57298938 diabetes mellitus type 2

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Diabetes mellitus type 2

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Diabetes mellitus type 2Diabetes mellitus type 2Classification and external resources

Universal blue circle symbol for diabetes. ICD-10 ICD-9 OMIM DiseasesDB MedlinePlus eMedicine MeSH E11. [2] [3]

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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.[10] Diabetes is often initially managed by increasing exercise and dietary modification. If the condition progresses, medications may be needed. Unlike type 1 d

iabetes, there is very little tendency toward ketoacidosis though it is not unheard of.[11] One effect that can occur is nonketonic hyperglycemia. Long-term complications from high blood sugar can include increased risk of heart attacks, strokes, amputation, and kidney failure. For extreme cases, circulation of limbs is affected, potentially requiring amputation. Loss of hearing, eyesight, and cognitive ability has also been linked to this condition.


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Signs and symptomsThe classic symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), fatigue and weight loss.[12]

CauseType2 diabetes is due to a combination of lifestyle and genetic factors.[13] [14]Recently, intrauterine growth restriction (IUGR) or prenatal undernutrition (macro- and micronutrient) was identified as another probable factor [15] A clue for this concept was the Dutch Hunger Winter and the pioneering work of ProfessorBarker.

LifestyleA number of lifestyle factors are known to be important to the development of type2 diabetes. In one study, those who had high levels of physical activity, a healthy diet, did not smoke, and consumed alcohol in moderation had an 82% lower ra

te of diabetes. When a normal weight was included, the rate was 89% lower. In this study, a healthy diet was defined as one high in fiber, with a high polyunsaturated to saturated fat ratio, and a lower mean glycemic index.[16] Obesity hasbeen found to contribute to approximately 55% of cases of type2 diabetes,[17] anddecreasing consumption of saturated fats and trans fatty acids while replacingthem with unsaturated fats may decrease the risk.[13] The increased rate of childhood obesity between the 1960s and 2000s is believed to have led to the increase in type2 diabetes in children and adolescents.[18] Environmental toxins may contribute to recent increases in the rate of type2 diabetes. A weak positive correlation has been found between the concentration in the urine of bisphenol A, a constituent of some plastics, and the incidence of type2 diabetes.[19]

Medical conditions

There are many factors which can potentially give rise to, or exacerbate, type 2diabetes. These include obesity, hypertension, elevated cholesterol (combined hyperlipidemia), and with the condition often termed metabolic syndrome (it is also known as Syndrome X, Reavan's syndrome, or CHAOS). Other causes include acromegaly, Cushing's syndrome, thyrotoxicosis, pheochromocytoma, chronic pancreatitis, cancer, and drugs. Additional factors found to increase the risk of type 2 diabetes include aging,[20] high-fat diets[21] and a less active lifestyle.[22] Subclinical Cushing's syndrome (cortisol excess) may be associated with type 1 diabetes.[23] The percentage of subclinical Cushing's syndrome in the diabetic population is about 9%.[24] Diabetic patients with a pituitary microadenoma can improve insulin sensitivity by removal of these microadenomas.[25] Hypogonadism is often associated with cortisol excess, and testosterone deficiency is also associated with type 2 diabetes,[26] [27] even if the exact mechanism by which testosterone improves insulin sensitivity is still not known.

GeneticsThere is also a strong inheritable genetic connection in type 2 diabetes: havingrelatives (especially first degree) with type 2 increases risks of developing type 2 diabetes substantially. In addition, there is also a mutation to the IsletAmyloid Polypeptide gene that results in an earlier onset, more severe, form ofdiabetes.[28] [29] About 55 percent of type 2 diabetes patients are obese at diagnosis[30] chronic obesity leads to increased insulin resistance that can develop into type 2 diabetes, most likely because adipose tissue (especially that in the abdomen around internal organs) is a source of several chemical signals to other tissues (hormones and cytokines). Other research shows that type 2 diabetes

causes obesity as an effect of the changes in metabolism and other deranged cellbehavior attendant on insulin resistance.[31]


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Diabetes mellitus type 2 However, environmental factors (almost certainly diet and weight) play a large part in the development of type 2 diabetes in addition to any genetic component. This can be seen from the adoption of the type 2 diabetes epidemiological pattern in those who have moved to a different environment ascompared to the same genetic pool who have not. Immigrants to Western developedcountries, for instance, as compared to lower incidence countries of origins.[32] There is a stronger inheritance pattern for type2 diabetes. Those with first-d

egree relatives with type2 diabetes have a much higher risk of developing type2 diabetes, increasing with the number of those relatives. Concordance among monozygotic twins is close to 100%, and about 25% of those with the disease have a family history of diabetes. Genes significantly associated with developing type2 diabetes, include TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX.[33] [34] KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11), encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2 (transcription factor 7like 2) regulates proglucagon gene expression andthus the production of glucagon-like peptide-1.[35] Moreover, obesity (which isan independent risk factor for type2 diabetes) is strongly inherited.[36] Monogenic forms, e.g., MODY, constitute 15 % of all cases.[37] Various hereditary conditions may feature diabetes, for example myotonic dystrophy and Friedreich's atax

ia. Wolfram's syndrome is an autosomal recessive neurodegenerative disorder thatfirst becomes evident in childhood. It consists of diabetes insipidus, diabetesmellitus, optic atrophy, and deafness, hence the acronym DIDMOAD.[38] Gene expression promoted by a diet of fat and glucose, as well as high levels of inflammation related cytokines found in the obese, results in cells that "produce fewerand smaller mitochondria than is normal," and are thus prone to insulin resistance.[39]

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PathophysiologyInsulin resistance means that body cells do not respond appropriately when insulin is present. This is a more complex problem than type 1, but is sometimes easi

er to treat, especially in the early years when insulin is often still being produced internally. Severe complications can result from improperly managed type 2diabetes, including renal failure, erectile dysfunction, blindness, slow healing wounds (including surgical incisions), and arterial disease, including coronary artery disease. The onset of type 2 diabetes has been most common in middle age and later life, although it is being more frequently seen in adolescents and young adults due to an increase in child obesity and inactivity. A type of diabetes called MODY is increasingly seen in adolescents, but this is classified as adiabetes due to a specific cause and not as type 2 diabetes. In the 2008 BantingLecture of the American Diabetes Association, DeFronzo enumerates eight main pathophysiological factors in the type 2 diabetic organism [40] Diabetes mellituswith 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 or diabetes due to a specific cause. Examples include diabetes mellitus such as MODY or those caused by hemochromatosis, pancreatic insufficiencies, or certain types of medications (e.g., long-term steroid use).

Diagnosis


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2006 WHO Diabetes criteria[41]Condition 2 hour glucose mmol/l(mg/dl) Normal Impaired fasting glycaemia Impaired glucose tolerance Diabetes mellitus


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PreventionOnset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise.[48] [49] Intensive lifestyle measures may reduce the risk by

over half.[14] Evidence for the benefit of dietary changes alone however is limited.[50] In those with impaired glucose tolerance diet and exercise and/or metformin or acarbose may decrease the risk of developing diabetes.[51] [14] Lifestyle interventions are more effective than metformin.[14]

ManagementManagement of type 2 diabetes focuses on lifestyle interventions, lowering othercardiovascular risk factors, and maintaining blood glucose levels in the normalrange.[14] Self-monitoring of blood glucose for people with newly diagnosed type 2 diabetes was recommended by the National Health Services in 2008[52] howeverthe benefit of self monitoring in those not using multi-dose insulin is questionable.[14]

LifestyleAerobic exercise is beneficial in diabetes with a greater amount of exercise yielding better results.[53] It leads to a decrease in HbA1C, improved insulin resistance, and a better V02 max.[53] Resistance training is also useful and the combination of both types of exercise may be most effective.[53] A diabetic diet that promotes weight loss is important.[54] While the best diet type to achieve this is controversial[54] a low glycemic index diet has been found to improve blood sugar control.[55] Culturally appropriate education may help people with type2 diabetes control their blood sugar levels, for up to six months at least.[56]

MedicationsThere are several classes of medications available. Metformin is generally recom

mended as a first line treatment as there is good evidence that it decreases mortality.[14] Injections of insulin may either be added to oral medication or usedalone.[14] Other classes of medications used to treat type 2 diabetes are sulfonylureas, nonsulfonylurea secretagogues, alpha glucosidase inhibitors, and thiazolidinediones.[14] InsulinMetformin 500mg tablets

When insulin is used, a long-acting formulation is usually added initially, while continuing oral medications.[14] Doses of insulin are increased to effect.[14]The initial insulin regimen is often chosen based on the patient's blood glucose profile.[57] Initially, adding nightly insulin to patients failing oral medications may be best.[58] Nightly insulin combines better with metformin than withsulfonylureas.[59] When nightly insulin is insufficient, choices include: Premixed insulin with a fixed ratio of short and intermediate acting insulin; this tends to be more effective than long acting insulin, but is associated with increased hypoglycemia.[60] [61] [62] Initial total daily dosage of biphasic insulin can be 10 units if the fasting plasma glucose values are less than 180mg/dl or 12 units when the fasting plasma glucose is above 180mg/dl".[61] A guide to titratingfixed ratio insulin is available.[57] Long acting insulins include insulin glargine and insulin detemir. A meta-analysis of randomized controlled trials by theCochrane Collaboration found "only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2".[63] More recently, a randomized controlled trial found that


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Diabetes mellitus type 2 although long acting insulins were less effective, theywere associated with reduced hypoglycemic episodes.[60]

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Cardiovascular risk factorsManaging other cardiovascular risk factors including hypertension, high choleste

rol, and microalbuminuria improves a person's life expectancy.[14]

SurgeryGastric Bypass procedures are currently considered an elective procedure with nouniversally accepted algorithm to decide who should have the surgery. In the diabetic patient, certain types result in 99-100% prevention of insulin resistanceand 80-90% clinical resolution or remission of type 2 diabetes. In 1991, the NIH (National Institutes of Health) Consensus Development Conference on Gastrointestinal Surgery for Obesity proposed that the body mass index (BMI) threshold toconsider surgery should drop from 40 to 35 in the appropriate patient. More recently, the American Society for Bariatric Surgery (ASBS) and the ASBS Foundationsuggested that the BMI threshold be lowered to 30 in the presence of severe co-m

orbidities.[64] Debate has flourished about the role of gastric bypass surgery in type 2 diabetics since the publication of The Swedish Obese Subjects Study. The largest prospective series showed a large decrease in the occurrence of type 2diabetes in the post-gastric bypass patient at both 2 years (odds ratio was 0.14) and at 10 years (odds ratio was 0.25).[65] A study of 20-years of Greenville(US) gastric bypass patients found that 80% of those with type 2 diabetes beforesurgery no longer required insulin or oral agents to maintain normal glucose levels. Weight loss occurred rapidly in many people in the study who had had the surgery. The 20% who did not respond to bypass surgery were, typically, those whowere older and had had diabetes for over 20 years.[66]

ProgressionThe way type 2 diabetes is managed may change with age. Insulin production decre

ases because of age-related impairment of pancreatic beta cells. Additionally, insulin resistance increases because of the loss of lean tissue and the accumulation of fat, particularly intra-abdominal fat, and the decreased tissue sensitivity to insulin. Glucose tolerance progressively declines with age, leading to a high prevalence of type2 diabetes and postchallenge hyperglycemia in the older population.[67] Age-related glucose intolerance is often accompanied by insulin resistance, but circulating insulin levels are similar to those of younger people.[68] Treatment goals for older patients with diabetes vary with the individual, and take into account health status, as well as life expectancy, level of dependence, and willingness to adhere to a treatment regimen.[69]

PrognosisIn adults type 2 diabetes is the primary cause of blindness and kidney failure.[14]

EpidemiologyGlobally in 2003 it was estimated that there were 150 million people with type 2diabetes.[70] The incidence varies substantially in different parts of the world, almost certainly because of environmental and lifestyle factors, though theseare not known in detail.[71] In the United States there are 23.6 million people(7.8% of the population) with diabetes with 17.9 million being diagnosed,[72] 90% of whom are type 2.[73] With prevalence rates doubling between 1990 and 2005,CDC has characterized the increase as an epidemic.[74] Traditionally considereda disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates [75] due to alterations in dietary patterns as w

ell as in life styles during childhood.[76]


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External links Diabetes mellitus type 2 (http://www.dmoz.org/Health/Conditions_and_Diseases/Endocrine_Disorders/ Pancreas/Diabetes/Type_2/) at the Open Directory Project Type2 Diabetes - General Information (http://www.diabetes.co.uk/type2-diabetes.html)

National Diabetes Information Clearinghouse (http://diabetes.niddk.nih.gov/) Centers for Disease Control (Endocrine pathology) (http://www.cdc.gov/diabetes/)


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Article Sources and Contributors

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Article Sources and ContributorsDiabetes mellitus type 2 Source: http://en.wikipedia.org/w/index.php?oldid=431524143 Contributors: 07parsonse, 4wajzkd02, 7, A3camero, Abaute, Abcd1234123, Afapro

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Image Sources, Licenses and ContributorsFile:Blue circle for diabetes.svg Source: http://en.wikipedia.org/w/index.php?title=File:Blue_circle_for_diabetes.svg License: Public Domain Contributors: User:Remember the dot Image:Metformin 500mg Tablets.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Metformin_500mg_Tablets.jpg License: Public Domain Contribut

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