Type 2 diabetes is initially managed by increasing exercise and dietary modification. If blood glucose levels are not adequately lowered by these measures, medications such as metformin or insulin may be needed. In those on insulin there is typically the requirement to routinely check blood sugar levels.

Rates of diabetes have increased markedly over the last 50 years in parallel with obesity. As of 2010 there are approximately 285 million people with the disease compared to around 30 million in 1985. Long-term complications from high blood sugar can include heart disease, strokes, diabetic retinopathy where eyesight is affected, kidney failure which may require dialysis, and poor circulation of limbs leading to amputations. The acute complication of ketoacidosis, a feature of type 1 diabetes, is uncommon.^[4] However, nonketotic hyperosmolar coma may occur.

The classic symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss.^[5] Other symptoms that are commonly present at diagnosis include: a history of blurred vision, itchiness, peripheral neuropathy, recurrent vaginal infections, and fatigue. Many people however have no symptoms during the first few years and are diagnosed on routine testing. People with type 2 diabetes mellitus may rarely present with nonketotic hyperosmolar coma (a condition of very high blood sugar associated with a decreased level of consciousness and low blood pressure).^[3]

A number of lifestyle factors are known to be important to the development of type 2 diabetes including: obesity (defined by a body mass index of greater than thirty), lack of physical activity, poor diet, stress, and urbanization.^[6] Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60-80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders.^[3] Those who are not obese often have a high waist–hip ratio.^[3] Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar sweetened drinks in excess is associated with an increased risk.^[12][13] The type of fats in the diet are also important, with saturated fats and trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk.^[9] Eating lots of white rice appears to also play a role in increasing risk.^[14] A lack of exercise is believed to cause 7% of cases.^[15]

Genetics

Most cases of diabetes involve many genes with each being a small contributor to an increased probability of becoming a type 2 diabetic.^[6] If one identical twin has diabetes the chance of the other developing diabetes within their lifetime is greater than 90% while the rate for non-identical siblings is 25-50%.^[3] As of 2011, more than 36 genes have been found that contribute to the risk of type 2 diabetes.^[16] All of these genes together still only account for 10% of the total heritable component of the disease. The TCF7L2 allele for example increases the risk of developing diabetes by 1.5 times and is the greatest risk of the common genetic variants. Most of the genes link to diabetes are involved in beta cell functions.^[3]

There are a number of rare cases of diabetes that arise due to an abnormality in a single gene (known as monogenic forms of diabetes or "other specific types of diabetes").^[3][6] These include maturity onset diabetes of the young (MODY), Donohue syndrome, and Rabson-Mendenhall syndrome, among others.^[6] Maturity onset diabetes of the young constitute 1–5 % of all cases of diabetes in young people.^[17]

Medical conditions

There are a number of medications and other health problems that can predispose to diabetes.^[18] Some of the medications include: glucocorticoids, thiazides, beta blockers, atypical antipsychotics,^[19] and statins.^[20] Those who have previously had gestational diabetes are at a higher risk of developing type 2 diabetes.^[5] Other health problems that are associated include: acromegaly, Cushing's syndrome, hyperthyroidism, pheochromocytoma, and certain cancers such as glucagonomas.^[18] Testosterone deficiency is also associated with type 2 diabetes.^[21][22]

Pathophysiology

Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance.^[3] Insulin resistance, which is the inability of cells to respond adequately to normal levels of insulin, occurs primarily within the muscles, liver and fat tissue.^[23] In the liver, insulin normally suppresses glucose release. However in the setting of insulin resistance, the liver inappropriately releases glucose into the blood.^[6] The proportion of insulin resistance versus beta cell dysfunction differs among individuals with some having primarily insulin resistance and only a minor defect in insulin secretion and others with slight insulin resistance and primarily a lack of insulin secretion.^[3]

Other potentially important mechanisms associated with type 2 diabetes and insulin resistance include: increased breakdown of lipids within fat cells, resistance to and lack of incretin, high glucagon levels in the blood, increased retention of salt and water by the kidneys, and inappropriate regulation of metabolism by the central nervous system.^[6] However not all people with insulin resistance develop diabetes, since an impairment of insulin secretion by pancreatic beta cells is also required.^[3]

The World Health Organization definition of diabetes (both type 1 and type 2) is for a single raised glucose reading with symptoms, otherwise raised values on two occasions, of either:^[26]

• fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl)

or

• with a glucose tolerance test, two hours after the oral dose a plasma glucose ≥ 11.1 mmol/l (200 mg/dl)

A random blood sugar of greater than 11.1 mmol/l (200 mg/dL) in association with typical symptoms^[5] or a glycated hemoglobin (HbA_1c) of greater than 6.5% is another method of diagnosing diabetes.^[6] In 2009 an International Expert Committee that included representatives of the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the European Association for the Study of Diabetes (EASD) recommended that a threshold of ≥6.5% HbA_1c should be used to diagnose diabetes. This recommendation was adopted by the American Diabetes Association in 2010.^[27] Positive tests should be repeated unless the person presents with typical symptoms and blood sugars >11.1 mmol/l (>200 mg/dl).^[28]

Threshold for diagnosis of diabetes are based on the relationship between results of glucose tolerance tests, fasting glucose or HbA_1c and complications such as retinal problems.^[6] A fasting or random blood sugar is preferred over the glucose tolerance test as they are more convenient for people.^[6] HbA_1c has the advantages that fasting is not required and results are more stable, but has the disadvantage that the test is more costly than measurement of blood glucose.^[29] It is estimated that 20% of people with diabetes in the United States do not realize that they have the disease.^[6] Diabetes mellitus type 2 is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency.^[2] This is in contrast to diabetes mellitus type 1 in which there is an absolute insulin deficiency due to destruction of islet cells in the pancreas and gestational diabetes mellitus that is a new onset of high blood sugars in associated with pregnancy.^[3] Type 1 and type 2 diabetes can typically be distinguished based on the presenting circumstances.^[28] If the diagnosis is in doubt antibody testing may be useful to confirm type 1 diabetes and C-peptide levels may be useful to confirm type 2 diabetes.^[30]

Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise.^[33][34] Intensive lifestyle measures may reduce the risk by over half.^[7] The benefit of exercise occurs regardless of the person's initial weight or subsequent weight loss.^[35] Evidence for the benefit of dietary changes alone, however, is limited,^[36] with some evidence for a diet high in green leafy vegetables^[37] and some for limiting the intake of sugary drinks.^[12] In those with impaired glucose tolerance, diet and exercise either alone or in combination with metformin or acarbose may decrease the risk of developing diabetes.^[7][38] Lifestyle interventions are more effective than metformin.^[7]

Management

Management of type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range.^[7] Self-monitoring of blood glucose for people with newly diagnosed type 2 diabetes was recommended by the National Health Services in 2008,^[39] however the benefit of self monitoring in those not using multi-dose insulin is questionable.^[7][40] Managing other cardiovascular risk factors including:hypertension, high cholesterol, and microalbuminuria, improves a person's life expectancy.^[7] Intensive blood sugar lowering (HbA1C<6%) as opposed to standard blood sugar lowering (HbA1C of 7-7.9%) does not appear to change mortality.^[41][42] The goal of treatment is typically an HbA1C of less than 7% or a fasting glucose of less than 6.7 mmol/L (120 mg/dL) however these goals may be changed after professional clinical consultation, taking into account particular risks of hypoglycemia and life expectancy.^[5] It is recommended that all people with type 2 diabetes get regular ophthalmology examination.^[3]

Lifestyle

A proper diet and exercise are the foundations of diabetic care^[5] with a greater amount of exercise yielding better results.^[43] Aerobic exercise leads to a decrease in HbA1C and improved insulin sensitivity.^[43] Resistance training is also useful and the combination of both types of exercise may be most effective.^[43] A diabetic diet that promotes weight loss is important.^[44] While the best diet type to achieve this is controversial^[44] a low glycemic index diet has been found to improve blood sugar control.^[45] Culturally appropriate education may help people with Type 2 diabetes control their blood sugar levels, for up to six months at least.^[46] If changes in lifestyle, in those with mild diabetes, has not resulted in improved blood sugars within six weeks medications should then be considered.^[5]