Insulin action and skeletal muscle blood flow in patients with Type 1 diabetes and microalbuminuria

• Published in: Diabetes research and clinical practice 2001-08, Vol.53 (2), p.73-83
• Main Authors: Wiggam, M.I, Hunter, S.J, Ennis, C.N, Sheridan, B, Atkinson, A.B, Bell, P.M
• Format: Article
• Language: English
• Subjects: Adult; Albuminuria - physiopathology; Biological and medical sciences; Blood Glucose - metabolism; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 1 - urine; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - physiopathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glucose - metabolism; Glucose Clamp Technique; Glycated Hemoglobin A - analysis; Humans; Hyperinsulinism - blood; Hyperinsulinism - physiopathology; Infusions, Intravenous; Insulin - administration & dosage; Insulin - blood; Insulin - pharmacology; Insulin resistance; Kinetics; Liver - metabolism; Male; Medical sciences; Microalbuminuria; Muscle, Skeletal - blood supply; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Type 1 diabetes; Venous occlusion plethysmography
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/S0168-8227(01)00244-3

Our objective was to determine whether Type 1 diabetic patients with microalbuminuria are less sensitive to the effects of insulin on glucose metabolism and skeletal muscle blood flow, compared to those with normal albumin excretion, after careful matching for confounding variables. We recruited 10 normotensive Type 1 diabetic patients with microalbuminuria and 11 with normoalbuminuria matched for age, sex, body mass index, duration of diabetes and HbA 1c. Peripheral and hepatic insulin action was assessed using a two-step euglycaemic hyperinsulinaemic clamp (2 h at 0.4 mU kg −1 min −1, 2 h at 2.0 mU kg −1 min −1) combined with isotope dilution methodology. Skeletal muscle blood flow was determined by venous occlusion plethysmography. During the clamps, glucose infusion rates required to maintain euglycaemia were similar in the microalbuminuric subjects and controls (step 1, 8.2±1.4 (SE) vs 9.2±1.3 μmol kg −1 min −1: step 2, 30.9±2.7 vs 32.0±3.8 μmol kg −1 min −1), as was hepatic glucose production basally and at steady state in step 1. In step 2, hepatic glucose production was lower in the microalbuminuric group (2.9±0.9 vs 6.4±0.7 μmol kg −1 min −1, P=0.005). During step 2, skeletal muscle blood flow increased significantly above baseline in the normoalbuminuric group (4.1±0.5 vs 3.2±0.4 ml 100-ml −1 min −1, P=0.01) but not in the microalbuminuric group (2.4±0.3 vs 2.3±0.4 ml 100-ml −1 min −1). In conclusion, microalbuminuria in Type 1 diabetes was found to be associated with impairment of insulin-mediated skeletal muscle blood flow, but not with insulin resistance.