High Proinsulin Levels Precede First-Ever Stroke in a Nondiabetic Population

Lindahl, Bernt; Dinesen, Bo; Eliasson, Mats; Röder, Michael; Hallmans, Göran; Stegmayr, Birgitta

doi:10.1161/01.str.31.12.2936

Cited by 52 publications

(53 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that high proinsulin concentrations reflect beta cell dysfunction and insufficient insulin processing by pancreatic beta cells [12]. Since our surrogate parameter of insulin sensitivity, IGR, was not related to the development of carotid plaques, our results lend support to earlier findings that proinsulin is an independent pro-atherosclerotic factor [2,8,17]. A tentative mechanism explaining this could be altered haemostasis through the association of proinsulin and increased plasminogen activator inhibitor-1 activity and increased fibrinogen levels [4,[18][19][20][21].…”

Section: Discussionsupporting

confidence: 87%

“…In the Caerphilly Study, proinsulin, but not insulin, predicted incident CHD during a 14 year follow-up study of 1,181 men, although the association was attenuated when corrections were made for HDL-cholesterol and triacylglycerol [1]. Our finding of sex differences in the relationship between proinsulin and plaque progression lends support to findings of a significant association between proinsulin and stroke among women (but not among men) in a study of 94 nondiabetic patients with first-ever stroke [8].…”

Section: Discussionsupporting

confidence: 72%

“…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]. Proinsulin predicted first-ever stroke in nondiabetic individuals, independently of insulin sensitivity [8]; and in one study, treatment of diabetic patients with proinsulin appeared to increase mortality compared with treatment with insulin [9]. Population-based studies of subclinical atherosclerotic progression have mainly assessed intima-media thickness (IMT) of the common carotid artery.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…10 A relation between proinsulin levels and stroke has previously been reported in a case-control study, 11 but longitudinal studies of detailed glucometabolic predictors of stroke are lacking.…”

mentioning

confidence: 93%

Metabolic Risk Factors for Stroke and Transient Ischemic Attacks in Middle-Aged Men

Wiberg

Sundström

Ärnlöv

et al. 2006

Stroke

View full text Add to dashboard Cite

Background and Purpose-The impact of lipometabolic and glucometabolic disturbances on stroke incidence remains to be characterized in detail. We investigated relations of a comprehensive panel of baseline lipometabolic and glucometabolic variables to incident fatal and nonfatal stroke or transient ischemic attack (TIA), and stroke subtypes. Methods-A community-based prospective study of 2313 middle-aged men invited to a health survey at age 50. Results-During a follow-up of up to 32 years, 421 developed stroke or TIA. In Cox proportional hazards analyses adjusting for treatment with cardiovascular drugs at baseline, 1-standard deviation increases in body mass index, systolic and diastolic blood pressures, serum proinsulin, and lipoprotein(a) were associated with 11 to 35% increased risk for subsequent stroke/TIA. Electrocardiographic left ventricular hypertrophy and smoking were also associated with a higher risk for stroke/TIA. Essentially the same variables were related to brain infarction/TIA. Higher proportions of palmitic (16:0), palmitoleic (16:1), and oleic acid (18:1) in cholesterol esters were associated with an increased risk, whereas a higher proportion of linoleic acid (18:2 n-6) was protective against stroke/TIA. Further adjusting all models also for hypertension, diabetes, the metabolic syndrome, serum cholesterol, atrial fibrillation, cardiovascular disease, smoking, and physical activity, essentially the same pattern was observed. Conclusions-Indices of an unhealthy dietary fat intake and a high serum lipoprotein (a) level predicted fatal and nonfatal stroke/TIA independently of established risk factors in a community-based sample of middle-aged men followed for 32 years. (Stroke. 2006;37:2898-2903.)

show abstract

“…A relation between elevated fasting proinsulin and stroke has previously been reported in a case-control study [2] and in a population-based cohort study [3]. However, longitudinal studies that include a detailed characterisation of glucose and insulin metabolism predictors of stroke, are lacking.…”

Section: Introductionmentioning

confidence: 94%

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

et al. 2008

View full text Add to dashboard Cite

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.

show abstract

High Proinsulin Levels Precede First-Ever Stroke in a Nondiabetic Population

Cited by 52 publications

References 34 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

Metabolic Risk Factors for Stroke and Transient Ischemic Attacks in Middle-Aged Men

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

Contact Info

Product

Resources

About