Relation Between Blood Glucose and Coronary Mortality Over 33 Years in the Whitehall Study

Abstract

Glucose intolerance is a risk factor for coronary disease, but there is uncertainty about the shape of the dose-response relationship between glucose level and risk of coronary mortality. We examined the prospective relation of 2-h postload blood glucose (2hBG) with coronary and other major causes of mortality over 33 years. A 50-g oral glucose tolerance test (OGTT) was performed at baseline (1967-1969) in 17,869 male civil servants aged 40-64 years. There were 3,561 coronary deaths during 451,787 person-years of observation. All-cause, cardiovascular, and respiratory mortality were elevated among participants with glucose intolerance. The hazard of coronary mortality rose from 2hBG = 4.6 mmol/l (83 mg/dl [95% CI 4.2-5.3]). The dose-response relation was best fitted by a single slope above this level, with no evidence of nonlinearity, compared with Cox models using other threshold levels, and those containing log 2hBG terms. There was no evidence for a dose-response relationship below 2hBG = 4.6 mmol/l. Between this level and 11.1 mmol/l (200 mg/dl), the age-adjusted hazard ratio was 3.62 (95% CI 2.3-5.6). The graded relationship was attenuated by 45% after adjustment for baseline coronary heart disease (CHD), BMI, systolic blood pressure, blood cholesterol, smoking, physical activity, lung function, and employment grade. A threshold model with linear slope best described the dose-response relationship between postload blood glucose and CHD mortality risk.