Type 2 Diabetes: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Genetics & Heredity
Contributor:
Bruce Ren

Type 2 diabetes is a disorder characterized by abnormally high blood sugar levels. In this form of diabetes, the body stops using and making insulin properly. Insulin is a hormone produced in the pancreas that helps regulate blood sugar levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source. When blood sugar levels are high (such as after a meal), the pancreas releases insulin to move the excess glucose into cells, which reduces the amount of glucose in the blood.

 

  • genetic conditions

1. Introduction

Most people who develop type 2 diabetes first have insulin resistance, a condition in which the body's cells use insulin less efficiently than normal. As insulin resistance develops, more and more insulin is needed to keep blood sugar levels in the normal range. To keep up with the increasing need, insulin-producing cells in the pancreas (called beta cells) make larger amounts of insulin. Over time, the beta cells become less able to respond to blood sugar changes, leading to an insulin shortage that prevents the body from reducing blood sugar levels effectively. Most people have some insulin resistance as they age, but inadequate exercise and excessive weight gain make it worse, greatly increasing the likelihood of developing type 2 diabetes.

Type 2 diabetes can occur at any age, but it most commonly begins in middle age or later. Signs and symptoms develop slowly over years. They include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet (diabetic neuropathy), sores that do not heal well, and weight loss. If blood sugar levels are not controlled through medication or diet, type 2 diabetes can cause long-lasting (chronic) health problems including heart disease and stroke; nerve damage; and damage to the kidneys, eyes, and other parts of the body.

2. Frequency

Type 2 diabetes is the most common type of diabetes, accounting for 90 to 95 percent of all cases. In 2015, more than 23 million people in the United States had diagnosed diabetes and an additional 7 million people likely had undiagnosed diabetes. The prevalence of diabetes increases with age, and the disease currently affects more than 20 percent of Americans over age 65. It is the seventh leading cause of death in the United States.

The risk of diabetes varies by ethnic and geographic background. In the United States, the disease is most common in Native Americans and Alaska Natives. It also has a higher prevalence among people of African American or Hispanic ancestry than those of non-Hispanic white or Asian ancestry. Geographically, diabetes is most prevalent in the southern and Appalachian regions of the United States.

The prevalence of diabetes is rapidly increasing worldwide. Due to an increase in inactive (sedentary) lifestyles, obesity, and other risk factors, the frequency of this disease has more than quadrupled in the past 35 years.

3. Causes

The causes of type 2 diabetes are complex. This condition results from a combination of genetic and lifestyle factors, some of which have not been identified.

Studies have identified at least 150 DNA variations that are associated with the risk of developing type 2 diabetes. Most of these changes are common and are present both in people with diabetes and in those without. Each person has some variations that increase risk and others that reduce risk. It is the combination of these changes that helps determine a person's likelihood of developing the disease.

The majority of genetic variations associated with type 2 diabetes are thought to act by subtly changing the amount, timing, and location of gene activity (expression). These changes in expression affect genes involved in many aspects of type 2 diabetes, including the development and function of beta cells in the pancreas, the release and processing of insulin, and cells' sensitivity to the effects of insulin. However, for many of the variations that have been associated with type 2 diabetes, the mechanism by which they contribute to disease risk is unknown.

Genetic variations likely act together with health and lifestyle factors to influence an individual's overall risk of type 2 diabetes. All of these factors are related, directly or indirectly, to the body's ability to produce and respond to insulin. Health conditions that predispose to the disease include overweight or obesity, insulin resistance, prediabetes (higher-than-normal blood sugar levels that do not reach the cutoff for diabetes), and a form of diabetes called gestational diabetes that occurs during pregnancy. Lifestyle factors including smoking, a poor diet, and physical inactivity also increase the risk of type 2 diabetes.

4. Inheritance

Type 2 diabetes does not have a clear pattern of inheritance, although many affected individuals have at least one close family member, such as a parent or sibling, with the disease. The risk of developing type 2 diabetes increases with the number of affected family members. The increased risk is likely due in part to shared genetic factors, but it is also related to lifestyle influences (such as eating and exercise habits) that are shared by members of a family.

5. Other Names for This Condition

  • adult-onset diabetes
  • adult-onset diabetes mellitus
  • AODM
  • diabetes mellitus, adult-onset
  • diabetes mellitus, non-insulin-dependent
  • diabetes mellitus, type 2
  • diabetes mellitus, type II
  • maturity-onset diabetes
  • maturity-onset diabetes mellitus
  • NIDDM
  • noninsulin-dependent diabetes mellitus
  • T2D
  • type 2 diabetes mellitus

This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/type-2-diabetes

References

  1. Andersen MK, Pedersen CE, Moltke I, Hansen T, Albrechtsen A, Grarup N.Genetics of Type 2 Diabetes: the Power of Isolated Populations. Curr Diab Rep.2016 Jul;16(7):65. doi: 10.1007/s11892-016-0757-z. Review.
  2. Centers for Disease Control and Prevention: National Diabetes Statistics Report, 2017
  3. Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017 Jun3;389(10085):2239-2251. doi: 10.1016/S0140-6736(17)30058-2.Review. Erratum in: Lancet. 2017 Jun 3;389(10085):2192.
  4. DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; AsianGenetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium; South AsianType 2 Diabetes (SAT2D) Consortium; Mexican American Type 2 Diabetes (MAT2D)Consortium; Type 2 Diabetes Genetic Exploration by Nex-generation sequencing inmuylti-Ethnic Samples (T2D-GENES) Consortium, Mahajan A, Go MJ, Zhang W, BelowJE, Gaulton KJ, Ferreira T, Horikoshi M, Johnson AD, Ng MC, Prokopenko I,Saleheen D, Wang X, Zeggini E, Abecasis GR, Adair LS, Almgren P, Atalay M, AungT, Baldassarre D, Balkau B, Bao Y, Barnett AH, Barroso I, Basit A, Been LF,Beilby J, Bell GI, Benediktsson R, Bergman RN, Boehm BO, Boerwinkle E,Bonnycastle LL, Burtt N, Cai Q, Campbell H, Carey J, Cauchi S, Caulfield M, Chan JC, Chang LC, Chang TJ, Chang YC, Charpentier G, Chen CH, Chen H, Chen YT, ChiaKS, Chidambaram M, Chines PS, Cho NH, Cho YM, Chuang LM, Collins FS, Cornelis MC,Couper DJ, Crenshaw AT, van Dam RM, Danesh J, Das D, de Faire U, Dedoussis G,Deloukas P, Dimas AS, Dina C, Doney AS, Donnelly PJ, Dorkhan M, van Duijn C,Dupuis J, Edkins S, Elliott P, Emilsson V, Erbel R, Eriksson JG, Escobedo J, EskoT, Eury E, Florez JC, Fontanillas P, Forouhi NG, Forsen T, Fox C, Fraser RM,Frayling TM, Froguel P, Frossard P, Gao Y, Gertow K, Gieger C, Gigante B,Grallert H, Grant GB, Grrop LC, Groves CJ, Grundberg E, Guiducci C, Hamsten A,Han BG, Hara K, Hassanali N, Hattersley AT, Hayward C, Hedman AK, Herder C,Hofman A, Holmen OL, Hovingh K, Hreidarsson AB, Hu C, Hu FB, Hui J, Humphries SE,Hunt SE, Hunter DJ, Hveem K, Hydrie ZI, Ikegami H, Illig T, Ingelsson E, Islam M,Isomaa B, Jackson AU, Jafar T, James A, Jia W, Jöckel KH, Jonsson A, Jowett JB,Kadowaki T, Kang HM, Kanoni S, Kao WH, Kathiresan S, Kato N, Katulanda P,Keinanen-Kiukaanniemi KM, Kelly AM, Khan H, Khaw KT, Khor CC, Kim HL, Kim S, Kim YJ, Kinnunen L, Klopp N, Kong A, Korpi-Hyövälti E, Kowlessur S, Kraft P, KravicJ, Kristensen MM, Krithika S, Kumar A, Kumate J, Kuusisto J, Kwak SH, Laakso M,Lagou V, Lakka TA, Langenberg C, Langford C, Lawrence R, Leander K, Lee JM, LeeNR, Li M, Li X, Li Y, Liang J, Liju S, Lim WY, Lind L, Lindgren CM, Lindholm E,Liu CT, Liu JJ, Lobbens S, Long J, Loos RJ, Lu W, Luan J, Lyssenko V, Ma RC,Maeda S, Mägi R, Männisto S, Matthews DR, Meigs JB, Melander O, Metspalu A, MeyerJ, Mirza G, Mihailov E, Moebus S, Mohan V, Mohlke KL, Morris AD, Mühleisen TW,Müller-Nurasyid M, Musk B, Nakamura J, Nakashima E, Navarro P, Ng PK, Nica AC,Nilsson PM, Njølstad I, Nöthen MM, Ohnaka K, Ong TH, Owen KR, Palmer CN, PankowJS, Park KS, Parkin M, Pechlivanis S, Pedersen NL, Peltonen L, Perry JR, PetersA, Pinidiyapathirage JM, Platou CG, Potter S, Price JF, Qi L, Radha V, RallidisL, Rasheed A, Rathman W, Rauramaa R, Raychaudhuri S, Rayner NW, Rees SD, RehnbergE, Ripatti S, Robertson N, Roden M, Rossin EJ, Rudan I, Rybin D, Saaristo TE,Salomaa V, Saltevo J, Samuel M, Sanghera DK, Saramies J, Scott J, Scott LJ, ScottRA, Segrè AV, Sehmi J, Sennblad B, Shah N, Shah S, Shera AS, Shu XO, ShuldinerAR, Sigurđsson G, Sijbrands E, Silveira A, Sim X, Sivapalaratnam S, Small KS, So WY, Stančáková A, Stefansson K, Steinbach G, Steinthorsdottir V, Stirrups K,Strawbridge RJ, Stringham HM, Sun Q, Suo C, Syvänen AC, Takayanagi R, Takeuchi F,Tay WT, Teslovich TM, Thorand B, Thorleifsson G, Thorsteinsdottir U, Tikkanen E, Trakalo J, Tremoli E, Trip MD, Tsai FJ, Tuomi T, Tuomilehto J, Uitterlinden AG,Valladares-Salgado A, Vedantam S, Veglia F, Voight BF, Wang C, Wareham NJ,Wennauer R, Wickremasinghe AR, Wilsgaard T, Wilson JF, Wiltshire S, Winckler W,Wong TY, Wood AR, Wu JY, Wu Y, Yamamoto K, Yamauchi T, Yang M, Yengo L, Yokota M,Young R, Zabaneh D, Zhang F, Zhang R, Zheng W, Zimmet PZ, Altshuler D, Bowden DW,Cho YS, Cox NJ, Cruz M, Hanis CL, Kooner J, Lee JY, Seielstad M, Teo YY, Boehnke M, Parra EJ, Chambers JC, Tai ES, McCarthy MI, Morris AP. Genome-widetrans-ancestry meta-analysis provides insight into the genetic architecture oftype 2 diabetes susceptibility. Nat Genet. 2014 Mar;46(3):234-44. doi:10.1038/ng.2897.
  5. Flannick J, Florez JC. Type 2 diabetes: genetic data sharing to advancecomplex disease research. Nat Rev Genet. 2016 Sep;17(9):535-49. doi:10.1038/nrg.2016.56.
  6. Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, MaC, Fontanillas P, Moutsianas L, McCarthy DJ, Rivas MA, Perry JRB, 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, vande 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, StitzelML, Pasko D, Parker SCJ, 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 MCY, 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, NealeBM, Purcell S, Butterworth AS, Howson JMM, Lee HM, Lu Y, Kwak SH, Zhao W, Danesh J, Lam VKL, Park KS, Saleheen D, So WY, Tam CHT, Afzal U, Aguilar D, Arya R, AungT, 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, ScottWR, Yengo L, Tan ST, Taylor HA Jr, Thameem F, Wilson G Sr, 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 ASF, 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, NarisuN, 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, deAngelis 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 CNA, Pedersen O, Rauramaa R, Tuomilehto J, SalomaaV, Watanabe RM, Syvänen AC, Bergman RN, Bharadwaj D, Bottinger EP, Cho YS,Chandak GR, Chan JCN, Chia KS, Daly MJ, Ebrahim SB, Langenberg C, Elliott P,Jablonski KA, Lehman DM, Jia W, Ma RCW, Pollin TI, Sandhu M, Tandon N, Froguel P,Barroso I, Teo YY, Zeggini E, Loos RJF, Small KS, Ried JS, DeFronzo RA, Grallert H, Glaser B, Metspalu A, Wareham NJ, Walker M, Banks E, Gieger C, Ingelsson E, ImHK, 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, ChambersJC, 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, SladekR, 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. Thegenetic architecture of type 2 diabetes. Nature. 2016 Aug 4;536(7614):41-47. doi:10.1038/nature18642.
  7. McCarthy MI. Genomics, type 2 diabetes, and obesity. N Engl J Med. 2010 Dec9;363(24):2339-50. doi: 10.1056/NEJMra0906948. Review.
  8. Mohlke KL, Boehnke M. Recent advances in understanding the geneticarchitecture of type 2 diabetes. Hum Mol Genet. 2015 Oct 15;24(R1):R85-92. doi:10.1093/hmg/ddv264.
  9. Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, Steinthorsdottir V, Strawbridge RJ, Khan H, Grallert H, Mahajan A, Prokopenko I, Kang HM, Dina C,Esko T, Fraser RM, Kanoni S, Kumar A, Lagou V, Langenberg C, Luan J, Lindgren CM,Müller-Nurasyid M, Pechlivanis S, Rayner NW, Scott LJ, Wiltshire S, Yengo L,Kinnunen L, Rossin EJ, Raychaudhuri S, Johnson AD, Dimas AS, Loos RJ, Vedantam S,Chen H, Florez JC, Fox C, Liu CT, Rybin D, Couper DJ, Kao WH, Li M, Cornelis MC, Kraft P, Sun Q, van Dam RM, Stringham HM, Chines PS, Fischer K, Fontanillas P,Holmen OL, Hunt SE, Jackson AU, Kong A, Lawrence R, Meyer J, Perry JR, Platou CG,Potter S, Rehnberg E, Robertson N, Sivapalaratnam S, Stančáková A, Stirrups K,Thorleifsson G, Tikkanen E, Wood AR, Almgren P, Atalay M, Benediktsson R,Bonnycastle LL, Burtt N, Carey J, Charpentier G, Crenshaw AT, Doney AS, DorkhanM, Edkins S, Emilsson V, Eury E, Forsen T, Gertow K, Gigante B, Grant GB, Groves CJ, Guiducci C, Herder C, Hreidarsson AB, Hui J, James A, Jonsson A, Rathmann W, Klopp N, Kravic J, Krjutškov K, Langford C, Leander K, Lindholm E, Lobbens S,Männistö S, Mirza G, Mühleisen TW, Musk B, Parkin M, Rallidis L, Saramies J,Sennblad B, Shah S, Sigurðsson G, Silveira A, Steinbach G, Thorand B, Trakalo J, Veglia F, Wennauer R, Winckler W, Zabaneh D, Campbell H, van Duijn C,Uitterlinden AG, Hofman A, Sijbrands E, Abecasis GR, Owen KR, Zeggini E, Trip MD,Forouhi NG, Syvänen AC, Eriksson JG, Peltonen L, Nöthen MM, Balkau B, Palmer CN, Lyssenko V, Tuomi T, Isomaa B, Hunter DJ, Qi L; Wellcome Trust Case ControlConsortium; Meta-Analyses of Glucose and Insulin-related traits Consortium(MAGIC) Investigators; Genetic Investigation of ANthropometric Traits (GIANT)Consortium; Asian Genetic Epidemiology Network–Type 2 Diabetes (AGEN-T2D)Consortium; South Asian Type 2 Diabetes (SAT2D) Consortium, Shuldiner AR, RodenM, Barroso I, Wilsgaard T, Beilby J, Hovingh K, Price JF, Wilson JF, Rauramaa R, Lakka TA, Lind L, Dedoussis G, Njølstad I, Pedersen NL, Khaw KT, Wareham NJ,Keinanen-Kiukaanniemi SM, Saaristo TE, Korpi-Hyövälti E, Saltevo J, Laakso M,Kuusisto J, Metspalu A, Collins FS, Mohlke KL, Bergman RN, Tuomilehto J, BoehmBO, Gieger C, Hveem K, Cauchi S, Froguel P, Baldassarre D, Tremoli E, HumphriesSE, Saleheen D, Danesh J, Ingelsson E, Ripatti S, Salomaa V, Erbel R, Jöckel KH, Moebus S, Peters A, Illig T, de Faire U, Hamsten A, Morris AD, Donnelly PJ,Frayling TM, Hattersley AT, Boerwinkle E, Melander O, Kathiresan S, Nilsson PM,Deloukas P, Thorsteinsdottir U, Groop LC, Stefansson K, Hu F, Pankow JS, DupuisJ, Meigs JB, Altshuler D, Boehnke M, McCarthy MI; DIAbetes Genetics ReplicationAnd Meta-analysis (DIAGRAM) Consortium. Large-scale association analysis providesinsights into the genetic architecture and pathophysiology of type 2 diabetes.Nat Genet. 2012 Sep;44(9):981-90. doi: 10.1038/ng.2383.
  10. Pal A, McCarthy MI. The genetics of type 2 diabetes and its clinicalrelevance. Clin Genet. 2013 Apr;83(4):297-306. doi: 10.1111/cge.12055.
More
©Text is available under the terms and conditions of the Creative Commons-Attribution ShareAlike (CC BY-SA) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
ScholarVision Creations
Feedback