Metabolite perturbations in type 1 diabetes associated with metabolic dysfunction-associated steatotic liver disease.

IF 3.9 2区医学 Q2 ENDOCRINOLOGY & METABOLISM

Frontiers in Endocrinology Pub Date : 2025-06-03 eCollection Date: 2025-01-01 DOI:10.3389/fendo.2025.1500242

Adeyinka Taiwo, Ronald A Merrill, Linder Wendt, Daniel Pape, Himani Thakkar, J Alan Maschek, James Cox, Scott A Summers, Bhagirath Chaurasia, Nikitha Pothireddy, Bianca B Carlson, Antonio Sanchez, Patrick Ten Eyck, Diana Jalal, Ayotunde Dokun, Eric B Taylor, William I Sivitz

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引用次数: 0

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Although MASLD has been widely studied in persons with Type 2 diabetes (T2D), far less in known about the pathogenesis and severity of MASLD in Type 1 diabetes (T1D).

Objectives: Determine metabolic perturbations associated with MASLD in persons with T1D.

Study design: We conducted a cross-sectional study of 30 participants with T1D. Based on the results of a FibroScan, participants were stratified as cases (MASLD) or controls. Metabolomic analyses were performed on plasma obtained from all participants after an overnight (after midnight) fast.

Results: 17 of 30 participants were classified as cases (MASLD) and 13 as controls. Cases had higher BMI (p=<0.001) and were taking higher daily insulin doses than controls (p=0.003). Metabolomic analyses revealed that those with MASLD had elevated levels of gluconeogenic substrates pyruvate (p=0.001) and lactate (p=0.043), gluconeogenic amino acids alanine (p<0.001) and glutamate (p=0.004), phenylalanine (p=0.003), and anthranilic acid (p=0.015). Lipidomics revealed, elevated ceramides (P=0.02), diacylglycerols (p=0.0009) and triacylglycerols (P=0.0004) in MASLD group. In those with MASLD, the acylcarnitines, isovalerylcarnitine (CAR.5.0) (P=0.002) and L-Palmitoylcarnitine (CAR.16.0) (P=0.048), were elevated. Pathway analyses using MetaboAnalyst 5.0 Software revealed that, pathways including phenylalanine and tyrosine metabolism, tryptophan metabolism, glucose-alanine cycle, glutamate metabolism, and glutathione metabolism were significantly enriched in those with MASLD.

Conclusion: Participants with T1D and MASLD manifest features of insulin resistance and metabolite perturbations suggesting enhanced gluconeogenesis, dysfunctional fat synthesis, and perturbed TCA cycle activity.

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代谢物紊乱与代谢功能障碍相关的1型糖尿病脂肪变性肝病

背景：代谢功能障碍相关脂肪性肝病（MASLD），以前称为非酒精性脂肪性肝病（NAFLD），是代谢综合征的肝脏表现。虽然MASLD在2型糖尿病（T2D）患者中已经被广泛研究，但对1型糖尿病（T1D） MASLD的发病机制和严重程度知之甚少。目的：确定T1D患者与MASLD相关的代谢紊乱。研究设计：我们对30名T1D患者进行了横断面研究。根据纤维扫描的结果，参与者被分层为病例（MASLD）或对照组。对所有参与者在一夜（午夜之后）禁食后获得的血浆进行代谢组学分析。结果：30例患者中17例为病例，13例为对照。结论：T1D和MASLD患者表现出胰岛素抵抗和代谢物紊乱的特征，表明糖异生增强，脂肪合成功能障碍，TCA循环活性紊乱。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Endocrinology Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

5.70

自引率

9.60%

发文量

3023

审稿时长

14 weeks

期刊介绍： Frontiers in Endocrinology is a field journal of the "Frontiers in" journal series. In today’s world, endocrinology is becoming increasingly important as it underlies many of the challenges societies face - from obesity and diabetes to reproduction, population control and aging. Endocrinology covers a broad field from basic molecular and cellular communication through to clinical care and some of the most crucial public health issues. The journal, thus, welcomes outstanding contributions in any domain of endocrinology. Frontiers in Endocrinology publishes articles on the most outstanding discoveries across a wide research spectrum of Endocrinology. The mission of Frontiers in Endocrinology is to bring all relevant Endocrinology areas together on a single platform.