OBJECTIVE - To evaluate the effects of intensive insulin therapy and subsequent optimized metabolic control on daily urinary mevalonic acid (MVA) excretion, an index of whole-body cholesterol synthesis, and the acute effects of insulin on plasma MVA concentrations in type II diabetes. RESEARCH DESIGN AND METHODS - Ten (five men and five postmenopausal women) nonobese, normolipidemic (total cholesterol <6.2 mmol/l, triglycerides <2.82 mmol/l), type II diabetic patients in poor metabolic control (HbA(1c) >10%, fasting plasma glucose >11 mmol/l) and receiving sulfonylurea treatment were selected. The 24-h urinary MVA excretion and plasma lipid values were determined before and after intensive insulin therapy. The acute effects of insulin on plasma MVA concentrations were also evaluated during a 3-h euglycemic hyperinsulinemic clamp study. RESULTS - Urinary MVA excretion rates (mu mol/24 h) were 1.82 +/- 0.21 in control subjects and 2.49 +/- 0.35 (P < 0.01 vs. control subjects) and 1.78 +/- 0.28 in patients before and after intensive insulin therapy, respectively. Total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides decreased by 9, 8, and 12%, respectively, after blood glucose optimization. Acute insulin infusion during the euglycemic clamp studies reduced mean plasma MVA concentrations al 120 and 180 min by 29 and 38%, respectively (P < 0.01 for both vs. baseline). CONCLUSIONS - Our study demonstrates that in nonobese, normolipidemic, type II diabetic patients under poor metabolic control, an increased cholesterol synthesis is normalized by insulin therapy. Hyperinsulinemia in the presence of euglycemia acutely decreases the circulating levels of MVA, the immediate product of hydroxymethylglutaryl-CoA reductase activity and an index of whole-body cholesterol synthesis.

Scoppola A., T.G. (1995). Effects of insulin on cholesterol synthesis in type II diabetes patients. DIABETES CARE, 18(10), 1362-1369.

Effects of insulin on cholesterol synthesis in type II diabetes patients

FRONTONI, SIMONA;
1995

Abstract

OBJECTIVE - To evaluate the effects of intensive insulin therapy and subsequent optimized metabolic control on daily urinary mevalonic acid (MVA) excretion, an index of whole-body cholesterol synthesis, and the acute effects of insulin on plasma MVA concentrations in type II diabetes. RESEARCH DESIGN AND METHODS - Ten (five men and five postmenopausal women) nonobese, normolipidemic (total cholesterol <6.2 mmol/l, triglycerides <2.82 mmol/l), type II diabetic patients in poor metabolic control (HbA(1c) >10%, fasting plasma glucose >11 mmol/l) and receiving sulfonylurea treatment were selected. The 24-h urinary MVA excretion and plasma lipid values were determined before and after intensive insulin therapy. The acute effects of insulin on plasma MVA concentrations were also evaluated during a 3-h euglycemic hyperinsulinemic clamp study. RESULTS - Urinary MVA excretion rates (mu mol/24 h) were 1.82 +/- 0.21 in control subjects and 2.49 +/- 0.35 (P < 0.01 vs. control subjects) and 1.78 +/- 0.28 in patients before and after intensive insulin therapy, respectively. Total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides decreased by 9, 8, and 12%, respectively, after blood glucose optimization. Acute insulin infusion during the euglycemic clamp studies reduced mean plasma MVA concentrations al 120 and 180 min by 29 and 38%, respectively (P < 0.01 for both vs. baseline). CONCLUSIONS - Our study demonstrates that in nonobese, normolipidemic, type II diabetic patients under poor metabolic control, an increased cholesterol synthesis is normalized by insulin therapy. Hyperinsulinemia in the presence of euglycemia acutely decreases the circulating levels of MVA, the immediate product of hydroxymethylglutaryl-CoA reductase activity and an index of whole-body cholesterol synthesis.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/13 - Endocrinologia
English
apolipoprotein a1; apolipoprotein b100; cholesterol; fatty acid; glucose; hemoglobin a1c; high density lipoprotein cholesterol; hydroxymethylglutaryl coenzyme a reductase; insulin; low density lipoprotein cholesterol; mevalonic acid; triacylglycerol; very low density lipoprotein cholesterol; adult; article; atherogenesis; cholesterol metabolism; cholesterol synthesis; clinical article; clinical trial; controlled clinical trial; controlled study; coronary artery atherosclerosis; female; glucose blood level; glucose metabolism; human; insulin treatment; lipid blood level; lipoprotein blood level; male; metabolic parameters; metabolic regulation; non insulin dependent diabetes mellitus; treatment outcome; urinary excretion; Apolipoprotein A-I; Apolipoprotein B-100; Apolipoproteins B; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Cholesterol, VLDL; Diabetes Mellitus, Type 2; Diabetic Diet; Eating; Energy Intake; Fasting; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Hemoglobin A, Glycosylated; Humans; Hypoglycemic Agents; Insulin; Male; Mevalonic Acid; Middle Aged; Reference Values; Triglycerides
Scoppola A., T.G. (1995). Effects of insulin on cholesterol synthesis in type II diabetes patients. DIABETES CARE, 18(10), 1362-1369.
Scoppola, A; Testa, G; Frontoni, S; Maddaloni, E; Gambardella, S; Menzinger, G; Lala, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/50474
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