Farhad Ghanaat | Search PubMed

PubMed2005

Growth hormone administration increases glucose production by preventing the expected decrease in glycogenolysis seen with fasting in healthy volunteers.

Twelve volunteers were fasted overnight and infused with [ 13 C]glucose (ul) to measure glucose production (GP), gluconeogenesis, and by subtraction, glycogenolysis. Glucose production, gluconeogenesis, and glycogenolysis were measured after a 3-hour baseline infusion and two 4-hour infusions. The first 4 hours of the pituitary-pancreatic clamp study (PPCS) with replacement insulin, cortisol, and glucagon was without growth hormone (GH) administration. The second 4 hours of the PPCS was with high-dose GH administration. Six fasting volunteers acted as controls over the 11-hour study period. Overnight 12-hour fasting measurements of hormones, glucose, GP, gluconeogenesis, and glycogenolysis were similar in both groups. The PPCS had no significant effect on GP (2.43 +/- 0.19 vs 2.07 +/- 0.11 mg/kg per minute, PPCS vs controls, mean +/- SEM). Glycogenolysis, as a percent of GP (43%-49%), was similar between PPCS and controls (43% +/- 3% vs 49% +/- 4%). High-dose GH for 4 hours increased GH (20.8 +/- 3.8 vs 2.0 +/- 0.9 ng/mL), blood glucose (127 +/- 28 vs 86 +/- 4 mg/dL, P < .05), GP (2.21 +/- 0.21 vs 1.81 +/- 0.12 mg/kg per minute, P < .05). The increase in GP was due to sustained glycogenolysis as compared to the observed fall in glycogenolysis seen with fasting alone (0.94 +/- 0.21 vs 0.53 +/- 0.07 mg/kg per minute, P < .05). Glycogenolysis, as a percent of GP, was significantly increased with high-dose GH (43 +/- 5% vs 29 +/- 3%, P < .05). High-dose GH had no effect on gluconeogenesis (1.26 +/- 0.15 vs 1.29 +/- 0.12 mg/kg per minute). High-dose GH prevents the fall in glycogenolysis observed with fasting alone.

Adult↗

PubMedDate not supplied

Peroxisome proliferator-activated receptor-gamma agonist increases both low-density lipoprotein cholesterol particle size and small high-density lipoprotein cholesterol in patients with type 2 diabetes independent of diabetic control.

OBJECTIVE: To ascertain whether troglitazone, independent of control of diabetes, increases low-density lipoprotein (LDL) particle size. METHODS: We administered 600 mg of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist) daily for 8 weeks to 10 patients with type 2 diabetes (8 of whom completed the study). Then troglitazone therapy was discontinued, and alternative medication for diabetic control was used for another 4 weeks. The LDL, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations and subpopulations, as well as blood glucose and hemoglobin A1c (HbA1c), were determined at weeks 0, 4, 8, and 12 and analyzed statistically. RESULTS: Small, dense LDL cholesterol is commonly seen in patients with diabetes and is thought to be associated with an increased risk for coronary artery disease. After both 4 and 8 weeks of troglitazone therapy, control of diabetes was significantly improved (mean HbA1c values at baseline, week 4, and week 8 were 8.0 +/- 0.7%, 7.4 +/- 0.5%, and 7.0 +/- 0.7%, respectively; P<0.05). HbA1c (6.5 +/- 0.6% at 12 weeks) and blood glucose levels (126 +/- 19 mg/dL at 8 weeks versus 145 +/- 9 mg/dL at 12 weeks) were not significantly different 4 weeks after troglitazone therapy was discontinued. Troglitazone treatment increased the large LDL particle at 4 and 8 weeks, a change that significantly (P<0.05) enlarged the LDL particle size (20.5 +/- 0.3 nm, 21.2 +/- 0.3 nm, and 21.3 +/- 0.2 nm at baseline, week 4, and week 8, respectively). After 8 weeks of troglitazone therapy, VLDL triglycerides were reduced (195 +/- 37 mg/dL versus 136 +/- 28 mg/dL; P<0.05) and HDL was increased (31.6 +/- 2.4 mg/dL versus 35.5 +/- 2.9 mg/dL; P<0.05). This greater HDL value was due to an increase in the small HDL particles. A decrease in the larger VLDL particles (V5 and V6) resulted in a reduction in the mean VLDL particle size (59 +/- 3 nm versus 46 +/- 2 nm; P<0.05). Despite the fact that control of diabetes remained significantly improved after troglitazone therapy was discontinued, the LDL particle size decreased to the baseline value. This change was due to a reduction in the large LDL cholesterol particle (L3). CONCLUSION: This study shows that troglitazone therapy increases LDL particle size, reduces VLDL particle size, and increases small HDL particles. These changes may lower the risk for coronary artery disease.

Blood Glucose↗