12765945

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6

The effect of pioglitazone on splanchnic glucose uptake (SGU), endogenous glucose production (EGP), and hepatic fat content was studied in 14 type 2 diabetic patients (age 50 +/- 2 years, BMI 29.4 +/- 1.1 kg/m(2), HbA(1c) 7.8 +/- 0.4%). Hepatic fat content (magnetic resonance spectroscopy) and SGU (oral glucose load- insulin clamp technique) were quantitated before and after pioglitazone (45 mg/day) therapy for 16 weeks. Subjects received a 7-h euglycemic insulin (100 mU. m(-2). min(-1)) clamp, and a 75-g oral glucose load was ingested 3 h after starting the insulin clamp. Following glucose ingestion, the steady-state glucose infusion rate during the insulin clamp was decreased appropriately to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in glucose infusion rate during the 4 h after glucose ingestion from the ingested glucose load. 3-[(3)H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of EGP and glucose disappearance (R(d)). Pioglitazone reduced fasting plasma glucose (10.0 +/- 0.7 to 7.5 +/- 0.6 mmol/l, P < 0.001) and HbA(1c) (7.8 +/- 0.4 to 6.7 +/- 0.3%, P < 0.001) despite increased body weight (83 +/- 3 to 86 +/- 3 kg, P < 0.001). During the 3-h insulin clamp period before glucose ingestion, pioglitazone improved R(d) (6.9 +/- 0.5 vs. 5.2 +/- 0.5 mg. kg(-1). min(- 1), P < 0.001) and insulin-mediated suppression of EGP (0.21 +/- 0.04 to 0.06 +/- 0.02 mg. kg(-1). min(-1), P < 0.01). Following pioglitazone treatment, hepatic fat content decreased from 19.6 +/- 3.6 to 10.4 +/- 2.1%, (P < 0.005), and SGU increased from 33.0 +/- 2.8 to 46.2 +/- 5.1% (P < 0.005). Pioglitazone treatment in type 2 diabetes 1) decreases hepatic fat content and improves insulin-mediated suppression of EGP and 2) augments splanchnic and peripheral tissue glucose uptake. Improved splanchnic/peripheral glucose uptake and enhanced suppression of EGP contribute to the improvement in glycemic control in patients with type 2 diabetes.

eng

AIM

MEDLINE

0012-1797

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NLM

1364-70

pubmed-meshheading:12765945-Adult, pubmed-meshheading:12765945-Alanine Transaminase, pubmed-meshheading:12765945-Aspartate Aminotransferases, pubmed-meshheading:12765945-Blood Glucose, pubmed-meshheading:12765945-Body Mass Index, pubmed-meshheading:12765945-Cholesterol, pubmed-meshheading:12765945-Cholesterol, LDL, pubmed-meshheading:12765945-Continental Population Groups, pubmed-meshheading:12765945-Diabetes Mellitus, Type 2, pubmed-meshheading:12765945-Fatty Acids, Nonesterified, pubmed-meshheading:12765945-Female, pubmed-meshheading:12765945-Glucose Clamp Technique, pubmed-meshheading:12765945-Glucose Tolerance Test, pubmed-meshheading:12765945-Hemoglobin A, Glycosylated, pubmed-meshheading:12765945-Humans, pubmed-meshheading:12765945-Hypoglycemic Agents, pubmed-meshheading:12765945-Insulin, pubmed-meshheading:12765945-Kinetics, pubmed-meshheading:12765945-Lipid Metabolism, pubmed-meshheading:12765945-Male, pubmed-meshheading:12765945-Middle Aged, pubmed-meshheading:12765945-Splanchnic Circulation, pubmed-meshheading:12765945-Texas, pubmed-meshheading:12765945-Thiazoles, pubmed-meshheading:12765945-Thiazolidinediones, pubmed-meshheading:12765945-Triglycerides

Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't