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Wikipedia

Type 2 diabetes

February 16, 2024

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin.[6] Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss.[3] Symptoms may also include increased hunger, having a sensation of pins and needles, and sores (wounds) that do not heal.[3] Often symptoms come on slowly.[6] Long-term complications from high blood sugar include heart disease, strokes, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations.[1] The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.[4][5]

Type 2 diabetes
Other namesDiabetes mellitus type 2;
adult-onset diabetes;[1]
noninsulin-dependent diabetes mellitus (NIDDM)
A blue circle is the universal symbol of diabetes.[2]
Pronunciation
SpecialtyEndocrinology
SymptomsIncreased thirst, frequent urination, unexplained weight loss, increased hunger[3]
ComplicationsHyperosmolar hyperglycemic state, diabetic ketoacidosis, heart disease, strokes, diabetic retinopathy, kidney failure, amputations[1][4][5]
Usual onsetMiddle or older age[6]
DurationLong term[6]
CausesObesity, lack of exercise, genetics[1][6]
Diagnostic methodBlood test[3]
PreventionMaintaining normal weight, exercising, healthy diet[1]
TreatmentDietary changes, metformin, insulin, bariatric surgery[1][7][8][9]
Prognosis10 year shorter life expectancy[10]
Frequency392 million (2015)[11]

Type 2 diabetes primarily occurs as a result of obesity and lack of exercise.[1] Some people are genetically more at risk than others.[6]

Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily to type 1 diabetes and gestational diabetes.[1] In type 1 diabetes there is a lower total level of insulin to control blood glucose, due to an autoimmune induced loss of insulin-producing beta cells in the pancreas.[12][13] Diagnosis of diabetes is by blood tests such as fasting plasma glucose, oral glucose tolerance test, or glycated hemoglobin (A1C).[3]

Type 2 diabetes is largely preventable by staying a normal weight, exercising regularly, and eating a healthy diet (high in fruits and vegetables and low in sugar and saturated fats).[1] Treatment involves exercise and dietary changes.[1] If blood sugar levels are not adequately lowered, the medication metformin is typically recommended.[7][14] Many people may eventually also require insulin injections.[9] In those on insulin, routinely checking blood sugar levels (such as through a continuous glucose monitor) is advised; however, this may not be needed in those who are not on insulin therapy.[15] Bariatric surgery often improves diabetes in those who are obese.[8][16]

Rates of type 2 diabetes have increased markedly since 1960 in parallel with obesity.[17] As of 2015 there were approximately 392 million people diagnosed with the disease compared to around 30 million in 1985.[11][18] Typically it begins in middle or older age,[6] although rates of type 2 diabetes are increasing in young people.[19][20] Type 2 diabetes is associated with a ten-year-shorter life expectancy.[10] Diabetes was one of the first diseases ever described, dating back to an Egyptian manuscript from c. 1500 BCE.[21] The importance of insulin in the disease was determined in the 1920s.[22]

Signs and symptoms

 
Overview of the most significant symptoms of diabetes

The classic symptoms of diabetes are frequent urination (polyuria), increased thirst (polydipsia), increased hunger (polyphagia), and weight loss.[23] Other symptoms that are commonly present at diagnosis include a history of blurred vision, itchiness, peripheral neuropathy, recurrent vaginal infections, and fatigue.[13] Other symptoms may include loss of taste.[24] Many people, however, have no symptoms during the first few years and are diagnosed on routine testing.[13] A small number of people with type 2 diabetes can develop a hyperosmolar hyperglycemic state (a condition of very high blood sugar associated with a decreased level of consciousness and low blood pressure).[13]

Complications

Main article: Complications of diabetes

Type 2 diabetes is typically a chronic disease associated with a ten-year-shorter life expectancy.[10] This is partly due to a number of complications with which it is associated, including: two to four times the risk of cardiovascular disease, including ischemic heart disease and stroke; a 20-fold increase in lower limb amputations, and increased rates of hospitalizations.[10] In the developed world, and increasingly elsewhere, type 2 diabetes is the largest cause of nontraumatic blindness and kidney failure.[25] It has also been associated with an increased risk of cognitive dysfunction and dementia through disease processes such as Alzheimer's disease and vascular dementia.[26] Other complications include hyperpigmentation of skin (acanthosis nigricans), sexual dysfunction, and frequent infections.[23] There is also an association between type 2 diabetes and mild hearing loss.[27]

Causes

The development of type 2 diabetes is caused by a combination of lifestyle and genetic factors.[25][28] While some of these factors are under personal control, such as diet and obesity, other factors are not, such as increasing age, female sex, and genetics.[10] Obesity is more common in women than men in many parts of Africa.[29] The nutritional status of a mother during fetal development may also play a role, with one proposed mechanism being that of DNA methylation.[30] The intestinal bacteria Prevotella copri and Bacteroides vulgatus have been connected with type 2 diabetes.[31]

Lifestyle

Main article: Lifestyle causes of type 2 diabetes

Lifestyle factors are important to the development of type 2 diabetes, including obesity and being overweight (defined by a body mass index of greater than 25), lack of physical activity, poor diet, psychological stress, and urbanization.[10][32] 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 cases in Pima Indians and Pacific Islanders.[13] Among those who are not obese, a high waist–hip ratio is often present.[13] Smoking appears to increase the risk of type 2 diabetes.[33] A lack of sleep has also been linked to type 2 diabetes.[34] Laboratory studies have linked short-term sleep deprivations to changes in glucose metabolism, nervous system activity, or hormonal factors that may lead to diabetes.[34]

Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.[35][36] The type of fats in the diet are important, with saturated fats and trans fatty acids increasing the risk, and polyunsaturated and monounsaturated fat decreasing the risk.[28] Eating a lot of white rice appears to play a role in increasing risk.[37] A lack of exercise is believed to cause 7% of cases.[38] Persistent organic pollutants may also play a role.[39]

Genetics

Main article: Genetic causes of type 2 diabetes

Most cases of diabetes involve many genes, with each being a small contributor to an increased probability of becoming a type 2 diabetic.[10] The proportion of diabetes that is inherited is estimated at 72%.[40] More than 36 genes and 80 single nucleotide polymorphisms (SNPs) had been found that contribute to the risk of type 2 diabetes.[41][42] All of these genes together still only account for 10% of the total heritable component of the disease.[41] 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.[13] Most of the genes linked to diabetes are involved in pancreatic beta cell functions.[13]

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").[10][13] These include maturity onset diabetes of the young (MODY), Donohue syndrome, and Rabson–Mendenhall syndrome, among others.[10] Maturity onset diabetes of the young constitute 1–5% of all cases of diabetes in young people.[43]

Epigenetics

Epigenetic regulation occurs at multiple levels including (1) direct methylation of cytosine and adenine residues in DNA, (2) covalent modification of histone proteins in chromatin, and (3) action of non coding microRNAs (for other examples, see Wikipedia article "Epigenetics"). On November 17–19, 2017, the American Diabetes Association held a research symposium entitled "Epigenetics and Epigenomics: Implications for Diabetes and Obesity." As a result of this symposium, an overview of the state of the field was presented in which it was noted that over 1,000 research articles have been published that address the intersection of diabetes and epigenetics or epigenomics.[44] The current state of knowledge in this field is addressed the Wikipedia article "Epigenetics of diabetes Type 2."

Medical conditions

There are a number of medications and other health problems that can predispose to diabetes.[45] Some of the medications include: glucocorticoids, thiazides, beta blockers, atypical antipsychotics,[46] and statins.[47] Those who have previously had gestational diabetes are at a higher risk of developing type 2 diabetes.[23] Other health problems that are associated include: acromegaly, Cushing's syndrome, hyperthyroidism, pheochromocytoma, and certain cancers such as glucagonomas.[45] Individuals with cancer may be at a higher risk of mortality if they also have diabetes.[48] Testosterone deficiency is also associated with type 2 diabetes.[49][50] Eating disorders may also interact with type 2 diabetes, with bulimia nervosa increasing the risk and anorexia nervosa decreasing it.[51]

Pathophysiology

Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance.[13] 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.[52] In the liver, insulin normally suppresses glucose release. However, in the setting of insulin resistance, the liver inappropriately releases glucose into the blood.[10] 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.[13]

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.[10] However, not all people with insulin resistance develop diabetes since an impairment of insulin secretion by pancreatic beta cells is also required.[13]

In the early stages of insulin resistance, the mass of beta cells expands, increasing the output of insulin to compensate for the insulin insensitivity.[53] But when type 2 diabetes has become manifest, a type 2 diabetic will have lost about half of their beta cells.[53]Fatty acids in the beta cells activate FOXO1, resulting in apoptosis of the beta cells.[53]

The causes of the aging-related insulin resistance seen in obesity and in type 2 diabetes are uncertain. Effects of intracellular lipid metabolism and ATP production in liver and muscle cells may contribute to insulin resistance.[54] New evidence also points to a role of a brain region called the hypothalamus in the development of insulin resistance. For one thing, a gene called Dusp8 is linked with an increased risk for diabetes.[55] This gene codes for a protein that regulates neuronal signaling in the hypothalamus. Also, infusions into the hypothalamus of a hormone called leptin normalize blood glucose and diminish insulin resistance in diabetic animals.[56] Activation of hypothalamic cells by leptin has an important role in maintaining normal levels of blood glucose. Thus, both the endocrine cells of the pancreas AND cells in the hypothalamus may have a role in the etiology of type 2 diabetes.

Hypothalamic cells regulate blood glucose via projections to the autonomic nervous system. Autonomic innervation of liver and muscle cells stimulates an increased uptake of glucose. In diabetic humans, the control of blood glucose by the autonomic nervous system is abnormal.[57] Leptin-sensitive, glucose regulating neurons become resistant to leptin during aging or during exposure to a high-fat diet. These leptin-resistant neurons fail to restrain food intake, obesity, and blood glucose. The reasons for this lowered responsiveness to leptin are uncertain and are part of the puzzle of the causes of type 2 diabetes.[58]

Blood glucose levels can also be normalized in diabetic rodents by a single intrahypothalamic infusion of Fibroblast Growth Factor 1 (FGF1), an effect that persists for months even in severely diabetic animals. This remarkable cure of diabetes is accomplished by a stimulation of accessory brain cells called astrocytes.[59][60] Hypothalamic astrocytes that produce Fatty Acid Binding Protein 7 (FABP7) are targets of FGF1; these cells are also in close contact with leptin-sensitive neurons, influence their function, and regulate leptin sensitivity.[61][62] An abnormal function of FABP7+ astrocytes thus may contribute to the resistance to leptin and insulin that appear during aging and during exposure to high-fat diets.

During aging, FABP7+ astrocytes develop cytoplasmic granules derived from degenerating mitochondria. This mitochondrial degeneration is partly due to the oxidative stress of the heightened amounts of fatty acids that are taken up by these cells and oxidized within mitochondria.[63][64] A pathological degeneration of mitochondria in these cells may compromise their normal functions and contribute to abnormalities in the control of blood glucose by the hypothalamus.

Diagnosis

WHO diabetes diagnostic criteria[65][66]  edit
Condition 2-hour glucose Fasting glucose HbA1c
Unit mmol/L mg/dL mmol/L mg/dL mmol/mol DCCT %
Normal < 7.8 < 140 < 6.1 < 110 < 42 < 6.0
Impaired fasting glycaemia < 7.8 < 140 6.1–7.0 110–125 42–46 6.0–6.4
Impaired glucose tolerance ≥ 7.8 ≥ 140 < 7.0 < 126 42–46 6.0–6.4
Diabetes mellitus ≥ 11.1 ≥ 200 ≥ 7.0 ≥ 126 ≥ 48 ≥ 6.5

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:[67]

  • fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL)
or

A random blood sugar of greater than 11.1 mmol/L (200 mg/dL) in association with typical symptoms[23] or a glycated hemoglobin (HbA1c) of ≥ 48 mmol/mol (≥ 6.5 DCCT %) is another method of diagnosing diabetes.[10] 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 ≥ 48 mmol/mol (≥ 6.5 DCCT %) should be used to diagnose diabetes.[68] This recommendation was adopted by the American Diabetes Association in 2010.[69] Positive tests should be repeated unless the person presents with typical symptoms and blood sugars >11.1 mmol/L (>200 mg/dL).[68]

ADA diabetes diagnostic criteria in 2015[70]  
Diabetes mellitus Prediabetes
HbA1c ≥6.5% 5.7–6.4%
Fasting glucose ≥126 mg/dL 100–125 mg/dL
2h glucose ≥200 mg/dL 140–199 mg/dL
Random glucose with classic symptoms ≥200 mg/dL Not available

Threshold for diagnosis of diabetes is based on the relationship between results of glucose tolerance tests, fasting glucose or HbA1c and complications such as retinal problems.[10] A fasting or random blood sugar is preferred over the glucose tolerance test, as they are more convenient for people.[10] HbA1c 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.[71] It is estimated that 20% of people with diabetes in the United States do not realize that they have the disease.[10]

Type 2 diabetes is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency.[72] This is in contrast to type 1 diabetes in which there is an absolute insulin deficiency due to destruction of islet cells in the pancreas and gestational diabetes that is a new onset of high blood sugars associated with pregnancy.[13] Type 1 and type 2 diabetes can typically be distinguished based on the presenting circumstances.[68] 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,[73] with C-peptide levels normal or high in type 2 diabetes, but low in type 1 diabetes.[74]

Screening

Universal screening for diabetes in people without risk factors or symptoms is not recommended.[75][76] Screening is recommended by the World Health Organization, the United States Preventive Services Task Force (USPSTF), and the American Diabetes Association for high-risk adults.[77][78][79] Risk factors considered by the USPSTF include adults over 35 years old who are overweight or have obesity and adults without symptoms whose blood pressure is greater than 135/80 mmHg.[80][needs update][77] For those whose blood pressure is less, the evidence is insufficient to recommend for or against screening.[80][needs update] The American Diabetes Society recommends screening for adults with a body mass index (BMI) over 25.[79] For people of Asian descent, screening is recommended if they have a BMI over 23.[79] Other high risk groups include people with a first degree relative with diabetes; some ethnic groups, including Hispanics, African-Americans, and Native-Americans; a history of gestational diabetes; polycystic ovary syndrome; excess weight; and conditions associated with metabolic syndrome.[23] There is no evidence that screening changes the risk of death and any benefit of screening on adverse effects, incidence of type 2 diabetes, HbA1c or socioeconomic effects are not clear.[76][81]

In the UK, NICE guidelines suggest taking action to prevent diabetes for people with a body mass index (BMI) of 30 or more.[82] For people of Black African, African-Caribbean, South Asian and Chinese descent the recommendation to start prevention starts at the BMI of 27,5.[82] A study based on a large sample of people in England suggest even lower BMIs for certain ethnic groups for the start of prevention, for example 24 in South Asian and 21 in Bangladeshi populations.[83][84]

Prevention

Main article: Prevention of type 2 diabetes

Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise.[85][86] Intensive lifestyle measures may reduce the risk by over half.[25][87] The benefit of exercise occurs regardless of the person's initial weight or subsequent weight loss.[88] High levels of physical activity reduce the risk of diabetes by about 28%.[89] Evidence for the benefit of dietary changes alone, however, is limited,[90] with some evidence for a diet high in green leafy vegetables[91] and some for limiting the intake of sugary drinks.[92] There is an association between higher intake of sugar-sweetened fruit juice and diabetes, but no evidence of an association with 100% fruit juice.[93] A 2019 review found evidence of benefit from dietary fiber.[94]

In those with impaired glucose tolerance, a 2019 systematic review found moderate-quality evidence that Metformin, when compared to diet and exercise or a placebo intervention, appeared to delay or reduce the risk of developing type 2 diabetes.[95] This same review found moderate-quality evidence that when compared to intensive diet and exercise, Metformin did not reduce risk of developing type 2 diabetes, as well as very low-quality evidence that combining Metformin with intensive diet and exercise does not appear to have any effect on risk of developing type 2 diabetes when compared to intensive diet and exercise alone.[95] This systematic review only found one suitable trial comparing Metformin with Sulphonylurea in reducing risk of type 2 diabetes but it did not report any patient-relevant outcomes.[95]

A Cochrane systematic review assessed the effect of alpha-glucosidase inhibitors in people with impaired glucose tolerance, impaired fasting blood glucose, elevated glycated hemoglobin A1c (HbA1c).[96] It was found that Acarbose appeared to reduce incidence of diabetes mellitus type 2 when compared to placebo, however there was no conclusive evidence that acarbose compare to diet and exercise, metformin, placebo, no intervention improved all-cause mortality, reduced or increased risk of cardiovascular mortality, serious or non-serious adverse events, non-fatal stroke, congestive heart failure, or non-fatal myocardial infarction.[96] The same review found that there was no conclusive evidence that voglibose compared to diet and exercise or placebo reduced incidence of diabetes mellitus type 2, or any of the other measured outcomes.[96]

A 2017 review found that, long term, lifestyle changes decreased the risk by 28%, while medication does not reduce risk after withdrawal.[97] While low vitamin D levels are associated with an increased risk of diabetes, correcting the levels by supplementing vitamin D3 does not improve that risk.[98]

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.[25] Self-monitoring of blood glucose for people with newly diagnosed type 2 diabetes may be used in combination with education,[99] although the benefit of self-monitoring in those not using multi-dose insulin is questionable.[25] In those who do not want to measure blood levels, measuring urine levels may be done.[100] Managing other cardiovascular risk factors, such as hypertension, high cholesterol, and microalbuminuria, improves a person's life expectancy.[25] Decreasing the systolic blood pressure to less than 140 mmHg is associated with a lower risk of death and better outcomes.[101] Intensive blood pressure management (less than 130/80 mmHg) as opposed to standard blood pressure management (less than 140-160 mmHg systolic to 85–100 mmHg diastolic) results in a slight decrease in stroke risk but no effect on overall risk of death.[102]

Intensive blood sugar lowering (HbA1c<6%) as opposed to standard blood sugar lowering (HbA1c of 7–7.9%) does not appear to change mortality.[103][104] The goal of treatment is typically an HbA1c of 7 to 8% or a fasting glucose of less than 7.2 mmol/L (130 mg/dL); however these goals may be changed after professional clinical consultation, taking into account particular risks of hypoglycemia and life expectancy.[79][105][106] Hypoglycemia is associated with adverse outcomes in older people with type 2 diabetes.[107] Despite guidelines recommending that intensive blood sugar control be based on balancing immediate harms with long-term benefits, many people – for example people with a life expectancy of less than nine years who will not benefit, are over-treated.[108]

It is recommended that all people with type 2 diabetes get regular eye examinations.[13] There is moderate evidence suggesting that treating gum disease by scaling and root planing results in an improvement in blood sugar levels for people with diabetes.[109]

Lifestyle

Exercise

A proper diet and regular exercise are foundations of diabetic care,[23] with one review indicating that a greater amount of exercise improved outcomes.[110] Regular exercise may improve blood sugar control, decrease body fat content, and decrease blood lipid levels.[111]

Diet

Further information: Diabetic diet

Calorie restriction to promote weight loss is generally recommended.[112][70] Around 80 percent of obese people with type 2 diabetes achieve complete remission with no need for medication if they sustain a weight loss of at least 15 kilograms (33 lb),[113][114] but most patients are not able to achieve or sustain significant weight loss.[115] Even modest weight loss can produce significant improvements in glycemic control and reduce the need for medication.[116]

Several diets may be effective such as the Dietary Approaches to Stop Hypertension (DASH), Mediterranean diet, low-fat diet, or monitored carbohydrate diets such as a low carbohydrate diet.[70][117][118] Other recommendations include emphasizing intake of fruits, vegetables, reduced saturated fat and low-fat dairy products, and with a macronutrient intake tailored to the individual, to distribute calories and carbohydrates throughout the day.[70][119] A 2021 review showed that consumption of tree nuts (walnuts, almonds, and hazelnuts) reduced fasting blood glucose in diabetic people.[120] As of 2015, there is insufficient data to recommend nonnutritive sweeteners, which may help reduce caloric intake.[121] An elevated intake of microbiota-accessible carbohydrates can help reducing the effects of T2D.[122] Viscous fiber supplements may be useful in those with diabetes.[123]

Culturally appropriate education may help people with type 2 diabetes control their blood sugar levels for up to 24 months.[124] There is not enough evidence to determine if lifestyle interventions affect mortality in those who already have type 2 diabetes.[87]

Stress management

Although psychological stress is recognized as a risk factor for type 2 diabetes,[10] the effect of stress management interventions on disease progression are not established.[125] A Cochrane review is under way to assess the effects of mindfulness‐based interventions for adults with type 2 diabetes.[126]

Medications

 
Metformin 500 mg tablets

Blood sugar control

See also: Anti-diabetic medication

There are several classes of anti-diabetic medications available. Metformin is generally recommended as a first line treatment as there is some evidence that it decreases mortality;[7][25][127] however, this conclusion is questioned.[128] Metformin should not be used in those with severe kidney or liver problems.[23] The American Diabetes Association and European Association for the Study of Diabetes recommend using a GLP-1 receptor agonist or SGLT2 inhibitor as the first-line treatment in patients who have or are at high risk for atherosclerotic cardiovascular disease, heart failure, or kidney disease.[129][130] The higher cost of these drugs compared to metformin has limited their use.[115][131][132]

A second oral agent of another class or insulin may be added if metformin is not sufficient after three months.[105] Other classes of medications include: sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists.[105] A 2018 review found that SGLT2 inhibitors and GLP-1 agonists, but not DPP-4 inhibitors, were associated with lower mortality than placebo or no treatment.[133] Rosiglitazone, a thiazolidinedione, has not been found to improve long-term outcomes even though it improves blood sugar levels.[134] Additionally it is associated with increased rates of heart disease and death.[135]

Injections of insulin may either be added to oral medication or used alone.[25] Most people do not initially need insulin.[13] When it is used, a long-acting formulation is typically added at night, with oral medications being continued.[23][25] Doses are then increased to effect (blood sugar levels being well controlled).[25] When nightly insulin is insufficient, twice daily insulin may achieve better control.[23] The long acting insulins glargine and detemir are equally safe and effective,[136] and do not appear much better than neutral protamine Hagedorn (NPH) insulin, but as they are significantly more expensive, they are not cost effective as of 2010.[137] In those who are pregnant, insulin is generally the treatment of choice.[23]

Blood pressure lowering

Many international guidelines recommend blood pressure treatment targets that are lower than 140/90 mmHg for people with diabetes.[138] However, there is only limited evidence regarding what the lower targets should be. A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg,[139] and a subsequent review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130–140mmHg, although there was an increased risk of adverse events.[140]

2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin-angiotensin system to reduce the risks of progression to end-stage renal disease, cardiovascular events, and death.[70] There is some evidence that angiotensin converting enzyme inhibitors (ACEIs) are superior to other inhibitors of the renin-angiotensin system such as angiotensin receptor blockers (ARBs),[141] or aliskiren in preventing cardiovascular disease.[142] Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes.[143] There is no evidence that combining ACEIs and ARBs provides additional benefits.[143]

Other

The use of aspirin to prevent cardiovascular disease in diabetes is controversial.[70] Aspirin is recommended in people at high risk of cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.[144] 2015 American Diabetes Association recommendations for aspirin use (based on expert consensus or clinical experience) are that low-dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease (10-year cardiovascular disease risk, 5–10%).[70]

Vitamin D supplementation to people with type 2 diabetes may improve markers of insulin resistance and HbA1c.[145]

Sharing their electronic health records with people who have type 2 diabetes helps them to reduce their blood sugar levels. It is a way of helping people understand their own health condition and involving them actively in its management.[146][147]

Surgery

Weight loss surgery in those who are obese is an effective measure to treat diabetes.[148] Many are able to maintain normal blood sugar levels with little or no medication following surgery[149] and long-term mortality is decreased.[150] There however is some short-term mortality risk of less than 1% from the surgery.[151] The body mass index cutoffs for when surgery is appropriate are not yet clear.[150] It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.[152][153]

Epidemiology

Further information: Epidemiology of diabetes
 
Prevalence of total diabetes by age and Global Burden of Disease super-region in 2021

The International Diabetes Federation estimates nearly 537 million people lived with diabetes worldwide in 2021,[154] 90–95% of whom have type 2 diabetes.[155] Diabetes is common both in the developed and the developing world.[10]

Some ethnic groups such as South Asians, Pacific Islanders, Latinos, and Native Americans are at particularly high risk of developing type 2 diabetes.[23] Type 2 diabetes in normal weight individuals represents 60 to 80 percent of all cases in some Asian countries. The mechanism causing diabetes in non-obese individuals is poorly understood.[156][157][158]

Rates of diabetes in 1985 were estimated at 30 million, increasing to 135 million in 1995 and 217 million in 2005.[18] This increase is believed to be primarily due to the global population aging, a decrease in exercise, and increasing rates of obesity.[18] Traditionally considered a disease of adults, type 2 diabetes is increasingly diagnosed in children in parallel with rising obesity rates.[10] The five countries with the greatest number of people with diabetes as of 2000 are India having 31.7 million, China 20.8 million, the United States 17.7 million, Indonesia 8.4 million, and Japan 6.8 million.[159] It is recognized as a global epidemic by the World Health Organization.[1]

History

Further information: History of diabetes

Diabetes is one of the first diseases described[21] with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine."[160] The first described cases are believed to be of type 1 diabetes.[160] Indian physicians around the same time identified the disease and classified it as madhumeha or honey urine noting that the urine would attract ants.[160] The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Apollonius Memphites.[160] The disease was rare during the time of the Roman empire with Galen commenting that he had only seen two cases during his career.[160]

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.[160] Effective treatment was not developed until the early part of the 20th century when the Canadians Frederick Banting and Charles Best discovered insulin in 1921 and 1922.[160] This was followed by the development of the long acting NPH insulin in the 1940s.[160]

In 1916, Elliot Joslin proposed that in people with diabetes, periods of fasting are helpful.[161] Subsequent research has supported this, and weight loss is a first line treatment in type 2 diabetes.[161]

Research

Researchers developed the Diabetes Severity Score (DISSCO), a tool that might better than the standard blood test at identify if a person's condition is declining. It uses a computer algorithm to analyse data from anonymised electronic patient records and produces a score based on 34 indicators.[162][163]

References

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Works cited

  • Kahn CR, Ferris HA, O'Neill BT (2020). "Pathophysiology of Type 1 Diabetes Mellitus". Williams Textbook of Endocrinology (14 ed.). Elsevier. pp. 1349–1370.
  • International Diabetes Federation (2021). IDF Diabetes Atlas (PDF) (10 ed.). International Diabetes Federation. ISBN 9782930229980. Retrieved 18 March 2022.

External links

  • IDF Diabetes Atlas 2015
  • National Diabetes Information Clearinghouse 2010-02-21 at the Wayback Machine
  • Centers for Disease Control (Endocrine pathology)
  • ADA's Standards of Medical Care in Diabetes 2019

February 16, 2024
type, diabetes, formerly, known, adult, onset, diabetes, form, diabetes, mellitus, that, characterized, high, blood, sugar, insulin, resistance, relative, lack, insulin, common, symptoms, include, increased, thirst, frequent, urination, fatigue, unexplained, w. Type 2 diabetes T2D formerly known as adult onset diabetes is a form of diabetes mellitus that is characterized by high blood sugar insulin resistance and relative lack of insulin 6 Common symptoms include increased thirst frequent urination fatigue and unexplained weight loss 3 Symptoms may also include increased hunger having a sensation of pins and needles and sores wounds that do not heal 3 Often symptoms come on slowly 6 Long term complications from high blood sugar include heart disease strokes diabetic retinopathy which can result in blindness kidney failure and poor blood flow in the limbs which may lead to amputations 1 The sudden onset of hyperosmolar hyperglycemic state may occur however ketoacidosis is uncommon 4 5 Type 2 diabetesOther namesDiabetes mellitus type 2 adult onset diabetes 1 noninsulin dependent diabetes mellitus NIDDM A blue circle is the universal symbol of diabetes 2 Pronunciation d aɪ e b iː t e s SpecialtyEndocrinologySymptomsIncreased thirst frequent urination unexplained weight loss increased hunger 3 ComplicationsHyperosmolar hyperglycemic state diabetic ketoacidosis heart disease strokes diabetic retinopathy kidney failure amputations 1 4 5 Usual onsetMiddle or older age 6 DurationLong term 6 CausesObesity lack of exercise genetics 1 6 Diagnostic methodBlood test 3 PreventionMaintaining normal weight exercising healthy diet 1 TreatmentDietary changes metformin insulin bariatric surgery 1 7 8 9 Prognosis10 year shorter life expectancy 10 Frequency392 million 2015 11 Type 2 diabetes primarily occurs as a result of obesity and lack of exercise 1 Some people are genetically more at risk than others 6 Type 2 diabetes makes up about 90 of cases of diabetes with the other 10 due primarily to type 1 diabetes and gestational diabetes 1 In type 1 diabetes there is a lower total level of insulin to control blood glucose due to an autoimmune induced loss of insulin producing beta cells in the pancreas 12 13 Diagnosis of diabetes is by blood tests such as fasting plasma glucose oral glucose tolerance test or glycated hemoglobin A1C 3 Type 2 diabetes is largely preventable by staying a normal weight exercising regularly and eating a healthy diet high in fruits and vegetables and low in sugar and saturated fats 1 Treatment involves exercise and dietary changes 1 If blood sugar levels are not adequately lowered the medication metformin is typically recommended 7 14 Many people may eventually also require insulin injections 9 In those on insulin routinely checking blood sugar levels such as through a continuous glucose monitor is advised however this may not be needed in those who are not on insulin therapy 15 Bariatric surgery often improves diabetes in those who are obese 8 16 Rates of type 2 diabetes have increased markedly since 1960 in parallel with obesity 17 As of 2015 there were approximately 392 million people diagnosed with the disease compared to around 30 million in 1985 11 18 Typically it begins in middle or older age 6 although rates of type 2 diabetes are increasing in young people 19 20 Type 2 diabetes is associated with a ten year shorter life expectancy 10 Diabetes was one of the first diseases ever described dating back to an Egyptian manuscript from c 1500 BCE 21 The importance of insulin in the disease was determined in the 1920s 22 Contents 1 Signs and symptoms 1 1 Complications 2 Causes 2 1 Lifestyle 2 2 Genetics 2 3 Epigenetics 2 4 Medical conditions 3 Pathophysiology 4 Diagnosis 5 Screening 6 Prevention 7 Management 7 1 Lifestyle 7 1 1 Exercise 7 1 2 Diet 7 1 3 Stress management 7 2 Medications 7 2 1 Blood sugar control 7 2 2 Blood pressure lowering 7 2 3 Other 7 3 Surgery 8 Epidemiology 9 History 10 Research 11 References 11 1 Works cited 12 External linksSigns and symptoms nbsp Overview of the most significant symptoms of diabetesThe classic symptoms of diabetes are frequent urination polyuria increased thirst polydipsia increased hunger polyphagia and weight loss 23 Other symptoms that are commonly present at diagnosis include a history of blurred vision itchiness peripheral neuropathy recurrent vaginal infections and fatigue 13 Other symptoms may include loss of taste 24 Many people however have no symptoms during the first few years and are diagnosed on routine testing 13 A small number of people with type 2 diabetes can develop a hyperosmolar hyperglycemic state a condition of very high blood sugar associated with a decreased level of consciousness and low blood pressure 13 Complications Main article Complications of diabetes Type 2 diabetes is typically a chronic disease associated with a ten year shorter life expectancy 10 This is partly due to a number of complications with which it is associated including two to four times the risk of cardiovascular disease including ischemic heart disease and stroke a 20 fold increase in lower limb amputations and increased rates of hospitalizations 10 In the developed world and increasingly elsewhere type 2 diabetes is the largest cause of nontraumatic blindness and kidney failure 25 It has also been associated with an increased risk of cognitive dysfunction and dementia through disease processes such as Alzheimer s disease and vascular dementia 26 Other complications include hyperpigmentation of skin acanthosis nigricans sexual dysfunction and frequent infections 23 There is also an association between type 2 diabetes and mild hearing loss 27 CausesThe development of type 2 diabetes is caused by a combination of lifestyle and genetic factors 25 28 While some of these factors are under personal control such as diet and obesity other factors are not such as increasing age female sex and genetics 10 Obesity is more common in women than men in many parts of Africa 29 The nutritional status of a mother during fetal development may also play a role with one proposed mechanism being that of DNA methylation 30 The intestinal bacteria Prevotella copri and Bacteroides vulgatus have been connected with type 2 diabetes 31 Lifestyle Main article Lifestyle causes of type 2 diabetes Lifestyle factors are important to the development of type 2 diabetes including obesity and being overweight defined by a body mass index of greater than 25 lack of physical activity poor diet psychological stress and urbanization 10 32 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 cases in Pima Indians and Pacific Islanders 13 Among those who are not obese a high waist hip ratio is often present 13 Smoking appears to increase the risk of type 2 diabetes 33 A lack of sleep has also been linked to type 2 diabetes 34 Laboratory studies have linked short term sleep deprivations to changes in glucose metabolism nervous system activity or hormonal factors that may lead to diabetes 34 Dietary factors also influence the risk of developing type 2 diabetes Consumption of sugar sweetened drinks in excess is associated with an increased risk 35 36 The type of fats in the diet are important with saturated fats and trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk 28 Eating a lot of white rice appears to play a role in increasing risk 37 A lack of exercise is believed to cause 7 of cases 38 Persistent organic pollutants may also play a role 39 Genetics Main article Genetic causes of type 2 diabetes Most cases of diabetes involve many genes with each being a small contributor to an increased probability of becoming a type 2 diabetic 10 The proportion of diabetes that is inherited is estimated at 72 40 More than 36 genes and 80 single nucleotide polymorphisms SNPs had been found that contribute to the risk of type 2 diabetes 41 42 All of these genes together still only account for 10 of the total heritable component of the disease 41 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 13 Most of the genes linked to diabetes are involved in pancreatic beta cell functions 13 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 10 13 These include maturity onset diabetes of the young MODY Donohue syndrome and Rabson Mendenhall syndrome among others 10 Maturity onset diabetes of the young constitute 1 5 of all cases of diabetes in young people 43 Epigenetics Epigenetic regulation occurs at multiple levels including 1 direct methylation of cytosine and adenine residues in DNA 2 covalent modification of histone proteins in chromatin and 3 action of non coding microRNAs for other examples see Wikipedia article Epigenetics On November 17 19 2017 the American Diabetes Association held a research symposium entitled Epigenetics and Epigenomics Implications for Diabetes and Obesity As a result of this symposium an overview of the state of the field was presented in which it was noted that over 1 000 research articles have been published that address the intersection of diabetes and epigenetics or epigenomics 44 The current state of knowledge in this field is addressed the Wikipedia article Epigenetics of diabetes Type 2 Medical conditions There are a number of medications and other health problems that can predispose to diabetes 45 Some of the medications include glucocorticoids thiazides beta blockers atypical antipsychotics 46 and statins 47 Those who have previously had gestational diabetes are at a higher risk of developing type 2 diabetes 23 Other health problems that are associated include acromegaly Cushing s syndrome hyperthyroidism pheochromocytoma and certain cancers such as glucagonomas 45 Individuals with cancer may be at a higher risk of mortality if they also have diabetes 48 Testosterone deficiency is also associated with type 2 diabetes 49 50 Eating disorders may also interact with type 2 diabetes with bulimia nervosa increasing the risk and anorexia nervosa decreasing it 51 PathophysiologyType 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance 13 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 52 In the liver insulin normally suppresses glucose release However in the setting of insulin resistance the liver inappropriately releases glucose into the blood 10 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 13 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 10 However not all people with insulin resistance develop diabetes since an impairment of insulin secretion by pancreatic beta cells is also required 13 In the early stages of insulin resistance the mass of beta cells expands increasing the output of insulin to compensate for the insulin insensitivity 53 But when type 2 diabetes has become manifest a type 2 diabetic will have lost about half of their beta cells 53 Fatty acids in the beta cells activate FOXO1 resulting in apoptosis of the beta cells 53 The causes of the aging related insulin resistance seen in obesity and in type 2 diabetes are uncertain Effects of intracellular lipid metabolism and ATP production in liver and muscle cells may contribute to insulin resistance 54 New evidence also points to a role of a brain region called the hypothalamus in the development of insulin resistance For one thing a gene called Dusp8 is linked with an increased risk for diabetes 55 This gene codes for a protein that regulates neuronal signaling in the hypothalamus Also infusions into the hypothalamus of a hormone called leptin normalize blood glucose and diminish insulin resistance in diabetic animals 56 Activation of hypothalamic cells by leptin has an important role in maintaining normal levels of blood glucose Thus both the endocrine cells of the pancreas AND cells in the hypothalamus may have a role in the etiology of type 2 diabetes Hypothalamic cells regulate blood glucose via projections to the autonomic nervous system Autonomic innervation of liver and muscle cells stimulates an increased uptake of glucose In diabetic humans the control of blood glucose by the autonomic nervous system is abnormal 57 Leptin sensitive glucose regulating neurons become resistant to leptin during aging or during exposure to a high fat diet These leptin resistant neurons fail to restrain food intake obesity and blood glucose The reasons for this lowered responsiveness to leptin are uncertain and are part of the puzzle of the causes of type 2 diabetes 58 Blood glucose levels can also be normalized in diabetic rodents by a single intrahypothalamic infusion of Fibroblast Growth Factor 1 FGF1 an effect that persists for months even in severely diabetic animals This remarkable cure of diabetes is accomplished by a stimulation of accessory brain cells called astrocytes 59 60 Hypothalamic astrocytes that produce Fatty Acid Binding Protein 7 FABP7 are targets of FGF1 these cells are also in close contact with leptin sensitive neurons influence their function and regulate leptin sensitivity 61 62 An abnormal function of FABP7 astrocytes thus may contribute to the resistance to leptin and insulin that appear during aging and during exposure to high fat diets During aging FABP7 astrocytes develop cytoplasmic granules derived from degenerating mitochondria This mitochondrial degeneration is partly due to the oxidative stress of the heightened amounts of fatty acids that are taken up by these cells and oxidized within mitochondria 63 64 A pathological degeneration of mitochondria in these cells may compromise their normal functions and contribute to abnormalities in the control of blood glucose by the hypothalamus DiagnosisWHO diabetes diagnostic criteria 65 66 edit Condition 2 hour glucose Fasting glucose HbA1cUnit mmol L mg dL mmol L mg dL mmol mol DCCT Normal lt 7 8 lt 140 lt 6 1 lt 110 lt 42 lt 6 0Impaired fasting glycaemia lt 7 8 lt 140 6 1 7 0 110 125 42 46 6 0 6 4Impaired glucose tolerance 7 8 140 lt 7 0 lt 126 42 46 6 0 6 4Diabetes mellitus 11 1 200 7 0 126 48 6 5The 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 67 fasting plasma glucose 7 0 mmol L 126 mg dL orwith 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 23 or a glycated hemoglobin HbA1c of 48 mmol mol 6 5 DCCT is another method of diagnosing diabetes 10 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 48 mmol mol 6 5 DCCT should be used to diagnose diabetes 68 This recommendation was adopted by the American Diabetes Association in 2010 69 Positive tests should be repeated unless the person presents with typical symptoms and blood sugars gt 11 1 mmol L gt 200 mg dL 68 ADA diabetes diagnostic criteria in 2015 70 Diabetes mellitus PrediabetesHbA1c 6 5 5 7 6 4 Fasting glucose 126 mg dL 100 125 mg dL2h glucose 200 mg dL 140 199 mg dLRandom glucose with classic symptoms 200 mg dL Not availableThreshold for diagnosis of diabetes is based on the relationship between results of glucose tolerance tests fasting glucose or HbA1c and complications such as retinal problems 10 A fasting or random blood sugar is preferred over the glucose tolerance test as they are more convenient for people 10 HbA1c 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 71 It is estimated that 20 of people with diabetes in the United States do not realize that they have the disease 10 Type 2 diabetes is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency 72 This is in contrast to type 1 diabetes in which there is an absolute insulin deficiency due to destruction of islet cells in the pancreas and gestational diabetes that is a new onset of high blood sugars associated with pregnancy 13 Type 1 and type 2 diabetes can typically be distinguished based on the presenting circumstances 68 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 73 with C peptide levels normal or high in type 2 diabetes but low in type 1 diabetes 74 ScreeningUniversal screening for diabetes in people without risk factors or symptoms is not recommended 75 76 Screening is recommended by the World Health Organization the United States Preventive Services Task Force USPSTF and the American Diabetes Association for high risk adults 77 78 79 Risk factors considered by the USPSTF include adults over 35 years old who are overweight or have obesity and adults without symptoms whose blood pressure is greater than 135 80 mmHg 80 needs update 77 For those whose blood pressure is less the evidence is insufficient to recommend for or against screening 80 needs update The American Diabetes Society recommends screening for adults with a body mass index BMI over 25 79 For people of Asian descent screening is recommended if they have a BMI over 23 79 Other high risk groups include people with a first degree relative with diabetes some ethnic groups including Hispanics African Americans and Native Americans a history of gestational diabetes polycystic ovary syndrome excess weight and conditions associated with metabolic syndrome 23 There is no evidence that screening changes the risk of death and any benefit of screening on adverse effects incidence of type 2 diabetes HbA1c or socioeconomic effects are not clear 76 81 In the UK NICE guidelines suggest taking action to prevent diabetes for people with a body mass index BMI of 30 or more 82 For people of Black African African Caribbean South Asian and Chinese descent the recommendation to start prevention starts at the BMI of 27 5 82 A study based on a large sample of people in England suggest even lower BMIs for certain ethnic groups for the start of prevention for example 24 in South Asian and 21 in Bangladeshi populations 83 84 PreventionMain article Prevention of type 2 diabetes Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise 85 86 Intensive lifestyle measures may reduce the risk by over half 25 87 The benefit of exercise occurs regardless of the person s initial weight or subsequent weight loss 88 High levels of physical activity reduce the risk of diabetes by about 28 89 Evidence for the benefit of dietary changes alone however is limited 90 with some evidence for a diet high in green leafy vegetables 91 and some for limiting the intake of sugary drinks 92 There is an association between higher intake of sugar sweetened fruit juice and diabetes but no evidence of an association with 100 fruit juice 93 A 2019 review found evidence of benefit from dietary fiber 94 In those with impaired glucose tolerance a 2019 systematic review found moderate quality evidence that Metformin when compared to diet and exercise or a placebo intervention appeared to delay or reduce the risk of developing type 2 diabetes 95 This same review found moderate quality evidence that when compared to intensive diet and exercise Metformin did not reduce risk of developing type 2 diabetes as well as very low quality evidence that combining Metformin with intensive diet and exercise does not appear to have any effect on risk of developing type 2 diabetes when compared to intensive diet and exercise alone 95 This systematic review only found one suitable trial comparing Metformin with Sulphonylurea in reducing risk of type 2 diabetes but it did not report any patient relevant outcomes 95 A Cochrane systematic review assessed the effect of alpha glucosidase inhibitors in people with impaired glucose tolerance impaired fasting blood glucose elevated glycated hemoglobin A1c HbA1c 96 It was found that Acarbose appeared to reduce incidence of diabetes mellitus type 2 when compared to placebo however there was no conclusive evidence that acarbose compare to diet and exercise metformin placebo no intervention improved all cause mortality reduced or increased risk of cardiovascular mortality serious or non serious adverse events non fatal stroke congestive heart failure or non fatal myocardial infarction 96 The same review found that there was no conclusive evidence that voglibose compared to diet and exercise or placebo reduced incidence of diabetes mellitus type 2 or any of the other measured outcomes 96 A 2017 review found that long term lifestyle changes decreased the risk by 28 while medication does not reduce risk after withdrawal 97 While low vitamin D levels are associated with an increased risk of diabetes correcting the levels by supplementing vitamin D3 does not improve that risk 98 ManagementFurther 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 25 Self monitoring of blood glucose for people with newly diagnosed type 2 diabetes may be used in combination with education 99 although the benefit of self monitoring in those not using multi dose insulin is questionable 25 In those who do not want to measure blood levels measuring urine levels may be done 100 Managing other cardiovascular risk factors such as hypertension high cholesterol and microalbuminuria improves a person s life expectancy 25 Decreasing the systolic blood pressure to less than 140 mmHg is associated with a lower risk of death and better outcomes 101 Intensive blood pressure management less than 130 80 mmHg as opposed to standard blood pressure management less than 140 160 mmHg systolic to 85 100 mmHg diastolic results in a slight decrease in stroke risk but no effect on overall risk of death 102 Intensive blood sugar lowering HbA1c lt 6 as opposed to standard blood sugar lowering HbA1c of 7 7 9 does not appear to change mortality 103 104 The goal of treatment is typically an HbA1c of 7 to 8 or a fasting glucose of less than 7 2 mmol L 130 mg dL however these goals may be changed after professional clinical consultation taking into account particular risks of hypoglycemia and life expectancy 79 105 106 Hypoglycemia is associated with adverse outcomes in older people with type 2 diabetes 107 Despite guidelines recommending that intensive blood sugar control be based on balancing immediate harms with long term benefits many people for example people with a life expectancy of less than nine years who will not benefit are over treated 108 It is recommended that all people with type 2 diabetes get regular eye examinations 13 There is moderate evidence suggesting that treating gum disease by scaling and root planing results in an improvement in blood sugar levels for people with diabetes 109 Lifestyle Exercise A proper diet and regular exercise are foundations of diabetic care 23 with one review indicating that a greater amount of exercise improved outcomes 110 Regular exercise may improve blood sugar control decrease body fat content and decrease blood lipid levels 111 Diet Further information Diabetic diet Calorie restriction to promote weight loss is generally recommended 112 70 Around 80 percent of obese people with type 2 diabetes achieve complete remission with no need for medication if they sustain a weight loss of at least 15 kilograms 33 lb 113 114 but most patients are not able to achieve or sustain significant weight loss 115 Even modest weight loss can produce significant improvements in glycemic control and reduce the need for medication 116 Several diets may be effective such as the Dietary Approaches to Stop Hypertension DASH Mediterranean diet low fat diet or monitored carbohydrate diets such as a low carbohydrate diet 70 117 118 Other recommendations include emphasizing intake of fruits vegetables reduced saturated fat and low fat dairy products and with a macronutrient intake tailored to the individual to distribute calories and carbohydrates throughout the day 70 119 A 2021 review showed that consumption of tree nuts walnuts almonds and hazelnuts reduced fasting blood glucose in diabetic people 120 As of 2015 update there is insufficient data to recommend nonnutritive sweeteners which may help reduce caloric intake 121 An elevated intake of microbiota accessible carbohydrates can help reducing the effects of T2D 122 Viscous fiber supplements may be useful in those with diabetes 123 Culturally appropriate education may help people with type 2 diabetes control their blood sugar levels for up to 24 months 124 There is not enough evidence to determine if lifestyle interventions affect mortality in those who already have type 2 diabetes 87 Stress management Although psychological stress is recognized as a risk factor for type 2 diabetes 10 the effect of stress management interventions on disease progression are not established 125 A Cochrane review is under way to assess the effects of mindfulness based interventions for adults with type 2 diabetes 126 Medications nbsp Metformin 500 mg tabletsBlood sugar control See also Anti diabetic medication There are several classes of anti diabetic medications available Metformin is generally recommended as a first line treatment as there is some evidence that it decreases mortality 7 25 127 however this conclusion is questioned 128 Metformin should not be used in those with severe kidney or liver problems 23 The American Diabetes Association and European Association for the Study of Diabetes recommend using a GLP 1 receptor agonist or SGLT2 inhibitor as the first line treatment in patients who have or are at high risk for atherosclerotic cardiovascular disease heart failure or kidney disease 129 130 The higher cost of these drugs compared to metformin has limited their use 115 131 132 A second oral agent of another class or insulin may be added if metformin is not sufficient after three months 105 Other classes of medications include sulfonylureas thiazolidinediones dipeptidyl peptidase 4 inhibitors SGLT2 inhibitors and GLP 1 receptor agonists 105 A 2018 review found that SGLT2 inhibitors and GLP 1 agonists but not DPP 4 inhibitors were associated with lower mortality than placebo or no treatment 133 Rosiglitazone a thiazolidinedione has not been found to improve long term outcomes even though it improves blood sugar levels 134 Additionally it is associated with increased rates of heart disease and death 135 Injections of insulin may either be added to oral medication or used alone 25 Most people do not initially need insulin 13 When it is used a long acting formulation is typically added at night with oral medications being continued 23 25 Doses are then increased to effect blood sugar levels being well controlled 25 When nightly insulin is insufficient twice daily insulin may achieve better control 23 The long acting insulins glargine and detemir are equally safe and effective 136 and do not appear much better than neutral protamine Hagedorn NPH insulin but as they are significantly more expensive they are not cost effective as of 2010 137 In those who are pregnant insulin is generally the treatment of choice 23 Blood pressure lowering Many international guidelines recommend blood pressure treatment targets that are lower than 140 90 mmHg for people with diabetes 138 However there is only limited evidence regarding what the lower targets should be A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg 139 and a subsequent review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130 140mmHg although there was an increased risk of adverse events 140 2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin angiotensin system to reduce the risks of progression to end stage renal disease cardiovascular events and death 70 There is some evidence that angiotensin converting enzyme inhibitors ACEIs are superior to other inhibitors of the renin angiotensin system such as angiotensin receptor blockers ARBs 141 or aliskiren in preventing cardiovascular disease 142 Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes 143 There is no evidence that combining ACEIs and ARBs provides additional benefits 143 Other The use of aspirin to prevent cardiovascular disease in diabetes is controversial 70 Aspirin is recommended in people at high risk of cardiovascular disease however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes 144 2015 American Diabetes Association recommendations for aspirin use based on expert consensus or clinical experience are that low dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease 10 year cardiovascular disease risk 5 10 70 Vitamin D supplementation to people with type 2 diabetes may improve markers of insulin resistance and HbA1c 145 Sharing their electronic health records with people who have type 2 diabetes helps them to reduce their blood sugar levels It is a way of helping people understand their own health condition and involving them actively in its management 146 147 Surgery Weight loss surgery in those who are obese is an effective measure to treat diabetes 148 Many are able to maintain normal blood sugar levels with little or no medication following surgery 149 and long term mortality is decreased 150 There however is some short term mortality risk of less than 1 from the surgery 151 The body mass index cutoffs for when surgery is appropriate are not yet clear 150 It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control 152 153 EpidemiologyFurther information Epidemiology of diabetes nbsp Prevalence of total diabetes by age and Global Burden of Disease super region in 2021The International Diabetes Federation estimates nearly 537 million people lived with diabetes worldwide in 2021 154 90 95 of whom have type 2 diabetes 155 Diabetes is common both in the developed and the developing world 10 Some ethnic groups such as South Asians Pacific Islanders Latinos and Native Americans are at particularly high risk of developing type 2 diabetes 23 Type 2 diabetes in normal weight individuals represents 60 to 80 percent of all cases in some Asian countries The mechanism causing diabetes in non obese individuals is poorly understood 156 157 158 Rates of diabetes in 1985 were estimated at 30 million increasing to 135 million in 1995 and 217 million in 2005 18 This increase is believed to be primarily due to the global population aging a decrease in exercise and increasing rates of obesity 18 Traditionally considered a disease of adults type 2 diabetes is increasingly diagnosed in children in parallel with rising obesity rates 10 The five countries with the greatest number of people with diabetes as of 2000 are India having 31 7 million China 20 8 million the United States 17 7 million Indonesia 8 4 million and Japan 6 8 million 159 It is recognized as a global epidemic by the World Health Organization 1 HistoryFurther information History of diabetes Diabetes is one of the first diseases described 21 with an Egyptian manuscript from c 1500 BCE mentioning too great emptying of the urine 160 The first described cases are believed to be of type 1 diabetes 160 Indian physicians around the same time identified the disease and classified it as madhumeha or honey urine noting that the urine would attract ants 160 The term diabetes or to pass through was first used in 230 BCE by the Greek Apollonius Memphites 160 The disease was rare during the time of the Roman empire with Galen commenting that he had only seen two cases during his career 160 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 160 Effective treatment was not developed until the early part of the 20th century when the Canadians Frederick Banting and Charles Best discovered insulin in 1921 and 1922 160 This was followed by the development of the long acting NPH insulin in the 1940s 160 In 1916 Elliot Joslin proposed that in people with diabetes periods of fasting are helpful 161 Subsequent research has supported this and weight loss is a first line treatment in type 2 diabetes 161 ResearchResearchers developed the Diabetes Severity Score DISSCO a tool that might better than the standard blood test at identify if a person s condition is declining It uses a computer algorithm to analyse data from anonymised electronic patient records and produces a score based on 34 indicators 162 163 References a b c d e f g h i j k Diabetes Fact sheet N 312 World Health Organization August 2011 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diabetes could help personalise treatment and improve outcomes NIHR Evidence Plain English summary National Institute for Health and Care Research 2020 08 07 doi 10 3310 alert 40652 S2CID 242997909 Zghebi SS Mamas MA Ashcroft DM Salisbury C Mallen CD Chew Graham CA et al May 2020 Development and validation of the DIabetes Severity SCOre DISSCO in 139 626 individuals with type 2 diabetes a retrospective cohort study BMJ Open Diabetes Research amp Care 8 1 e000962 doi 10 1136 bmjdrc 2019 000962 PMC 7228474 PMID 32385076 Works cited Kahn CR Ferris HA O Neill BT 2020 Pathophysiology of Type 1 Diabetes Mellitus Williams Textbook of Endocrinology 14 ed Elsevier pp 1349 1370 International Diabetes Federation 2021 IDF Diabetes Atlas PDF 10 ed International Diabetes Federation ISBN 9782930229980 Retrieved 18 March 2022 External linksDiabetes mellitus at Wikipedia s sister projects nbsp Definitions from Wiktionary nbsp Media from Commons nbsp News from Wikinews nbsp Quotations from Wikiquote nbsp Texts from Wikisource nbsp Textbooks from Wikibooks nbsp Resources from Wikiversity IDF Diabetes Atlas 2015 National Diabetes Information Clearinghouse Archived 2010 02 21 at the Wayback Machine Centers for Disease Control Endocrine pathology ADA s Standards of Medical Care in Diabetes 2019 Retrieved from https en wikipedia org w index php title Type 2 diabetes amp oldid 1199146097, wikipedia, wiki, book, books, library,

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