Type 2 diabetes
Type 2 diabetes | |
---|---|
Other names | Diabetes mellitus type 2; adult-onset diabetes; |
Prognosis | 10 year shorter life expectancy[10] |
Frequency | 392 million (2015)[11] |
Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of
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
Type 2 diabetes is largely preventable by staying at a normal weight,
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
The classic symptoms of diabetes are frequent urination (
Complications
Type 2 diabetes is typically a chronic disease associated with a ten-year-shorter life expectancy.
Causes
The development of type 2 diabetes is caused by a combination of lifestyle and genetic factors.
Lifestyle
Lifestyle factors are important to the development of type 2 diabetes, including obesity and being
Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.
Genetics
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%.[44] More than 36 genes and 80 single nucleotide polymorphisms (SNPs) had been found that contribute to the risk of type 2 diabetes.[45][46] All of these genes together still only account for 10% of the total heritable component of the disease.[45] 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
Epigenetics
Medical conditions
There are a number of medications and other health problems that can predispose to diabetes.
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.[56] 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
In the early stages of insulin resistance, the mass of beta cells expands, increasing the output of insulin to compensate for the insulin insensitivity.[57] But when type 2 diabetes has become manifest, a type 2 diabetic will have lost about half of their beta cells.[57]
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.[58] New evidence also points to a role of a brain region called the hypothalamus in the development of insulin resistance. A gene called Dusp8 is linked with an increased risk for diabetes.[59] 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.[60] 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.[61] 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.[62]
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.[63][64] 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.[65][66] 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
Diagnosis
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:[71]
- fasting plasma glucose ≥ 7.0 mmol/L (126 mg/dL)
- or
- with 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
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.[75] 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.[76] 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.[72] 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,[77] with C-peptide levels normal or high in type 2 diabetes, but low in type 1 diabetes.[78]
Screening
Universal
In the UK, NICE guidelines suggest taking action to prevent diabetes for people with a body mass index (BMI) of 30 or more.[86] For people of Black African, African-Caribbean, South Asian and Chinese descent the recommendation to start prevention starts at the BMI of 27,5.[86] 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.[87][88]
Prevention
Onset of type 2 diabetes can be delayed or prevented through proper nutrition and regular exercise.[89][90] Intensive lifestyle measures may reduce the risk by over half.[26][91] The benefit of exercise occurs regardless of the person's initial weight or subsequent weight loss.[92] High levels of physical activity reduce the risk of diabetes by about 28%.[93] Evidence for the benefit of dietary changes alone, however, is limited,[94] with some evidence for a diet high in green leafy vegetables[95] and some for limiting the intake of sugary drinks.[96] There is an association between higher intake of sugar-sweetened fruit juice and diabetes, but no evidence of an association with 100% fruit juice.[97] A 2019 review found evidence of benefit from dietary fiber.[98]
In those with
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).[100] 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.[100] 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.[100]
A 2017 review found that, long term, lifestyle changes decreased the risk by 28%, while medication does not reduce risk after withdrawal.[101] 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.[102]
Management
Management of type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range.
Intensive blood sugar lowering (HbA1c<6%) as opposed to standard blood sugar lowering (HbA1c of 7–7.9%) does not appear to change mortality.[107][108] 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.[83][109][110] Hypoglycemia is associated with adverse outcomes in older people with type 2 diabetes.[111] 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.[112]
It is recommended that all people with type 2 diabetes get regular
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.[114] Regular exercise may improve blood sugar control, decrease body fat content, and decrease blood lipid levels.[115]
Diet
Calorie restriction to promote weight loss is generally recommended.[116][74] 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),[117][118] but most patients are not able to achieve or sustain significant weight loss.[119] Even modest weight loss can produce significant improvements in glycemic control and reduce the need for medication.[120]
Several diets may be effective such as the
Culturally appropriate education may help people with type 2 diabetes control their blood sugar levels for up to 24 months.[128] There is not enough evidence to determine if lifestyle interventions affect mortality in those who already have type 2 diabetes.[91]
Stress management
Although psychological stress is recognized as a risk factor for type 2 diabetes,
Medications
Blood sugar control
There are several classes of
A second oral agent of another class or insulin may be added if metformin is not sufficient after three months.[109] Other classes of medications include: sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists.[109] 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.[137] Rosiglitazone, a thiazolidinedione, has not been found to improve long-term outcomes even though it improves blood sugar levels.[138] Additionally it is associated with increased rates of heart disease and death.[139]
Injections of insulin may either be added to oral medication or used alone.
Blood pressure lowering
Many international guidelines recommend blood pressure treatment targets that are lower than 140/90 mmHg for people with diabetes.[142] 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,[143] 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.[144]
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.
Other
The use of aspirin to prevent cardiovascular disease in diabetes is controversial.[74] 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.[148] 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%).[74]
Vitamin D supplementation to people with type 2 diabetes may improve markers of insulin resistance and HbA1c.[149]
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.[150][151]
Surgery
Weight loss surgery in those who are obese is an effective measure to treat diabetes.[152] Many are able to maintain normal blood sugar levels with little or no medication following surgery[153] and long-term mortality is decreased.[154] There however is some short-term mortality risk of less than 1% from the surgery.[155] The body mass index cutoffs for when surgery is appropriate are not yet clear.[154] It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.[156][157]
Epidemiology
The
Some ethnic groups such as
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.[163] It is recognized as a global epidemic by the World Health Organization.[1]
History
Diabetes is one of the first diseases described
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.[164] 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.[164] This was followed by the development of the long acting NPH insulin in the 1940s.[164]
In 1916, Elliot Joslin proposed that in people with diabetes, periods of fasting are helpful.[166] Subsequent research has supported this, and weight loss is a first line treatment in type 2 diabetes.[166]
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.[167][168] It uses a computer algorithm to analyse data from anonymised electronic patient records and produces a score based on 34 indicators.[169][170]
References
- ^ a b c d e f g h i j k "Diabetes Fact sheet N°312". World Health Organization. August 2011. Archived from the original on 26 August 2013. Retrieved 2012-01-09.
- ^ "Diabetes Blue Circle Symbol". International Diabetes Federation. 17 March 2006. Archived from the original on 5 August 2007.
- ^ a b c d e "Diagnosis of Diabetes and Prediabetes". National Institute of Diabetes and Digestive and Kidney Diseases. June 2014. Archived from the original on 6 March 2016. Retrieved 10 February 2016.
- ^ PMID 25342831.
- ^ PMID 18939392.
- ^ a b c d e f g "Causes of Diabetes". National Institute of Diabetes and Digestive and Kidney Diseases. June 2014. Archived from the original on 2 February 2016. Retrieved 10 February 2016.
- ^ S2CID 32016657.
- ^ PMID 26090370.
- ^ S2CID 29670619.
- ^ ISBN 978-1-4377-0324-5.
- ^ PMID 27733282.
- OCLC 965646175.
- ^ OCLC 613429053.
- PMID 16034881. (Retracted)
- S2CID 205176936.
- PMID 25859264.
- OCLC 758391750.
- ^ S2CID 1042625.
- PMID 19466209.
- PMID 23173134.
- ^ OCLC 725919496.
- S2CID 28169759.
- ^ S2CID 207535925.
- PMID 31747182.
- ^ "Developing tools to help predict future risk for diabetes and heart attack". Faculty of Biology, Medicine and Health. Retrieved 2024-03-20.
- ^ PMID 19145963.
- PMID 21211730.
- ^ "Diabetic ketoacidosis: Know the warning signs-Diabetic ketoacidosis - Symptoms & causes". Mayo Clinic. Retrieved 2024-03-20.
- ^ "WHAT IS TYPE 2 DIABETES?". Diabetes Daily. December 29, 2021. Archived from the original on 2024-03-19. Retrieved 2024-03-20.
- S2CID 25569962.
- ^ PMID 19032965.
- PMID 23071876.
- PMID 24101783.
- PMID 20071652.
- S2CID 4459808.[permanent dead link]
- PMID 20493574.
- PMID 26388413.
- ^ S2CID 45708828.
- PMID 20308626.
- PMID 20693348.
- PMID 22422870.
- PMID 22818936.
- S2CID 41018361.
- PMID 26678054.
- ^ S2CID 43548816.
- PMID 27398621.
- ^ "Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young". National Diabetes Information Clearinghouse (NDIC). National Institute of Diabetes and Digestive and Kidney Diseases, NIH. March 2007. Archived from the original on 2008-07-04. Retrieved 2008-08-04.
- ^ Rosen ED, Kaestner KH, Natarajan R, Patti ME, Sallari R, Sander M, Susztak K. Epigenetics and Epigenomics: Implications for Diabetes and Obesity. Diabetes. 2018 Oct;67(10):1923-1931. doi: 10.2337/db18-0537. PMID 30237160; PMCID: PMC6463748
- ^ OCLC 261324723.
- S2CID 21532595.
- PMID 21499090.
- PMID 20587728.
- S2CID 22222112.
- PMID 18832284.
- S2CID 3688434.
- ISBN 978-1-58255-732-8.
- ^ S2CID 209341381.
- PMID 34413662.
- PMID 32780722.
- PMID 20424233.
- PMID 33241460.
- S2CID 209510992.
- PMID 33043401.
- PMID 32895383.
- PMID 33021965.
- S2CID 4632807.
- S2CID 9757285.
- PMID 21170680.
- ISBN 978-92-4-159493-6.
- PMID 20194231.
- ^ World Health Organization. "Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1. Diagnosis and classification of diabetes mellitus". Archived from the original on 2007-05-29. Retrieved 2007-05-29.
- ^ PMID 19502545.
- PMID 20042775.
- ^ PMID 26246459.
- PMID 22187472.
- ISBN 978-0-7216-0187-8.
- ISBN 978-1-58255-732-8.
- OCLC 859778842.
- PMID 20144319.
- ^ PMID 25867111.
- ^ a b "Recommendation: Prediabetes and Type 2 Diabetes: Screening | United States Preventive Services Taskforce". www.uspreventiveservicestaskforce.org. Retrieved 2023-01-13.
- PMID 26501513.
- ^ PMID 25537706.
- ^ a b "Archived: Diabetes Mellitus (Type 2) in Adults: Screening". U.S. Preventive Services Task Force. June 2008. Archived from the original on 2014-02-07. Retrieved 2014-03-16.
- PMID 32470201.
- ^ S2CID 251299176.
- S2CID 247390548.
- PMID 33989535.
- S2CID 26714233.
- PMID 29205264.
- ^ PMID 24126648.
- PMID 21855702.
- PMID 27510511.
- S2CID 23039006. (Retracted)
- PMID 20724400.
- PMID 28397016.
- PMID 24682091.
- S2CID 58632705.
- ^ PMID 31794067.
- ^ PMID 30592787.
- PMID 29114778.
- PMID 25062463.
- S2CID 244580173.
- ^ "Type 2 diabetes: The management of type 2 diabetes". May 2009. Archived from the original on 2015-05-22.
- PMID 25668264.
- PMID 22868819.
- PMID 21791495.
- S2CID 20819316.
- ^ PMID 25583541.
- PMID 29507945.
- PMID 23589542.
- PMID 28069712.
- PMID 35420698.
- PMID 27747395.
- S2CID 25505640.
- PMID 19421969.
- S2CID 220651657.
A weight loss of ~15 kg, achieved by calorie restriction as part of an intensive management programme, can lead to remission of T2DM in ~80% of patients with obesity and T2DM.
- ^ "Achieving Type 2 Diabetes Remission through Weight Loss". National Institute of Diabetes and Digestive and Kidney Diseases. 30 September 2020. Retrieved 29 November 2023.
- ^ a b "Initial management of hyperglycemia in adults with type 2 diabetes mellitus". UpToDate. September 2023. Retrieved 29 November 2023.
- S2CID 228087486.
- PMID 19160276.
- PMID 25287761.
- PMID 24357208.
- S2CID 226250006.
- PMID 22778165.
- PMID 33693499.
- S2CID 58665219.
- PMID 25188210.
- S2CID 34925223.
- PMC 8701561.
- PMID 27434443.
- PMID 22509138.
- S2CID 226280186.
- S2CID 245538347.
- PMID 36191315.
- PMID 33489086.
- PMID 29677303.
- PMID 17636824.
- PMID 23217404.
- PMID 21735405.
- PMID 20646668.
- PMID 31451236.
- PMID 26920333.
- PMID 31575567.
- PMID 24687000.
- PMID 28844155.
- ^ PMID 26954482.
- PMID 20508233.
- PMID 28957454.
- PMID 32532814.
- S2CID 242149388.
- PMID 19726018.
- S2CID 31797748.
- ^ PMID 19625245.
- S2CID 207551737.
- S2CID 5198462.
- PMID 27222544.
- ^ International Diabetes Federation 2021, p. 33.
- ^ Kahn, Ferris & O'Neill 2020, Epidemiology.
- PMID 32399348.
- PMID 36614099.
- PMID 35432755.
- PMID 15111519.
- ^ OCLC 663097550.
- ^ Sajida S (2021-01-26). A Hand Book On Diabetes. OrangeBooks Publication. p. 2.
- ^ PMID 31520618.
- ^ "Developing tools to help predict future risk for diabetes and heart attack". Faculty of Biology, Medicine and Health. Retrieved 2024-03-20.
- PMID 32385076.
- S2CID 242997909.
- 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 978-2-930229-98-0. Retrieved 18 March 2022.