Pioglitazone improvement of fasting and postprandial hyperglycaemia in Mexican-American patients with Type 2 diabetes: a double tracer OGTT study.
OBJECTIVE
By using tracer techniques, we explored the metabolic mechanisms by which pioglitazone treatment for 16 weeks improves oral glucose tolerance in patients with type 2 diabetes when compared to subjects without diabetes.


METHODS
In all subjects, before and after treatment, we measured rates of tissue glucose clearance (MCR), oral glucose appearance (RaO) and endogenous glucose production (EGP) during a (4-h) double tracer oral glucose tolerance test (OGTT) (1-(14)C-glucose orally and 3-(3)H-glucose intravenously). Basal hepatic insulin resistance index (HepIR) was calculated as EGPxFPI. beta-cell function was assessed as the incremental ratio of insulin to glucose (DeltaI/DeltaG) during the OGTT.


RESULTS
Pioglitazone decreased fasting plasma glucose concentration (10.5 +/- 0.7 to 7.8 +/- 0.6 mM, P < 0.0003) and HbA1c (9.7 +/- 0.7 to 7.5 +/- 0.5%, P < 0.003) despite increased body weight and no change in plasma insulin concentrations. This was determined by a decrease both in fasting EGP (20.0 +/- 1.1 to 17.3 +/- 0.8 micromol/kg(ffm) min, P < 0.005) and HepIR (from 8194 declined by 49% to 3989, P < 0.002). During the OGTT, total glucose Ra during the 0- to 120-min time period following glucose ingestion decreased significantly because of a reduction in EGP. During the 0- to 240-min time period, pioglitazone caused only a modest increase in MCR (P < 0.07) but markedly increased DeltaI/DeltaG (P = 0.003). The decrease in 2h-postprandial hyperglycaemia correlated closely with the increase in DeltaI/DeltaG (r = -0.76, P = 0.004) and tissue clearance (r = -0.74, P = 0.006) and with the decrease in HepIR (r = 0.62, P = 0.006).


CONCLUSIONS
In diabetic subjects with poor glycaemic control, pioglitazone improves oral glucose tolerance mainly by enhancing the suppression of EGP and improving beta-cell function.
Glass
Leonard C
LC
Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
Cusi
Kenneth
K
Berria
Rachele
R
Petz
Roberta
R
Cersosimo
Eugenio
E
Defronzo
Ralph A
RA
Gastaldelli
Amalia
A
D001786:Blood Glucose / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000517:prevention & control*; D005215:Fasting / Q000097:blood; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D017058:Mexican Americans; D008875:Middle Aged; D000077205:Pioglitazone; D013781:Texas; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014316:Tritium / Q000493:pharmacokinetics
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D045162:Thiazolidinediones; D014316:Tritium; D005947:Glucose; D000077205:Pioglitazone
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