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.

Impaired fasting glucose: Pro-diabetic, “atheroprotective” and modified by metabolic syndrome

“…We have pointed out that Turkish women are more prone to IGT than men due to a greater participation of chronic low-grade inflammation and HDL dysfunction [8] .…”

“…A further difference is the lack of change in Lp (a) concentration in males with IFG which is consistent with MetS, rather than diabetes, mediating CHD risk in men, in contrast to Turkish women in whom impaired glucose tolerance [8] and diabetes lead to the development of CHD [14] .…”

“…IFG status did not significantly improve metrics of vascular disease prediction when added to information about several conventional risk factors [1] . Heterogeneity in screened populations is suggested by individual studies that have reported no excess cardiovascular risk [5][6][7][8] . A meta-analysis of clinical trials on interventions in subjects with pre-diabetes did not show reductions in all causes or cardiovascular mortality, contrasted to preventing progression to overt diabetes [9] .…”

Gender specific association of ABCA1 gene R219K variant in coronary disease risk through interactions with serum triglyceride elevation in Turkish adults

“…Turkish adults are prone to metabolic syndrome (MetS) (16) and women display a high burden of CHD (17) and diabetes for which elevated TG and proinflammatory state appear pivotal (18,19).…”

Clinical biomarkers of high-density lipoprotein dysfunction among middle-aged Turks

“…Given that HDL dysfunction is an important element in the development of cardiometabolic risk among middle-aged and elderly Turks (14,21), we sought to delineate most suitable clinical biomarkers of impaired HDL function. The high Trg-normal HDL-cholesterol category revealed presence of HDL dysfunction independent of CRP by conferring significant risk of diabetes in both sexes and CHD in men.…”