All Pre-Diabetes Is Not the Same: Metabolic and Vascular Risks of Impaired Fasting Glucose at 100 Versus 110 mg/dl

The Screening for Impaired Glucose Tolerance Study 1 (SIGT 1)

• FPG, fasting plasma glucose
• IFG, impaired fasting glucose
• IGT, impaired glucose tolerance
• NCEP, National Cholesterol Education Program
• NGT, normal glucose tolerance
• OGTT, oral glucose tolerance test

The dramatic increase in incidence of diabetes (1) has prompted efforts to identify individuals who have milder glucose intolerance, because early management with lifestyle change and/or medication can delay progression to diabetes with its attendant morbidity, mortality, and cost (2). It has long been recognized that impaired glucose tolerance (IGT) is a diabetes precursor, but recognition of IGT requires oral glucose tolerance tests (OGTTs), which many health care providers are reluctant to order (3). As a more convenient alternative, the American Diabetes Association has emphasized screening by measurement of fasting plasma glucose (FPG) and lowered the cutoff for abnormal FPG progressively from 140 to 125 to 110 mg/dl. However, compared with IGT, an impaired fasting glucose (IFG) cutoff of 110 mg/dl provided good specificity but reduced sensitivity for detecting risk of developing diabetes (4–6).

To obtain increased sensitivity, the American Diabetes Association recently lowered the cutoff for IFG from 110 to 100 mg/dl (7), and application of this cutoff has increased the number of Americans thought to have “pre-diabetes” to 41 million (8). Although such individuals are considered candidates for management aimed at decreasing their risk of progressing to diabetes (9), the metabolic and cardiovascular risks of individuals with very modest abnormalities in FPG are not well understood. In this study, we compared measures of risk in individuals with fasting glucose 100–109 mg/dl (IFG100) with those with fasting glucose 110–125 mg/dl (IFG110).