A 27-year-old asymptomatic Hispanic American woman is evaluated for risk of diabetes mellitus. She developed gestational diabetes with her first pregnancy, which ended successfully 12 months ago. She has a strong family history of type 2 diabetes mellitus.
On physical examination, she is 165 cm (64 in) tall and weighs 90 kg (198 lb); the body mass index is 34. The random plasma glucose level is 135 mg/dL. A 75-g glucose tolerance test shows a fasting plasma glucose level of 112 mg/dL and a 2-hour value of 178 mg/dL.
What is the most appropriate next step in the management of this patient?
A. Repeat the glucose tolerance test in 1 year
B. Begin thiazolidinedione therapy
C. Begin acarbose therapy
D. Begin metformin therapy
E. Begin intensive lifestyle intervention

The correct answer is E
Educational Objectives
Recognize prediabetes as a treatable risk factor for type 2 diabetes.
The patient has four identified risk factors for the development of diabetes: strong family history, membership in a high-risk ethnic group, obesity, and a history of gestational diabetes mellitus. The random glucose level is suspicious but nondiagnostic of an abnormality of carbohydrate tolerance. The fasting glucose level is consistent with impaired fasting glucose, and the 2-hour value is consistent with impaired glucose tolerance. These characteristics are now called ‘prediabetes, a state of great risk for type 2 diabetes. Prospective, randomized controlled trials have demonstrated an annual incidence of diabetes of 11% among persons with these characteristics.
Multiple interventions are effective in delaying or preventing the development of diabetes. The Finnish Diabetes Prevention Study and the Diabetes Prevention Program demonstrated a 58% reduction in the cumulative incidence of diabetes in patients with impaired glucose tolerance after initiation of an intensive lifestyle intervention. The goals of the intervention were to increase exercise to at least 150 minutes weekly and achieve and maintain a 7% weight loss by reducing caloric intake. The magnitude and consistency of the effects of lifestyle intervention make it the optimal initial therapeutic approach.
Thiazolidinedione therapy with troglitazone was shown to prevent diabetes in Hispanic American women with a history of gestational diabetes mellitus. However, the study was ended prematurely, and troglitazone was withdrawn from the market because of hepatotoxicity. Ongoing trials with the remaining thiazolidinediones (rosiglitazone and pioglitazone) aim to show that these agents also prevent diabetes, but no conclusions can be yet drawn.
Acarbose therapy was shown to delay the onset of diabetes in a similar population with impaired glucose tolerance. The effect was smaller (25% reduction) than that seen with lifestyle intervention in the Diabetes Prevention Study or the Diabetes Prevention Program. The rate of diabetes development in the intervention group after discontinuation of acarbose therapy matched that of the placebo group. Early reports suggest, however, that acarbose also reduced the incidence of cardiovascular disease in this high-risk group.
In the Diabetes Prevention Program, metformin therapy reduced development of diabetes, but not to the same extent as lifestyle intervention (31% vs. 58%, respectively). By the end of the study, 20% of patients randomized to metformin therapy were taking less than 80% of the prescribed dose because of contraindications or unacceptable side effects. In addition, metformin is not approved for this indication by the U.S. Food and Drug Administration.