[Steps toward the primary prevention of type II diabetes mellitus. Various epidemiological considerations]

Non-insulin-dependent diabetes mellitus (NIDDM), or type II diabetes is rapidly becoming one of the most common chronic disease in the United States and worldwide, with more than 7% of the adult population affected. NIDDM is even more common in the elderly and in minority population including Hispanic Americans, African Americans, Asian and Pacific Island Americans, and Native Americans. In these populations, NIDDM may be present in 10% to as much as 50% of the adult population. However diagnosed NIDDM is only the tip of the iceberg of an epidemic of glucose intolerance. Impaired glucose intolerance (IGT) is even more prevalent that NIDDM; and in addition to be a major risk factor for the development of NIDDM, IGT is associated with an increased risk of macrovascular disease. Recent advances in research into the etiology and natural history of diabetes have increased the knowledge to such an extent that primary prevention of NIDDM is becoming a reality. This primary prevention can be implemented a) through a population strategy, i.e. changing the lifestyle and environmental determinants that are known to be risk factors for diabetes, and b) through high-risk strategy, i.e. targeting preventive measures only at those specific individuals or groups that are at high risk for the future development of NIDDM. The latter is the strategy of the Diabetes Prevention Program (DDP), a clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Disease in USA. Twenty five centers were selected to participate in this program. The purpose of DPP is prevent or delay the development of NIDDM in those persons who are at high risk because they have IGT. DPP will also evaluate if the interventions selected to prevent the development of NIDDM can decrease the frequency of cardiovascular events and the occurrence and magnitude of the cardiovascular risk factors that accompany NIDDM and IGT. Four thousand volunteers will be recruited from populations known to be at particular high risk fo IGT and NIDDM including the following: elderly, overweight individuals, persons with family history of NIDDM, women with history of gestational diabetes, and minority populations. In order to be eligible, persons who are older than 25 years will have to demonstrate IGT with plasma glucose levels 100-139 mg/dl fasting and 140-199 mg/dL two hours after a 75 g OGTT. Three study intervention were selected based on their potential efficacy in ameliorating abnormal glucose metabolism in IGT and on their safety and tolerable profile of side-effects. The interventions include: intensive lifestyle intervention which focuses on a healthy diet to achieve and maintain at least a 7% loss of body weight and an increase in caloric expenditure of at least 700 kcal per week. The drug therapy interventions include the biguanide metformin and the thiazolidinedione troglizatone. Standard life-style recommendations, which include conventional instructions regarding diet and exercise, will be provided to all participants, including a placebo treated group which will serve as the control group for the study. After randomization, participants will have quarterly evaluations and have, in addition, a fasting plasma glucose at semi-annual visits and a 75 g OGTT at annual visits. All participants will be followed for three years after the study-wide closing date for recruitment, resulting in 3 to 6 years of participant follow-up. The primary outcome is the development of NIDDM according to WHO criteria (fasting plasma glucose level 140 mg/dL or 2-hour plasma glucose 200 mg/dL after a 75 g OGTT). Secondary outcome will focus en cardiovascular disease and its risk factors and change of glycemia, insulin secretion and sensitivity, obesity, physical activity and nutrient intake, quality of life, and the occurrence of adverse events.