Residual Beta Cell Function in Newly Diagnosed Type 1 Diabetes after Treatment with Atorvastatin: The Randomized DIATOR Trial

BackgroundRecent 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 FindingsThe 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.
ConclusionsAtorvastatin 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 RegistrationClinicalTrials.gov NCT00974740

背景
近期研究证据表明，调脂药物阿托伐他汀（atorvastatin）同时也是一种强效免疫调节剂。本研究旨在探讨阿托伐他汀对新发1型糖尿病患者残留β细胞功能衰退的潜在影响。

方法与结果
这项随机安慰剂对照的糖尿病与阿托伐他汀（Diabetes and Atorvastatin, DIATOR）试验在德国12个研究中心开展，共纳入89名新诊断1型糖尿病且胰岛自身抗体（islet autoantibodies）阳性的患者（平均年龄30岁，女性占比40%）。受试者被分配接受安慰剂或80mg/d剂量的阿托伐他汀治疗，疗程为18个月。
本研究的主要结局指标为：在受试者接受标准混合液体餐（standardized liquid mixed meal）后90分钟时，检测其血清刺激后C肽（stimulated serum C-peptide）水平。本研究采用意向性治疗分析（intent-to-treat analysis）。
治疗18个月时，两组患者的空腹及刺激后C肽水平均无显著差异。然而，安慰剂组患者的空腹血清C肽中位数水平从基线至12个月、18个月时呈显著下降趋势（从0.34 nmol/l降至0.23 nmol/l、0.20 nmol/l，p<0.001）；而阿托伐他汀组仅出现无统计学意义的下降（从0.34 nmol/l降至0.27 nmol/l、0.30 nmol/l，ns，即无统计学差异）。
基线至12个月期间，两组患者的刺激后C肽浓度中位数均有所下降（安慰剂组从0.89 nmol/l降至0.71 nmol/l，阿托伐他汀组从0.88 nmol/l降至0.73 nmol/l，两组均p<0.01）；至18个月时，安慰剂组的刺激后C肽水平出现大幅下降（降至0.48 nmol/l，p=0.047），而阿托伐他汀组未出现此类变化（降至0.71 nmol/l，ns）。
仅阿托伐他汀组患者的总胆固醇与C反应蛋白（C-reactive protein, CRP）中位数水平出现下降（p<0.001，p=0.04）。两组患者的代谢控制情况无显著差异。

结论
尽管阿托伐他汀治疗可能延缓了β细胞功能的衰退趋势（该结果有待进一步研究验证），但其并未显著改善患者的β细胞功能保留情况。

试验注册
ClinicalTrials.gov NCT00974740