Ketone Bodies Derived From Medium-Chain Triglycerides Support Brain Metabolism and Function Under Hypoglycemia in Type 1 Diabetes Mellitus

IF 9.3 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Pub Date : 2026-07-01 DOI:10.2337/db26-0293

Domenico Tricò, Lihong Jiang, Daniel Spicer, Kathleen Page, Renata Belfort de Aguiar, Sarita Naik, Mary Savoye, Donna M. Caseria, Jagriti Arora, Graeme F. Mason, Todd Constable, Douglas L. Rothman, Raimund I. Herzog

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Abstract

Impaired cognitive function caused by insulin-induced hypoglycemia is a complication of type 1 diabetes mellitus (T1DM) for which no protective strategies are currently available. In this first-in-human mechanistic study using magnetic resonance spectroscopy, the direct contribution of the infused ketone β-hydroxybutyrate (BHB) to brain metabolism during clamped hypoglycemia was greater in participants with T1DM than healthy participants. In a randomized dietary intervention trial of participants with T1DM and recurrent hypoglycemia, receiving medium-chain triglycerides (MCTs) as a dietary ketone precursor was associated with higher working memory performance and greater regional brain activation during clamped hypoglycemia compared with an isocaloric standard diet. Counterregulatory hormone responses to hypoglycemia were not affected by MCT supplementation. We conclude that ketone bodies are well suited to support brain metabolism in persons with T1DM experiencing insulin-induced hypoglycemia. Dietary MCT supplementation raising BHB may represent a novel strategy to prevent hypoglycemia-induced brain injury in this vulnerable patient population. Article Highlights There are currently no strategies to prevent cognitive impairment caused by insulin-induced hypoglycemia in type 1 diabetes mellitus (T1DM). We examined whether β-hydroxybutyrate (BHB) supports brain metabolism during clamped hypoglycemia and whether dietary medium-chain triglycerides (MCTs), by raising BHB availability, elicit this protective effect. BHB contributed more to brain metabolism in participants with T1DM than in healthy control participants, and long-term MCT supplementation improved working memory and brain activation during hypoglycemia. Dietary MCT supplementation may protect against hypoglycemia-related cognitive deficits in T1DM.

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中链甘油三酯衍生的酮体支持1型糖尿病低血糖下的脑代谢和功能

胰岛素诱导的低血糖引起的认知功能受损是1型糖尿病（T1DM）的一种并发症，目前尚无有效的保护策略。在这项首次使用磁共振波谱技术进行的人体机制研究中，输注的酮β-羟基丁酸酯（BHB）对钳型低血糖患者脑代谢的直接贡献大于健康参与者。在一项针对T1DM和复发性低血糖患者的随机饮食干预试验中，与等热量标准饮食相比，接受中链甘油三酯（mct）作为饮食酮前体的患者在夹紧性低血糖期间具有更高的工作记忆表现和更大的区域脑激活。抗调节激素对低血糖的反应不受MCT补充的影响。我们的结论是，酮体非常适合支持胰岛素诱导低血糖的T1DM患者的脑代谢。饮食中补充MCT提高BHB可能是一种预防低血糖引起的脑损伤的新策略。目前还没有预防1型糖尿病（T1DM）患者胰岛素诱导的低血糖引起的认知障碍的策略。我们研究了β-羟基丁酸酯（BHB）是否支持钳型低血糖期间的脑代谢，以及饮食中链甘油三酯（mct）是否通过提高BHB的可用性来引发这种保护作用。与健康对照组相比，BHB对T1DM参与者的脑代谢贡献更大，长期补充MCT可改善低血糖期间的工作记忆和大脑激活。膳食中补充MCT可防止T1DM患者出现与低血糖相关的认知缺陷。

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来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.