Relationship between serum sex hormones and glucose, insulin and lipid abnormalities in men with myocardial infarction.

Abstract

Fifteen patients who had had a myocardial infarction before the age of 43 were compared with thirteen age-matched normal subjects. Twelve of the patients and three of the controls had a delayed glucose and insulin peak in the glucose tolerance test. Curves with delayed peaks defin larger mean glucose and insulin areas than normal curves. When the measurements of the four patients with the largest areas under the glucose tolerance curve were separated, significant correlations were observed in the remaining patients and controls.The ratio in serum of the concentrations of estradiol-17j# to testosterone (E/) correlated with serum glucose area (r = +0.69, P < 0.001), insulin area (r = +0.80, P < 0.001), and the ratio of insulin area to glucose area (I/G) (r = +0.64, P < 0.005) in the glucose tolerance test. Serum cholesterol concentration correlated with E/T, insulin area, and I/G, and serum triglyceride concentration correlated with glucose area, I/G, and serum cholesterol concentration. The hypothesis is presented (i) that in men who have had a myocardial infarction, an abnormality in glucose tolerance and insulin response and elevation in serum cholesterol and triglyceride concentrations are all part of the same defect (glucose-insulin-lipid defect), (ii) that this glucose-insulin-lipid defect when glucose intolerance is present is the "mild diabetes" commonly associated with myocardial infarction but is based on a mechanism different from that of classical diabetes, (iii) that this glucose-insulin-lipid defect is secondary to an elevation in E/T, and (iv) that an alteration in the sex hormone milieu is the major predisposing factor for myocardial infarction.An abnormality in glucose tolerance, insulin response, serum lipid or lipoprotein concentrations, or some combination of these has been reported to occur in 80-96% of patients with coronary heart disease (1-7). In a previous study (8), a high incidence of hyperestrogenemia was observed in men under 44 years of age with myocardial infarction. The present report describes further investigations carried out on the patients and normal subjects of that study in order to determine whether the hyperestrogenemia was related to the glucose, insulin, and lipid abnormalities. The results of these investigations show a high level of correlation between the degrees of the glucose and insulin defects and the ratio of the weight concentrations in serum of estradiol-17fl to testosterone (E/T). The degree of the glucose-insulin defect was also found to correlate with the serum cholesterol and triglyceride concentrations, suggesting that an elevation in the concentrations of these lipids is part of the same defect (glucose-insulin-lipid defect). These observations raise the possibility that this glucose-insulin-lipid defect is secondary to an elevation in E/T and that a disturbance in the relationships of serum sex hormones is the major predisposing factor for myocardial infarction in men.

The association of hypotestosteronemia with coronary artery disease in men.

“…These correlations further support the possibility that hypotestosteronemia may be a prospective factor for MI as well as the hypothesis that risk factors for MI may be linked by an underlying alteration in the sex hormone milieu. 2 -3 In the present study and as found previously, testosterone correlated negatively with PAI-1 27 ' 37 and insulin 2 …”

“…When the patient group was successively reduced to a final study group of 34 men by excluding the patients with other major disorders, the testosterone and free testosterone correlations persisted (r=-.43, P<.02 and r=-.62, /><.001, respectively). Neither estradiol nor the risk factors, except for T he observations in men of hyperestrogenemia after myocardial infarction (MI), 1 of an association of sex hormones with risk factors for MI, 2 ' 3 and of a concurrence of risk factors for MI in clinical states other than MI and in populations 24 led to the hypothesis that an elevation in the estradiol-to-testosterone ratio or some closely related hormonal alteration may underlie risk factors and that hyperestrogenemia may lead to MI in men. 2 ' 3 Most laboratories studying sex hormones and MI in men have reported a high estradiol level after MI, both acutely 59 and months to years later.…”

“…Neither estradiol nor the risk factors, except for T he observations in men of hyperestrogenemia after myocardial infarction (MI), 1 of an association of sex hormones with risk factors for MI, 2 ' 3 and of a concurrence of risk factors for MI in clinical states other than MI and in populations 24 led to the hypothesis that an elevation in the estradiol-to-testosterone ratio or some closely related hormonal alteration may underlie risk factors and that hyperestrogenemia may lead to MI in men. 2 ' 3 Most laboratories studying sex hormones and MI in men have reported a high estradiol level after MI, both acutely 59 and months to years later. 612 Other laboratories have observed a low testosterone level, 1316 and yet others have observed both abnormalities 17 ' 20 after MI.…”

The Mediterranean food pattern: a good recipe for patients with the metabolic syndrome

“…In 1967, Avogaro et al described six obese patients with diabetes, hypercholesterolaemia, and marked hypertriglyceridaemia, all of whom improved on a hypocaloric and low-carbohydrate diet [3]. In the 1970s, Phillips suggested associations of aging, obesity and sex hormone-associated clinical manifestations with heart disease [4,5]. In the late 1980s, Reaven proposed insulin resistance as the critical factor and coined the name syndrome-X [6].…”

Animal Models as Tools for Translational Research: Focus on Atherosclerosis, Metabolic Syndrome and Type-II Diabetes Mellitus

“…In the 1970s, for the first time, Haller [3] used the term "metabolic syndrome" (MetS) for associations of obesity, diabetes mellitus (DM), hyperlipoproteinemia, hyperuricemia, and hepatic steatosis when describing the additive effects of risk factors on atherosclerosis. Phillips developed the concept of metabolic risk factors for myocardial infarction and described a cluster of abnormalities including glucose intolerance, hyperinsulinemia, hyperlipidemia, and hypertension [4,5]. In 1988, Reaven, an American endocrinologist, propounded that insulin resistance (IR) was the cause of glucose intolerance, hyperinsulinaemia, increased very-lowdensity lipoprotein cholesterol (VLDL-C), decreased high-density lipoprotein cholesterol (HDL-C) and hypertension and named the constellation of abnormalities "syndrome X" [6].…”