U-SHAPED AND J-SHAPED RELATIONSHIPS BETWEEN SERUM-INSULIN AND CORONARY HEART-DISEASE IN THE GENERAL-POPULATION - THE BRUNECK STUDY

OBJECTIVE - To evaluate the relationship existing between serum insuli n and coronary heart disease (CHD) in the general population. RESEARCH DESIGN AND METHODS - In a cross-sectional survey on atherosclerosis a nd its risk factors, 500 men and 500 women aged 40-79 years were rando mly selected from the population of Bruneck, Italy Clinical, biochemic al, and behavioral risk factors of atherosclerosis were assessed in th e 936 subjects who participated in the study. Serum insulin was measur ed at fasting (n = 888) and 2 h (n = 811, known diabetic subjects were excluded) after an oral glucose load. CHD was ascertained by an abnor mal electrocardiogram and/or a history of angina or myocardial infarct ion. RESULTS - Subjects were stratified according to serum insulin qui ntiles at fasting or 2 h after glucose loading. After adjustment for s ex, age, BMI, smoking, physical activity, alcohol intake, and socioeco nomic status (analysis of covariance), cardiovascular risk factors clu stered in subjects of the top insulin quintile. Multiple logistic regr ession analysis, including sex and age in model 1, sex, age, BMI, gluc ose tolerance, socioeconomic status, and behavioral variables in model 2, or this set of variables together with triglycerides and apoprotei ns al and B, fibrinogen, and blood pressure status in model 3, reveale d a significant association between high serum insulin and CHD when me dian insulin quintile was used as the reference class. Moreover, low s erum insulin levels, such as those found in subjects of the lowest qui ntile, were independently related to CHD. These results were found eit her before (model 1) or after (models 2 and 3) adjusting for several c ovariates. Consistent results were found in men and women, as well as in younger and older subjects. CONCLUSIONS - Results of the present st udy suggest that both hyperinsulinemia and ''hypoinsulinemia'' are ind ependent indicators of CHD. Furthermore, it is proposed that the relat ionship between CHD and fasting insulin is U-shaped, whereas that betw een CHD and postglucose insulin may be J-shaped.