Vitamin D deficiency increases vulnerability to canagliflozin-induced adverse effects on 1,25-dihydroxyvitamin D and PTH.
Vitamin D deficiency increases vulnerability to canagliflozin-induced adverse effects on 1,25-dihydroxyvitamin D and PTH.
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维生素 D 缺乏会增加卡格列净对 1,25-二羟基维生素 D 和 PTH 产生不利影响的可能性。
DOI：
10.1101/2023.05.11.23289854
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Taylor,SimeonI
中科院分区：
文献类型：
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作者：
Yazdi,ZhinousShahidzadeh;Streeten,ElizabethA;Whitlatch,HilaryB;Montasser,MayE;Beitelshees,AmberL;Taylor,SimeonI
据报道，卡格列净可能通过减少1，25-二羟维生素D（1，25（OH）2D）和增加甲状旁腺激素（PTH）来增加骨质疏松的风险。这项工作调查了基线维生素D（VitD）缺乏是否使个体易受这种不良反应的影响，以及维生素D3补充是否具有保护作用。门诊研究采用配对设计，比较个体参与者补充VitD 3前后的情况。从宾夕法尼亚州兰开斯特的阿米什人中招募了11名维生素D缺乏（25-羟基维生素D [25（OH）D] ≤ 20 ng/mL）的个体。参与者接受了2次卡格列净激发方案（每日300 mg，持续5天）：第一次在补充VitD 3之前，第二次在补充VitD 3之后。在VitD 3补充方案中，参与者接受VitD 3补充（50 000 IU，每周一次或两次，根据体重指数持续4-6周），以达到30 ng/mL或更高的25（OH）D。确定了两个共同主要终点：维生素D3补充对卡格列净诱导的1，25（OH）2D和PTH变化的影响。次要终点包括补充VitD 3对VitD代谢物和PTH基线水平的影响。结果补充VitD 3使平均25（OH）D从16.5 ± 1.6增加到44.3 ± 5.5 ng/mL（P= 0.0006），使平均24，25-二羟维生素D（24，25（OH）2D）从1.0 ± 0.1增加到4.3 ± 0.6 ng/mL（P= 0.0002）。平均1，25（OH）2D和PTH无变化。维生素D3补充降低了卡格列净诱导的1，25（OH）2D（从−31.3%±4.7%至−9.3%±8.3%;P= .04）和PTH（从+36.2%至6.2%至+9.7%至3.7%;P= .005）变化幅度。维生素D3补充剂对卡格列净对1，25（OH）2D和PTH的短期不良反应具有保护作用。
ContextCanagliflozin has been reported to increase the risk of bone fracture—possibly mediated by decreasing 1,25-dihydroxyvitamin D (1,25(OH)2D) and increasing parathyroid hormone (PTH).ObjectiveThis work investigated whether baseline vitamin D (VitD) deficiency renders individuals vulnerable to this adverse effect and whether VitD3supplementation is protective.MethodsThis community-based, outpatient study had a paired design comparing individual participants before and after VitD3supplementation. Eleven VitD-deficient (25-hydroxyvitamin D [25(OH)D] ≤ 20 ng/mL) individuals were recruited from the Amish population in Lancaster, Pennsylvania. Participants underwent 2 canagliflozin challenge protocols (300 mg daily for 5 days): the first before and the second after VitD3supplementation. In the VitD3supplementation protocol, participants received VitD3supplementation (50 000 IU once or twice a week depending on body mass index for 4-6 weeks) to achieve 25(OH)D of 30 ng/mL or greater. Two coprimary end points were identified: effects of VitD3supplementation on canagliflozin-induced changes in 1,25(OH)2D and PTH. Secondary end points included effects of VitD3supplementation on baseline levels of VitD metabolites and PTH.ResultsVitD3supplementation increased mean 25(OH)D from 16.5 ± 1.6 to 44.3 ± 5.5 ng/mL (P= .0006) and 24,25-dihydroxyvitamin D (24,25(OH)2D) from 1.0 ± 0.1 to 4.3 ± 0.6 ng/mL (P= .0002). Mean 1,25(OH)2D and PTH were unchanged. VitD3supplementation decreased the magnitude of canagliflozin-induced changes in 1,25(OH)2D (from −31.3%±4.7% to −9.3%±8.3%;P= .04) and PTH (from +36.2%±6.2% to +9.7%±3.7%;P= .005).ConclusionVitD deficiency rendered individuals more vulnerable to adverse effects of canagliflozin on biomarkers associated with bone health. VitD3supplementation was protective against canagliflozin's short-term adverse effects on 1,25(OH)2D and PTH.