期刊
METABOLISM-CLINICAL AND EXPERIMENTAL
卷 58, 期 1, 页码 93-101出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.metabol.2008.08.011
关键词
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资金
- Lundbeck Foundation
- NOVO Nordic Foundation
- Jacob Madsens and Olga Madsens Foundation
- Foundation of 1870
- Danish National Research Council
- Aase and Ejnar Danielsen Foundation
- European Union [LSHM-CT-2004-005272]
First-degree relatives (FDR) of patients with type 2 diabetes mellitus are at increased risk of developing type 2 diabetes mellitus. We studied if endothelial dysfunction of the resistance vessels is present and may coexist with metabolic insulin resistance in FDR. Male FDR (n = 13; 26 +/- 1 years; body mass index, 25 +/- 1 kg m(2) [mean +/- SEM]) and matched control subjects (CON) (n = 22; 25 +/- 1 years; body mass index, 24 +/- 1 kg m(2)) were studied by hyperinsulinemic (40 mU min(-1). m(-2)) isoglycemic clamp combined with brachial arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF) was Measured by venous occlusion plethysmography upon stimulation with systemic hyperinsulinemia (291 +/- 11 pmol/L, pooled data from both groups) and upon intraarterial infusion of adenosine (ADN) and acetylcholine (ACH) +/- hyperinsulinemia. Forearm blood flow response to ADN and ACH was less in FDR vs CON (P <.05); systemic hyperinsulinemia added to the FBF effect of ADN in CON (P <.05) but not in FDR. In addition, FDR demonstrated impaired FBF to hyperinsulinemia (2.1 +/- 0.2 vs 4.0 +/- 0.6 mL 100 mL(-1) min(-1)) in FDR and CON, respectively (P <.05). Both M-value (5.0 +/- 0.7 vs 7.0 +/- 0.5 mg min(-1) kg(-1)) and forearm glucose clearance (0.6 +/- 0.1 vs 1.4 +/- 0.4 mL(-1) 100 mL(-1) . min(-1)) were diminished in FDR compared with CON (all P <.05). FDR demonstrated endothelial dysfunction of the resistance vessels in addition to impaired insulin-stimulated increase in bulk flow. Moreover, FDR demonstrated whole-body insulin resistance as well as decreased basal and insulin-stimulated forearm glucose uptake. It remains to be established whether FDR also demonstrate impaired insulin-stimulated microvascular function. (C) 2009 Elsevier Inc. All rights reserved.
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