Fasting, non-fasting glucose and HDL dysfunction in risk of pre-diabetes, diabetes, and coronary disease in non-diabetic adults

Abstract

We determined in non-diabetic persons the risk of fasting and non-fasting glucose levels for pre-diabetes, diabetes, and coronary heart disease (CHD), including the roles of serum C-reactive protein (CRP) and HDL cholesterol, and delineated risk profiles of the pre-diabetic states. Over 7¼ years, 2,619 middle-aged Turkish adults free of diabetes and CHD were studied prospectively. Using different serum glucose categories including impaired fasting glucose (IFG, 6.1-6.97 mmol/L) and impaired glucose tolerance (IGT), outcomes were analyzed by Cox regression. IFG was identified at baseline in 112 and IGT in 33 participants. Metabolic syndrome components distinguished individuals with IFG from those with normoglycemia. Participants with IGT tended to differ from adults in normal postprandial glucose categories in regard to high levels of triglycerides, apoA-I, and CRP. Diabetes risk, adjusted for sex, age, waist circumference, CRP, and HDL cholesterol, commenced at a fasting 5.6-6.1 mmol/L threshold, was fourfold at levels 6.1-6.97 mmol/L. Optimal glucose values regarding CHD risk were 5.0-6.1 mmol/L. Fasting and postprandial glucose values were not related to CHD risk in men; IGT alone predicted risk in women (HR 3.74 [1.16;12.0]), independent of age, systolic blood pressure, non-HDL cholesterol, waist circumference, smoking status, and CRP. HDL cholesterol was unrelated to the development of IFG, IGT, and diabetes, while CRP elevation independently predicted the development of diabetes. IGT independently predicts CHD risk, especially in women. HDL dysfunction associated with low-grade inflammation is a co-determinant of pre-diabetic states and their progression to diabetes.