Type2 diabetes is largely preventable by staying at a normal weight, exercising regularly, and eating a healthy diet (high in fruits and vegetables and low in sugar and saturated fat).[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 type2 diabetes have increased markedly since 1960 in parallel with obesity.[17] As of 2015, there were approximately 392million people diagnosed with the disease compared to around 30million in 1985.[11][18] Typically, it begins in middle or older age,[6] although rates of type2 diabetes are increasing in young people.[19][20] Type2 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.1500BCE.[21] Type1 and type2 diabetes were identified as separate conditions in 400–500CE with type1 associated with youth and type2 with being overweight.[22] The importance of insulin in the disease was determined in the 1920s.[23]
Type2 diabetes is typically a chronic disease associated with a ten-year-shorter life expectancy.[10][26] 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, type2 diabetes is the largest cause of nontraumatic blindness and kidney failure.[27] 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.[28] Other complications include hyperpigmentation of skin (acanthosis nigricans), sexual dysfunction, diabetic ketoacidosis, and frequent infections.[24][29][30] There is also an association between type 2 diabetes and mild hearing loss.[31]
Causes
The development of type2 diabetes is caused by a combination of lifestyle and genetic factors.[27][32] 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]Generous consumption of alcohol is also a risk factor.[33]Obesity is more common in women than men in many parts of Africa.[34] The nutritional status of a mother during fetal development may also play a role.[35]
Lifestyle factors are important to the development of type2 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][36] 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 type2 diabetes.[37]Lack of sleep has also been linked to type2 diabetes.[38] Laboratory studies have linked short-term sleep deprivations to changes in glucose metabolism, nervous system activity, or hormonal factors that may lead to diabetes.[38]
Most cases of diabetes involve many genes, with each being a small contributor to an increased probability of becoming a type2 diabetic.[10] The proportion of diabetes that is inherited is estimated at 72%.[45] More than 36genes and 80single nucleotide polymorphisms (SNPs) had been found that contribute to the risk of type2 diabetes.[46][47] All of these genes together still only account for 10% of the total heritable component of the disease.[46] The TCF7L2allele, for example, increases the risk of developing diabetes by 1.5times 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]
Type2 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.[60] 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 type2 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, so that the disposition index remains constant.[61] But when type2 diabetes has become manifest, the person will have lost about half of their beta cells.[61]
The causes of the aging-related insulin resistance seen in obesity and in type2 diabetes are uncertain. Effects of intracellular lipid metabolism and ATP production in liver and muscle cells may contribute to insulin resistance.[62]
The World Health Organization definition of diabetes (both type1 and type2) is for a single raised glucose reading with symptoms, otherwise raised values on two occasions, of either:[65]
fasting plasma glucose ≥ 7.0mmol/L (126mg/dL)
or
glucose tolerance test with two hours after the oral dose a plasma glucose ≥ 11.1mmol/L (200mg/dL)
A random blood sugar of greater than 11.1mmol/L (200mg/dL) in association with typical symptoms[24] or a glycated hemoglobin (HbA1c) of ≥48mmol/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 HbA1c threshold of ≥48mmol/mol (≥6.5 DCCT%) should be used to diagnose diabetes.[66] This recommendation was adopted by the American Diabetes Association in 2010.[67] Positive tests should be repeated unless the person presents with typical symptoms and blood sugar >11.1mmol/L (>200mg/dL).[66]
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.[69] It is estimated that 20% of people with diabetes in the United States do not realize that they have the disease.[10]
Type2 diabetes is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency.[70] 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] Type1 and type2 diabetes can typically be distinguished based on the presenting circumstances.[66] If the diagnosis is in doubt antibody testing may be useful to confirm type1 diabetes and C-peptide levels may be useful to confirm type2 diabetes,[71] with C-peptide levels normal or high in type2 diabetes, but low in type1 diabetes.[72]
Screening
Universal screening for diabetes in people without risk factors or symptoms is not recommended.[73]
There is no evidence that screening changes the risk of death and any benefit of screening on adverse effects, incidence of type2 diabetes, HbA1c or socioeconomic effects are not clear.[74][75]
In the UK, NICE guidelines suggest taking action to prevent diabetes for people with a body mass index (BMI) of 30 or more.[76] For people of Black African, African-Caribbean, South Asian and Chinese descent the recommendation to start prevention starts at the BMI of 27,5.[76] 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.[77][78]
Onset of type2 diabetes can be delayed or prevented through proper nutrition and regular exercise.[79][80] Intensive lifestyle measures may reduce the risk by over half.[27][81] The benefit of exercise occurs regardless of the person's initial weight or subsequent weight loss.[82] High levels of physical activity reduce the risk of diabetes by about 28%.[83] Evidence for the benefit of dietary changes alone, however, is limited,[80] with some evidence for a diet high in green leafy vegetables[84] and some for limiting the intake of sugary drinks.[85] There is an association between higher intake of sugar-sweetened fruit juice and diabetes, but no evidence of an association with 100% fruit juice.[86] A 2019 review found evidence of benefit from dietary fiber.[87]
A 2017 review found that, long term, lifestyle changes decreased the risk by 28%, while medication does not reduce risk after withdrawal.[88] 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.[89]
In those with prediabetes, diet in combination with physical activity delays or reduces the risk of type2 diabetes, according to a 2017 Cochrane review.[80] In those with prediabetes, metformin may delay or reduce the risk of developing type2 diabetes compared to diet and exercise or a placebo intervention, but not compared to intensive diet and exercise, and there was not enough data on outcomes such as mortality and diabetic complications and health-related quality of life, according to a 2019 Cochrane review.[90] In those with prediabetes, alpha-glucosidase inhibitors such as acarbose may delay or reduce the risk of type2 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.[91] In those with prediabetes, pioglitazone may delay or reduce the risk of developing type2 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.[92] In those with prediabetes, there was insufficient data to draw any conclusions on whether SGLT2 inhibitors may delay or reduce the risk of developing type2 diabetes, according to a 2016 Cochrane review.[93]
Management of type2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range.[27] Self-monitoring of blood glucose for people with newly diagnosed type2 diabetes may be used in combination with education,[94] although the benefit of self-monitoring in those not using multi-dose insulin is questionable.[27] In those who do not want to measure blood levels, measuring urine levels may be done.[95] Managing other cardiovascular risk factors, such as hypertension, high cholesterol, and microalbuminuria, improves a person's life expectancy.[27] Decreasing the systolic blood pressure to less than 140mmHg is associated with a lower risk of death and better outcomes.[96] Intensive blood pressure management (less than 130/80mmHg) 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.[97]
Intensive blood sugar lowering (HbA1c < 6%) as opposed to standard blood sugar lowering (HbA1c of 7–7.9%) does not appear to change mortality.[98][99] The goal of treatment is typically an HbA1c of 7 to 8% or a fasting glucose of less than 7.2mmol/L (130mg/dL); however these goals may be changed after professional clinical consultation, taking into account particular risks of hypoglycemia and life expectancy.[100][101] Hypoglycemia is associated with adverse outcomes in older people with type 2 diabetes.[102] 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.[103]
It is recommended that all people with type2 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.[104]
Lifestyle
Exercise
A proper diet and regular exercise are foundations of diabetic care,[24] with one review indicating that a greater amount of exercise improved outcomes.[105] Regular exercise may improve blood sugar control, decrease body fat content, and decrease blood lipid levels.[106]
Calorie restriction to promote weight loss is generally recommended.[107] Around 80 percent of obese people with type2 diabetes achieve complete remission with no need for medication if they sustain a weight loss of at least 15 kilograms (33lb),[108][109] but most patients are not able to achieve or sustain significant weight loss.[110] Even modest weight loss can produce significant improvements in glycemic control and reduce the need for medication.[111]
Culturally appropriate education may help people with type2 diabetes control their blood sugar levels for up to 24 months.[120] There is not enough evidence to determine if lifestyle interventions affect mortality in those who already have type2 diabetes.[81]
Stress management
Although psychological stress is recognized as a risk factor for type2 diabetes,[10] the effect of stress management interventions on disease progression are not established.[121] A Cochrane review is under way to assess the effects of mindfulness‐based interventions for adults with type 2 diabetes.[122]
Injections of insulin may either be added to oral medication or used alone.[27] 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.[24][27] Doses are then increased to effect (blood sugar levels being well controlled).[27] When nightly insulin is insufficient, twice daily insulin may achieve better control.[24] The long acting insulins glargine and detemir are equally safe and effective,[132] and do not appear much better than NPH insulin, but as they are significantly more expensive, they are not cost effective as of 2010.[133] In those who are pregnant, insulin is generally the treatment of choice.[24]
Blood pressure lowering
Many international guidelines recommend blood pressure treatment targets that are lower than 140/90mmHg for people with diabetes.[134] 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 140mmHg,[135] 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.[136]
The use of statins in diabetes to prevent cardiovascular disease should be considered after evaluating the person's total risk for cardiovascular disease.[141]
The use of aspirin (acetylsalicylic acid) to prevent cardiovascular disease in diabetes is controversial.[141] Aspirin is recommended in people with previous cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.[142] 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.[141]
Vitamin D supplementation to people with type2 diabetes may improve markers of insulin resistance and HbA1c.[143]
Sharing their electronic health records with people who have type2 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.[144][145]
Surgery
Weight loss surgery in those who are obese is an effective measure to treat diabetes.[146] Many are able to maintain normal blood sugar levels with little or no medication following surgery[147] and long-term mortality is decreased.[148] There however is some short-term mortality risk of less than 1% from the surgery.[149] The body mass index cutoffs for when surgery is appropriate are not yet clear.[148] It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.[150][151]
Some ethnic groups such as South Asians, Pacific Islanders, Latinos, and Native Americans are at particularly high risk of developing type2 diabetes.[24] Type2 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.[154][155][156]
Rates of diabetes in 1985 were estimated at 30million, increasing to 135million in 1995 and 217million 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, type2 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 31.7million, China 20.8million, the United States 17.7million, Indonesia 8.4million, and Japan 6.8million.[157] It is recognized as a global epidemic by the World Health Organization.[1]
Diabetes is one of the first diseases described[21] with an Egyptian manuscript from c.1500BCE mentioning "too great emptying of the urine."[22][158] The first described cases are believed to be of type1 diabetes.[22] Indian physicians around the same time identified the disease and classified it as madhumeha or honey urine noting that the urine would attract ants.[22] The term "diabetes" or "to pass through" was first used in 230BCE by the Greek Apollonius Memphites.[22] The disease was rare during the time of the Roman empire with Galen commenting that he had only seen two cases during his career.[22]
Type1 and type2 diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400–500CE with type1 associated with youth and type2 with being overweight.[22] 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.[22] This was followed by the development of the longer acting NPH insulin in the 1940s.[22]
In 1916, Elliot Joslin proposed that in people with diabetes, periods of fasting are helpful.[159] Subsequent research has supported this, and weight loss is a first line treatment in type2 diabetes.[159]
Research
In 2020, Diabetes Severity Score (DISSCO) was developed which is a tool that might better than HbA1c identify if a person's condition is declining.[26][160] It uses a computer algorithm to analyse data from anonymised electronic patient records and produces a score based on 34 indicators.[161][160]
In April 2024 scientists reported the first case of reversion of type 2 diabetes by use of stem cells in a 59-year old man treated in 2021 who has since remain insulin-free.[162][163] Replication in more patients and evidence over longer periods would be needed before considering this treatment as a possible cure.
Related Research Articles
Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL).
Insulin resistance (IR) is a pathological condition in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.
Blood glucose monitoring is the use of a glucose meter for testing the concentration of glucose in the blood (glycemia). Particularly important in diabetes management, a blood glucose test is typically performed by piercing the skin to draw blood, then applying the blood to a chemically active disposable 'test-strip'. The other main option is continuous glucose monitoring (CGM). Different manufacturers use different technology, but most systems measure an electrical characteristic and use this to determine the glucose level in the blood. Skin-prick methods measure capillary blood glucose, whereas CGM correlates interstitial fluid glucose level to blood glucose level. Measurements may occur after fasting or at random nonfasting intervals, each of which informs diagnosis or monitoring in different ways.
Hyperglycemia or hyperglycaemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L after fasting for 8 hours and 10 mmol/L 2 hours after eating.
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome, and is sometimes used as an off-label adjunct to lessen the risk of metabolic syndrome in people who take antipsychotic medication. It has been shown to inhibit inflammation, and is not associated with weight gain. Metformin is taken by mouth.
Drugs used in diabetes treat types of diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.
Pioglitazone, sold under the brand name Actos among others, is an anti-diabetic medication used to treat type 2 diabetes. It may be used with metformin, a sulfonylurea, or insulin. Use is recommended together with exercise and diet. It is not recommended in type 1 diabetes. It is taken by mouth.
Gestational diabetes is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, obesity increases the rate of pre-eclampsia, cesarean sections, and embryo macrosomia, as well as gestational diabetes. Babies born to individuals with poorly treated gestational diabetes are at increased risk of macrosomia, of having hypoglycemia after birth, and of jaundice. If untreated, diabetes can also result in stillbirth. Long term, children are at higher risk of being overweight and of developing type 2 diabetes.
Sulfonylureas or sulphonylureas are a class of organic compounds used in medicine and agriculture. The functional group consists of a sulfonyl group (-S(=O)2) with its sulphur atom bonded to a nitrogen atom of a ureylene group (N,N-dehydrourea, a dehydrogenated derivative of urea). The side chains R1 and R2 distinguish various sulfonylureas. Sulfonylureas are the most widely used herbicide.
The main goal of diabetes management is to keep blood glucose (BG) levels as normal as possible. If diabetes is not well controlled, further challenges to health may occur. People with diabetes can measure blood sugar by various methods, such as with a BG meter or a continuous glucose monitor, which monitors over several days. Glucose can also be measured by analysis of a routine blood sample. Usually, people are recommended to control diet, exercise, and maintain a healthy weight, although some people may need medications to control their blood sugar levels. Other goals of diabetes management are to prevent or treat complications that can result from the disease itself and from its treatment.
Inhibitors of dipeptidyl peptidase 4 are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4). They can be used to treat diabetes mellitus type 2.
A diabetic diet is a diet that is used by people with diabetes mellitus or high blood sugar to minimize symptoms and dangerous complications of long-term elevations in blood sugar.
Prediabetes is a component of metabolic syndrome and is characterized by elevated blood sugar levels that fall below the threshold to diagnose diabetes mellitus. It usually does not cause symptoms but people with prediabetes often have obesity, dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. It is also associated with increased risk for cardiovascular disease (CVD). Prediabetes is more accurately considered an early stage of diabetes as health complications associated with type 2 diabetes often occur before the diagnosis of diabetes.
Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1DAs, or incretin mimetics, are a class of anorectic drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1, which is released by the gut after eating.
Complications of diabetes are secondary diseases that are a result of elevated blood glucose levels that occur in diabetic patients. These complications can be divided into two types: acute and chronic. Acute complications are complications that develop rapidly and can be exemplified as diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), lactic acidosis (LA), and hypoglycemia. Chronic complications develop over time and are generally classified in two categories: microvascular and macrovascular. Microvascular complications include neuropathy, nephropathy, and retinopathy; while cardiovascular disease, stroke, and peripheral vascular disease are included in the macrovascular complications.
Prevention of type 2 diabetes can be achieved with both lifestyle changes and use of medication. The American Diabetes Association categorizes people with prediabetes, who have glycemic levels higher than normal but do not meet criteria for diabetes, as a high-risk group. Without intervention, people with prediabetes progress to type 2 diabetes with a 5% to 10% rate. Diabetes prevention is achieved through weight loss and increased physical activity, which can reduce the risk of diabetes by 50% to 60%.
Empagliflozin, sold under the brand name Jardiance, among others, is an antidiabetic medication used to improve glucose control in people with type2 diabetes. It is taken by mouth.
Diabetes, also known as diabetes mellitus, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body becoming unresponsive to the hormone's effects. Classic symptoms include polydipsia, polyuria, weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the cardiovascular system, eye, kidney, and nerves. Diabetes accounts for approximately 4.2 million deaths every year, with an estimated 1.5 million caused by either untreated or poorly treated diabetes.
Frank B. Hu is a Chinese American nutrition and diabetes researcher. He is Chair of the Department of Nutrition and the Fredrick J. Stare Professor of Nutrition and Epidemiology at the Harvard T.H. Chan School of Public Health, and Professor of Medicine at the Harvard Medical School.
SGLT2 inhibitors are a class of medications that inhibit sodium-glucose transport proteins in the nephron, unlike SGLT1 inhibitors that perform a similar function in the intestinal mucosa. The foremost metabolic effect of this is to inhibit reabsorption of glucose in the kidney and therefore lower blood sugar. They act by inhibiting sodium/glucose cotransporter 2 (SGLT2). SGLT2 inhibitors are used in the treatment of type 2 diabetes. Apart from blood sugar control, gliflozins have been shown to provide significant cardiovascular benefit in people with type 2 diabetes. As of 2014, several medications of this class had been approved or were under development. In studies on canagliflozin, a member of this class, the medication was found to enhance blood sugar control as well as reduce body weight and systolic and diastolic blood pressure.
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