Hyperinsulinemia Predicts Coronary Heart Disease Risk in Healthy Middle-aged Men

Pyörälä, Marja; Miettinen, Heikki; Laakso, Markku; Pyörälà, Kalevi

doi:10.1161/01.cir.98.5.398

Cited by 326 publications

(151 citation statements)

References 47 publications

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“…Two previous cohort studies of whites showed a significant independent relationship between serum insulin levels and risks of total [19] and ischaemic [20] strokes among non-diabetic individuals, while other studies in whites [20,21] did not show an independent relationship.…”

Section: Discussionmentioning

confidence: 64%

Type 2 diabetes and risk of non-embolic ischaemic stroke in Japanese men and women

et al. 2004

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Aims/hypothesis. The aim of this study was to examine the relationship between type 2 diabetes and risk of ischaemic stroke in Asian populations. Methods. We conducted a 17-year prospective cohort study in 10,582 Japanese individuals (4287 men and 6295 women) aged 40-69 years living in five communities in Japan. All subjects were free of stroke and CHD at baseline. Diabetes was defined as a fasting glucose level of ≥7.0 mmol/l, a non-fasting glucose of ≥11.1 mmol/l, or receiving medication for diabetes.Results. The risk of non-embolic ischaemic stroke was approximately two-fold higher in diabetic subjects than in subjects with normal glucose levels. The multivariate relative risk after adjustment for age, community, hypertensive status, BMI, triceps and subscapular skinfold thickness (TSF and SSF), and other known cardiovascular risk factors was 1.8 (95% CI 1.0-3.2) for men and 2.2 (1.2-4.0) for women. This excess risk was primarily observed among non-hypertensive subjects and individuals with higher values for measures of adiposity (BMI, TSF and SSF values above the median), particularly those with higher values for SSF. The association between non-embolic ischaemic stroke and glucose abnormality was particularly strong among nonhypertensive subjects with higher SSF values: the multivariate relative risk was 1.9 (1.0-3.7) for borderline diabetes and 4.9 (2.5-9.5) for diabetes. Conclusions/interpretation. In this cohort, type 2 diabetes was a significant risk factor for non-embolic ischaemic stroke, particularly in non-hypertensive and non-lean individuals. Due to the nationwide decrease in blood pressure and increase in mean BMI among the Japanese population, with current levels approaching those observed in Western countries, the impact of glucose abnormalities on risk of ischaemic stroke represents a forthcoming public health issue in Japan.

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Section: Discussionmentioning

confidence: 64%

Type 2 diabetes and risk of non-embolic ischaemic stroke in Japanese men and women

et al. 2004

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“…Obesity is often accompanied by disturbances in blood pressure (BP) or lipid metabolism related to insulin resistance. Insulin resistance or hyperinsulinemia has been associated with coronary artery disease, suggesting that previously unmeasured factors may be involved in the link between insulin resistance or hyperinsulinemia, and atherosclerosis (3,4).…”

Section: Introductionmentioning

confidence: 99%

Decreased plasma adiponectin concentrations in nondiabetic women with elevated homeostasis model assessment ratios

Matsubara

Katayose

Maruoka

2003

European Journal of Endocrinology

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Objective: Whether the adipocyte-derived protein adiponectin is associated with insulin resistance independently of the effects of adiposity and the diabetic state is an important question. We explored, in a cross-sectional study of 486 Japanese nondiabetic women, the relationship between the calculated insulin resistance (homeostasis model assessment ratio (HOMA-R)) and adiponectin levels determined using a validated sandwich ELISA. Design and methods: All participants were stratified into tertiles for HOMA-R (, , 1.5, 1.5 # , , 3.0, 3.0 # , ) and the differences across tertiles of continuous variables were tested with ANOVA. Two-way ANOVA was used to determine possible relationships for plasma adiponectin between tertiles of HOMA-R and several stratified parameters. Multiple regression analyses were performed with HOMA-R or fasting serum insulin as dependent variable, and diastolic blood pressure (BP), body mass index (BMI), serum triglyceride (TG), leptin and adiponectin as independent determinants. Results: Mean plasma adiponectin in the high HOMA-R group decreased compared with that in the low HOMA-R group both before (mean^S.E.M. 6:2^0:6 vs 9:2^0:3 mg=ml; P , 0:001) and after adjustment for body fat mass (BFM) as kg or percent ð0:31^0:04 vs 0:69^0:03; 0:18^0:02 vs 0:340 :01; both P , 0:001). HOMA-R was inversely associated with adiponectin levels both before ðr ¼ 20:37; P , 0:001Þ and after adjustment for BFM ðr ¼ 20:49; 20.46, both P , 0:001Þ: After covariate adjustment for age, diastolic BP, BMI and serum TG, HOMA-R retained a significant correlation with adiponectin/BFM (kg). Both adiponectin and leptin were the significant determinants of HOMA-R or fasting insulin in multiple regression models. Conclusions: Adiponectin was inversely associated with insulin resistance in nondiabetic subjects, independently from age, BP, adiposity and serum lipids. Because adiponectin is thought to have an antiatherogenic action, the presence of hypoadiponectinemia may predispose subjects to atherosclerosis, and may progress the atherogenesis in insulin resistance.

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“…However, a comparable relationship was observed between fasting insulin concentration and stroke incidence in the Helsinki Policemen's Study [28]. In that study, a significant trend for an association of fasting insulin concentrations with age-adjusted stroke incidence was described, but stroke incidence appeared to be slightly higher in the second quintile (almost 8%) than in the first (less than 4%) or the third (less than 6%) ones.…”

Section: Discussionmentioning

confidence: 54%

Fasting insulin concentrations and coronary heart disease incidence in France and Northern Ireland: The PRIME study

Bataille

Fougère

Troughton

et al. 2006

International Journal of Cardiology

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Background: Reports about the relationships between insulin concentrations and CHD risk are controversial. The objective of this survey was to study the association between insulin levels and CHD risk in middle-aged male participants of the PRIME Study after 5 years of follow-up. Methods: Our study adopted a nested case-control design including 294 cases of CHD and 536 controls randomly selected among healthy participants from the PRIME cohort. Data were obtained by questionnaires (medical history, lifestyle), standardised clinical measurements (blood pressure, anthropometric measurements), and a blood sample was obtained for biological measurements. Odds-Ratios for associations of four ordered classes of insulin concentration with CHD risk after adjustment for confounding factors were estimated using conditional logistic regression. Results: In Belfast, a significant trend ( p < 0.03) was observed between insulin classes and CHD risk in bivariate analyses, but this association lost its significance after multiple adjustments. In the French centres, a high risk of CHD .85], p < 0.0001) was observed only for the second class of insulin concentration (6.5 to 9.9 mIU/l), compared with the reference class (< 6.5 mIU/l). After multiple adjustments, this association remained highly significant (OR = 2.92 [1. 44 -5.92], p < 0.005). Conclusions: In Belfast (high-risk population), a significant trend was observed between insulin concentration classes and CHD risk but hyperinsulinaemia lost its association with CHD risk in multivariate analyses. In the French centres (lower risk population), slightly increased insulin concentrations were associated with a high risk of CHD, independently of cardiovascular risk factors and other features of the metabolic syndrome, but very high insulin concentrations were not. D

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Hyperinsulinemia Predicts Coronary Heart Disease Risk in Healthy Middle-aged Men

Cited by 326 publications

References 47 publications

Type 2 diabetes and risk of non-embolic ischaemic stroke in Japanese men and women

Type 2 diabetes and risk of non-embolic ischaemic stroke in Japanese men and women

Decreased plasma adiponectin concentrations in nondiabetic women with elevated homeostasis model assessment ratios

Fasting insulin concentrations and coronary heart disease incidence in France and Northern Ireland: The PRIME study

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