title: Impaired endothelial function and insulin action in first-degree relatives of patients with type 2 diabetes mellitus.
abstract: 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 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.
authors.affiliation: Department of Biomedical Sciences, Section of Systems Biology Research, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. msonne@mfi.ku.dk
authors.forename: Mette P
authors.initials: MP
authors.lastname: Sonne
authors.forename: Lise
authors.initials: L
authors.lastname: Højbjerre
authors.forename: Amra A
authors.initials: AA
authors.lastname: Alibegovic
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.forename: Bente
authors.initials: B
authors.lastname: Stallknecht
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000328:Adult; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005190:Family; D015309:Glucose Clamp Technique; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D010991:Plethysmography; D011188:Potassium / Q000097:blood; D018709:Statistics, Nonparametric; D014655:Vascular Resistance / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D014665:Vasodilator Agents; D006710:Homocysteine; D002097:C-Reactive Protein; D002784:Cholesterol; D000241:Adenosine; D000109:Acetylcholine; D011188:Potassium