title: Effects of insulin on cholesterol synthesis in type II diabetes patients.
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.
  
  
  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 (HbA1c > 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 (mumol/24h) 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 at 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.
authors.affiliation: Department of Endocrinology, University of Rome Tor Vergata, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Scoppola
authors.forename: G
authors.initials: G
authors.lastname: Testa
authors.forename: S
authors.initials: S
authors.lastname: Frontoni
authors.forename: E
authors.initials: E
authors.lastname: Maddaloni
authors.forename: S
authors.initials: S
authors.lastname: Gambardella
authors.forename: G
authors.initials: G
authors.lastname: Menzinger
authors.forename: A
authors.initials: A
authors.lastname: Lala
mesh_terms: D016632:Apolipoprotein A-I / Q000097:blood; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D003927:Diet, Diabetic; D004435:Eating; D002149:Energy Intake; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008798:Mevalonic Acid / Q000097:blood* / Q000652:urine; D008875:Middle Aged; D012016:Reference Values; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001786:Blood Glucose; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008798:Mevalonic Acid; D014280:Triglycerides