Insenser María Rosa, Nattero-Chávez Lía, Luque-Ramírez Manuel, Quiñones Sara de Lope, Quintero-Tobar Alejandra, Samino Sara, Amigó Núria, Dorado Avendaño Beatriz, Fiers Tom, Escobar-Morreale Héctor F
Diabetes, Obesity and Human Reproduction Research Group, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) & Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Universidad de Alcalá, 28034 Madrid, Spain.
Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain.
Metabolites. 2024 Aug 6;14(8):436. doi: 10.3390/metabo14080436.
Sexual dimorphism influences cardiovascular outcomes in type 1 diabetes (T1D), with women facing a higher relative risk of macrovascular events compared to men, especially after menopause. This study hypothesizes that abnormalities in intermediate metabolism may be associated with cardiac autonomic neuropathy (CAN) in T1D. We aim to assess low molecular weight metabolites (LMWM) as markers of CAN in T1D, considering the effects of sexual dimorphism and age. In this cross-sectional study, we included 323 subjects with T1D (147 women and 176 men), with a mean age of 41 ± 13 years. A total of 44 women and 41 men were over 50 years old. CAN was assessed using Ewing's tests, and serum metabolites were analyzed by proton nuclear magnetic resonance spectroscopy (H-NMR). Patients with CAN had lower levels of valine, isoleucine, and threonine, and higher levels of lactate, compared to those without CAN. These differences persisted after adjusting for BMI and estimated glucose disposal rate (eGDR). In a logistic regression model (R² = 0.178, < 0.001), the main determinants of CAN included isoleucine [Exp(β) = 0.972 (95% CI 0.952; 0.003)], age [Exp(β) = 1.031 (95% CI 1.010; 1.053)], A [Exp(β) = 1.361 (95% CI 1.058; 1.752)], and microangiopathy [Exp(β) = 2.560 (95% CI 1.372; 4.778)]. Sex influenced LMWM profiles, with over half of the metabolites differing between men and women. However, no interactions were found between CAN and sex, or between sex, age, and CAN, on metabolomics profiles. Our findings suggest an association between CAN and LMWM levels in T1D. The sexual dimorphism observed in amino acid metabolites was unaffected by the presence of CAN.
性别差异影响1型糖尿病（T1D）患者的心血管结局，与男性相比，女性发生大血管事件的相对风险更高，尤其是在绝经后。本研究假设，中间代谢异常可能与T1D患者的心脏自主神经病变（CAN）有关。我们旨在评估低分子量代谢物（LMWM）作为T1D患者CAN的标志物，并考虑性别差异和年龄的影响。在这项横断面研究中，我们纳入了323例T1D患者（147例女性和176例男性），平均年龄为41±13岁。共有44名女性和41名男性年龄超过50岁。使用尤因测试评估CAN，并通过质子核磁共振波谱（H-NMR）分析血清代谢物。与无CAN的患者相比，CAN患者的缬氨酸、异亮氨酸和苏氨酸水平较低，乳酸水平较高。在调整体重指数（BMI）和估计的葡萄糖处置率（eGDR）后，这些差异仍然存在。在逻辑回归模型（R² = 0.178，P < 0.001）中，CAN的主要决定因素包括异亮氨酸[Exp(β) = 0.972（95%CI 0.952；0.003）]、年龄[Exp(β) = 1.031（95%CI 1.010；1.053）]、白蛋白[Exp(β) = 1.361（95%CI 1.058；1.752）]和微血管病变[Exp(β) = 2.560（95%CI 1.372；4.778）]。性别影响LMWM谱，超过一半的代谢物在男性和女性之间存在差异。然而，在代谢组学谱上，未发现CAN与性别之间，或性别、年龄与CAN之间存在相互作用。我们的研究结果表明，T1D患者的CAN与LMWM水平之间存在关联。在氨基酸代谢物中观察到的性别差异不受CAN存在的影响。
