Evidence map›Paper›PMID 42384016›Full record

Trial reportDiabetes2026

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

Domenico Tricò, Lihong Jiang, Daniel Spicer, Kathleen Page, Renata Belfort de Aguiar, Sarita Naik, Mary Savoye, Donna M Caseria, Jagriti Arora, Graeme F Mason and 3 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Domenico TricòSection of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.ORCID 0000-0002-7633-1346
Lihong JiangMagnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT.
Daniel SpicerSection of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
Kathleen PageSection of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
Renata Belfort de AguiarSection of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
Sarita NaikSection of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
Mary SavoyeSection of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
Donna M CaseriaHospital Research Unit Bionutritional Services, Yale New Haven Hospital, New Haven, CT.
Jagriti AroraMagnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT.
Graeme F MasonMagnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT.
Todd ConstableMagnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT.
Douglas L RothmanMagnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT.
Raimund I HerzogSection of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.ORCID 0009-0009-1632-1435

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Kevan C Herold, GERALD I SHULMAN · 1993 to 2026
$44.0M
GLUCOREGULATORY HORMONE INTERACTIONS IN DIABETESR01DK020495 · NIDDK · YALE UNIVERSITY · PI ROTHMAN, DOUGLAS LYLE · 1986 to 2022
$6.6M
Regulation of Brain Glucose Metabolism in Type 1 DiabetesR01DK101984 · NIDDK · YALE UNIVERSITY · PI HERZOG, RAIMUND INGO · 2014 to 2023
$3.8M
Drinking, Brain Acetate, and StressR01AA031401 · NIAAA · YALE UNIVERSITY · PI Graeme F Mason · 2024 to 2026
$2.0M
Adaptations of Brain Energy Metabolism to HypoglycemiaK08DK082618 · NIDDK · YALE UNIVERSITY · PI HERZOG, RAIMUND INGO · 2010 to 2014
$722k
Human Brain Ketone Metabolism in Type 1 Diabetes and Hypoglycemia.R03DK100709 · NIDDK · YALE UNIVERSITY · PI HERZOG, RAIMUND INGO · 2014 to 2015
$164k
JDRF 4-2010-433NCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1TR001863NIAAA NIH HHS R01 AA031401NIDDK NIH HHS K08 DK082618NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK020495NIDDK NIH HHS R01 DK101984NIDDK NIH HHS R03 DK100709NIH/NIDDK K08 DK082618NIH/NIDDK P30 DK045735NIH/NIDDK R01 DK020495NIH/NIDDK R01 DK101984NIH/NIDDK R03 DK100709
6 · The paper itself

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.

Indexed as

BrainDiabetes Mellitus, Type 1HypoglycemiaKetone BodiesTriglycerides3-Hydroxybutyric AcidAdultFemaleHumansInsulinMagnetic Resonance SpectroscopyMale3-Hydroxybutyric AcidInsulinKetone BodiesTriglycerides

Identifiers

PMID42384016
PMCPMC13493211

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.