Publications (2)5.68 Total impact
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Article: Metabolic effects of Troglitazone in patients with diet-controlled type 2 diabetes.
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ABSTRACT: In order to study the mechanisms of action of Troglitazone (TGZ) in vivo in Type 2 diabetes, its effects were studied on glucose metabolism, lipolysis and very low-density lipoprotein (VLDL) apolipoprotein B100 (apoB) kinetics. A placebo-controlled, double-blind study was performed in 24 diet-treated patients randomized to receive TGZ 600 mg day(-1), TGZ 200 mg day(-1) or placebo for 8 weeks. Glucose and glycerol turnover were assessed after an overnight fast, and during sequential low-dose insulin infusions (0.01 U kg(-1) h(-1) followed by 0.015 U kg(-1) h(-1)) using 6,6-2H Glucose and 1,2,3-2H Glycerol. Very low-density lipoprotein apoB secretion was measured using l-13C-leucine, monitoring isotopic enrichment by gas chromatography-mass spectrometry. Treatment effects were analyzed by analysis of covariance, adjusting for baseline. Therapy resulted in a significant group differences in fasting plasma glucose adjusting for baseline (P=0.039). This was most evident at TGZ 600 mg daily [glucose decrease from (mean +/- SD) 9.2 +/- 2.7 to 6.6 +/- 0.9 mmol L(-1)]. HbA1c and insulin levels did not change significantly. Plasma nonesterified fatty acid (NEFA) levels decreased (P=0.045), most evidently at TGZ 200 mg daily, but glycerol was not significantly affected. Although no significant effects were observed on VLDL apoB or triglyceride concentrations, there were treatment differences in the absolute secretion rate of VLDL apoB of borderline (P=0.056) statistical significance, with a decrease observed at TGZ 600 mg daily [geometric mean, SD range, 0.94 (0.41-2.15) to 0.40 (0.14-1.13 mg kg(-1) h(-1))]. Very low-density lipoprotein apoB fractional secretion rate and pool size were unaffected. The VLDL triglyceride: apoB molar ratio differed between treatment groups (P=0.013), being higher in the TGZ 600 mg group [5714 (4128-7741) to 8092 (5669-11552)]. Neither glucose nor glycerol rates of appearance were significantly altered by TGZ and nor did TGZ affect their suppression by insulin. The PPARgamma agonist, troglitazone, decreases fasting glucose and NEFA levels in diet-treated Type 2 diabetes. It may also decrease VLDL particle secretion. These effects would be considered beneficial. The biological importance of the increase in VLDL-triglyceride enrichment warrants further study.European Journal of Clinical Investigation 02/2004; 34(1):29-36. · 3.02 Impact Factor -
Article: Effects of growth hormone treatment on very-low density lipoprotein apolipoprotein B100 turnover in adult hypopituitarism.
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ABSTRACT: Adult hypopituitarism is associated with hyperlipidemia, mainly due to an increase of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels. Recent studies have shown that such patients exhibit increased hepatic secretion of VLDL apolipoprotein B100 (VLDL apo B100). To examine the effects of growth hormone (GH) replacement on VLDL apo B100 turnover, 13 GH-deficient hypopituitary patients (8 women and 5 men; aged 47 +/- 3 years, mean +/- SEM; body mass index [BMI], 30 +/- 2 kg/m2) entered a double-blind placebo-controlled study for 6 months (GH 0.125 IU/kg/wk for 4 weeks, and then 0.25 IU/kg/wk). GH was subsequently used in all patients for a further 6 months. A 6-hour [1-13C] leucine infusion was administered at baseline and at 6 months. The secretion rate of VLDL apo B100 was derived by kinetic analysis following quantitation of isotopic enrichment by gas chromatography/mass spectrometry. The GH-treated group (6 patients) demonstrated a similar fractional secretion rate (FSR) for VLDL apo B100 at 0 and 6 months. The pool size and absolute secretion rate (ASR) also were unaffected significantly by GH therapy. No significant changes were observed in the placebo group (7 patients). Treatment with GH for 6 months caused an increase in the high-density lipoprotein (HDL) cholesterol concentration (13 patients, 1.27 +/- 0.13 v 1.16 +/- 0.10 mmol/L, respectively, P = .05), whereas total cholesterol and triglyceride concentrations did not change. Nonesterified fatty acids (NEFAs) increased during GH therapy (471 +/- 43 micromol/L at 6 months v 349 +/- 49 micromol/L at baseline, P < .0005). The data suggest that GH does not affect VLDL apo B100 turnover in a significant way.Metabolism 05/2000; 49(5):563-6. · 2.66 Impact Factor
