Residual beta cell function in newly diagnosed type 1 diabetes after treatment with atorvastatin: the Randomized DIATOR Trial

Abstract

Background: Recent evidence suggests that the lipid-lowering agent atorvastatin is also a potent immunomodulator. The aim of this study was to investigate the possible effect of atorvastatin on the decline of residual beta cell function in recent-onset type 1 diabetes.

Methods and findings: The randomised placebo-controlled Diabetes and Atorvastatin (DIATOR) Trial included 89 patients with newly diagnosed type 1 diabetes and islet autoantibodies (mean age 30 years, 40% females), in 12 centres in Germany. Patients received placebo or 80 mg/d atorvastatin for 18 months. As primary outcome stimulated serum C-peptide levels were determined 90 min after a standardized liquid mixed meal. An intent-to-treat analysis was performed. Fasting and stimulated C-peptide levels were not significantly different between groups at 18 months. However, median fasting serum C-peptide levels dropped from baseline to 12 and 18 months in the placebo group (from 0. 34 to 0.23 and 0.20 nmol/l, p<0.001) versus a nonsignificant decline in the atorvastatin group (from 0.34 to 0.27 and 0.30 nmol/l, ns). Median stimulated C-peptide concentrations declined between baseline and 12 months (placebo from 0.89 to 0.71 nmol/l, atorvastatin from 0.88 to 0.73 nmol/l, p<0.01 each) followed by a major loss by month 18 in the placebo group (to 0.48 nmol/l, p = 0.047) but not in the atorvastatin group (to 0.71 nmol/l, ns). Median levels of total cholesterol and C-reactive protein decreased in the atorvastatin group only (p<0.001 and p = 0.04). Metabolic control was similar between groups.

Conclusions: Atorvastatin treatment did not significantly preserve beta cell function although there may have been a slower decline of beta-cell function which merits further study.

Trial registration: ClinicalTrials.gov NCT00974740.

Figure 1. Study flow diagram.

Patients were screened in 12 participating centers by using the inclusion and exclusion criteria.

Figure 2. Course of C-peptide secretion in the study groups.

Fasting serum C-peptide concentrations (a) were the mean of two blood samples obtained 5 min apart, samples for stimulated serum C-peptide (b) were obtained 90 min after a standard liquid mixed meal. Numbers in columns indicate the IQR. Filled bars, atorvastatin, empty bars, placebo. Differences between groups were not significant. Comparison between groups by Mann-Whitey-u-test, within groups by Wilcoxon signed rank test.

Figure 3. Effect of atorvastatin on blood lipid levels.

Shown are mean levels of total (black lines) and LDL-cholesterol (blue lines) (a), HDL-cholesterol (black lines) and triglycerides (blue lines) (b), bars indicate standard deviation, dotted lines depict placebo, continuous lines atorvastatin. * p<0.05, ** p<0.01, *** p<0.001 for comparison with baseline values. Only changes for the atorvastatin group are significant.

Figure 4. Metabolic control during the study (HbA1c (a), insulin dose (b).

Filled bars, atorvastatin, empty bars, placebo. Bars indicate standard deviation, for HbA1c p-values describe differences of mean values from baseline determined by ANCOVA with correction for baseline HbA1c and BMI (which correlated with later HbA1c levels), **, p<0.01; ***, p<0.001. Mean insulin doses per kg bodyweight were different between groups at 12 months (p = 0.007, comparison of log-transformed mean values by ANCOVA with correction for baseline insulin dose and age (which correlated with later insulin doses).