Insulin resistance is localized to skeletal but not heart muscle in type 1 diabetes.
To determine the tissue localization of insulin resistance in type 1 diabetic patients, whole body and regional glucose uptake rates were determined under euglycemic hyperinsulinemic conditions. Leg, arm, and heart glucose uptake rates were measured using positron emission tomography-derived 2-deoxy-2-[18F]-fluoro-D-glucose kinetics and the three-compartment model described by Sokoloff et al. (L. Sokoloff, M. Reivich, C. Kennedy, M.C. DesRosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897-916, 1977) in eight type 1 diabetic patients and eight matched normal subjects. Whole body glucose uptake was quantitated by the euglycemic insulin clamp technique. Whole body glucose uptake was approximately 31% lower in the diabetic patients (P < 0.01) than in the normal subjects, thus confirming the presence of whole body insulin resistance. The rate of glucose uptake was approximately 45% lower in leg muscle when measured in the femoral region (55 +/- 7 vs. 102 +/- 13 mumol.kg muscle-1.min-1, diabetic patients vs. normal subjects, P < 0.05) and approximately 27% lower in the arm muscles (66 +/- 4 vs. 90 +/- 13 mumol.kg muscle-1.min-1, respectively, P < 0.05), whereas no difference was observed in heart glucose uptake [789 +/- 80 vs. 763 +/- 58 mumol.kg muscle-1.min-1 not significant (NS)]. Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.93, P < 0.005) and arm muscles (r = 0.66, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). We conclude that insulin resistance in type 1 diabetic patients is localized to skeletal muscle, whereas heart glucose uptake is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Turku Medical Cyclotron-Positron Emission Tomography Center, University of Turku, Finland.
P
P
Nuutila
J
J
Knuuti
U
U
Ruotsalainen
V A
VA
Koivisto
E
E
Eronen
M
M
Teräs
J
J
Bergman
M
M
Haaparanta
L M
LM
Voipio-Pulkki
J
J
Viikari
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007333:Insulin Resistance; D009132:Muscles / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D012016:Reference Values; D014055:Tomography, Emission-Computed
D001786:Blood Glucose; D002096:C-Peptide; D003847:Deoxyglucose; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin