Hyperinsulinaemia as a predictor of coronary heart disease mortality in a healthy population: the Paris Prospective Study, 15-year follow-up

Abstract

The Paris Prospective Study is a long-term, large-scale study of the factors predicting coronary heart disease. The first follow-up examination included, for subjects not known as having diabetes mellitus, a 75 g oral glucose tolerance test with measurement of plasma insulin and glucose levels, fasting and 2 h post-load. Between 1968 and 1973, 6903 men aged 43-54 years were thus examined. Causes of death were ascertained within this group after 15 years of mean follow-up. The baseline variables were tested as predictors of death from coronary heart disease by a Cox regression analysis. Significant independent predictors of coronary heart disease death were: systolic blood pressure, number of cigarettes per day, plasma cholesterol level, and 2 h post-load plasma insulin level when entered as a categorical variable (below or above 452 pmol/l. i.e. the lower limit of the fifth quintile of the distribution). This dichotomization was performed to account for the non-linear univariate distribution of deaths with increasing post-load insulin values. Fasting plasma insulin level was not an independent predictor of death by coronary heart disease over this long-term follow-up. Levels of blood glucose were not significant independent predictors of death by coronary heart disease when plasma insulin levels were included in the model. The same applied to abnormalities of glucose tolerance when the 125 men with known non-insulin-treated diabetes at baseline were added to the group. Under the assumption that hyperinsulinaemia is a marker of insulin resistance, the results are consistent with the hypothesis that insulin resistance is associated with a higher risk of coronary heart disease mortality. However, it is doubtful that circulating insulin per se is a direct cause of arterial complications.

A randomized, double-blind, placebo-controlled, clinical trial of the effects of pioglitazone on glycemic control and dyslipidemia in oral antihyperglycemic medication-naive patients with type 2 diabetes mellitus

“…25-27 In patients with type 2 diabetes mellitus, dyslipidemia often consists of elevated TGs, decreased HDL-C, and reduced LDL particle size, whereas TC and LDL may or may not be in the normal range. 5,28 In the present study, pioglitazone 30 and 45 mg increased HDL-C compared with placebo (P = 0.028 and P < 0.001, respectively) and had no treatment effect on TC or LDL-C.…”

“…5,6 Pharmacotherapy that increases insulin sensitivity has been shown to improve both glycemic and lipid profiles] Pioglitazone, a thiazolidinedione insulin sensitizer, has been shown in clinical studies to reduce glycated hemoglobin (HbAI,. ), TGs, and free fatty acids while enhancing insulin sensitivity and elevating HDL-C. 8-1° Moreover, a recent study 11 has shown that pioglitazone reduces the atherogenic index of plasma (AIP), 12 an indicator of risk for cardiovascular disease.…”

Asymptomatic hyperglycaemia is associated with increased intimal plus medial thickness of the carotid artery

“…Among these risk factors, the significance of systolic blood pressure and smoking was pointed out by the Whitehall study [1,2] and the Bedford survey [3]. Higher plasma insulin level was found to be a risk factor in the Paris study [4][5][6][7] and the Helsinki Policemen study [8]. In the Paris study, the plasma triglyceride level was the only factor positively and significantly associated with coronary death [6].…”

“…Several prospective studies [1][2][3][4][5][6][7][8][9][10][11][12] have suggested the occurrence of advanced atherosclerosis in coronary arteries and cerebral arteries in subjects with elevated blood glucose concentrations. In the Whitehall study [1,2], stroke mortality and coronary heart disease (CHD) mortality were increased approximately twofold for subjects with impaired glucose tolerance (IGT), defined as a blood-glucose level above 5.3 mmol/1.…”

“…The Paris prospective study [4][5][6][7] pointed out that the annual CHD mortality rates were increased almost twofold in subjects with IGT compared with those in normoglycaemic subjects. However, although symptomatic subjects have been examined by invasive coronary angiography [13,14], information on asymptomatic atherosclerosis in asymptomatic hyperglycaemia is scarce.…”