Metabolic Risk Factors Worsen Continuously across the Spectrum of Nondiabetic Glucose Tolerance: The Framingham Offspring Study

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Abstract
Categorical definitions for glucose intolerance imply that risk thresholds exist, but metabolic risk for type 2 diabetes mellitus or cardiovascular disease may increase continuously as glucose intolerance increases. To examine the distributions of the following metabolic risk factors across the spectrum of glucose tolerance: overall and central obesity, hypertension, low levels of high-density lipoprotein cholesterol, and increased triglyceride and insulin levels. Cross-sectional analysis. The community-based Framingham Offspring Study. 2583 adults without previously diagnosed diabetes. Clinical data; fasting glucose, insulin, and lipid levels; and glucose and insulin levels taken 2 hours after oral challenge were collected from 1991 to 1993. Glucose tolerance was determined by 1980 World Health Organization criteria. Patients with normal glucose tolerance were categorized into quintiles of fasting glucose. The distributions of each metabolic risk factor and the metabolic sum of the six risk factors were assessed across seven categories from the lowest quintile of normal fasting glucose level through impaired glucose tolerance and previously undiagnosed diabetes. The mean age of patients was 54 years (range, 26 to 82 years); 52.7% of patients were women, Glucose tolerance testing found that 12.7% of patients had impaired glucose tolerance and 4.8% had previously undiagnosed diabetes. Multivariable-adjusted mean measures of risk factors and odds ratios for obesity, elevated waist-to-hip ratio, hypertension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and hyperinsulinemia showed continuous increases across the spectrum of nondiabetic glucose tolerance. Although a threshold effect near the upper range of nondiabetic glucose tolerance could not be ruled out for triglyceride levels in men and for insulin levels 2 hours after oral challenge in men and women, no other metabolic risk factors showed clear evidence of thresholds for increased risk. Metabolic risk factors for type 2 diabetes mellitus and for cardiovascular disease worsen continuously across the spectrum of glucose tolerance categories, beginning in the lowest quintiles of normal fasting glucose level.