Sunday, February 1, 2009

Diabetes mellitus (contents)

General information


Type 1 Diabetes mellitus

Type 2 Diabetes mellitus

Diabetes and pregnancy

Investigations
Management

Oral antidiabetic drugs

Insulin

Diabetic emergencies

Complications of diabetes

Diabetes insipidus

Erectile dysfunction and diabetes


Diabetes and other conditions

New developments

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What is diabetes mellitus?

Diabetes mellitus is a metabolic disorder. patients with diabetes mellitus have a high blood sugar (glucose) due to the lack of insulin or due to increased resistance to insulin. Diabetes mellitus is the new world pandemic. Now diabetes is considered as a part of metabolic syndrome.

There are four types of diabetes;

  1. Type 1 diabetes mellitus ( due to lack of insulin)
  2. Type 2 diabetes mellitus (due to increased resistence to insulin)
  3. Type 3 diabetes mellitus ( secondary to other illness)
  4. Type 4 diabetes mellitus (diabets mellitus during pregnancy)


Universal blue circle symbol for diabetes

clinical features, management and different aspects of diabetes mellitus depend on the type of diabetes mellitus.

Clinical presentation of diabetes mellitus

There are four ways of presentations;

  1. asymptomatic( incidental finding)
  2. presentation with acute symptoms
  3. subacute presentation
  4. presentation with complications



Asymptomatic presentation

This is the commonest presentation and it is an incidental finding during routine examination or medical examination for insurance/ license/ employment

There is no evidence of ill health

Elevated blood sugar level could be a finding at those routine examinations. There can be glucose in the urine as well, even though it is a clue of hyperglycemia, not diagnostic

Further investigations should be done

Acute presentation

Usually these patients present with classic triad of symptoms;

  1. polyuria
  2. polydipsia
  3. weight loss

They have a brief history (2-6 weeks)

Usually patients with type 2 diabetes present like this

Subacute presentation

These patients have symptoms over a period of months or years. Common symptoms are polyuria, polydipsia, and weight loss.

They can also present with non-specific symptoms such as:

  1. lack of energy
  2. visual blurring
  3. pruritus vulvae
  4. balanitis

This is the usual presentation of type 2 diabetes mellitus.

Presentation with complications

Types of complications are;

1. microvascular
2. macrovascular
3. others

Microvascular complications;

1. nephropathy
2. neuropathy
3. retinopathy

Macrovascular complications;

1. Ischemic heart disease
2. stroke
3. peripheral vascular disease

Others;

1. staphylococcal skin infections (furuncles, carbuncles, abscesses)
2. wound infections
3. fungal infections

What are the types of diabetes mellitus?

DEFINITION

Diabetes is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion or insulin action or both.

TYPES OF DIABETES

There are four types of diabetes.

1. Type 1 diabetes.
2. Type 2 diabetes.
3. Diabetes secondary to other diseases
4. Diabetes during pregnancy.




Type 1 diabetes

This is due to the lack of insulin. Insulin deficiency is due to the beta cell destruction by an autoimmune process. There are two types of type 1 diabetes according to the presence of immunological markers.
Type 1A diabetes is a condition resulting from autoimmune destruction of beta cells in which immunological markers can be detected whereas in Type 2B immunological markers cannot be detected.
Type 1 diabetes is common among younger people especially children. But it can affect any age group.
Latent Autoimmune Diabetes of Adults (LADA) is a variant of type 1 diabetes but it is difficult to distinguish from type 2 diabetes mellitus.

Type 2 diabetes

This is the commonest form of diabetes and it carries a significant risk of morbidities and mortalities. 90-95% of patients with diabetes belong to this category. This condition is due to the resistance to insulin. But sometime it can be due to the lack of insulin or both. Majority of patients are middle or older age group.

Diabetes secondary to other diseases

1-2% of diabetes patients belong to this group. This condition can be cured if the underlying cause is identified. This can be due to liver disorders, pancreatic disorders, other endocrinopathies or drug induced.

Diabetes during pregnancy (gestational diabetes mellitus).

This is a special category and it occurs during pregnancy and disappears after the delivery. But it is a real burden for the patient and doctors as it can be difficult to control. Obesity, family history of diabetes and past history of gestational diabetes are some risk factors.

What is pre-diabetes?

Introduction

Pre-diabetes is a condition that comes before type 2 diabetes. Blood glucose (sugar) levels are higher than normal but aren’t high enough to be called diabetes. Pre-diabetes is a silent disease, meaning you can have it but not know it. By reducing the calorie intake, being physically active and loosing weight can delay the type 2 diabetes mellitus.

Prevention of type 2 diabetes mellitus

People with risk factors should be identified and they should be educated on how to reduce those risk factors.

Cut down calorie intake
Stop smoking
Exercise about 30 minutes per day
Loosing weight

People who are at risks;

You’re at risk for diabetes if you

  1. are overweight
  2. are physically inactive
  3. have a parent, brother, or sister with diabetes
  4. are African American, Native American, Asian American, Pacific Islander, or Hispanic American
  5. have had a baby weighing more than 9 pounds or have had gestational diabetes
  6. have high blood pressure (over 140/90 mmHg)
  7. have low HDL cholesterol (35 mg/dl or lower)
  8. or high triglycerides (250 mg/dl or higher)

Investigations

It does not have any symptoms therefore people with risk factors should undergo investigations.

1. fasting blood glucose

Pre-diabetes is diagnosed when fasting glucose levels are between 100 and 125 mg/dl. A fasting plasma glucose of 126 mg/dl or higher means diabetes.

2. oral glucose tolerance test

Pre-diabetes is diagnosed when blood glucose is between 140 and 199 mg/dl 2 hours after drinking glucose drink. These glucose levels are above normal but not high enough to be called diabetes. A 2-hour blood glucose of 200 mg/dl or higher means diabetes.


Treatment

There are no drugs to be effective in this condition. Only measures that patient should take is reduction of risk factors and undergoing regular assessments.

Maturity onset Diabetes of the Young (MODY)

Introduction

Diabetes is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion or insulin action or both. Several types of diabetes mellitus were described. Maturity onset diabetes of the young is a special type. The different MODY genotypes are associated with different clinical phenotypes. MODY should be considered in young people presenting with a typical family history (diabetes affecting a parent and 50% expression of the disease in the family) plus a form of early-onset diabetes which appears easy to control.

Maturity onset diabetes of the young (MODY) is a subtype of DM. It is characterized by autosomal dominant inheritance, early onset of hyperglycemia, and impairment in insulin secretion. Several monogenic forms of DM have been identified.

1. MODY 1

2. MODY 2

3. MODY 3

4. MODY 4

5. MODY 5

6. MODY 6

The glucokinase gene is intimately involved in the glucose-sensing mechanism within the pancreatic beta-cell. The hepatic nuclear factor (HNF) genes and the insulin promoter factor-1 (IPF-1) gene control nuclear transcription in the beta-cell where they regulate its development and function. Abnormal nuclear transcription genes may cause pancreatic agenesis or more subtle progressive pancreatic damage

MODY 1

This is caused by mutations in the hepatocyte nuclear transcription factors (HNF) 4a.

Chromosomal location

20q

Proportion of all MODY cases

5%

Onset

Teens to thirties

Progression

Progressive hyperglycemia

Microvascular complications

Frequent

Other features

None

MODY 2

MODY 2 is the result of mutations in the glucokinase gene that lead to mild-to-moderate hyperglycemia. Glucokinase catalyzes the formation of glucose-6-phosphate from glucose.

Chromosomal location

7q

Proportion of all MODY cases

15%

Onset

Present from birth

Progression

Little deterioration with age

Microvascular complications

Rare

Other features

Reduced birthweight

MODY 3

This is caused by mutations in the hepatocyte nuclear transcription factors (HNF) 1a.

Chromosomal location

12q

Proportion of all MODY cases

12q

Onset

teens/twenties

Progression

Progressive hyperglycemia

Microvascular complications

frequent

Other features

sensitive to sulphonylurea

MODY 4

This is a rare variant caused by mutations in the insulin promoter factor (IPF) 1, which is a transcription factor that regulates pancreatic development and insulin gene transcription.

Chromosomal location

13q

Proportion of all MODY cases

<1%

Onset

teens to thirties

Progression

Progression unclear

Microvascular complications

few data

Other features

Pancreatic agenesis in homozygotes

MODY 5

This is caused by mutations in the hepatocyte nuclear transcription factors (HNF) 1b.

Chromosomal location

17q

Proportion of all MODY cases

2%

Onset

Teens/twenties

Progression

Progression unclear

Microvascular complications

Frequent

Other features

Renal cysts, Proteinuria, Renal failure

MODY 6

This is due to the mutation in the neurogenic differention factor1 (NeuroD1)

Chromosomal location

2q

Proportion of all MODY cases

<7%

Onset


Progression


Microvascular complications


Other features


Epidemiology of Diabetes

Type 1 diabetes

The acute onset of type 1 diabetes and the fact that almost all cases rapidly reach medical attention means that registers of new cases can be relatively easily established. Provided ascertainment can be verified, these data can be combined with population denominator data to give age-specific and sex-specific rates.

1. Geographical variation

There is a marked geographical variation in the incidence of type 1 diabetes.In Finland, the age-standardized incidence in children aged 14 years and under is 36.8/100,000/year. A high rate is also observed in Sardinia (36.5/100,000/year) that is notably discordant with the incidence in Italy as a whole. These two countries have incidences 350-fold greater than those in Zunyi, China and Caracas, Venezuela, where the incidence is 0.1/100,000/year. In general, countries in Europe and North America have either high or intermediate incidences. The incidence in Africa is generally intermediate, and that in
Asia is low. Variation in incidence by age and sex – in the UK, wellestablished registers with high ascertainment (98.6%) (e.g. in Scotland) show an incidence of 15.3/100,000/year in children aged 0–4 years, rising to 24.4/100,000/year at 5–9 years and 31.9/100,000/year at 10–14 years. Overall, the incidence is slightly higher in boys than in girls (ratio 1.08:1). The peak incidence in boys is at 12–13 years,whereas in girls the peak occurs at 9–12 years.

2. Temporal variation

In the Scottish register, a steady increase in the incidence of type 1 diabetes of about 2% per annum was described during the period 1984–1993. This increase is seen in other studies worldwide in both low incidence and high-incidence areas. The overall pooled increase in 37 countries was 3.0% per year; the increase was relatively greater in populations with the lowest incidence. The incidence of type 1 diabetes also varies with season, being highest in autumn and winter.

3. Aetiological factors

genetic susceptibility is necessary but not sufficient as a cause of type 1 diabetes. The nature of the environmental factors that impact on this genetic predisposition are unclear. Studies have concentrated on the ecological correlation between incidence and geographical variation in environmental factors. These have includedsocial factors such as population density, household overcrowding and population mixing. These studies are ecological because the data on the risk of outcome (diabetes) is not collected from the same individuals as that on exposure (social factors). Inferences about causality from such data are weaker than evidence from studies based on the association between individual exposure and risk. However, prospective cohort studies are difficult to conduct in type 1 diabetes because of the relatively low incidence – many individuals would have to be recruited and assessed and only a few would progress to disease.The case-control approach is efficient, but is subject to recall bias because exposure is assessed by proxy from parents after the diagnosis has been made. Case-control studies havedemonstrated associations with early social mixing, viral infections, toxins and dietary factors such as exclusive breastfeeding and delayed introduction of cows’ milk.

Type 2 diabetes

1. geographical variation

The slow onset of type 2 diabetes, and its presentation without the acute metabolic disturbance seen in type 1 diabetes, means that the true time of onset is difficult to determine. Thus, the distinction between abnormality and normality is more blurred, there is a long pre-detection period, and as many as one-half of cases in the population at any one time are undiagnosed. Data on the prevalence of clinically detected type 2 diabetes provide information that is useful for health service planning, but cannot provide any insight into the true prevalence unless the prevalence of undetected diabetes is also known. Because the ratio of detected to undetected cases may vary over time and between places, epidemiological research aimed at defining the true prevalence of type 2 diabetes has had to rely on special studies in which the presence and absence of disease is defined by the oral glucose tolerance test (OGTT). However, the distinction between normality and abnormality is unclear, and debate continues about how it should be defined. The WHO currently recommends use of the 75-g OGTT, with diabetes defined by fasting glucose 7.0 mmol/litre or more and/or 2-hour post-challenge glucose 11.1 mmol/litre or more. Geographical variation – Figure 2 shows the agestandardized and sex-standardized prevalence of type 2 diabetes and impaired glucose tolerance as defined by the 75-g OGTT in various countries. As in type 1 diabetes, there is marked geographical variation, but the pattern is different. The prevalence is lowest in rural areas of developing countries, is generally intermediate in developed countries, and is highest in certain ethnic groups who have adopted Western lifestyle patterns. The populations with the highest prevalences (Pima Indians in Arizona and Nauruans in Micronesia) have a high prevalence of obesity. It is hypothesized that genetic susceptibility to obesity in these populations would be disadvantageous in times of food abundance, but would be advantageous when food is scarce, giving rise to maintenance of the gene by natural selection. This ‘thrifty genotype’ hypothesis is supported by evidence of gene–environment interaction – individuals who migrate from low prevalence areas (e.g. Japan) to the West are at increased risk of type 2 diabetes.

In the UK, the prevalence of known diabetes is about 2% and the age-standardized prevalence of undiagnosed diabetes is 2% in the over-40s. The true incidence of the disease is difficult to determine because this requires repeated glucose tolerance testing. However, such studies have been undertaken and the incidence found to be about 6/1000 personyears of follow-up. The incidence in individuals known to have impaired glucose tolerance is about eight times greater than in those with normal glucose tolerance; the absolute cumulative incidence is 10% over 5 years in Caucasians, but may be higher in high-risk populations. The risk of future progression to diabetes is also greater in those with other hyperglycaemic states, including gestational diabetes mellitus.

2. Temporal variation

data from studies such as the National Health and Nutrition Examination Survey (NHANES III) demonstrate that the prevalence of type 2 diabetes in the USA increased by 33%, from 4.9% in 1990 to 6.5% in 1998. This increase mirrors the increasing prevalence of obesity. Repeated surveys in developing countries show even more marked increases, particularly in areas where populations are rapidly adopting Western lifestyles . The increase in the prevalence of obesity in childhood has led to the appearance of type 2 diabetes in children and young adults, particularly those in highly susceptible ethnic groups.

3. Aetiological factors

Prospective population-based cohort studies suggest that the main pathophysiological defects leading to type 2 diabetes are insulin resistance and a relative insulin secretory defect. The main aetiological risk factors for type 2 diabetes are age, obesity, family history, physical inactivity and dietary factors such as a high proportion of energy consumed as saturated fat and low intake of fruit and vegetables. The observation of an association between low birth weight and risk of diabetes in later life has led to the development of an alternative to the thrifty genotype hypothesis. In this ‘thrifty phenotype’ hypothesis, the risk of diabetes and other adult disorders is programmed by fetal nutrition and the pattern of early growth. The causal nature of these associations is strengthened by data from studies in which the incidence of diabetes is reduced by interventions aimed at reducing weight, increasing activity and improving diet.

Type 1 diabetes mellitus

Introduction

Diabetes mellitus is a multisystem. Consequences are in the form of biochemical and anatomical. Disturbances in the metabolism of carbohydrates, protein and fat are the biochemical consequences whereas macrovascular and microvascular complications are the anatomical derangements. Absence or deficiency of insulin is the cause which result all the consequences of the type 1 DM. This is a disease of young individuals, not always.

How does it happen (Pathophysiology)?

Type 1 DM is a catabolic disorder in which circulating insulin is very low or absent. This is due to the failure of pancreatic beta cells to respond to all insulin-secretory stimuli. Therefore patients require exogenous insulin to reverse this catabolic condition, prevent ketosis, and normalize lipid and protein metabolism.

This is an autoimmune disease. There are histological evidence of immunological involvement such as lymphocytic infiltration and destruction of insulin-secreting cells of the islets of Langerhans, causing insulin deficiency. Approximately 85% of patients have circulating islet cell antibodies, and the majority also has detectable anti-insulin antibodies before receiving insulin therapy. Most islet cell antibodies are directed against glutamic acid decarboxylase (GAD) within pancreatic B cells.

There is another school of thought and it says that pancreatic beta cell destruction is due to an infectious or environmental agent. It triggers the immune system in a genetically susceptible individual to develop an autoimmune response against altered pancreatic beta cell antigens or molecules in beta cells that resemble a viral protein. Environmental agents that have been hypothesized to induce an attack on beta cell function include viruses (eg, mumps, rubella, Coxsackie B4), toxic chemicals, and exposure to cow's milk in infancy, and cytotoxins.

Recent evidence suggests a role for vitamin D in the pathogenesis and prevention of diabetes mellitus as well.

Epidemiology

This is the commonest metabolic disorder of childhood. Scandinavia has the highest prevalence rates for type 1 DM (ie, approximately 20% of the total number of people with DM), while China and Japan have the lowest prevalence rates, with less than 1% of all people with diabetes. Some of these differences may relate to definitional issues and the completeness of reporting.

Type 1 DM is more common in men than in women.

Type 1 DM usually starts in children aged 4 years or older, with the peak incidence of onset at 11-13 years of age, coinciding with early adolescence and puberty.

Type 1 DM is more common among non-Hispanic whites, followed by African Americans and Hispanic Americans. It is comparatively uncommon among Asians

Type 1 DM is associated with a high morbidity and premature mortality due to complications.

Clinical features of type 1diabetes mellitus

In clinical practice, history, examination and investigations are important to diagnose the disease. History and examinations are the fundamental things and they give evidence of the condition.

History

Polyuria (increased frequency of urination), polydipsia (thirst), and polyphagia (Increased appetite) are the cardinal features of type 1 diabetes. Patients can have other features like lassitude, nausea and blurred vision as well. These symptoms are due to the hyperglycemic state. Usually the onset is sudden. Disease maybe diagnosed following an infection. Usually patients are lean and present with features of ketoacidosis. History may reveal following features;

  1. Polyuria: this is due to osmotic diuresis secondary to hyperglycemia.
  2. Thirst is due to the hyperosmolar state and dehydration.
  3. Polyphagia with weight loss: The weight loss with a normal or increased appetite is due to depletion of water and a catabolic state with reduced glycogen, proteins, and triglycerides.
  4. Fatigue and weakness: This may be due to muscle wasting from the catabolic state of insulin deficiency, hypovolemia, and hypokalemia.
  5. Muscle cramps: This is due to electrolyte imbalance.
  6. Nocturnal enuresis: Severe enuresis secondary to polyuria can be an indication of onset of diabetes in young children.
  7. Blurred vision: This also is due to the effect of the hyperosmolar state on the lens and vitreous humor. Glucose and its metabolites cause dilation of the lens, altering its normal focal length.
  8. Gastrointestinal symptoms: Nausea, abdominal discomfort or pain, and change in bowel movements may accompany acute DKA. Acute fatty liver may lead to distention of the hepatic capsule, causing right upper quadrant pain. Persistent abdominal pain may indicate another serious abdominal cause of DKA, eg, pancreatitis. Chronic gastrointestinal symptoms in the later stage of diabetes are due to visceral autonomic neuropathy.
  9. Patients may maintain their normal weight or exhibit wasting, depending on the interval between the onset of the disease and initiation of treatment.
  10. Peripheral neuropathy: It presents as numbness and tingling in both hands and feet, in a glove and stocking pattern. It is bilateral, symmetric, and ascending neuropathy, which results from many factors, including the accumulation of sorbitol in peripheral sensory nerves due to sustained hyperglycemia.
  11. Symptoms at the time of the first clinical presentation usually can be traced back several days to several weeks; however, beta cell destruction may have started months, or even years, before the onset of clinical symptoms.

Examination findings

Usually physical examination is normal. If the patient present with diabetes ketoacidosis, signs of Kussmaul respiration, dehydration, hypotension will be there.
In established cases, patients should be examined every 3 months for macrovascular and microvascular complications. They should have funduscopic examination for retinopathy and monofilament testing for peripheral neuropathy.

Investigations for type1 diabetes mellitus

Investigations are important to diagnose the diabetes and to identify the type of the diabetes as well. Types of investigations are;

1. hematological
2. genetic studies


Hematological investigations (Blood tests)

  • Blood glucose: This is the mainstay of test to diagnose. Results are interpreted according to the
  • Serum electrolytes: to identify the renal involvement.
  • Urinalysis for glucose, ketones, and protein: these are important to detect renal involvement and diabetes ketoacidosis.
  • White blood cell count and blood and urine cultures to rule out infections.
  • Glycosylated hemoglobin (Hb)/Hb A1c ; this is a good test to recognize the glycemic control
  • Oral glucose tolerance test with insulin levels: Although this test usually is considered unnecessary to make the diagnosis in type 1 DM, with the dramatic increase of type 2 diabetes in the young population, assessment of insulin secretion may become more important.
  • To determine whether the individual has type 1 rather than type 2 DM, an insulin and/or C-peptide level below 5 µU/mL, or 0.6 ng/mL, suggests type 1. C-peptide is formed during conversion of proinsulin to insulin. A high positive titre of glutamic acid decarboxylase antibodies also suggests type 1 DM. An exception is the individual with type 2 DM who presents with a very high glucose, eg, above 300 mg/dL, who temporarily has a low insulin and/or C-peptide level but who will recover insulin production once normal glucose is restored.
  • Islet cell antibodies
  • Thyroxine (T4) and thyroid antibodies
Genetic studies
  • HLA typing may be considered.

Overview of management of type 1 diabetes mellitus

Treatment of this disease requires a multidisciplinary approach by physician, nurse, and dietitian.

Medical Care

Type 1 DM patients require insulin therapy to control initial hyperglycemia and maintain serum electrolytes and hydration. At times, the first incidence of ketoacidosis is followed by a symptom-free period where patients do not need treatment. This "honeymoon period" follows the initial treatment, in which the disease remits and the patient requires little or no insulin. This remission is due to a partial return of endogenous insulin, which may last for several weeks or months (and sometimes 1-2 y). Ultimately, however, the disease recurs, and patients require insulin therapy.

Multiple subcutaneous insulin injections are administered to control hyperglycemia after meals and to maintain normal plasma glucose levels throughout the day. This may increase the risks of hypoglycemia. Therefore, patients should be well educated about their disease and about self-monitoring of plasma glucose levels.


Surgical Care

Pancreatic transplantation is a possibility in some referral centers and is performed most commonly with simultaneous kidney transplantation for end-stage renal disease.

Consultations

These patients should be referred to an endocrinologist for multidisciplinary management.
These patients should have a complete retinal examination by an ophthalmologist at least once a year.The patients with significant proteinuria or a reduced creatinine clearance should be referred to a nephrologist.

Diet

One of the first steps in managing type 1 DM is diet control. Diet recommendations should be made in view of the patient's eating habits and lifestyle.Diet management includes education about the timing, size, frequency, or composition of meals to avoid hypoglycemia or postprandial hyperglycemia. All patients on insulin should receive a comprehensive diet plan that includes a daily caloric intake prescription; recommendations for amounts of dietary carbohydrate, fat, and protein; and how to divide calories between meals and snacks. A professional dietitian should be involved to create the individual diet plan.

Activity

Exercise is an important aspect of diabetes management. Patients should be encouraged to exercise regularly. Educate the patients about the effects of exercise on the blood glucose level. If patients are planning to participate in rigorous exercise for more than 30 minutes, they may develop hypoglycemia. To prevent hypoglycemia, they either can decrease the insulin by 10-20% or can have an extra snack. These patients must maintain their hydration status during exercise

Medication for type 1diabetes mellitus

Subcutaneous insulin is the mainstay of treatment for the type 1 diabetes mellitus. But there are different types of insulin available depending on their onset of action and the duration of the action. These types of insulins are as follows:

1. short acting insulin
2. intermediate acting insulin
3. long acting insulin
4. mixtures

Short acting insulin

Rapid- and short-acting insulins have the most rapid onsets of action and are used whenever quick glucose utilization is needed
There are two types;

1. soluble insulin
2. rapid acting insulin analogue

Soluble insulin

Human insulin currently is the best species of insulin available, and it is less antigenic than previously used animal-derived varieties. It can be given subcutaneous, intravenous and intramuscular routes.

Rapid acting insulin analogue

Rapid-acting insulins include regular insulin, lispro, and aspart insulin. Regular insulin is a preparation of zinc insulin crystals in solution. Its onset of action is 0.5-1 h, it peaks at 2.5-5 h, and duration of action is 6-8 h. Lispro insulin is a form of regular insulin that is genetically engineered with the reversal of the amino acids lysine and proline in the B chain. Aspart insulin has aspartic acid substituted for proline in position 28 of the B chain. Both of these insulins are absorbed more quickly and have a rapid onset (5-10 min), peak (1 h), and duration (4 h) of action. Therefore, they have the advantage that they may be administered shortly before eating. Semilente insulin is like regular insulin and is slightly slower rapid-acting insulin. It contains zinc insulin microcrystals in an acetate buffer and is not readily available.


Intermediate acting insulin

Intermediate-acting insulins have slower onsets of action and longer durations of action and are usually administered in combination with faster-acting insulins to maximize benefits of a single injection.


Intermediate-acting insulins include neutral protamine Hagedorn (NPH) insulin, which contains a mixture of regular, and protamine zinc insulin, and lente insulin, which contain 30% semilente insulin and 70% ultralente insulin in an acetate buffer.


Long acting insulin

These insulins offer a very long duration of action and, when combined with faster-acting insulins, offer better glucose control for some patients.


Long-acting insulins include ultralente insulin, containing large zinc insulin crystals in an acetate buffer, and glargine insulin, newer long-acting insulin that has no peak and produces a relatively stable level lasting more than 24 hours. Both insulins can supply basal 24-hour insulin with a single daily injection.


Mixtures


Mixtures of insulin preparations with different onsets and durations of action frequently are administered in a single injection by drawing measured doses of 2 preparations into the same syringe immediately before use. The exception is glargine insulin, which should not be mixed with any other form of insulin. Preparations that contain a mixture of 70% NPH and 30% regular human insulin (ie, Novolin 70/30, Humulin 70/30) are available, as is Humulin 50/50, but the fixed ratios of intermediate-acting to rapid-acting insulin may restrict their use. In addition, a 25/75 mixture of NPH and lispro insulin is available.

Follow up plan for type 1diabetes mellitus

After diagnosis of the diabetes, the Clinician and the patient should discuss to set a follow up plan. The aim of the follow up plan is to ensure that the patient is compliance with treatments and at the same time the patient should have a normal life as well.

Points are as follows;

1. Stick to treatment regimes
2. care during surgical procedures
3. regular assessment
4. foot care
5. patient education

Stick to treatment regime

Patients with type 1diabetes require lifetime insulin in order to have a normal life. This is a huge burden for the patients but the importance of continuation should be emphasized. This is important to have a good blood sugar control.

Regular insulin doses may cause hypoglycemia if the patient becomes anorectic or has another cause for reduced food intake, has gastroparesis, or is vomiting. Therefore insulin dose should be changed to tally the requirement.

The insulin coverage, with a sliding scale for insulin administration, should not be the only intervention because it is reactive, rather than proactive, in correcting hyperglycemia. Also, insulin may be used inappropriately when hyperglycemia reflects hepatic gluconeogenesis in response to previously uncorrected hypoglycemia.


Care during surgical procedures


Surgical procedures, inclusive of pre-surgery emotional stress, the effects of general anesthesia, and the trauma of the procedure, can markedly increase plasma glucose levels and induce DKA in patients with type 1 DM. In patients who normally take 1-2 daily injections of insulin, a third to a half of the usual morning dose can be administered in the morning before the operation and an IV infusion of 5% glucose in either 0.9% sodium chloride solution or water administered at a rate of 1 L (50 g glucose) over 6-8 hours.

Some physicians prefer to withhold subcutaneous insulin on the day of the operation and to add 6-10 units of regular insulin to 1 L of 5% glucose in 0.9% sodium chloride solution or water infused initially at 150 mL/h on the morning of the operation, depending on the plasma glucose level. The infusion is continued through recovery, with insulin adjustments depending on the plasma glucose levels obtained in the recovery room and at 2- to 4-hour intervals thereafter. The use of an intravenous insulin infusion in the postoperative period after major surgical procedures now is considered the standard of care in most hospitals.


Regular assessment

This is very important to ensure the good blood sugar control. Clinical examination should be carried out to detect complications. Several investigations should be done regularly;

1. Fasting blood sugar
2. Lipid profile


Foot care

This is a special topic. Read more


Patient education

Education is the most important aspect of diabetes management. The physician or the health care provider should educate the patient and, in the case of children, the parents about the disease process, management, goals, and long-term complications. They should be made aware of the signs and symptoms of hypoglycemia and ways to manage it.

A dietitian should provide specific diet control education to the patient and family.

A nurse should educate the patient about self–insulin injection and performing finger sticks for blood glucose level monitoring.

Type 2 diabetes mellitus

Introduction
This is a group of disorders characterized by hyperglycemia and associated with microvascular, macrovascular complications. Unlike type 1 diabetes mellitus, the patients are not absolutely dependent upon insulin for life, even though many of these patients ultimately are treated with insulin.
How does it happen (Pathophysiology)?
Muscles, fat and liver are the major sites where insulin acts. But in type 2 DM these sites offer a resistance to insulin therefore metabolism of carbohydrates, fat and protein become abnormal. This pathophysiologic abnormality results in decreased glucose transport in muscle, elevated hepatic glucose production, and increased breakdown of fat. Therefore hyperglycemia will result.
The genetic aspects of this condition is very complex and not completely understood, but presumably this disease is related to multiple genes (with the exception of maturity-onset diabetes of the young [MODY]). Evidence supports inherited components for both pancreatic beta cell failure and insulin resistance.
Recent work has suggested that elevated free fatty acids may be the driving force behind insulin resistance and perhaps even beta cell dysfunction. If this defect is more proximal than defects specifically related to glycemia, then therapies aimed at correcting this phenomenon would be highly beneficial.
Hyperglycemia appears to be the determinant of microvascular and metabolic complications. However, glycemia is much less related to macrovascular disease. Insulin resistance with concomitant lipid (ie, small dense low-density lipoprotein [LDL] particles, low high-density lipoprotein-cholesterol [HDL-C] levels, elevated triglyceride-rich remnant lipoproteins) and thrombotic (ie, elevated type-1 plasminogen activator inhibitor [PAI-1], elevated fibrinogen) abnormalities, as well as conventional atherosclerotic risk factors (eg, family history, smoking, hypertension, elevated low-density lipoprotein-cholesterol [LDL-C], low HDL-C), determine cardiovascular risk.
Epidemiology
Type 2 diabetes mellitus is less common in non-Western countries where the diet contains fewer calories and caloric expenditure on a daily basis is higher. However, as people in these countries adopt Western lifestyles, weight gain and type 2 diabetes mellitus are becoming virtually epidemic.
The prevalence of type 2 diabetes mellitus varies widely among various racial and ethnic groups Type 2 diabetes mellitus is becoming virtually pandemic in some groups of Native Americans and Hispanic people. Recent work suggests more retinopathy and nephropathy in blacks, Native Americans, and Hispanic groups.
Type 2 diabetes mellitus is slightly more common in older women than men.
While type 2 diabetes mellitus traditionally has been thought to affect individuals older than 40 years, it is being recognized increasingly in younger persons, particularly in highly susceptible racial and ethnic groups.

Type 2 diabetes mellitus is slightly more common in older women than men.
Diabetes mellitus is one of the leading causes of morbidity and mortality because of its role in the development of optic, renal, neuropathic, and cardiovascular disease. These complications, particularly cardiovascular disease (~50-75% of medical expenditures), are the major sources of expenses for patients with diabetes mellitus.

Clinical features of type 2 diabetes mellitus

In clinical practice, history, examination and investigations are important to diagnose the disease. History and examinations are the fundamental things and they give evidence of the condition.

History
Most patients with type 2 diabetes mellitus are asymptomatic for years. Classic symptoms are polyuria, polydipsia, polyphagia and weight loss. Other symptoms that might suggest hyperglycemia include blurred vision, lower extremity paresthesias, or yeast infections, particularly balanitis in men.

The possible presence of diabetes mellitus should be considered in patients with risk factors;
1. obese
2. patients with a first-degree relative with type 2 diabetes mellitus
3. members of high-risk ethnic groups ( black, Hispanic, Native American, Asian American, Pacific Islander) women with a previous delivery of a large infant (>9 lb)
4. a history of gestational diabetes mellitus
5. patients with hypertension
6. Patients with high triglycerides (>250 mg/dL) or low HDL-C (<35 mg/dL).
7. Evidence of polycystic ovary disease


Examination findings
Usually patients with type 2diabetes mellitus present with macrovascular and microvascular complications. Therefore there can be examination findings as well.
1. Evidence of infections (abscesses)
2. skin colour changes
3. parasthesea
4. high blood pressure
5. retinal changes
6. diabetic foot changes

Investigations for type 2 diabetes mellitus

Investigations are important to diagnose the diabetes and to identify the type of the diabetes as well. Aims of investigations are;
1. to confirm the disease
2. to detect the glycemic control over a period
3. to detect complications
4. to assess the severity of the disease
5. to detect associated conditions

Tests to confirm the disease

1. Fasting blood sugar; this is the basic and the simplest method of diagnosing diabetes.
2. Random blood sugar

the diagnosis is made when the health care provider discovers either fasting plasma glucose (FPG) greater than or equal to 126 mg/dL on 2 occasions or random glucose greater than or equal to 200 mg/dL and classic symptoms of diabetes mellitus (ie, polyuria, polydipsia, polyphagia, weight loss).

Tests to detect glycemic control

Glycosylated hemoglobin (GHb) measurement is the popular method which is used to determine the glycemic control over a period of 3 months.

Tests to detect complications

1. ECG and Echocardiogram
2. urine micro albumin
3. serum electrolyte and blood urea
4. funduscopy

Tests to assess the severity

1. blood sugar level
2. HbA1C

Tests to detect associated conditions

1. Lipid profile
2. thyroxin level

Overview of management of type 2 diabetes mellitus

Treatment of this disease requires a multidisciplinary approach by physician, nurse, and dietitian.

Medical Care
The goals in caring for patients with diabetes mellitus include the elimination of symptoms; microvascular risk reduction through control of glycemia and blood pressure; macrovascular risk reduction through control of lipids and hypertension, smoking cessation, and utilizing aspirin therapy; and metabolic risk reduction through control of glycemia. Such care requires appropriate goal setting, regular complications monitoring, dietary and exercise modifications, medications, appropriate self-monitoring of blood glucose (SMBG), and laboratory assessment. Focus on glucose alone does not provide adequate treatment for patients with diabetes mellitus. Treatment involves multiple goals
Complications monitoring: The American Diabetes Association recommends initiation of complications monitoring at the time of diagnosis of diabetes mellitus. This regimen should include yearly dilated eye examinations, yearly microalbumin checks, and foot examinations at each visit.
Laboratory monitoring: Because diabetes mellitus is a multisystem disease, focusing solely on blood sugar is inadequate.
Intercurrent medical illness: Patients with intercurrent illness become more insulin resistant because of the effects of increased counter-regulatory (ie, anti-insulin) hormones. Therefore, despite decreased nutritional intake, glycemia may worsen. Patients on oral agents may need transient therapy with insulin to achieve adequate glycemic control. In patients requiring insulin, scheduled doses of insulin, as opposed to sliding scale insulin, are far more effective in achieving glycemic control.
Surgical Care
Bariatric surgery has been shown to improve diabetes control and, in some situations, normalize glucose tolerance in morbidly obese patients. It is certainly a reasonable alternative in carefully selected patients if an experienced team (providing appropriate preoperative evaluation as well as technical surgical expertise) is available.
Consultations
Primary care physicians can care for patients with type 2 diabetes mellitus adequately. The multiple facets of disease treatment (eg, nutrition, exercise, smoking cessation, medications, complications monitoring) and data management (eg, glucose levels, BP, lipids, complications monitoring) must be continually noted. Inability to achieve adequate glycemic (or BP or lipid) control usually should be a clear indication to consult a diabetes specialist. When a patient has developed advanced complications, a diabetes specialist cannot be expected to be able to lessen the burden of these complications.
Diet
For most patients, the best diet is of what they are currently eating. Time honored attachments to a precise macronutrient composition of the diet to control diabetes are generally not supported by the research. Caloric restriction is of first importance. After that, individual preference is reasonable. Modest restriction of saturated fats and simple sugars is reasonable. However, some patients have remarkable short-term success with high-fat low-carbohydrate diets of various sorts. Therefore, the author always stresses weight management in general and is flexible regarding the actual diet that the patient consumes. Also, the practitioner should advocate a diet using foods that are within the financial reach and cultural milieu of the patient.
Activity
In general, most patients with type 2 diabetes mellitus can benefit from increased activity. Aerobic exercise improves insulin sensitivity and may improve glycemia markedly in some patients.
• The patient should choose an activity that she or he is likely to continue. Walking is accessible to most patients in terms of time and financial expenditure.
• A previously sedentary patient should start activities slowly.
• Older patients, patients with long-standing disease, patients with multiple risk factors, and patients with previous evidence of atherosclerotic disease should have a cardiovascular evaluation, probably including an imaging study, prior to beginning a significant exercise regime.

Medication for type 2 diabetes mellitus

Pharmacologic therapy has changed dramatically in the last 10 years. New drug classes and new drugs effectively treat type 2 diabetes mellitus, allowing glycemic control previously beyond the reach of medical therapy.
Treatment options;
1. Oral hypoglycemic agents
2. Insulin

Oral hypoglycemic agents
1. Sulfonylureas are time-honored insulin secretagogues (and probably have the greatest efficacy for glycemic lowering of any of the oral agents.

2. Meglitinides are much more short-acting insulin secretagogues than sulfonylureas, with preprandial dosing potentially achieving more physiologic insulin release and less risk for hypoglycemia.


3. Biguanides are old agents that reduce hepatic glucose production and may have a minor effect on glucose utilization in the periphery (ie, antihyperglycemics, hepatic insulin sensitizers). Insulin must be present for biguanides to work.

4. Alpha-glucosidase inhibitors prolong the absorption of carbohydrates. Their induction of flatulence greatly limits their use. These agents should be titrated slowly to reduce gastrointestinal intolerance.


5. Thiazolidinediones (glitazones) are a new class of drugs that reduce insulin resistance in the periphery (ie, sensitize muscle and fat to the actions of insulin) and perhaps to a small degree in the liver (ie, insulin sensitizers, antihyperglycemics). They activate peroxisome proliferator–activated receptor (PPAR) gamma, a nuclear transcription factor that is important in fat cell differentiation and fatty acid metabolism.
Insulin
Ultimately, many patients with type 2 diabetes mellitus become markedly insulinopenic. The only therapy that corrects this defect is insulin. Because most patients are insulin resistant, small changes in insulin dosage may make no difference in glycemia in some patients. Furthermore, because insulin resistance is variable from patient to patient, therapy must be individualized in each patient.
Types of isulins available are as follows;
1. short acting insulin
2. intermediate acting insulin
3. long acting insulin
4. mixtures