The Paris Prospective Study is a long-term investigation of the incidence of coronary heart disease in a large population of working men. The first follow-up examination involved 7,038 men, aged 43-54 years. Subjects with impaired glucose tolerance or diabetes (n = 943) were selected from the total population for a separate analysis of coronary heart disease mortality risk factors. During a mean follow-up of 11 years, 26 of these 943 subjects with abnormal glucose tolerance died from coronary heart disease. Univariate analysis showed that plasma triglyceride level (p less than 0.006), plasma cholesterol level (p less than 0.02), and plasma insulin level both fasting and 2-h post-glucose load (p less than 0.02), were significantly higher in subjects who died from coronary heart disease compared to those who did not. In multivariate regression analysis using the Cox model, plasma triglyceride level was the only factor positively and significantly associated with coronary death. The distribution of plasma triglyceride levels was clearly higher for the subjects who died from coronary heart disease compared to those who did not die from this cause or were alive at the end of the follow-up. This new epidemiological evidence that hypertriglyceridaemia is an important predictor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes suggests a possible role of dyslipidaemia in the excessive occurrence of atherosclerotic vascular disease in this category of subjects.
The diabetogenic effect of streptozotocin was investigated in the rat during the fetal and neonatal life. Streptozotocin was directly injected in the vitellin vein of the fetus or in the saphenous vein of the neonate. In the 21.5 day old fetus, diabetogenic activity was demonstrated with a single dose of 100 μg/gm. administered the day before, and this was indicated by a fall in the pancreatic insulin content to 20 per cent and a lowering of the plasma insulin to 60 per cent of the controls. A single dose (100 μg/gm.) of streptozotocin administered on the day of birth produced an overt diabetes in the neonate: the maximal fall in the pancreatic insulin content (7 per cent of the controls) was observed four days after the streptozotocin injection, during the highest blood glucose level (300 per cent of the controls). A significant increase in the pancreatic glucagon content was observed twenty-four hours after the maximal insulin depletion. Liver glycogen content was occasionally decreased. More severe diabetes was obtained by two streptozotocin injections (50μg/gm.), with lowest pancreatic and highest blood glucose levels at 1 per cent and 60 per cent, respectively. A clearcut drop of the plasma insulin/glucose ratio was observed in the drug-treated animals. Three weeks after injection(s), basal blood glucose and plasma insulin levels were normal, although impairment of insulin secretion still appeared after glucose load and insulin pancreatic content was still slightly lower. A rapid and spontaneous, if not quite complete recovery, is a characteristic pattern of the streptozotocin diabetes in the neonate as compared to that in the adult.
The possible role of plasma insulin levels as a risk factor of coronary heart disease has been studied in a population of 7246 non diabetic, working men, aged 43-54 years, initially free from heart disease, and followed for 63 months on average. 128 new coronary heart disease events (non fatal myocardial infarction and coronary related deaths) were detected during this period. The annual risk is analysed by a multivariate model including age, serum cholesterol and triglycerides, blood pressure, smoking, obesity, plasma glucose and insulin fasting and 2 hours after a 75 g oral glucose load. It is shown that the fasting plasma insulin level and the fasting insulin-glucose ratio are positively associated with risk independent of the other factors. The same variables, 2 hours after the glucose load are also positively associated with risk but their contributions are not significant in the multivariate analysis. It is concluded that high insulin levels may constitute an independet risk factor for coronary heart disease complications in middle aged non diabetic men.
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