Prevent type 2 diabetes mellitus with weight loss and exercise

Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 44-year-old man is evaluated during a routine examination. He is concerned about his general health and risk of diabetes mellitus. He has no medical problems. Both parents and his sister have type 2 diabetes mellitus.

On physical examination, temperature is normal, blood pressure is 130/79 mm Hg, pulse rate is 66/min, and respiration rate is 14/min. BMI is 28. The remainder of the physical examination is normal.

Laboratory studies show fasting glucose 104 mg/dL (5.8 mmol/L), total cholesterol 247 mg/dL (6.40 mmol/L), HDL cholesterol 50 mg/dL (1.30 mmol/L), LDL cholesterol 177 mg/dL (4.58 mmol/L), and triglycerides 100 mg/dL (1.13 mmol/L).

Which of the following interventions is the most appropriate initial strategy to decrease this patient’s chance of developing type 2 diabetes mellitus?

A. Acarbose
B. Metformin
C. Pioglitazone
D. Weight loss and exercise

MKSAP Answer and Critique

The correct answer is D. Weight loss and exercise.

The most appropriate therapies to prevent type 2 diabetes mellitus in this patient are weight loss and exercise. This patient has a strong family history of type 2 diabetes mellitus and impaired fasting glucose, defined as a fasting plasma glucose level of 100 to 125 mg/dL (5.6 to 7.0 mmol/L). Based on multiple clinical trials, lifestyle modification has been shown to be the most effective intervention to prevent type 2 diabetes and its associated cardiovascular consequences.

The Finnish Diabetes Prevention Study and the U.S. Diabetes Prevention Program (USDPP) both demonstrated a 58% relative risk reduction in the progression to diabetes with these methods in generally obese, middle-aged persons with impaired glucose tolerance. The American Diabetes Association recommends that lifestyle modifications continue to be the standard approach in diabetes prevention, with the goal being to increase regular physical activity by approximately 30 minutes on most days of the week and to reduce calories (to reduce weight) by 7%.

The USDPP reported a 31% risk reduction in the development of diabetes in patients treated with metformin. Acarbose reduced the risk of diabetes by 25% in the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) trial but had a high drop-out rate owing to gastrointestinal adverse effects. Other studies have shown a 62% reduction in progression to diabetes with rosiglitazone in patients with impaired glucose tolerance or impaired fasting glucose and an 82% reduction in the progression to diabetes with pioglitazone. However, the thiazolidinediones are associated with significant potential adverse effects, and the harm of these drugs may outweigh the benefit of their use in this patient population. Despite these findings, currently no drugs are FDA-approved for the prevention of diabetes. In patients with impaired fasting glucose and other risk factors (BMI ≥35, a strong family history, elevated triglyceride level, reduced HDL cholesterol level, hypertension, HbA1c >6.0%), some clinicians will use metformin if lifestyle modifications have not been successful.

Key Point

The most appropriate therapies to prevent type 2 diabetes mellitus are weight loss and exercise.

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