Insulin, Intact and Split Proinsulin, and Coronary Artery Disease in Young Men

Båvenholm, Peter; Proudler, Anthony J.; Tornvall, Per; Godsland, Ian F.; Landou, Christian; Fairé, Ulf dé; Hamsten, Anders

doi:10.1161/01.cir.92.6.1422

Cited by 86 publications

(66 citation statements)

References 29 publications

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“…Many studies have shown a relationship between proinsulin, proinsulin split products, and atherosclerotic lesions, but they were all cross-sectional studies, and the majority of them included only men [1,5,22]. In a crosssectional analysis of 1,456 nondiabetic participants in the Rancho Bernardo Study, proinsulin was positively associated with prevalent CHD in men and women [23].…”

Section: Discussionmentioning

confidence: 99%

“…When we corrected statistically for the non-fasting condition or linearly for hours since last meal intake, the results did not change substantially. Furthermore, proinsulin may be a more reliable measure of beta cell activity due to its longer half-life and lower variability than specific insulin when assessed in plasma samples [5]. This may favour proinsulin compared with insulin in regression analyses, and proinsulin is probably better than insulin for estimating future risk for CVD.…”

Section: Discussionmentioning

confidence: 99%

“…Whether increased proinsulin is simply an indicator of insulin resistance [3], or if it has other proatherogenic actions has been debated [4]. The relationship between proinsulin and CVD has not been fully clarified, and the results of earlier studies are inconsistent [1,5,6]. In some studies, the association between proinsulin and CVD was stronger than that between insulin and CVD [1], and proinsulin has been suggested to have a greater proatherogenic effect than insulin [7].…”

Section: Introductionmentioning

confidence: 99%

“…However, plaque size and growth are probably just as good or even better markers of atherosclerosis and CHD [10,11]. Most studies that assess proinsulin as a risk factor for CVD include only men [1,[5][6][7]. Furthermore, the relationship between proinsulin or insulin and carotid atherosclerosis has not been explored with a populationbased prospective design.…”

Section: Introductionmentioning

confidence: 99%

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Proinsulin:insulin and insulin:glucose ratios as predictors of carotid plaque growth: a population-based 7 year follow-up of the Tromsø Study

et al. 2007

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Aims/hypothesis Proinsulin is increased in persons at cardiovascular risk. Increased secretion of proinsulin relative to insulin has been suggested as a sign of defective conversion of proinsulin to insulin and C-peptide and is associated with beta cell dysfunction. It has also been suggested that proinsulin has more of a pro-atherogenic effect than insulin, the levels of which are also increased in the insulin resistance state. In this prospective populationbased study, we examined whether the proinsulin:insulin ratio (PIR) or insulin:glucose ratio (IGR, an insulin resistance surrogate) predicted carotid plaque size in nondiabetic participants. Materials and methods The study included 1,859 men and 1,998 women aged 25-82 years from the Tromsø Study, who were examined with B-mode high resolution ultrasound at baseline in 1994-1995 and at follow-up in [2001][2002]. All images were computer processed to yield mm 2 measures of plaque. Proinsulin and insulin were measured at baseline. All analyses were stratified for sex. Results After adjusting for age, baseline plaque area, BMI, cholesterol, HDL-cholesterol, HbA 1c , IGR, albumin:creatinine ratio, fibrinogen, BP and lifestyle factors (tobacco smoking, alcohol consumption, physical activity), PIR was significantly associated with plaque size at follow-up in women but not men. For each SD in the PIR in women, the mean plaque area increased by 0.97 mm 2 (95% CI 0.44-1.50). IGR was not associated with carotid plaque size. Conclusions/interpretation The PIR is associated with progressive carotid artery plaque size in women.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Proinsulin:insulin and insulin:glucose ratios as predictors of carotid plaque growth: a population-based 7 year follow-up of the Tromsø Study

et al. 2007

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“…There are numerous possible explanations for the observed relation of proinsulin and insulin resistance to the incidence of stroke/TIA. First, high plasma proinsulin concentrations are associated with coronary artery atherosclerosis [13] and with an increased intima-media thickness in the common carotid artery [14]. In clinical trials greatly increased human proinsulin was found to be associated with a greater increase in cardiovascular events in comparison with elevated human insulin, suggesting that thromboembolic mechanisms had been activated [15].…”

Section: Discussionmentioning

confidence: 99%

Insulin sensitivity measured by the euglycaemic insulin clamp and proinsulin levels as predictors of stroke in elderly men

et al. 2008

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Aims/hypothesis Our aim was to investigate the predictive power of a panel of variables in glucose and insulin metabolism for the incidence of stroke or transient ischaemic attacks (TIA). We hypothesised that proinsulin and insulin resistance contributes to an increase of risk for fatal and non-fatal stroke/TIA, independently of diabetes and established risk factors. Methods The study is based on the Uppsala Longitudinal Study of Adult Men cohort. The examinations were performed at age 70 years. Results In 1,151 men free from stroke at baseline, 150 developed stroke or TIA during a median follow-up of 8.8 years. In unadjusted Cox proportional hazards analyses, a 1 SD increase of a predictor variable was associated with an increased risk for stroke/TIA, e.g. plasma insulin (HR 1.19, 95% CI 1.01-1.40), fasting intact proinsulin (HR 1.28, 95% CI 1.09-1.49); whereas a 1 SD increase in insulin sensitivity measured by the euglycaemic insulin clamp method decreased the risk for stroke/TIA (HR 0.81, 95% CI 0.68-0.96). The predictive values of fasting intact proinsulin and insulin sensitivity endured but not that of plasma insulin when adjusting for diabetes. In models adjusting for diabetes, hypertension, atrial fibrillation, electrocardiographic left ventricular hypertrophy, serum cholesterol and smoking, proinsulin remained as a significant predictor of later stroke/TIA (HR 1.22, 95% CI 1.00-1.48) whereas clamp insulin sensitivity did not (HR 0.87, 95% CI 0.71-1.07). Conclusions/interpretation Fasting intact proinsulin level and insulin sensitivity at clamp predicted subsequent fatal and non-fatal stroke/TIA, independently of diabetes in elderly men whereas fasting insulin did not.

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Diabetes and Atherosclerosis

Beckman¹,

Creager²,

Libby³

2002

JAMA

2,260

570

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Insulin, Intact and Split Proinsulin, and Coronary Artery Disease in Young Men

Abstract: This study shows that young, nondiabetic, male survivors of myocardial infarction are truly hyperinsulinemic during an OGTT and suggests a close association between proinsulin and coronary atherosclerosis.

Cited by 86 publications

References 29 publications

Proinsulin:insulin and insulin:glucose ratios as predictors of carotid plaque growth: a population-based 7 year follow-up of the Tromsø Study

Proinsulin:insulin and insulin:glucose ratios as predictors of carotid plaque growth: a population-based 7 year follow-up of the Tromsø Study

Insulin sensitivity measured by the euglycaemic insulin clamp and proinsulin levels as predictors of stroke in elderly men

Diabetes and Atherosclerosis

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