Inflammatory Markers, Adiponectin, and Risk of Type 2 Diabetes in the Pima Indian
- Jonathan Krakoff, MD1,
- Tohru Funahashi, MD, PHD2,
- Coen D.A. Stehouwer, MD3,
- Casper G. Schalkwijk, MD3,
- Sachiyo Tanaka, BS2,
- Yuji Matsuzawa, MD, PHD2,
- Sayuko Kobes, BS1,
- P. Antonio Tataranni, MD1,
- Robert L. Hanson, MD, MPH1,
- William C. Knowler, MD, DRPH1 and
- Robert S. Lindsay, MB, PHD1
- 1National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona
- 2Department of Internal Medicine and Molecular Science, Osaka University, Osaka, Japan
- 3Department of Internal Medicine, University Hospital Vrije Universiteit, Amsterdam, the Netherlands
Abstract
OBJECTIVE—To examine the association between adiponectin, a known predictor of diabetes in Pima Indians, and markers of inflammation and endothelial function in nondiabetic subjects and to assess whether these markers predict later diabetes in a case-control study within a longitudinal health study in Pima Indians.
RESEARCH DESIGN AND METHODS—Participants with normal glucose tolerance at baseline were selected. Case subjects (who later developed type 2 diabetes), and control subjects (n = 71 pairs) were matched for BMI, age, and sex. Adiponectin, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-α, phospholipase A2 (sPLA2), soluble E-selectin (SE-selectin), soluble intracellular adhesion molecule-1, soluble vascular adhesion molecule-1, and von Willebrand factor (vWF) were measured in baseline samples.
RESULTS—Adiponectin was negatively correlated with CRP (r = −0.25, P < 0.05), IL-6 (r = −0.20, P < 0.05), sPLA2 (r = −0.22, P < 0.05), and SE-selectin (r = −0.20, P < 0.05). CRP and IL-6 did not predict diabetes. Only vWF predicted the development of diabetes (incidence rate ratio 0.67 for a 1-SD difference, 95% CI 0.41–1.00, P = 0.05), but this was not significant after adjustment for age, glucose, HbA1c, waist circumference, and fasting insulin (hazard rate ratio 0.73, 95% CI 0.46–1.16, P = 0.18).
CONCLUSIONS—Adiponectin is negatively correlated with markers of inflammation in vivo. In case and control subjects matched for BMI, with the exception of vWF, none of the inflammatory markers predicted diabetes. Adiponectin may be the link between adiposity, inflammation, and type 2 diabetes.
- ARIC, Atherosclerosis Risk in Communities
- CRP, C-reactive protein
- ELISA, enzyme-linked immunosorbent assay
- IL, interleukin
- IRR, incidence rate ratio
- OGTT, oral glucose tolerance test
- SE-selectin, soluble E-selectin
- sICAM, soluble intracellular adhesion molecule
- sPLA2, phospholipase A2
- sVCAM, soluble vascular adhesion molecule
- TNF-α, tumor necrosis factor-α
- vWF, von Willebrand factor
- WBC, white blood cell count
Footnotes
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Address correspondence and reprint requests to Jonathan Krakoff, MD, Diabetes and Arthritis Epidemiology Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 1550 East Indian School Rd., Phoenix, AZ 85014. E-mail: jkrakoff{at}mail.nih.gov.
Received for publication 18 July 2002 and accepted in revised form 5 March 2003.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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