Diabetes mellitus type 2 overview

# Overview
Diabetes mellitus type 2 (T2DM) (formerly called non insulin-dependent diabetes (NIDDM), obesity related diabetes, or adult-onset diabetes) is a metabolic disorder that is primarily characterized by insulin resistance, relative insulin deficiency, and hyperglycemia. The defective responsiveness of body tissues to insulin almost certainly involves the insulin receptor in cell membranes. In the early stage the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood. At this stage hyperglycemia can be managed by engaging in exercise, modifying one's diet and medications that improve insulin sensitivity or reduce glucose production by the liver. As the disease progresses the impairment of insulin secretion worsens, and therapeutic replacement of insulin often becomes necessary. It is rapidly increasing in the developed world, and there is some evidence that this pattern will be followed in much of the rest of the world in coming years. The CDC has characterized the increase as an epidemic.

# Historical Perspective
Diabetes mellitus is a well-recognized disease from ancient times. In 1812 diabetes mellitus became a recognized clinical entity in The New England Journal of Medicine and Surgery. In 1889, the pancreas was identified as playing a major role in the pathogenesis of the disease. The discovery of insulin in 1921 was a major turning point in the history of diabetes when Frederick Banting and Charles Best were able to reverse the diabetic state in dogs by injecting the pancreatic isolate from healthy dogs.

# Classification
Type 2 diabetes doesn't have any specific classification. Although diabetes mellitus is classified in to 3 main categories:
- Diabetes mellitus type 1(T1DM)
- Diabetes mellitus type 2(T2DM)
- Gestational diabetes

# Pathophysiology
The underlying pathology is the development of insulin resistance. Contrary to T1DM, patients with T2DM sufficiently produce insulin; however, cellular response to the circulating insulin is diminished. The mechanism by which the insulin resistance develops is postulated to be influenced by both genetic and environmental factors. Environmental influences on the pathogenesis of T2DM include high glycemic diets, central obesity, older age, male gender, low-fiber diet, and high saturated fat diet.

# Causes
The underlying cause of T2DM is insulin resistance. The exact cause of insulin resistance is not known, however several theories exist. Central obesity, aging, and high glycemic diets are most commonly implicated in the development of T2DM.

# Differentiating Diabetes mellitus type 2 from other Diseases
T2DM must be differentiated from other disorders that may present with polyuria, polydipsia, weight loss or weight gain. Such disorders may include other forms of diabetes mellitus (e.g.T1DM, MODY) or other endocrine disorders (e.g. hypothyroidism, cushing's syndrome, wolfram syndrome, alstrom syndrome) or drug that can cause hyperglycemia (e.g. glucocorticoids)

# Epidemiology and Demographics
The prevalence of T2DM (DM) is well studied in the United States and other developed countries. However, worldwide there is a large variation in the results of the population studies in developing countries and particularly in rural areas with poor access to healthcare. For this reason, diabetes is estimated to be undiagnosed in approximately 50% of adults worldwide. In the United States, African Americans, Mexican Americans, American Indians and non-Hispanic blacks are at a higher risk of developing T2DM compared to non-Hispanic whites. It is more prevalent among those older than 65 years, although there is a growing tend of childhood-onset of the disease. In 2011, 335 million people were estimated to have T2DM and that number is on a trajectory to reach over 500 million people by 2050. These figures correlate with a prevalence of approximately 5000 and 7500 per 100,000 in 2011 and 2050, respectively. T2DM is more prevalent among men than women and in countries with low to mid income levels compared to high income level countries. It is classified as a global epidemic that is growing in parallel to massive urbanization.

# Risk Factors
Common risk factors associated with development of T2DM include: positive family history, certain ethnicity, obesity, smoking, physical inactivity, poor dietary habits, certain drugs (.eg. glucocorticoids) and certain medical conditions that may result in weight gain and inactivity.

# Screening
Diabetes screening is recommended for many people at various stages of life, and for those with any of several risk factors. Screening tests are the same tests used for diagnosis. Early diagnosis and treatment can control the complications and result in better clinical outcomes.

# Natural History, Complications and Prognosis
If T2DM left untreated, it may result in hyperosmolar hyperglycemic state (HHS) and in rare circumstances diabetic ketoacidosis (DKA). These are classified as acute complications of diabetes. Chronic complications of diabetes mellitus include microvascular and macrovascular complications. Early diagnosis and prompt treatment of these complications may result in improved prognosis and less long term morbidity and mortalities.

# Diagnosis

## History and Symptoms
A detailed history must be taken from every person presenting with diabetes symptoms. Classic symptoms of diabetes include: weight loss, polyphagia, polydipsia and polyuria. Less common symptoms include vision changes, tingling or numbness in exterimities, fatigue and skin changes.

## Physical Examination
Usually patients with T2DM have normal physical examination findings unless complications develop in these patients. Common physical examination findings include, pigmented skin patches and acanthosis nigricans.

## Laboratory Findings
Laboratory findings of T2DM are diagnostic for this disease. Diabetes may be diagnosed based on plasma glucose criteria, either the fasting plasma glucose (FPG) or the 2-hours plasma glucose (2-h PG) value after a 75-g oral glucose tolerance test (OGTT) or A1C criteria. All of these measurements are equally appropriate in diagnosis.

# Treatment
Life style modification is fundamental for diabetes management and it's a part of therapy. It include, diabetes self-management education (DSME), diabetes self-management support (DSMS), nutrition therapy, physical activity, smoking cessation counseling, and psychosocial care. The overall objectives of DSME and DSMS are to support informed decision making, self-care behaviors, problem solving, and active collaboration with the health care team to improve clinical outcomes, health status, and quality of life in a cost-effective manner.

## Medical Therapy
The main goals of treatment are, eliminate hyperglycemic symptoms, control the long term complications and improve the patient's quality of life.
T2DM is initially treated by life style modification and weight loss, especially in obese patients. Metformin is the first line pharmacologic therapy prescribed once the diagnosis is confirmed unless contraindications exist. If glycemic goals are not achieved, a second agent must be added to metformin. A wide range of options are available to add as combination therapy based on the patient's condition and comorbidities.
Medical therapy: Metformin monotherapy unless there is a contraindication to it. In the following conditions, dual therapy is initiated:
- HbA1C greater than 9 commence dual oral blood glucose lowering agent.
- HbA1C greater than 10 OR blood glucose level greater than 300 mg/dl OR a markedly symptomatic patient; consider combination therapy with insulin.

## Surgery
Pancreas and islet cell transplantation is considered in patients with chronic diabetes who have frequent metabolic complications and are intolerant to exogenous insulin or have failed insulin therapy.

## Primary Prevention
Life style modification is the mainstay for diabetes mellitus prevention. Metformin is another adjunctive measure to prevent diabetes in high risk persons. Studies have shown that 7% weight loss within a duration of 6 months in obese individuals is effective for diabetes prevention.

## Secondary Prevention
The most important secondary prevention strategy in T2DM is to decrease the macrovascular complications. Lipid control, smoking cessation and treatment of hypertension are the most important secondary preventive measures.