PMID- 37484958 OWN - NLM STAT- MEDLINE DCOM- 20230726 LR - 20230726 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - Efficacy and safety of high-dose intramuscular vitamin D(2) injection in type 2 diabetes mellitus with distal symmetric polyneuropathy combined with vitamin D insufficiency: study protocol for a multicenter, randomized, double-blinded, and placebo-controlled trial. PG - 1202917 LID - 10.3389/fendo.2023.1202917 [doi] LID - 1202917 AB - BACKGROUND: Distal symmetric polyneuropathy (DSPN) is the most common chronic complication of type 2 diabetes mellitus (T2DM). DSPN may lead to more serious complications, such as diabetic foot ulcer, amputation, and reduced life expectancy. Observational studies have suggested that vitamin D deficiency may be associated with the development of DSPN in T2DM. However, interventional studies have found that low-dose vitamin D supplementation does not significantly improve neuropathy in DSPN. This study aims to evaluate the efficacy and safety of intramuscular injection of high-dose vitamin D (HDVD) in T2DM with DSPN combined with vitamin D insufficiency. METHODS AND ANALYSIS: We will conduct a multicenter, randomized, double-blinded, and placebo-controlled trial in four large hospitals. All eligible participants will be randomly assigned to either the vitamin D(2) supplement or placebo control group and injected intramuscularly monthly for 3 months. Additionally, anthropometric measurements and clinical data will be collected at baseline and 3 months. Adverse events will be collected at 1, 2, and 3 months. The primary outcome measure is the change in the mean Michigan Neuropathy Screening Instrument (MNSI) score at baseline and 3 months post-intervention. We will use the gold-standard liquid chromatography-tandem mass spectrometry method to distinguish between 25(OH)D(2) and 25(OH)D(3) levels. The MNSN score before the intervention will be used as a covariate to compare the changes between both groups before and after the intervention, and the analysis of covariance will be used to analyze the change in the MNSI score after HDVD supplementation. DISCUSSION: Glycemic control alone does not prevent the progression of DSPN in T2DM. Some studies have suggested that vitamin D may improve DSPN; however, the exact dose, method, and duration of vitamin D supplementation are unknown. Additionally, neuropathy repair requires HDVD supplementation to sustain adequate vitamin D levels. This once-a-month intramuscular method avoids daily medication; therefore, compliance is high. This study will be the first randomized controlled trial in China to analyze the efficacy and safety of HDVD supplementation for patients with T2DM and DSPN and will provide new ideas for pharmacological research and clinical treatment of diabetic neuropathy. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/, identifier ChiCTR2200062266. CI - Copyright (c) 2023 Chen, Xing, Huang, Tu, Lai, Wen, Cai, Lin, Zheng, Lin, Xu, Qiu, Qiu, Xu and Wu. FAU - Chen, Tao AU - Chen T AD - Department of Endocrinology, Clinical Research Center for Metabolic Diseases of Fujian Province, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. AD - Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China. FAU - Xing, Xiaoyan AU - Xing X AD - Department of Endocrinology and Metabolism, China-Japan Friendship Hospital, Beijing, China. FAU - Huang, Lihua AU - Huang L AD - Department of Tumor Radiotherapy, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China. FAU - Tu, Mei AU - Tu M AD - Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China. FAU - Lai, Xiaoli AU - Lai X AD - Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China. FAU - Wen, Shidi AU - Wen S AD - Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China. FAU - Cai, Jin AU - Cai J AD - Department of Endocrinology and Metabolism, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China. FAU - Lin, Shenglong AU - Lin S AD - Department of Severe Liver Disease, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China. FAU - Zheng, Youping AU - Zheng Y AD - Department of Ultrasound, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, China. FAU - Lin, Yuehui AU - Lin Y AD - Department of Endocrinology and Metabolism, Longyan Traditional Chinese Medicine Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Longyan, China. FAU - Xu, Lijuan AU - Xu L AD - Department of Endocrinology and Metabolism, Longyan Traditional Chinese Medicine Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Longyan, China. FAU - Qiu, Yuwen AU - Qiu Y AD - Department of Endocrinology and Metabolism, Longyan Shanghang County Hospital, Longyan, China. FAU - Qiu, Lumin AU - Qiu L AD - Department of Endocrinology and Metabolism, Longyan Shanghang County Hospital, Longyan, China. FAU - Xu, Yuebo AU - Xu Y AD - Department of Diabetes, Longyan Boai Hospital, Longyan, China. FAU - Wu, Peiwen AU - Wu P AD - Department of Endocrinology, Clinical Research Center for Metabolic Diseases of Fujian Province, the First Affiliated Hospital, Fujian Medical University, Fuzhou, China. LA - eng PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230707 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 1406-16-2 (Vitamin D) RN - 0 (Vitamins) SB - IM MH - Humans MH - Vitamin D/therapeutic use MH - *Diabetes Mellitus, Type 2/complications MH - Double-Blind Method MH - Vitamins/therapeutic use MH - *Vitamin D Deficiency/complications MH - *Polyneuropathies/complications MH - Randomized Controlled Trials as Topic MH - Multicenter Studies as Topic PMC - PMC10361572 OTO - NOTNLM OT - Michigan neuropathy screening instrument OT - distal symmetric polyneuropathy OT - high-dose vitamin D supplementation OT - randomized controlled trial OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/07/24 06:43 MHDA- 2023/07/26 06:42 PMCR- 2023/01/01 CRDT- 2023/07/24 04:51 PHST- 2023/04/09 00:00 [received] PHST- 2023/06/19 00:00 [accepted] PHST- 2023/07/26 06:42 [medline] PHST- 2023/07/24 06:43 [pubmed] PHST- 2023/07/24 04:51 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1202917 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Jul 7;14:1202917. doi: 10.3389/fendo.2023.1202917. eCollection 2023.