications In general; the target A1C should be 7.0%.
Glycosylated hemoglobin is the combination of hemoglobin and glucose. When the blood sugar level is higher than normal for long period, hemoglobin is glycosylated. Glycosylation of hemoglobin occurs as a two-step reaction, resulting in the formation of a covalent bond between the glucose molecule and the terminal valine of the β chain of the hemoglobin molecule. The rate at which this reaction occurs is related to the prevailing glucose concentration.
Glycosylated haemoglobin is expressed as a percentage of the normal haemoglobin (standardized range 4-6.5%). This test provides an index of the average blood glucose concentration over the life of the haemoglobin molecule (approximately 6 weeks). The figure will be misleading if the life-span of the red cell is reduced or if an abnormal haemoglobin or thalassaemia is present. There are considerable inter-individual variations in HbA1c levels, even in normal people. Although the glycosylated haemoglobin test provides a rapid assessment of the level of glycaemic control in a given patient, blood glucose testing is needed before the clinician can know what to do about it.
Important HbA1C values are;
HbA1c <6.5% Good glycemic control
HbA1C 6.5-8.5% Moderate glycemic control
HbA1C >8.5% Bad glycemic control
Assessment of Long-Term Glycemic Control
Measurement of glycated hemoglobin is the standard method for assessing long-term glycemic control. When plasma glucose is consistently elevated, there is an increase in nonenzymatic glycation of hemoglobin; this alteration reflects the glycemic history over the previous 2 to 3 months, since erythrocytes have an average life span of 120 days.
Glycated hemoglobin or A1C should be measured in all individuals with DM during their initial evaluation and as part of their comprehensive diabetes care. As the primary predictor of long-term complications of DM, the A1C should mirror, to a certain extent, the short term measurements.
In standardized assays, the A1C approximates the following mean plasma glucose values:
1. HbA1C of 6% is 7.5 mmol/L (135 mg/ dL),
2. HbA1C of 7% is 9.5 mmol/L (170 mg/dL),
3. HbA1C of 8% is 11.5 mmol/L (205 mg/dL),
4. A 1% rise in the A1C translates into a 2.0-mmol/L (35 mg/dL) increase in the mean glucose
ESTABLISHMENT OF A TARGET LEVEL OF GLYCEMIC CONTROL
Because the complications of DM are related to glycemic control, normoglycemia or near normoglycemia is the desired, but often elusive, goal for most patients. However, normalization of the plasma glucose for long periods of time is extremely difficult. Regardless of the level of hyperglycemia, improvement in glycemiccontrol will lower the risk of diabetes complications In general; the target A1C should be 7.0%.
Nutrition and diabetes mellitus
Nutrition in diabetes mellitus is an important part of alongandhealthy life. The newest concept is the medical nutrition therapy
What is medical nutrition therapy (MNT)?
Medical nutrition therapy (MNT) is a term used to describe the optimal coordination of caloric intake with other aspects of diabetes therapy (insulin, exercise, weight loss). For example, MNT now includes foods with sucrose and seeks to modify other risk factors such as hyperlipidemia and hypertension rather than focusing exclusively on weight loss in individuals with type 2 DM. Like other aspects of DM therapy, MNT must be adjusted to meet the goals of the individual patient. Main aims of MNT are prevention of short term and long term complications.
Nutrition and Type1 Diabetes mellitus
The goal of MNT in the individual with type 1 DM is to coordinate and match the caloric intake, both temporally and quantitatively, with the appropriate amount of insulin. MNT in type 1 DM and self-monitoring of blood glucose must be integrated to define the optimal insulin regimen. MNT must be flexible enough to allow for exercise, and the insulin regimen must allow for deviations in caloric intake. An important component of MNT in type 1 DM is to minimize the weight gain often associated with intensive diabetes management.
Nutrition and Type2 Diabetes mellitus
The goals of MNT in type 2 DM are slightly different and address the greatly increased prevalence of cardiovascular risk factors (hypertension, dyslipidemia, obesity) and disease in this population. The majority of these individuals are obese, and weight loss is strongly encouraged and should remain an important goal. Hypocaloric diets and modest weight loss often result in rapid and dramatic glucose lowering in individuals with new-onset type 2 DM. Current MNT for type 2 DM should emphasize modest caloric reduction, reduced fat intake, increased physical activity, and reduction of hyperlipidemia and hypertension. Increased consumption of soluble, dietary fiber may improve glycemic control in individuals with type 2 DM.
Dietary constituents and Diabetes mellitus
1. Carbohydrates
• 50-55% of calorie should be provided by carbohydrates
• consume unrefined carbohydrates (parboiled rice) rather than simple sugars (glucose)
• foods with low glycemic index aids the metabolic control
• high fiber diets are considered as foods with low glycemic index
2. Protein
• 10-20% of calorie should come from protein
• protein should be cut down if nephropathy is present
3. Fat
• Fat should provide 30% of the caloric need
10% unsaturated fat
10% poly saturated fat
10% monosaturated fat
• if the patient is hyperlipedimic, fat should be cut down
4. Alcohol
• Alcohol consumption is same as for the general public
2drinks/day for male
1drink/day for female
• Patients on insulin therapy should avoid alcohol as it can precipitate hypoglycemic attacks.
What is medical nutrition therapy (MNT)?
Medical nutrition therapy (MNT) is a term used to describe the optimal coordination of caloric intake with other aspects of diabetes therapy (insulin, exercise, weight loss). For example, MNT now includes foods with sucrose and seeks to modify other risk factors such as hyperlipidemia and hypertension rather than focusing exclusively on weight loss in individuals with type 2 DM. Like other aspects of DM therapy, MNT must be adjusted to meet the goals of the individual patient. Main aims of MNT are prevention of short term and long term complications.
Nutrition and Type1 Diabetes mellitus
The goal of MNT in the individual with type 1 DM is to coordinate and match the caloric intake, both temporally and quantitatively, with the appropriate amount of insulin. MNT in type 1 DM and self-monitoring of blood glucose must be integrated to define the optimal insulin regimen. MNT must be flexible enough to allow for exercise, and the insulin regimen must allow for deviations in caloric intake. An important component of MNT in type 1 DM is to minimize the weight gain often associated with intensive diabetes management.
Nutrition and Type2 Diabetes mellitus
The goals of MNT in type 2 DM are slightly different and address the greatly increased prevalence of cardiovascular risk factors (hypertension, dyslipidemia, obesity) and disease in this population. The majority of these individuals are obese, and weight loss is strongly encouraged and should remain an important goal. Hypocaloric diets and modest weight loss often result in rapid and dramatic glucose lowering in individuals with new-onset type 2 DM. Current MNT for type 2 DM should emphasize modest caloric reduction, reduced fat intake, increased physical activity, and reduction of hyperlipidemia and hypertension. Increased consumption of soluble, dietary fiber may improve glycemic control in individuals with type 2 DM.
Dietary constituents and Diabetes mellitus
1. Carbohydrates
• 50-55% of calorie should be provided by carbohydrates
• consume unrefined carbohydrates (parboiled rice) rather than simple sugars (glucose)
• foods with low glycemic index aids the metabolic control
• high fiber diets are considered as foods with low glycemic index
2. Protein
• 10-20% of calorie should come from protein
• protein should be cut down if nephropathy is present
3. Fat
• Fat should provide 30% of the caloric need
10% unsaturated fat
10% poly saturated fat
10% monosaturated fat
• if the patient is hyperlipedimic, fat should be cut down
4. Alcohol
• Alcohol consumption is same as for the general public
2drinks/day for male
1drink/day for female
• Patients on insulin therapy should avoid alcohol as it can precipitate hypoglycemic attacks.
Oral glucose lowering agents (oral hypoglycemic agents)
Introduction
Oral antidiabetic drugs are used for the treatment of type 2 diabetes mellitus. They should be prescribed only if the patient fails to respond adequately to at least 3 months restriction of energy and carbohydrates intake and an increase in physical activity. They should be used to augment the effect of diet and exercise, and not to replace them.
Advances in the therapy of type 2 DM have generated considerable enthusiasm for oral glucose-lowering agents that target different pathophysiologic processes in type 2 DM. Based on their mechanisms of action, oral glucose-lowering agents are subdivided into agents that;
1. increase insulin secretion,
2. reduce glucose production, or
3. increase insulin sensitivity .
Agents that increase insulin secretion (INSULIN SECRETAGOGUES)
Insulin secretagogues stimulate insulin secretion by interacting with the ATP-sensitive potassium channel on the beta cell. These drugs are most effective in individuals with type 2 DM of relatively recent onset, who tend to be obese and have residual endogenous insulin production. At maximum doses, first-generation sulfonylureas are similar in potency to second-generation agents but have a longer half-life, a greater incidence of hypoglycemia, and more frequent drug interactions. Thus, second-generation sulfonylureas are generally preferred.
Agents that reduce glucose production
Glucosidase inhibitors (acarbose and miglitol) reduce postprandial hyperglycemia by delaying glucose absorption; they do not affect glucose utilization or insulin secretion. Postprandial hyperglycemia, secondary to impaired hepatic and peripheral glucose disposal, contributes significantly to the hyperglycemic state in type 2 DM. These drugs, taken just before each meal, reduce glucose absorption by inhibiting the enzyme that cleaves oligosaccharides into simple sugars in the intestinal lumen. Therapy should be initiated at a low dose.
Metformin is representative of this class of agents. It reduces hepatic glucose production through an undefined mechanism and improves peripheral glucose utilization slightly
Agents that increase insulin sensitivity or reduce resistance
Thiazolidinediones reduce insulin resistance. These drugs bind to the PPAR (peroxisome proliferator-activated receptor) nuclear receptor. The PPAR-_ receptor is found at highest levels in adipocytes but is expressed at lower levels in many other tissues.
Classes of drugs
Read more
1. Sulphonylureas
2. Biguanides
3. Thiazolidinediones (Glitazones)
4. Alpha-Glucosidase inhibitors
5. Meglitinides
Oral antidiabetic drugs are used for the treatment of type 2 diabetes mellitus. They should be prescribed only if the patient fails to respond adequately to at least 3 months restriction of energy and carbohydrates intake and an increase in physical activity. They should be used to augment the effect of diet and exercise, and not to replace them.
Advances in the therapy of type 2 DM have generated considerable enthusiasm for oral glucose-lowering agents that target different pathophysiologic processes in type 2 DM. Based on their mechanisms of action, oral glucose-lowering agents are subdivided into agents that;
1. increase insulin secretion,
2. reduce glucose production, or
3. increase insulin sensitivity .
Agents that increase insulin secretion (INSULIN SECRETAGOGUES)
Insulin secretagogues stimulate insulin secretion by interacting with the ATP-sensitive potassium channel on the beta cell. These drugs are most effective in individuals with type 2 DM of relatively recent onset, who tend to be obese and have residual endogenous insulin production. At maximum doses, first-generation sulfonylureas are similar in potency to second-generation agents but have a longer half-life, a greater incidence of hypoglycemia, and more frequent drug interactions. Thus, second-generation sulfonylureas are generally preferred.
Agents that reduce glucose production
Glucosidase inhibitors (acarbose and miglitol) reduce postprandial hyperglycemia by delaying glucose absorption; they do not affect glucose utilization or insulin secretion. Postprandial hyperglycemia, secondary to impaired hepatic and peripheral glucose disposal, contributes significantly to the hyperglycemic state in type 2 DM. These drugs, taken just before each meal, reduce glucose absorption by inhibiting the enzyme that cleaves oligosaccharides into simple sugars in the intestinal lumen. Therapy should be initiated at a low dose.
Metformin is representative of this class of agents. It reduces hepatic glucose production through an undefined mechanism and improves peripheral glucose utilization slightly
Agents that increase insulin sensitivity or reduce resistance
Thiazolidinediones reduce insulin resistance. These drugs bind to the PPAR (peroxisome proliferator-activated receptor) nuclear receptor. The PPAR-_ receptor is found at highest levels in adipocytes but is expressed at lower levels in many other tissues.
Classes of drugs
Read more
1. Sulphonylureas
2. Biguanides
3. Thiazolidinediones (Glitazones)
4. Alpha-Glucosidase inhibitors
5. Meglitinides
Sulphonylureas
Introduction
The Sulphonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta cells activity is present; during long term administration they also have extra-pancreatic actions. All may cause hypoglycemia but this is uncommon and usually indicates excessive dose. Followings are the common drugs;
1. Tolbutamide
2. Chlorprapamide
3. Glibenclamide
4. Glipizide
Mechanism of action
They bind with potassium channels on the cell membrane of beta cells and reduce the potassium permeability. Therefore cell membrane becomes depolarized. Thus calcium will influx to the cell. This will result insulin secretion.
Mode of actions
1. increase insulin secretion
2. increase peripheral sensitivity for insulin
3. extra-pancreatic functions are;
I. reduce hepatic glucose production
II. reverse post receptor defect in insulin action
III. increase number of insulin receptors
Pharmacokinetics
Oral absorption is good and it achieves peak plasma concentration within 2-4 hours after the ingestion. Sulphonylureas bind strongly with albumin therefore they implicate with other drugs which have an affinity towards albumin such as salicylate and sulfonamide. These drugs are excreted via urine therefore extra precautions should be taken when prescribing for a patient with renal failure. Sulphonylureas are contraindicated during pregnancy as they cross the placenta (except glibenclamide).
Adverse drug reactions
1. They cause hypoglycemia. This effect is highest with chlorprapamide and glibenclamide and lowest with tolbutamide.
2. They increase appetite therefore increases the weight gain.
3. 3% of patients experience gastrointestinal disturbances.
4. They can cause allergic skin reaction
5. Bone marrow suppression is a dreaded drawback of these drugs but it occurs rarely.
Drug interaction
1. following drugs can augment the hypoglycemic effect of Sulphonylureas by replacing them from albumin
I. Non-steroidal anti-inflammatory drugs(Diclofenac sodium)
II. Uricosuric drugs(Sulfinpyrazone)
III. Alcohol
IV. Mono Amine Oxidase inhibitors (Phenalzine)
V. Antibacterial agents (sulfonamide, trimethoprime, chloramphenicol)
VI. Antifungal agents (imidazole)
2. Following drugs reduce the effects of Sulphonylureas
I. Thiazide diuretics (HCT)
II. Corticosteroids
Clinical uses
1. Useful in early stages of type 2 diabetes mellitus
2. They can be combined with Metformin or Glitazones.
3. Sulphonylureas are given ½ hour prior to the meal
4. Glibenclamide should not be given to elderly patients and patients with renal failure.
The Sulphonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta cells activity is present; during long term administration they also have extra-pancreatic actions. All may cause hypoglycemia but this is uncommon and usually indicates excessive dose. Followings are the common drugs;
1. Tolbutamide
2. Chlorprapamide
3. Glibenclamide
4. Glipizide
Mechanism of action
They bind with potassium channels on the cell membrane of beta cells and reduce the potassium permeability. Therefore cell membrane becomes depolarized. Thus calcium will influx to the cell. This will result insulin secretion.
Mode of actions
1. increase insulin secretion
2. increase peripheral sensitivity for insulin
3. extra-pancreatic functions are;
I. reduce hepatic glucose production
II. reverse post receptor defect in insulin action
III. increase number of insulin receptors
Pharmacokinetics
Oral absorption is good and it achieves peak plasma concentration within 2-4 hours after the ingestion. Sulphonylureas bind strongly with albumin therefore they implicate with other drugs which have an affinity towards albumin such as salicylate and sulfonamide. These drugs are excreted via urine therefore extra precautions should be taken when prescribing for a patient with renal failure. Sulphonylureas are contraindicated during pregnancy as they cross the placenta (except glibenclamide).
Adverse drug reactions
1. They cause hypoglycemia. This effect is highest with chlorprapamide and glibenclamide and lowest with tolbutamide.
2. They increase appetite therefore increases the weight gain.
3. 3% of patients experience gastrointestinal disturbances.
4. They can cause allergic skin reaction
5. Bone marrow suppression is a dreaded drawback of these drugs but it occurs rarely.
Drug interaction
1. following drugs can augment the hypoglycemic effect of Sulphonylureas by replacing them from albumin
I. Non-steroidal anti-inflammatory drugs(Diclofenac sodium)
II. Uricosuric drugs(Sulfinpyrazone)
III. Alcohol
IV. Mono Amine Oxidase inhibitors (Phenalzine)
V. Antibacterial agents (sulfonamide, trimethoprime, chloramphenicol)
VI. Antifungal agents (imidazole)
2. Following drugs reduce the effects of Sulphonylureas
I. Thiazide diuretics (HCT)
II. Corticosteroids
Clinical uses
1. Useful in early stages of type 2 diabetes mellitus
2. They can be combined with Metformin or Glitazones.
3. Sulphonylureas are given ½ hour prior to the meal
4. Glibenclamide should not be given to elderly patients and patients with renal failure.
Metformin (Biguanides)
Introduction
Metformin is the only available drug in this class and it has a different mode of action from the Sulphonylureas, and it is not interchangeable with them. Metformin is the drug of first choice in overweight patients in whom strict dieting has failed to control diabetes.
Mechanism of action
This is very complex and incompletely understood
Mode of actions
1. it increases the peripheral sensitivity for insulin by;
I. increasing glucose uptake and utilization by skeleton muscles
II. reducing insulin resistance
2. it reduces LDL and VLDL level
3. It increase HDL level
Pharmacokinetics
Oral bio-availability is 50-60%.The half life of metformin is about 3 hours. It is excreted via urine as it is.
Adverse drug reactions
1. Dose related gastrointestinal disturbances(anorexia, diarrhea, nausea)
2. It can cause lactic acidosis. Even though this is rare it can be fatal. Therefore Metformin should not be given to patients with renal/ hepatic disease, hypoxic pulmonary disease, heart failure or shock.
3. Long term use may interfere with vitamin B12 absorption.
4. teratogenic
Clinical uses
1. Start with smaller doses and gradually increase the dose to over come the adverse effects.
2. given immediately after the meal
3. Drug of choice for patients with type2 DM and obesity.
4. can be combined with Sulphonylureas, Glitazones or insulin
5. does not cause hypoglycemia
6. preserved for middle and old age patients
Metformin is the only available drug in this class and it has a different mode of action from the Sulphonylureas, and it is not interchangeable with them. Metformin is the drug of first choice in overweight patients in whom strict dieting has failed to control diabetes.
Mechanism of action
This is very complex and incompletely understood
Mode of actions
1. it increases the peripheral sensitivity for insulin by;
I. increasing glucose uptake and utilization by skeleton muscles
II. reducing insulin resistance
2. it reduces LDL and VLDL level
3. It increase HDL level
Pharmacokinetics
Oral bio-availability is 50-60%.The half life of metformin is about 3 hours. It is excreted via urine as it is.
Adverse drug reactions
1. Dose related gastrointestinal disturbances(anorexia, diarrhea, nausea)
2. It can cause lactic acidosis. Even though this is rare it can be fatal. Therefore Metformin should not be given to patients with renal/ hepatic disease, hypoxic pulmonary disease, heart failure or shock.
3. Long term use may interfere with vitamin B12 absorption.
4. teratogenic
Clinical uses
1. Start with smaller doses and gradually increase the dose to over come the adverse effects.
2. given immediately after the meal
3. Drug of choice for patients with type2 DM and obesity.
4. can be combined with Sulphonylureas, Glitazones or insulin
5. does not cause hypoglycemia
6. preserved for middle and old age patients
Glitazones (Thiazolidinediones)
Introduction
The thiazolidnediones reduce peripheral insulin resistance, leading to a reduction of blood glucose concentration. Either drug may be used alone or in combination with metformin or with a Sulphonylurea. Following are the examples for thiazolidnediones;
1. Rosiglitazones
2. Pioglitazones
3. Ciglitazones (not in use due to the hepatotoxicity)
4. Troglitazones (not in use due to the hepatotoxicity)
Mechanism of actions
Glitazones bind with a nuclear receptor called Peroxisomal Proliferator-Activated Receptor Gamma (PPARγ), which is complexed with retinoid X-receptor (RXR). This binding will cause a conformational change in the PPARγ-RXR complex. Thus, this complex binds with DNA and promotes transcription of several genes. Therefore following proteins result. These are important in insulin signaling.
Lipoprotein lipase
Fatty acid transporter protein
Adipocytes fatty acid binding protein
Glut 4 receptors
Phophoenolpyruvate carboxykinase
PPARγ is mainly found adipose tissue, muscles and liver. It mediates differentiation of adipocytes, increase lipogenesis and enhances uptake of fatty acid and glucose.
Effects of Glitazones
1. reduce hepatic glucose out put
2. increase glucose uptake into muscles
3. enhances the effectiveness of endogenous insulin
4. reduce the amount of exogenous insulin needed to maintain a given blood sugar level by 30%
5. reduce circulating insulin and fatty acids
6. reduce small density LDL, which is more atherogenic
7. increase weight gain
8. cause fluid retention
9. increase extravascular fluids
10. increase deposition of subcutaneous fat.
Pharmacokinetics
Oral absorption is rapid and complete. They achieve peak plasma concentration within 2 hours. They are highly bound to plasma protein. They undergo hepatic metabolism. Half life is less than 7 hours for parent drug but the half life of rosiglitazone is 150hous whereas the half life of pioglitazone is 24 hours. Rosiglitazone is excretd via urine whereas pioglitazone is excreted via bile.
Side effects
1. hepatotoxicity ( uncommon with newer drugs)
2. weight gaining and fluid retention
3. headache
4. fatigue
5. gastrointestinal disturbances
6. may resume ovulation in women who are anovulatory. This is due to the reduction insulin resistance. Therefore precautions should be taken
7. teratogenic
Drug interaction
1. additive with other oral hypoglycemic agents
2. increase the risk of heart failure with insulin
Clinical uses
1. useful in type 2 diabetes mellitus
2. good for patient who cannot tolerate metformin
3. can be combined with other oral hypoglycemic agents
4. monotherapy or polytherapy is possible
The thiazolidnediones reduce peripheral insulin resistance, leading to a reduction of blood glucose concentration. Either drug may be used alone or in combination with metformin or with a Sulphonylurea. Following are the examples for thiazolidnediones;
1. Rosiglitazones
2. Pioglitazones
3. Ciglitazones (not in use due to the hepatotoxicity)
4. Troglitazones (not in use due to the hepatotoxicity)
Mechanism of actions
Glitazones bind with a nuclear receptor called Peroxisomal Proliferator-Activated Receptor Gamma (PPARγ), which is complexed with retinoid X-receptor (RXR). This binding will cause a conformational change in the PPARγ-RXR complex. Thus, this complex binds with DNA and promotes transcription of several genes. Therefore following proteins result. These are important in insulin signaling.
Lipoprotein lipase
Fatty acid transporter protein
Adipocytes fatty acid binding protein
Glut 4 receptors
Phophoenolpyruvate carboxykinase
PPARγ is mainly found adipose tissue, muscles and liver. It mediates differentiation of adipocytes, increase lipogenesis and enhances uptake of fatty acid and glucose.
Effects of Glitazones
1. reduce hepatic glucose out put
2. increase glucose uptake into muscles
3. enhances the effectiveness of endogenous insulin
4. reduce the amount of exogenous insulin needed to maintain a given blood sugar level by 30%
5. reduce circulating insulin and fatty acids
6. reduce small density LDL, which is more atherogenic
7. increase weight gain
8. cause fluid retention
9. increase extravascular fluids
10. increase deposition of subcutaneous fat.
Pharmacokinetics
Oral absorption is rapid and complete. They achieve peak plasma concentration within 2 hours. They are highly bound to plasma protein. They undergo hepatic metabolism. Half life is less than 7 hours for parent drug but the half life of rosiglitazone is 150hous whereas the half life of pioglitazone is 24 hours. Rosiglitazone is excretd via urine whereas pioglitazone is excreted via bile.
Side effects
1. hepatotoxicity ( uncommon with newer drugs)
2. weight gaining and fluid retention
3. headache
4. fatigue
5. gastrointestinal disturbances
6. may resume ovulation in women who are anovulatory. This is due to the reduction insulin resistance. Therefore precautions should be taken
7. teratogenic
Drug interaction
1. additive with other oral hypoglycemic agents
2. increase the risk of heart failure with insulin
Clinical uses
1. useful in type 2 diabetes mellitus
2. good for patient who cannot tolerate metformin
3. can be combined with other oral hypoglycemic agents
4. monotherapy or polytherapy is possible
Alpha-Glucosidase inhibitors(Arcabose)
Introduction
Alpha-Glucosidase is an enzyme found in the intestinal brush border. It involves with carbohydrates metabolism.
Arcabose is the available Alpha-Glucosidase inhibitor. It has a small but significant effect in lowering blood glucose and is used either on its own or as an adjunct to metformin or Sulphonylureas when they prove inadequate.
Mechanism of actions
Acarbose is a competitive inhibitor of Alpha-Glucosidase enzyme. Thereby it reduces the carbohydrate breakdown and it will slow down the glucose absorption. The ultimate result is reduction of postprandial blood glucose level.
Pharmacokinetics
It is given orally. Small amount of the drug is absorbed into the circulation.
Side effects
1. Abdominal discomfort, flatulence and diarrhea due to the fermentation of undigested carbohydrates.
2. If it is absorbed into the circulation in large dose, it can cause liver dysfunction
Clinical uses
1. Useful for patients with type 2 diabetes mellitus whose blood sugar control is inadequate with diet and other oral hypoglycemic drugs.
2. good for obese patients
3. It can be used to reduce the post-prandial blood sugar in patients with type1 diabetes mellitus.
Alpha-Glucosidase is an enzyme found in the intestinal brush border. It involves with carbohydrates metabolism.
Arcabose is the available Alpha-Glucosidase inhibitor. It has a small but significant effect in lowering blood glucose and is used either on its own or as an adjunct to metformin or Sulphonylureas when they prove inadequate.
Mechanism of actions
Acarbose is a competitive inhibitor of Alpha-Glucosidase enzyme. Thereby it reduces the carbohydrate breakdown and it will slow down the glucose absorption. The ultimate result is reduction of postprandial blood glucose level.
Pharmacokinetics
It is given orally. Small amount of the drug is absorbed into the circulation.
Side effects
1. Abdominal discomfort, flatulence and diarrhea due to the fermentation of undigested carbohydrates.
2. If it is absorbed into the circulation in large dose, it can cause liver dysfunction
Clinical uses
1. Useful for patients with type 2 diabetes mellitus whose blood sugar control is inadequate with diet and other oral hypoglycemic drugs.
2. good for obese patients
3. It can be used to reduce the post-prandial blood sugar in patients with type1 diabetes mellitus.
Meglitinides
Introduction
This is a newer class of insulin secretagogues. Meglitinide is the non-sulphonylurea moiety of glibenclamide. This drug stimulates the insulin secretion. Followings are the examples for Meglitinides;
1. Nateglinide
2. Repaglinide
Mechanism of action
Meglitinides close the potassium channel in the cell membrane of pancreatic beta cell. It causes depolarization of the cell membrane thus calcium will influx to the beta cell. This will result in secretion of insulin. This mechanism is different from Sulphonylureas.
Effects
1. Increase insulin secretion
2. risk of hypoglycemia between meal is less
Pharmacokinetics
Onset of action is quicker and duration of action is shorter than that of Sulphonylureas.
Side effects
1. hypersensitivity reactions
2. hypoglycemia
Clinical uses
1. useful in type 2 diabetes mellitus
2. can be given with metformin
This is a newer class of insulin secretagogues. Meglitinide is the non-sulphonylurea moiety of glibenclamide. This drug stimulates the insulin secretion. Followings are the examples for Meglitinides;
1. Nateglinide
2. Repaglinide
Mechanism of action
Meglitinides close the potassium channel in the cell membrane of pancreatic beta cell. It causes depolarization of the cell membrane thus calcium will influx to the beta cell. This will result in secretion of insulin. This mechanism is different from Sulphonylureas.
Effects
1. Increase insulin secretion
2. risk of hypoglycemia between meal is less
Pharmacokinetics
Onset of action is quicker and duration of action is shorter than that of Sulphonylureas.
Side effects
1. hypersensitivity reactions
2. hypoglycemia
Clinical uses
1. useful in type 2 diabetes mellitus
2. can be given with metformin
PHYSIOLOGY OF INSULIN
What is insulin?
Insulin is a hormone which is secreted by the pancreatic beta cells. It is a protein. This hormone is essential for the metabolism of carbohydrates, protein and fat.
Biosynthesize
Insulin is produced in the beta cells of the pancreatic islets. It is initially synthesized as a single-chain 86-amino-acid precursor polypeptide, preproinsulin. Subsequent proteolytic processing removes the aminoterminal signal peptide, giving rise to proinsulin. Proinsulin is structurally related to insulin-like growth factors I and II, which bind weakly to the insulin receptor. Cleavage of an internal 31-residue fragment from proinsulin generates the C peptide and the A (21 amino acids) and B (30 amino acids) chains of insulin, which are connected by disulfide bonds.
The mature insulin molecule and C peptide are stored together and cosecreted from secretory granules in the beta cells. Because the C peptide is less susceptible than insulin to hepatic degradation, it is a useful marker of insulin secretion
Secretion
Glucose enters to the beta cells via GLUT 2 receptors
Metabolized by the Glucokinase
Produce ATP
ATP inhibits potassium channel
Depolarization of the cell membrane
Opening of voltage dependant calcium channel
calcium influx
Insulin secretion
Action
Insulin acts on almost all the tissues but liver, muscles and adipose tissues are the main sites. Overall effect is to conserve fuel by facilitating the uptake and storage of glucose , amino acids and fatty acids following a meal.
Insulin binding to its receptor stimulates intrinsic tyrosine kinase activity, leading to receptor autophosphorylation and the recruitment of intracellular signaling molecules, such as insulin receptor substrates (IRS). These and other adaptor proteins initiate a complex cascade of phosphorylation and dephosphorylation reactions, resulting in
the widespread metabolic and mitogenic effects of insulin.
Structure
Insulin consists of two amino acids; A chain (21 amino acids): B chain (30 amino acids).
These two amino acids chains are combined with two sulphide bonds.
Insulin is a hormone which is secreted by the pancreatic beta cells. It is a protein. This hormone is essential for the metabolism of carbohydrates, protein and fat.
Biosynthesize
Insulin is produced in the beta cells of the pancreatic islets. It is initially synthesized as a single-chain 86-amino-acid precursor polypeptide, preproinsulin. Subsequent proteolytic processing removes the aminoterminal signal peptide, giving rise to proinsulin. Proinsulin is structurally related to insulin-like growth factors I and II, which bind weakly to the insulin receptor. Cleavage of an internal 31-residue fragment from proinsulin generates the C peptide and the A (21 amino acids) and B (30 amino acids) chains of insulin, which are connected by disulfide bonds.
The mature insulin molecule and C peptide are stored together and cosecreted from secretory granules in the beta cells. Because the C peptide is less susceptible than insulin to hepatic degradation, it is a useful marker of insulin secretion
Secretion
Glucose enters to the beta cells via GLUT 2 receptors
Metabolized by the Glucokinase
Produce ATP
ATP inhibits potassium channel
Depolarization of the cell membrane
Opening of voltage dependant calcium channel
calcium influx
Insulin secretion
Action
Insulin acts on almost all the tissues but liver, muscles and adipose tissues are the main sites. Overall effect is to conserve fuel by facilitating the uptake and storage of glucose , amino acids and fatty acids following a meal.
Insulin binding to its receptor stimulates intrinsic tyrosine kinase activity, leading to receptor autophosphorylation and the recruitment of intracellular signaling molecules, such as insulin receptor substrates (IRS). These and other adaptor proteins initiate a complex cascade of phosphorylation and dephosphorylation reactions, resulting in
the widespread metabolic and mitogenic effects of insulin.
Structure
Insulin consists of two amino acids; A chain (21 amino acids): B chain (30 amino acids).
These two amino acids chains are combined with two sulphide bonds.
TYPES OF INSULIN
1. Short acting insulin
I. Soluble insulin
II. Rapid acting insulin analogues
2. Intermediate acting insulin
3. Long acting insulin
4. Mixed insulin
Soluble insulin
Soluble insulin is a short acting insulin. This is the most appropriate form of insulin for use in diabetic emergencies and at the time of surgery. There are two types of soluble insulins;
1. Soluble human insulin (Product of DNA recombinant technique)
2. Soluble animal insulin (Bovine and porcine)
Soluble insulin is injected 15-30 minutes prior to a meal. It reaches peak concentration within 60-90 minutes and duration of action is about 8 hours. It can be administrate in intravenous, intramuscular and subcutaneous routes.
Rapid acting insulin analogue
The structure of the insulin molecule is modified as to change its pharmacokinetics without altering the biological effects
The human insulin analogues have a faster onset and shorter duration of action; as a result, compared to soluble insulin, fasting and pre-prandial blood glucose concentration is a little lower, and hypoglycemia occurs slightly less likely. Route of administration is subcutaneous. There are two types of analogues available;
1. Insulin lispro
2. Insulin aspart
Intermediate acting insulin
When they are given in subcutaneous route, the onset of action is 1-2 hours and duration of action is about 18-24 hours. There are two types of intermediate acting insulin;
1. Isophane insulin (NPH: Neutral Protamine Hagedorn);
This is prepared by adding protamine into soluble insulin. It has a cloudy appearance. This can be pre-mixed with soluble insulin or can be combined with insulin analogues as well
2. Insulin Zn suspension (Crystalline/ lente insulin);
Prepared by adding Zn into soluble insulin
Duration of action is longer than that of NPH
Cannot be pre-mixed with soluble insulin, but can be mixed just prior to inject.
Long acting insulin
Onset of action is 4-6 hours and duration of action is 24-36 hours when given subcutaneously. There are mainly two types;
1. Insulin gargling
This is an insulin analogue. It has a prolonged duration of action and it is given once a daily basis.
2. Protamine Zn insulin (ultralente)
Given once a daily basis
Usually given with soluble insulin
Rarely used.
Mixed insulin
This is the commonest way of giving insulin. Preparations are made to suit the patients’ need. There are several preparations available;
1. Biphasic insulin aspart
This is the mixture of insulin aspart(30%) and isophane insulin(70%).
2. Biphasic insulin lispro
This is the mixture of insulin lispro and isophane insulin. Percentages can be varying.
Eg; Biphasic insulin lispro 25 (25% insulin lispro and 75% isophane insulin)
Biphasic insulin lispro 50 (50% insulin lispro and 50% isophane insulin)
3. Biphasic isophane insulin
This is the mixture of soluble insulin and isophane insulin. Percentages can be varying.
Eg; Biphasic isophane insulin30/70(30% soluble insulin and 70% isophane insulin)
Biphasic isophane insulin10 (10% soluble insulin and 90% isophane insulin)
Biphasic isophane insulin20 (20% soluble insulin and 80% isophane insulin)
Biphasic isophane insulin40 (40% soluble insulin and 60% isophane insulin)
I. Soluble insulin
II. Rapid acting insulin analogues
2. Intermediate acting insulin
3. Long acting insulin
4. Mixed insulin
Soluble insulin
Soluble insulin is a short acting insulin. This is the most appropriate form of insulin for use in diabetic emergencies and at the time of surgery. There are two types of soluble insulins;
1. Soluble human insulin (Product of DNA recombinant technique)
2. Soluble animal insulin (Bovine and porcine)
Soluble insulin is injected 15-30 minutes prior to a meal. It reaches peak concentration within 60-90 minutes and duration of action is about 8 hours. It can be administrate in intravenous, intramuscular and subcutaneous routes.
Rapid acting insulin analogue
The structure of the insulin molecule is modified as to change its pharmacokinetics without altering the biological effects
The human insulin analogues have a faster onset and shorter duration of action; as a result, compared to soluble insulin, fasting and pre-prandial blood glucose concentration is a little lower, and hypoglycemia occurs slightly less likely. Route of administration is subcutaneous. There are two types of analogues available;
1. Insulin lispro
2. Insulin aspart
Intermediate acting insulin
When they are given in subcutaneous route, the onset of action is 1-2 hours and duration of action is about 18-24 hours. There are two types of intermediate acting insulin;
1. Isophane insulin (NPH: Neutral Protamine Hagedorn);
This is prepared by adding protamine into soluble insulin. It has a cloudy appearance. This can be pre-mixed with soluble insulin or can be combined with insulin analogues as well
2. Insulin Zn suspension (Crystalline/ lente insulin);
Prepared by adding Zn into soluble insulin
Duration of action is longer than that of NPH
Cannot be pre-mixed with soluble insulin, but can be mixed just prior to inject.
Long acting insulin
Onset of action is 4-6 hours and duration of action is 24-36 hours when given subcutaneously. There are mainly two types;
1. Insulin gargling
This is an insulin analogue. It has a prolonged duration of action and it is given once a daily basis.
2. Protamine Zn insulin (ultralente)
Given once a daily basis
Usually given with soluble insulin
Rarely used.
Mixed insulin
This is the commonest way of giving insulin. Preparations are made to suit the patients’ need. There are several preparations available;
1. Biphasic insulin aspart
This is the mixture of insulin aspart(30%) and isophane insulin(70%).
2. Biphasic insulin lispro
This is the mixture of insulin lispro and isophane insulin. Percentages can be varying.
Eg; Biphasic insulin lispro 25 (25% insulin lispro and 75% isophane insulin)
Biphasic insulin lispro 50 (50% insulin lispro and 50% isophane insulin)
3. Biphasic isophane insulin
This is the mixture of soluble insulin and isophane insulin. Percentages can be varying.
Eg; Biphasic isophane insulin30/70(30% soluble insulin and 70% isophane insulin)
Biphasic isophane insulin10 (10% soluble insulin and 90% isophane insulin)
Biphasic isophane insulin20 (20% soluble insulin and 80% isophane insulin)
Biphasic isophane insulin40 (40% soluble insulin and 60% isophane insulin)
Insulin injection technique
Introduction
Diabetes is one of the most common and serious chronic diseases. A third of its victims remain unaware that they have it. Each year, approximately 800,000 people are diagnosed with diabetes, its prevalence increasing steadily over the last half of this century. Incidence is expected to continue rising with the aging.
When talking about insulin injection techniques, followings should be considered.
1. Syringes
2. Insulin pen
3. other insulin aids
4. site selection
5. mixing of insulin
6. injection technique
SYRINGES
Insulin syringes are in the four basic capacities;
1. 1 cc (100 units)
2. 1/2 cc (50 units)
3. 3/10 cc (30 units)
4. 200-unit syringes (used in rare cases where patients require doses in excess of 100 units)
The unit scale or graduations on the barrel of the syringe may differ depending on the size of the syringe and the manufacturer;
1. 1 cc syringes usually marked in 2-unit intervals
2. 1/2 cc and 3/10 cc syringes in 1-unit intervals
The barrels of the smaller-capacity syringes are narrower to allow expansion of scales and easier reading, so patients should generally be counseled to use syringes with the smallest capacity that will accommodate the required dose.
Insulin syringes are also fitted with different needle gauges and lengths ranging from 28G, 29G and 30G. As with other needles, the higher the number of the needle gauge, the smaller the diameter of the needle. In general, patients prefer the thinner needles, associating thinner needles with greater comfort. Patients should be warned that with the thinner gauge needle also comes increased needle flexibility.
Insulin syringe needles are available in;
1. The standard 1/2-inch (12.7mm)
2. A shorter 5/16-inch (8 mm)
A patient changing needle lengths may experience a change in glycemic control, as absorption from a different subcutaneous depth can affect rate and extent of insulin absorption.
Insulin Pens
Insulin pens have become especially convenient for active people or those who have difficulty drawing insulin from a vial. They are compact, easy to carry and store, and discreet to use; and they eliminate the need to carry vials of insulin. Insulin is stored in a cartridge inside the pen, and the delivered dose is selected by turning a dial prior to activation of the device.
Other Injection Aids
Injecting insulin may become more difficult for patients with compromised dexterity or eyesight, so various injection aids have been designed to help overcome these difficulties. A magnifier fits around the syringe to enable the user with compromised visual acuity to read syringe measurements more accurately.
Automatic injector devices facilitate ease of administration, some delivering needle and insulin simultaneously and others requiring the user to push a syringe plunger after the needle has pierced the skin. Such a device may be helpful for people who have a fear of needles or of self-injection, as the injection is not directly observable.
Site Selection
Insulin is injected into the fatty tissue under the skin from which it is absorbed into the blood stream at rates that vary with the site of injection, so blood glucose values may also vary with injection site.
Common sites are;
1. Abdomen
2. Arms
3. Hip
4. Buttocks
5. Thigh
Absorption is most rapid from sites in the abdomen, somewhat slower from the arms, slower still from the legs, and slowest from the hip or buttock area.
Patients may choose one area over others because of comfort, or how quickly or slowly insulin is absorbed. Rotating injection sites within one area is generally recommended over rotating to a different area due to the variable absorption between the different sites. Increasing exercise of the injection site increases the rate of insulin absorption by enhancing blood flow to the area. Preferred sites for insulin injections include the upper arm, the anterior and lateral aspects of the thigh, the buttocks, and the abdomen (stomach area).
Mixing Insulins
Certain short-acting and long-acting insulins can be mixed in the same syringe to minimize the number of injections. The short-acting (clear) insulin should be drawn up first, followed by the long-acting insulin, as follows.
Hands should be cleaned with soap and water before mixixng
Mixing should be done gently by rolling the vial between the palms of the hands, or gently turning the bottle from end to end a few times. Do NOT shake!
Injection Technique
Detailed information regarding insulin injection technique should provided to the patient.
All the equipment should be ready. Then select the site.
Wash hands with warm, soapy water prior to the procedure.
After choosing an injection site, clean the area with an alcohol swab.
Pick up the syringe and uncap if previously recapped. “Pinch” the area of skin to be injected, and quickly push the needle through the skin at a 90° angle. Inject the insulin by pushing down on the plunger, release the pinched skin, and pull the needle straight out of the site. Press gently over the area injected with a finger or alcohol swab, but do not rub the area.
Dispose of used needles and syringes safely.
How do you minimize the pain?
1. Inject insulin at room temperature.
2. Remove all air bubbles from the syringe before injection.
3. Wait until topical alcohol has evaporated before injecting.
4. Keep muscles in the injection area relaxed during injection.
5. Penetrate the skin quickly.
6. Avoid changing direction of the needle during insertion or removal.
7. Do not reuse disposable needles.
Diabetes is one of the most common and serious chronic diseases. A third of its victims remain unaware that they have it. Each year, approximately 800,000 people are diagnosed with diabetes, its prevalence increasing steadily over the last half of this century. Incidence is expected to continue rising with the aging.
When talking about insulin injection techniques, followings should be considered.
1. Syringes
2. Insulin pen
3. other insulin aids
4. site selection
5. mixing of insulin
6. injection technique
SYRINGES
Insulin syringes are in the four basic capacities;
1. 1 cc (100 units)
2. 1/2 cc (50 units)
3. 3/10 cc (30 units)
4. 200-unit syringes (used in rare cases where patients require doses in excess of 100 units)
The unit scale or graduations on the barrel of the syringe may differ depending on the size of the syringe and the manufacturer;
1. 1 cc syringes usually marked in 2-unit intervals
2. 1/2 cc and 3/10 cc syringes in 1-unit intervals
The barrels of the smaller-capacity syringes are narrower to allow expansion of scales and easier reading, so patients should generally be counseled to use syringes with the smallest capacity that will accommodate the required dose.
Insulin syringes are also fitted with different needle gauges and lengths ranging from 28G, 29G and 30G. As with other needles, the higher the number of the needle gauge, the smaller the diameter of the needle. In general, patients prefer the thinner needles, associating thinner needles with greater comfort. Patients should be warned that with the thinner gauge needle also comes increased needle flexibility.
Insulin syringe needles are available in;
1. The standard 1/2-inch (12.7mm)
2. A shorter 5/16-inch (8 mm)
A patient changing needle lengths may experience a change in glycemic control, as absorption from a different subcutaneous depth can affect rate and extent of insulin absorption.
Insulin Pens
Insulin pens have become especially convenient for active people or those who have difficulty drawing insulin from a vial. They are compact, easy to carry and store, and discreet to use; and they eliminate the need to carry vials of insulin. Insulin is stored in a cartridge inside the pen, and the delivered dose is selected by turning a dial prior to activation of the device.
Other Injection Aids
Injecting insulin may become more difficult for patients with compromised dexterity or eyesight, so various injection aids have been designed to help overcome these difficulties. A magnifier fits around the syringe to enable the user with compromised visual acuity to read syringe measurements more accurately.
Automatic injector devices facilitate ease of administration, some delivering needle and insulin simultaneously and others requiring the user to push a syringe plunger after the needle has pierced the skin. Such a device may be helpful for people who have a fear of needles or of self-injection, as the injection is not directly observable.
Site Selection
Insulin is injected into the fatty tissue under the skin from which it is absorbed into the blood stream at rates that vary with the site of injection, so blood glucose values may also vary with injection site.
Common sites are;
1. Abdomen
2. Arms
3. Hip
4. Buttocks
5. Thigh
Absorption is most rapid from sites in the abdomen, somewhat slower from the arms, slower still from the legs, and slowest from the hip or buttock area.
Patients may choose one area over others because of comfort, or how quickly or slowly insulin is absorbed. Rotating injection sites within one area is generally recommended over rotating to a different area due to the variable absorption between the different sites. Increasing exercise of the injection site increases the rate of insulin absorption by enhancing blood flow to the area. Preferred sites for insulin injections include the upper arm, the anterior and lateral aspects of the thigh, the buttocks, and the abdomen (stomach area).
Mixing Insulins
Certain short-acting and long-acting insulins can be mixed in the same syringe to minimize the number of injections. The short-acting (clear) insulin should be drawn up first, followed by the long-acting insulin, as follows.
Hands should be cleaned with soap and water before mixixng
Mixing should be done gently by rolling the vial between the palms of the hands, or gently turning the bottle from end to end a few times. Do NOT shake!
Injection Technique
Detailed information regarding insulin injection technique should provided to the patient.
All the equipment should be ready. Then select the site.
Wash hands with warm, soapy water prior to the procedure.
After choosing an injection site, clean the area with an alcohol swab.
Pick up the syringe and uncap if previously recapped. “Pinch” the area of skin to be injected, and quickly push the needle through the skin at a 90° angle. Inject the insulin by pushing down on the plunger, release the pinched skin, and pull the needle straight out of the site. Press gently over the area injected with a finger or alcohol swab, but do not rub the area.
Dispose of used needles and syringes safely.
How do you minimize the pain?
1. Inject insulin at room temperature.
2. Remove all air bubbles from the syringe before injection.
3. Wait until topical alcohol has evaporated before injecting.
4. Keep muscles in the injection area relaxed during injection.
5. Penetrate the skin quickly.
6. Avoid changing direction of the needle during insertion or removal.
7. Do not reuse disposable needles.
Insulin Resistance
Introduction
Insulin resistance is a condition that increases your chances of developing type 2 diabetes and heart disease. When you have insulin resistance, your body has problems responding to insulin. Eventually, your blood glucose (sugar) levels rise above normal. The good news is that cutting calories, adding physical activity to your daily routine, and losing weight can reverse insulin resistance and lessen your chances of getting type 2 diabetes and heart disease.
Risk factors for insulin resistance
You’re more likely to have insulin resistance if you
• are overweight
• are physically inactive
• are a woman with a waist measurement at your belly button over 35 inches or a man with a waist measure over 40 inches
• have a parent, brother, or sister with type 2 diabetes
• have polycystic ovary syndrome
• are over age 45
• have a blood pressure over 140/90 mmHg
• have low HDL (good) cholesterol levels (35 mg/dl or lower)
• have high levels of a fat called triglycerides in the blood (250 mg/dl or higher)
All of these risk factors put you at risk for heart disease as well.
How is insulin resistance diagnosed?
At this time, there is no commonly used test to diagnose insulin resistance. People with insulin resistance usually have no symptoms. Your doctor can review your risk factors and then consider whether you’re likely to be insulin resistant. If you have a risk factor for insulin resistance, your doctor should check your fasting blood glucose levels to see whether you have pre-diabetes or even diabetes.
How can I prevent or reverse insulin resistance?
You can cut calories and be physically active. If you do, it’s more likely you’ll lose weight. Remember, you don’t have to lose a lot; even a loss of 10 pounds can help.
Insulin resistance is a condition that increases your chances of developing type 2 diabetes and heart disease. When you have insulin resistance, your body has problems responding to insulin. Eventually, your blood glucose (sugar) levels rise above normal. The good news is that cutting calories, adding physical activity to your daily routine, and losing weight can reverse insulin resistance and lessen your chances of getting type 2 diabetes and heart disease.
Risk factors for insulin resistance
You’re more likely to have insulin resistance if you
• are overweight
• are physically inactive
• are a woman with a waist measurement at your belly button over 35 inches or a man with a waist measure over 40 inches
• have a parent, brother, or sister with type 2 diabetes
• have polycystic ovary syndrome
• are over age 45
• have a blood pressure over 140/90 mmHg
• have low HDL (good) cholesterol levels (35 mg/dl or lower)
• have high levels of a fat called triglycerides in the blood (250 mg/dl or higher)
All of these risk factors put you at risk for heart disease as well.
How is insulin resistance diagnosed?
At this time, there is no commonly used test to diagnose insulin resistance. People with insulin resistance usually have no symptoms. Your doctor can review your risk factors and then consider whether you’re likely to be insulin resistant. If you have a risk factor for insulin resistance, your doctor should check your fasting blood glucose levels to see whether you have pre-diabetes or even diabetes.
How can I prevent or reverse insulin resistance?
You can cut calories and be physically active. If you do, it’s more likely you’ll lose weight. Remember, you don’t have to lose a lot; even a loss of 10 pounds can help.
C-peptide
C-peptide is a peptide which is made when proinsulin is split into insulin and C-peptide. They split before proinsulin is released from endocytic vesicles within the pancreas -- one C-peptide for each insulin molecule.
C-peptide is the abbreviation for "connecting peptide", although its name was probably also inspired by the fact that insulin is also composed of an "A" chain and a "B" chain. C-peptide was discovered in 1967. It should not to be confused with c-reactive protein or Protein C. The first documented use of the C-peptide test was in 1972.
Function
Cellular effects of C-peptide: C-peptide binds to a receptor at the cell surface and activates signal transduction pathways that result in stimulation of Na+,K+ATPase and endothelial nitric oxide synthase (eNOS), both of which are enzymes with reduced activitities in type I diabetes.
C-peptide functions in repair of the muscular layer of the arteries.
C-peptide also exerts beneficial therapeutic effects on many complications associated with diabetes mellitus,[2] such as diabetic neuropathy[3] and other diabetes-induced ailments. In the kidneys, C-peptide prevents diabetic nephropathy,[4][5] and in the heart blood flow is improved in diabetic patients.[6]
In spite of these physiological functions, C-peptide is not present in pharmaceutical preparations of insulin sold by drug companies that are in wide-scale clinical usage today, a practice seen as unethical in light of more research suggesting the peptide's utility.
Ironically, back in 1997, insulin manufacturer Eli Lilly and Company jointly funded research into C-Peptide as a possible therapeutic. In the research undertaken by researchers at Washington University School of Medicine in St. Louis, they determined that C-Peptide may effectively prevent and even reverse cardiovascular disease and nerve damage in people with diabetes, although their studies were only on rodent models of the disease.[7][8] However, the company never pursued commercialization of the product. But in a 2007 letter to the Indianapolis Star, company executive John C. Lechleiter did indicate that the company was pursuing development of drugs to treat diabetes-induced complications.
Uses
• Newly diagnosed diabetes patients often get their C-peptide levels measured as a means of distinguishing type 1 diabetes and type 2 diabetes. C-peptide levels are measured instead of insulin levels because insulin concentration in the portal vein ranges from two to ten times higher than in the peripheral circulation. The liver extracts about half the insulin reaching it in the plasma, but this varies with the nutritional state. The pancreas of patients with type 1 diabetes is unable to produce insulin and therefore they will usually have a decreased level of C-peptide, whereas C-peptide levels in type 2 patients are normal or higher than normal. Measuring C-peptide in patients injecting insulin can help to determine how much of their own natural insulin these patients are still producing. C-peptide is easily detected because antibodies that are sensitive to it are readily available, whereas antibodies to insulin are much more difficult to obtain.
• C-peptide is also used for determining the possibility of gastrinomas associated with Multiple Endocrine Neoplasm syndromes (MEN 1). Since a significant amount of gastrinomas also include MEN which include pancreatic, parathyroid, and pituitary adenomas, higher levels of C-peptide together with the presence of a gastrinoma suggest that organs besides the stomach may harbor neoplasms.
• Can be used for identifying malingering: hypoglycemia with low C-peptide level may indicate abuse of insulin.
• C-peptide levels are checked in women with Polycystic Ovarian Syndrome (PCOS) to determine degree of insulin resistance.
Both excess body weight and a high plasma concentration of C-peptide predispose men with a subsequent diagnosis of prostate cancer to an increased likelihood of dying of the disease, according to the results of a long-term survival analysis reported in the October 6, 2008 Online First issue of Lancet Oncology.
[edit] Therapeutics
C-peptide has been administered experimentally to improve neuropathy and other symptoms of diabetes.[9] [10] [11] [12] [13] [2] [14] [15] [16].
A company based in Stockholm, Sweden called Creative Peptides has secured manufacturing and other patents in a number of countries for C-peptide, and aims to commercialize it as a therapeutic. It is now undergoing human clinical trials. However since C-Peptide was discovered in 1967, patenting the peptide itself is not possible, only the processes to create it. This makes it very difficult to obtain research dollars from pharmaceutical companies to conduct research. Creative Pepides solution is to patent processes to create C-Peptide, thus making the product more profitable to invest in for pharmaceutical companies.
After delays due to lack of funding, Creative Peptides has now obtain funding based on a process that will make it possible to inject C-peptide once a week instead of daily. Stage 3 Clinical Trials are set for late 2009.
C-peptide is the abbreviation for "connecting peptide", although its name was probably also inspired by the fact that insulin is also composed of an "A" chain and a "B" chain. C-peptide was discovered in 1967. It should not to be confused with c-reactive protein or Protein C. The first documented use of the C-peptide test was in 1972.
Function
Cellular effects of C-peptide: C-peptide binds to a receptor at the cell surface and activates signal transduction pathways that result in stimulation of Na+,K+ATPase and endothelial nitric oxide synthase (eNOS), both of which are enzymes with reduced activitities in type I diabetes.
C-peptide functions in repair of the muscular layer of the arteries.
C-peptide also exerts beneficial therapeutic effects on many complications associated with diabetes mellitus,[2] such as diabetic neuropathy[3] and other diabetes-induced ailments. In the kidneys, C-peptide prevents diabetic nephropathy,[4][5] and in the heart blood flow is improved in diabetic patients.[6]
In spite of these physiological functions, C-peptide is not present in pharmaceutical preparations of insulin sold by drug companies that are in wide-scale clinical usage today, a practice seen as unethical in light of more research suggesting the peptide's utility.
Ironically, back in 1997, insulin manufacturer Eli Lilly and Company jointly funded research into C-Peptide as a possible therapeutic. In the research undertaken by researchers at Washington University School of Medicine in St. Louis, they determined that C-Peptide may effectively prevent and even reverse cardiovascular disease and nerve damage in people with diabetes, although their studies were only on rodent models of the disease.[7][8] However, the company never pursued commercialization of the product. But in a 2007 letter to the Indianapolis Star, company executive John C. Lechleiter did indicate that the company was pursuing development of drugs to treat diabetes-induced complications.
Uses
• Newly diagnosed diabetes patients often get their C-peptide levels measured as a means of distinguishing type 1 diabetes and type 2 diabetes. C-peptide levels are measured instead of insulin levels because insulin concentration in the portal vein ranges from two to ten times higher than in the peripheral circulation. The liver extracts about half the insulin reaching it in the plasma, but this varies with the nutritional state. The pancreas of patients with type 1 diabetes is unable to produce insulin and therefore they will usually have a decreased level of C-peptide, whereas C-peptide levels in type 2 patients are normal or higher than normal. Measuring C-peptide in patients injecting insulin can help to determine how much of their own natural insulin these patients are still producing. C-peptide is easily detected because antibodies that are sensitive to it are readily available, whereas antibodies to insulin are much more difficult to obtain.
• C-peptide is also used for determining the possibility of gastrinomas associated with Multiple Endocrine Neoplasm syndromes (MEN 1). Since a significant amount of gastrinomas also include MEN which include pancreatic, parathyroid, and pituitary adenomas, higher levels of C-peptide together with the presence of a gastrinoma suggest that organs besides the stomach may harbor neoplasms.
• Can be used for identifying malingering: hypoglycemia with low C-peptide level may indicate abuse of insulin.
• C-peptide levels are checked in women with Polycystic Ovarian Syndrome (PCOS) to determine degree of insulin resistance.
Both excess body weight and a high plasma concentration of C-peptide predispose men with a subsequent diagnosis of prostate cancer to an increased likelihood of dying of the disease, according to the results of a long-term survival analysis reported in the October 6, 2008 Online First issue of Lancet Oncology.
[edit] Therapeutics
C-peptide has been administered experimentally to improve neuropathy and other symptoms of diabetes.[9] [10] [11] [12] [13] [2] [14] [15] [16].
A company based in Stockholm, Sweden called Creative Peptides has secured manufacturing and other patents in a number of countries for C-peptide, and aims to commercialize it as a therapeutic. It is now undergoing human clinical trials. However since C-Peptide was discovered in 1967, patenting the peptide itself is not possible, only the processes to create it. This makes it very difficult to obtain research dollars from pharmaceutical companies to conduct research. Creative Pepides solution is to patent processes to create C-Peptide, thus making the product more profitable to invest in for pharmaceutical companies.
After delays due to lack of funding, Creative Peptides has now obtain funding based on a process that will make it possible to inject C-peptide once a week instead of daily. Stage 3 Clinical Trials are set for late 2009.
Diabetic ketoacidosis (DKA)
Introduction
Diabetes ketoacidosis is an acute complication of diabetes as hyperglycemic hyperosmolar state (HHS).It was formerly considered a hallmark of type 1 DM, but it also occurs in individuals with type 2 diabetes mellitus as well. This is associated with potentially serious complications if not promptly diagnosed and treated.
Clinical Features
The symptoms and physical signs of DKA are listed below and usually develop over 24 hours. DKA may be the initial presentation of type 1 DM, but more frequently it occurs in individuals with established diabetes. Nausea and vomiting are often prominent,
1. Symptoms
Nausea
Vomiting
Thirst
Polyuria
Abdominal pain
Shortness of breath
2. Physical findings
Tachycardia
Dry mucous membranes
Reduced skin turgor
Dehydration
Hypotension
Tachypnea
Kussmaul respirations
Respiratory distress
Abdominal tenderness (may resemble acute pancreatitis or surgical abdomen)
Lethargy
Obtundation
Cerebral
Edema
Possibly coma
3. Precipitating events
Inadequate insulin administration
Infection (pneumonia/UTI/gastroenteritis/sepsis)
Infarction (cerebral, coronary, mesenteric, peripheral)
Drugs (cocaine)
Pregnancy
Pathophysiology
DKA results from relative or absolute insulin deficiency combined with counterregulatory hormone excess (glucagon, catecholamines, cortisol, and growth hormone). Both insulin deficiency and glucagon excess, in particular, are necessary for DKA to develop. The decreased ratio of insulin to glucagon promotes gluconeogenesis, glycogenolysis, and ketone body formation in the liver, as well as increases in substrate delivery from fat and muscle (free fatty acids, amino acids) to the liver.
Laboratory Abnormalities and Diagnosis
The timely diagnosis of DKA is crucial and allows for prompt initiation of therapy. DKA is characterized by hyperglycemia, ketosis, and metabolic acidosis (increased anion gap) along with a number of secondary metabolic derangements;
Glucose 13.9–33.3 mmol/L (250–600 mg/dL)
Sodium 125–135 meq/L
Potassium Normal to higher
Magnesium Normal to higher
Chloride Normal
Phosphate Normal
Creatinine Slightly high
Osmolality 300–320 mOsm/mL
Plasma ketones ++++
Serum bicarbonate >15 meq/L
Arterial pH 6.8–7.3
Arterial PCO 20–30mmHg
Anion gap [Na-(Cl+HCO3)] higher
Treatment
1) Confirm diagnosis
2) Admit to hospital; intensive-care setting
3) Assess: Serum
4) Replace fluids
5) Administer regular insulin
6) Assess patient: What precipitated the
7) Measure capillary glucose every 1–2 h
8) Monitor blood pressure, pulse, respirations, mental status, fluid intake and output every 1–4 h.
9) Replace potassium
10) Continue above until patient is stable
11) Administer intermediate or long-acting insulin as soon as patient is eating. Allow for overlap in insulin infusion and subcutaneous insulin injection.
Diabetes ketoacidosis is an acute complication of diabetes as hyperglycemic hyperosmolar state (HHS).It was formerly considered a hallmark of type 1 DM, but it also occurs in individuals with type 2 diabetes mellitus as well. This is associated with potentially serious complications if not promptly diagnosed and treated.
Clinical Features
The symptoms and physical signs of DKA are listed below and usually develop over 24 hours. DKA may be the initial presentation of type 1 DM, but more frequently it occurs in individuals with established diabetes. Nausea and vomiting are often prominent,
1. Symptoms
Nausea
Vomiting
Thirst
Polyuria
Abdominal pain
Shortness of breath
2. Physical findings
Tachycardia
Dry mucous membranes
Reduced skin turgor
Dehydration
Hypotension
Tachypnea
Kussmaul respirations
Respiratory distress
Abdominal tenderness (may resemble acute pancreatitis or surgical abdomen)
Lethargy
Obtundation
Cerebral
Edema
Possibly coma
3. Precipitating events
Inadequate insulin administration
Infection (pneumonia/UTI/gastroenteritis/sepsis)
Infarction (cerebral, coronary, mesenteric, peripheral)
Drugs (cocaine)
Pregnancy
Pathophysiology
DKA results from relative or absolute insulin deficiency combined with counterregulatory hormone excess (glucagon, catecholamines, cortisol, and growth hormone). Both insulin deficiency and glucagon excess, in particular, are necessary for DKA to develop. The decreased ratio of insulin to glucagon promotes gluconeogenesis, glycogenolysis, and ketone body formation in the liver, as well as increases in substrate delivery from fat and muscle (free fatty acids, amino acids) to the liver.
Laboratory Abnormalities and Diagnosis
The timely diagnosis of DKA is crucial and allows for prompt initiation of therapy. DKA is characterized by hyperglycemia, ketosis, and metabolic acidosis (increased anion gap) along with a number of secondary metabolic derangements;
Glucose 13.9–33.3 mmol/L (250–600 mg/dL)
Sodium 125–135 meq/L
Potassium Normal to higher
Magnesium Normal to higher
Chloride Normal
Phosphate Normal
Creatinine Slightly high
Osmolality 300–320 mOsm/mL
Plasma ketones ++++
Serum bicarbonate >15 meq/L
Arterial pH 6.8–7.3
Arterial PCO 20–30mmHg
Anion gap [Na-(Cl+HCO3)] higher
Treatment
1) Confirm diagnosis
2) Admit to hospital; intensive-care setting
3) Assess: Serum
4) Replace fluids
5) Administer regular insulin
6) Assess patient: What precipitated the
7) Measure capillary glucose every 1–2 h
8) Monitor blood pressure, pulse, respirations, mental status, fluid intake and output every 1–4 h.
9) Replace potassium
10) Continue above until patient is stable
11) Administer intermediate or long-acting insulin as soon as patient is eating. Allow for overlap in insulin infusion and subcutaneous insulin injection.
Hyperglycemic hyperosmolar state (HHS)
Introduction
Hyperglycemic hyperosmolar state (HHS) is an acute complication of diabetes as DKA. HHS is primarily seen in individuals with type 2 DM.
Clinical Features
The prototypical patient with HHS is an elderly individual with type 2 DM, with a several week history of polyuria, weight loss, and diminished oral intake that culminates in mental confusion, lethargy, or coma.
The physical examination reflects profound dehydration and hyperosmolality and reveals hypotension, tachycardia, and altered mental status.
Notably absent are symptoms of nausea, vomiting, and abdominal pain and the Kussmaul respirations characteristic of DKA. HHS is often precipitated by a serious, concurrent illness such as myocardial infarction or stroke. Sepsis, pneumonia, and other serious infections are frequent precipitants and should be sought.
Pathophysiology
Relative insulin deficiency and inadequate fluid intake are the underlying causes of HHS. Insulin deficiency increases hepatic glucose production (through glycogenolysis and gluconeogenesis) and impairs glucose utilization in skeletal muscle (see above discussion of DKA). Hyperglycemia induces an osmotic diuresis that leads to intravascular volume depletion, which is exacerbated by inadequate fluid replacement. The absence of ketosis in HHS is not completely understood.
Laboratory Abnormalities and Diagnosis
The laboratory features in HHS are summarized as follows;
Glucose 33.3–66.6 (mmol/L (600-1200 mg/dL)
Sodium 135–145 meq/L
Potassium Normal
Magnesium Normal
Chloride Normal
Phosphate Normal
Creatinine Moderately high
Osmolality 330–380 mOsm/mL
Plasma ketones +/-
Serum bicarbonate Normal to slightly low
Arterial pH >7.3
Arterial PCO Normal
Anion gap [Na-(Cl+HCO3)] Normal to slightly higher
Treatment
Volume depletion and hyperglycemia are prominent features of both HHS and DKA. In both disorders, careful monitoring of the patient’s fluid status, laboratory values, and insulin infusion rate is crucial. Underlying or precipitating problems should be aggressively sought and treated. In HHS, fluid losses and dehydration are usually more pronounced than in DKA due to the longer duration of the illness. The patient with HHS is usually older, more likely to have mental status changes, and more likely to have a life-threatening precipitating event with accompanying comorbidities. Even with proper treatment, HHS has a substantially higher mortality than DKA (up to 15% in some clinical series).
Hyperglycemic hyperosmolar state (HHS) is an acute complication of diabetes as DKA. HHS is primarily seen in individuals with type 2 DM.
Clinical Features
The prototypical patient with HHS is an elderly individual with type 2 DM, with a several week history of polyuria, weight loss, and diminished oral intake that culminates in mental confusion, lethargy, or coma.
The physical examination reflects profound dehydration and hyperosmolality and reveals hypotension, tachycardia, and altered mental status.
Notably absent are symptoms of nausea, vomiting, and abdominal pain and the Kussmaul respirations characteristic of DKA. HHS is often precipitated by a serious, concurrent illness such as myocardial infarction or stroke. Sepsis, pneumonia, and other serious infections are frequent precipitants and should be sought.
Pathophysiology
Relative insulin deficiency and inadequate fluid intake are the underlying causes of HHS. Insulin deficiency increases hepatic glucose production (through glycogenolysis and gluconeogenesis) and impairs glucose utilization in skeletal muscle (see above discussion of DKA). Hyperglycemia induces an osmotic diuresis that leads to intravascular volume depletion, which is exacerbated by inadequate fluid replacement. The absence of ketosis in HHS is not completely understood.
Laboratory Abnormalities and Diagnosis
The laboratory features in HHS are summarized as follows;
Glucose 33.3–66.6 (mmol/L (600-1200 mg/dL)
Sodium 135–145 meq/L
Potassium Normal
Magnesium Normal
Chloride Normal
Phosphate Normal
Creatinine Moderately high
Osmolality 330–380 mOsm/mL
Plasma ketones +/-
Serum bicarbonate Normal to slightly low
Arterial pH >7.3
Arterial PCO Normal
Anion gap [Na-(Cl+HCO3)] Normal to slightly higher
Treatment
Volume depletion and hyperglycemia are prominent features of both HHS and DKA. In both disorders, careful monitoring of the patient’s fluid status, laboratory values, and insulin infusion rate is crucial. Underlying or precipitating problems should be aggressively sought and treated. In HHS, fluid losses and dehydration are usually more pronounced than in DKA due to the longer duration of the illness. The patient with HHS is usually older, more likely to have mental status changes, and more likely to have a life-threatening precipitating event with accompanying comorbidities. Even with proper treatment, HHS has a substantially higher mortality than DKA (up to 15% in some clinical series).
Complications of diabetes mellitus
There are mainly two types of complications associatedwith diabetes
Acute complications
1. Diabetic ketoacidosis (DKA)
2. Hyperglycemic hyperosmolar state (HHS)
Chronic complications
1. Microvascular
I. Eye disease; Retinopathy (nonproliferative/proliferative): Macular edema
II. Neuropathy; Sensory: motor (mono- and polyneuropathy):Autonomic
III. Nephropathy
2. Macrovascular
I. Coronary artery disease
II. Peripheral vascular disease
III. Cerebrovascular disease
3. Other
I. Gastrointestinal (gastroparesis, diarrhea)
II. Genitourinary (uropathy/sexual dysfunction)
III. Dermatologic
IV. Infectious
V. Cataracts
VI. Glaucoma
VII. Psychological problems
Acute complications
1. Diabetic ketoacidosis (DKA)
2. Hyperglycemic hyperosmolar state (HHS)
Chronic complications
1. Microvascular
I. Eye disease; Retinopathy (nonproliferative/proliferative): Macular edema
II. Neuropathy; Sensory: motor (mono- and polyneuropathy):Autonomic
III. Nephropathy
2. Macrovascular
I. Coronary artery disease
II. Peripheral vascular disease
III. Cerebrovascular disease
3. Other
I. Gastrointestinal (gastroparesis, diarrhea)
II. Genitourinary (uropathy/sexual dysfunction)
III. Dermatologic
IV. Infectious
V. Cataracts
VI. Glaucoma
VII. Psychological problems
Diabetic Nephropathy
Introduction
Diabetic nephropathy is one of the leading causes of ESRD and it is also a leading cause of DM-related morbidity and mortality. Proteinuria in individuals with DM is associated with markedly reduced survival and increased risk of cardiovascular disease. Individuals with diabetic nephropathy almost always have diabetic retinopathy.
Pathogenesis
Chronic hyperglycemia is the fundamental cause of diabetic nephropathy as in other microvascular complications. The mechanisms by which chronic hyperglycemia leads to end stage renal disease, though incompletely defined, involve the effects of soluble factors (growth factors, angiotensin II, endothelin, AGEs), hemodynamic alterations in the renal microcirculation (glomerular hyperfiltration or hyperperfusion, increased glomerular capillary pressure), and structural changes in the glomerulus (increased extracellular matrix, basement membrane thickening, mesangial expansion, fibrosis). Some of these effects may be mediated through angiotensin II receptors.
Clinical course
It is important to note that diabetic nephropathy is a multistage condition that takes several years to become clinically overt.
Microalbuminuria: the definition of diabetic nephropathy used to be dictated by the lower limit of detection of the assays for urinary albumin available at the time. Microalbuminuria is the first indication of diabetic nephropathy, and is defined as a persistent increase in urinary albumin excretion rate to 20–200 μg/minute (30–300 mg/ day).
Persistent albuminuria: an increase in albumin excretion to persistently more than 200 μg/minute (> 300 mg/day) marks the onset of clinically defined overt diabetic nephropathy.
Uraemia: persistent albuminuria is accompanied by a gradual decline in GFR. If untreated, this eventually leads to uraemia and death after an average of 7–10 years.
Diagnosis
Normally, there is little urinary albumin; normal ranges are:
1. urine albumin concentration < 20 mg/litre
2. albumin:creatinine ratio < 2.5 mg/mmol in men and < 3.5 mg/mmol in women
3. albumin excretion rate < 20 μg/minute.
Treatment
The optimal therapy for diabetic nephropathy is prevention. As part of comprehensive diabetes care, microalbuminuria should be detected at an early stage when effective therapies can be instituted. Interventions effective in slowing progression from Microalbuminuria to overt nephropathy include:
(1) Near normalization of glycemia,
(2) Strict blood pressure control, and
(3) Administration of ACE inhibitors or ARBs, and
(4) Treatment of dyslipidemia.
Diabetic nephropathy is one of the leading causes of ESRD and it is also a leading cause of DM-related morbidity and mortality. Proteinuria in individuals with DM is associated with markedly reduced survival and increased risk of cardiovascular disease. Individuals with diabetic nephropathy almost always have diabetic retinopathy.
Pathogenesis
Chronic hyperglycemia is the fundamental cause of diabetic nephropathy as in other microvascular complications. The mechanisms by which chronic hyperglycemia leads to end stage renal disease, though incompletely defined, involve the effects of soluble factors (growth factors, angiotensin II, endothelin, AGEs), hemodynamic alterations in the renal microcirculation (glomerular hyperfiltration or hyperperfusion, increased glomerular capillary pressure), and structural changes in the glomerulus (increased extracellular matrix, basement membrane thickening, mesangial expansion, fibrosis). Some of these effects may be mediated through angiotensin II receptors.
Clinical course
It is important to note that diabetic nephropathy is a multistage condition that takes several years to become clinically overt.
Microalbuminuria: the definition of diabetic nephropathy used to be dictated by the lower limit of detection of the assays for urinary albumin available at the time. Microalbuminuria is the first indication of diabetic nephropathy, and is defined as a persistent increase in urinary albumin excretion rate to 20–200 μg/minute (30–300 mg/ day).
Persistent albuminuria: an increase in albumin excretion to persistently more than 200 μg/minute (> 300 mg/day) marks the onset of clinically defined overt diabetic nephropathy.
Uraemia: persistent albuminuria is accompanied by a gradual decline in GFR. If untreated, this eventually leads to uraemia and death after an average of 7–10 years.
Diagnosis
Normally, there is little urinary albumin; normal ranges are:
1. urine albumin concentration < 20 mg/litre
2. albumin:creatinine ratio < 2.5 mg/mmol in men and < 3.5 mg/mmol in women
3. albumin excretion rate < 20 μg/minute.
Treatment
The optimal therapy for diabetic nephropathy is prevention. As part of comprehensive diabetes care, microalbuminuria should be detected at an early stage when effective therapies can be instituted. Interventions effective in slowing progression from Microalbuminuria to overt nephropathy include:
(1) Near normalization of glycemia,
(2) Strict blood pressure control, and
(3) Administration of ACE inhibitors or ARBs, and
(4) Treatment of dyslipidemia.
Diabetic neuropathy
Introduction
Diabetic neuropathy occurs in approximately 50% of individuals with long-standing type 1 and type 2 DM. There are two types of neuropathies; Microvascular and macrovascular
1. Microvascular
I. Hyperglycemic neuropathy
II. Acute painful sensory neuropathy
III. Sensory motor polyneuropathy
IV. Mononeuropathy
V. Diabetic truncal neuropathy
VI. Proximal diabetic neuropathy
VII. Autonomic neuropathy
2. Macrovascular
I. TIA & Strokes
Hyperglycemic neuropathy
This is common among newly diagnosed or poorly controlled diabetic patients. This is a very uncomfortable dysasthesiae affecting feet and lower legs. This condition is rapidly resolved with the establishment of euglycemia.
Acute painful sensory neuropathy
This condition is common among diabetic male whose glycemic control is poor. The patient will experience burning and aching pain. There is a widespread Cutaneous contact hyperesthesia. This is associated with depression and impotence. Proper control of blood sugar is the treatment.
Mononeuropathy
This is a dysfunction of isolated cranial or peripheral Nerves and it is less common than polyneuropathy in DM and presents with pain and motor weakness in the distribution of a single nerve. A vascular etiology has been suggested, but the pathogenesis is unknown. Involvement of the third cranial nerve is most common and is heralded by diplopia.
Diabetic truncal neuropathy
This occurs in thoracic nerve roots and it could be unilateral. Patient may have symptoms of chest pain or abdominal pain. This is commonly associated with Sensory motor and autonomic neuropathy
Proximal diabetic neuropathy/ proximal amyotrophy
• Involvement of lumbo - sacral nerves
• Metabolic in origin
• Middle aged or elderly
• Symptoms unilaterally or bilaterally
• Clinical features
• Prognosis - Good
Autonomic neuropathy
• Prevalence increases with poor control of DM and longer duration
• Poor prognostic indicator
• Symptoms
– Gustatory sweating
– Postural hypotension
– Diarrhoea alternating constipation
– Anhidrosis of limbs
– Small pupil
– Dysphagia and vomiting due to gastroparesis
– Impotence
TIA & Strokes
• Commonest brain disorder responsible for deaths and disability of adults.
• What are the risk factors?
• What are the clinical features?
• Characteristic feature is sudden onset of symptoms with maximum disability in the acute stage
Treatment
• Near normal glycaemic control
– DCCT -Reduced clinical neuropathy by 60% in Type I
– UKPDS - Reduced micro vascular complications by 25% in Type II
• Prevention of foot damage
– Screening
• Drugs
– Amitriptyline - Side effects
– Imipramine
– Carbemazepine
– Phenytoin
– GLA
Diabetic neuropathy occurs in approximately 50% of individuals with long-standing type 1 and type 2 DM. There are two types of neuropathies; Microvascular and macrovascular
1. Microvascular
I. Hyperglycemic neuropathy
II. Acute painful sensory neuropathy
III. Sensory motor polyneuropathy
IV. Mononeuropathy
V. Diabetic truncal neuropathy
VI. Proximal diabetic neuropathy
VII. Autonomic neuropathy
2. Macrovascular
I. TIA & Strokes
Hyperglycemic neuropathy
This is common among newly diagnosed or poorly controlled diabetic patients. This is a very uncomfortable dysasthesiae affecting feet and lower legs. This condition is rapidly resolved with the establishment of euglycemia.
Acute painful sensory neuropathy
This condition is common among diabetic male whose glycemic control is poor. The patient will experience burning and aching pain. There is a widespread Cutaneous contact hyperesthesia. This is associated with depression and impotence. Proper control of blood sugar is the treatment.
Mononeuropathy
This is a dysfunction of isolated cranial or peripheral Nerves and it is less common than polyneuropathy in DM and presents with pain and motor weakness in the distribution of a single nerve. A vascular etiology has been suggested, but the pathogenesis is unknown. Involvement of the third cranial nerve is most common and is heralded by diplopia.
Diabetic truncal neuropathy
This occurs in thoracic nerve roots and it could be unilateral. Patient may have symptoms of chest pain or abdominal pain. This is commonly associated with Sensory motor and autonomic neuropathy
Proximal diabetic neuropathy/ proximal amyotrophy
• Involvement of lumbo - sacral nerves
• Metabolic in origin
• Middle aged or elderly
• Symptoms unilaterally or bilaterally
• Clinical features
• Prognosis - Good
Autonomic neuropathy
• Prevalence increases with poor control of DM and longer duration
• Poor prognostic indicator
• Symptoms
– Gustatory sweating
– Postural hypotension
– Diarrhoea alternating constipation
– Anhidrosis of limbs
– Small pupil
– Dysphagia and vomiting due to gastroparesis
– Impotence
TIA & Strokes
• Commonest brain disorder responsible for deaths and disability of adults.
• What are the risk factors?
• What are the clinical features?
• Characteristic feature is sudden onset of symptoms with maximum disability in the acute stage
Treatment
• Near normal glycaemic control
– DCCT -Reduced clinical neuropathy by 60% in Type I
– UKPDS - Reduced micro vascular complications by 25% in Type II
• Prevention of foot damage
– Screening
• Drugs
– Amitriptyline - Side effects
– Imipramine
– Carbemazepine
– Phenytoin
– GLA
Diabetic Retinopathy
Introduction
Diabetes is the leading cause of blindness between the ages of 20 and 74 years.
Individuals with DM are 25 times more likely to become legally blind than individuals without DM. Blindness is primarily the result of progressive diabetic retinopathy and clinically significant macular edema.
Pathogenesis
Diabetic retinopathy is a microvascular disease that leads to capillary occlusion. It affects the retinal precapillary, arterioles, capillaries and venules. Early pathological features include thickening of the basement membrane, loss of pericytes and the development of microaneurysms. Persistent hyperglycemia is considered to be the primary cause of changes in the vascular endothelium. The end result is an ischaemic retina, which releases cytokines that promote the growth of new blood vessels, particularly vascular endothelial growth factor, which is also involved in the early stages of increased vascular permeability.
Risk factors
1. Duration of diabetes
2. Poor control
3. Pregnancy
4. Hypertension
5. Hyperlipidaemia
6. Nephropathy
7. Cataract surgery
Classification
Diabetic retinopathy is classified into two stages:
1. Nonproliferative
2. Proliferative.
1. Nonproliferative diabetic retinopathy
This usually appears late in the first decade or early in the second decade of the disease and is marked by retinal vascular microaneurysms, blot hemorrhages, and cotton wool spots. Mild nonproliferative retinopathy progresses to more extensive disease, characterized by changes in venous vessel caliber, intraretinal microvascular abnormalities, and more numerous microaneurysms and hemorrhages.
2. proliferative diabetic retinopathy
The appearance of neovascularization in response to retinal hypoxia is the hallmark of proliferative diabetic retinopathy. These newly formed vessels appear near the optic nerve and/or macula and rupture easily, leading to vitreous hemorrhage, fibrosis, and ultimately retinal detachment.
Management
1. Control of risk factors delays the onset of retinopathy and can slow progression of the disease
2. Laser treatment is the only known means of stopping the progression of diabetic eye disease.
Screening
It is important to screen all patients with diabetes for eye disease. It can prevent blindness and has been shown to be cost-effective. The GP, the optometrist or the diabetologist may undertake this, depending on local policy.
Diabetes is the leading cause of blindness between the ages of 20 and 74 years.
Individuals with DM are 25 times more likely to become legally blind than individuals without DM. Blindness is primarily the result of progressive diabetic retinopathy and clinically significant macular edema.
Pathogenesis
Diabetic retinopathy is a microvascular disease that leads to capillary occlusion. It affects the retinal precapillary, arterioles, capillaries and venules. Early pathological features include thickening of the basement membrane, loss of pericytes and the development of microaneurysms. Persistent hyperglycemia is considered to be the primary cause of changes in the vascular endothelium. The end result is an ischaemic retina, which releases cytokines that promote the growth of new blood vessels, particularly vascular endothelial growth factor, which is also involved in the early stages of increased vascular permeability.
Risk factors
1. Duration of diabetes
2. Poor control
3. Pregnancy
4. Hypertension
5. Hyperlipidaemia
6. Nephropathy
7. Cataract surgery
Classification
Diabetic retinopathy is classified into two stages:
1. Nonproliferative
2. Proliferative.
1. Nonproliferative diabetic retinopathy
This usually appears late in the first decade or early in the second decade of the disease and is marked by retinal vascular microaneurysms, blot hemorrhages, and cotton wool spots. Mild nonproliferative retinopathy progresses to more extensive disease, characterized by changes in venous vessel caliber, intraretinal microvascular abnormalities, and more numerous microaneurysms and hemorrhages.
2. proliferative diabetic retinopathy
The appearance of neovascularization in response to retinal hypoxia is the hallmark of proliferative diabetic retinopathy. These newly formed vessels appear near the optic nerve and/or macula and rupture easily, leading to vitreous hemorrhage, fibrosis, and ultimately retinal detachment.
Management
1. Control of risk factors delays the onset of retinopathy and can slow progression of the disease
2. Laser treatment is the only known means of stopping the progression of diabetic eye disease.
Screening
It is important to screen all patients with diabetes for eye disease. It can prevent blindness and has been shown to be cost-effective. The GP, the optometrist or the diabetologist may undertake this, depending on local policy.
DIABETIC FOOT
Introduction
This is a serious burden for both the patient and physician. Once it occurs, it is very difficult to treat. Therefore prevention is the best option.
Prevalence and prognosis
1. 5-15% of Diabetics develop foot ulcers
2. 70% of healed Diabetic ulcer are likely to recur within 5 years
3. 85% of non traumatic lower limb amputations follow diabetic foot ulcers
Why do Diabetics sustain trauma to feet?
There are two main factors which make the diabetic patient more susceptible for trauma
1. Extrinsic
I. Poor vision
II. Falls due to joint immobility
III. strokes
IV. Edema due to Cardiac causes
2. Intrinsic
I. Neuropathy
II. Arterial Disease
III. Abnormal tissue response to trauma and sepsis
I) Neuropathy
a. Sensory – loss of pressure, pain, temperature and joint sense. i.e. removes warning signals
b. Motor – weakness and atrophy of intrinsic muscles of foot, hence altered foot structure and leading to deformity and altered biomechanics
c. Autonomic – AV shunting affects maintenance of skin integrity and vascular tone. i.e. warm, dry, fissured foot
What is Charcot foot?
This is the extreme end of diabetic foot disease. This occurs due to the long standing neuropathy. Other factors that contribute to charcot foot are as follows;
a) Long duration Diabetic neuropathy
b) Hyperaemic response
c) Osteopenia
d) Local fractures
e) Inflammatory response
f) Proprioception – Deformity
g) 0.2% of Diabetics
II) Arterial Disease
There are two types;
A. Macrovascular
B. Microvascular
A) Macrovascular Disease
Atherosclerosis is the main form of macrovascular disease affecting the foot and it increases the risk 4 to 20 times than in non-diabetics. In atherosclerosis;
Systemic disease Coronaries, Cerebrals
Calcification Unreliable AB index
Collateral disease Poor reserve
Angiography often foot vessels preserved
B) Microvascular Disease
1. Early onset of micro-vascular dysfunction
2. Affects arterioles an capillaries of several organs
3. Basement membrane thickening may impair oxygen diffusion
4. Reduced tissue response to sepsis
Wound healing is affected by...
Growth factors deficiency
Impaired fibroblast response
Abnormalities of Extracellular matrix
Neuroinflammatory response
Hyperaemic response
Thermoregulatory response
Diabetic foot Infections
Cell mediated immunity depressed
Phagocytic function of multinuclear leukocytes affected
Leucocyte migration at microcirculatory level is affected
Hyperglycaemia associated with mycotic infections could contribute
Painless collection of pus
Tracking of pus along tendon sheaths
Staphylococcus aureus is common
Foot compartments
CLINICAL ASSESSMENT OF A DIABETIC FOOT
A) General
Glycaemic control
Smoking
Renal disease
Poor social circumstance
B) Extent of Neuropathy
Vibration sense – using tuning fork
Discriminating touch – 10g monofilament Nylon
Ankle jerks
C) Extent of Ischaemia
Pulse examination – Aortoiliac and FemPop bruits
Skin color, Temperature
ABPI
X ray medial calcinosis
D) Extent of Neuroischaemia and sepsis
Wargner 1-5 a Global Severity Score
1: Superficial ulceration limited to dermis
2: Ulceration down to fascia or bone without abscess or osteomyelitis
3: Deep ulcers with abscess or osteomyelitis
4: Localized gangrene confined to the toes or forefoot
5: Gangrene requiring immediate major (above ankle) amputation
Extent of Infection Is Due to..
Walking on pus
Tracking of pus along tendons
Foot compartments
Septicaemia
This is a serious burden for both the patient and physician. Once it occurs, it is very difficult to treat. Therefore prevention is the best option.
Prevalence and prognosis
1. 5-15% of Diabetics develop foot ulcers
2. 70% of healed Diabetic ulcer are likely to recur within 5 years
3. 85% of non traumatic lower limb amputations follow diabetic foot ulcers
Why do Diabetics sustain trauma to feet?
There are two main factors which make the diabetic patient more susceptible for trauma
1. Extrinsic
I. Poor vision
II. Falls due to joint immobility
III. strokes
IV. Edema due to Cardiac causes
2. Intrinsic
I. Neuropathy
II. Arterial Disease
III. Abnormal tissue response to trauma and sepsis
I) Neuropathy
a. Sensory – loss of pressure, pain, temperature and joint sense. i.e. removes warning signals
b. Motor – weakness and atrophy of intrinsic muscles of foot, hence altered foot structure and leading to deformity and altered biomechanics
c. Autonomic – AV shunting affects maintenance of skin integrity and vascular tone. i.e. warm, dry, fissured foot
What is Charcot foot?
This is the extreme end of diabetic foot disease. This occurs due to the long standing neuropathy. Other factors that contribute to charcot foot are as follows;
a) Long duration Diabetic neuropathy
b) Hyperaemic response
c) Osteopenia
d) Local fractures
e) Inflammatory response
f) Proprioception – Deformity
g) 0.2% of Diabetics
II) Arterial Disease
There are two types;
A. Macrovascular
B. Microvascular
A) Macrovascular Disease
Atherosclerosis is the main form of macrovascular disease affecting the foot and it increases the risk 4 to 20 times than in non-diabetics. In atherosclerosis;
Systemic disease Coronaries, Cerebrals
Calcification Unreliable AB index
Collateral disease Poor reserve
Angiography often foot vessels preserved
B) Microvascular Disease
1. Early onset of micro-vascular dysfunction
2. Affects arterioles an capillaries of several organs
3. Basement membrane thickening may impair oxygen diffusion
4. Reduced tissue response to sepsis
Wound healing is affected by...
Growth factors deficiency
Impaired fibroblast response
Abnormalities of Extracellular matrix
Neuroinflammatory response
Hyperaemic response
Thermoregulatory response
Diabetic foot Infections
Cell mediated immunity depressed
Phagocytic function of multinuclear leukocytes affected
Leucocyte migration at microcirculatory level is affected
Hyperglycaemia associated with mycotic infections could contribute
Painless collection of pus
Tracking of pus along tendon sheaths
Staphylococcus aureus is common
Foot compartments
CLINICAL ASSESSMENT OF A DIABETIC FOOT
A) General
Glycaemic control
Smoking
Renal disease
Poor social circumstance
B) Extent of Neuropathy
Vibration sense – using tuning fork
Discriminating touch – 10g monofilament Nylon
Ankle jerks
C) Extent of Ischaemia
Pulse examination – Aortoiliac and FemPop bruits
Skin color, Temperature
ABPI
X ray medial calcinosis
D) Extent of Neuroischaemia and sepsis
Wargner 1-5 a Global Severity Score
1: Superficial ulceration limited to dermis
2: Ulceration down to fascia or bone without abscess or osteomyelitis
3: Deep ulcers with abscess or osteomyelitis
4: Localized gangrene confined to the toes or forefoot
5: Gangrene requiring immediate major (above ankle) amputation
Extent of Infection Is Due to..
Walking on pus
Tracking of pus along tendons
Foot compartments
Septicaemia
Diabetes insipidus
Clinical Characteristics
Decreased secretion or action of AVP usually manifests as DI, a syndrome characterized by the production of abnormally large volumes of dilute urine. The 24-h urine volume is >50 mL/kg body weight and the osmolarity is <300 mosmol/L. The polyuria produces symptoms of urinary frequency, enuresis, and/or nocturia, which may disturb sleep and cause mild daytime fatigue or somnolence. It is also associated with thirst and a commensurate increase in fluid intake (polydipsia). Clinical signs of dehydration are uncommon unless fluid intake is impaired.
Etiology
Deficient secretion of AVP can be primary or secondary. The primary form usually results from agenesis or irreversible destruction of the neurohypophysis and is variously referred to as neurohypophyseal DI, pituitary DI, or central DI.
Pathophysiology
When the secretion or action of AVP is reduced to <80>
Decreased secretion or action of AVP usually manifests as DI, a syndrome characterized by the production of abnormally large volumes of dilute urine. The 24-h urine volume is >50 mL/kg body weight and the osmolarity is <300 mosmol/L. The polyuria produces symptoms of urinary frequency, enuresis, and/or nocturia, which may disturb sleep and cause mild daytime fatigue or somnolence. It is also associated with thirst and a commensurate increase in fluid intake (polydipsia). Clinical signs of dehydration are uncommon unless fluid intake is impaired.
Etiology
Deficient secretion of AVP can be primary or secondary. The primary form usually results from agenesis or irreversible destruction of the neurohypophysis and is variously referred to as neurohypophyseal DI, pituitary DI, or central DI.
Pathophysiology
When the secretion or action of AVP is reduced to <80>
Male Erectile Failure and Diabetes
Erectile failure is particularly common in men with diabetes;
it affects up to 30%, and the prevalence increases further
with age, duration of diabetes, and the presence of microvascular
and macrovascular complications. It can be distressing
for both the man and his partner. There is now increasing
awareness of the importance of the problem, and the increased
effi cacy and availability of treatment makes it correctable
in more than 80% of cases.
Why is erectile dysfunction so common in men
with diabetes?
Normal erectile function is physiologically complex. It depends
on:
• normal psychological and endocrine status for libido and
arousal
• neural integrity
• normally responsive corpora cavernosal smooth muscle
• adequate arterial infl ow
• adequate veno-occlusive mechanisms.
These factors are all vulnerable in diabetes and its complications.
• Diabetes may cause psychological problems, and concomitant
endocrine and other disorders can also reduce libido and
arousal.
• Poor metabolic control, autonomic neuropathy, peripheral
vascular disease and cardiovascular risk factors such as
smoking and dyslipidaemia may all contribute.
• Hypertension is common in type 2 diabetes and, together
with increasingly intensive antihypertensive drug regimens,
may disturb erectile function.
• Corpora cavernosal smooth muscle may be directly affected
by microvascular disease and impaired endothelial cellmediated
relaxation.
• Other primary penile problems (e.g. balanitis, phimosis,
Peyronie’s disease) may be associated with diabetes.
Awareness, assessment and investigation
Diabetes service providers should screen high-risk men, or
should at least have posters on display and information leafl ets
available, to make men aware of the fact that the team is
cognizant of erectile dysfunction and can offer help.
History and examination
History and examination are essential. Clinicians should
ascertain the extent and likely causes of the problem, to enable
them to give an informed explanation and constructive
advice to patients, and to determine the appropriate treatment.
The history and examination (which must include the genitalia)
should determine the patient’s general health, degree of
metabolic control and complication status, and the relevance
of associated conditions.
The sexual history should aim to answer the following
questions.
• What exactly is the problem?
• Why is it a problem?
• What is the partner’s attitude?
• What does the patient and/or partner want to be done about
the problem?
Investigations
Investigations are necessary only when the history or examination
suggests a specifi c cause (e.g. endocrine) or further
assessment of associated conditions (particularly cardiovascular
disease and risk factors) is required. Many possible penile
investigations are listed in the literature (e.g. nocturnal tumescence
tests, cavernosography), but their results do not influence
initial medical treatment and they can be reserved
for research or further assessment before surgical corrective
treatment.
it affects up to 30%, and the prevalence increases further
with age, duration of diabetes, and the presence of microvascular
and macrovascular complications. It can be distressing
for both the man and his partner. There is now increasing
awareness of the importance of the problem, and the increased
effi cacy and availability of treatment makes it correctable
in more than 80% of cases.
Why is erectile dysfunction so common in men
with diabetes?
Normal erectile function is physiologically complex. It depends
on:
• normal psychological and endocrine status for libido and
arousal
• neural integrity
• normally responsive corpora cavernosal smooth muscle
• adequate arterial infl ow
• adequate veno-occlusive mechanisms.
These factors are all vulnerable in diabetes and its complications.
• Diabetes may cause psychological problems, and concomitant
endocrine and other disorders can also reduce libido and
arousal.
• Poor metabolic control, autonomic neuropathy, peripheral
vascular disease and cardiovascular risk factors such as
smoking and dyslipidaemia may all contribute.
• Hypertension is common in type 2 diabetes and, together
with increasingly intensive antihypertensive drug regimens,
may disturb erectile function.
• Corpora cavernosal smooth muscle may be directly affected
by microvascular disease and impaired endothelial cellmediated
relaxation.
• Other primary penile problems (e.g. balanitis, phimosis,
Peyronie’s disease) may be associated with diabetes.
Awareness, assessment and investigation
Diabetes service providers should screen high-risk men, or
should at least have posters on display and information leafl ets
available, to make men aware of the fact that the team is
cognizant of erectile dysfunction and can offer help.
History and examination
History and examination are essential. Clinicians should
ascertain the extent and likely causes of the problem, to enable
them to give an informed explanation and constructive
advice to patients, and to determine the appropriate treatment.
The history and examination (which must include the genitalia)
should determine the patient’s general health, degree of
metabolic control and complication status, and the relevance
of associated conditions.
The sexual history should aim to answer the following
questions.
• What exactly is the problem?
• Why is it a problem?
• What is the partner’s attitude?
• What does the patient and/or partner want to be done about
the problem?
Investigations
Investigations are necessary only when the history or examination
suggests a specifi c cause (e.g. endocrine) or further
assessment of associated conditions (particularly cardiovascular
disease and risk factors) is required. Many possible penile
investigations are listed in the literature (e.g. nocturnal tumescence
tests, cavernosography), but their results do not influence
initial medical treatment and they can be reserved
for research or further assessment before surgical corrective
treatment.
Management of erectile dysfunction in diabetic patients
Management
Some men are satisfied with just an explanation of their
erectile failure, but many want treatment to correct the problem.
Some men regain normal function after regular physical
treatments.
Counselling
General counselling is an important adjunct to all treatments,
to help the patient overcome anxiety and understand any
relationship problems. It is helpful if the patient’s partner is
present at the discussion.
Partner communication and performance anxiety may
be helped by discussing the modifi ed Masters and Johnson
‘sensate focusing’ technique.
Psychosexual therapy
In most men with diabetes, erectile dysfunction has an organic
basis and psychosexual therapy alone has little place in
treatment. However, it should be considered essential in men
with general psychological or relationship problems of which
erectile dysfunction is just a part. (Physical treatments can be
of major benefit in men with predominantly psychological
causes of erectile dysfunction.)
Viagra (sildenafi l citrate)
Until recently, results of treatment with tablets and/or topical
creams have been disappointing. Treatment has been revolutionized
by the availability of Viagra, which is successful in
more than 60% of men with type 1 or type 2 diabetes and is
now the usual treatment of choice. Sildenafi l is a phosphodiesterase
5 inhibitor that relatively specifically increases
cyclic GMP activity and thereby smooth muscle relaxation
in the corpora cavernosa. It requires sexual arousal, and
thus activation of the nitric oxide pathway, to be effective.
Men should start with a dose of 50 mg, but most require
100 mg tablets. Side-effects of dyspepsia, fl ushing or dizziness
are usually minimal. Concomitant use of nitrates is
an absolute contraindication, but in some men discontinuing
or replacing them can be considered. The presence of
cardiovascular disease or multiple risk factors is not a
contraindication to use of Viagra. Viagra should be tried on
at least six occasions before it is abandoned as ineffective.
Other agents
Other oral and topical agents, including newer agents such
as apomorphine, remain disappointing in diabetes-related
erectile dysfunction. Newer phosphodiesterase inhibitors are
under development.
Intracorporeal self-injection therapy
Intracorporeal self-injection therapy (Figures 1 and 2) continues
to be a useful and effective second-line treatment. It
is well tolerated, and is easy and painless to administer. Men
should be carefully taught the technique and advised to use
only the lowest effective dose, to prevent a prolonged erection
(> 6 hours) that may require emergency aspiration detumescence.
Complications include bruising, fi brosis (uncommon)
and discomfort in the erect penis. Alprostadil remains the
preferred drug, and is available as Caverject and Viridal.
Both are available in dual-chamber injector devices; Caverject
Dual Chamber is the simplest preparation to use. Other drugs
and combinations, including papaverine, phentolamine and
vasoactive intestinal peptide, can be considered, but are not
currently licensed.
Medicated urethral system for erection (MUSE)
MUSE was developed as an alternative to injection therapy. A
high-dose alprostadil pellet (500 or 100 ｵg) is placed into
the urethra using a special introducer, and diffuses into the
corpora cavernosa. This treatment is not very effective in
men with diabetes, and discomfort and lack of effi cacy limit
its usefulness.
Vacuum tumescence devices
Vacuum tumescence devices (Figure 3) are effective and well
tolerated. A cylinder with an attached vacuum pump is placed
over the penis and used to create an ‘erectile state’. A retention
band is then slipped off the cylinder and onto the base
of the penis to maintain the erection.
Surgical treatment
Surgical referral for the insertion of a penile prosthesis can
be considered, but this is now usually reserved for men who
have failed to respond to medical treatments or who have
structural penile abnormalities requiring such treatment. Prostheses
may be semi-rigid or infl atable.
Microvascular revascularization techniques remain largely
experimental.
Some men are satisfied with just an explanation of their
erectile failure, but many want treatment to correct the problem.
Some men regain normal function after regular physical
treatments.
Counselling
General counselling is an important adjunct to all treatments,
to help the patient overcome anxiety and understand any
relationship problems. It is helpful if the patient’s partner is
present at the discussion.
Partner communication and performance anxiety may
be helped by discussing the modifi ed Masters and Johnson
‘sensate focusing’ technique.
Psychosexual therapy
In most men with diabetes, erectile dysfunction has an organic
basis and psychosexual therapy alone has little place in
treatment. However, it should be considered essential in men
with general psychological or relationship problems of which
erectile dysfunction is just a part. (Physical treatments can be
of major benefit in men with predominantly psychological
causes of erectile dysfunction.)
Viagra (sildenafi l citrate)
Until recently, results of treatment with tablets and/or topical
creams have been disappointing. Treatment has been revolutionized
by the availability of Viagra, which is successful in
more than 60% of men with type 1 or type 2 diabetes and is
now the usual treatment of choice. Sildenafi l is a phosphodiesterase
5 inhibitor that relatively specifically increases
cyclic GMP activity and thereby smooth muscle relaxation
in the corpora cavernosa. It requires sexual arousal, and
thus activation of the nitric oxide pathway, to be effective.
Men should start with a dose of 50 mg, but most require
100 mg tablets. Side-effects of dyspepsia, fl ushing or dizziness
are usually minimal. Concomitant use of nitrates is
an absolute contraindication, but in some men discontinuing
or replacing them can be considered. The presence of
cardiovascular disease or multiple risk factors is not a
contraindication to use of Viagra. Viagra should be tried on
at least six occasions before it is abandoned as ineffective.
Other agents
Other oral and topical agents, including newer agents such
as apomorphine, remain disappointing in diabetes-related
erectile dysfunction. Newer phosphodiesterase inhibitors are
under development.
Intracorporeal self-injection therapy
Intracorporeal self-injection therapy (Figures 1 and 2) continues
to be a useful and effective second-line treatment. It
is well tolerated, and is easy and painless to administer. Men
should be carefully taught the technique and advised to use
only the lowest effective dose, to prevent a prolonged erection
(> 6 hours) that may require emergency aspiration detumescence.
Complications include bruising, fi brosis (uncommon)
and discomfort in the erect penis. Alprostadil remains the
preferred drug, and is available as Caverject and Viridal.
Both are available in dual-chamber injector devices; Caverject
Dual Chamber is the simplest preparation to use. Other drugs
and combinations, including papaverine, phentolamine and
vasoactive intestinal peptide, can be considered, but are not
currently licensed.
Medicated urethral system for erection (MUSE)
MUSE was developed as an alternative to injection therapy. A
high-dose alprostadil pellet (500 or 100 ｵg) is placed into
the urethra using a special introducer, and diffuses into the
corpora cavernosa. This treatment is not very effective in
men with diabetes, and discomfort and lack of effi cacy limit
its usefulness.
Vacuum tumescence devices
Vacuum tumescence devices (Figure 3) are effective and well
tolerated. A cylinder with an attached vacuum pump is placed
over the penis and used to create an ‘erectile state’. A retention
band is then slipped off the cylinder and onto the base
of the penis to maintain the erection.
Surgical treatment
Surgical referral for the insertion of a penile prosthesis can
be considered, but this is now usually reserved for men who
have failed to respond to medical treatments or who have
structural penile abnormalities requiring such treatment. Prostheses
may be semi-rigid or infl atable.
Microvascular revascularization techniques remain largely
experimental.
Diabetes and Hypertension
Hypertension occurs more often in patients with diabetes
than in individuals without diabetes. This 1.5–2-fold excess
of hypertension can be accounted for by several clinical and
pathophysiological factors including diabetic nephropathy,
altered neuroendocrine and sodium-volume determinants of
blood pressure, disturbed vascular tone and altered blood
pressure regulation (Figure 1). Hypertension is also a major
cause of diabetic nephropathy. The prevalence of hypertension
in type 2 diabetes has been reported to be 30–80%.
In type 1 diabetes, the prevalence is up to 25%, and hypertension
is usually seen in association with nephropathy.
Importance of hypertension in diabetes
Hypertension is important in diabetes mellitus because it accelerates
both macrovascular (ischaemic heart disease, stroke,
peripheral arterial disease, heart failure) and microvascular
complications. The presence of proteinuria (i.e. diabetic
nephropathy) is associated with a marked increase in overall
mortality from cardiovascular disease and end-stage renal
failure. Most diabetic complications occur in association with
hypertension. Cardiovascular complications account for up
to 75% of mortality in patients with type 2 diabetes.
What level of blood pressure requires treatment?
The most recent guidelines (Figure 2) have incorporated findings
from the major hypertension intervention trials that have
data specific for patients with diabetes (Figure 3).
In the UK Prospective Diabetes Study (UKPDS), patients
with type 2 diabetes (mean age 56 years) were treated for
8.4 years with either a β-blocker or an angiotensin-converting
enzyme (ACE) inhibitor-based regimen to achieve ‘tight’ blood
pressure control (mean 144/82 mm Hg). Compared with less
tight control (mean 154/87 mm Hg), there were significant
reductions in diabetes-related deaths (32%), stroke (44%),
heart failure (56%) and progression of retinopathy (37%), despite
drug side-effects and compliance problems. This study
showed that the clinical benefit of reducing blood pressure by
10/5 mm Hg was greater than that of intensive glucose lowering.
The lower blood pressure required mainly combination
therapy and not any specific single-drug treatment, there
was no threshold or ‘J-shaped’ effect of treatment, and the
benefits of treatment exceeded the benefits expected from
epidemiological data.
The Hypertension Optimal Treatment (HOT) study con-
firmed a reduction in cardiovascular events with combination
treatment, based on a calcium channel blocker (felodipine)
regimen. Treatment targets were diastolic blood pressure less
than 80 mm Hg, less than 85 mm Hg and less than 90 mm Hg.
The 4 mm Hg difference between the less than 80 mm Hg and
less than 90 mm Hg target groups was associated with a 51%
reduction in major cardiovascular events and a 67% reduction
in cardiovascular mortality. New findings were the additional
cardiovascular benefit of the addition of aspirin,
75 mg, and the safety of calcium channel blocker therapy.
Management
Non-drug treatment (Figure 4)
In combination with maximal diabetic control and attention
to other cardiovascular risk factors, non-drug treatments
(weight loss for obesity-related hypertension and aerobic
exercise) confer benefit. Reduction in dietary sodium intake
significantly reduces both systolic and diastolic blood
pressure.
than in individuals without diabetes. This 1.5–2-fold excess
of hypertension can be accounted for by several clinical and
pathophysiological factors including diabetic nephropathy,
altered neuroendocrine and sodium-volume determinants of
blood pressure, disturbed vascular tone and altered blood
pressure regulation (Figure 1). Hypertension is also a major
cause of diabetic nephropathy. The prevalence of hypertension
in type 2 diabetes has been reported to be 30–80%.
In type 1 diabetes, the prevalence is up to 25%, and hypertension
is usually seen in association with nephropathy.
Importance of hypertension in diabetes
Hypertension is important in diabetes mellitus because it accelerates
both macrovascular (ischaemic heart disease, stroke,
peripheral arterial disease, heart failure) and microvascular
complications. The presence of proteinuria (i.e. diabetic
nephropathy) is associated with a marked increase in overall
mortality from cardiovascular disease and end-stage renal
failure. Most diabetic complications occur in association with
hypertension. Cardiovascular complications account for up
to 75% of mortality in patients with type 2 diabetes.
What level of blood pressure requires treatment?
The most recent guidelines (Figure 2) have incorporated findings
from the major hypertension intervention trials that have
data specific for patients with diabetes (Figure 3).
In the UK Prospective Diabetes Study (UKPDS), patients
with type 2 diabetes (mean age 56 years) were treated for
8.4 years with either a β-blocker or an angiotensin-converting
enzyme (ACE) inhibitor-based regimen to achieve ‘tight’ blood
pressure control (mean 144/82 mm Hg). Compared with less
tight control (mean 154/87 mm Hg), there were significant
reductions in diabetes-related deaths (32%), stroke (44%),
heart failure (56%) and progression of retinopathy (37%), despite
drug side-effects and compliance problems. This study
showed that the clinical benefit of reducing blood pressure by
10/5 mm Hg was greater than that of intensive glucose lowering.
The lower blood pressure required mainly combination
therapy and not any specific single-drug treatment, there
was no threshold or ‘J-shaped’ effect of treatment, and the
benefits of treatment exceeded the benefits expected from
epidemiological data.
The Hypertension Optimal Treatment (HOT) study con-
firmed a reduction in cardiovascular events with combination
treatment, based on a calcium channel blocker (felodipine)
regimen. Treatment targets were diastolic blood pressure less
than 80 mm Hg, less than 85 mm Hg and less than 90 mm Hg.
The 4 mm Hg difference between the less than 80 mm Hg and
less than 90 mm Hg target groups was associated with a 51%
reduction in major cardiovascular events and a 67% reduction
in cardiovascular mortality. New findings were the additional
cardiovascular benefit of the addition of aspirin,
75 mg, and the safety of calcium channel blocker therapy.
Management
Non-drug treatment (Figure 4)
In combination with maximal diabetic control and attention
to other cardiovascular risk factors, non-drug treatments
(weight loss for obesity-related hypertension and aerobic
exercise) confer benefit. Reduction in dietary sodium intake
significantly reduces both systolic and diastolic blood
pressure.
Surgery in Patients with Diabetes
Diabetes presents several special problems during surgery.
Fasting causes particular problems in type 1 diabetes. Such
patients need basal insulin to prevent ketosis, and develop
hypoglycaemia without additional carbohydrate intake. Fasting
is of little signifi cance in type 2 diabetes, unless the patient
has received oral hypoglycaemic agents.
Metabolic changes include the following.
• Increases in circulating adrenaline, adrenocorticotrophic
hormone, cortisol and growth hormone aggravate insulin
defi ciency and insulin resistance. These changes are a normal
response to surgery and proportional to the severity of
the operation. They antagonize the actions of insulin and its
secretion, resulting in catabolism with increased glycogenolysis,
gluconeogenesis, proteolysis and lipolysis. In diabetes,
the effects are compounded by insulin defi ciency.
• Gluconeogenesis from precursors such as lactate, pyruvate,
alanine and glutamine is increased in the liver and kidney,
and muscle and adipose tissue take up less glucose. The resultant
hyperglycaemia is more pronounced in patients with
diabetes than in non-diabetic patients.
• Without insulin, lipolysis is stimulated and leads to ketogenesis.
Plasma levels of free fatty acids, glycerol and ketone
bodies increase, and metabolic acidosis may develop even in
the presence of near-normal plasma glucose.
All these changes are aggravated by some types of anaesthesia,
particularly high doses of opiates or regional blockade.
They increase insulin requirements in patients with type 1
diabetes, and may cause those with type 2 diabetes to become
temporarily insulin-requiring.
Recognizing hypoglycaemia may be difficult in unconscious
patients.
Subcutaneous insulin absorption is poor or unpredictable
when peripheral vessels are constricted.
Principles of management
The fundamental principle of surgical management in diabetes
is that capillary blood glucose is measured regularly and
accurately, and that these results are recorded and acted on.
Most problems occur because staff have forgotten to measure
blood glucose, or because very low values have been ignored
or wrongly attributed to faulty meters.
Target glucose – during surgery, blood glucose should be
7–11 mmol/litre. At normal levels, patients are too close to
hypoglycaemia. At levels above 11 mmol/litre, urine output
increases and dehydration may ensue.
Fluids – any other fl uids given during the surgical period
should not contain glucose. Use of Hartmann’s solution
(Ringer lactate) in patients with diabetes remains controversial.
The lactate contained in this crystalloid is used for
gluconeogenesis, particularly in starved or catabolic patients.
In patients with type 2 diabetes, an infusion of Hartmann’s
solution may cause blood glucose levels to rise signifi cantly.
If fluids have to be restricted, glucose may be given as a
20% or 50% solution. This must be administered via a central
venous catheter, to avoid venous thrombosis.
Electrolytes – potassium levels should be monitored regularly
perioperatively. Serum potassium varies according to:
• the effects of insulin, which promotes potassium uptake
by muscle, liver and adipose tissue
• dehydration, which may cause a shift in potassium from
the intracellular to the extracellular space
• acidosis, which leads to hydrogen and potassium exchange
in the kidneys, potassium retention and hyperkalaemia.
Most patients with normal renal function require 20 mmol
potassium/litre fl uid given, but the requirement is often higher
in patients with diabetes.
Analgesia – in the past, there was a view among anaesthetists
that regional blockade (including spinal and epidural)
was undesirable in diabetes. This originated from fear
of aggravating (possibly latent) neuropathy, of uncontrolled
hypotension in those with signifi cant autonomic neuropathy,
or of causing infection at the site of the block. This view is no
longer valid. The advantages of regional blockade, which provides
excellent analgesia and blunting of the stress response,
outweigh any disadvantages in most patients with diabetes.
Fasting causes particular problems in type 1 diabetes. Such
patients need basal insulin to prevent ketosis, and develop
hypoglycaemia without additional carbohydrate intake. Fasting
is of little signifi cance in type 2 diabetes, unless the patient
has received oral hypoglycaemic agents.
Metabolic changes include the following.
• Increases in circulating adrenaline, adrenocorticotrophic
hormone, cortisol and growth hormone aggravate insulin
defi ciency and insulin resistance. These changes are a normal
response to surgery and proportional to the severity of
the operation. They antagonize the actions of insulin and its
secretion, resulting in catabolism with increased glycogenolysis,
gluconeogenesis, proteolysis and lipolysis. In diabetes,
the effects are compounded by insulin defi ciency.
• Gluconeogenesis from precursors such as lactate, pyruvate,
alanine and glutamine is increased in the liver and kidney,
and muscle and adipose tissue take up less glucose. The resultant
hyperglycaemia is more pronounced in patients with
diabetes than in non-diabetic patients.
• Without insulin, lipolysis is stimulated and leads to ketogenesis.
Plasma levels of free fatty acids, glycerol and ketone
bodies increase, and metabolic acidosis may develop even in
the presence of near-normal plasma glucose.
All these changes are aggravated by some types of anaesthesia,
particularly high doses of opiates or regional blockade.
They increase insulin requirements in patients with type 1
diabetes, and may cause those with type 2 diabetes to become
temporarily insulin-requiring.
Recognizing hypoglycaemia may be difficult in unconscious
patients.
Subcutaneous insulin absorption is poor or unpredictable
when peripheral vessels are constricted.
Principles of management
The fundamental principle of surgical management in diabetes
is that capillary blood glucose is measured regularly and
accurately, and that these results are recorded and acted on.
Most problems occur because staff have forgotten to measure
blood glucose, or because very low values have been ignored
or wrongly attributed to faulty meters.
Target glucose – during surgery, blood glucose should be
7–11 mmol/litre. At normal levels, patients are too close to
hypoglycaemia. At levels above 11 mmol/litre, urine output
increases and dehydration may ensue.
Fluids – any other fl uids given during the surgical period
should not contain glucose. Use of Hartmann’s solution
(Ringer lactate) in patients with diabetes remains controversial.
The lactate contained in this crystalloid is used for
gluconeogenesis, particularly in starved or catabolic patients.
In patients with type 2 diabetes, an infusion of Hartmann’s
solution may cause blood glucose levels to rise signifi cantly.
If fluids have to be restricted, glucose may be given as a
20% or 50% solution. This must be administered via a central
venous catheter, to avoid venous thrombosis.
Electrolytes – potassium levels should be monitored regularly
perioperatively. Serum potassium varies according to:
• the effects of insulin, which promotes potassium uptake
by muscle, liver and adipose tissue
• dehydration, which may cause a shift in potassium from
the intracellular to the extracellular space
• acidosis, which leads to hydrogen and potassium exchange
in the kidneys, potassium retention and hyperkalaemia.
Most patients with normal renal function require 20 mmol
potassium/litre fl uid given, but the requirement is often higher
in patients with diabetes.
Analgesia – in the past, there was a view among anaesthetists
that regional blockade (including spinal and epidural)
was undesirable in diabetes. This originated from fear
of aggravating (possibly latent) neuropathy, of uncontrolled
hypotension in those with signifi cant autonomic neuropathy,
or of causing infection at the site of the block. This view is no
longer valid. The advantages of regional blockade, which provides
excellent analgesia and blunting of the stress response,
outweigh any disadvantages in most patients with diabetes.
Psychological Aspects of Diabetes Management
Diabetes mellitus is a largely self-managed disease. If the patient
is unwilling or unable to self-manage his or her diabetes
on a day-to-day basis, the outcome will be poor, regardless
of how advanced the treatment technology is. As Glasgow
et al. recently noted: ‘Diabetes is at heart a behavioural issue’.
Psychological and social factors have a vital role in diabetes
management.
Coping with diabetes
Treatment of diabetes is complex and demanding, and has
a major impact on the psychosocial functioning of patients
and their family, yet most patients, both children and adults,
seem to cope reasonably well with the strains of the disease.
The diagnosis of diabetes may come as a shock, and can
induce serious emotional distress in both patient and family.
Research indicates that emotional equilibrium is restored
within several months to 1 year after diagnosis in most patients,
and that they learn to integrate diabetes into their
daily lives. The onset of diabetes-related complications can be
significantly delayed by maintaining strict glycaemic control,
but many patients develop them at some time. Complications
such as eyesight problems or amputation can induce profound
psychological reactions, ranging from anger and guilt to
apathy and depression. At this stage, patients may be inclined
to stop their self-care activities.
Patients with diabetes need to come to terms with the fact
that they have a chronic disease and must ‘learn to live with
it’. However, to prevent diabetes-related complications, active,
problem-focused coping behaviour is required – patients
must take responsibility for daily management of the disease,
in different situations and over a long period of time.
Performing self-care tasks (particularly daily self-injections
of insulin and finger-pricks) and always having to think about
what can or cannot be eaten are generally found burdensome.
Adherence to the treatment regimen is complicated
by the fact that it often does not ‘pay off’ – that is, patients
receive little or no positive feedback in the short term to
help reinforce their daily efforts. This can be demotivating,
particularly in younger patients, who are more concerned
with the ‘here and now’ than the distant future. Also, ‘good’
behaviour does not always translate into good results, and
this is a major cause of frustration that can ultimately lead to
‘diabetes burnout’ (see below). It is not surprising that many
patients find it difficult to adhere to the treatment regimen
all the time. Even in the Diabetes Control and Complications
Trial, in which patients were self-selected and highly motivated,
less than one-half reached the target HbA1c level, and
only 5% maintained that level of control throughout the study.
is unwilling or unable to self-manage his or her diabetes
on a day-to-day basis, the outcome will be poor, regardless
of how advanced the treatment technology is. As Glasgow
et al. recently noted: ‘Diabetes is at heart a behavioural issue’.
Psychological and social factors have a vital role in diabetes
management.
Coping with diabetes
Treatment of diabetes is complex and demanding, and has
a major impact on the psychosocial functioning of patients
and their family, yet most patients, both children and adults,
seem to cope reasonably well with the strains of the disease.
The diagnosis of diabetes may come as a shock, and can
induce serious emotional distress in both patient and family.
Research indicates that emotional equilibrium is restored
within several months to 1 year after diagnosis in most patients,
and that they learn to integrate diabetes into their
daily lives. The onset of diabetes-related complications can be
significantly delayed by maintaining strict glycaemic control,
but many patients develop them at some time. Complications
such as eyesight problems or amputation can induce profound
psychological reactions, ranging from anger and guilt to
apathy and depression. At this stage, patients may be inclined
to stop their self-care activities.
Patients with diabetes need to come to terms with the fact
that they have a chronic disease and must ‘learn to live with
it’. However, to prevent diabetes-related complications, active,
problem-focused coping behaviour is required – patients
must take responsibility for daily management of the disease,
in different situations and over a long period of time.
Performing self-care tasks (particularly daily self-injections
of insulin and finger-pricks) and always having to think about
what can or cannot be eaten are generally found burdensome.
Adherence to the treatment regimen is complicated
by the fact that it often does not ‘pay off’ – that is, patients
receive little or no positive feedback in the short term to
help reinforce their daily efforts. This can be demotivating,
particularly in younger patients, who are more concerned
with the ‘here and now’ than the distant future. Also, ‘good’
behaviour does not always translate into good results, and
this is a major cause of frustration that can ultimately lead to
‘diabetes burnout’ (see below). It is not surprising that many
patients find it difficult to adhere to the treatment regimen
all the time. Even in the Diabetes Control and Complications
Trial, in which patients were self-selected and highly motivated,
less than one-half reached the target HbA1c level, and
only 5% maintained that level of control throughout the study.
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