title: Pioglitazone improvement of fasting and postprandial hyperglycaemia in Mexican-American patients with Type 2 diabetes: a double tracer OGTT study.
abstract: 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.
authors.affiliation: Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Glass
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cusi
authors.forename: Rachele
authors.initials: R
authors.lastname: Berria
authors.forename: Roberta
authors.initials: R
authors.lastname: Petz
authors.forename: Eugenio
authors.initials: E
authors.lastname: Cersosimo
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Defronzo
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D045162:Thiazolidinediones; D014316:Tritium; D005947:Glucose; D000077205:Pioglitazone
references.citation: Diabetes Care. 2006 Oct;29(10):2275-81
references.pmid: 17003306
references.citation: Diabetes. 2002 Mar;51(3):797-802
references.pmid: 11872682
references.citation: J Clin Invest. 1995 May;95(5):2232-8
references.pmid: 7738188
references.citation: Ann Intern Med. 1998 Feb 1;128(3):176-85
references.pmid: 9454525
references.citation: Diabetes. 1985 Jun;34(6):580-8
references.pmid: 3891471
references.citation: J Clin Endocrinol Metab. 2004 Sep;89(9):4312-9
references.pmid: 15356026
references.citation: Diabetologia. 2004 Jan;47(1):31-9
references.pmid: 14666364
references.citation: Metabolism. 1988 Jan;37(1):79-85
references.pmid: 3275860
references.citation: Am J Physiol. 1992 Aug;263(2 Pt 1):E400-15
references.pmid: 1514623
references.citation: Diabetes. 1988 Jun;37(6):667-87
references.pmid: 3289989
references.citation: Horm Metab Res. 1986 Sep;18(9):587-9
references.pmid: 3781478
references.citation: Diabetologia. 2001 Dec;44(12):2210-9
references.pmid: 11793023
references.citation: Diabetes. 2002 Feb;51(2):443-8
references.pmid: 11812753
references.citation: Ann Intern Med. 1999 Aug 17;131(4):281-303
references.pmid: 10454950
references.citation: Diabetes. 1992 Dec;41(12):1575-86
references.pmid: 1446799
references.citation: J Clin Invest. 1989 Jul;84(1):205-13
references.pmid: 2661589
references.citation: J Clin Endocrinol Metab. 2004 Dec;89(12):6048-53
references.pmid: 15579757
references.citation: Diabetes Care. 2001 Apr;24(4):710-9
references.pmid: 11315836
references.citation: Diabetes Care. 2002 Mar;25(3):517-23
references.pmid: 11874940
references.citation: Diabetes Care. 1999 Sep;22(9):1462-70
references.pmid: 10480510
references.citation: Diabetologia. 1977 May;13(3):201-6
references.pmid: 873087
references.citation: Clin Pharmacol Ther. 2007 Feb;81(2):205-12
references.pmid: 17259945