Epidemiology of Insulin and Dehydroepiandrosterone Sulfate and Coronary Heart Disease Mortality
Epidemiology of Insulin and Dehydroepiandrosterone Sulfate and Coronary Heart Disease Mortality
To determine whether serum insulin is a risk factor for coronary heart disease morbidity and
 mortality and whether dehydroepiandrosterone sulfate (DHEAS) is a risk factor for coronary
 heart disease mortality. Also, to ascertain the determinants of serum insulin levels among
 middle-aged men.
BACKGROUND:

 In 1972, the Multiple Risk Factor Intervention Trial began recruiting 12,866 men, ages 35 to
 57, selected for elevation of one or more risk factors but free from coronary heart disease
 and followed them for an average of seven years after randomization to a risk factor
 modification group or to a control group referred to their own physicians for treatment. The
 serum from MRFIT had been stored since 1972. Detailed follow-up for the cohort was completed
 through 1985 and was extended through 1988 using the National Death Index.

 The role of insulin as a major risk factor for atherosclerosis resurfaced in the 1980s and
 was the subject of much research at the basic science, clinical, and epidemiological levels.
 The MRFIT serum data base probably was the only remaining such serum bank in the United
 States that could test the relationship between insulin levels and coronary heart disease
 mortality that included detailed measurements of other major cardiovascular risk factors, as
 well as both baseline and two-hour post-load glucose levels in a predominantly non-diabetic
 population.

 DHEAS is the most abundant circulating steroid hormone in man and is readily converted to
 DHEA which is a potent non-competitive inhibitor of glucose-6-phosphate dehydrogenase, the
 rate limiting enzyme of the pentose cycle. Several studies suggest a key role of DHEAS in
 obesity, lipid metabolism, cellular proliferation, and atherosclerosis. Barrett-Connor in
 1986 reported that low levels of this hormone were a risk factor for cardiovascular disease
 in men. Other studies report that administration of DHEAS to laboratory animals appears to
 delay aging, prevent obesity, and lower serum cholesterol levels.

 DESIGN NARRATIVE:

 A nested case-control study was conducted using the stored blood serum. Laboratory
 measurements were done blindly without knowledge of whether the specimen was from a case or a
 control. Insulin was measured in all 600 specimens. DHEAS was measured in 200 cases and 100
 controls. The means and distribution of insulin or DHEAS levels were compared between cases
 and controls. The analysis was done separately for the coronary heart disease deaths and
 surviving myocardial infarction cases and, if there were no differences between the case
 groups, they were pooled for comparison with the controls. The relationships were determined
 among the potential confounders, coronary heart disease morbidity and mortality and serum
 insulin or DHEAS levels. This analysis also included data on baseline serum cholesterol,
 systolic and diastolic blood pressure, cigarette smoking, serum thiocyanate, HDL and LDL
 cholesterol, triglycerides, basal metabolic index, fasting and one-hour blood glucose.
 Alcohol intake, physical activity, pulmonary function, and education were also evaluated. The
 relationships among insulin or DHEAS and coronary heart disease morbidity and mortality were
 evaluated after adjusting for possible confounders.

 The study completion date listed in this record was obtained from the "End Date" entered in
 the Protocol Registration and Results System (PRS) record.
No eligibility criteria