title: Insulin resistance and endothelial dysfunction in type 2 diabetes patients with or without microalbuminuria.
abstract: OBJECTIVE
  To evaluate the relationship between insulin resistance and endothelial function in type 2 diabetes patients with or without microalbuminuria and to explore the pathophysiological mechanisms of the increased macrovascular risk in type 2 diabetes mellitus.
  
  
  METHODS
  Twelve type 2 diabetes patients with microalbuminuria (urinary albumin 30-300 g/mg creatinine, DM-MA) and 12 type 2 diabetes patients without microalbuminuria (urinary albumin <30 g/mg creatinine, DM-NA) were recruited, matched for their sex, age, body mass index (BMI), diabetes duration, antidiabetic therapy. Their hemoglobin (HbA1C) was less than 7.5% and the blood pressure was lower than 140/90 mmHg. None had evidence of macrovascular disease and serum cholesterol levels were normal. Twelve healthy volunteers (C) were enrolled as controls. All subjects received a hyperinsulinemic euglycemic clamp study (insulin infusion rate, 120 mU/m2/min) to assess the peripheral glucose disposal rate (GDR) in the steady state and had a high-resolution ultrasonography to measure vasodilation in the brachial artery diameter in response to reactive hyperemia (endothelium-dependent) and administration of glyceryl trinitrate (endothelium-independent). Plasma free fatty acids (FFAs), plasminogen activator inhibitor type I (PAI-1), and von Willebrand factor (vWF) were also measured.
  
  
  RESULTS
  The GDR was lower in type 2 diabetes patients with microalbuminuria (7.90 +/- 1.79 mg/kg/min) than in patients without microalbuminuria (9.46 +/- 1.59 mg/kg/min, P<0.05), and the GDR in both diabetes groups was decreased, compared with the findings from the healthy control group (13.06 +/- 1.98 mg/kg/min, P<0.01). Plasma FFAs concentration was different among the three groups (DM-MA-1008 +/- 229 mol/l, DM-NA-675 +/- 201 mol/l, P<0.01; C-364 +/- 169 mol/l, P<0.01). Endothelium-dependent vasodilation was impaired in the microalbuminuric patients (8.0 +/- 3.8%) compared with the normoalbuminuria patients (9.7 +/- 4.3%, P>0.05) and the healthy controls (14.2 +/- 5.0, P<0.05). Plasma PAI-1 and vWF levels increased in the microalbuminuric patients (61.9 +/- 18.2 ng/ml, 126.8 (76.5-212.7) %) compared with the levels in the normoalbuminuric patients (45.4 +/- 16.3 ng/ml, 87.9 (84.2-114) %) (PAI-1, P<0.05; vWF, P>0.05) and in the healthy controls (33.6 +/- 10.6 ng/ml, 67.2 (61.5-75.4) %, both P<0.01). In addition, the partial correlation analysis revealed a significant positive correlation between GDR and endothelium-dependent vasodilation (r=0.465, P<0.01, n=36), and a negative correlation between GDR and plasma FFA levels (P<0.05).
  
  
  CONCLUSIONS
  Compared with type 2 diabetes patients with normoalbuminuria, patients with microalbuminuria had more severe insulin resistance, more prominent endothelial dysfunction, and higher plasma FFA, PAI-1, and vWF levels. Therefore we speculate that insulin resistance and endothelial dysfunction may act within the metabolic syndrome to increase the cardiovasular risk in this subset of patients, and improving insulin resistance and endothelial dysfunction may reduce the morbidity and mortality from macrovascular complications in type 2 diabetes patients.
authors.affiliation: Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, 37 Guo Xue Lane, Chengdu, Sichuan 610041, PR China. yerongyu@hotmail.com
authors.forename: Yerong
authors.initials: Y
authors.lastname: Yu
authors.forename: Lixia
authors.initials: L
authors.lastname: Suo
authors.forename: Hongling
authors.initials: H
authors.lastname: Yu
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Tang
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D001916:Brachial Artery / Q000000981:diagnostic imaging; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000503:physiopathology; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D014463:Ultrasonography
chemical_list: D001786:Blood Glucose