Circulating Adiponectin Levels Are Reduced in Nonobese but Insulin-Resistant First-Degree Relatives of Type 2 Diabetic Patients
- F. Pellmé1,
- U. Smith1,
- T. Funahashi2,
- Y. Matsuzawa2,
- H. Brekke3,
- O. Wiklund4,
- M.-R. Taskinen5 and
- P.-A. Jansson1
- 1The Lundberg Laboratory for Diabetes Research, the Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
- 2Department of Internal Medicine and Molecular Science, Osaka University, Osaka, Japan
- 3Department of Clinical Nutrition, the Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
- 4Wallenberg Laboratory for Cardiovascular Research, the Sahlgrenska Academy at Göteborg University, Göteborg, Sweden
- 5Department of Medicine, University of Helsinki, Helsinki, Finland
Abstract
Adiponectin, one of the most abundant gene transcript proteins in human fat cells, has been shown to improve insulin action and is also suggested to exert antiatherogenic effects. We measured circulating adiponectin levels and risk factors for atherosclerosis in 45 healthy first-degree relatives of type 2 diabetic subjects (FDR) as well as 40 healthy control subjects (CON) without a known family history of diabetes. Insulin sensitivity (Si) was studied with the minimal model, and measurements of adiponectin, metabolic variables, inflammatory markers, and endothelial injury markers, as well as lipoprotein concentrations, were performed. FDR were insulin resistant (3.3 ± 2.4 vs. 4.5 ± 2.6 × 10−4 × min−1 per μU/ml [mean ± SD], P < 0.01), and their circulating plasma adiponectin levels (6.6 ± 1.8 vs. 8.1 ± 3.0 μg/ml, P < 0.03) were decreased. After adjustments for age in FDR, adiponectin levels were negatively correlated with fasting proinsulin (r −0.64, P < 0.001), plasminogen activator inhibitor (PAI)-1 activity (r −0.56, P < 0.001), fasting insulin (r −0.55, P < 0.001), and acute insulin response (r −0.40, P < 0.05); they were positively related to HDL cholesterol (r 0.48, P < 0.01) and Si (r 0.41, P < 0.01). Furthermore, when adjusted for age, waist, and Si, adiponectin was associated with HDL cholesterol and proinsulin, which explained 51% of the variation in adiponectin in multiple regression analyses in that group. In conclusion, circulating plasma adiponectin levels were decreased in nonobese but insulin-resistant FDR and, in addition, related to several facets of the insulin resistance syndrome (IRS). Thus, hypoadiponectinemia may be an important component of the association between cardiovascular disease and IRS.
Footnotes
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Address correspondence and reprint requests to Dr. Per-Anders Jansson, The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital S–413 45 Göteborg, Sweden. E-mail: per-anders.jansson{at}medic.gu.se.
Received for publication 7 August 2002 and accepted in revised form 21 January 2003
CON, control subjects; CRP, C-reactive protein; CVD, cardiovascular disease; FDR, first-degree relatives of type 2 diabetic subjects; IRS, insulin resistance syndrome; OGTT, oral glucose tolerance test; PAI, plasminogen activator inhibitor; PPAR, peroxisome proliferator–activated receptor; Si, insulin sensitivity index; TNF, tumor necrosis factor.
- DIABETES
