Aims/hypothesis

Vitamin D insufficiency is associated with an elevated risk of type 2 diabetes, but evidence from randomised trials on the benefits of vitamin D supplementation is limited, especially for average-risk populations. The Finnish Vitamin D Trial (FIND) investigated the effects of vitamin D₃ supplementation at two different doses on the incidence of type 2 diabetes in a generally healthy older adult population.

Methods

FIND was a 5 year randomised placebo-controlled, parallel-arm trial among 2271 male and female participants aged ≥60 years and ≥65 years, respectively, from a general Finnish population who were free of CVD or cancer and did not use diabetes medications. The study had three arms: placebo, 1600 IU/day of vitamin D₃ or 3200 IU/day of vitamin D₃. A non-study group statistician carried out sex-stratified simple randomisation in a 1:1:1 ratio, based on computerised random number generation. The participants, investigators and study staff were masked to group assignment. National health registries were used to collect event data. A representative subcohort of 505 participants had more detailed in-person investigations at months 0, 6, 12 and 24.

Results

During the mean follow-up of 4.2 years, there were 38 (5.0%), 31 (4.2%) and 36 (4.7%) type 2 diabetes events in the placebo (n=760), 1600 IU/day vitamin D₃ (n=744; vs placebo: HR 0.81; 95% CI 0.50, 1.30) and 3200 IU/day vitamin D₃ (n=767; vs placebo: HR 0.92, 95% CI 0.58, 1.45) arms, respectively (p-trend=0.73). When the two vitamin D₃ arms were combined and compared with the placebo arm, the HR was 0.86 (95% CI 0.58, 1.29). In the analyses stratified by BMI (<25 kg/m² [n=813, number of type 2 diabetes events=12], 25–30 kg/m² [n=1032, number of events=38], ≥30 kg/m² [n=422, number of events=54]), the HRs in the combined vitamin D₃ arms vs the placebo were 0.43 (95% CI 0.14, 1.34), 0.97 (0.50, 1.91) and 1.00 (0.57, 1.75), respectively (p-interaction <0.001). In the subcohort, the mean (SD) baseline serum 25-hydroxyvitamin D₃ (25(OH)D₃) concentration was 74.5 (18.1) nmol/l. After 12 months, the concentrations were 72.6 (17.7), 99.3 (20.8) and 120.9 (22.1) nmol/l in the placebo, 1600 IU/day vitamin D₃ and 3200 IU/day vitamin D₃ arms, respectively. In the subcohort, no differences were observed in changes in plasma glucose or insulin concentrations, BMI or waist circumference during the 24 month follow-up (p values ≥0.19).

Conclusion/interpretation

Among generally healthy older adults who are not at high risk for diabetes and who have serum 25(OH)D₃ levels that are sufficient for bone health, vitamin D₃ supplementation did not significantly reduce the risk of developing diabetes.

Trial registration

ClinicalTrials.gov NCT01463813.

Graphical Abstract

中文翻译：

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补充维生素 D3 对非糖尿病高危健康老年人 2 型糖尿病发病率的影响 （FIND）：一项随机对照试验

 目标/假设

维生素 D 缺乏与 2 型糖尿病风险升高有关，但关于维生素 D 补充剂益处的随机试验证据有限，尤其是对于平均风险人群。芬兰维生素 D 试验 （FIND） 调查了两种不同剂量的维生素_{D 3} 补充剂对总体健康老年人群 2 型糖尿病发病率的影响。

 方法

FIND 是一项为期 5 年的随机安慰剂对照平行组试验，在 2271 名男性和女性参与者中，年龄分别为 ≥60 岁和 ≥65 岁，来自普通芬兰人群，没有 CVD 或癌症，也没有使用糖尿病药物。该研究分为三组：安慰剂、1600 IU/天的维生素 D₃ 或 3200 IU/天的维生素 D₃。一名非研究组统计学家根据计算机随机数生成，以 1：1：1 的比例进行了性别分层简单随机化。参与者、研究人员和研究人员被设盲以进行小组分配。使用国家卫生登记处收集事件数据。由 505 名参与者组成的代表性亚队列在第 0 、 6 、 12 和 24 个月进行了更详细的面对面调查。

 结果

在平均 4.2 年的随访期间，安慰剂组 （n=760）、1600 IU/天维生素_{D 3}（n=744;与安慰剂相比：HR 0.81;95% CI 0.50、1.30）和 3200 IU/天维生素 D₃（n=767;与安慰剂相比：HR 0.92,95% CI 0.58， 1.45） 组 （p-trend=0.73）。当两个维生素 D₃ 组合并并与安慰剂组相比时，HR 为 0.86 （95% CI 0.58， 1.29）。在按 BMI（<25 kg/m² [n=813,2 型糖尿病事件数=12]、25-30 kg/m² [n=1032，事件数=38]、≥30 kg/m² [n=422，事件数=54]）分层的分析中，维生素_{D 3} 联合组与安慰剂组的 HR 为 0.43（95% CI 0.14， 1.34）、0.97 （0.50， 1.91） 和 1.00 （0.57， 1.75） （p 交互作用 <0.001）。在亚组中，平均 （SD） 基线血清 25-羟基维生素 D₃ （25（OH）D₃） 浓度为 74.5 （18.1） nmol/l。12 个月后，安慰剂组、1600 IU/天维生素 D₃ 组和 3200 IU/天维生素 D₃ 组的浓度分别为 72.6 （17.7） 、99.3 （20.8） 和 120.9 （22.1） nmol/l。在亚组中，在 24 个月的随访期间，血浆葡萄糖或胰岛素浓度、BMI 或腰围的变化未观察到差异 （p 值 ≥0.19）。

结论/解释

在糖尿病风险不高且血清 25（OH）D₃ 水平足以促进骨骼健康的老年人中，维生素 D₃ 补充剂并未显著降低患糖尿病的风险。

 试用注册

ClinicalTrials.gov NCT01463813。

 图形摘要