1型糖尿病中与代谢功能障碍相关脂肪性肝病相关的代谢物扰动。
Metabolite perturbations in type 1 diabetes associated with metabolic dysfunction-associated steatotic liver disease.
作者信息
Taiwo Adeyinka, Merrill Ronald A, Wendt Linder, Pape Daniel, Thakkar Himani, Maschek J Alan, Cox James, Summers Scott A, Chaurasia Bhagirath, Pothireddy Nikitha, Carlson Bianca B, Sanchez Antonio, Ten Eyck Patrick, Jalal Diana, Dokun Ayotunde, Taylor Eric B, Sivitz William I
机构信息
Division of Endocrinology, Department of Internal Medicine, University of Iowa Health Care, Iowa City, IA, United States.
Fraternal Order of Eagles Diabetes Center, University of Iowa, Iowa City, IA, United States.
出版信息
Front Endocrinol (Lausanne). 2025 Jun 3;16:1500242. doi: 10.3389/fendo.2025.1500242. eCollection 2025.
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.
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。尽管MASLD在2型糖尿病（T2D）患者中已得到广泛研究，但关于1型糖尿病（T1D）中MASLD的发病机制和严重程度的了解却少得多。
目的
确定T1D患者中与MASLD相关的代谢紊乱。
研究设计
我们对30名T1D参与者进行了一项横断面研究。根据FibroScan的结果，将参与者分为病例组（MASLD）或对照组。在参与者午夜后禁食过夜后，对其血浆进行代谢组学分析。
结果
30名参与者中有17名被分类为病例组（MASLD），13名作为对照组。病例组的体重指数（BMI）较高（p<0.001），且每日胰岛素剂量高于对照组（p=0.003）。代谢组学分析显示，患有MASLD的患者中糖异生底物丙酮酸（p=0.001）和乳酸（p=0.043）、糖异生氨基酸丙氨酸（p<0.001）和谷氨酸（p=0.004）、苯丙氨酸（p=0.003）和邻氨基苯甲酸（p=0.015）的水平升高。脂质组学显示，MASLD组中神经酰胺（P=0.02）、二酰甘油（p=0.0009）和三酰甘油（P=0.0004）升高。在患有MASLD的患者中，酰基肉碱、异戊酰肉碱（CAR.5.0）（P=0.002）和L-棕榈酰肉碱（CAR.16.0）（P=0.048）升高。使用MetaboAnalyst 5.0软件进行的通路分析显示，包括苯丙氨酸和酪氨酸代谢、色氨酸代谢、葡萄糖-丙氨酸循环、谷氨酸代谢和谷胱甘肽代谢在内的通路在患有MASLD的患者中显著富集。
结论
T1D和MASLD参与者表现出胰岛素抵抗和代谢紊乱的特征，提示糖异生增强、脂肪合成功能障碍和三羧酸循环活性紊乱。
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