Chen Xiaohong, Peng Bi, Ye Wenchun, Wu Bitao, Yang Qiang, Tang Jie, Yang Yuwei
Mianyang Central Hospital, Affiliated to School of Medicine, University of Electronic Science and Technology of China, Mianyang, China.
The Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, China.
Eur J Med Res. 2024 Dec 23;29(1):617. doi: 10.1186/s40001-024-02212-9.
Recent Mendelian randomization and meta analysis suggest a controversial causality between C3-epimer of 25 hydroxyvitamin D3 (C3-epi-D3) and type 2 diabetes mellitus (T2DM). The clinical evidence regarding the impact of C3-epi-D3 on the progression of T2DM is currently insufficient. This study aims to investigate whether C3-epi-D3 has any effect on metabolic disorders of T2DM patients.
A total of 1222 patients with T2DM were prospectively enrolled in this study and followed up every 1 to 2 months for 3 to 6 months. Kidney biomarkers, lipids, electrolytes, and 25 hydroxyvitamin D (25-OHD) metabolites were measured as required during follow-up, to investigate the association of C3-epi-D3 levels and %C3-epi-D3 with metabolic disorders, including dyslipidemia, chronic kidney disease (CKD), and calcium-phosphorus metabolic disorder.
Among these T2DM patients, there were age and seasonal differences in C3-epi-D3 levels (χ = 10.419 and 19.609, P = 0.034 and < 0.001), but only seasonal difference in %C3-epi-D3 (χ = 79.299, P < 0.001). C3-epi-D3 levels showed an evident correlation with calcium-phosphorus product during autumn and winter (ρ = - 0.336 and - 0.304, both P < 0.001), and was confirmed as an independent factor on calcium-phosphorus metabolic disorder during autumn and winter by subsequent partial correlation analysis (r = - 0.300 and - 0.319, both P < 0.001). Both C3-epi-D3 levels and %C3-epi-D3 showed evident correlation with the severity of chronic kidney disease (CKD) in summer (ρ = 0.344 and 0.445, both P < 0.001). But subsequent multinomial logistic regression confirmed that only %C3-epi-D3 independently associated with moderate CKD severity in summer (OR = 1.348, P < 0.001), as well as serious CKD severity in spring, summer, and autumn (OR = 1.324, 1.342, and 1.698, all P < 0.001). Additionally, no evident correlation was observed between C3-epi-D3 and dyslipidemia.
Our study releases a seasonally differential impact of C3-epi-D3 levels and proportions on metabolic disorders of T2DM patients, considering to be potentially related to their pathogenesis of different metabolic disorders. The independent association between %C3-epi-D3 and CKD suggests a potential pathological relevance involving C3-epi-D3 itself.
近期的孟德尔随机化和荟萃分析表明，25-羟基维生素D3的C3差向异构体（C3-epi-D3）与2型糖尿病（T2DM）之间存在有争议的因果关系。目前，关于C3-epi-D3对T2DM进展影响的临床证据不足。本研究旨在探讨C3-epi-D3对T2DM患者代谢紊乱是否有任何影响。
本研究前瞻性纳入了1222例T2DM患者，每1至2个月随访一次，共随访3至6个月。随访期间根据需要检测肾脏生物标志物、血脂、电解质和25-羟基维生素D（25-OHD）代谢产物，以研究C3-epi-D3水平和C3-epi-D3百分比与代谢紊乱（包括血脂异常、慢性肾脏病（CKD）和钙磷代谢紊乱）之间的关联。
在这些T2DM患者中，C3-epi-D3水平存在年龄和季节差异（χ=10.419和19.609，P=0.034和<0.001），但C3-epi-D3百分比仅存在季节差异（χ=79.299，P<0.001）。C3-epi-D3水平在秋冬季节与钙磷乘积呈显著相关性（ρ=-0.336和-0.304，均P<0.001），随后的偏相关分析证实其为秋冬季节钙磷代谢紊乱的独立影响因素（r=-0.300和-0.319，均P<0.001）。C3-epi-D3水平和C3-epi-D3百分比在夏季均与慢性肾脏病（CKD）的严重程度呈显著相关性（ρ=0.344和0.445，均P<0.001）。但随后的多项logistic回归证实，仅C3-epi-D3百分比在夏季与中度CKD严重程度独立相关（OR=1.348，P<0.001），在春季、夏季和秋季与重度CKD严重程度独立相关（OR=1.324、1.342和1.698，均P<0.001）。此外，未观察到C3-epi-D3与血脂异常之间存在显著相关性。
我们的研究揭示了C3-epi-D3水平和比例对T2DM患者代谢紊乱的季节性差异影响，认为这可能与其不同代谢紊乱的发病机制有关。C3-epi-D3百分比与CKD之间的独立关联提示了C3-epi-D3本身潜在的病理相关性。
