Objective To assess whether eldecalcitol, an active vitamin D analogue2, can reduce the development of type 2 diabetes among adults with impaired glucose tolerance. Design Double blinded, multicentre, randomised, placebo controlled trial. Setting Three hospitals in Japan, between June 2013 and August 2019. Participants People aged 30 years and older who had impaired glucose tolerance defined by using a 75 g oral glucose tolerance test and glycated haemoglobin level. Interventions Participants were randomised to receive active vitamin D (eldecalcitol 0.75 μg per day; n=630) or matching placebo (n=626) for three years. Main outcomes The primary endpoint was incidence of diabetes. Prespecified secondary endpoints were regression to normoglycaemia and incidence of type 2 diabetes after adjustment for confounding factors at baseline. In addition, bone densities and bone and glucose metabolism markers were assessed. Results Of the 1256 participants, 571 (45.5%) were women and 742 (59.1%) had a family history of type 2 diabetes. The mean age of participants was 61.3 years. The mean serum 25-hydroxyvitamin D concentration at baseline was 20.9 ng/mL (52.2 nmol/L); 548 (43.6%) participants had concentrations below 20 ng/mL (50 nmol/L). During a median follow-up of 2.9 years, 79 (12.5%) of 630 participants in the eldecalcitol group and 89 (14.2%) of 626 in the placebo group developed type 2 diabetes (hazard ratio 0.87, 95% confidence interval 0.67 to 1.17; P=0.39). Regression to normoglycaemia was achieved in 145 (23.0%) of 630 participants in the eldecalcitol group and 126 (20.1%) of 626 in the placebo group (hazard ratio 1.15, 0.93 to 1.41; P=0.21). After adjustment for confounding factors by multivariable fractional polynomial Cox regression analysis, eldecalcitol significantly lowered the development of diabetes (hazard ratio 0.69, 0.51 to 0.95; P=0.020). In addition, eldecalcitol showed its beneficial effect among the participants with the lower level of basal insulin secretion (hazard ratio 0.41, 0.23 to 0.71; P=0.001). During follow-up, bone mineral densities of the lumbar spine and femoral neck and serum osteocalcin concentrations significantly increased with eldecalcitol compared with placebo (all P<0.001). No significant difference in serious adverse events was observed. Conclusions Although treatment with eldecalcitol did not significantly reduce the incidence of diabetes among people with pre-diabetes, the results suggested the potential for a beneficial effect of eldecalcitol on people with insufficient insulin secretion. Trial registration UMIN Clinical Trials Registry UMIN000010758. Relevant anonymised patient level data are available from the corresponding author on reasonable request.

中文翻译：

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活性维生素 D 治疗对 2 型糖尿病发展的影响：日本人群 DPVD 随机对照试验

目的 评估艾地骨化醇（一种活性维生素 D 类似物 2）是否可以减少糖耐量受损成人 2 型糖尿病的发生。设计 双盲、多中心、随机、安慰剂对照试验。设置 2013 年 6 月至 2019 年 8 月期间在日本的三家医院。参与者 30 岁及以上的糖耐量受损的人，通过使用 75 克口服葡萄糖耐量测试和糖化血红蛋白水平定义。干预 参与者被随机分配接受活性维生素 D（eldecalcitol 每天 0.75 μg；n=630）或匹配安慰剂（n=626）为期三年。主要结果 主要终点是糖尿病的发病率。预先设定的次要终点是在基线时调整混杂因素后回归正常血糖和 2 型糖尿病的发病率。此外，评估了骨密度以及骨和葡萄糖代谢标志物。结果 在 1256 名参与者中，571 名（45.5%）为女性，742 名（59.1%）有 2 型糖尿病家族史。参与者的平均年龄为 61.3 岁。基线时的平均血清 25-羟基维生素 D 浓度为 20.9 ng/mL (52.2 nmol/L)；548 名 (43.6%) 参与者的浓度低于 20 ng/mL (50 nmol/L)。在 2.9 年的中位随访期间，艾地骨化醇组 630 名参与者中有 79 名（12.5%）和安慰剂组 626 名参与者中有 89 名（14.2%）发展为 2 型糖尿病（风险比 0.87，95% 置信区间 0.67 至 1.17 ; P = 0.39)。埃尔地骨化醇组 630 名参与者中有 145 名（23.0%）和安慰剂组 626 名参与者中有 126 名（20.1%）达到血糖正常（风险比 1.15，0.93 至 1.41；P=0.21）。通过多变量分数多项式 Cox 回归分析调整混杂因素后，eldecalcitol 显着降低了糖尿病的发展（风险比 0.69，0.51 至 0.95；P=0.020）。此外，eldecalcitol 在基础胰岛素分泌水平较低的参与者中显示出有益作用（风险比 0.41、0.23 至 0.71；P=0.001）。在随访期间，与安慰剂相比，eldecalcitol 组腰椎和股骨颈的骨矿物质密度和血清骨钙素浓度显着增加（均 P<0.001）。未观察到严重不良事件的显着差异。结论 虽然 eldecalcitol 治疗并未显着降低糖尿病前期人群的糖尿病发病率，但 结果表明，eldecalcitol 可能对胰岛素分泌不足的人产生有益作用。试验注册 UMIN 临床试验注册 UMIN000010758。相关匿名患者水平数据可根据合理要求从相应作者处获得。