Evidence mapPaperPMID 40045281Full record

Trial reportCardiovascular diabetology2025

A one-week reduced-carbohydrate diet to mitigate iatrogenic peripheral hyperinsulinemia does not improve insulin sensitivity or endothelial function in a randomized, crossover trial in patients with type 1 diabetes.

Justin M Gregory, T Jordan Smith, Sara H Duffus, David Brooks, M Naweed Akbar, Margaret-Anne Huntley, JoAnn A Gottlieb, Lauren M LeStourgeon, Christopher S Wilson, Joshua A Beckman and 1 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04118374 (A Study to Determine Iatrogenic Hyperinsulinemia's Contribution to Insulin Resistance and Endothelial Dysfunction in Type 1 Diabetes), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

NCT04118374 nacompletednot on this map

A Study to Determine Iatrogenic Hyperinsulinemia's Contribution to Insulin Resistance and Endothelial Dysfunction in Type 1 Diabetes

TypeinterventionalSponsorVanderbilt University Medical CenterRan2021 to 2024Enrolled14ConditionsDiabetes Mellitus, Type 1ArmsStandard Carb Diet, Low Carb Diet
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

11 authors.

Justin M GregoryIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, 1500 21st Avenue South, Suite 1514, Nashville, TN, 37212-3157, USA. justin.m.gregory.1@vumc.org.
T Jordan SmithIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, 1500 21st Avenue South, Suite 1514, Nashville, TN, 37212-3157, USA.
Sara H DuffusIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, 1500 21st Avenue South, Suite 1514, Nashville, TN, 37212-3157, USA.
David BrooksMildred Stahlman Division of Neonatology, Vanderbilt University School of Medicine, 1161 21st Ave S A0126, Nashville, TN, 37232, USA.
M Naweed AkbarIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, 1500 21st Avenue South, Suite 1514, Nashville, TN, 37212-3157, USA.
Margaret-Anne HuntleyIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, 1500 21st Avenue South, Suite 1514, Nashville, TN, 37212-3157, USA.
JoAnn A GottliebVanderbilt Institute for Clinical and Translational Research, Vanderbilt University School of Medicine, 2525 West End Ave., Nashville, TN, 37203-8820, USA.
Lauren M LeStourgeonDepartment of Internal Medicine, Vanderbilt University School of Medicine, 1161 21st Ave S, Nashville, TN, 37232, USA.
Christopher S WilsonIan Burr Division of Pediatric Endocrinology and Diabetes, Vanderbilt University School of Medicine, 1500 21st Avenue South, Suite 1514, Nashville, TN, 37212-3157, USA.
Joshua A BeckmanDivision of Vascular Medicine, University of Texas Southwestern, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA.
Alan D CherringtonDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 2301 Vanderbilt Place, Nashville, TN, 37240, USA.

Funding

Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR002243 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$10.7M
UAB Diabetes Research CenterP30DK079626 · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2025 to 2025
$1.3M
Juvenile Diabetes Research Foundation United States of America 5-ECR-2020-950-A-NNCATS NIH HHS TR002243NCATS NIH HHS UL1 TR002243NIDDK NIH HHS DK00706NIDDK NIH HHS DK123392NIDDK NIH HHS P30 DK079626
6 · The paper itself

Abstract

backgroundIatrogenic peripheral hyperinsulinemia, resulting from peripheral insulin administration in type 1 diabetes, may increase insulin resistance and impair endothelial function. We hypothesized that lowering iatrogenic peripheral hyperinsulinemia via a one-week, reduced-carbohydrate diet (RCD) would improve insulin sensitivity and endothelial function compared with an isocaloric standard carbohydrate diet (SCD).

methodsIn this randomized, single-blinded, crossover trial, we studied 12 adults with type 1 diabetes. Participants completed both a one-week RCD and a one-week SCD, separated by a three-week washout. After each intervention, we measured insulin sensitivity using a hyperinsulinemic-euglycemic clamp and assessed endothelial function via brachial-artery flow-mediated vasodilation (FMD).

resultsThe RCD reduced total daily insulin doses by 16% compared with the SCD. Despite this reduction, insulin sensitivity did not improve (median glucose infusion rates: RCD 8.1 mg/kg FFM/min [IQR 6.7-10.1] vs. SCD 8.6 mg/kg FFM/min [7.0-11.0], p = 0.47). Similarly, endothelial function did not differ significantly (FMD after RCD 7.50% [3.25-15.5] vs. SCD 9.81% [4.96-14.3], p = 0.91). Although higher insulin doses correlated with lower insulin sensitivity under both conditions, lowering insulin dose through the RCD alone did not yield measurable improvements.

conclusionsAlthough a one-week RCD significantly lowered insulin requirements, it failed to enhance insulin sensitivity or endothelial function in adults with type 1 diabetes. These findings underscore the complex and dynamic relationship between insulin exposure and cardiometabolic health. Similar basal overnight insulin delivery may have masked potential benefits by the time of testing, highlighting the need for further studies to refine strategies aimed at mitigating hyperinsulinemia's adverse effects.

trial registrationClinicalTrials.gov NCT04118374.

Indexed as

Diabetes Mellitus, Type 1Diet, Carbohydrate-RestrictedEndothelium, VascularHyperinsulinismHypoglycemic AgentsInsulinInsulin ResistanceAdultBiomarkersBlood GlucoseBrachial ArteryCross-Over StudiesFemaleGlucose Clamp TechniqueHumansMaleBiomarkersBlood GlucoseHypoglycemic AgentsInsulinEndothelial dysfunctionEndothelial functionHyperinsulinemiaInsulin resistanceInsulin sensitivityReduced-carbohydrate dietType 1 diabetes

Identifiers

PMID40045281
PMCPMC11884211

What Socratic holds

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Registered trials

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 Socratic graph.