Prevention of Type 2 Diabetes

  • William C. KnowlerEmail author
Reference work entry
Part of the Endocrinology book series (ENDOCR)


Diabetes is defined by elevated plasma glucose concentrations and characterized by metabolic disturbances and widespread tissue damage. Diagnostic criteria and classification of types of diabetes and the risk factors for T2DM are described in other chapters of this book. This chapter considers only T2DM. Diagnostic cut-points for diabetes have often been chosen to correspond to degrees of hyperglycemia associated with diabetes complications, usually retinopathy or nephropathy. Thus, it is widely believed that preventing increases in hyperglycemia to levels that are diagnostic of diabetes and associated with development of complications will also prevent development of the complications. It is also hypothesized that preventing diabetes complications is more feasible in this way than by postponing interventions until the disease is diagnosed, at which time some tissue damage may have already occurred and hyperglycemia may be more difficult to control. While these are very natural assumptions, evidence supporting them has been difficult to obtain. The assumption that preventing T2DM will also prevent its complications provides the main justification for the concept that it is better to prevent diabetes than to wait until it develops and then treat it.


Type 2 diabetes Prevention 



This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases.


  1. Ackermann RT, Holmes AM, Saha C. Designing a natural experiment to evaluate a national health care – community partnership to prevent type 2 diabetes. Prev Chronic Dis. 2013;10:120149.CrossRefGoogle Scholar
  2. Ackermann RT, Duru OK, Albu JB, Schmittdiel JA, Soumerai WB, Wharam JF, Ali MK, Mangione CM, Gregg ES, NEXT-D Study Group. Evaluating diabetes health policies using natural experiments: the natural experiments for translation in diabetes study. Am J Prev Med. 2015;48:747–54.CrossRefGoogle Scholar
  3. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1):S62–9.CrossRefGoogle Scholar
  4. Batis C, Rivera JA, Popkin BM, Taillie LS. First-year evaluation of Mexico’s tax on nonessential energy-dense foods: an observational study. PLoS Med. 2016;5:e1002057.CrossRefGoogle Scholar
  5. Buchanan TA, Xiang AH, Peters RK, Kjos SL, Marroquin A, Goico J, Ochoa C, Tan S, Berkowitz K, Hodis HN, Azen SP. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes. 2002;51:2796–280.CrossRefGoogle Scholar
  6. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet. 2002;359:2072–7.CrossRefGoogle Scholar
  7. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance. The STOP-NIDDM Trial. JAMA. 2003;290:486–94.CrossRefGoogle Scholar
  8. Crandall JP, Knowler WC, Kahn SE, Marrero D, Florez JC, Bray GA, Haffner SM, Hoskin M, Nathan DM, for the Diabetes Prevention Program Research Group. The prevention of type 2 diabetes. Nat Clin Pract Endocrinol Metab. 2008;4:382–93.CrossRefGoogle Scholar
  9. DeFronzo RA, Tripathy D, Schwenke DC, Banerji M, Bray GA, Buchanan TA, Clement SC, Henry RR, Hodis HN, Kitabchi AE, Mack WJ, Mudaliar S, Ratner RE, Williams K, Stentz FB, Musi N, Reaven PD. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med. 2011;364:1104–15.CrossRefGoogle Scholar
  10. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403.CrossRefGoogle Scholar
  11. Diabetes Prevention Program Research Group. Prevention of type 2 diabetes with troglitazone in the Diabetes Prevention Program. Diabetes. 2005a;54:1150–6.CrossRefGoogle Scholar
  12. Diabetes Prevention Program Research Group. Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and metformin. Diabetes. 2005b;54:2404–14.CrossRefGoogle Scholar
  13. Diabetes Prevention Program Research Group. Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care. 2006;29:2102–7.CrossRefGoogle Scholar
  14. Diabetes Prevention Program Research Group. Factors associated with diabetes onset during metformin versus placebo therapy in the Diabetes Prevention Program. Diabetes. 2007;56:1153–9.CrossRefGoogle Scholar
  15. Diabetes Prevention Program Research Group. Prevention of diabetes in women with a history of gestational diabetes mellitus: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab. 2008;93:4772–9.Google Scholar
  16. Diabetes Prevention Program Research Group. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374:1677–86.CrossRefGoogle Scholar
  17. Diabetes Prevention Program Research Group. The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention. Diabetes Care. 2012;35:723–30.CrossRefGoogle Scholar
  18. Diabetes Prevention Program Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015a;3:866–75.CrossRefGoogle Scholar
  19. Diabetes Prevention Program Research Group. The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program Outcomes Study 10-year follow up. J Clin Endocrinol Metab. 2015b;100:1646–53.CrossRefGoogle Scholar
  20. Diabetes Prevention Program Research Group. HbA1c as a predictor of diabetes and as an outcome in the Diabetes Prevention Program: a randomized controlled trial. Diabetes Care. 2015c;38:51–8.CrossRefGoogle Scholar
  21. DREAM Trial Investigators, Bosch J, Yusuf S, Gerstein HC, Pogue J, Sheridan P, Dagenais G, Diaz R, Avezum A, Lanas F, Probstfield J, Fodor G, Holmann RR. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006a;355:1551–62.CrossRefGoogle Scholar
  22. DREAM Trial Investigators, Gerstein HC, Yusuf S, Bosch J, Pogue J, Sheridan P, Dinccag N, Hanefeld M, Hoogwerf B, Laakso M, Mohan V, Shaw J, Zinman B, Holman RR. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006b;368:1096–105.CrossRefGoogle Scholar
  23. Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, Knowler WC, Nathan DM, Altshuler D, for the Diabetes Prevention Program Research Group. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med. 2006;355:241–50.CrossRefGoogle Scholar
  24. Garvey WT, Ryan DH, Look M, Gadde KM, Allison DB, Peterson CA, Schwiers M, Day WW, Bowden CH. Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J Clin Nutr. 2012;95:297–308.CrossRefGoogle Scholar
  25. Gong Q, Gregg EW, Wang J, An Y, Zhang P, Yang W, Li H, Li H, Jiang Y, Shuai Y, Zhang B, Zhang J, Gerzoff RB, Roglic G, Hu Y, Li G, Bennett PH. Long-term effects of a randomised trial of a 6-year lifestyle intervention in impaired glucose tolerance on diabetes-related microvascular complications: the China Da Qing Diabetes Prevention Outcome Study. Diabetologia. 2011;54:300–7.CrossRefGoogle Scholar
  26. Hanefeld M, Chiasson JL, Koehler C, Henkel E, Schaper F, Temelkova-Kurktschiev T. Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance. Stroke. 2004;35:1073–8.CrossRefGoogle Scholar
  27. Heymsfield SB, Segal KR, Hauptman J, Lucas CP, Boldrin MN, Rissanen A, Wilding JP, Sjöström L. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med. 2000;160:1321–6.CrossRefGoogle Scholar
  28. Hivert MF, Jablonski KA, Perreault L, Saxena R, McAteer JB, Franks PW, Hamman RF, Kahn SE, Haffner S, the DIAGRAM Consortium, Meigs JB, Altshuler D, Knowler WC, Florez JC, for the Diabetes Prevention Program Research Group. Updated genetic score based on 34 confirmed type 2 diabetes loci is associated with diabetes incidence and regression to normoglycemia in the Diabetes Prevention Program. Diabetes. 2011;60:1340–8.CrossRefGoogle Scholar
  29. Hivert M-F, Christophi CA, Franks PW, Jablonski KA, Ehrmann DA, Kahn SE, Horton ES, Pollin TI, Mather KJ, Perreault L, Barrett-Connor E, Knowler WC, Florez JC, for the Diabetes Prevention Program Research Group. Lifestyle and metformin ameliorate insulin sensitivity independently of the genetic burden of established insulin resistance variants in Diabetes Prevention Program participants. Diabetes. 2016;65:520–6.CrossRefGoogle Scholar
  30. International Expert Committee. International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care. 2009;32:1327–34.CrossRefGoogle Scholar
  31. Jablonski KA, McAteer JB, deBakker PIW, Franks PW, Pollin TI, Hanson RL, Saxena R, Fowler S, Shuldiner AR, Knowler WC, Altshuler D, Florez JC, for the Diabetes Prevention Program Research Group. Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle interventions in the Diabetes Prevention Program. Diabetes. 2010;59:2672–81.CrossRefGoogle Scholar
  32. Jarrett RJ, Keen H, Fuller JH, McCartney M. Worsening to diabetes in men with impaired glucose tolerance (“borderline diabetes”). Diabetologia. 1979;16:25–30.CrossRefGoogle Scholar
  33. Kawamori R, Tajima N, Iwamoto Y, Kashiwagi A, Shimamoto K, Kaku K. Voglibose Ph-3 Study Group: Voglibose for prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese individuals with impaired glucose tolerance. Lancet. 2009;373:1607–14.CrossRefGoogle Scholar
  34. Keen H, Jarrett RJ, Fuller JH. Toldbutamide and arterial disease in borderline diabetics. In: Malaisse WJ, Pirart J, Vallance-Owen J, editors. Proceedings of the eighth congress of the international diabetes federation. Amsterdam: Excerpta Medica; 1974.Google Scholar
  35. Keen H, Jarrett RJ, McCartney P. The ten-year follow-up of the Bedford survey (1962–1972): glucose tolerance and diabetes. Diabetologia. 1982;22:73–8.CrossRefGoogle Scholar
  36. Knowler WC. Prevention of type 2 diabetes: how and in whom? Arch Intern Med. 2011;171:1361–2.CrossRefGoogle Scholar
  37. Knowler WC, Ackermann RT. Preventing diabetes in American Indian communities. Diabetes Care. 2013;36:1820–2.CrossRefGoogle Scholar
  38. Knowler WC, Narayan KM, Hanson RL, Nelson RG, Bennett PH, Tuomilehto J, Scherstén B, Pettitt DJ. Preventing non-insulin-dependent diabetes. Diabetes. 1995;44:483–8.CrossRefGoogle Scholar
  39. Knowler WC, Sartor G, Melander A, Scherstén B. Glucose tolerance and mortality, including a substudy of tolbutamide treatment. Diabetologia. 1997;40:680–6.CrossRefGoogle Scholar
  40. Knowler WC, Crandall JP, Chiasson J-L, Nathan DM. Prevention of type 2 diabetes. Chapter 38 in Diabetes in America. In: Cowie CC et al (ed). 3rd ed. Bethesda, MD, National Institute of Health, NIH Pub No. 17–1468. (in press).Google Scholar
  41. Kosaka K, Noda M, Kuzuya T. Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males. Diabetes Res Clin Pract. 2005;67:152–62.CrossRefGoogle Scholar
  42. Le Roux CW, Astrup A, Fujioka K, Greenway F, Lau DC, Van Gaal L, Ortiz RV, Wilding JP, Skjøth TV, Manning LS, Pi-Sunyer X, SCALE Obesity Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. 2017;389:1399–409.CrossRefGoogle Scholar
  43. Li G, Zhang P, Wang J, An Y, Gong Q, Gregg EW, Yang W, Zhang B, Shuai Y, Hong J, Engelgau MM, Li H, Roglic G, Hu Y, Bennett PH. Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study. Lancet Diabetes Endocrinol. 2014;2:474–280.CrossRefGoogle Scholar
  44. Lindström J, Peltonen M, Eriksson JG, Ilanne-Parikka P, Aunola S, Keinänen-Kiukaanniemi S, Uusitupa M, Tuomilehto J, Finnish Diabetes Prevention Study (DPS). Improved lifestyle and decreased diabetes risk over 13 years: long-term follow-up of the randomised Finnish Diabetes Prevention Study (DPS). Diabetologia. 2013;56:284–93.CrossRefGoogle Scholar
  45. Mason CC, Hanson RL, Knowler WC. Progression to type 2 diabetes characterized by moderate then rapid glucose increases. Diabetes. 2007;56:2054–61.CrossRefGoogle Scholar
  46. McCance DR, Hanson RL, Charles MA, Jacobsson LTH, Pettitt DJ, Bennett PH, Knowler WC. Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes. Br Med J. 1994;308:1323–8.CrossRefGoogle Scholar
  47. Navigator Study Group. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010a;362:1463–76.CrossRefGoogle Scholar
  48. Navigator Study Group. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010b;362:1477–90.CrossRefGoogle Scholar
  49. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997;20:537–44.CrossRefGoogle Scholar
  50. 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.CrossRefGoogle Scholar
  51. Ramachandran A, Snehalatha C, Mary S, Mukesh B, Bhaskar AD, Vijay V. The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1). Diabetologia. 2006;49:289–97.CrossRefGoogle Scholar
  52. Saito T, Watanabe M, Nishida J, Izumi T, Omura M, Takagi T, Fukunaga R, Bandai Y, Tajima N, Nakamura Y, Ito M, Zensharen Study for Prevention of Lifestyle Diseases Group. Lifestyle modification and prevention of type 2 diabetes in overweight Japanese with impaired fasting glucose levels: a randomized controlled trial. Arch Intern Med. 2011;171:1352–60.CrossRefGoogle Scholar
  53. Sartor G, Scherstén B, Carlström S, Melander A, Nordén A, Persson G. Ten-year follow-up of subjects with impaired glucose tolerance: prevention of diabetes by tolbutamide and diet regulation. Diabetes. 1980;29:41–9.CrossRefGoogle Scholar
  54. Stevenson M, Thompson J, Hérick de Sá T, Ewing R, Mohan D, McClure R, Roberts I, Tiwari G, Giles-Corti B, Sun X, Wallace M, Woodcock J. Urban design, transport, and health 2: land use, transport, and population health: estimating the health benefits of compact cities. Lancet. 2016;388:2925–35.CrossRefGoogle Scholar
  55. Tabak AG, Jokela M, Akbaraly TN, Brunner EJ, Kivimäki M, Witte DR. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet. 2009;373:2215–21.CrossRefGoogle Scholar
  56. 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.CrossRefGoogle Scholar
  57. Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M, Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:1343–50.CrossRefGoogle Scholar
  58. Uusitupa M, Peltonen M, Lindström J, Aunola S, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Valle TT, Eriksson JG, Tuomilehto J, Finnish Diabetes Prevention Study Group. Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study–secondary analysis of the randomized trial. PLoS One. 2009;4:e5656.CrossRefGoogle Scholar
  59. Vijayakumar P, Nelson RG, Hanson RL, Knowler WC, Sinha M. HbA1c and the prediction of type 2 diabetes in children and adults. Diabetes Care. 2017;40:16–21.CrossRefGoogle Scholar
  60. Wareham NJ, Herman WH. The clinical and public heath challenges of diabetes prevention: a search for sustainable solutions. PLoS Med. 2016;10:e1002097.CrossRefGoogle Scholar
  61. Warren B, Pankow JS, Matsushita K, Punjabi NM, Daya NR, Grams M, Woodward M, Selvin E. Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study. Lancet Diabetes Endocrinol. 2017;5:34–42.CrossRefGoogle Scholar
  62. White M. Population approaches to prevention of type 2 diabetes. PLoS Med. 2016;13:e1002080.CrossRefGoogle Scholar
  63. World Health Organization. Diabetes mellitus: report of a WHO study group. WHO Tech Rep Ser. 1985;727:7–113.Google Scholar
  64. Yusuf S, Gerstein H, Hoogwerf B, Pogue J, Bosch J, Wolffenbuttel BH, Zinman B, HOPE Study Investigators. Ramipril and the development of diabetes. JAMA. 2001;286:1882–5.CrossRefGoogle Scholar
  65. Zinman B, Harris SB, Neuman J, Gerstein H, Retnakaran RR, Raboud J, Qi Y, Hanley AJG. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomized controlled study. Lancet. 2010;376:103–11.CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Diabetes Epidemiology and Clinical Research SectionNational Institute of Diabetes and Digestive and Kidney DiseasesPhoenixUSA

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