Clinical Review

Prevention of Type 2 Diabetes: Evidence and Strategies

Journal of Clinical Outcomes Management. 2017 April;24(4)

References

1. International Diabetes Federation. Diabetes facts and figures. www.idf.org/about-diabetes/facts-figures. Accessed on January 29, 2017.

2. Centers for Disease Control and Prevention. National diabetes statistics report, 2014. www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf. Accessed on January 29, 2017.

3. Centers for Disease Control and Prevention. Number of Americans with diabetes projected to double or triple by 2050. www.cdc.gov/media/pressrel/2010/r101022.html. Accessed on January 29, 2017.

4. World Health Organization (WHO). Diabetes fact sheet. No. 312. November 2016. www.who.int/mediacentre/factsheets/fs312/en/. Accessed on January 29, 2017.

5. Karam JG, McFarlane SI. Update on the prevention of type 2 diabetes. Curr Diab Rep 2011;11:56–63.

6. Menke A, Rust KF, Fradkin J, et al. Associations between trends in race/ethnicity, aging, and body mass index with diabetes prevalence in the United States: a series of cross-sectional studies. Ann Intern Med 2014;161:328–85.

7. Ford ES, Li C, Sattar N . Metabolic syndrome and incident diabetes: current state of the evidence. Diabetes Care 2008;31:1898–904.

8. American Diabetes Association. Standards of medical care in diabetes—2017. Diabetes Care 2017;40(Suppl. 1).

9. Kruszynska YT, Olefsky JM. Cellular and molecular mechanisms of non-insulin dependent diabetes mellitus. J Investig Med 1996;44:413–28..

10. Butler AE, Janson J, Bonner-Weir S, et al. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003;52:102–10.

11. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Report of a WHO and IDF Consultation. 2006. http://apps.who.int/iris/bitstream/10665/
43588/1/9241594934_eng.pdf. Accessed on February 1, 2017.

12. Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors. 2001 JAMA 2003;289:76–9.

13. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe. Lancet 1999;354:617–21.

14. Barr EL, Zimmet PZ, Welborn TA, et al. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose, and impaired glucose tolerance: the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). Circulation 2007;116:151–7.

15. Xu T, Liu W, Cai X, et al. Risk of coronary heart disease in different criterion of impaired fasting glucose: a meta-analysis. Medicine 2015;94:e1740.

16. Huang Y, Cai X, Mai W, et al. Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis. BMJ 2016;355:i5953.

17. Nagi DK, Pettitt DJ, Bennett PH, et al. Diabetic retinopathy assessed by fundus photography in Pima Indians with impaired glucose tolerance and NIDDM. Diabet Med 1997;14:449 –56.

18. Diabetes Prevention Program Research Group. The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program. Diabet Med 2007;24:137–44

19. Putz Z, Tabák AG, Tóth N, et al. Noninvasive evaluation of neural impairment in subjects with impaired glucose tolerance. Diabetes Care 2009;32:181–3.

20. Hoffman-Snyder C, Smith BE, Ross MA, et al. Value of the oral glucose tolerance test in the evaluation of chronic idiopathic axonal polyneuropathy. Arch Neurol 2006;63:1075–9.

21. Plantinga LC, Crews DC, Coresh J, et al; CDC CKD Surveillance Team. Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin J Am Soc Nephrol 2010;5:673–82.

22. Pan XR, Li GW, Hu YH, et al. 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.

23. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343–50.

24. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393–403.

25. 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.

26. Ramachandran A, Snehalatha C, Mary S, et al; Indian Diabetes Prevention Programme (IDPP).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.

27. Saito T, Watanabe M, Nishida J, et al; 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.

28. Li G, Zhang P, Wang J, et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet 2008;371:1783–9.

29. Li G, Zhang P, Wang J, et al. 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;2:474–80.

30. Li G, Zhang P, Wang J, et al. 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;2:474–80.

31. Lindstrom J, Ilanne-Parikka P, Peltonen M, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet 2006;368:673–9.

32. Diabetes Prevention Research Group, Knowler WC, Fowler SE, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet 2009;374:1677–86.

33. Salas-Salvadó J, Bulló M, Babio N, et al. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care 2011;34:14–19.

34. Wang P, Fang J, Gao Z, et al. Higher intake of fruits, vegetables or their fiber reduces the risk of type 2 diabetes: A meta‐analysis. J Diabetes Investig 2016;7:56–69.

35. Devlin JT. Effects of exercise on insulin sensitivity in humans. Diabetes Care 1992;15:1690–3.

36. Jeon CY, Lokken RP, Hu FB, van Dam RM. Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review. Diabetes Care 2007;30:744–52.

37. Slentz C, Bateman L, Willis L, et al. Effects of exercise training alone vs a combined exercise and nutritional lifestyle intervention on glucose homeostasis in prediabetic individuals: a randomised controlled trial. Diabetologia 2016;59:2088–98.

38. Hamman RF, Wing RR, Edelstein SL, et al. Effect of weight loss with lifestyle intervention on risk of diabetes. Diabetes Care. 2006;29:2102–7.

39. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med 2002;137:25–33.

40. Ratner RE, Christophi CA, Metzger BE, et al. Prevention of diabetes in women with a history of gestational diabetes: effects of metformin and lifestyle interventions. J Clin Endocrinol Metab 2008;93:4774–9.

41. Diabetes Prevention Program Research Group. Effects of withdrawal from metformin on the development of diabetes in the diabetes prevention program. Diabetes Care 2003;26:977–80.

42. Salpeter SR, Buckley NS, Kahn JA, Salpeter EE. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus. Am J Med 2008;121:149–57.

43. El-Atat F, Nicasio J, Clarke L, et al. Beneficial cardiovascular effects of thiazolidinediones. Therapy 2005;2:113–19.

44. Buchanan TA, Xiang AH, Peters RK, et al. 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;51:2796–2803.

45. Azen SP, Peters RK, Berkowitz K. TRIPOD (Troglitazone In the Prevention Of Diabtes): a randomized placebo-controlled study of troglitazone in women with prior gestational diabetes mellitus. Control Clin Trials 1998;19:217–31.

46. Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006;368:1096–1105.

47. DREAM Investigators, Gerstein HC, Mohan V, Avezum A, et al. Long-term effect of rosiglitazone and/or ramipril on the incidence of diabetes. Diabetologia 2011;54:487–95.

48. DeFronzo RA, Tripathy D, Schwenke DC, et al. Pioglitazone for diabetes prevention in impaired glucose tolerance. N Engl J Med 2011;364:1104–15.

49. Ramachandran A, Snehalatha C, Mary S, et al. Pioglitazone does not enhance the effectiveness of lifestyle modification in preventing conversion of impaired glucose tolerance to diabetes in Asian Indians: results of the Indian Diabetes Prevention Programme-2 (IDPP-2). Diabetologia 2009;52:1019–26.

50 Zinman B, Harris SB, Neuman J, et al. Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study. Lancet 2010;376:103–11.

51. Chiasson JL, Josse RG, Leiter LA, et al. The effect of acarbose on insulin sensitivity in subjects with impaired glucose tolerance. Diabetes Care 1996;19:1190–3.

52. Van de Laar FA, Lucassen PL, Akkermans RP, et al. Alpha-glucosidase inhibitors for people with impaired glucose tolerance or impaired fasting blood glucose. Cochrane Database Syst Rev 2006(4):CD005061.

53. Chiasson JL, Josse RG, Gomis R, et al. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002;359:2072–7.

54. Kawamori R, Tajima N, Iwamoto Y, et al. 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.

55. Holman RR, North BV, Tunbridge FK. Possible prevention of type 2 diabetes with acarbose or metformin. Diabetes 2000;49:Suppl 1:A111.

56. Holman RR, Blackwell L, Stratton IM et al. Six-year results from the Early Diabetes Intervention Trial. Diabet Med 2003;20(Suppl 2):15.

57. Holman RR, Haffner SM, McMurray JJ, et al. Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med 2010;362:1463–76.

58. Pi-Sunyer X, Astrup A, Fujioka K et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med 2015;373:11–22.

59. ORIGIN Trial Investigators, Gerstein HC, Bosch J, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012;367:319–28.

60. Yusuf S, Gerstein H, Hoogwerf B, et al. Ramipril and the development of diabetes. JAMA 2001;286:1882–5.

61. Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999;353:611–6.

62. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981–97.

63. Lindholm LH, Ibsen H, Dahlof B, et al. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:1004–10.

64. Gillespie EL, White CM, Kardas M, et al. The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes. Diabetes Care 2005;28:2261–6.

65. Bosch J, Yusuf S, Gerstein HC, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med 2006;355:1551–62.

66. McMurray JJ, Holman RR, Haffner SM, et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med 2010;362:1477–90.

67. McFarlane SI, Kumar A, Sowers JR. Mechanisms by which angiotensin-converting enzyme inhibitors prevent diabetes and cardiovascular disease. Am J Cardiol 2003;91(12A):30H–37H.

68. Heymsfield SB, Segal KR, Hauptman J, et al. 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.

69. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom 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.

70. Rovellini A, Sommariva D, Branchi A, et al. Effects of slow release bezafibrate on the lipid pattern and on blood glucose of type 2 diabetic patients with hyperlipidaemia. Pharmacol Res 1992;25:237–45.

71. Tenenbaum A, Motro M, Fisman EZ. Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc Diabetol 2005;4:14.

72. Tenenbaum A, Motro M, Fisman EZ, et al. Effect of bezafibrate on incidence of type 2 diabetes mellitus in obese patients. Eur Heart J 2005;26:2032–8.

73. Tenenbaum A, Motro M, Fisman EZ, et al. Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease. Circulation 2004;109:2197–202.

74. Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351:2683–93.

75. Sjostrom CD. Surgery as an intervention for obesity. Results from the Swedish obese subjects study. Growth Horm IGF Res 2003;13 Suppl A:S22–26.

76. Carlsson LM, Peltonen M, Ahlin S, et al. Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects. N Engl J Med 2012;367:695–704.

77. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg 1995;222:339–50.

78. Long SD, O’Brien K, MacDonald KG Jr, et al. Weight loss in severely obese subjects prevents the progression of impaired glucose tolerance to type II diabetes. A longitudinal interventional study. Diabetes Care 1994;17:372–5.

79. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724–37.

80. Tejirian T, Jensen C, Dutson E. Bariatric surgery and type 2 diabetes mellitus: surgically induced remission. J Diabetes Sci Technol 2008;2:685–91.

In a recent NIH-funded trial designed to examine the relative contribution of exercise alone to the overall beneficial effect of lifestyle changes in the DPP study, a total of 237 adults with IFG were randomly assigned to 4 different groups: low-amount moderate intensity exercise (similar to exercise followed in DPP), high-amount moderate intensity exercise, high-amount vigorous intensity exercise, and a combination of diet, weight loss, and low-amount moderate exercise. Only the diet and exercise group experienced a decrease in fasting glucose, whereas similar improvements in glucose tolerance were observed in both the diet and exercise group and the high-amount moderate-intensity exercise group, suggesting that such an exercise regimen may be as effective as a more intensive multicomponent approach involving diet, exercise, and weight loss for preventing diabetes [37].

Weight Loss

Weight reduction in prediabetic individuals has been consistently associated with reduced incidence of diabetes. Furthermore, the amount of weight loss needed to achieve this benefit seems to be relatively modest and a realistic goal to set for patients. Indeed, in the DPP trial, an average weight loss of only 5.6 kg was associated with a 58% lower incidence of diabetes [24]. Moreover, on further analysis of the DPP trial, and among weight, diet, and exercise, diabetes prevention correlated most strongly with weight loss, with an estimated 16% diabetes risk reduction for every single kilogram of weight reduction [38]. Similarly, within the same lifestyle intervention group in the FDPS, the participants who were able to achieve an initial body weight loss greater than 5% at 1 year had a nearly 70% relative risk reduction in progression to diabetes, when compared to their peers in the intervention group who had less or no weight loss [23].

In summary, numerous randomized controlled studies from various populations have proved that lifestyle modifications, including healthy diet, moderate weight loss, and moderate-intensity exercise, represent a very effective strategy to prevent diabetes in patients at risk, mostly patients with IGT, and this protective effect seems to be sustained over time.

Pharmacologic Interventions

Metformin

Metformin is an antidiabetic agent that works mostly at the liver site by suppressing hepatic glucose production and inhibiting production and oxidation of free fatty acids (FFA), thereby reducing FFA-induced insulin resistance and promoting peripheral glucose uptake [39]. This effect has the potential of preserving beta cell function by reducing the demand for insulin secretion.

In the DPP trial, metformin, although generally less effective than lifestyle changes, was associated with a significant 31% reduction in diabetes incidence (cumulative incidence of 22% in metformin group vs 29% in placebo group) and significant weight reduction (average of 2 kg) [24]. Further analysis of the DPP results showed that metformin efficacy, compared to placebo, was greater in patients who were younger, had higher BMI, and had higher FBG levels. In addition, a DPP substudy of 350 women with history of gestational diabetes and IGT revealed that this group of women, who had a higher risk of progression to diabetes (71% at 3 years) when compared to women with no history of gestational diabetes, despite similar baseline glucose levels, had similar diabetes risk reduction of 50% with both metformin and lifestyle changes [40].