Insulin action and skeletal muscle blood flow in patients with Type 1 diabetes and microalbuminuria.
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 x kg(-1) x min(-1), 2 h at 2.0 mU x kg(-1) x 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 micromol x kg(-1) x min(-1): step 2, 30.9+/-2.7 vs 32.0+/-3.8 micromol x kg(-1) x 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 micromol x kg(-1) x 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 x 100-ml(-1) x min(-1), P=0.01) but not in the microalbuminuric group (2.4+/-0.3 vs 2.3+/-0.4 ml x 100-ml(-1) x 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.
Wiggam
M I
MI
Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, BT12 6BA, Northern Ireland, Belfast, UK.
Hunter
S J
SJ
Ennis
C N
CN
Sheridan
B
B
Atkinson
A B
AB
Bell
P M
PM
D000328:Adult; D000419:Albuminuria / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000503:physiopathology; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000503:physiopathology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin