Improved preservation of residual beta cell function by atorvastatin in patients with recent onset type 1 diabetes and high CRP levels (DIATOR trial)

Abstract

Background: A recent randomized placebo-controlled trial of the effect of atorvastatin treatment on the progression of newly diagnosed type 1 diabetes suggested a slower decline of residual beta cell function with statin treatment. Aim of this secondary analysis was to identify patient subgroups which differ in the decline of beta cell function during treatment with atorvastatin.

Methodology/principal findings: The randomized placebo-controlled Diabetes and Atorvastatin (DIATOR) Trial included 89 patients with newly diagnosed type 1 diabetes and detectable islet autoantibodies (mean age 30 years, 40% females), in 12 centers 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. For this secondary analysis patients were stratified by single baseline characteristics which were considered to possibly be modified by atorvastatin treatment. Subgroups defined by age, sex or by baseline metabolic parameters like body mass index (BMI), total serum cholesterol or fasting C-peptide did not differ in C-peptide outcome after atorvastatin treatment. However, the subgroup defined by high (above median) baseline C-reactive protein (CRP) concentrations exhibited higher stimulated C-peptide secretion after statin treatment (p = 0.044). Individual baseline CRP levels correlated with C-peptide outcome in the statin group (r(2) = 0.3079, p<0.004). The subgroup with baseline CRP concentrations above median differed from the corresponding subgroup with lower CRP levels by higher median values of BMI, IL-6, IL-1RA, sICAM-1 and E-selectin.

Conclusions/significance: Atorvastatin treatment may be effective in slowing the decline of beta cell function in a patient subgroup defined by above median levels of CRP and other inflammation associated immune mediators.

Trial registration: ClinicalTrials.gov NCT00974740.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts: T. Heise and L. Heinemann are employed by Profil Institute of Metabolic Research which was contracted to conduct the trial. N.C. Schloot is employed by Lilly Deutschland GmbH. The study was funded by an unrestricted grant from Pfizer Pharma GmbH, Berlin. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. No other potential conflicts of interest relevant to this article were reported.

Figures

Figure 1. Correlation analysis of baseline CRP or total serum cholesterol concentrations with C-peptide outcome.

Of individual patients, baseline CRP concentrations (a) or baseline total cholesterol levels (b) were compared to stimulated C-peptide concentrations at 18 months (18 m). The vertical line indicates the median of baseline CRP or cholesterol concentrations, respectively, the red line indicates the linear regression line obtained by the Pearson's correlation test.

Figure 2. Correlation analysis of atorvastatin effects on cholesterol or CRP levels with C-peptide outcome.

Of individual patients, the change of CRP concentrations (a) or total cholesterol concentrations (b) from baseline to 3 months of atorvastatin treatment (“delta”) were compared to stimulated C-peptide concentrations at 18 months (18 m).