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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.

Risk factors for non-insulin-dependent diabetes mellitus (NIDDM) were assessed in a population of 5042 middle-aged white men, initially nondiabetic, who were followed 3 yr. The subjects were participants in the Paris Prospective Study I. Sixty-three subjects developed diabetes during the follow-up. Plasma glucose concentration in the years before the occurrence of the disease was a major risk factor. Subjects with normal glucose tolerance but elevated fasting plasma glucose exhibited a similar risk of developing NIDDM as did subjects classified as having impaired glucose tolerance on the basis of 2-h postload glucose. In a multiple logistic regression, a high fasting plasma insulin concentration and a low 2-h plasma insulin concentration after a glucose load in association with a high body mass index were independent predictors of conversion to NIDDM from impaired glucose tolerance. Previously, this result had been found only in Nauruans, Pima Indians, and Japanese. This demonstrates for the first time in a white population that a high fasting and low 2-h insulin concentration is predictive of conversion to NIDDM from impaired glucose tolerance.

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 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.