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Diabetes mellitus type 2 or type 2 diabetes (formerly called non-insulin-dependent diabetes mellitus (NIDDM), or adult-onset diabetes) is a disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. While it is often initially managed by increasing exercise and dietary modification, medications are typically needed as the disease progresses. There are an estimated 23.6 million people in the U.S. (7.8% of the population) with diabetes with 17.9 million being diagnosed, 90% of whom are type 2. With prevalence rates doubling between 1990 and 2005, CDC has characterized the increase as an epidemic.

Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates due to alterations in dietary patterns as well as in life styles during childhood.

Unlike type 1 diabetes, there is very little tendency toward ketoacidosis in type 2 diabetes, though it is not unknown. One effect that can occur is nonketonic hyperglycemia which also is quite dangerous, though it must be treated very differently. Complex and multifactorial metabolic changes very often 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.

Overview of insulin secretion

Symptoms

• Early symptoms may be nothing more than chronic fatigues, generalised weakness and malaise (feeling of unease)
• Excessive urine production
• Excessive thirst and increased fluid intake
• Blurred vision (typically from lens shape alterations, due to osmotic effects, e.g., high blood glucose levels)
• Unexplained weight loss
• Lethargy
• Itching of external genitalia

Treatment

Diabetes mellitus type 2 is a chronic, progressive disease that has no established cure, but does have well-established treatments which can delay or prevent entirely the formerly inevitable consequences of the condition. Often, the disease is viewed as progressive since poor management of blood sugar leads to a myriad of steadily worsening complications. However, if blood sugar is properly maintained, then the disease is effectively cured - that is, patients are at no heightened risk for neuropathy, blindness, or any other high blood sugar complication. There are two main goals of treatment:

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., to near 'normal' blood glucose levels); the reduction in severity of diabetic side effects has been very well demonstrated in several large clinical trials and is established beyond controversy. The second goal is often addressed (in developed countries) by support and care from teams of diabetic health workers (usually physician, PA, nurse, dietitian or a certified diabetic educator). Endocrinologists, family practitioners, and general internists are the physician specialties most likely to treat people with diabetes. Knowledgeable patient participation is vital to clinical success, and so patient education is a crucial aspect of this effort.

Type 2 is initially treated by adjustments in diet and exercise, and by weight loss, most especially in obese patients. The amount of weight loss which improves the clinical picture is sometimes modest (2–5 kg or 4.4-11 lb); this is almost certainly due to currently poorly understood aspects of fat tissue activity, for instance chemical signaling (especially in visceral fat tissue in and around abdominal organs). In many cases, such initial efforts can substantially restore insulin sensitivity.[citation needed] In some cases strict diet can adequately control the glycemic levels.

Antidiabetic drugs

There are several drugs available for type 2 diabetics—most are unsuitable or even dangerous for use by type 1 diabetics. They fall into several classes and are not equivalent, nor can they be simply substituted one for another. All are prescription drugs.

One of the most widely used drugs now used for type 2 diabetes is the biguanide metformin; it works primarily by reducing liver release of blood glucose from glycogen stores and secondarily by provoking some increase in cellular uptake of glucose in body tissues. Both historically, and currently, the most commonly used drugs are in the Sulfonylurea group, of which several members (including glibenclamide and gliclazide) are widely used; these increase glucose stimulated insulin secretion by the pancreas and so lower blood glucose even in the face of insulin resistance.

Newer drug classes include:

• Testosterone treatment is very efficient to reduce insulin resistance without digestive problems (a very common side effect of other anti-diabetes drugs)
• Thiazolidinediones (TZDs) (rosiglitazone, pioglitazone, and troglitazone -- the last, as Rezulin, was withdrawn from the US market because of an increased risk of systemic acidosis). These increase tissue insulin sensitivity by affecting gene expression
• α-glucosidase inhibitors (acarbose and miglitol) which interfere with absorption of some glucose containing nutrients, reducing (or at least slowing) the amount of glucose absorbed
• Meglitinides which stimulate insulin release (nateglinide, repaglinide, and their analogs) quickly; they can be taken with food, unlike the sulfonylureas which must be taken prior to food (sometimes some hours before, depending on the drug)
• Peptide analogs which work in a variety of ways:
  • Incretin mimetics which increase insulin output from the beta cells among other effects. These includes the Glucagon-like peptide (GLP) analog exenatide, sometimes referred to as lizard spit as it was first identified in Gila monster saliva
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors increase Incretin levels (sitagliptin) by decreasing their deactivation rates
  • Amylin agonist analog, which slows gastric emptying and suppresses glucagon (pramlintide)

A systematic review of randomized controlled trials found that metformin and second-generation sulfonylureas are the preferred choices for most with type 2 diabetes, especially those early in the course of the disease. Failure of response after a time is not unknown with most of these agents: 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 to be 15% with rosiglitazone, 21% with metformin, and 34% with glyburide". Of these, rosiglitazone users showed more weight gain and edema than did non-users. Rosiglitazone may increase risk of death from cardiovascular causes though the causal connection is unclear. Pioglitazone and rosiglitazone may also increase the risk of fractures.

For patients who also have heart failure, metformin may be the best tolerated drug.

The variety of available agents can be confusing, and the clinical differences among type 2 diabetics compounds the problem. At present, choice of drugs for type 2 diabetics is rarely straightforward and in most instances has elements of repeated trial and adjustment.

If antidiabetic drugs fail (ie, the clinical benefit stops), insulin therapy may be necessary – usually in addition to oral medication therapy – to maintain normal or near normal glucose levels.

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