Insulin Sensitivity Measured With Euglycemic Clamp Is Independently Associated With Glomerular Filtration Rate in a Community-Based Cohort

  1. Elisabet Nerpin, MMED1,
  2. Ulf Risérus, MMED, PHD2,
  3. Erik Ingelsson, MD, PHD3,
  4. Johan Sundström, MD, PHD4,
  5. Magnus Jobs, MSC, PHD1,
  6. Anders Larsson, MD, PHD4,
  7. Samar Basu, MSC, PHD2 and
  8. Johan Ärnlöv, MD, PHD1,3
  1. 1Department of Health and Social Sciences, Högskolan Dalarna, Falun, Sweden
  2. 2Section of Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden
  3. 3Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
  4. 4Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  1. Corresponding author: Johan Ärnlöv, johan.arnlov{at}pubcare.uu.se

Abstract

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 m2) 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.

Footnotes

  • Published ahead of print at http://care.diabetesjournals.org on 28 May 2008.

    The funding sources did not play any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Received February 20, 2008.
    • Accepted May 15, 2008.
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  1. Published online before print May 28, 2008, doi: 10.2337/dc08-0369 Diabetes Care August 2008 vol. 31 no. 8 1550-1555
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