View source for Medicine:Type 2 diabetes

{{Short description|Type of diabetes mellitus with high blood sugar and insulin resistance}}
{{pp-semi-indef}}
{{Infobox medical condition (new)
| image         = Blue circle for diabetes.svg
| image_size    = 200px
| caption       = A blue circle is the universal symbol of diabetes.<ref>{{Cite web|title=Diabetes Blue Circle Symbol| url=http://www.diabetesbluecircle.org| date=17 March 2006| publisher=International Diabetes Federation |url-status=dead |archive-date=5 August 2007 |archive-url=https://web.archive.org/web/20070805042346/http://www.diabetesbluecircle.org/ }}</ref>
| field         = [[Biology:Endocrinology|Endocrinology]]
| synonyms      = Diabetes mellitus type 2;<br />adult-onset diabetes;<ref name=WHO2015/><br />noninsulin-dependent diabetes mellitus (NIDDM)
| pronounce     = {{IPAc-en|d|aɪ|ə|b|iː|t|ə|s}}
| symptoms      = Increased thirst, frequent urination, unexplained weight loss, increased hunger<ref name=NIH2014Diag/>
| complications = [[Medicine:Hyperosmolar hyperglycemic state|Hyperosmolar hyperglycemic state]], [[Medicine:Diabetic ketoacidosis|diabetic ketoacidosis]], heart disease, [[Medicine:Stroke|stroke]]s, [[Medicine:Diabetic retinopathy|diabetic retinopathy]], [[Medicine:Kidney failure|kidney failure]], [[Medicine:Amputation|amputation]]s<ref name=WHO2015/><ref name=Pas2014/><ref name=Fas2008/>
| onset         = Middle or older age<ref name=NIH2014Cause/>
| duration      = Long term<ref name=NIH2014Cause/>
| causes        = Obesity, lack of exercise, [[Biology:Heredity|genetics]]<ref name=WHO2015/><ref name=NIH2014Cause/>
| risks         = 
| diagnosis     = Blood test<ref name=NIH2014Diag/>
| differential  = 
| prevention    = Maintaining normal weight, exercising, healthy diet<ref name=WHO2015/>
| treatment     = Dietary changes, [[Chemistry:Metformin|metformin]], insulin, bariatric surgery<ref name=WHO2015/><ref name=Ann2016/><ref name=Cet2015/><ref name=Kre2005/>
| medication    = 
| prognosis     = 10 year shorter [[Biology:Life expectancy|life expectancy]]<ref name=Will2011/>
| frequency     = 392 million (2015)<ref name=GBD2015Pre/>
| deaths        = 
| name          = 
}}
<!-- Definition and symptoms -->
'''Type 2 diabetes''' ('''T2D'''), formerly known as '''adult-onset diabetes''', is a form of [[Medicine:Diabetes mellitus|diabetes mellitus]] that is characterized by [[Medicine:Hyperglycemia|high blood sugar]], insulin resistance, and relative lack of [[Biology:Insulin|insulin]].<ref name=NIH2014Cause>{{cite web|title=Causes of Diabetes|url=http://www.niddk.nih.gov/health-information/health-topics/Diabetes/causes-diabetes/Pages/index.aspx|website=National Institute of Diabetes and Digestive and Kidney Diseases|access-date=10 February 2016|date=June 2014 |url-status=live |archive-date=2 February 2016 |archive-url=https://web.archive.org/web/20160202083725/http://www.niddk.nih.gov/health-information/health-topics/Diabetes/causes-diabetes/Pages/index.aspx }}</ref> Common symptoms include increased thirst, frequent urination, [[Medicine:Fatigue|fatigue]] and unexplained weight loss.<ref name=NIH2014Diag/> Symptoms may also include increased hunger,  having a sensation of pins and needles, and sores (wounds) that do not heal.<ref name=NIH2014Diag/> Often symptoms come on slowly.<ref name=NIH2014Cause/> Long-term complications from high blood sugar include heart disease, [[Medicine:Stroke|stroke]]s, [[Medicine:Diabetic retinopathy|diabetic retinopathy]] which can result in [[Medicine:Blindness|blindness]], [[Medicine:Kidney failure|kidney failure]], and poor blood flow in the limbs which may lead to [[Medicine:Amputation|amputation]]s.<ref name=WHO2015/> The sudden onset of [[Medicine:Hyperosmolar hyperglycemic state|hyperosmolar hyperglycemic state]] may occur; however, [[Medicine:Diabetic ketoacidosis|ketoacidosis]] is uncommon.<ref name=Pas2014>{{cite journal | vauthors = Pasquel FJ, Umpierrez GE | title = Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment | journal = Diabetes Care | volume = 37 | issue = 11 | pages = 3124–31 | date = November 2014 | pmid = 25342831 | pmc = 4207202 | doi = 10.2337/dc14-0984 }}</ref><ref name=Fas2008>{{cite journal | vauthors = Fasanmade OA, Odeniyi IA, Ogbera AO | title = Diabetic ketoacidosis: diagnosis and management | journal = African Journal of Medicine and Medical Sciences | volume = 37 | issue = 2 | pages = 99–105 | date = June 2008 | pmid = 18939392 }}</ref>

<!-- Cause and diagnosis -->
Type&nbsp;2 diabetes primarily occurs as a result of obesity and lack of exercise.<ref name=WHO2015/> Some people are [[Biology:Heredity|genetically]] more at risk than others.<ref name=NIH2014Cause/>

Type 2 diabetes makes up about 90% of cases of [[Medicine:Diabetes|diabetes]], with the other 10% due primarily to [[Medicine:Type 1 diabetes|type 1 diabetes]] and [[Medicine:Gestational diabetes|gestational diabetes]].<ref name=WHO2015/> 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.<ref>{{cite book| veditors = MacKay I, Rose N |title=The Autoimmune Diseases| publisher=Academic Press| isbn=978-0-123-84929-8| year=2014| page=575 |oclc=965646175 }}</ref><ref name=Green2011>{{cite book | veditors = Gardner DG, Shoback D |title=Greenspan's basic & clinical endocrinology|year=2011|publisher=McGraw-Hill Medical|location=New York|isbn=978-0-07-162243-1|chapter=Chapter 17: Pancreatic hormones & diabetes mellitus |edition=9th |oclc=613429053 }}</ref> Diagnosis of diabetes is by blood tests such as fasting plasma glucose, oral glucose tolerance test, or [[Biology:Glycated hemoglobin|glycated hemoglobin]] (A1C).<ref name="NIH2014Diag">{{cite web |date=June 2014 |title=Diagnosis of Diabetes and Prediabetes |url=http://www.niddk.nih.gov/health-information/health-topics/Diabetes/diagnosis-diabetes-prediabetes/Pages/index.aspx |url-status=dead |archive-url=https://web.archive.org/web/20160306174631/http://www.niddk.nih.gov/health-information/health-topics/Diabetes/diagnosis-diabetes-prediabetes/Pages/index.aspx |archive-date=6 March 2016 |access-date=10 February 2016 |website=National Institute of Diabetes and Digestive and Kidney Diseases}}</ref>

<!-- Prevention and treatment -->
Type&nbsp;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).<ref name=WHO2015/> Treatment involves exercise and dietary changes.<ref name=WHO2015/> If blood sugar levels are not adequately lowered, the medication [[Chemistry:Metformin|metformin]] is typically recommended.<ref name=Ann2016>{{cite journal | vauthors = Maruthur NM, Tseng E, Hutfless S, Wilson LM, Suarez-Cuervo C, Berger Z, Chu Y, Iyoha E, Segal JB, Bolen S | title = Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis | journal = Annals of Internal Medicine | volume = 164 | issue = 11 | pages = 740–51 | date = June 2016 | pmid = 27088241 | doi = 10.7326/M15-2650 | s2cid = 32016657 }}</ref><ref name=Fer005>{{cite journal | vauthors = Saenz A, Fernandez-Esteban I, Mataix A, Ausejo M, Roque M, Moher D | title = Metformin monotherapy for type 2 diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD002966 | date = July 2005 | pmid = 16034881 | doi = 10.1002/14651858.CD002966.pub3 | veditors = Saenz A }}{{Retracted|intentional=yes}}</ref> Many people may eventually also require insulin injections.<ref name=Kre2005>{{cite journal | vauthors = Krentz AJ, Bailey CJ | title = Oral antidiabetic agents: current role in type 2 diabetes mellitus | journal = Drugs | volume = 65 | issue = 3 | pages = 385–411 | date = February 2005 | pmid = 15669880 | doi = 10.2165/00003495-200565030-00005 | s2cid = 29670619 }}</ref> In those on insulin, routinely checking blood sugar levels (such as through a [[Medicine:Continuous glucose monitor|continuous glucose monitor]]) is advised; however, this may not be needed in those who are not on insulin therapy.<ref>{{cite journal | vauthors = Malanda UL, Welschen LM, Riphagen II, Dekker JM, Nijpels G, Bot SD | title = Self-monitoring of blood glucose in patients with type 2 diabetes mellitus who are not using insulin | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD005060 | date = January 2012 | pmid = 22258959 | doi = 10.1002/14651858.CD005060.pub3 | hdl = 1871/48558 | s2cid = 205176936 | url = https://research.vu.nl/en/publications/733717bc-2021-43dc-ad10-540cdca45380 }}</ref> Bariatric surgery often improves diabetes in those who are obese.<ref name=Cet2015>{{cite journal | vauthors = Cetinkunar S, Erdem H, Aktimur R, Sozen S | title = Effect of bariatric surgery on humoral control of metabolic derangements in obese patients with type 2 diabetes mellitus: How it works | journal = World Journal of Clinical Cases | volume = 3 | issue = 6 | pages = 504–9 | date = June 2015 | pmid = 26090370 | pmc = 4468896 | doi = 10.12998/wjcc.v3.i6.504 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ganguly S, Tan HC, Lee PC, Tham KW | title = Metabolic bariatric surgery and type 2 diabetes mellitus: an endocrinologist's perspective | journal = Journal of Biomedical Research | volume = 29 | issue = 2 | pages = 105–11 | date = April 2015 | pmid = 25859264 | pmc = 4389109 | doi = 10.7555/JBR.29.20140127 }}</ref>

<!--Epidemiology and history -->
Rates of type&nbsp;2 diabetes have increased markedly since 1960 in parallel with obesity.<ref>{{cite book | vauthors = Moscou S |chapter=Getting the word out: advocacy, social marketing, and policy development and enforcement | veditors = Truglio-Londrigan M, Lewenson SB |title=Public health nursing: practicing population-based care|date=2013|publisher=Jones & Bartlett Learning|location=Burlington, MA |isbn=978-1-4496-4660-8 |page=[https://books.google.com/books?id=kgA8xfbxIRwC&pg=PA317 317] |edition=2nd |oclc=758391750 }}</ref> As of 2015 there were approximately 392&nbsp;million people diagnosed with the disease compared to around 30&nbsp;million in 1985.<ref name=GBD2015Pre>{{cite journal | vauthors = Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, etal | collaboration = GBD 2015 Disease and Injury Incidence and Prevalence Collaborators | title = Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1545–1602 | date = October 2016 | pmid = 27733282 | pmc = 5055577 | doi = 10.1016/S0140-6736(16)31678-6 }}</ref><ref name=Epi2006>{{cite journal | vauthors = Smyth S, Heron A | title = Diabetes and obesity: the twin epidemics | journal = Nature Medicine | volume = 12 | issue = 1 | pages = 75–80 | date = January 2006 | pmid = 16397575 | doi = 10.1038/nm0106-75 | s2cid = 1042625 }}</ref> Typically it begins in middle or older age,<ref name=NIH2014Cause/> although rates of type 2 diabetes are increasing in young people.<ref>{{cite journal | vauthors = Tfayli H, Arslanian S | title = Pathophysiology of type 2 diabetes mellitus in youth: the evolving chameleon | journal = Arquivos Brasileiros de Endocrinologia e Metabologia | volume = 53 | issue = 2 | pages = 165–74 | date = March 2009 | pmid = 19466209 | pmc = 2846552 | doi = 10.1590/s0004-27302009000200008 }}</ref><ref>{{cite journal | vauthors = Imperatore G, Boyle JP, Thompson TJ, Case D, Dabelea D, Hamman RF, Lawrence JM, Liese AD, Liu LL, Mayer-Davis EJ, Rodriguez BL, Standiford D | title = Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2050: dynamic modeling of incidence, mortality, and population growth | journal = Diabetes Care | volume = 35 | issue = 12 | pages = 2515–20 | date = December 2012 | pmid = 23173134 | pmc = 3507562 | doi = 10.2337/dc12-0669 }}</ref> Type 2 diabetes is associated with a ten-year-shorter life expectancy.<ref name=Will2011>{{cite book | veditors = Melmed S, Polonsky KS, Larsen PR, Kronenberg HM |title=Williams textbook of endocrinology.|publisher=Elsevier/Saunders|location=Philadelphia|isbn=978-1-4377-0324-5|pages=1371–1435|edition=12th|year=2011 }}</ref> Diabetes was one of the first diseases ever described, dating back to an Egyptian manuscript from {{circa|1500}} [[Common Era|BCE]].<ref name=Rip2011>{{cite book |chapter=Diabetes | vauthors = Leutholtz BC, Ripoll I |title=Exercise and disease management|publisher=CRC Press|location=Boca Raton|isbn=978-1-4398-2759-8|pages = 25 | chapter-url = https://books.google.com/books?id=eAn9-bm_pi8C&pg=PA25 |edition=2nd|date=2011 |oclc=725919496 }}</ref> The importance of insulin in the disease was determined in the 1920s.<ref>{{cite journal | vauthors = Zaccardi F, Webb DR, Yates T, Davies MJ | title = Pathophysiology of type 1 and type 2 diabetes mellitus: a 90-year perspective | journal = Postgraduate Medical Journal | volume = 92 | issue = 1084 | pages = 63–9 | date = February 2016 | pmid = 26621825 | doi = 10.1136/postgradmedj-2015-133281 | s2cid = 28169759 }}</ref>

==Signs and symptoms==
[[File:Main symptoms of diabetes.svg|thumb|upright=1.8|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.<ref name=Vij2010>{{cite journal | vauthors = Vijan S | title = In the clinic. Type 2 diabetes | journal = Annals of Internal Medicine | volume = 152 | issue = 5 | pages = ITC31–15; quiz ITC316 | date = March 2010 | pmid = 20194231 | doi = 10.7326/0003-4819-152-5-201003020-01003 | s2cid = 207535925 }}</ref> Other symptoms that are commonly present at diagnosis include a history of blurred vision, itchiness, [[Medicine:Peripheral neuropathy|peripheral neuropathy]], recurrent vaginal infections, and fatigue.<ref name=Green2011/> Other symptoms may include loss of taste.<ref>{{cite book | vauthors = Rathee M, Prachi J |title=StatPearls |date=2019 |publisher=StatPearls Publishing |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK549775/ |chapter=Ageusia|pmid=31747182 }}</ref>  Many people, however, have no symptoms during the first few years and are diagnosed on routine testing.<ref name=Green2011/> A small number of people with type&nbsp;2 diabetes can develop a [[Medicine:Hyperosmolar hyperglycemic state|hyperosmolar hyperglycemic state]] (a condition of very high blood sugar associated with a decreased level of consciousness and [[Medicine:Hypotension|low blood pressure]]).<ref name=Green2011/>

===Complications===
Type 2 diabetes is typically a chronic disease associated with a ten-year-shorter life expectancy.<ref name=Will2011/> This is partly due to a number of complications with which it is associated, including: two to four times the risk of [[Medicine:Cardiovascular disease|cardiovascular disease]], including ischemic heart disease and [[Medicine:Stroke|stroke]]; a 20-fold increase in lower limb amputations, and increased rates of hospitalizations.<ref name=Will2011/> In the developed world, and increasingly elsewhere, type&nbsp;2 diabetes is the largest cause of nontraumatic [[Medicine:Blindness|blindness]] and [[Medicine:Chronic kidney disease|kidney failure]].<ref name=AFP09/> It has also been associated with an increased risk of cognitive dysfunction and [[Medicine:Dementia|dementia]] through disease processes such as [[Medicine:Alzheimer's disease|Alzheimer's disease]] and [[Medicine:Vascular dementia|vascular dementia]].<ref>{{cite journal | vauthors = Pasquier F | title = Diabetes and cognitive impairment: how to evaluate the cognitive status? | journal = Diabetes & Metabolism | volume = 36 | issue = Suppl 3 | pages = S100-5 | date = October 2010 | pmid = 21211730 | doi = 10.1016/S1262-3636(10)70475-4 }}</ref> Other complications include hyperpigmentation of skin ([[Medicine:Acanthosis nigricans|acanthosis nigricans]]), [[Medicine:Sexual dysfunction|sexual dysfunction]], and frequent infections.<ref name=Vij2010/> There is also an association between type 2 diabetes and mild hearing loss.<ref>{{cite journal | vauthors = Akinpelu OV, Mujica-Mota M, Daniel SJ | title = Is type 2 diabetes mellitus associated with alterations in hearing? A systematic review and meta-analysis | journal = The Laryngoscope | volume = 124 | issue = 3 | pages = 767–776 | date = March 2014 | pmid = 23945844 | doi = 10.1002/lary.24354 | s2cid = 25569962 }}</ref>

==Causes==
The development of type&nbsp;2 diabetes is caused by a combination of lifestyle and genetic factors.<ref name=AFP09/><ref name=Fat2009>{{cite journal | vauthors = Risérus U, Willett WC, Hu FB | title = Dietary fats and prevention of type 2 diabetes | journal = Progress in Lipid Research | volume = 48 | issue = 1 | pages = 44–51 | date = January 2009 | pmid = 19032965 | pmc = 2654180 | doi = 10.1016/j.plipres.2008.10.002 | author2-link = Walter Willett }}</ref> 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.<ref name=Will2011/> Obesity is more common in women than men in many parts of Africa.<ref>{{cite journal | vauthors = Hilawe EH, Yatsuya H, Kawaguchi L, Aoyama A | title = Differences by sex in the prevalence of diabetes mellitus, impaired fasting glycaemia and impaired glucose tolerance in sub-Saharan Africa: a systematic review and meta-analysis | journal = Bulletin of the World Health Organization | volume = 91 | issue = 9 | pages = 671–682D | date = September 2013 | pmid = 24101783 | pmc = 3790213 | doi = 10.2471/BLT.12.113415 }}</ref> The [[Biology:Nutrition|nutrition]]al status of a mother during fetal development may also play a role, with one proposed mechanism being that of [[Biology:DNA methylation|DNA methylation]].<ref>{{cite journal | vauthors = Christian P, Stewart CP | title = Maternal micronutrient deficiency, fetal development, and the risk of chronic disease | journal = The Journal of Nutrition | volume = 140 | issue = 3 | pages = 437–45 | date = March 2010 | pmid = 20071652 | doi = 10.3945/jn.109.116327 | doi-access = free }}</ref> The intestinal bacteria ''Prevotella copri'' and ''Bacteroides vulgatus'' have been connected with type&nbsp;2 diabetes.<ref>{{cite journal | vauthors = Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, etal | title = Human gut microbes impact host serum metabolome and insulin sensitivity | journal = Nature | volume = 535 | issue = 7612 | pages = 376–81 | date = July 2016 | pmid = 27409811 | doi = 10.1038/nature18646 | bibcode = 2016Natur.535..376P | s2cid = 4459808 | url = https://zenodo.org/record/3425712 }}{{Dead link|date=November 2021 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

===Lifestyle===
Lifestyle factors are important to the development of type&nbsp;2 diabetes, including obesity and being overweight (defined by a [[Body mass index|body mass index]] of greater than 25), lack of physical activity, poor diet, [[Medicine:Psychological stress|psychological stress]], and [[Earth:Urbanization|urbanization]].<ref name=Will2011/><ref>{{cite journal | vauthors = Abdullah A, Peeters A, de Courten M, Stoelwinder J | title = The magnitude of association between overweight and obesity and the risk of diabetes: a meta-analysis of prospective cohort studies | journal = Diabetes Research and Clinical Practice | volume = 89 | issue = 3 | pages = 309–19 | date = September 2010 | pmid = 20493574 | doi = 10.1016/j.diabres.2010.04.012 }}</ref> 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.<ref name=Green2011/> Among those who are not obese, a high [[Waist–hip ratio|waist–hip ratio]] is often present.<ref name=Green2011/> Smoking appears to increase the risk of type&nbsp;2 diabetes.<ref>{{cite journal | vauthors = Pan A, Wang Y, Talaei M, Hu FB, Wu T | title = Relation of active, passive, and quitting smoking with incident type 2 diabetes: a systematic review and meta-analysis | journal = The Lancet. Diabetes & Endocrinology | volume = 3 | issue = 12 | pages = 958–67 | date = December 2015 | pmid = 26388413 | pmc = 4656094 | doi = 10.1016/S2213-8587(15)00316-2 }}</ref>  A lack of sleep [[Medicine:Sleep deprivation#Type 2 diabetes|has also been linked]] to type&nbsp;2 diabetes.<ref name=Sleep2011>{{cite journal | vauthors = Touma C, Pannain S | title = Does lack of sleep cause diabetes? | journal = Cleveland Clinic Journal of Medicine | volume = 78 | issue = 8 | pages = 549–58 | date = August 2011 | pmid = 21807927 | doi = 10.3949/ccjm.78a.10165 | s2cid = 45708828 | doi-access = free }}</ref> Laboratory studies have linked short-term sleep deprivations to changes in glucose metabolism, nervous system activity, or hormonal factors that may lead to diabetes.<ref name=Sleep2011/>

Dietary factors also influence the risk of developing type&nbsp;2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.<ref name=SSB2010>{{cite journal | vauthors = Malik VS, Popkin BM, Bray GA, Després JP, Hu FB | title = Sugar-sweetened beverages, obesity, type 2 diabetes mellitus, and cardiovascular disease risk | journal = Circulation | volume = 121 | issue = 11 | pages = 1356–64 | date = March 2010 | pmid = 20308626 | pmc = 2862465 | doi = 10.1161/CIRCULATIONAHA.109.876185 }}</ref><ref>{{cite journal | vauthors = Malik VS, Popkin BM, Bray GA, Després JP, Willett WC, Hu FB | title = Sugar-sweetened beverages and risk of metabolic syndrome and type 2 diabetes: a meta-analysis | journal = Diabetes Care | volume = 33 | issue = 11 | pages = 2477–83 | date = November 2010 | pmid = 20693348 | pmc = 2963518 | doi = 10.2337/dc10-1079 }}</ref> The type of fats in the diet are important, with [[Chemistry:Saturated fat|saturated fat]]s and trans fatty acids increasing the risk, and [[Chemistry:Polyunsaturated fat|polyunsaturated]] and [[Chemistry:Monounsaturated fat|monounsaturated fat]] decreasing the risk.<ref name=Fat2009 /> Eating a lot of white rice appears to play a role in increasing risk.<ref>{{cite journal | vauthors = Hu EA, Pan A, Malik V, Sun Q | title = White rice consumption and risk of type 2 diabetes: meta-analysis and systematic review | journal = BMJ | volume = 344 | pages = e1454 | date = March 2012 | pmid = 22422870 | pmc = 3307808 | doi = 10.1136/bmj.e1454 }}</ref> A lack of exercise is believed to cause 7% of cases.<ref>{{cite journal | vauthors = Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT | title = Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy | journal = Lancet | volume = 380 | issue = 9838 | pages = 219–29 | date = July 2012 | pmid = 22818936 | pmc = 3645500 | doi = 10.1016/S0140-6736(12)61031-9 }}</ref> Persistent organic pollutants may also play a role.<ref>{{cite journal | vauthors = Lind L, Lind PM | title = Can persistent organic pollutants and plastic-associated chemicals cause cardiovascular disease? | journal = Journal of Internal Medicine | volume = 271 | issue = 6 | pages = 537–53 | date = June 2012 | pmid = 22372998 | doi = 10.1111/j.1365-2796.2012.02536.x | s2cid = 41018361 | doi-access = free }}</ref>

===Genetics===
Most cases of diabetes involve many [[Biology:Gene|gene]]s, with each being a small contributor to an increased probability of becoming a type&nbsp;2 diabetic.<ref name=Will2011/> The proportion of diabetes that is [[Philosophy:Heritability|inherited]] is estimated at 72%.<ref name=Will2016>{{cite journal | vauthors = Willemsen G, Ward KJ, Bell CG, Christensen K, Bowden J, Dalgård C, Harris JR, Kaprio J, Lyle R, Magnusson PK, Mather KA, Ordoňana JR, Perez-Riquelme F, Pedersen NL, Pietiläinen KH, Sachdev PS, Boomsma DI, Spector T | display-authors = 6 | title = The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium | journal = Twin Research and Human Genetics | volume = 18 | issue = 6 | pages = 762–771 | date = December 2015 | pmid = 26678054 | doi = 10.1017/thg.2015.83 | doi-access = free }}</ref> More than 36&nbsp;genes and 80&nbsp;[[Biology:Single-nucleotide polymorphism|single nucleotide polymorphisms]] (SNPs) had been found that contribute to the risk of type&nbsp;2 diabetes.<ref name=Genetic2011>{{cite journal | vauthors = Herder C, Roden M | title = Genetics of type 2 diabetes: pathophysiologic and clinical relevance | journal = European Journal of Clinical Investigation | volume = 41 | issue = 6 | pages = 679–692 | date = June 2011 | pmid = 21198561 | doi = 10.1111/j.1365-2362.2010.02454.x | s2cid = 43548816 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, Ma C, Fontanillas P, Moutsianas L, McCarthy DJ, Rivas MA, Perry JR, Sim X, Blackwell TW, Robertson NR, Rayner NW, Cingolani P, Locke AE, Tajes JF, Highland HM, Dupuis J, Chines PS, Lindgren CM, Hartl C, Jackson AU, Chen H, Huyghe JR, van de Bunt M, Pearson RD, Kumar A, Müller-Nurasyid M, Grarup N, Stringham HM, Gamazon ER, Lee J, Chen Y, Scott RA, Below JE, Chen P, Huang J, Go MJ, Stitzel ML, Pasko D, Parker SC, Varga TV, Green T, Beer NL, Day-Williams AG, Ferreira T, Fingerlin T, Horikoshi M, Hu C, Huh I, Ikram MK, Kim BJ, Kim Y, Kim YJ, Kwon MS, Lee J, Lee S, Lin KH, Maxwell TJ, Nagai Y, Wang X, Welch RP, Yoon J, Zhang W, Barzilai N, Voight BF, Han BG, Jenkinson CP, Kuulasmaa T, Kuusisto J, Manning A, Ng MC, Palmer ND, Balkau B, Stančáková A, Abboud HE, Boeing H, Giedraitis V, Prabhakaran D, Gottesman O, Scott J, Carey J, Kwan P, Grant G, Smith JD, Neale BM, Purcell S, Butterworth AS, Howson JM, Lee HM, Lu Y, Kwak SH, Zhao W, Danesh J, Lam VK, Park KS, Saleheen D, So WY, Tam CH, Afzal U, Aguilar D, Arya R, Aung T, Chan E, Navarro C, Cheng CY, Palli D, Correa A, Curran JE, Rybin D, Farook VS, Fowler SP, Freedman BI, Griswold M, Hale DE, Hicks PJ, Khor CC, Kumar S, Lehne B, Thuillier D, Lim WY, Liu J, van der Schouw YT, Loh M, Musani SK, Puppala S, Scott WR, Yengo L, Tan ST, Taylor HA, Thameem F, Wilson G, Wong TY, Njølstad PR, Levy JC, Mangino M, Bonnycastle LL, Schwarzmayr T, Fadista J, Surdulescu GL, Herder C, Groves CJ, Wieland T, Bork-Jensen J, Brandslund I, Christensen C, Koistinen HA, Doney AS, Kinnunen L, Esko T, Farmer AJ, Hakaste L, Hodgkiss D, Kravic J, Lyssenko V, Hollensted M, Jørgensen ME, Jørgensen T, Ladenvall C, Justesen JM, Käräjämäki A, Kriebel J, Rathmann W, Lannfelt L, Lauritzen T, Narisu N, Linneberg A, Melander O, Milani L, Neville M, Orho-Melander M, Qi L, Qi Q, Roden M, Rolandsson O, Swift A, Rosengren AH, Stirrups K, Wood AR, Mihailov E, Blancher C, Carneiro MO, Maguire J, Poplin R, Shakir K, Fennell T, DePristo M, de Angelis MH, Deloukas P, Gjesing AP, Jun G, Nilsson P, Murphy J, Onofrio R, Thorand B, Hansen T, Meisinger C, Hu FB, Isomaa B, Karpe F, Liang L, Peters A, Huth C, O'Rahilly SP, Palmer CN, Pedersen O, Rauramaa R, Tuomilehto J, Salomaa V, Watanabe RM, Syvänen AC, Bergman RN, Bharadwaj D, Bottinger EP, Cho YS, Chandak GR, Chan JC, Chia KS, Daly MJ, Ebrahim SB, Langenberg C, Elliott P, Jablonski KA, Lehman DM, Jia W, Ma RC, Pollin TI, Sandhu M, Tandon N, Froguel P, Barroso I, Teo YY, Zeggini E, Loos RJ, Small KS, Ried JS, DeFronzo RA, Grallert H, Glaser B, Metspalu A, Wareham NJ, Walker M, Banks E, Gieger C, Ingelsson E, Im HK, Illig T, Franks PW, Buck G, Trakalo J, Buck D, Prokopenko I, Mägi R, Lind L, Farjoun Y, Owen KR, Gloyn AL, Strauch K, Tuomi T, Kooner JS, Lee JY, Park T, Donnelly P, Morris AD, Hattersley AT, Bowden DW, Collins FS, Atzmon G, Chambers JC, Spector TD, Laakso M, Strom TM, Bell GI, Blangero J, Duggirala R, Tai ES, McVean G, Hanis CL, Wilson JG, Seielstad M, Frayling TM, Meigs JB, Cox NJ, Sladek R, Lander ES, Gabriel S, Burtt NP, Mohlke KL, Meitinger T, Groop L, Abecasis G, Florez JC, Scott LJ, Morris AP, Kang HM, Boehnke M, Altshuler D, McCarthy MI | display-authors = 6 | title = The genetic architecture of type 2 diabetes | journal = Nature | volume = 536 | issue = 7614 | pages = 41–47 | date = August 2016 | pmid = 27398621 | pmc = 5034897 | doi = 10.1038/nature18642 | bibcode = 2016Natur.536...41F }}</ref> All of these genes together still only account for 10% of the total heritable component of the disease.<ref name=Genetic2011/> The [[Biology:TCF7L2|TCF7L2]] [[Biology:Allele|allele]], for example, increases the risk of developing diabetes by 1.5&nbsp;times and is the greatest risk of the common genetic variants.<ref name=Green2011/> Most of the genes linked to diabetes are involved in pancreatic beta cell functions.<ref name=Green2011/>

There are a number of rare cases of diabetes that arise due to an abnormality in a single gene (known as [[Medicine:Genetic disorder|monogenic]] forms of diabetes or [[Medicine:Diabetes#Other types|"other specific types of diabetes"]]).<ref name=Will2011/><ref name=Green2011/> These include [[Medicine:Maturity onset diabetes of the young|maturity onset diabetes of the young]] (MODY), [[Medicine:Donohue syndrome|Donohue syndrome]], and [[Medicine:Rabson–Mendenhall syndrome|Rabson–Mendenhall syndrome]], among others.<ref name=Will2011/> Maturity onset diabetes of the young constitute 1–5% of all cases of diabetes in young people.<ref>{{cite news|title=Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-onset Diabetes of the Young|date=March 2007|publisher=National Institute of Diabetes and Digestive and Kidney Diseases, NIH|url=http://www.diabetes.niddk.nih.gov/dm/pubs/mody/|work=National Diabetes Information Clearinghouse (NDIC)|access-date=2008-08-04|url-status=live|archive-url=https://web.archive.org/web/20080704103703/http://diabetes.niddk.nih.gov/dm/pubs/mody/|archive-date=2008-07-04}}</ref>

===Epigenetics===

Epigenetic regulation occurs at multiple levels including (1) direct [[Biology:Methylation|methylation]] of [[Chemistry:Cytosine|cytosine]] and [[Chemistry:Adenine|adenine]] residues in [[Biology:DNA|DNA]], (2) covalent modification of [[Biology:Histone|histone]] proteins in [[Biology:Chromatin|chromatin]], and (3) action of non coding [[Biology:MicroRNA|microRNA]]s (for other examples, see Wikipedia article "[[Biology:Epigenetics|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.<ref>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</ref>  The current state of knowledge in this field is addressed the Wikipedia article "[[Biology:Epigenetics of diabetes Type 2|Epigenetics of diabetes Type 2]]."

===Medical conditions===
There are a number of medications and other health problems that can predispose to diabetes.<ref name=BookDM2008>{{cite book | vauthors = Funnell MM, Anderson RM |chapter=Influencing self-management: from compliance to collaboration | veditors = Bethel MN, Feinglos MA |title=Type 2 diabetes mellitus: an evidence-based approach to practical management |series=Contemporary endocrinology |year=2008|publisher=Humana Press|location=Totowa, NJ|isbn=978-1-58829-794-5 |oclc=261324723 |page=462 |chapter-url=https://books.google.com/books?id=Cn-9BAAAQBAJ&pg=PA455 }}</ref> Some of the medications include: [[Chemistry:Glucocorticoid|glucocorticoid]]s, [[Chemistry:Thiazide|thiazide]]s, [[Chemistry:Beta blocker|beta blocker]]s, [[Chemistry:Atypical antipsychotic|atypical antipsychotic]]s,<ref>{{cite journal | vauthors = Izzedine H, Launay-Vacher V, Deybach C, Bourry E, Barrou B, Deray G | title = Drug-induced diabetes mellitus | journal = Expert Opinion on Drug Safety | volume = 4 | issue = 6 | pages = 1097–1109 | date = November 2005 | pmid = 16255667 | doi = 10.1517/14740338.4.6.1097 | s2cid = 21532595 }}</ref> and [[Biology:Statin|statin]]s.<ref>{{cite journal | vauthors = Sampson UK, Linton MF, Fazio S | title = Are statins diabetogenic? | journal = Current Opinion in Cardiology | volume = 26 | issue = 4 | pages = 342–347 | date = July 2011 | pmid = 21499090 | pmc = 3341610 | doi = 10.1097/HCO.0b013e3283470359 }}</ref> Those who have previously had [[Medicine:Gestational diabetes|gestational diabetes]] are at a higher risk of developing type&nbsp;2 diabetes.<ref name=Vij2010/> Other health problems that are associated include: [[Medicine:Acromegaly|acromegaly]], [[Medicine:Cushing's syndrome|Cushing's syndrome]], [[Medicine:Hyperthyroidism|hyperthyroidism]], [[Medicine:Pheochromocytoma|pheochromocytoma]], and certain [[Medicine:Cancer|cancer]]s such as [[Medicine:Glucagonoma|glucagonoma]]s.<ref name=BookDM2008/> Individuals with cancer may be at a higher risk of mortality if they also have diabetes.<ref>{{cite journal | vauthors = Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D | display-authors = 6 | title = Diabetes and cancer: a consensus report | journal = Diabetes Care | volume = 33 | issue = 7 | pages = 1674–1685 | date = July 2010 | pmid = 20587728 | pmc = 2890380 | doi = 10.2337/dc10-0666 | type = Professional society guidelines }}</ref> Testosterone deficiency is also associated with type&nbsp;2 diabetes.<ref name=pmid19444934>{{cite journal | vauthors = Saad F, Gooren L | title = The role of testosterone in the metabolic syndrome: a review | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 114 | issue = 1–2 | pages = 40–43 | date = March 2009 | pmid = 19444934 | doi = 10.1016/j.jsbmb.2008.12.022 | s2cid = 22222112 }}</ref><ref name=pmid18832284>{{cite journal | vauthors = Farrell JB, Deshmukh A, Baghaie AA | title = Low testosterone and the association with type 2 diabetes | journal = The Diabetes Educator | volume = 34 | issue = 5 | pages = 799–806 | year = 2008 | pmid = 18832284 | doi = 10.1177/0145721708323100 | doi-access = free }}</ref> [[Medicine:Eating disorder|Eating disorder]]s may also interact with type&nbsp;2 diabetes, with [[Medicine:Bulimia nervosa|bulimia nervosa]] increasing the risk and [[Medicine:Anorexia nervosa|anorexia nervosa]] decreasing it.<ref>{{cite journal | vauthors = Nieto-Martínez R, González-Rivas JP, Medina-Inojosa JR, Florez H | title = Are Eating Disorders Risk Factors for Type 2 Diabetes? A Systematic Review and Meta-analysis | journal = Current Diabetes Reports | volume = 17 | issue = 12 | pages = 138 | date = November 2017 | pmid = 29168047 | doi = 10.1007/s11892-017-0949-1 | type = Systematic review and meta-analysis | s2cid = 3688434 }}</ref>

==Pathophysiology==
Type&nbsp;2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance.<ref name=Green2011/> Insulin resistance, which is the inability of [[Biology:Cell|cells]] to respond adequately to normal levels of insulin, occurs primarily within the muscles, [[Biology:Liver|liver]], and fat tissue.<ref>{{cite book|title=Diabetes mellitus a guide to patient care.|year=2007|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-1-58255-732-8|page=[https://archive.org/details/diabetesmellitus0000unse_k9g1/page/15 15]|url=https://archive.org/details/diabetesmellitus0000unse_k9g1|url-access=registration}}</ref> In the liver, insulin normally suppresses [[Chemistry:Glucose|glucose]] release. However, in the setting of insulin resistance, the liver inappropriately releases glucose into the blood.<ref name=Will2011/> 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.<ref name=Green2011/>

Other potentially important mechanisms associated with type&nbsp;2 diabetes and insulin resistance include: increased breakdown of lipids within fat cells, resistance to and lack of [[Biology:Incretin|incretin]], high [[Biology:Glucagon|glucagon]] levels in the blood, increased retention of salt and water by the kidneys, and inappropriate regulation of metabolism by the [[Biology:Central nervous system|central nervous system]].<ref name=Will2011/> However, not all people with insulin resistance develop diabetes since an impairment of insulin secretion by pancreatic beta cells is also required.<ref name=Green2011/>

In the early stages of insulin resistance, the mass of beta cells expands, increasing the output of insulin to compensate for the insulin insensitivity.<ref name="pmid31831356">{{cite journal | vauthors=Sun T, Han X | title=Death versus dedifferentiation: The molecular bases of beta cell mass reduction in type 2 diabetes | journal=[[Biology:Seminars in Cell and Developmental Biology|Seminars in Cell and Developmental Biology]] | year=2019 | volume=103 | pages=76–82 | doi = 10.1016/j.semcdb.2019.12.002 | pmid=31831356| s2cid=209341381 }}</ref> But when type 2 diabetes has become manifest, a type 2 diabetic will have lost about half of their beta cells.<ref name="pmid31831356" />
[[Chemistry:Fatty acid|Fatty acid]]s in the beta cells activate [[Biology:FOXO1|FOXO1]], resulting in apoptosis of the beta cells.<ref name="pmid31831356" />

The causes of the aging-related insulin resistance seen in obesity and in type&nbsp;2 diabetes are uncertain. Effects of intracellular lipid metabolism and ATP production in liver and muscle cells may contribute to insulin resistance.<ref>{{cite journal | vauthors = Reed J, Bain S, Kanamarlapudi V | title = A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives | journal = Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy| volume = 14 | pages = 3567–3602 | date = August 2021 | pmid = 34413662 | pmc = 8369920 | doi = 10.2147/DMSO.S319895 | doi-access = free }}</ref>  New evidence also points to a role of a brain region called the [[Biology:Hypothalamus|hypothalamus]] in the development of insulin resistance. For one thing, a gene called Dusp8 is linked with an increased risk for diabetes.<ref>{{cite journal | vauthors = Schriever SC, Kabra DG, Pfuhlmann K, Baumann P, Baumgart EV, Nagler J, Seebacher F, Harrison L, Irmler M, Kullmann S, Corrêa-da-Silva F, Giesert F, Jain R, Schug H, Castel J, Martinez S, Wu M, Häring HU, de Angelis MH, Beckers J, Müller TD, Stemmer K, Wurst W, Rozman J, Nogueiras R, De Angelis M, Molkentin JD, Krahmer N, Yi CX, Schmidt MV, Luquet S, Heni M, Tschöp MH, Pfluger PT | display-authors = 6 | title = Type 2 diabetes risk gene Dusp8 regulates hypothalamic Jnk signaling and insulin sensitivity | journal = The Journal of Clinical Investigation | volume = 130 | issue = 11 | pages = 6093–6108 | date = November 2020 | pmid = 32780722 | pmc = 7598066 | doi = 10.1172/JCI136363 }}</ref> 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.<ref>{{cite journal | vauthors = German JP, Wisse BE, Thaler JP, Oh-I S, Sarruf DA, Ogimoto K, Kaiyala KJ, Fischer JD, Matsen ME, Taborsky GJ, Schwartz MW, Morton GJ | display-authors = 6 | title = Leptin deficiency causes insulin resistance induced by uncontrolled diabetes | journal = Diabetes | volume = 59 | issue = 7 | pages = 1626–1634 | date = July 2010 | pmid = 20424233 | pmc = 2889761 | doi = 10.2337/db09-1918 }}</ref> Activation of hypothalamic cells by [[Biology:Leptin|leptin]] has an important role in maintaining normal levels of blood glucose. Thus, both the endocrine cells of the pancreas AND cells in the [[Biology:Hypothalamus|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.<ref>{{cite journal | vauthors = Lundqvist MH, Almby K, Wiklund U, Abrahamsson N, Kamble PG, Pereira MJ, Eriksson JW | title = Altered hormonal and autonomic nerve responses to hypo- and hyperglycaemia are found in overweight and insulin-resistant individuals and may contribute to the development of type 2 diabetes | journal = Diabetologia | volume = 64 | issue = 3 | pages = 641–655 | date = March 2021 | pmid = 33241460 | pmc = 7864814 | doi = 10.1007/s00125-020-05332-z }}</ref> 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&nbsp;2 diabetes.<ref>{{cite journal | vauthors = Salazar J, Chávez-Castillo M, Rojas J, Ortega A, Nava M, Pérez J, Rojas M, Espinoza C, Chacin M, Herazo Y, Angarita L, Rojas DM, D'Marco L, Bermudez V | display-authors = 6 | title = Is "Leptin Resistance" Another Key Resistance to Manage Type 2 Diabetes? | journal = Current Diabetes Reviews | volume = 16 | issue = 7 | pages = 733–749 | date = 2020-07-23 | pmid = 31886750 | doi = 10.2174/1573399816666191230111838 | s2cid = 209510992 }}</ref>

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 [[Biology:Astrocyte|astrocyte]]s.<ref>{{cite journal | vauthors = Alonge KM, D'Alessio DA, Schwartz MW | title = Brain control of blood glucose levels: implications for the pathogenesis of type 2 diabetes | journal = Diabetologia | volume = 64 | issue = 1 | pages = 5–14 | date = January 2021 | pmid = 33043401 | pmc = 7718404 | doi = 10.1007/s00125-020-05293-3 }}</ref><ref>{{cite journal | vauthors = Bentsen MA, Rausch DM, Mirzadeh Z, Muta K, Scarlett JM, Brown JM, Herranz-Pérez V, Baquero AF, Thompson J, Alonge KM, Faber CL, Kaiyala KJ, Bennett C, Pyke C, Ratner C, Egerod KL, Holst B, Meek TH, Kutlu B, Zhang Y, Sparso T, Grove KL, Morton GJ, Kornum BR, García-Verdugo JM, Secher A, Jorgensen R, Schwartz MW, Pers TH | display-authors = 6 | title = Transcriptomic analysis links diverse hypothalamic cell types to fibroblast growth factor 1-induced sustained diabetes remission | journal = Nature Communications | volume = 11 | issue = 1 | pages = 4458 | date = September 2020 | pmid = 32895383 | pmc = 7477234 | doi = 10.1038/s41467-020-17720-5 | bibcode = 2020NatCo..11.4458B }}</ref>  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.<ref>{{cite journal | vauthors = Adlanmerini M, Nguyen HC, Krusen BM, Teng CW, Geisler CE, Peed LC, Carpenter BJ, Hayes MR, Lazar MA | display-authors = 6 | title = Hypothalamic REV-ERB nuclear receptors control diurnal food intake and leptin sensitivity in diet-induced obese mice | journal = The Journal of Clinical Investigation | volume = 131 | issue = 1 | pages = e140424 | date = January 2021 | pmid = 33021965 | pmc = 7773391 | doi = 10.1172/JCI140424 }}</ref><ref>{{cite journal | vauthors = Yasumoto Y, Miyazaki H, Ogata M, Kagawa Y, Yamamoto Y, Islam A, Yamada T, Katagiri H, Owada Y | display-authors = 6 | title = Glial Fatty Acid-Binding Protein 7 (FABP7) Regulates Neuronal Leptin Sensitivity in the Hypothalamic Arcuate Nucleus | journal = Molecular Neurobiology | volume = 55 | issue = 12 | pages = 9016–9028 | date = December 2018 | pmid = 29623545 | doi = 10.1007/s12035-018-1033-9 | s2cid = 4632807 }}</ref> 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 [[Biology:Mitochondria|mitochondria]]. This mitochondrial degeneration is partly due to the [[Biology:Oxidative stress|oxidative stress]] of the heightened amounts of fatty acids that are taken up by these cells and oxidized within mitochondria.<ref>{{cite journal | vauthors = Young JK, Baker JH, Muller T | title = Immunoreactivity for brain-fatty acid binding protein in gomori-positive astrocytes | journal = Glia | volume = 16 | issue = 3 | pages = 218–226 | date = March 1996 | pmid = 8833192 | doi = 10.1002/(SICI)1098-1136(199603)16:3<218::AID-GLIA4>3.0.CO;2-Y | s2cid = 9757285 }}</ref><ref>{{cite journal | vauthors = Schmidt SP, Corydon TJ, Pedersen CB, Vang S, Palmfeldt J, Stenbroen V, Wanders RJ, Ruiter JP, Gregersen N | display-authors = 6 | title = Toxic response caused by a misfolding variant of the mitochondrial protein short-chain acyl-CoA dehydrogenase | journal = Journal of Inherited Metabolic Disease | volume = 34 | issue = 2 | pages = 465–475 | date = April 2011 | pmid = 21170680 | pmc = 3063561 | doi = 10.1007/s10545-010-9255-7 }}</ref>  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==
The [[Organization:World Health Organization|World Health Organization]] definition of diabetes (both type&nbsp;1 and type&nbsp;2) is for a single raised glucose reading with symptoms, otherwise raised values on two occasions, of either:<ref name=who-99>{{Cite web |url=https://www.who.int/diabetes/publications/en/ |author=World Health Organization |title=Definition, diagnosis and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1. Diagnosis and classification of diabetes mellitus |access-date=2007-05-29 |url-status=dead |archive-url=https://web.archive.org/web/20070529092627/http://www.who.int/diabetes/publications/en/ |archive-date=2007-05-29 }}</ref>
* fasting plasma glucose ≥ 7.0&nbsp;mmol/L (126&nbsp;mg/dL)
:or
* with a [[Medicine:Glucose tolerance test|glucose tolerance test]], two hours after the oral dose a plasma glucose ≥ 11.1&nbsp;mmol/L (200&nbsp;mg/dL)
A random blood sugar of greater than 11.1&nbsp;mmol/L (200&nbsp;mg/dL) in association with typical symptoms<ref name=Vij2010/> or a [[Biology:Glycated hemoglobin|glycated hemoglobin]] (HbA<sub>1c</sub>) of ≥&nbsp;48&nbsp;mmol/mol (≥&nbsp;6.5 DCCT %) is another method of diagnosing diabetes.<ref name=Will2011/> 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 ≥&nbsp;48&nbsp;mmol/mol (≥&nbsp;6.5 DCCT %) should be used to diagnose diabetes.<ref name=Expert2009/> This recommendation was adopted by the American Diabetes Association in 2010.<ref>{{cite journal | title = Diagnosis and classification of diabetes mellitus | journal = Diabetes Care | volume = 33 | issue = Supplement_1 | pages = S62-9 | date = January 2010 | pmid = 20042775 | pmc = 2797383 | doi = 10.2337/dc10-S062 | author1 = American Diabetes Association }}</ref> Positive tests should be repeated unless the person presents with typical symptoms and blood sugars >11.1&nbsp;mmol/L (>200&nbsp;mg/dL).<ref name=Expert2009>{{cite journal | title = International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes | journal = Diabetes Care | volume = 32 | issue = 7 | pages = 1327–34 | date = July 2009 | pmid = 19502545 | pmc = 2699715 | doi = 10.2337/dc09-9033 | author1 = International Expert Committee }}</ref>

{| class="wikitable" style = "float: right; margin-left:15px; text-align:center"
|+ADA diabetes diagnostic criteria in 2015<ref name="ADA2015-2">{{cite journal | vauthors = Fox CS, Golden SH, Anderson C, Bray GA, Burke LE, de Boer IH, Deedwania P, Eckel RH, Ershow AG, Fradkin J, Inzucchi SE, Kosiborod M, Nelson RG, Patel MJ, Pignone M, Quinn L, Schauer PR, Selvin E, Vafiadis DK | display-authors = 6 | title = Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence: A Scientific Statement From the American Heart Association and the American Diabetes Association | journal = Diabetes Care | volume = 38 | issue = 9 | pages = 1777–1803 | date = September 2015 | pmid = 26246459 | pmc = 4876675 | doi = 10.2337/dci15-0012 | type = Professional society guidelines }}</ref>
&nbsp;
!
!Diabetes mellitus
!Prediabetes
|-
|HbA<sub>1c</sub>
|≥6.5%
|5.7–6.4%
|-
|Fasting glucose
|≥126&nbsp;mg/dL
|100–125&nbsp;mg/dL
|-
|2h glucose
|≥200&nbsp;mg/dL
|140–199&nbsp;mg/dL
|-
|Random glucose with classic symptoms
|≥200&nbsp;mg/dL
|Not available
|}

Threshold for diagnosis of diabetes is based on the relationship between results of glucose tolerance tests, fasting glucose or HbA<sub>1c</sub> and complications such as [[Medicine:Retinopathy|retinal problems]].<ref name=Will2011/> A fasting or random blood sugar is preferred over the glucose tolerance test, as they are more convenient for people.<ref name=Will2011/> HbA<sub>1c</sub> 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.<ref>{{cite journal | title = Diagnosis and classification of diabetes mellitus | journal = Diabetes Care | volume = 35 | issue = Suppl 1 | pages = S64-71 | date = January 2012 | pmid = 22187472 | pmc = 3632174 | doi = 10.2337/dc12-s064 | author1 = American Diabetes Association }}</ref> It is estimated that 20% of people with diabetes in the United States do not realize that they have the disease.<ref name=Will2011/>

Type&nbsp;2 diabetes is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency.<ref name="Pathologic Basis of Disease">{{Cite book | vauthors = Kumar V, Fausto N, Abbas AK, Cotran RS, Robbins SL |title=Robbins and Cotran Pathologic Basis of Disease|year=2005|edition=7th|publisher=Saunders|location=Philadelphia, Pa.|isbn=978-0-7216-0187-8|pages=1194–95}}</ref> This is in contrast to [[Medicine:Type 1 diabetes|type 1 diabetes]] in which there is an absolute insulin deficiency due to destruction of islet cells in the pancreas and [[Medicine:Gestational diabetes|gestational diabetes]] that is a new onset of high blood sugars associated with pregnancy.<ref name="Green2011"/> Type&nbsp;1 and type&nbsp;2 diabetes can typically be distinguished based on the presenting circumstances.<ref name=Expert2009/> If the diagnosis is in doubt [[Biology:Antibody|antibody]] testing may be useful to confirm type&nbsp;1 diabetes and [[Chemistry:C-peptide|C-peptide]] levels may be useful to confirm type&nbsp;2 diabetes,<ref>{{cite book|title=Diabetes mellitus a guide to patient care.|year=2007|publisher=Lippincott Williams & Wilkins|location=Philadelphia|isbn=978-1-58255-732-8|page=[https://archive.org/details/diabetesmellitus0000unse_k9g1/page/201 201]|url=https://archive.org/details/diabetesmellitus0000unse_k9g1|url-access=registration}}</ref> with C-peptide levels normal or high in type&nbsp;2 diabetes, but low in type&nbsp;1 diabetes.<ref>{{cite book | vauthors = Vivian EM, Blackorbay B | veditors = Lee M |title=Basic Skills in Interpreting Laboratory Data |edition=5th |date=2013 |publisher=American Society of Health-System Pharmacists |location=Bethesda, MD |isbn=978-1-58528-345-3 |oclc=859778842 |chapter=Chapter 13: Endocrine Disorders |chapter-url=https://books.google.com/books?id=5WW1AAAAQBAJ&pg=PT539}}</ref>

==Screening==
Universal [[Medicine:Screening|screening]] for diabetes in people without risk factors or symptoms is not recommended.<ref name=Screen09>{{cite journal | vauthors = Valdez R | title = Detecting undiagnosed type 2 diabetes: family history as a risk factor and screening tool | journal = Journal of Diabetes Science and Technology | volume = 3 | issue = 4 | pages = 722–6 | date = July 2009 | pmid = 20144319 | pmc = 2769984 | doi = 10.1177/193229680900300417 }}</ref><ref name=Selph_et_al-2015>{{cite journal | vauthors = Selph S, Dana T, Blazina I, Bougatsos C, Patel H, Chou R | title = Screening for type 2 diabetes mellitus: a systematic review for the U.S. Preventive Services Task Force | journal = Annals of Internal Medicine | volume = 162 | issue = 11 | pages = 765–76 | date = June 2015 | pmid = 25867111 | doi = 10.7326/M14-2221 | doi-access = free }}</ref> Screening is recommended by the [[Organization:World Health Organization|World Health Organization]], the United States Preventive Services Task Force (USPSTF), and the American Diabetes Association for high-risk adults.<ref name="uspreventiveservicestaskforce.org">{{Cite web |title=Recommendation: Prediabetes and Type 2 Diabetes: Screening {{!}} United States Preventive Services Taskforce |url=https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/screening-for-prediabetes-and-type-2-diabetes |access-date=2023-01-13 |website=www.uspreventiveservicestaskforce.org |language=en}}</ref><ref>{{cite journal |vauthors=Siu AL |date=December 2015 |title=Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus: U.S. Preventive Services Task Force Recommendation Statement |journal=Annals of Internal Medicine |volume=163 |issue=11 |pages=861–8 |doi=10.7326/M15-2345 |pmid=26501513 |doi-access=free}}</ref><ref name="ADA21015">{{cite journal |date=January 2015 |title=Standards of medical care in diabetes--2015: summary of revisions |journal=Diabetes Care |volume=38 |issue=38 |pages=S4 |doi=10.2337/dc15-S003 |pmid=25537706 |doi-access=free}}</ref>  Risk factors considered by the USPSTF include adults over 35 years old who are overweight or have obesity and adults without symptoms whose [[Physics:Blood pressure|blood pressure]] is greater than 135/80&nbsp;mmHg.<ref name=US08>{{cite web |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspsdiab.htm |title=Archived: Diabetes Mellitus (Type 2) in Adults: Screening |date=June 2008 |work=U.S. Preventive Services Task Force |access-date=2014-03-16 |url-status=live |archive-url=https://web.archive.org/web/20140207214318/http://www.uspreventiveservicestaskforce.org/uspstf/uspsdiab.htm |archive-date=2014-02-07 }}</ref>{{Update inline|date=January 2023}}<ref name="uspreventiveservicestaskforce.org"/> For those whose blood pressure is less, the evidence is insufficient to recommend for or against screening.<ref name=US08/>{{Update inline|date=January 2023}} The American Diabetes Society recommends screening for adults with a body mass index (BMI) over 25.<ref name="ADA21015" /> For people of Asian descent, screening is recommended if they have a BMI over 23.<ref name="ADA21015" /> 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 [[Medicine:Gestational diabetes|gestational diabetes]]; [[Medicine:Polycystic ovary syndrome|polycystic ovary syndrome]]; excess weight; and conditions associated with [[Medicine:Metabolic syndrome|metabolic syndrome]].<ref name="Vij2010" /> There is no evidence that screening changes the risk of death and any benefit of screening on adverse effects, incidence of type 2 diabetes, HbA<sub>1c</sub> or socioeconomic effects are not clear.<ref name=Selph_et_al-2015/><ref name=":2">{{cite journal |vauthors=Peer N, Balakrishna Y, Durao S |date=May 2020 |title=Screening for type 2 diabetes mellitus |journal=The Cochrane Database of Systematic Reviews |volume=5 |issue=6 |pages=CD005266 |doi=10.1002/14651858.cd005266.pub2 |pmc=7259754 |pmid=32470201}}</ref>

In the UK, [[Organization:National Institute for Health and Care Excellence|NICE]] guidelines suggest taking action to prevent diabetes for people with a body mass index (BMI) of 30 or more.<ref name=":4" /> For people of Black African, African-Caribbean, South Asian and Chinese descent the recommendation to start prevention starts at the BMI of 27,5.<ref name=":4">{{Cite journal |date=2022-07-26 |title=Diabetes: putting people at the heart of services |url=https://evidence.nihr.ac.uk/collection/diabetes-putting-people-at-the-heart-of-services/ |journal=NIHR Evidence |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_52026|s2cid=251299176 }}</ref> 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.<ref>{{Cite journal |date=2022-03-10 |title=Are you at risk of diabetes? Research finds prevention should start at a different BMI for each ethnic group |url=https://evidence.nihr.ac.uk/alert/diabetes-prevention-should-start-at-different-bmi-for-each-ethnic-group/ |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/alert_48878|s2cid=247390548 }}</ref><ref>{{cite journal | vauthors = Caleyachetty R, Barber TM, Mohammed NI, Cappuccio FP, Hardy R, Mathur R, Banerjee A, Gill P | display-authors = 6 | title = Ethnicity-specific BMI cutoffs for obesity based on type 2 diabetes risk in England: a population-based cohort study | journal = The Lancet. Diabetes & Endocrinology | volume = 9 | issue = 7 | pages = 419–426 | date = July 2021 | pmid = 33989535 | pmc = 8208895 | doi = 10.1016/S2213-8587(21)00088-7 }}</ref>

==Prevention==
Onset of type&nbsp;2 diabetes can be delayed or prevented through proper nutrition and regular exercise.<ref>{{cite journal | vauthors = Raina Elley C, Kenealy T | title = Lifestyle interventions reduced the long-term risk of diabetes in adults with impaired glucose tolerance | journal = Evidence-Based Medicine | volume = 13 | issue = 6 | pages = 173 | date = December 2008 | pmid = 19043031 | doi = 10.1136/ebm.13.6.173 | s2cid = 26714233 }}</ref><ref>{{cite journal | vauthors = Hemmingsen B, Gimenez-Perez G, Mauricio D, Roqué I, Figuls M, Metzendorf MI, Richter B | title = Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 12 | pages = CD003054 | date = December 2017 | pmid = 29205264 | pmc = 6486271 | doi = 10.1002/14651858.CD003054.pub4 }}</ref> Intensive lifestyle measures may reduce the risk by over half.<ref name=AFP09/><ref name=Schellenberg2013>{{cite journal | vauthors = Schellenberg ES, Dryden DM, Vandermeer B, Ha C, Korownyk C | title = Lifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysis | journal = Annals of Internal Medicine | volume = 159 | issue = 8 | pages = 543–551 | date = October 2013 | pmid = 24126648 | doi = 10.7326/0003-4819-159-8-201310150-00007 | doi-access = free }}</ref> The benefit of exercise occurs regardless of the person's initial weight or subsequent weight loss.<ref>{{cite journal | vauthors = O'Gorman DJ, Krook A | title = Exercise and the treatment of diabetes and obesity | journal = The Medical Clinics of North America | volume = 95 | issue = 5 | pages = 953–969 | date = September 2011 | pmid = 21855702 | doi = 10.1016/j.mcna.2011.06.007 }}</ref> High levels of physical activity reduce the risk of diabetes by about 28%.<ref name=BMJ2016>{{cite journal | vauthors = Kyu HH, Bachman VF, Alexander LT, Mumford JE, Afshin A, Estep K, Veerman JL, Delwiche K, Iannarone ML, Moyer ML, Cercy K, Vos T, Murray CJ, Forouzanfar MH | display-authors = 6 | title = Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013 | journal = BMJ | volume = 354 | pages = i3857 | date = August 2016 | pmid = 27510511 | pmc = 4979358 | doi = 10.1136/bmj.i3857 | doi-access = free }}</ref> Evidence for the benefit of dietary changes alone, however, is limited,<ref>{{cite journal | vauthors = Nield L, Summerbell CD, Hooper L, Whittaker V, Moore H | title = Dietary advice for the prevention of type 2 diabetes mellitus in adults | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD005102 | date = July 2008 | pmid = 18646120 | doi = 10.1002/14651858.CD005102.pub2 | veditors = Nield L | s2cid = 23039006 | hdl = 10149/92337 }}{{Retracted|intentional=yes}}</ref> with some evidence for a diet high in green leafy vegetables<ref>{{cite journal | vauthors = Carter P, Gray LJ, Troughton J, Khunti K, Davies MJ | title = Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis | journal = BMJ | volume = 341 | pages = c4229 | date = August 2010 | pmid = 20724400 | pmc = 2924474 | doi = 10.1136/bmj.c4229 }}</ref> and some for limiting the intake of sugary drinks.<ref name="Schwing">{{cite journal | vauthors = Schwingshackl L, Hoffmann G, Lampousi AM, Knüppel S, Iqbal K, Schwedhelm C, Bechthold A, Schlesinger S, Boeing H | display-authors = 6 | title = Food groups and risk of type 2 diabetes mellitus: a systematic review and meta-analysis of prospective studies | journal = European Journal of Epidemiology | volume = 32 | issue = 5 | pages = 363–375 | date = May 2017 | pmid = 28397016 | pmc = 5506108 | doi = 10.1007/s10654-017-0246-y }}</ref> There is an association between higher intake of sugar-sweetened fruit juice and diabetes, but no evidence of an association with 100% fruit juice.<ref>{{cite journal | vauthors = Xi B, Li S, Liu Z, Tian H, Yin X, Huai P, Tang W, Zhou D, Steffen LM | display-authors = 6 | title = Intake of fruit juice and incidence of type 2 diabetes: a systematic review and meta-analysis | journal = PLOS ONE | volume = 9 | issue = 3 | pages = e93471 | date = 2014 | pmid = 24682091 | pmc = 3969361 | doi = 10.1371/journal.pone.0093471 | doi-access = free | bibcode = 2014PLoSO...993471X }}</ref> A 2019 review found evidence of benefit from dietary fiber.<ref>{{cite journal | vauthors = Reynolds A, Mann J, Cummings J, Winter N, Mete E, Te Morenga L | title = Carbohydrate quality and human health: a series of systematic reviews and meta-analyses | journal = Lancet | volume = 393 | issue = 10170 | pages = 434–445 | date = February 2019 | pmid = 30638909 | doi = 10.1016/S0140-6736(18)31809-9 | s2cid = 58632705 | doi-access = free }}</ref>

In those with impaired glucose tolerance, a 2019 [[Systematic review|systematic review]] found moderate-quality evidence that [[Chemistry:Metformin|Metformin]], when compared to diet and exercise or a [[Medicine:Placebo|placebo]] intervention, appeared to delay or reduce the risk of developing type 2 diabetes.<ref name=":3">{{cite journal | vauthors = Madsen KS, Chi Y, Metzendorf MI, Richter B, Hemmingsen B | title = Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 12 | pages = CD008558 | date = December 2019 | pmid = 31794067 | pmc = 6889926 | doi = 10.1002/14651858.CD008558.pub2 | collaboration = Cochrane Metabolic and Endocrine Disorders Group }}</ref> 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.<ref name=":3" /> This systematic review only found one suitable trial comparing Metformin with [[Chemistry:Sulfonylurea|Sulphonylurea]] in reducing risk of type 2 diabetes but it did not report any patient-relevant outcomes.<ref name=":3" />

A [[Organization:Cochrane (organisation)|Cochrane]] [[Systematic review|systematic review]] assessed the effect of [[Biology:Alpha-glucosidase inhibitor|alpha-glucosidase inhibitor]]s in people with impaired glucose tolerance, impaired [[Medicine:Glucose test|fasting blood glucose]], elevated [[Biology:Glycated hemoglobin|glycated hemoglobin A1c]] (HbA1c).<ref name=":03">{{Cite journal |last1=Moelands |first1=Suzanne VL |last2=Lucassen |first2=Peter LBJ |last3=Akkermans |first3=Reinier P |last4=De Grauw |first4=Wim JC |last5=Van de Laar |first5=Floris A |date=2018-12-28 |editor-last=Cochrane Metabolic and Endocrine Disorders Group |title=Alpha-glucosidase inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus |journal=Cochrane Database of Systematic Reviews |language=en |volume=2018 |issue=12 |pages=CD005061 |doi=10.1002/14651858.CD005061.pub3 |pmc=6517235 |pmid=30592787}}</ref> 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, [[Chemistry:Metformin|metformin]], [[Medicine:Placebo|placebo]], no intervention improved [[Mortality rate|all-cause mortality]], reduced or increased risk of cardiovascular mortality, serious or non-serious adverse events, non-fatal [[Medicine:Stroke|stroke]], [[Medicine:Heart failure|congestive heart failure]], or non-fatal [[Medicine:Myocardial infarction|myocardial infarction]].<ref name=":03"/> 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.<ref name=":03" />

A 2017 review found that, long term, lifestyle changes decreased the risk by 28%, while medication does not reduce risk after withdrawal.<ref>{{cite journal | vauthors = Haw JS, Galaviz KI, Straus AN, Kowalski AJ, Magee MJ, Weber MB, Wei J, Narayan KM, Ali MK | title = Long-term Sustainability of Diabetes Prevention Approaches: A Systematic Review and Meta-analysis of Randomized Clinical Trials | journal = JAMA Internal Medicine | volume = 177 | issue = 12 | pages = 1808–1817 | date = December 2017 | pmid = 29114778 | pmc = 5820728 | doi = 10.1001/jamainternmed.2017.6040 }}</ref> While low [[Chemistry:Vitamin D|vitamin D]] levels are associated with an increased risk of diabetes, correcting the levels by supplementing vitamin D3 does not improve that risk.<ref>{{cite journal | vauthors = Seida JC, Mitri J, Colmers IN, Majumdar SR, Davidson MB, Edwards AL, Hanley DA, Pittas AG, Tjosvold L, Johnson JA | title = Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 99 | issue = 10 | pages = 3551–60 | date = October 2014 | pmid = 25062463 | pmc = 4483466 | doi = 10.1210/jc.2014-2136 }}</ref>

==Management==
Management of type&nbsp;2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range.<ref name=AFP09>{{cite journal | vauthors = Ripsin CM, Kang H, Urban RJ | title = Management of blood glucose in type 2 diabetes mellitus | journal = American Family Physician | volume = 79 | issue = 1 | pages = 29–36 | date = January 2009 | pmid = 19145963 }}</ref> Self-monitoring of blood glucose for people with newly diagnosed type&nbsp;2 diabetes may be used in combination with education,<ref>{{cite journal | vauthors = Mannucci E, Giaccari A, Gallo M, Bonifazi A, Belén ÁD, Masini ML, Trento M, Monami M | display-authors = 6 | title = Self-management in patients with type 2 diabetes: Group-based versus individual education. A systematic review with meta-analysis of randomized trails | journal = Nutrition, Metabolism, and Cardiovascular Diseases | volume = 32 | issue = 2 | pages = 330–336 | date = February 2022 | pmid = 34893413 | doi = 10.1016/j.numecd.2021.10.005 | s2cid = 244580173 }}</ref> although the benefit of self-monitoring in those not using multi-dose insulin is questionable.<ref name=AFP09/> In those who do not want to measure blood levels, measuring urine levels may be done.<ref name="NICE2009Self">{{Cite web|date=May 2009|title=Type 2 diabetes: The management of type 2 diabetes|url=http://www.nice.org.uk/guidance/cg87/chapter/1-recommendations#self-monitoring-of-plasma-glucose|url-status=live|archive-url=https://web.archive.org/web/20150522055955/http://www.nice.org.uk/guidance/cg87/chapter/1-recommendations#self-monitoring-of-plasma-glucose|archive-date=2015-05-22}}</ref> Managing other cardiovascular risk factors, such as [[Medicine:Hypertension|hypertension]], high cholesterol, and microalbuminuria, improves a person's life expectancy.<ref name=AFP09/> Decreasing the systolic blood pressure to less than 140&nbsp;mmHg is associated with a lower risk of death and better outcomes.<ref>{{cite journal | vauthors = Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A | title = Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis | journal = JAMA | volume = 313 | issue = 6 | pages = 603–615 | date = February 2015 | pmid = 25668264 | doi = 10.1001/jama.2014.18574 | doi-access = free }}</ref> Intensive blood pressure management (less than 130/80&nbsp;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.<ref>{{cite journal | vauthors = McBrien K, Rabi DM, Campbell N, Barnieh L, Clement F, Hemmelgarn BR, Tonelli M, Leiter LA, Klarenbach SW, Manns BJ | display-authors = 6 | title = Intensive and Standard Blood Pressure Targets in Patients With Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis | journal = Archives of Internal Medicine | volume = 172 | issue = 17 | pages = 1296–1303 | date = September 2012 | pmid = 22868819 | doi = 10.1001/archinternmed.2012.3147 | doi-access = free }}</ref>

Intensive blood sugar lowering (HbA<sub>1c</sub><6%) as opposed to standard blood sugar lowering (HbA<sub>1c</sub> of 7–7.9%) does not appear to change mortality.<ref>{{cite journal | vauthors = Boussageon R, Bejan-Angoulvant T, Saadatian-Elahi M, Lafont S, Bergeonneau C, Kassaï B, Erpeldinger S, Wright JM, Gueyffier F, Cornu C | title = Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials | journal = BMJ | volume = 343 | pages = d4169 | date = July 2011 | pmid = 21791495 | pmc = 3144314 | doi = 10.1136/bmj.d4169 }}</ref><ref>{{cite journal | vauthors = Webster MW | title = Clinical practice and implications of recent diabetes trials | journal = Current Opinion in Cardiology | volume = 26 | issue = 4 | pages = 288–93 | date = July 2011 | pmid = 21577100 | doi = 10.1097/HCO.0b013e328347b139 | s2cid = 20819316 }}</ref> The goal of treatment is typically an HbA<sub>1c</sub> of 7 to 8% or a fasting glucose of less than 7.2&nbsp;mmol/L (130&nbsp;mg/dL); however these goals may be changed after professional clinical consultation, taking into account particular risks of [[Medicine:Hypoglycemia|hypoglycemia]] and life expectancy.<ref name=ADA21015 /><ref name=ADA2015/><ref>{{cite journal | vauthors = Qaseem A, Wilt TJ, Kansagara D, Horwitch C, Barry MJ, Forciea MA | title = Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians | journal = Annals of Internal Medicine | volume = 168 | issue = 8 | pages = 569–576 | date = April 2018 | pmid = 29507945 | doi = 10.7326/M17-0939 | doi-access = free }}</ref> Hypoglycemia is associated with adverse outcomes in older people with type 2 diabetes.<ref>{{cite journal | vauthors = Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, Heller SR, Rodriguez H, Rosenzweig J, Vigersky R | display-authors = 6 | title = Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society | journal = Diabetes Care | volume = 36 | issue = 5 | pages = 1384–1395 | date = May 2013 | pmid = 23589542 | pmc = 3631867 | doi = 10.2337/dc12-2480 | type = Professional society guidelines }}</ref> Despite guidelines recommending that intensive blood sugar control be based on balancing immediate harms with long-term benefits, many people&nbsp;– for example people with a life expectancy of less than nine years who will not benefit, are over-treated.<ref>{{cite journal | vauthors = Makam AN, Nguyen OK | title = An Evidence-Based Medicine Approach to Antihyperglycemic Therapy in Diabetes Mellitus to Overcome Overtreatment | journal = Circulation | volume = 135 | issue = 2 | pages = 180–195 | date = January 2017 | pmid = 28069712 | pmc = 5502688 | doi = 10.1161/CIRCULATIONAHA.116.022622 }}</ref>

It is recommended that all people with type&nbsp;2 diabetes get regular [[Medicine:Eye examination|eye examination]]s.<ref name=Green2011/> There is moderate evidence suggesting that treating gum disease by [[Medicine:Scaling and root planing|scaling and root planing]] results in an improvement in blood sugar levels for people with diabetes.<ref name="Simpson2015">{{cite journal |vauthors=Simpson TC, Clarkson JE, Worthington HV, MacDonald L, Weldon JC, Needleman I, Iheozor-Ejiofor Z, Wild SH, Qureshi A, Walker A, Patel VA, Boyers D, Twigg J |date=April 14, 2022 |title=Treatment of periodontitis for glycaemic control in people with diabetes mellitus |journal=The Cochrane Database of Systematic Reviews |volume= 2022|issue= 4|pages= CD004714|doi=10.1002/14651858.CD004714.pub4 |pmc= 9009294|pmid=35420698|hdl=2164/20480|hdl-access=free}}</ref>

===Lifestyle===
==== Exercise ====
A proper diet and regular exercise are foundations of diabetic care,<ref name=Vij2010/> with one review indicating that a greater amount of exercise improved outcomes.<ref>{{cite journal|vauthors=Smith AD, Crippa A, Woodcock J, Brage S|date=December 2016|title=Physical activity and incident type 2 diabetes mellitus: a systematic review and dose-response meta-analysis of prospective cohort studies|journal=Diabetologia|volume=59|issue=12|pages=2527–2545|doi=10.1007/s00125-016-4079-0|pmc=6207340|pmid=27747395}}</ref> Regular exercise may improve blood sugar control, decrease body fat content, and decrease blood lipid levels.<ref>{{cite journal|vauthors=Thomas DE, Elliott EJ, Naughton GA|date=July 2006|title=Exercise for type 2 diabetes mellitus|journal=The Cochrane Database of Systematic Reviews|volume=2009|issue=3|pages=CD002968|doi=10.1002/14651858.CD002968.pub2|pmid=16855995|pmc=8989410|s2cid=25505640}}</ref>

==== Diet ====
[[Biology:Calorie restriction|Calorie restriction]] to promote weight loss is generally recommended.<ref name="Diet09">{{cite journal | vauthors = Davis N, Forbes B, Wylie-Rosett J | title = Nutritional strategies in type 2 diabetes mellitus | journal = The Mount Sinai Journal of Medicine, New York | volume = 76 | issue = 3 | pages = 257–268 | date = June 2009 | pmid = 19421969 | doi = 10.1002/msj.20118 }}</ref><ref name="ADA2015-2"/> 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 {{convert|15|kg}},<ref>{{cite journal |last1=Magkos |first1=Faidon |last2=Hjorth |first2=Mads F. |last3=Astrup |first3=Arne |title=Diet and exercise in the prevention and treatment of type 2 diabetes mellitus |journal=Nature Reviews Endocrinology |date=October 2020 |volume=16 |issue=10 |pages=545–555 |doi=10.1038/s41574-020-0381-5 |pmid=32690918 |s2cid=220651657 |url=https://www.nature.com/articles/s41574-020-0381-5 |language=en |issn=1759-5037|quote=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.}}</ref><ref>{{cite web |title=Achieving Type 2 Diabetes Remission through Weight Loss |url=https://www.niddk.nih.gov/health-information/professionals/diabetes-discoveries-practice/achieving-type-2-diabetes-remission-through-weight-loss |website=National Institute of Diabetes and Digestive and Kidney Diseases |access-date=29 November 2023 |date=30 September 2020}}</ref> but most patients are not able to achieve or sustain significant weight loss.<ref name="UpToDate" /> Even modest weight loss can produce significant improvements in glycemic control and reduce the need for medication.<ref>{{cite journal |title=8. Obesity Management for the Treatment of Type 2 Diabetes: Standards of Medical Care in Diabetes—2021 |journal=Diabetes Care |date=1 January 2021 |volume=44 |issue=Supplement_1 |pages=S100–S110 |doi=10.2337/dc21-S008|pmid=33298419 |author1=American Diabetes Association |s2cid=228087486 |doi-access=free }}</ref>

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.<ref name="ADA2015-2" /><ref>{{cite journal | vauthors = Thomas D, Elliott EJ | title = Low glycaemic index, or low glycaemic load, diets for diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD006296 | date = January 2009 | volume = 2009 | pmid = 19160276 | pmc = 6486008 | doi = 10.1002/14651858.CD006296.pub2 | veditors = Thomas D }}</ref><ref>{{cite journal | vauthors = Feinman RD, Pogozelski WK, Astrup A, Bernstein RK, Fine EJ, Westman EC, Accurso A, Frassetto L, Gower BA, McFarlane SI, Nielsen JV, Krarup T, Saslow L, Roth KS, Vernon MC, Volek JS, Wilshire GB, Dahlqvist A, Sundberg R, Childers A, Morrison K, Manninen AH, Dashti HM, Wood RJ, Wortman J, Worm N | display-authors = 6 | title = Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base | journal = Nutrition | volume = 31 | issue = 1 | pages = 1–13 | date = January 2015 | pmid = 25287761 | doi = 10.1016/j.nut.2014.06.011 | doi-access = free }}</ref> 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.<ref name="ADA2015-2" /><ref name="ADA2013-nutrition">{{cite journal | vauthors = Evert AB, Boucher JL, Cypress M, Dunbar SA, Franz MJ, Mayer-Davis EJ, Neumiller JJ, Nwankwo R, Verdi CL, Urbanski P, Yancy WS | display-authors = 6 | title = Nutrition therapy recommendations for the management of adults with diabetes | journal = Diabetes Care | volume = 37 | issue = Supplement_1 | pages = S120–S143 | date = January 2014 | pmid = 24357208 | doi = 10.2337/dc14-S120 | type = Professional society guidelines | doi-access = free }}</ref> A 2021 review showed that consumption of tree nuts ([[Biology:Walnut|walnut]]s, [[Biology:Almond|almond]]s, and [[Biology:Hazelnut|hazelnut]]s) reduced fasting blood glucose in diabetic people.<ref>{{cite journal | vauthors = Muley A, Fernandez R, Ellwood L, Muley P, Shah M | title = Effect of tree nuts on glycemic outcomes in adults with type 2 diabetes mellitus: a systematic review | journal = JBI Evidence Synthesis | volume = 19 | issue = 5 | pages = 966–1002 | date = May 2021 | pmid = 33141798 | doi = 10.11124/JBISRIR-D-19-00397 | s2cid = 226250006 }}</ref> {{As of|2015}}, there is insufficient data to recommend nonnutritive sweeteners, which may help reduce caloric intake.<ref>{{cite journal | vauthors = Gardner C, Wylie-Rosett J, Gidding SS, Steffen LM, Johnson RK, Reader D, Lichtenstein AH | title = Nonnutritive sweeteners: current use and health perspectives: a scientific statement from the American Heart Association and the American Diabetes Association | journal = Diabetes Care | volume = 35 | issue = 8 | pages = 1798–1808 | date = August 2012 | pmid = 22778165 | doi = 10.2337/dc12-9002 | pmc = 3402256 }}</ref> An elevated intake of [[Chemistry:Resistant starch|microbiota-accessible carbohydrates]] can help reducing the effects of T2D.<ref>{{cite journal | vauthors = Xu B, Fu J, Qiao Y, Cao J, Deehan EC, Li Z, Jin M, Wang X, Wang Y | display-authors = 6 | title = Higher intake of microbiota-accessible carbohydrates and improved cardiometabolic risk factors: a meta-analysis and umbrella review of dietary management in patients with type 2 diabetes | journal = The American Journal of Clinical Nutrition | volume = 113 | issue = 6 | pages = 1515–1530 | date = June 2021 | pmid = 33693499 | doi = 10.1093/ajcn/nqaa435 | doi-access = free }}</ref> Viscous fiber supplements may be useful in those with diabetes.<ref>{{cite journal | vauthors = Jovanovski E, Khayyat R, Zurbau A, Komishon A, Mazhar N, Sievenpiper JL, Blanco Mejia S, Ho HV, Li D, Jenkins AL, Duvnjak L, Vuksan V | display-authors = 6 | title = Should Viscous Fiber Supplements Be Considered in Diabetes Control? Results From a Systematic Review and Meta-analysis of Randomized Controlled Trials | journal = Diabetes Care | volume = 42 | issue = 5 | pages = 755–766 | date = May 2019 | pmid = 30617143 | doi = 10.2337/dc18-1126 | s2cid = 58665219 | doi-access = free }}</ref>

Culturally appropriate education may help people with type&nbsp;2 diabetes control their blood sugar levels for up to 24 months.<ref>{{cite journal | vauthors = Attridge M, Creamer J, Ramsden M, Cannings-John R, Hawthorne K | title = Culturally appropriate health education for people in ethnic minority groups with type 2 diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD006424 | date = September 2014 | volume = 2014 | pmid = 25188210 | doi = 10.1002/14651858.CD006424.pub3 | pmc = 10680058 }}</ref> There is not enough evidence to determine if lifestyle interventions affect mortality in those who already have type 2 diabetes.<ref name="Schellenberg2013" />

==== Stress management ====
Although psychological stress is recognized as a risk factor for type 2 diabetes,<ref name=Will2011/> the effect of [[Social:Stress management|stress management]] interventions on disease progression are not established.<ref>{{Cite journal |last1=Hackett |first1=Ruth A. |last2=Steptoe |first2=Andrew |date=2017 |title=Type 2 diabetes mellitus and psychological stress — a modifiable risk factor |url=http://www.nature.com/articles/nrendo.2017.64 |journal=Nature Reviews Endocrinology |language=en |volume=13 |issue=9 |pages=547–560 |doi=10.1038/nrendo.2017.64 |pmid=28664919 |s2cid=34925223 |issn=1759-5029}}</ref> A Cochrane review is under way to assess the effects of [[Philosophy:Mindfulness|mindfulness]]‐based interventions for adults with type 2 diabetes.<ref>{{Cite journal |last1=Ee |first1=Carolyn C |last2=Armour |first2=Mike |last3=Piya |first3=Milan K |last4=McMorrow |first4=Rita |last5=Al-Kanini |first5=Ieman |last6=Sabag |first6=Angelo |date=2021-12-23 |editor-last=Cochrane Metabolic and Endocrine Disorders Group |title=Mindfulness-based interventions for adults with type 2 diabetes mellitus |journal=Cochrane Database of Systematic Reviews |language=en |volume=2021 |issue=12 |pages=CD014881 |doi=10.1002/14651858.CD014881 |pmc=8701561}}</ref>

===Medications===
[[File:Metformin 500mg Tablets.jpg|thumb|upright=1.4|Metformin 500&nbsp;mg tablets]]

==== Blood sugar control ====
There are several classes of anti-diabetic medications available. [[Chemistry:Metformin|Metformin]] is generally recommended as a first line treatment as there is some evidence that it decreases mortality;<ref name="Ann2016" /><ref name="AFP09" /><ref>{{cite journal | vauthors = Palmer SC, Mavridis D, Nicolucci A, Johnson DW, Tonelli M, Craig JC, Maggo J, Gray V, De Berardis G, Ruospo M, Natale P, Saglimbene V, Badve SV, Cho Y, Nadeau-Fredette AC, Burke M, Faruque L, Lloyd A, Ahmad N, Liu Y, Tiv S, Wiebe N, Strippoli GF | title = Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis | journal = JAMA | volume = 316 | issue = 3 | pages = 313–24 | date = July 2016 | pmid = 27434443 | doi = 10.1001/jama.2016.9400 | doi-access = free }}</ref> however, this conclusion is questioned.<ref>{{cite journal | vauthors = Boussageon R, Supper I, Bejan-Angoulvant T, Kellou N, Cucherat M, Boissel JP, Kassai B, Moreau A, Gueyffier F, Cornu C | title = Reappraisal of metformin efficacy in the treatment of type 2 diabetes: a meta-analysis of randomised controlled trials | journal = PLOS Medicine | volume = 9 | issue = 4 | pages = e1001204 | year = 2012 | pmid = 22509138 | pmc = 3323508 | doi = 10.1371/journal.pmed.1001204 | veditors = Groop L | doi-access = free }}</ref> Metformin should not be used in those with severe kidney or liver problems.<ref name="Vij2010" /> The American Diabetes Association and European Association for the Study of Diabetes recommend using a GLP-1 receptor agonist or [[Chemistry:SGLT2 inhibitor|SGLT2 inhibitor]] as the first-line treatment in patients who have or are at high risk for atherosclerotic cardiovascular disease, [[Medicine:Heart failure|heart failure]], or kidney disease.<ref>{{cite journal |last1=Marx |first1=Nikolaus |last2=Davies |first2=Melanie J |last3=Grant |first3=Peter J |last4=Mathieu |first4=Chantal |last5=Petrie |first5=John R |last6=Cosentino |first6=Francesco |last7=Buse |first7=John B |title=Guideline recommendations and the positioning of newer drugs in type 2 diabetes care |journal=The Lancet Diabetes & Endocrinology |date=January 2021 |volume=9 |issue=1 |pages=46–52 |doi=10.1016/S2213-8587(20)30343-0|pmid=33159841 |s2cid=226280186 |url=https://figshare.com/articles/journal_contribution/13221455 }}</ref><ref name="pmid34964831">{{cite journal |last=American Diabetes Association Professional Practice Committee |date=January 2022 |title=9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022 |journal=Diabetes Care |volume=45 |issue=Suppl 1 |pages=S125–S143 |doi=10.2337/dc22-S009 |pmid=34964831 |s2cid=245538347 |doi-access=free}}</ref> The higher cost of these drugs compared to metformin has limited their use.<ref name="UpToDate">{{cite web |title=Initial management of hyperglycemia in adults with type 2 diabetes mellitus |url=https://www.uptodate.com/contents/initial-management-of-hyperglycemia-in-adults-with-type-2-diabetes-mellitus |website=[[Medicine:UpToDate|UpToDate]] |access-date=29 November 2023 |date=September 2023}}</ref><ref>{{cite journal |last1=Choi |first1=Jin G. |last2=Winn |first2=Aaron N. |last3=Skandari |first3=M. Reza |last4=Franco |first4=Melissa I. |last5=Staab |first5=Erin M. |last6=Alexander |first6=Jason |last7=Wan |first7=Wen |last8=Zhu |first8=Mengqi |last9=Huang |first9=Elbert S. |last10=Philipson |first10=Louis |last11=Laiteerapong |first11=Neda |title=First-Line Therapy for Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists : A Cost-Effectiveness Study |journal=Annals of Internal Medicine |date=October 2022 |volume=175 |issue=10 |pages=1392–1400 |doi=10.7326/M21-2941 |pmid=36191315 |pmc=10155215 |issn=1539-3704}}</ref><ref>{{cite journal |last1=Baker |first1=Chelsea |last2=Retzik-Stahr |first2=Cimmaron |last3=Singh |first3=Vatsala |last4=Plomondon |first4=Renee |last5=Anderson |first5=Victoria |last6=Rasouli |first6=Neda |title=Should metformin remain the first-line therapy for treatment of type 2 diabetes? |journal=Therapeutic Advances in Endocrinology and Metabolism |date=13 January 2021 |volume=12 |pages=2042018820980225 |doi=10.1177/2042018820980225 |pmid=33489086 |pmc=7809522 |issn=2042-0188}}</ref>

A second oral agent of another class or insulin may be added if metformin is not sufficient after three months.<ref name=ADA2015>{{cite journal | vauthors = Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR | title = Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes | journal = Diabetologia | volume = 58 | issue = 3 | pages = 429–42 | date = March 2015 | pmid = 25583541 | doi = 10.1007/s00125-014-3460-0 | doi-access = free }}</ref> Other classes of medications include: [[Chemistry:Sulfonylurea|sulfonylurea]]s, thiazolidinediones, [[Biology:Dipeptidyl peptidase-4 inhibitor|dipeptidyl peptidase-4 inhibitor]]s, SGLT2 inhibitors, and GLP-1 receptor agonists.<ref name=ADA2015/> 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.<ref>{{cite journal | vauthors = Zheng SL, Roddick AJ, Aghar-Jaffar R, Shun-Shin MJ, Francis D, Oliver N, Meeran K | title = Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis | journal = JAMA | volume = 319 | issue = 15 | pages = 1580–1591 | date = April 2018 | pmid = 29677303 | pmc = 5933330 | doi = 10.1001/jama.2018.3024 }}</ref> [[Chemistry:Rosiglitazone|Rosiglitazone]], a thiazolidinedione, has not been found to improve long-term outcomes even though it improves blood sugar levels.<ref>{{cite journal | vauthors = Richter B, Bandeira-Echtler E, Bergerhoff K, Clar C, Ebrahim SH | title = Rosiglitazone for type 2 diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD006063 | date = July 2007 | volume = 2007 | pmid = 17636824 | doi = 10.1002/14651858.CD006063.pub2 | pmc = 7389529 | url = http://researchonline.lshtm.ac.uk/20292/1/20292.pdf | veditors = Richter B }}</ref> Additionally it is associated with increased rates of heart disease and death.<ref>{{cite journal | vauthors = Chen X, Yang L, Zhai SD | title = Risk of cardiovascular disease and all-cause mortality among diabetic patients prescribed rosiglitazone or pioglitazone: a meta-analysis of retrospective cohort studies | journal = Chinese Medical Journal | volume = 125 | issue = 23 | pages = 4301–6 | date = December 2012 | pmid = 23217404 }}</ref>

Injections of insulin may either be added to oral medication or used alone.<ref name=AFP09/> Most people do not initially need insulin.<ref name=Green2011/> When it is used, a long-acting formulation is typically added at night, with oral medications being continued.<ref name=Vij2010/><ref name=AFP09/> Doses are then increased to effect (blood sugar levels being well controlled).<ref name=AFP09/> When nightly insulin is insufficient, twice daily insulin may achieve better control.<ref name=Vij2010/> The long acting insulins [[Biology:Insulin glargine|glargine]] and [[Chemistry:Insulin detemir|detemir]] are equally safe and effective,<ref>{{cite journal | vauthors = Swinnen SG, Simon AC, Holleman F, Hoekstra JB, Devries JH | title = Insulin detemir versus insulin glargine for type 2 diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | issue = 7 | pages = CD006383 | date = July 2011 | volume = 2011 | pmid = 21735405 | pmc = 6486036 | doi = 10.1002/14651858.CD006383.pub2 | veditors = Simon AC }}</ref> and do not appear much better than neutral protamine Hagedorn [[Biology:NPH insulin|(NPH) insulin]], but as they are significantly more expensive, they are not cost effective as of 2010.<ref>{{cite journal | vauthors = Waugh N, Cummins E, Royle P, Clar C, Marien M, Richter B, Philip S | title = Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation | journal = Health Technology Assessment | volume = 14 | issue = 36 | pages = 1–248 | date = July 2010 | pmid = 20646668 | doi = 10.3310/hta14360 | doi-access = free }}</ref> In those who are pregnant, insulin is generally the treatment of choice.<ref name=Vij2010/>

==== Blood pressure lowering ====
Many international guidelines recommend blood pressure treatment targets that are lower than 140/90&nbsp;mmHg for people with diabetes.<ref>{{cite journal | vauthors = Mitchell S, Malanda B, Damasceno A, Eckel RH, Gaita D, Kotseva K, Januzzi JL, Mensah G, Plutzky J, Prystupiuk M, Ryden L, Thierer J, Virani SS, Sperling L | display-authors = 6 | title = A Roadmap on the Prevention of Cardiovascular Disease Among People Living With Diabetes | journal = Global Heart | volume = 14 | issue = 3 | pages = 215–240 | date = September 2019 | pmid = 31451236 | doi = 10.1016/j.gheart.2019.07.009 | doi-access = free }}</ref> 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,<ref>{{cite journal | vauthors = Brunström M, Carlberg B | title = Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses | journal = BMJ | volume = 352 | pages = i717 | date = February 2016 | pmid = 26920333 | pmc = 4770818 | doi = 10.1136/bmj.i717 }}</ref> 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.<ref>{{cite journal | vauthors = Brunström M, Carlberg B | title = Benefits and harms of lower blood pressure treatment targets: systematic review and meta-analysis of randomised placebo-controlled trials | journal = BMJ Open | volume = 9 | issue = 9 | pages = e026686 | date = September 2019 | pmid = 31575567 | pmc = 6773352 | doi = 10.1136/bmjopen-2018-026686 }}</ref>

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.<ref name="ADA2015-2" /> 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),<ref>{{cite journal | vauthors = Cheng J, Zhang W, Zhang X, Han F, Li X, He X, Li Q, Chen J | display-authors = 6 | title = Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis | journal = JAMA Internal Medicine | volume = 174 | issue = 5 | pages = 773–785 | date = May 2014 | pmid = 24687000 | doi = 10.1001/jamainternmed.2014.348 | doi-access = free }}</ref> or [[Chemistry:Aliskiren|aliskiren]] in preventing cardiovascular disease.<ref>{{cite journal | vauthors = Zheng SL, Roddick AJ, Ayis S | title = Effects of aliskiren on mortality, cardiovascular outcomes and adverse events in patients with diabetes and cardiovascular disease or risk: A systematic review and meta-analysis of 13,395 patients | journal = Diabetes & Vascular Disease Research | volume = 14 | issue = 5 | pages = 400–406 | date = September 2017 | pmid = 28844155 | pmc = 5600262 | doi = 10.1177/1479164117715854 }}</ref> Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes.<ref name=":1">{{cite journal|author5-link=Barry R. Davis | vauthors = Catalá-López F, Macías Saint-Gerons D, González-Bermejo D, Rosano GM, Davis BR, Ridao M, Zaragoza A, Montero-Corominas D, Tobías A, de la Fuente-Honrubia C, Tabarés-Seisdedos R, Hutton B | display-authors = 6 | title = Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Adult Patients with Diabetes Mellitus: A Systematic Review with Network Meta-Analyses | journal = PLOS Medicine | volume = 13 | issue = 3 | pages = e1001971 | date = March 2016 | pmid = 26954482 | pmc = 4783064 | doi = 10.1371/journal.pmed.1001971 | doi-access = free }}</ref> There is no evidence that combining ACEIs and ARBs provides additional benefits.<ref name=":1" />

==== Other ====
The use of [[Chemistry:Aspirin|aspirin]] to prevent cardiovascular disease in diabetes is controversial.<ref name="ADA2015-2" /> 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.<ref>{{cite journal|vauthors=Pignone M, Alberts MJ, Colwell JA, Cushman M, Inzucchi SE, Mukherjee D, Rosenson RS, Williams CD, Wilson PW, Kirkman MS|date=June 2010|title=Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation|journal=Diabetes Care|volume=33|issue=6|pages=1395–402|doi=10.2337/dc10-0555|pmc=2875463|pmid=20508233}}</ref> 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%).<ref name="ADA2015-2" />

[[Chemistry:Vitamin D|Vitamin D]] supplementation to people with type 2 diabetes may improve markers of insulin resistance and HbA1c.<ref>{{cite journal | vauthors = Mirhosseini N, Vatanparast H, Mazidi M, Kimball SM | title = The Effect of Improved Serum 25-Hydroxyvitamin D Status on Glycemic Control in Diabetic Patients: A Meta-Analysis | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 102 | issue = 9 | pages = 3097–3110 | date = September 2017 | pmid = 28957454 | doi = 10.1210/jc.2017-01024 | doi-access = free }}</ref>

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.<ref>{{cite journal | vauthors = Neves AL, Freise L, Laranjo L, Carter AW, Darzi A, Mayer E | title = Impact of providing patients access to electronic health records on quality and safety of care: a systematic review and meta-analysis | journal = BMJ Quality & Safety | volume = 29 | issue = 12 | pages = 1019–1032 | date = December 2020 | pmid = 32532814 | pmc = 7785164 | doi = 10.1136/bmjqs-2019-010581 }}</ref><ref>{{Cite journal |date=2020-10-21 |title=Sharing electronic records with patients led to improved control of type two diabetes |url=https://evidence.nihr.ac.uk/alert/sharing-electronic-records-with-patients-led-to-improved-control-of-type-two-diabetes/ |journal=NIHR Evidence |type=Plain English summary |language=en |doi=10.3310/alert_42103|s2cid=242149388 }}</ref>

===Surgery===
Weight loss surgery in those who are obese is an effective measure to treat diabetes.<ref>{{cite journal | vauthors = Picot J, Jones J, Colquitt JL, Gospodarevskaya E, Loveman E, Baxter L, Clegg AJ | title = The clinical effectiveness and cost-effectiveness of bariatric (weight loss) surgery for obesity: a systematic review and economic evaluation | journal = Health Technology Assessment | volume = 13 | issue = 41 | pages = 1–190, 215–357, iii–iv | date = September 2009 | pmid = 19726018 | doi = 10.3310/hta13410 | hdl = 10536/DRO/DU:30064294 | doi-access = free | hdl-access = free }}</ref> Many are able to maintain normal blood sugar levels with little or no medication following surgery<ref>{{cite journal | vauthors = Frachetti KJ, Goldfine AB | title = Bariatric surgery for diabetes management | journal = Current Opinion in Endocrinology, Diabetes and Obesity | volume = 16 | issue = 2 | pages = 119–24 | date = April 2009 | pmid = 19276974 | doi = 10.1097/MED.0b013e32832912e7 | s2cid = 31797748 | doi-access = free }}</ref> and long-term mortality is decreased.<ref name=Schum2009/> There however is some short-term mortality risk of less than 1% from the surgery.<ref>{{cite journal | vauthors = Colucci RA | title = Bariatric surgery in patients with type 2 diabetes: a viable option | journal = Postgraduate Medicine | volume = 123 | issue = 1 | pages = 24–33 | date = January 2011 | pmid = 21293081 | doi = 10.3810/pgm.2011.01.2242 | s2cid = 207551737 }}</ref> The [[Body mass index|body mass index]] cutoffs for when surgery is appropriate are not yet clear.<ref name=Schum2009>{{cite journal | vauthors = Schulman AP, del Genio F, Sinha N, Rubino F | title = "Metabolic" surgery for treatment of type 2 diabetes mellitus | journal = Endocrine Practice | volume = 15 | issue = 6 | pages = 624–31 | date = September–October 2009 | pmid = 19625245 | doi = 10.4158/EP09170.RAR }}</ref> It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.<ref>{{cite journal | vauthors = Dixon JB, le Roux CW, Rubino F, Zimmet P | title = Bariatric surgery for type 2 diabetes | journal = Lancet | volume = 379 | issue = 9833 | pages = 2300–11 | date = June 2012 | pmid = 22683132 | doi = 10.1016/S0140-6736(12)60401-2 | s2cid = 5198462 }}</ref><ref>{{cite journal | vauthors = Rubino F, Nathan DM, Eckel RH, Schauer PR, Alberti KG, Zimmet PZ, Del Prato S, Ji L, Sadikot SM, Herman WH, Amiel SA, Kaplan LM, Taroncher-Oldenburg G, Cummings DE | title = Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes: A Joint Statement by International Diabetes Organizations | journal = Diabetes Care | volume = 39 | issue = 6 | pages = 861–77 | date = June 2016 | pmid = 27222544 | doi = 10.2337/dc16-0236 | doi-access = free }}</ref>

==Epidemiology==
{{Further|Medicine:Epidemiology of diabetes}}
[[File:Prevalence of total diabetes by age and GBD super-region in 2021.jpg|thumb|upright=1.5|Prevalence of total diabetes by age and Global Burden of Disease super-region in 2021]]

The [[Organization:International Diabetes Federation|International Diabetes Federation]] estimates nearly 537 million people lived with diabetes worldwide in 2021,{{sfn|International Diabetes Federation|2021|p=33}} 90–95% of whom have type 2 diabetes.{{sfn|Kahn|Ferris|O'Neill|2020|loc=Epidemiology}} Diabetes is common both in the developed and the developing world.<ref name=Will2011/>

Some ethnic groups such as South Asians, Pacific Islanders, Latinos, and Native Americans are at particularly high risk of developing type 2 diabetes.<ref name=Vij2010/> 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.<ref>{{cite journal |last1=Olaogun |first1=Idowu |last2=Farag |first2=Mina |last3=Hamid |first3=Pousettef |title=The Pathophysiology of Type 2 Diabetes Mellitus in Non-obese Individuals: An Overview of the Current Understanding |journal=Cureus |date=2020 |volume=12 |issue=4 |pages=e7614 |doi=10.7759/cureus.7614 |doi-access=free |pmid=32399348 |pmc=7213678 |issn=2168-8184}}</ref><ref>{{cite journal |last1=Salvatore |first1=Teresa |last2=Galiero |first2=Raffaele |last3=Caturano |first3=Alfredo |last4=Rinaldi |first4=Luca |last5=Criscuolo |first5=Livio |last6=Di Martino |first6=Anna |last7=Albanese |first7=Gaetana |last8=Vetrano |first8=Erica |last9=Catalini |first9=Christian |last10=Sardu |first10=Celestino |last11=Docimo |first11=Giovanni |last12=Marfella |first12=Raffaele |last13=Sasso |first13=Ferdinando Carlo |title=Current Knowledge on the Pathophysiology of Lean/Normal-Weight Type 2 Diabetes |journal=International Journal of Molecular Sciences |date=30 December 2022 |volume=24 |issue=1 |pages=658 |doi=10.3390/ijms24010658 |pmid=36614099 |pmc=9820420 |issn=1422-0067 |doi-access=free }}</ref><ref>{{cite journal |last1=Vipin |first1=Vidyadharan Alukkal |last2=Blesson |first2=Chellakkan Selvanesan |last3=Yallampalli |first3=Chandra |title=Maternal low protein diet and fetal programming of lean type 2 diabetes |journal=World Journal of Diabetes |date=15 March 2022 |volume=13 |issue=3 |pages=185–202 |doi=10.4239/wjd.v13.i3.185 |pmid=35432755 |pmc=8984567 |issn=1948-9358 |doi-access=free }}</ref>

Rates of diabetes in 1985 were estimated at 30&nbsp;million, increasing to 135&nbsp;million in 1995 and 217&nbsp;million in 2005.<ref name=Epi2006/> This increase is believed to be primarily due to the global population aging, a decrease in exercise, and increasing rates of obesity.<ref name=Epi2006/> Traditionally considered a disease of adults, type&nbsp;2 diabetes is increasingly diagnosed in children in parallel with rising obesity rates.<ref name=Will2011/> The five countries with the greatest number of people with diabetes as of 2000 are India having 31.7&nbsp;million, China 20.8&nbsp;million, the United States 17.7&nbsp;million, Indonesia 8.4&nbsp;million, and Japan 6.8&nbsp;million.<ref name = "Wild 2004">{{cite journal | vauthors = Wild S, Roglic G, Green A, Sicree R, King H | title = Global prevalence of diabetes: estimates for the year 2000 and projections for 2030 | journal = Diabetes Care | volume = 27 | issue = 5 | pages = 1047–53 | date = May 2004 | pmid = 15111519 | doi = 10.2337/diacare.27.5.1047 | doi-access = free }}</ref> It is recognized as a global [[Medicine:Epidemic|epidemic]] by the [[Organization:World Health Organization|World Health Organization]].<ref name=WHO2015>{{cite web|title=Diabetes Fact sheet N°312 |url=https://www.who.int/mediacentre/factsheets/fs312/en/ |website=World Health Organization |access-date=2012-01-09 |date=August 2011 |url-status=dead |archive-url=https://web.archive.org/web/20130826174444/http://www.who.int/mediacentre/factsheets/fs312/en/  |archive-date=26 August 2013 }}</ref>

==History==
Diabetes is one of the first diseases described<ref name=Rip2011/> with an Egyptian manuscript from {{circa|1500}} [[Common Era|BCE]] mentioning "too great emptying of the urine."<ref name=History2010/> The first described cases are believed to be of type&nbsp;1 diabetes.<ref name=History2010>{{cite book | vauthors = Zajac J, Shrestha A, Patel P, Poretsky L | name-list-style = vanc |chapter=The Main Events in the History of Diabetes Mellitus | veditors = Poretsky L |title=Principles of diabetes mellitus|year=2009|publisher=Springer|location=New York|isbn=978-0-387-09840-1|chapter-url = https://books.google.com/books?id=i0qojvF1SpUC&pg=PA3 | pages = 3–16 |edition=2nd |oclc=663097550 }}</ref> Indian physicians around the same time identified the disease and classified it as ''madhumeha'' or ''honey urine'' noting that the urine would attract ants.<ref name=History2010/> The term "diabetes" or "to pass through"  was first used in 230&nbsp;BCE by the Greek Apollonius Memphites.<ref name=History2010/> The disease was rare during the time of the Roman empire with [[Biography:Galen|Galen]] commenting that he had only seen two cases during his career.<ref name=History2010/>

Type&nbsp;1 and type&nbsp;2 diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400–500&nbsp;AD with type&nbsp;1 associated with youth and type&nbsp;2 with being overweight.<ref name=History2010/> Effective treatment was not developed until the early part of the 20th century when the Canadians [[Biography:Frederick Banting|Frederick Banting]] and Charles Best discovered insulin in 1921 and 1922.<ref name=History2010/> This was followed by the development of the long acting NPH insulin in the 1940s.<ref name=History2010/>

In 1916, Elliot Joslin proposed that in people with diabetes, periods of fasting are helpful.<ref name="Koutroumpakis2019">{{cite journal | vauthors = Koutroumpakis E, Jozwik B, Aguilar D, Taegtmeyer H | title = Strategies of Unloading the Failing Heart from Metabolic Stress | journal = The American Journal of Medicine | volume = 133 | issue = 3 | pages = 290–296 | date = March 2020 | pmid = 31520618 | pmc = 7054139 | doi = 10.1016/j.amjmed.2019.08.035 | type = Review }}</ref> Subsequent research has supported this, and weight loss is a first line treatment in type 2 diabetes.<ref name="Koutroumpakis2019" />

== 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.<ref>{{Cite journal |date=2020-08-07 |title=New tool for assessing the severity of type 2 diabetes could help personalise treatment and improve outcomes |url=https://evidence.nihr.ac.uk/alert/new-tool-for-assessing-the-severity-of-type-2-diabetes-could-help-personalise-treatment-and-improve-outcomes/ |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/alert_40652|s2cid=242997909 }}</ref><ref>{{cite journal | vauthors = Zghebi SS, Mamas MA, Ashcroft DM, Salisbury C, Mallen CD, Chew-Graham CA, Reeves D, Van Marwijk H, Qureshi N, Weng S, Holt T, Buchan I, Peek N, Giles S, Rutter MK, Kontopantelis E | display-authors = 6 | title = Development and validation of the DIabetes Severity SCOre (DISSCO) in 139 626 individuals with type 2 diabetes: a retrospective cohort study | journal = BMJ Open Diabetes Research & Care | volume = 8 | issue = 1 | pages = e000962 | date = May 2020 | pmid = 32385076 | pmc = 7228474 | doi = 10.1136/bmjdrc-2019-000962 }}</ref>

== References ==
{{Reflist}}

===Works cited===
* {{cite book|vauthors=Kahn CR, Ferris HA, O'Neill BT |chapter=Pathophysiology of Type 1 Diabetes Mellitus |title=Williams Textbook of Endocrinology |edition=14 |publisher=Elsevier |date=2020 |pages=1349–1370}}
* {{cite book|author=International Diabetes Federation |date=2021 |title=IDF Diabetes Atlas |publisher=International Diabetes Federation |edition=10 |url=https://diabetesatlas.org/idfawp/resource-files/2021/07/IDF_Atlas_10th_Edition_2021.pdf |accessdate=18 March 2022 |isbn=9782930229980}}

== External links ==
* [https://diabetesatlas.org/ IDF Diabetes Atlas 2015]
* [http://diabetes.niddk.nih.gov/ National Diabetes Information Clearinghouse] {{Webarchive|url=https://web.archive.org/web/20100221034416/http://diabetes.niddk.nih.gov/ |date=2010-02-21 }}
* [https://www.cdc.gov/diabetes/index.html Centers for Disease Control (Endocrine pathology)]
* [https://diabetesjournals.org/care/issue/42/Supplement_1 ADA's Standards of Medical Care in Diabetes 2019]

{{Medical condition classification and resources
 | DiseasesDB     = 3661
 | ICD10          = {{ICD10|E|11||e|10}}
 | ICD9           = {{ICD9|250.00}}, {{ICD9|250.02}}
 | ICDO           =
 | OMIM           = 125853
 | MedlinePlus    = 000313
 | eMedicineSubj  = article
 | eMedicineTopic = 117853
 | MeshID         = D003924
}}

{{DEFAULTSORT:Diabetes Mellitus Type 2}}
[[Category:Aging-associated diseases]]

{{Sourceattribution|Type 2 diabetes|1}}