Insulin-mediated hepatic glucose uptake is impaired in type 2 diabetes: evidence for a relationship with glycemic control.
Impaired hepatic glucose uptake (HGU) has been implicated in the development of hyperglycemia in type 2 diabetes; the relative impact of plasma glucose and insulin levels on this process remains controversial. We compared the effects of euglycemic hyperinsulinemia on HGU, skeletal muscle glucose uptake, and hepatic influx rate-constant (H-Ki) in 38 diet-treated diabetic patients and 22 nondiabetic controls, using positron emission tomography with (18)F-fluorodeoxyglucose and the insulin clamp technique. Control subjects were divided into two subgroups: one including older, heavier, insulin-resistant controls (whole-body glucose uptake, M = 21.4 +/- 5.4 micromol x min(-1) x kg(-1)) to match characteristics of diabetic patients (M = 20.4 +/- 9.9); the other including younger, leaner, insulin-sensitive controls (M = 48.2 +/- 9.9, P < 0.01). Skeletal muscle glucose uptake showed a similar group distribution as the M value. Insulin clearance rates were lower, whereas glycosylated hemoglobin and clamp plasma insulin levels were higher in diabetic patients than in controls. HGU and H-Ki were similar in the two nondiabetic subgroups and lower in diabetic patients than in controls (1.9 +/- 0.5 vs. 2.3 +/- 0.7 micromol x min(-1) x 100 ml(-1), and 0.37 +/- 0.09 vs. 0.44 +/- 0.14 ml x min(-1) x 100 ml(-1), P < or = 0.01). In the whole dataset, H-Ki was inversely related to fasting plasma glucose (correlation coefficient = -0.40, P = 0.0018). In diabetic subjects, H-Ki was reciprocally related to glycosylated hemoglobin (correlation coefficient = -0.36, P = 0.029). We conclude that insulin-mediated HGU is impaired, in type 2 diabetes, in some proportion to the degree of glycemic control.
Iozzo
Patricia
P
Turku PET Centre, Department of Nuclear Medicine and Medicine, University of Turku, FIN-20520 Turku, Finland. patrizia.iozzo@ifc.cnr.it
Hallsten
Kirsti
K
Oikonen
Vesa
V
Virtanen
Kirsi A
KA
Kemppainen
Jukka
J
Solin
Olof
O
Ferrannini
Ele
E
Knuuti
Juhani
J
Nuutila
Pirjo
P
D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D001824:Body Constitution; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000628:therapy*; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007333:Insulin Resistance; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D012044:Regression Analysis; D014055:Tomography, Emission-Computed
D001786:Blood Glucose; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D019344:Lactic Acid