Prevention of Type 2 Diabetes

The prevalence of diabetes is escalating[1] as the rates of obesity and sedentary behavior continue to rise.[2] Further, epidemiological projections point to a continued increase.[1] Diabetes is known to have a long preclinical phase of approximately 10-12 years,[3] during which time metabolic changes may already be causing microvascular and macrovascular complications.[4-6] Accordingly, recent research has focused on the prevention and/or delay of type 2 diabetes. Current emphasis is placed on lifestyle interventions, as they have proven to be more effective than medications,[7] do not cause any unwanted side effects, and confer additional benefits over and above the prevention or delay of type 2 diabetes, such as weight reduction and reduction of cardiovascular risk.[8] Although no medications are currently approved for the prevention of type 2 diabetes, several classes of glucose-lowering agents have been investigated for this purpose.

Lifestyle treatments

Four major research studies have demonstrated that type 2 diabetes can be prevented or delayed among people with prediabetes. The Malmo feasibility study[9] demonstrated that even modest weight loss was associated with glycemic improvements. Among intervention participants, 50% returned to normoglycemia. The Da Qing IGT and Diabetes Study[10] was a large multicenter trial conducted in China in 1986. This study showed that either diet, exercise, or a combination of diet and exercise decreased the incidence of type 2 diabetes among people with impaired glucose tolerance, as compared with the usual-care control group. The diet intervention consisted of reduced–calorie meals (25-30 kcaL per kg of body weight), with approximately one half to two thirds of caloric intake coming from carbohydrates. The exercise group was encouraged to increase their leisure-time physical activity. The combined intervention group simply received dietary and exercise intervention. The results demonstrated that the incidence of type 2 diabetes at follow-up was 43.8% for the diet group, 41.1% for the exercise group, and 46% for the combined group, as compared with an incidence of 67.7% in the control group.

Similar findings were observed in the Finnish Diabetes Prevention Study,[11] which found that overweight participants with impaired glucose tolerance who participated in intensive lifestyle intervention reduced their risk of type 2 diabetes by 58%. In this study, the lifestyle intervention consisted of individualized counseling designed to help participants lose weight, decrease dietary fat intake, and increase dietary fiber intake and physical activity.

The results of these studies were replicated in the Diabetes Prevention Program (DPP), a large multicenter study conducted in the US.[7] People with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) were randomized to receive either a placebo, 850 mg of metformin, or lifestyle intervention. The lifestyle intervention consisted of a healthy low-fat diet and at least 150 minutes of physical activity (eg, brisk walking) per week. At 6-month follow-up, 50% of the lifestyle participants had met their dietary goals and 75% had met their activity goals. In spite of the less-than-perfect adherence, participants in the lifestyle group demonstrated a 58% reduction in type 2 diabetes, as compared with the group receiving placebo. Results of the lifestyle prevention studies are presented in Table 1.

Table 1. Prevention of type 2 diabetes with lifestyle intervention

Pharmacologic therapy

Although no medications are currently approved for the prevention of type 2 diabetes, research has been conducted to test the efficacy of several different classes of glucose-lowering medications for that purpose, including biguanides, α-glucosidase inhibitors, and thiazolidinediones (TZDs).

In addition to the effect of the lifestyle intervention, the DPP study also showed that metformin can reduce the likelihood of developing type 2 diabetes among people with IGT or IFG by 31%. The effectiveness of metformin was greater among younger people and people with a body mass index (BMI) of greater than 35 kg/m.[7]

There is some evidence to suggest that α-glucosidase inhibitors are also beneficial for the treatment of prediabetes and prevention of type 2 diabetes. In a randomized trial comparing the effects of the α-glucosidase inhibitor acarbose with placebo in patients with IGT, 32% of the acarbose-treated patients developed diabetes, as compared with 42% of the placebo patients. Further, patients treated with acarbose were significantly more likely to return to normal glucose tolerance than were placebo patients.[12]

The third class of medications that may be beneficial for people with prediabetes is the TZDs. One study demonstrated that the TZD troglitazone (no longer available due to the occurrence of adverse liver effects) was an effective way to reduce the incidence of type 2 diabetes among high-risk women with a history of gestational diabetes.[13] Incidence of type 2 diabetes in the placebo group was 12.1% as compared with 5.4% in the troglitazone group. A small preliminary study showed similar effectiveness using rosiglitazone.[14] A summary of the medications that have been shown to be useful for the prevention of type 2 diabetes appears in Table 2.

Table 2. Medications used in type 2 diabetes prevention trials

Cost effectiveness of type 2 diabetes prevention efforts

Interventions to prevent type 2 diabetes can be costly. The lifestyle intervention arm of the DPP was very labor-intensive, providing participants with access to a lifestyle coach and involvement in an intensive intervention.[15] The cost of glucose-lowering medications is escalating.[16] Because of these facts, questions have been raised regarding the cost effectiveness of type 2 diabetes prevention. Both the lifestyle intervention and the metformin intervention in the DPP required more resources than the placebo condition, but were cost effective from a health system, as well as from a societal, perspective.[17] However, of greater concern is their ability to be implemented on a larger scale. Research in the area of diabetes translation is addressing this issue.

References

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2. Wadden TA, Brownell KD, Foster GD. Obesity: responding to the global epidemic. J Consult Clin Psychol. 2002;70:510-525.
3. Harris R, Donahue K, Rathore SS, Frame P, Woolf SH. Screening adults for type 2 diabetes: a review of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2003;138:215-234.
4. Wang WQ, Ip TP, Lam KS. Changing prevalence of retinopathy in newly diagnosed non-insulin-dependent diabetes mellitus patients in Hong Kong. Diabetes Res Clin Pract. 1998;39:185-191.
5. Klein R, Klein BEK, Moss SE. Prevalence of microalbuminuria in older-onset diabetes. Diabetes Care. 1993;16:1325-1330.
6. Eastman RC. Neuropathy in diabetes. In: National Diabetes Data Group, eds. Diabetes in America. 2nd ed. Bethesda, MD: National Institutes of Health, National Institutes of Diabetes and Digestive and Kidney Diseases; 1996:339-348.
7. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
8. Dunn AL, Marcus BH, Kampert JB, Garcia ME, Kohl HW III, Blair SN. Reduction in cardiovascular disease risk factors: 6-month results from Project Active. Prev Med. 1997;26:883-892.
9. Erikson KF, Lindgarde F. Prevention of type 2 (non-insulin-dependent) diabetes mellitus by diet and physical exercise. The 6-year Malmo feasibility study. Diabetologia. 1991;34:891-898.
10. 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;20:537-544.
11. Lindstrom J, Eriksson JG, Valle TT, et al. Prevention of diabetes mellitus in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study: results from a randomized clinical trial. J Am Soc Nephrol. 2003;14:S108-S113.
12. Chiasson LJ, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M for the STOP-NIDDM Trial Research Group. Acarbose for the prevention of type 2 diabetes mellitus: The STOP-NIDDM randomized trial. Lancet. 2002;359:2072-2077.
13. Buchanan TA, Xiang AH, Peters RK, et al. Preservation of pancreatic β-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes. 2002;51:2796-2803.
14. Bennett SMA, Agrawal A, Elasha H, et al. Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance. Diabetic Med. 2004;21:415-422.
15. The Diabetes Prevention Program Research Group. Description of the lifestyle intervention. Diabetes Care. 2002;25:2165-2171.
16. Brown JB, Nichols GA, Glauber HS, Bakst AW, Schaeffer M, Kelleher CC. Health care costs associated with escalation of drug treatment in type 2 diabetes. Am J Health-System Pharm. 2001;15:151-157.
17. The Diabetes Prevention Program Research Group. Within-trial cost-effectiveness of lifestyle intervention or metformin for the primary prevention of type 2 diabetes. Diabetes Care. 2003;26:2518-2523.