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Diabetes mellitus type 2

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Diabetes mellitus type 2
Classification and external resources

Universal blue circle symbol for diabetes.[1]
ICD-10 E11
ICD-9 250.00, 250.02
OMIM 125853
DiseasesDB 3661
MedlinePlus 000313
eMedicine article/117853
MeSH D003924

Diabetes mellitus type 2 – formerly non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes – is a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency.[2] The classic symptoms are excess thirst, frequently having to urinate, and constant hunger. Type 2 diabetes makes up about 90% of cases of diabetes with the other 10% due primarily to diabetes mellitus type 1 and gestational diabetes. Obesity is the primary cause of type 2 diabetes in people who are genetically predisposed to the disease.

Type 2 diabetes is initially managed by increasing exercise and dietary modification. If blood sugars are not 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 attacks, strokes, diabetic retinopathy where eye sight is affected, kidney failure which may require dialysis, and poor circulation of limbs leading to amputations. The acute complication ketoacidosis is uncommon unlike in type 1 diabetes,[3] nonketonic hyperglycemia however may occur.

Contents

[edit] Signs and symptoms

Overview of the most significant symptoms of diabetes.

The classic symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss.[4]

[edit] Complications

Main article: Complications of diabetes mellitus

Type 2 diabetes is typically a chronic disease, associated with a ten year shorter life expectancy.[5] This is partly due to a number of complications with which it is associated including: two to four times the risk of cardiovascular disease and stroke, a 20 fold increase in lower limb amputations, and increased rates of hospitalizations.[5] In the developed world, and increasingly elsewhere, type 2 diabetes is the largest cause of non-traumatic blindness and kidney failure.[6] It has been associated with an increased risk of cognitive dysfunction and dementia through disease processes such as Alzheimer's disease and vascular dementia.[7] Other complications include: acanthosis nigricans, sexual dysfunction, and frequent infections.[4]

[edit] Cause

The development of type 2 diabetes is caused by a combination of lifestyle and genetic factors.[8][6] While some are under personal control such as diet and obesity others such as age, gender, and genetics are not.[5] A lack of sleep has been linked to type 2 diabetes[9] as has nutritional status during fetal development.[10]

[edit] Lifestyle

Main article: Lifestyle causes of diabetes mellitus type 2

A number of lifestyle factors are known to be important to the development of type 2 diabetes including: obesity, physical activity, diet, stress, and urbanization.[5] Excess body fat underlies 64% of cases of diabetes in men and 77% of cases in women.[11] A number of dietary factors such as sugar sweetened drinks[12][13] and the type of fats in the diet appear to play a role.[8]

[edit] Genetics

Main article: Genetic causes of diabetes mellitus type 2

Most cases of diabetes involved many genes contributing small amount to the overall condition.[5] As of 2011 more than 36 genes have been found that contribute to the risk of type 2 diabetes.[14] All of these genes together still only account for 10% of the total genetic component of the disease.[14]

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).[5] These include maturity onset diabetes of the young (MODY), Donohue syndrome, and Rabson-Mendenhall syndrome, among others.[5] Maturity onset diabetes of the young constitute 1–5 % of all cases of diabetes in young people.[15]

[edit] Medical conditions

There are a number of medications and other health problems that can predispose to diabetes.[16] Some of the medications include: glucocorticoids, thiazides, beta-adrenergic agonist, alpha interferon.[16] Those who have previously had gestational diabetes are at a higher risk of developing type 2 diabetes.[4] Other health problems that are associated include: acromegaly, Cushing's syndrome, hyperthyroidism, pheochromocytoma, and certain cancers such as glucagonomas.[16] Testosterone deficiency is also associated with type 2 diabetes.[17][18]

[edit] Pathophysiology

Type 2 diabetes is due to insulin resistance primarily within the muscles and fat tissue and inadequate insulin production from the beta cells to compensate.[19] This occurs in combination with increased glucose release from the liver and thus results in the classic finding of high blood sugar.[5] Other potential important mechanisms include: increased break down of lipids with in the fat cell, resistance to and lack of incretin, high glucagon levels in the blood, increased absorption of fluids in the kidneys, and the central nervous system not appropriately regulating metabolism.[5]

[edit] Diagnosis

Diabetes diagnostic criteria[20][21]  edit
Condition 2 hour glucose Fasting glucose HbA1c
mmol/l(mg/dl) mmol/l(mg/dl) %
Normal <7.8 (<140) <6.1 (<110) <6.0
Impaired fasting glycaemia <7.8 (<140) ≥ 6.1(≥110) & <7.0(<126) 6.0-6.4
Impaired glucose tolerance ≥7.8 (≥140) <7.0 (<126) 6.0-6.4
Diabetes mellitus ≥11.1 (≥200) ≥7.0 (≥126) ≥6.5

The World Health Organization definition of diabetes is for a single raised glucose reading with symptoms, otherwise raised values on two occasions, of either:[22]

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

A glycated hemoglobin (HbA1c) of greater than 6.5% is another method of diagnosis diabetes[5] as is a random blood sugar of greater than 11.1 mmol/l (200 mg/dL) in association with typical symptoms.[4] These cut off have been decided based on the fact that complicates such as retinal problems begin to increase at greater values.[5] A fasting or random blood sugar is preferred over the glucose tolerance test for most diagnosis as they are more convenient for people.[5] It is estimated that 20% of people with diabetes in the United States do not realize that they have the disease.[5]

[edit] Screening

No major organization recommends universal screening for diabetes as there is no evidence that such a program would improve outcomes.[23] Screening is recommended by the United States Preventive Services Task Force in adults without symptoms whose blood pressure is greater than 135/80 mmHg.[24] For those whose blood pressure is less, the evidence is insufficient to recommend for or against screening.[24] The World Health Organization recommends only testing those groups at high risk.[23] High risk groups in the United States include: those over 45 years old, those with a first degree relative with the same, certain ethnic groups such as Hispanics, African-Americans, and Native-Americans, a history of gestational diabetes, polycystic ovary syndrome, excess weight, and conditions associated with metabolic syndrome.[4]

[edit] Prevention

Main article: Prevention of diabetes mellitis type 2

Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise.[25][26] Intensive lifestyle measures may reduce the risk by over half.[6] The benefit of exercise occur regardless of the persons initial weight or subsequent weight loss.[27] Evidence for the benefit of dietary changes alone however is limited;[28] with some evidence for a diet high in green leafy vegetables[29] and some for limiting the intake of sugary drinks.[12] In those with impaired glucose tolerance, diet and exercise and/or metformin or acarbose may decrease the risk of developing diabetes.[6][30] Lifestyle interventions are more effective than metformin.[6]

[edit] Management

Further information: Diabetes management

Management of type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range.[6] Self-monitoring of blood glucose for people with newly diagnosed type 2 diabetes was recommended by the National Health Services in 2008,[31] however the benefit of self monitoring in those not using multi-dose insulin is questionable.[6] Managing other cardiovascular risk factors including hypertension, high cholesterol, and microalbuminuria improves a person's life expectancy.[6] Intensive blood sugar lowering as opposed to standard blood sugar lowering does not appear to change mortality.[32] 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 altered by a persons risk of hypoglycemia and life expectancy.[4]

[edit] Lifestyle

A proper diet and exercise are the foundations of diabetic care[4] with a greater amount of exercise yielding better results.[33] Anaerobic exercise leads to a decrease in HbA1C and improved insulin sensitivity.[33] Resistance training is also useful and the combination of both types of exercise may be most effective.[33] A diabetic diet that promotes weight loss is important.[34] While the best diet type to achieve this is controversial[34] a low glycemic index diet has been found to improve blood sugar control.[35] Culturally appropriate education may help people with type 2 diabetes control their blood sugar levels, for up to six months at least.[36] If lifestyle measures in those with mildly elevated blood sugars have not resulted in an improvement within six weeks medications should than be considered.[4]

[edit] Medications

Metformin 500mg tablets

There are several classes of anti-diabetic medications available. Metformin is generally recommended as a first line treatment as there is good evidence that it decreases mortality.[6] Injections of insulin may either be added to oral medication or used alone.[6] Other classes of medications used to treat type 2 diabetes are sulfonylureas, nonsulfonylurea secretagogues, alpha glucosidase inhibitors, and thiazolidinediones.[6] Metformin however should not be used in those with severe kidney or liver problems.[4]

When insulin is used, a long-acting formulation is typically added initially at night, while oral medications are continued.[6][4] Doses are than increased to effect.[6] When nightly insulin is insufficient twice daily insulin may achieve better control.[4] The long acting insulins, glargine and detemir, do not appear much better than NPH but have a significantly greater cost making them as of 2010 not cost effective.[37] In those who are pregnant insulin is generally the treatment of choice.[4]

[edit] Surgery

Weight loss surgery in those who are obese appears to be an effective measure to treat diabetes.[38] Many are able to maintain normal blood sugar levels with little or no medications following surgery[39] and long term mortality is decreased.[40] There however is some short term mortality risk of less than 1% from the surgery.[41] The body mass index cutoffs for when surgery is appropriate are not yet clear.[40]

[edit] Epidemiology

Prevalence of diabetes worldwide in 2000 (per 1000 inhabitants). World average was 2.8%.
  no data
  ≤ 7.5
  7.5–15
  15–22.5
  22.5–30
  30–37.5
  37.5–45
  45–52.5
  52.5–60
  60–67.5
  67.5–75
  75–82.5
  ≥ 82.5

Globally as of 2010 it is estimated that there are 285 million people with type 2 diabetes making up about 90% of diabetes cases.[5] This is equivalent to about 6% of the worlds adult population.[42] It is common both in the developed and the developing world.[5] Women seem to be at a greater risk as do certain ethnic groups[5] such as Pacific Islanders, Latinos, and Native Americans.[4] This may be due to certain ethnic group's sensitivity to a Western lifestyle.[43] Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates.[5]

Rates of diabetes in 1985 were estimated at 30 million, increasing to 135 million in 1995 and 217 million in 2005.[44] This increase is believed to be primarily due to the global population aging, a decrease in exercise, and increasing rates of obesity.[44] It is recognized as a global epidemic by the World Health Organization.[45]

[edit] History

Main article: History of diabetes

Diabetes is one of the first diseases described[46] with an Egyptian manuscript from c. 1500 BCE mentioning “too great emptying of the urine.”[47] The first described cases are believed to be of type 1 diabetes.[47] Indian physicians around the same time identified the disease and classified it as madhumeha or honey urine noting that the urine would attract ants.[47] The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Appollonius Of Memphis.[47] The disease was rare during the time of the Roman empire with Galen commenting that he had only seen two cases during his career.[47] Type 1 and type 2 diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400-500 AD with type 1 associated with youth and type 2 with being overweight.[47] The term "mellitus" or "from honey" was added by the Britain John Rolle in the late 1700s to separate the condition from diabetes insipidus which is also associated with frequent urination.[47] While many measure where tried effective treatment was not developed until the early part of the 20th century when the Canadians Frederick Banting and Charles Best developed insulin in 1921 and 1922.[47] This was followed by the development of the long acting insulin NPH in the 1940s.[47]

[edit] References

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