The effect of rosuvastatin on insulin sensitivity and pancreatic beta-cell function in nondiabetic renal transplant recipients.
Interventions to attenuate abnormal glycemia posttransplantation are required. In addition, surrogate markers of declining glycemic control are valuable. Statins may have pleiotropic properties that attenuate abnormal glucose metabolism. We hypothesized statins would improve glucose metabolism and HbA1c would be advantageous as a surrogate for worsening glycemia. We conducted a prospective, randomized, placebo controlled, crossover study in 20 nondiabetic renal transplant recipients at low risk for NODAT and compared effects of rosuvastatin on insulin secretion/sensitivity. Mathematical model analysis of an intravenous glucose tolerance test determined first-phase insulin secretion, insulin sensitivity and disposition index. Second-phase insulin secretion was determined with a meal tolerance test. Biochemical/clinical parameters were also assessed. Rosuvastatin significantly improved total cholesterol (-30%, p < 0.001), LDL cholesterol (-44%, p < 0.001) and triglycerides (-19%, p = 0.013). C-reactive protein decreased but failed to achieve statistical significance (-31%, p = 0.097). Rosuvastatin failed to influence any glycemic physiological parameter, although an inadequate timeframe to allow pleiotropic mechanisms to clinically manifest raises the possibility of a type II statistical error. On multivariate analysis, glycated hemoglobin (HbA1c) correlated with disposition index (R(2)= 0.201, p = 0.006), first-phase insulin secretion (R(2)= 0.106, p = 0.049) and insulin sensitivity (R(2)= 0.136, p = 0.029). Rosuvastatin fails to modify glucose metabolism in low-risk patients posttransplantation but HbA1c is a useful surrogate for declining glycemic control.
Sharif
A
A
University Hospital Birmingham, Edgbaston, Birmingham, United Kingdom. sharif_adnan@hotmail.com
Ravindran
V
V
Moore
R
R
Dunseath
G
G
Luzio
S
S
Owens
D
D
Baboolal
K
K
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D016030:Kidney Transplantation / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D012044:Regression Analysis; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D015415:Biomarkers; D001786:Blood Glucose; D005464:Fluorobenzenes; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D008055:Lipids; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides; C517652:hemoglobin A1c protein, human