Division of Endocrinology and Metabolism, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
Veterans Affairs Puget Sound Health Care System, Seattle, WA, United States.
Nutr Metab Cardiovasc Dis. 2024 Mar;34(3):633-641. doi: 10.1016/j.numecd.2023.10.026. Epub 2023 Oct 29.
To prospectively investigate associations of plasma sphingolipids with insulin sensitivity, β-cell function, and incident diabetes in the Japanese American Community Diabetes Study.
Baseline plasma samples from adults without diabetes (n = 349; mean age 56.7 years, 51 % men) were assayed for circulating ceramide and sphingomyelin species. Adjusted regression models examined cross-sectional and longitudinal associations with insulin sensitivity (HOMA2-%S), β-cell function (oral disposition index: DIo) and with incident diabetes over 5 years follow-up. Concentrations of four species (Ceramide C16:0, C18:0, C20:0, and C22:0) were inversely associated with HOMA2-%S at baseline (all P values < 0.05, Q values < 0.05) and change in HOMA2-%S over 5 years (all P values < 0.05, Q values < 0.05). No sphingolipids were associated with baseline or change in DIo. Of the four species associated with HOMA2-%S, only Ceramide C18:0 was significantly and positively associated with incident diabetes (RR/1SD 1.44, 95 % CI 1.10-1.80, P = 0.006, Q = 0.024). The association of plasma Ceramide C18:0 with the risk of diabetes was partially mediated by change in HOMA2-%S between baseline and 5 years (mediation proportion: 61.5 %, 95 % CI 21.1%-212.5 %).
Plasma Ceramide C18:0 was associated with higher risk of incident diabetes which was partially mediated through a decrease in insulin sensitivity between baseline and five years. Circulating Ceramide C18:0 could be a potential biomarker for identifying those at risk of developing diabetes.
本前瞻性研究旨在探究血浆神经酰胺和鞘磷脂与日本裔美国人社区糖尿病研究中个体胰岛素敏感性、β细胞功能及糖尿病发病的相关性。
本研究纳入了 349 名无糖尿病的成年人（平均年龄 56.7 岁，51%为男性）的基线血浆样本，检测了循环神经酰胺和鞘磷脂种类。调整后的回归模型分别检测了这些种类与胰岛素敏感性（HOMA2-%S）、β细胞功能（口服葡萄糖处置指数：DIo）以及 5 年随访期间糖尿病发病的横断面和纵向相关性。基线时，四种神经酰胺（Ceramide C16:0、C18:0、C20:0 和 C22:0）的浓度与 HOMA2-%S 呈负相关（所有 P 值均<0.05，Q 值均<0.05），与 5 年内 HOMA2-%S 的变化呈负相关（所有 P 值均<0.05，Q 值均<0.05）。没有神经酰胺与基线或 DIo 的变化相关。在与 HOMA2-%S 相关的四种神经酰胺中，只有神经酰胺 C18:0 与糖尿病发病显著正相关（RR/1SD 1.44，95%CI 1.10-1.80，P=0.006，Q=0.024）。血浆神经酰胺 C18:0 与糖尿病风险的相关性部分通过基线和 5 年之间 HOMA2-%S 的变化来介导（中介比例：61.5%，95%CI 21.1%-212.5%）。
血浆神经酰胺 C18:0 与糖尿病发病风险升高相关，部分通过基线和 5 年内胰岛素敏感性降低来介导。循环神经酰胺 C18:0 可能是识别糖尿病高危人群的潜在生物标志物。
