Diabetes and Obesity

  • Matthias Blüher
  • Michael Stumvoll
Living reference work entry
Part of the Endocrinology book series (ENDOCR)


The prevalence of obesity and diabetes has reached epidemic proportions worldwide and contributes to premature mortality. Obesity describes an abnormal or excessive fat accumulation and is defined by a body mass index ≥30 kg/m2. Obesity increases the risk for metabolic and cardiovascular diseases, musculoskeletal disorders, some types of cancer, pulmonary, and psychological diseases. A doubling of the obesity prevalence since the 1980s may be caused by a globally increased intake of energy-dense foods with a parallel decrease in daily physical activity due to the increasingly sedentary nature of many forms of work, changing modes of transportation, and increasing urbanization. Obesity represents the strongest modifiable risk factor for type 2 diabetes (T2D). Obesity and T2D may develop on a common genetic risk background. Mechanisms linking obesity to T2D include abdominal fat distribution, adipose tissue dysfunction, or inflammation characterized by the secretion of a diabetogenic adipokine pattern which contributes to impaired insulin action in skeletal muscle, liver, brain, and other organs. In patients with obesity and T2D, therapeutic weight reduction leads to improvements of all metabolic disturbances including beneficial effects on insulin sensitivity, lipid metabolism, liver fat, and chronic inflammation. Weight loss could be achieved by caloric restriction combined with increased physical activity and behavior training in the context of multimodal interventions. Pharmacotherapies may support additional weight loss, and for patients with overweight or obesity-associated T2D antihyperglycemic treatment strategies which promote weight loss should be preferred. However, bariatric surgery is the approach with the best long-term efficacy to treat morbid obesity and may lead to significant improvements on obesity-comorbidities including a high remission rate of T2D.


Obesity Diabetes Adipose tissue Insulin resistance Adipokines Beta cell function Fat distribution Genetics Weight loss Diet Pharmacotherapy Bariatric surgery 


  1. American Diabetes Association (ADA). Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2010;33(Suppl 1):S62–S69.Google Scholar
  2. American Diabetes Association (ADA). Classification and diagnosis of diabetes. Diabetes Care. 2015;38(Suppl 1):S8–S16.Google Scholar
  3. Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr. 2001;74:579–84.CrossRefPubMedGoogle Scholar
  4. Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, Ryan DH, Still CD. Pharmacological management of obesity: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015;100:342.CrossRefPubMedGoogle Scholar
  5. Belfort R, Mandarino L, Kashyap S, et al. Dose response effect of elevated plasma FFA on insulin signaling. Diabetes. 2005;54:1640–8.CrossRefPubMedGoogle Scholar
  6. Birkmeyer JD, Finks JF, O’Reilly A, Oerline M, Carlin AM, Nunn AR, Dimick J, Banerjee M, Birkmeyer NJ, Michigan Bariatric Surgery Collaborative. Surgical skill and complication rates after bariatric surgery. N Engl J Med. 2013;369:1434–42.CrossRefPubMedGoogle Scholar
  7. Bjorntorp P. Metabolic implications of body-fat distribution. Diabetes Care. 1991;14:1132–43.CrossRefPubMedGoogle Scholar
  8. Blüher M. Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes. 2009;117:241–50.CrossRefPubMedGoogle Scholar
  9. Blüher M. Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract Res Clin Endocrinol Metab. 2013;27:163–77.CrossRefPubMedGoogle Scholar
  10. Blüher M. Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance? Clin Sci (Lond). 2016;130:1603–14.CrossRefGoogle Scholar
  11. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and b-cell dysfunction. Eur J Clin Investig. 2002;32:14–23.CrossRefGoogle Scholar
  12. Bray GA, Frühbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. 2016;387:1947–56.CrossRefPubMedGoogle Scholar
  13. Brunzell JD, Robertson RP, Lerner RL, Hazzard WR, Ensinck JW, Bierman EL, Porte D Jr. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. J Clin Endocrinol Metab. 1976;42:222–9.CrossRefPubMedGoogle Scholar
  14. Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122:248–56.CrossRefPubMedGoogle Scholar
  15. Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumié A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clément K. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes. 2005;54:2277–86.CrossRefPubMedGoogle Scholar
  16. Chang SH, Stoll CR, Song J, Varela JE, Eagon CJ, Colditz GA. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003–2012. JAMA Surg. 2014;149:275–87.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Cinti S. The adipose organ at a glance. Dis Model Mech. 2012;5:588–94.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res. 2005;46:2347–55.CrossRefPubMedGoogle Scholar
  19. Cohen P, Spiegelman BM. Brown and beige fat: molecular parts of a thermogenic machine. Diabetes. 2015;64:2346–51.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122:481–6.CrossRefPubMedGoogle Scholar
  21. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360:1509–17.CrossRefPubMedPubMedCentralGoogle Scholar
  22. DeFronzo RA. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia. 2010;53:1270–87.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Despres JP, Nadeau A, Tremblay A, et al. Role of deep abdominal fat in the association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes. 1989;38:304–9.CrossRefPubMedGoogle Scholar
  24. Drucker DJ, Nauck MA. The incretin system: glucagon-like-peptide-1 receptor agonists and dipeptidyl pepdidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368:1696–705.CrossRefPubMedGoogle Scholar
  25. Farooqi IS, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341:879–84.CrossRefPubMedGoogle Scholar
  26. Fasshauer M, Blüher M. Adipokines in health and disease. Trends Pharmacol Sci. 2015;36(7):461–70.
  27. Foster MC, Hwang SJ, Porter SA, Massaro JM, Hoffmann U, Fox CS. Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study. Hypertension. 2011;58:784–90.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Franks PW, McCarthy MI. Exposing the exposures responsible for type 2 diabetes and obesity. Science. 2016;354:69–73.CrossRefPubMedGoogle Scholar
  29. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316:889–94.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:1341–52.CrossRefPubMedGoogle Scholar
  31. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385:117–71.CrossRefGoogle Scholar
  32. Gloyn AL, Weedon MN, Owen KR, et al. Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes. 2003;52:568–72.CrossRefPubMedGoogle Scholar
  33. Goldstein BJ. Protein-tyrosine phosphatases and the regulation of insulin action. In: LeRoith D, Taylor SI, Olefsky JM, editors. Diabetes mellitus: a fundamental and clinical text. Philadelphia: Lippincott; 2003. p. 255–68.Google Scholar
  34. Greenberg I, Stampfer MJ, Schwarzfuchs D, Shai I, DIRECT Group. Adherence and success in long-term weight loss diets: the dietary intervention randomized controlled trial (DIRECT). J Am Coll Nutr. 2009;28(2):159–68.CrossRefPubMedGoogle Scholar
  35. Gudzune KA, Doshi RS, Mehta AK, et al. Efficacy of commercial weight-loss programs: an updated systematic review. Ann Intern Med. 2015;162:501–12.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Haase J, Weyer U, Immig K, Klöting N, Blüher M, Eilers J, Bechmann I, Gericke M. Local proliferation of macrophages in adipose tissue during obesity-induced inflammation. Diabetologia. 2014;57:562–71.CrossRefPubMedGoogle Scholar
  37. Hauner H. Diabetes and obesity. In: Holt RIG, Cockram CS, Flyvbjerg A, Goldstein BJ (eds), Textbook of diabetes. 4th edition. Blackwell, Chichester, UK; 2010. ISBN 978-1-405-19181-4.Google Scholar
  38. Hu T, Mills KT, Yao L, et al. Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol. 2012;176:S44–54.CrossRefPubMedPubMedCentralGoogle Scholar
  39. Huo R, Du T, Xu Y, et al. Effects of Mediterranean-style diet on glycemic control, weight loss and cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis. Eur J Clin Nutr. 2014;69:1200–8.CrossRefPubMedGoogle Scholar
  40. Jakicic JM, Egan CM, Fabricatore AN, Look AHEAD Research Group, et al. Four-year change in cardiorespiratory fi tness and influence on glycemic control in adults with type 2 diabetes in a randomized trial: the Look AHEAD trial. Diabetes Care. 2013;36:1297–303.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Johnston BC, Kanters S, Bandayrel K, Wu P, Naji F, Siemieniuk RA, Ball GD, Busse JW, Thorlund K, Guyatt G, Jansen JP, Mills EJ. Comparison of weight loss among named diet programs in overweight and obese adults: a meta-analysis. JAMA. 2014;312:923–33.CrossRefPubMedGoogle Scholar
  42. Klein S, Fontana L, Young VL, et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med. 2004;350:2549–57.CrossRefPubMedGoogle Scholar
  43. Klöting N, Fasshauer M, Dietrich A, Kovacs P, Schön MR, Kern M, Stumvoll M, Blüher M. Insulin-sensitive obesity. Am J Physiol Endocrinol Metab. 2010;299:E506–15.CrossRefPubMedGoogle Scholar
  44. Knowler WC, Fowler SE, Hamman RF, Diabetes Prevention Program Research Group, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374:1677–86.CrossRefPubMedGoogle Scholar
  45. Konrad D, Rudich A, Schoenle EJ. Improved glucose tolerance in mice receiving intraperitoneal transplantation of normal fat tissue. Diabetologia. 2007;50:833–9.CrossRefPubMedGoogle Scholar
  46. Kühnen P, Clément K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, Mai K, Blume-Peytavi U, Grüters A, Krude H. Proopiomelanocortin deficiency treated with a melanocortin-4 receptor agonist. N Engl J Med. 2016;375:240–6.CrossRefPubMedGoogle Scholar
  47. Lebovitz HE. Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes. 2001;109:S135–48.CrossRefPubMedGoogle Scholar
  48. LeFevre ML, U.S. Preventive Services Task Force. Behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention in adults with cardiovascular risk factors: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2014;161:587–93.CrossRefPubMedGoogle Scholar
  49. Li SX, Imamura F, Ye Z, Schulze MB, Zheng J, Ardanaz E, Arriola L, Boeing H, Dow C, Fagherazzi G, Franks PW, Agudo A, Grioni S, Kaaks R, Katzke VA, Key TJ, Khaw KT, Mancini FR, Navarro C, Nilsson PM, Onland-Moret NC, Overvad K, Palli D, Panico S, Quirós JR, Rolandsson O, Sacerdote C, Sánchez MJ, Slimani N, Sluijs I, Spijkerman AM, Tjonneland A, Tumino R, Sharp SJ, Riboli E, Langenberg C, Scott RA, Forouhi NG, Wareham NJ. Interaction between genes and macronutrient intake on the risk of developing type 2 diabetes: systematic review and findings from European Prospective Investigation into Cancer (EPIC)-InterAct. Am J Clin Nutr. 2017. pii: ajcn150094.
  50. Look AHEAD Research Group, Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM, Espeland MA, Evans M, Foreyt JP, Ghazarian S, Gregg EW, Harrison B, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Reboussin D, Regensteiner JG, Rickman AD, Ryan DH, Safford M, Wadden TA, Wagenknecht LE, West DS, Williamson DF, Yanovski SZ. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013;369(2):145–54.
  51. Mingrone G, Panunzi S, De Gaetano A, Guidone C, Iaconelli A, Leccesi L, Nanni G, Pomp A, Castagneto M, Ghirlanda G, Rubino F. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366:1577–85.CrossRefPubMedGoogle Scholar
  52. Moitra J, Mason MM, Olive M, Krylov D, Gavrilova O, Marcus-Samuels B, Feigenbaum L, Lee E, Aoyama T, Eckhaus M, Reitman ML, Vinson C. Life without white fat: a transgenic mouse. Genes Dev. 1998;12:3168–81.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Lifetime risk for diabetes mellitus in the United States. JAMA. 2003;290:1884–90.CrossRefPubMedGoogle Scholar
  54. National Institute for Health and Clinical Excellence: Guidance. Obesity: identification, assessment and management of overweight and obesity in children, young people and adults: partial update of CG43, National Clinical Guideline Centre (UK). London: National Institute for Health and Care Excellence (UK); 2014.Google Scholar
  55. National Task Force on the Prevention and Treatment of Obesity. Long-term pharmacotherapy in the management of obesity. JAMA. 1996;276:1907–15.CrossRefGoogle Scholar
  56. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:766–81.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J. Pharmacotherapy for weight loss in adults with type 2 diabetes mel- litus. Cochrane Database Syst Rev. 2005;1:CD004096.Google Scholar
  58. Padwal RS, Pajewski NM, Allison DB, Sharma AM. Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ. 2011;183(14):E1059–66.
  59. Paffenbarger RS Jr, Hyde RT, Wing AL, Hsieh CC. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med. 1986;314:605–13.CrossRefPubMedGoogle Scholar
  60. Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DC, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JP, SCALE Obesity and Prediabetes NN8022-1839 Study Group. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11–22.CrossRefPubMedGoogle Scholar
  61. Porzio O, Federici M, Hribal ML, et al. The Gly972→Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic beta cells. J Clin Invest. 1999;104:357–64.CrossRefPubMedPubMedCentralGoogle Scholar
  62. Purnell JQ, Hokanson JE, Marcovina SM, Steffes MW, Cleary PA, Brunzell JD. Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT. JAMA. 1998;280:140–6.CrossRefPubMedPubMedCentralGoogle Scholar
  63. Ravussin E, Lillioja S, Knowler WC, Christin L, Freymond D, Abbott WG, et al. Reduced rate of energy expenditure as a risk factor for body weight gain. N Engl J Med. 1988;318:467–72.CrossRefPubMedGoogle Scholar
  64. Robbins AL, Savage DB. The genetics of lipid storage and human lipodystrophies. Trends Mol Med. 2015;21:433–8.CrossRefPubMedGoogle Scholar
  65. Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003;52:581–7.CrossRefPubMedGoogle Scholar
  66. 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, Delegates of the 2nd Diabetes Surgery Summit. Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Diabetes Care. 2016;39:861–77.CrossRefPubMedGoogle Scholar
  67. Ryan D, Heaner M. Guidelines (2013) for managing overweight and obesity in adults. Preface to the full report. Obesity (Silver Spring). 2014;22(suppl 2):S1–3.CrossRefGoogle Scholar
  68. Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, McManus K, Champagne CM, Bishop LM, Laranjo N, Leboff MS, Rood JC, de Jonge L, Greenway FL, Loria CM, Obarzanek E, Williamson DA. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360:859–73.CrossRefPubMedPubMedCentralGoogle Scholar
  69. Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366:1567–76.CrossRefPubMedPubMedCentralGoogle Scholar
  70. Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, Aminian A, Pothier CE, Kim ES, Nissen SE, Kashyap SR, STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes – 3-year outcomes. N Engl J Med. 2014;370:2002–13.CrossRefPubMedPubMedCentralGoogle Scholar
  71. Schleinitz D, Böttcher Y, Blüher M, Kovacs P. The genetics of fat distribution. Diabetologia. 2014;57:1276–86.CrossRefPubMedGoogle Scholar
  72. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404:661–71.CrossRefPubMedGoogle Scholar
  73. Scott RA, Scott LJ, Mägi R, Marullo L, Gaulton KJ, Kaakinen M, Pervjakova N, Pers TH, Johnson AD, Eicher JD, Jackson AU, Ferreira T, Lee Y, Ma C, Steinthorsdottir V, Thorleifsson G, Qi L, Van Zuydam NR, Mahajan A, Chen H, Almgren P, Voight BF, Grallert H, Müller-Nurasyid M, Ried JS, Rayner WN, Robertson N, Karssen LC, van Leeuwen EM, Willems SM, Fuchsberger C, Kwan P, Teslovich TM, Chanda P, Li M, Lu Y, Dina C, Thuillier D, Yengo L, Jiang L, Sparso T, Kestler HA, Chheda H, Eisele L, Gustafsson S, Frånberg M, Strawbridge RJ, Benediktsson R, Hreidarsson AB, Kong A, Sigurðsson G, Kerrison ND, Luan J, Liang L, Meitinger T, Roden M, Thorand B, Esko T, Mihailov E, Fox C, Liu CT, Rybin D, Isomaa B, Lyssenko V, Tuomi T, Couper DJ, Pankow JS, Grarup N, Have CT, Jørgensen ME, Jørgensen T, Linneberg A, Cornelis MC, van Dam RM, Hunter DJ, Kraft P, Sun Q, Edkins S, Owen KR, Perry JR, Wood AR, Zeggini E, Tajes-Fernandes J, Abecasis GR, Bonnycastle LL, Chines PS, Stringham HM, Koistinen HA, Kinnunen L, Sennblad B, Mühleisen TW, Nöthen MM, Pechlivanis S, Baldassarre D, Gertow K, Humphries SE, Tremoli E, Klopp N, Meyer J, Steinbach G, Wennauer R, Eriksson JG, Mӓnnistö S, Peltonen L, Tikkanen E, Charpentier G, Eury E, Lobbens S, Gigante B, Leander K, McLeod O, Bottinger EP, Gottesman O, Ruderfer D, Blüher M, Kovacs P, Tonjes A, Maruthur NM, Scapoli C, Erbel R, Jöckel KH, Moebus S, de Faire U, Hamsten A, Stumvoll M, Deloukas P, Donnelly PJ, Frayling TM, Hattersley AT, Ripatti S, Salomaa V, Pedersen NL, Boehm BO, Bergman RN, Collins FS, Mohlke KL, Tuomilehto J, Hansen T, Pedersen O, Barroso I, Lannfelt L, Ingelsson E, Lind L, Lindgren CM, Cauchi S, Froguel P, Loos RJ, Balkau B, Boeing H, Franks PW, Gurrea AB, Palli D, van der Schouw YT, Altshuler D, Groop LC, Langenberg C, Wareham NJ, Sijbrands E, van Duijn CM, Florez JC, Meigs JB, Boerwinkle E, Gieger C, Strauch K, Metspalu A, Morris AD, Palmer CN, Hu FB, Thorsteinsdottir U, Stefansson K, Dupuis J, Morris AP, Boehnke M, McCarthy MI, Prokopenko I, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. An expanded genome-wide association study of type 2 diabetes in Europeans. Diabetes. 2017. pii: db161253.
  74. Sell H, Habich C, Eckel J. Adaptive immunity in obesity and insulin resistance. Nat Rev Endocrinol. 2012;8:709–16.CrossRefPubMedGoogle Scholar
  75. Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, Golan R, Fraser D, Bolotin A, Vardi H, Tangi-Rozental O, Zuk-Ramot R, Sarusi B, Brickner D, Schwartz Z, Sheiner E, Marko R, Katorza E, Thiery J, Fiedler GM, Blüher M, Stumvoll M, Stampfer MJ, Dietary Intervention Randomized Controlled Trial (DIRECT) Group. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008;359:229–41.CrossRefPubMedGoogle Scholar
  76. Sharma AM, Kushner RF. A proposed clinical staging system for obesity. Int J Obes. 2009;33(3):289–95.
  77. Sjöström L, Narbro K, Sjöström CD, Karason K, Larsson B, Wedel H, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357:741–52.CrossRefPubMedGoogle Scholar
  78. Sjöström L, Peltonen M, Jacobson P, et al. Bariatric surgery and long-term cardiovascular events. JAMA. 2012;307:56–65.CrossRefPubMedGoogle Scholar
  79. Smith SR, Weissman NJ, Anderson CM, Behavioral Modifi cation and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363:245–56.CrossRefPubMedGoogle Scholar
  80. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Näslund E, Britton T, Concha H, Hassan M, Rydén M, Frisén J, Arner P. Dynamics of fat cell turnover in humans. Nature. 2008;453:783–7.CrossRefPubMedGoogle Scholar
  81. Speliotes EK, Massaro JM, Hoffmann U, et al. Fatty liver is associated with dyslipidemia and dysglycemia independent of visceral fat: the Framingham Heart Study. Hepatology. 2010;51:1979–87.CrossRefPubMedPubMedCentralGoogle Scholar
  82. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365:1333–46.CrossRefPubMedGoogle Scholar
  83. Stunkard AJ, Foch TT, Hrubec Z. A twin study of human obesity. JAMA. 1986a;256:51–4.CrossRefPubMedGoogle Scholar
  84. Stunkard AJ, Sorensen TI, Hanis C, Teasdale TW, Chakraborty R, Schull WJ, et al. An adoption study of human obesity. N Engl J Med. 1986b;314:193–8.CrossRefPubMedGoogle Scholar
  85. Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378:804–14.CrossRefPubMedGoogle Scholar
  86. Tack J, Deloose E. Complications of bariatric surgery: dumping syndrome, reflux and vitamin deficiencies. Best Pract Res Clin Gastroenterol. 2014;28:741–9.CrossRefPubMedGoogle Scholar
  87. Tham JC, Howes N, le Roux CW. The role of bariatric surgery in the treatment of diabetes. Ther Adv Chronic Dis. 2014;5:149–57.CrossRefPubMedPubMedCentralGoogle Scholar
  88. Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P. A pilot study of long-term effects of a novel obesity treatment: omentectomy in connection with adjustable gastric banding. Int J Obes Relat Metab Disord. 2002;26:193–9.CrossRefPubMedGoogle Scholar
  89. Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27:155–61.CrossRefPubMedGoogle Scholar
  90. Tran TT, Yamamoto Y, Gesta S, Kahn CR. Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab. 2008;7:410–20.CrossRefPubMedPubMedCentralGoogle Scholar
  91. UKPDS. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;12:837–52.Google Scholar
  92. Unick JL, Neiberg RH, Hogan PE, Look AHEAD Research Group, et al. Weight change in the first 2 months of a lifestyle intervention predicts weight changes 8 years later. Obesity (Silver Spring). 2015;23:1353–6.CrossRefGoogle Scholar
  93. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360:1500–8.CrossRefPubMedGoogle Scholar
  94. Waldén TB, Hansen IR, Timmons JA, Cannon B, Nedergaard J. Recruited vs. nonrecruited molecular signatures of brown, “brite,” and white adipose tissues. Am J Physiol Endocrinol Metab. 2012;302:E19–31.CrossRefPubMedGoogle Scholar
  95. Wardle J, Carnell S, Haworth CM, Plomin R. Evidence for a strong genetic influence on childhood obesity despite the force of the obesogenic environment. Am J Clin Nutr. 2008;87:398–404.CrossRefPubMedGoogle Scholar
  96. Wei M, Kampert JB, Barlow CE, Nichaman MZ, Gibbons LW, Paffenbarger RS Jr, Blair SN. Relationship between low cardiorespiratory fitness and mortality in normal-weight, overweight, and obese men. JAMA. 1999;282:1547–53.CrossRefPubMedGoogle Scholar
  97. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–808.CrossRefPubMedPubMedCentralGoogle Scholar
  98. White MF. IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab. 2002;283:E413–22.CrossRefPubMedGoogle Scholar
  99. WHO Expert Committee on Definition. Diagnosis and classification of diabetes mellitus and its complications. Geneva: World Health Organisation; 1999. p. 1–59.Google Scholar
  100. Wu T, Gao X, Chen M, van Dam RM. Long-term eff ectiveness of diet-plus-exercise interventions versus diet-only interventions for weight loss: a meta-analysis. Obes Rev. 2009;10:313–23.CrossRefPubMedGoogle Scholar
  101. Zhang Y, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–32.CrossRefPubMedGoogle Scholar
  102. Zhou B, Lu Y, Hajifathalian K, Bentham J, Di Cesare M, Danaei G, Bixby H, Cowan MJ, Ali MK, Taddei C, Lo WC, Reis-Santos B, Stevens GA, Riley LM, Miranda JJ, Bjerregaard P, Rivera JA, Fouad HM, Ma G, Mbanya JC, McGarvey ST, Mohan V, Onat A, Pilav A, Ramachandran A, Romdhane HB, Paciorek CJ, Bennett JE, Ezzati M, Abdeen ZA, Abdul Kadir K, Abu-Rmeileh NM, Acosta-Cazares B, Adams R, Aekplakorn W, Aguilar-Salinas CA, Agyemang C, Ahmadvand A, Al-Othman AR, Alkerwi A, Amouyel P, Amuzu A, Andersen LB, Anderssen SA, Anjana RM, Aounallah-Skhiri H, Aris T, Arlappa N, Arveiler D, Assah FK, Avdicová M, Azizi F, Balakrishna N, Bandosz P, Barbagallo CM, Barceló A, Batieha AM, Baur LA, Romdhane HB, Benet M, Bernabe-Ortiz A, Bharadwaj S, Bhargava SK, Bi Y, Bjerregaard P, Bjertness E, Bjertness MB, Björkelund C, Blokstra A, Bo S, Boehm BO, Boissonnet CP, Bovet P, Brajkovich I, Breckenkamp J, Brenner H, Brewster LM, Brian GR, Bruno G, Bugge A, Cabrera de León A, Can G, Cândido AP, Capuano V, Carlsson AC, Carvalho MJ, Casanueva FF, Casas JP, Caserta CA, Castetbon K, Chamukuttan S, Chaturvedi N, Chen CJ, Chen F, Chen S, Cheng CY, Chetrit A, Chiou ST, Cho Y, Chudek J, Cifkova R, Claessens F, Concin H, Cooper C, Cooper R, Costanzo S, Cottel D, Cowell C, Crujeiras AB, D’Arrigo G, Dallongeville J, Dankner R, Dauchet L, de Gaetano G, De Henauw S, Deepa M, Dehghan A, Deschamps V, Dhana K, Di Castelnuovo AF, Djalalinia S, Doua K, Drygas W, Du Y, Dzerve V, Egbagbe EE, Eggertsen R, El Ati J, Elosua R, Erasmus RT, Erem C, Ergor G, Eriksen L, Escobedo-de la Peña J, Fall CH, Farzadfar F, Felix-Redondo FJ, Ferguson TS, Fernández-Bergés D, Ferrari M, Ferreccio C, Feskens EJ, Finn JD, Föger B, Foo LH, Forslund AS, Fouad HM, Francis DK, Franco Mdo C, Franco OH, Frontera G, Furusawa T, Gaciong Z, Garnett SP, Gaspoz JM, Gasull M, Gates L, Geleijnse JM, Ghasemian A, Ghimire A, Giampaoli S, Gianfagna F, Giovannelli J, Giwercman A, Gross MG, González Rivas JP, Gorbea MB, Gottrand F, Grafnetter D, Grodzicki T, Grøntved A, Gruden G, Gu D, Guan OP, Guerrero R, Guessous I, Guimaraes AL, Gutierrez L, Hambleton IR, Hardy R, Hari Kumar R, Hata J, He J, Heidemann C, Herrala S, Hihtaniemi IT, Ho SY, Ho SC, Hofman A, Hormiga CM, Horta BL, Houti L, Howitt C, Htay TT, Htet AS, Htike MM, Hu Y, Hussieni AS, Huybrechts I, Hwalla N, Iacoviello L, Iannone AG, Ibrahim MM, Ikeda N, Ikram MA, Irazola VE, Islam M, Iwasaki M, Jacobs JM, Jafar T, Jamil KM, Jasienska G, Jiang CQ, Jonas JB, Joshi P, Kafatos A, Kalter-Leibovici O, Kasaeian A, Katz J, Kaur P, Kavousi M, Keinänen-Kiukaanniemi S, Kelishadi R, Kengne AP, Kersting M, Khader YS, Khalili D, Khang YH, Kiechl S, Kim J, Kolsteren P, Korrovits P, Kratzer W, Kromhout D, Kujala UM, Kula K, Kyobutungi C, Laatikainen T, Lachat C, Laid Y, Lam TH, Landrove O, Lanska V, Lappas G, Laxmaiah A, Leclercq C, Lee J, Lee J, Lehtimäki T, Lekhraj R, León-Muñoz LM, Li Y, Lim WY, Lima-Costa MF, Lin HH, Lin X, Lissner L, Lorbeer R, Lozano JE, Luksiene D, Lundqvist A, Lytsy P, Ma G, Machado-Coelho GL, Machi S, Maggi S, Magliano DJ, Makdisse M, Mallikharjuna Rao K, Manios Y, Manzato E, Margozzini P, Marques-Vidal P, Martorell R, Masoodi SR, Mathiesen EB, Matsha TE, Mbanya JC, McFarlane SR, McGarvey ST, McLachlan S, McNulty BA, Mediene-Benchekor S, Meirhaeghe A, Menezes AM, Merat S, Meshram II, Mi J, Miquel JF, Miranda JJ, Mohamed MK, Mohammad K, Mohammadifard N, Mohan V, Mohd Yusoff MF, Møller NC, Molnár D, Mondo CK, Morejon A, Moreno LA, Morgan K, Moschonis G, Mossakowska M, Mostafa A, Mota J, Motta J, Mu TT, Muiesan ML, Müller-Nurasyid M, Mursu J, Nagel G, Námešná J, Nang EE, NangThetia VB, Navarrete-Muñoz EM, Ndiaye NC, Nenko I, Nervi F, Nguyen ND, Nguyen QN, Nieto-Martínez RE, Ning G, Ninomiya T, Noale M, Noto D, Nsour MA, Ochoa-Avilés AM, Oh K, Onat A, Ordunez P, Osmond C, Otero JA, Owusu-Dabo E, Pahomova E, Palmieri L, Panda-Jonas S, Panza F, Parsaeian M, Peixoto SV, Peltonen M, Peters A, Peykari N, Pham ST, Pilav A, Pitakaka F, Piwonska A, Piwonski J, Plans-Rubió P, Porta M, Portegies ML, Poustchi H, Pradeepa R, Price JF, Punab M, Qasrawi RF, Qorbani M, Radisauskas R, Rahman M, Raitakari O, Rao SR, Ramachandran A, Ramke J, Ramos R, Rampal S, Rathmann W, Redon J, Reganit PF, Rigo F, Robinson SM, Robitaille C, Rodríguez-Artalejo F, Rodriguez-Perez Mdel C, Rodríguez-Villamizar LA, Rojas-Martinez R, Ronkainen K, Rosengren A, Rubinstein A, Rui O, Ruiz-Betancourt BS, Russo Horimoto RV, Rutkowski M, Sabanayagam C, Sachdev HS, Saidi O, Sakarya S, Salanave B, Salonen JT, Salvetti M, Sánchez-Abanto J, Santos D, dos Santos RN, Santos R, Saramies JL, Sardinha LB, Sarrafzadegan N, Saum KU, Scazufca M, Schargrodsky H, Scheidt-Nave C, Sein AA, Sharma SK, Shaw JE, Shibuya K, Shin Y, Shiri R, Siantar R, Sibai AM, Simon M, Simons J, Simons LA, Sjostrom M, Slowikowska-Hilczer J, Slusarczyk P, Smeeth L, Snijder MB, So HK, Sobngwi E, Söderberg S, Solfrizzi V, Sonestedt E, Soumare A, Staessen JA, Stathopoulou MG, Steene-Johannessen J, Stehle P, Stein AD, Stessman J, Stöckl D, Stokwiszewski J, Stronks K, Strufaldi MW, Sun CA, Sundström J, Sung YT, Suriyawongpaisal P, Sy RG, Tai ES, Tamosiunas A, Tang L, Tarawneh M, Tarqui-Mamani CB, Taylor A, Theobald H, Thijs L, Thuesen BH, Tolonen HK, Tolstrup JS, Topbas M, Torrent M, Traissac P, Trinh OT, Tulloch-Reid MK, Tuomainen TP, Turley ML, Tzourio C, Ueda P, Ukoli FA, Ulmer H, Uusitalo HM, Valdivia G, Valvi D, van Rossem L, van Valkengoed IG, Vanderschueren D, Vanuzzo D, Vega T, Velasquez-Melendez G, Veronesi G, Verschuren WM, Verstraeten R, Viet L, Vioque J, Virtanen JK, Visvikis-Siest S, Viswanathan B, Vollenweider P, Voutilainen S, Vrijheid M, Wade AN, Wagner A, Walton J, Wan Mohamud WN, Wang F, Wang MD, Wang Q, Wang YX, Wannamethee SG, Weerasekera D, Whincup PH, Widhalm K, Wiecek A, Wijga AH, Wilks RJ, Willeit J, Wilsgaard T, Wojtyniak B, Wong TY, Woo J, Woodward M, Wu FC, Wu SL, Xu H, Yan W, Yang X, Ye X, Yoshihara A, Younger-Coleman NO, Zambon S, Zargar AH, Zdrojewski T, Zhao W, Zheng Y, Zuñiga Cisneros J. Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016;387:1513–30.CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of MedicineUniversity of LeipzigLeipzigGermany

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