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Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Clinical Nutrition)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. (Geriatrics)ORCID iD: 0000-0003-2256-6972
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.ORCID iD: 0000-0003-2247-8454
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2008 (English)In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 8, 1550-1555 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with prespecified subgroup analyses in normoglycemic individuals with normal GFR. RESEARCH DESIGN AND METHODS: We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1,070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. RESULTS: Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19 [95% CI 0.69-1.68]; P < 0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, and 2-h glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, and smoking), and lifestyle factors (BMI, physical activity, and consumption of tea, coffee, and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR also remained statistically significant in participants with normal fasting plasma glucose, normal glucose tolerance, and normal GFR (n = 443; P < 0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR <50 ml/min per 1.73 m(2)) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58 [95% CI 0.40-0.84]; P < 0.004). CONCLUSIONS: Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, before the onset of diabetes or prediabetic glucose elevations. Further studies are needed in order to establish causality.

Place, publisher, year, edition, pages
2008. Vol. 31, no 8, 1550-1555 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-16917DOI: 10.2337/dc08-0369ISI: 000258482000017PubMedID: 18509205OAI: oai:DiVA.org:uu-16917DiVA: diva2:44688
Available from: 2008-08-15 Created: 2008-08-15 Last updated: 2017-12-08Bibliographically approved
In thesis
1. The Kidney in Different Stages of the Cardiovascular Continuum
Open this publication in new window or tab >>The Kidney in Different Stages of the Cardiovascular Continuum
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with chronic kidney disease are at higher risk of developing cardiovascular disease. The complex, interaction between the kidney and the cardiovascular system is incompletely understood, particularly at the early stages of the cardiovascular continuum.

The overall aim of this thesis was to clarify novel aspects of the interplay between the kidney and the cardiovascular system at different stages of the cardiovascular continuum; from risk factors such as insulin resistance, inflammation and oxidative stress, via sub-clinical cardiovascular damage such as endothelial dysfunction and left ventricular dysfunction, to overt cardiovascular death.

This thesis is based on two community-based cohorts of elderly, Uppsala Longitudinal Study of Adult Men (ULSAM) and Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS).

The first study, show that higher insulin sensitivity, measured with euglycemic-hyperinsulinemic clamp technique was associated to improve estimated glomerular filtration rate (eGFR) in participants with normal fasting plasma glucose, normal glucose tolerance and normal eGFR. In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function during follow-up. In the second study, eGFR was inversely associated with different inflammatory markers (C-reactive protein, interleukin-6, serum amyloid A) and positively associated with a marker of oxidative stress (urinary F2-isoprostanes). In line with this, the urinary albumin/creatinine ratio was positively associated with these inflammatory markers, and negatively associated with oxidative stress.

In study three, higher eGFR was associated with better endothelial function as assessed by the invasive forearm model. Further, in study four, higher eGFR was significantly associated with higher left ventricular systolic function (ejection fraction). The 5th study of the thesis shows that higher urinary albumin excretion rate (UAER) and lower eGFR was independently associated with an increased risk for cardiovascular mortality. Analyses of global model fit, discrimination, calibration, and reclassification suggest that UAER and eGFR add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent cardiovascular disease.

Conclusion: this thesis show that the interaction between the kidney and the cardiovascular system plays an important role in the development of cardiovascular disease and that this interplay begins at an early asymptomatic stage of the disease process.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 72 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 946
Keyword
epidemiology, chronic kidney disease, cystatin C, glomerular filtration rate, albuminuria, euglycemic hyperinsulinemic clamp, insulin sensitivity, inflammation, oxidative stress, endothelial dysfunction and left ventricular dysfunction
National Category
Cardiac and Cardiovascular Systems Urology and Nephrology Gerontology, specializing in Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-209644 (URN)978-91-554-8792-8 (ISBN)
Public defence
2013-12-05, Universitetshuset, sal IX, Biskopsgatan 3, Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-11-14 Created: 2013-10-22 Last updated: 2014-01-23

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Risérus, UlfIngelsson, ErikSundström, JohanJobs, MagnusLarsson, AndersBasu, Samar

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