Diabetes Mellitus Type 2

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Diabetes mellitus type 2 (formerly called diabetes mellitus type II, 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. It is often managed by engaging in exercise and modifying one's diet. 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.

Unlike Type 1 diabetes, there is little tendency toward ketoacidosis in Type 2 diabetes, though it is not unknown. Complex and multifactorial metabolic changes lead to damage and function impairment of many organs, most importantly the cardiovascular system in both types. This leads to substantially increased morbidity and mortality in both Type 1 and Type 2 patients, but the two have quite different origins and treatments despite the similarity in complications.

Current Research

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For current research articles click - here

Pathophysiology

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Genetic factors, usually polygenic, are present in most patients. However, environmental factors such as obesity, lack of exercise and a sedentary lifestyle are thought by most observers to lead to insulin resistance. Certainly not all type 2 diabetics have a family history of the condition.

Insulin resistance means that body cells do not respond appropriately when insulin is present.

Other important contributing factors:

• Increased hepatic glucose production (e.g., from glycogen degradation), especially at inappropriate times
• Decreased insulin-mediated glucose transport in (primarily) muscle and adipose tissues (receptor and post-receptor defects)
• Impaired beta-cell function—loss of early phase of insulin release in response to hyperglycemic stimuli
• Cancer survivors who received allogenic Hematopoeitic Cell Transplantation (HCT) are 3.65 times more likely to report type 2 diabetes than their siblings. Total body irradiation (TBI) is also associated with a higher risk of developing diabetes.

This is a more complex problem than type 1, but is sometimes easier to treat, especially in the initial years when insulin is often still being produced internally. Type 2 may go unnoticed for years in a patient before diagnosis, since the symptoms are typically milder (no ketoacidosis) and can be sporadic. However, severe complications can result from unnoticed type 2 diabetes, including renal failure, blindness, wounds that fail to heal, and coronary artery disease. The onset of the disease is most common in middle age and later life.

Diabetes mellitus type 2 is presently of unknown etiology (i.e., origin). Diabetes mellitus with a known etiology, such as secondary to other diseases, known gene defects, trauma or surgery, or the effects of drugs, is more appropriately called secondary diabetes mellitus. Examples include diabetes mellitus caused by hemochromatosis, pancreatic insufficiency, or certain types of medications (e.g. long-term steroid use).

About 90–95% of all North American cases of diabetes are type 2, and about 20% of the population over the age of 65 has diabetes mellitus type 2. The fraction of type 2 diabetics in other parts of the world varies substantially, almost certainly for environmental and lifestyle reasons, though these are not known in detail. There is also a strong inheritable genetic connection in type 2 diabetes: having relatives (especially first degree) with type 2 is a considerable risk factor for developing type 2 diabetes. About 55 percent of type 2 are obese[2] —chronic obesity leads to increased insulin resistance that can develop into diabetes, most likely because adipose tissue is a (recently identified) source of chemical signals (hormones and cytokines). Other research shows that type 2 diabetes causes obesity.

Diabetes mellitus type 2 is often associated with obesity and hypertension and high cholesterol (combined hyperlipidemia), and with the condition Metabolic syndrome (also known as Syndrome X, Reavan's syndrome, or CHAOS). It is also associated with acromegaly, Cushing's syndrome and a number of other endocrinological disorders.

Screening and Prevention

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Interest has arisen in preventing diabetes due to research on the benefits of treating patients before overt diabetes. Although the U.S. Preventive Services Task Force (USPSTF) concluded that "the evidence is insufficient to recommend for or against routinely screening asymptomatic adults for type 2 diabetes, impaired glucose tolerance, or impaired fasting glucose"[4][5], this was a grade I recommendation when published in 2003.

Since publication of the USPSTF statement, a randomized controlled trial of prescribing acarbose to patients with "high-risk population of men and women between the ages of 40 and 70 years with a body mass index (BMI), calculated as weight in kilograms divided by the square of height in meters, between 25 and 40. They were eligible for the study if they had IGT according to the World Health Organization criteria, plus a fasting plasma glucose concentration of between 100 and 140 mg/dL (5.5 and 7.8 mmol/L)" found a number needed to treat of 44 (over 3.3 years) to prevent a major cardiovascular event.

Other studies have shown that life-style changes and metformin can delay the onset of diabetes.

Treatment

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Diabetes mellitus type 2 is a chronic, progressive disease that cannot now be cured. There are two main goals of treatment of the disease:

1. Reduction of mortality and concomitant morbidity (from assorted diabetic complications)
2. Preservation of quality of life

The first goal can be achieved through close glycemic control (i.e., blood glucose levels); the reduction effect in diabetic complications has been well demonstrated in several extensive clinical trials and is thus well established. The second goal is often addressed (in developed countries) by support and care from teams of diabetic health workers (physician or PA, nurse, dietitian, certified diabetic educator, ...). Knowledgeable patient participation is vital and so patient education is a crucial aspect of this effort.

Type 2 is initially treated by adjustment in diet and exercise, and by weight loss, especially in obese patients. The amount of weight loss which improves the clinical picture is sometimes modest (5–10 lb); this is almost certainly due to currently poorly understood aspects of fat tissue chemical signalling (especially in visceral fat tissue in and around abdominal organs). In many cases, such initial efforts can substantially restore insulin sensitivity.

Antidiabetic Drugs

The next step, if necessary, is treatment with antidiabetic drugs (all are oral agents "OA"s, with the exception of the GLP analogues, which are injected):

• Sulfonylureas
• Biguanides (metformin)
• Thiazolidinediones (rosiglitazone and pioglitazone)
• α-glucosidase inhibitors (acarbose, miglitol)
• Meglitinides (nateglinide, repaglinide, and their analogs)
• Peptide analogs
  • Incretin mimetics (insulin secretagogues)
    • Glucagon-like peptide (GLP) analogs (subcutaneous administration)
      • Exenatide
      • Liraglutide (not FDA approved)
    • Gastric inhibitory peptide (GIP) analogs
      • None are FDA approved
  • Incretin enhancers
    • Sitagliptin
  • Amylin agonist analog (slows gastric emptying and suppresses glucagon)
    • Pramlintide

The initial choice of anti-diabetic drug has been compared in a randomized controlled trial which found "cumulative incidence of monotherapy failure at 5 years of 15% with rosiglitazone, 21% with metformin, and 34% with glyburide." Rosiglitazone had more weight gain and edema.[9] Rosiglitazone may increase risk of death from cardiovascular causes. Pioglitazone and rosiglitazone may increase the risk of fractures.

Insulin Preparations

If antidiabetic drugs fail to help (or stop helping), insulin therapy may be necessary, usually as an adjunct to oral medication therapy, to maintain normal glucose levels. Thus, the term non-insulin-dependent diabetes is inaccurate and misleading. The classification, or type, of diabetes is determined by the underlying cause of the diabetes, not the type of therapy that is used to treat the diabetes. Many patients with type 2 diabetes will progress to insulin therapy to control of blood glucose levels, but these patients are still type 2 diabetics.

Long Acting Insulins A meta-analysis of randomized controlled trials by the international Cochrane Collaboration found "only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2."

• Insulin glargine
• Insulin detemir

Other Treatments

Carnitine has been shown to increase insulin sensitivity in humans[citation needed]. Taurine has also shown a similar effect, but only in rats thus far.


(adapted from Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Type_2_Diabetes)