Treatment with rosiglitazone reduces hyperinsulinemia and improves arterial elasticity in patients with type 2 diabetes mellitus.
OBJECTIVE
The aim of this study was to determine whether reduction of hyperinsulinemia with rosiglitazone will improve vascular elasticity in patients with non-insulin dependent diabetes mellitus.


METHODS
In an open label study 52 patients with non-insulin dependent diabetes mellitus and at least one additional cardiovascular risk factor, were treated for 6 months with 4 mg of rosiglitazone, and uptitrated to 8 mg after 3 months of treatment, if needed. At the beginning of the study and at its end, blood was drawn for insulin, C- peptide, and 24-h urine collected for microalbuminuria/proteinuria. Glucose, chemistry, lipid profile, and hemoglobin A1C were determined at 0, 3, and 6 months. Vascular compliance was measured in monthly intervals.


RESULTS
Treatment increased significantly small artery elasticity from 1.45 to 2.43 mL/mm Hg x 100. Large artery elasticity tended to increase toward the end of the study (P = not significant). Systolic blood pressure (BP)decreased from 144 to 124 mm Hg and diastolic BP decreased from 80 to 62.5 mm Hg, despite mild weight gain [corrected]. Heart rate tended to decrease from 76.3 to 74.7 beats/min (P = not significant). Systemic vascular resistance decreased from 1789.8 to 1329.4 dyne sec/cm(5). Plasma insulin, in patients not treated with insulin, decreased from 42.45 +/- 24.90 to 27.86 +/- 14.86 IU/mL (P =.0001).


CONCLUSIONS
Treatment with rosiglitazone reduced hyperinsulinemia and improved small artery elasticity with a tendency to improve large artery elasticity, in hypertensive and in normotensive patients. Because rosiglitazone improves insulin receptor sensitivity (IRS), it is logical to assume that the reduction in hyperinsulinemia reflects improvement in IRS. Our data support the hypothesis that hyperinsulinemia and IRS participate in the mechanisms of tissue injury and their improvement induces improvement in arterial elasticity.
Shargorodsky
Marina
M
Department of Endocrinology and Diabetes, Wolfson Medical Center, Holon 58100, Israel.
Wainstein
Julio
J
Gavish
Dov
D
Leibovitz
Eyal
E
Matas
Ziporah
Z
Zimlichman
Reuven
R
Wainstein
Gulio
G
Gavish
Eyal
E
Leibovitz
Ziporah
Z
Matas
Dov
D
D000328:Adult; D000368:Aged; D001158:Arteries / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003187:Compliance; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D004548:Elasticity; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone