176
Effect of the Prostaglandin El Analog Enisoproston Glucose and Lipid Metabolism in Patients with Type II Diabetes Mellitus
Summary Short-term studies have suggested that analogs of prostaglandin E may have favorable effects on the carbohydrate and lipid metabolism in patients with type II diabetes mellitus. The present study was undertaken to investigate the long-term effects of a prostaglandin El analog on the regulation of glyeemic control and plasma lipids. Twenty patients with type II diabetes received enisoprost, 300 mcg/day, for three months. Fasting serum glucose, glycosylated hemoglobin, insulin and C-peptide levels as well as triglyceride, total cholesterol, high density lipoprotein cholesterol and its subfractions, apolipoproteins B and AI and post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. During the first month, enisoprost treatment caused significant decreases in plasma glucose (baseline = 8.72 ±0.39 mmol/L, 4 week = 7.78 + 0.5 mmol/L, change = — 0.94 + 0.28 mmol/L, p < 0.01) and total cholesterol (baseline = 5.30+ 0.23 mmol/L, 4 week = 5.01+0.26 mmol/L, change = - 0.28 + 0.06 mmol/L, p < 0.05). The decrease in cholesterol level was due to a reduction in high density lipoprotein, specifically in high density lipop r o t e i n fraction (baseline = 1.29 ± 0.1 mmol/L, 4
Introduction Short-term studies demonstrated that prostaglandins of E (PGE) series lower blood pressure (BP) (Horrobin 1988), inhibit insulin secretion (Horrobin 1988) and alter plasma lipid levels {Davis, Proby, Strong, Thompson, Massey, Scott and Bloom 1989; Reaven, Swislocki, Jeng, Hollenbeck, Schwartz and Chen 1988) in man. They may also be the mediators of the decrease in plasma triglyceride and the rise in plasma glucose seen during supplementation of omega-3 fatty acids (Kasim, Stern, Khilnani, McLin, Baciorowski and Jen 1988). To investigate their long-term effects on the regulation of glycemic control and plasma lipids, an analog of PGE1 (enisoprost), 300 mcg/day for three months, was administered orally to patients with type II diabetes mellitus. During the first month, enisoprost treatment was associated with sig-
Horm.metab.Res.24(1992) 176-180 © Georg Thieme Verlag Stuttgart • New York
week =1.12 + 0.08 mmol/L, change = - 0 . 0 1 8 ±0.04 mmol/L, p < 0.05 for the former and baseline = 0.40 + 0.06 mmol/L, 4 week = 0.27+ 0.03 mmol/L, change = - 0 . 1 2 + 0.03 mmol/L, p < 0.05 for the latter): All of these values returned to the pretreatment levels despite continuation of enisoprost. Glycosylated hemoglobin, insulin, C-peptide, triglyceride, low density lipoprotein-cholesterol, apoprotein B and AI concentrations and post-heparin lipoprotein lipase or hepatic triglyceride activities did not change significantly. In summary, enisoprost treatment reduced the plasma glucose, cholesterol and high density lipoprotein cholesterol levels in type II diabetic patients. However, these effects were not sustained during long-term treatment. Therefore, further studies are needed to determine the long-term metabolic effects of various prostaglandin analogs. Key words Prostaglandin El — Type II Diabetes Mellitus — Lipids — LipoproteinLipase — Hepatic Lipase
nificant decreases in the fasting serum glucose total cholesterol, and high density lipoprotein (HDL)-cholesterol, specifically in the HDL2 subfraction. However, these values returned to the pretreatment levels despite continuation of the therapy. Blood pressure, glycosylated hemoglobin concentration, plasma insulin, C-peptide and triglyceride levels were not affected. Concentrations of plasma low density lipoprotein (LDL)-cholesterol, apoproteins (apo) B and AI and activities of post-heparin lipolytic enzymes did not change either. The findings of the present study demonstrate that the effects of PGE1 on carbohydrate and lipid metabolism are transient and very different than those of omega-3 fatty acids.
Received: 31 Dec. 1990
Accepted: 23 July 1991 after revision
Downloaded by: Universite Laval. Copyrighted material.
S. E. Kasim, M. Moran, Sheila Khilnani, Marilyn A. West and K.-L. Catherine Jen Veterans Administration Medical Center, Allen Park, Wayne State University, Detroit, Michigan Clinical Research, G. D. Searle Co., Skokie, Illinois, U. S. A.
Prostaglandins, Blood Pressure, Plasma Glucose and Lipids
Horm. metab. Res. 24 (1992)
\11
Table 1 Changes in clinical parameters, glycemic control and fasting insulin and C-peptide levels during Enisoprost treatment.
Wt (kg) BMI (kg/m2) SBP (mmHg) DBP (mmHg) FSG (mmol/L) HgbA 1 (%) Insulin (pmol/L) C-peptide (pmol/L)
n
Pretreatment
4 wk
8wk
12 wk
Wash-out
20 20 12 12 16 13 13 16
92.5 ±4.2 29.3±1.2 143 + 5 84±3 8.72 + 0.39 7.7 + 0.6 165 ±29 960 ±99
92.7 ±4.4 29.3 ±1.3 137 ± 4 81 ± 3 7.78 ±0.5* 8.2 ±0.6 172 ±22 1092 ±99
92.2 ±4.1 29.2 ±1.2 140 ± 5 81 ± 3 8.56 ±0.61 7.8 ±0.4 165 ±22 1059 ±99
91.6 ±3.9 29.0 ±1.2 139 ± 5 83±3 8.56 ±0.83 7.9 ±0.4 172 ±22 1159 ±132
91.6 ±3.8 29.0 ±1.2 136±4 81 ± 3 9.44 ±0.89 8.0 ±0.6 201 ± 22 1225 ±132
Mean±SEM, Wt = weight, SBP = systolic blood pressure, DBP = diastolic blood pressure, FSG = fasting serum glucose, *P
Effect of the Prostaglandin El Analog Enisoproston Glucose and Lipid Metabolism in Patients with Type II Diabetes Mellitus
Summary Short-term studies have suggested that analogs of prostaglandin E may have favorable effects on the carbohydrate and lipid metabolism in patients with type II diabetes mellitus. The present study was undertaken to investigate the long-term effects of a prostaglandin El analog on the regulation of glyeemic control and plasma lipids. Twenty patients with type II diabetes received enisoprost, 300 mcg/day, for three months. Fasting serum glucose, glycosylated hemoglobin, insulin and C-peptide levels as well as triglyceride, total cholesterol, high density lipoprotein cholesterol and its subfractions, apolipoproteins B and AI and post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. During the first month, enisoprost treatment caused significant decreases in plasma glucose (baseline = 8.72 ±0.39 mmol/L, 4 week = 7.78 + 0.5 mmol/L, change = — 0.94 + 0.28 mmol/L, p < 0.01) and total cholesterol (baseline = 5.30+ 0.23 mmol/L, 4 week = 5.01+0.26 mmol/L, change = - 0.28 + 0.06 mmol/L, p < 0.05). The decrease in cholesterol level was due to a reduction in high density lipoprotein, specifically in high density lipop r o t e i n fraction (baseline = 1.29 ± 0.1 mmol/L, 4
Introduction Short-term studies demonstrated that prostaglandins of E (PGE) series lower blood pressure (BP) (Horrobin 1988), inhibit insulin secretion (Horrobin 1988) and alter plasma lipid levels {Davis, Proby, Strong, Thompson, Massey, Scott and Bloom 1989; Reaven, Swislocki, Jeng, Hollenbeck, Schwartz and Chen 1988) in man. They may also be the mediators of the decrease in plasma triglyceride and the rise in plasma glucose seen during supplementation of omega-3 fatty acids (Kasim, Stern, Khilnani, McLin, Baciorowski and Jen 1988). To investigate their long-term effects on the regulation of glycemic control and plasma lipids, an analog of PGE1 (enisoprost), 300 mcg/day for three months, was administered orally to patients with type II diabetes mellitus. During the first month, enisoprost treatment was associated with sig-
Horm.metab.Res.24(1992) 176-180 © Georg Thieme Verlag Stuttgart • New York
week =1.12 + 0.08 mmol/L, change = - 0 . 0 1 8 ±0.04 mmol/L, p < 0.05 for the former and baseline = 0.40 + 0.06 mmol/L, 4 week = 0.27+ 0.03 mmol/L, change = - 0 . 1 2 + 0.03 mmol/L, p < 0.05 for the latter): All of these values returned to the pretreatment levels despite continuation of enisoprost. Glycosylated hemoglobin, insulin, C-peptide, triglyceride, low density lipoprotein-cholesterol, apoprotein B and AI concentrations and post-heparin lipoprotein lipase or hepatic triglyceride activities did not change significantly. In summary, enisoprost treatment reduced the plasma glucose, cholesterol and high density lipoprotein cholesterol levels in type II diabetic patients. However, these effects were not sustained during long-term treatment. Therefore, further studies are needed to determine the long-term metabolic effects of various prostaglandin analogs. Key words Prostaglandin El — Type II Diabetes Mellitus — Lipids — LipoproteinLipase — Hepatic Lipase
nificant decreases in the fasting serum glucose total cholesterol, and high density lipoprotein (HDL)-cholesterol, specifically in the HDL2 subfraction. However, these values returned to the pretreatment levels despite continuation of the therapy. Blood pressure, glycosylated hemoglobin concentration, plasma insulin, C-peptide and triglyceride levels were not affected. Concentrations of plasma low density lipoprotein (LDL)-cholesterol, apoproteins (apo) B and AI and activities of post-heparin lipolytic enzymes did not change either. The findings of the present study demonstrate that the effects of PGE1 on carbohydrate and lipid metabolism are transient and very different than those of omega-3 fatty acids.
Received: 31 Dec. 1990
Accepted: 23 July 1991 after revision
Downloaded by: Universite Laval. Copyrighted material.
S. E. Kasim, M. Moran, Sheila Khilnani, Marilyn A. West and K.-L. Catherine Jen Veterans Administration Medical Center, Allen Park, Wayne State University, Detroit, Michigan Clinical Research, G. D. Searle Co., Skokie, Illinois, U. S. A.
Prostaglandins, Blood Pressure, Plasma Glucose and Lipids
Horm. metab. Res. 24 (1992)
\11
Table 1 Changes in clinical parameters, glycemic control and fasting insulin and C-peptide levels during Enisoprost treatment.
Wt (kg) BMI (kg/m2) SBP (mmHg) DBP (mmHg) FSG (mmol/L) HgbA 1 (%) Insulin (pmol/L) C-peptide (pmol/L)
n
Pretreatment
4 wk
8wk
12 wk
Wash-out
20 20 12 12 16 13 13 16
92.5 ±4.2 29.3±1.2 143 + 5 84±3 8.72 + 0.39 7.7 + 0.6 165 ±29 960 ±99
92.7 ±4.4 29.3 ±1.3 137 ± 4 81 ± 3 7.78 ±0.5* 8.2 ±0.6 172 ±22 1092 ±99
92.2 ±4.1 29.2 ±1.2 140 ± 5 81 ± 3 8.56 ±0.61 7.8 ±0.4 165 ±22 1059 ±99
91.6 ±3.9 29.0 ±1.2 139 ± 5 83±3 8.56 ±0.83 7.9 ±0.4 172 ±22 1159 ±132
91.6 ±3.8 29.0 ±1.2 136±4 81 ± 3 9.44 ±0.89 8.0 ±0.6 201 ± 22 1225 ±132
Mean±SEM, Wt = weight, SBP = systolic blood pressure, DBP = diastolic blood pressure, FSG = fasting serum glucose, *P
