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Type 2 diabetes

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. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Other symptoms include increased hunger, having a sensation of pins and needles, and sores (wounds) that heal slowly. Symptoms often develop slowly. Long-term complications from high blood sugar include heart disease; stroke; diabetic retinopathy, which can result in blindness; kidney failure; and poor blood flow in the lower limbs, which may lead to amputations. A sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

Signs and symptoms
The classic symptoms of diabetes are frequent urination (polyuria), increased thirst (polydipsia), increased hunger (polyphagia), and weight loss. Other symptoms that are commonly present at diagnosis include a history of blurred vision, itchiness, peripheral neuropathy, recurrent vaginal infections, and fatigue. Other symptoms may include loss of taste. Many people, however, have no symptoms during the first few years and are diagnosed on routine testing. 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. Other complications include hyperpigmentation of skin (acanthosis nigricans), sexual dysfunction, diabetic ketoacidosis, and frequent infections. There is also an association between type 2 diabetes and mild hearing loss. ==Causes==
Causes
The development of type 2 diabetes is caused by a combination of lifestyle and genetic factors. 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. Obesity is more common in women than men in many parts of Africa. The nutritional status of a mother during fetal development may also play a role. Lifestyle 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. 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. Lack of sleep has also been linked to type 2 diabetes. Laboratory studies have linked short-term sleep deprivations to changes in glucose metabolism, nervous system activity, or hormonal factors that may lead to diabetes. The type of fats in the diet are important, with saturated fat and trans fatty acids increasing the risk, and polyunsaturated and monounsaturated fat decreasing the risk. A lack of exercise is believed to cause 7% of cases. Sedentary lifestyle is another risk factor. Persistent organic pollutants may also play a role. Genetics Most cases of diabetes involve many genes, with each being a small contributor to an increased probability of becoming a type 2 diabetic. More than 36 genes and 80 single nucleotide polymorphisms (SNPs) had been found that contribute to the risk of type 2 diabetes. All of these genes together still only account for 10% of the total heritable component of the disease. Epigenetic regulation may have a role in type 2 diabetes. Medical conditions There are a number of medications and other health problems that can predispose to diabetes. Some of the medications include: glucocorticoids, thiazides, beta blockers, atypical antipsychotics, and statins. Those who have previously had gestational diabetes are at a higher risk of developing type 2 diabetes. Testosterone deficiency is also associated with type 2 diabetes. Eating disorders may also interact with type 2 diabetes, with bulimia nervosa increasing the risk and anorexia nervosa decreasing it. ==Pathophysiology==
Pathophysiology
integrate beta cell function and insulin sensitivity in a way so that the results remain constant across dynamical compensation. Changed from Cobelli et al. 2007, Hannon et al. 2018 and Dietrich et al. 2024 Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance. Insulin resistance occurs within the muscles, liver, and fat tissue. In the liver, insulin normally suppresses glucose release. However, in the setting of insulin resistance, the liver inappropriately releases glucose into the blood. 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. But when type 2 diabetes has become manifest, the person will have lost about half of their beta cells. ==Diagnosis==
Diagnosis
The World Health Organization definition of diabetes (both type 1 and type 2) is for a single raised glucose reading with symptoms, or for raised glucose readings on two separate dates, of either: • fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL) :or • glucose tolerance test with 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 Positive tests should be repeated unless the person presents with typical symptoms and blood sugar >11.1 mmol/L (>200 mg/dL). 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. It is estimated that 20% of people with diabetes in the United States do not realize that they have the disease. 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. with C-peptide levels normal or high in type 2 diabetes, but low in type 1 diabetes. ==Screening==
Screening
The United States Preventive Services Task Force (USPSTF) recommended in 2021 screening for type 2 diabetes in adults aged 35 to 70 years old who are overweight (i.e. BMI over 25) or have obesity. However, the American Diabetes Association (ADA) recommended in 2024 screening in all adults from the age of 35 years. ADA also recommends screening in adults of all ages with a BMI over 25 (or over 23 in Asian Americans) with another risk factor: first-degree relative with diabetes, ethnicity at high risk for diabetes, blood pressure ≥130/80 mmHg or on therapy for hypertension, history of cardiovascular disease, physical inactivity, polycystic ovary syndrome or severe obesity. In the UK, NICE guidelines suggest taking action to prevent diabetes for people with a body mass index (BMI) of 30 or more. 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. ==Prevention==
Prevention
Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise. Intensive lifestyle measures may reduce the risk by over half. The benefit of exercise occurs regardless of the person's initial weight or subsequent weight loss. High levels of physical activity reduce the risk of diabetes by about 28%. Evidence for the benefit of dietary changes alone, however, is limited, and some for limiting the intake of sugary drinks. There is an association between higher intake of sugar-sweetened fruit juice and diabetes, but no evidence of an association with 100% fruit juice. A 2019 review found evidence of benefit from dietary fiber. A 2017 review found that, long term, lifestyle changes decreased the risk by 28%, while medication does not reduce risk after withdrawal. 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. In those with prediabetes, diet in combination with physical activity delays or reduces the risk of type 2 diabetes, according to a 2017 Cochrane review. In those with prediabetes, alpha-glucosidase inhibitors such as acarbose may delay or reduce the risk of type 2 diabetes when compared to placebo, however there was no conclusive evidence that acarbose improved cardiovascular mortality or cardiovascular events, according to a 2018 Cochrane review. In those with prediabetes, pioglitazone may delay or reduce the risk of developing type 2 diabetes compared to placebo or no intervention, but no difference was seen compared to metformin, and data were missing on mortality and complications and quality of life, according to a 2020 Cochrane review. In those with prediabetes, there was insufficient data to draw any conclusions on whether SGLT2 inhibitors may delay or reduce the risk of developing type 2 diabetes, according to a 2016 Cochrane review. ==Management==
Management
Management of type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range. Self-monitoring of blood glucose for people with newly diagnosed type 2 diabetes may be used in combination with education, although the benefit of self-monitoring in those not using multi-dose insulin is questionable. Managing other cardiovascular risk factors, such as hypertension, high cholesterol, and microalbuminuria, improves a person's life expectancy. 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. Intensive blood sugar lowering (HbA1c 1c of 7–7.9%) does not appear to change mortality. 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. Hypoglycemia is associated with adverse outcomes in older people with type 2 diabetes. 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. It is recommended that all people with type 2 diabetes get regular eye examinations. Lifestyle Exercise A proper diet and regular exercise are foundations of diabetic care, Regular exercise may improve blood sugar control, decrease body fat content, and decrease blood lipid levels. Diet Calorie restriction to promote weight loss is generally recommended. 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 , but most patients are not able to achieve or sustain significant weight loss. Several diets may be effective such as the DASH diet, Mediterranean diet, low-fat diet, or monitored carbohydrate diets such as a low carbohydrate diet. 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. A 2021 review showed that consumption of tree nuts (walnuts, almonds, and hazelnuts) reduced fasting blood glucose in diabetic people. , there is insufficient data to recommend nonnutritive sweeteners, which may help reduce caloric intake. An elevated intake of microbiota-accessible carbohydrates can help reducing the effects of T2D. Viscous fiber supplements may be useful in those with diabetes. Culturally appropriate education may help people with type 2 diabetes control their blood sugar levels for up to 24 months. There is not enough evidence to determine if lifestyle interventions affect mortality in those who already have type 2 diabetes. A Cochrane review is under way to assess the effects of mindfulness‐based interventions for adults with type 2 diabetes. Medications Blood sugar control There are several classes of diabetes medications available. Metformin is generally recommended as a first line treatment as there is some evidence that it decreases mortality; however, this conclusion is questioned. Metformin should not be used in those with severe kidney or liver problems. The higher cost of these drugs compared to metformin has limited their use. Other classes of medications include: sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists. Rosiglitazone, a thiazolidinedione, has not been found to improve long-term outcomes even though it improves blood sugar levels. Additionally it is associated with increased rates of heart disease and death. Injections of insulin may either be added to oral medication or used alone. and do not appear much better than NPH insulin, but as they are significantly more expensive, they are not cost effective as of 2010. In those who are pregnant, insulin is generally the treatment of choice. 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, and a subsequent review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130 and 140 mmHg, although there was an increased risk of adverse events. 2023 European Society of Cardiology guidelines recommend systolic blood pressure lowering to 130 mmHg in most people with diabetes. In people with diabetes and hypertension and either albuminuria or chronic kidney disease, an inhibitor of the renin-angiotensin system (such as an ACE inhibitor or angiotensin receptor blocker) to reduce the risks of progression of kidney disease and present cardiovascular events. 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), or aliskiren in preventing cardiovascular disease. Although a 2016 review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes. There is no evidence that combining ACEIs and ARBs provides additional benefits. The use of aspirin (acetylsalicylic acid) to prevent cardiovascular disease in diabetes is controversial. Aspirin as primary prevention may have greater risk than benefit, but could be considered in people aged 50 to 70 with another significant cardiovascular risk factor and low risk of bleeding after information about possible risks and benefits as part of shared-decision making. 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. Surgery Weight loss surgery in those who are obese is an effective measure to treat diabetes. Many are able to maintain normal blood sugar levels with little or no medication following surgery and long-term mortality is decreased. The body mass index cutoffs for when surgery is appropriate are not yet clear. It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control. ==Epidemiology==
Epidemiology
super-region in 2021 The International Diabetes Federation estimates nearly 537 million people lived with diabetes worldwide in 2021, 90–95% of whom have type 2 diabetes. Diabetes is common both in the developed and the developing world. Rates of diabetes in 1985 were estimated at 30 million, increasing to 135 million in 1995 and 217 million in 2005. It is recognized as a global epidemic by the World Health Organization. ==History==
History
Diabetes is one of the first diseases described The first described cases are believed to be of type 1 diabetes. Indian physicians around the same time identified the disease and classified it as madhumeha or honey urine noting that the urine would attract ants. Subsequent research has supported this, and weight loss is a first line treatment in type 2 diabetes. == Research ==
Research
In 2020, Diabetes Severity Score (DISSCO) was developed which is a tool that could be better than HbA1c identify if a person's condition is declining. It uses a computer algorithm to analyze data from anonymized electronic patient records and produces a score based on 34 indicators. Replication in more patients and evidence over longer periods would be needed before considering this treatment as a possible cure. == References ==
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