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Objective: To determine whether there are thresholds for fasting and for 2-h glucose above which the risk of death from all causes and from coronary heart disease (CHD) increases., Research Design and Methods: We studied 23-year mortality data from the Paris Prospective Study of the 7,018 men, aged 44-55 years, who were not known as diabetic at the baseline examination. The effect of glucose concentrations on mortality was studied using the observed relative risks and an age-adjusted Cox proportional hazards model., Results: For all causes of death, there were J-shaped relationships with both fasting and 2-h glucose concentrations, and the lowest observed death rates were in the intervals centered on 5.5 mmol/l for fasting glucose and 5.0 mmol/l for 2-h glucose. The death rates for CHD were low in this population: for fasting glucose, the hazards ratio was best modeled by a positive linear relationship; for 2-h glucose, it was modeled by a J-shaped curve and the lowest observed death rate was in the interval centered on 6.0 mmol/l., Conclusions: In the Paris Prospective Study, there were no clear thresholds for fasting or 2-h glucose concentrations above which mortality sharply increased; in the upper levels of the glucose distributions, the risk of death progressively increased with increasing fasting and 2-h glucose concentrations.

The Paris Prospective Study is a long-term investigation of cardiovascular diseases in a population of 7164 working men, aged 43-54 years. The first annual follow-up session (1968-73) included a 0-2 hr 75 g OGTT with measurement of plasma insulin and glucose levels beside the major coronary heart disease (CHD) risk factors: arterial pressure, cigarette smoking, weight, cholesterol, triglycerides. After a mean 11.2 years follow-up, 651 deaths, among them 126 due to CHD, were recorded. The annual CHD mortality rates were respectively 1.4, 2.7 and 3.2 per 1000 for the 6055 normoglycaemic, 690 impaired glucose tolerance, and 293 new and known diabetic subjects (1980 WHO classification) (p less than 0.01). The annual risk was analyzed by the multivariate Cox model. It showed that the fasting plasma insulin was positively associated with risk independent of the other factors (p less than 0.05), whereas glucose tolerance, including overt diabetes, was not significantly associated. We conclude that high insulin levels may constitute a more sensitive predictor of CHD than the degree of glucose intolerance, it could be useful to avoid excessive insulin plasma concentration, and even to lower its level.

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.

Beside arterial hypertension, hypercholesterolaemia and smoking habits, diabetes is considered as a risk factor of coronary heart disease (CHD). However, the role of impaired glucose tolerance (IGT) has not been demonstrated in the different epidemiological studies in the world which are summarized here; hyperinsulinaemia was also suspected and its independent role--investigated in only three prospective surveys--was demonstrated. The recent data of the Paris Prospective Study, where normoglycaemic, IGT and diabetic patients were analysed together, show that hyperinsulinaemia may be the first and genuine marker of the carbohydrate metabolism disturbance connected to the clinical manifestations of atherosclerosis.

The Paris Prospective Study I (7434 men) is a long-term investigation of cardiovascular diseases. A previous analysis has shown that high plasma insulin level was a more sensitive marker than glucose intolerance in the prediction of coronary heart disease (CHD). In order to ascertain the risk model for CHD in relation to high circulating plasma insulin level, we studied CHD mortality rates in groups of participants to the study with similar profiles of risk factors. The risk factors considered to cross-classify the subjects were: serum cholesterol level, blood pressure, fasting plasma insulin level (all the significant predictors of CHD mortality in the Cox regression model), plus body mass index (BMI) and 2-h post-load blood glucose level. Serum cholesterol level was linearly related to CHD mortality risk. The strength of the association of blood pressure to the risk was reduced when BMI increased. By contrast, the association of blood pressure to the risk remained linear when plasma insulin level rather than BMI was considered. Plasma insulin level was a more sensitive marker of CHD risk than glucose intolerance in the overweight group. Moreover, in this group, the relation to CHD mortality risk was stronger for plasma insulin level than for blood pressure.

The Paris Prospective Study is a long-term investigation of coronary heart disease (CHD) conducted on 7038 working men, aged 43-54 years and followed 11.2 years in mean. The first examination included a 0-2 h 75 g OGTT with measurement of plasma insulin and glucose levels, beside the major CHD risk factors. 651 deaths (CHD = 126) were recorded. The annual CHD mortality rates were respectively 1.4, 2.7 and 3.5 per 1000 for the 6055 normoglycaemic, 690 impaired glucose tolerance and 293 new and known diabetic subjects (1980 WHO classification) (p less than 0.001). It showed that the fasting plasma insulin was positively associated with risk independent of the other factors (p less than 0.05), whereas glucose tolerance, including overt diabetes, was not significantly associated. Thus, high insulin levels may constitute a more sensitive predictor of CHD than the degree of glucose intolerance and it could be useful to avoid excessive insulin plasma concentration, and even to lower its levels.