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Insulin sensitivity measured by the euglycaemic insulin clamp and proinsulin levels as predictors of stroke in elderly men
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
2009 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, no 1, 90-6 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2009. Vol. 52, no 1, 90-6 p.
Keyword [en]
Clamp, Insulin resistance, Proinsulin, Risk factors, Stroke
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-103482DOI: 10.1007/s00125-008-1171-0ISI: 000261375400014PubMedID: 18949454OAI: oai:DiVA.org:uu-103482DiVA: diva2:218319
Available from: 2009-05-19 Created: 2009-05-19 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Risk Factors for Stroke in Adult Men: A Population-based Study
Open this publication in new window or tab >>Risk Factors for Stroke in Adult Men: A Population-based Study
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the last decades our knowledge concerning cardiovascular risk factors has grown rapidly through results from longitudinal studies. However, despite new treatment, in Western countries coronary heart disease remains the leading cause of death and stroke is still the leading cause of severe disability.

The studies reported in these papers examine the relationships between stroke/transient ischaemic attack (TIA) and a number of different factors measured on two different occasions in men born in Uppsala 1920-1924 and are epidemiological in their character.

The findings indicate that in addition to already established risk factors, indices of an unhealthy dietary fat intake and high serum lipoprotein(a) are independent predictors of stroke/TIA. Among different glucometabolic variables a low insulin sensitivity index derived from the euglycaemic insulin clamp and proinsulin carries a high predictive value for later stroke, independently of diabetes.

Moreover, cognitive test performance measured with Trail Making Test B at age 70 is a strong and independent predictor of brain infarction, indicating that the risk is already increased in the subclinical phase of milder cognitive dysfunction. Performance at a pre-stroke Trail Making Test is also of predictive value for mortality after first-ever stroke/TIA, but none of the studied pre-stroke variables or cognitive tests was found to be related to dependency after an event.

In summary these studies provide further knowledge about predictors of stroke and of mortality after first-ever stroke. They also indicate the possible importance of new markers of risk, such as the level of lipoprotein(a), profile of fatty acids in the diet, low insulin sensitivity derived from clamp investigations, level of proinsulin, and cognitive performance measured with Trail Making Tests.

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 540
Keyword
risk factor, stroke, TIA, lipoproteins, fatty acids, insulin resistance, proinsulin, clamp, cognitive function, epidemiology, Trail Making Test, stroke mortality, dependency
National Category
Geriatrics
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-120542 (URN)978-91-554-7753-0 (ISBN)
Public defence
2010-05-11, Konferenssalen, Blå Korset, Akademiska sjukhuset, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2010-04-20 Created: 2010-03-12 Last updated: 2011-06-28Bibliographically approved

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