Evidence mapPaperPMID 40971195Full record

ArticleDiabetes2025

Genome-Wide Association Study of Hypoglycemia in Adults With Diabetes in the Million Veteran Program.

Sridharan Raghavan, Elizabeth Litkowski, Aubrey Jensen, Brian Charest, Zeyuan Wang, Qin Hui, Hua-Chang Chen, Mary K Rhee, Aaron Leong, James B Meigs and 8 more

Abstract read
In one paragraph

Article in Diabetes, 2025. 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

18 authors.

Sridharan RaghavanSection of Academic Primary Care, U.S. Department of Veterans Affairs Eastern Colorado Health Care System, Aurora, CO.ORCID 0000-0003-0643-4873
Elizabeth LitkowskiSection of Academic Primary Care, U.S. Department of Veterans Affairs Eastern Colorado Health Care System, Aurora, CO.
Aubrey JensenPhoenix Veterans Affairs Medical Center, Phoenix, AZ.
Brian CharestU.S. Department of Veterans Affairs Boston Healthcare System, Boston, MA.
Zeyuan WangAtlanta Veterans Affairs Medical Center, Decatur, GA.
Qin HuiAtlanta Veterans Affairs Medical Center, Decatur, GA.
Hua-Chang ChenVeterans Affairs Tennessee Valley Healthcare System, Nashville, TN.
Mary K RheeAtlanta Veterans Affairs Medical Center, Decatur, GA.
Aaron LeongDepartment of Medicine, Massachusetts General Hospital, Boston, MA.
James B MeigsDepartment of Medicine, Massachusetts General Hospital, Boston, MA.ORCID 0000-0002-2439-2657
Leslie LangeDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO.
Ethan LangeDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO.
Peter ReavenPhoenix Veterans Affairs Medical Center, Phoenix, AZ.
Adriana HungVeterans Affairs Tennessee Valley Healthcare System, Nashville, TN.
Jin ZhouPhoenix Veterans Affairs Medical Center, Phoenix, AZ.
Yan V SunAtlanta Veterans Affairs Medical Center, Decatur, GA.
Lawrence S PhillipsAtlanta Veterans Affairs Medical Center, Decatur, GA.
Million Veteran Program*

Funding

Continuation of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) StudyU01DK098246 · NIDDK · GEORGE WASHINGTON UNIVERSITY · PI Heidi Krause-Steinrauf, JOHN M LACHIN · 2021 to 2022
$21.0M
Georgia Clinical & Translational Science Alliance (Georgia CTSA)UL1TR002378 · EMORY UNIVERSITY · 2025 to 2025
$9.3M
CHANGING THE NATURAL HISTORY OF TYPE 2 DIABETES – “CHANGE” STUDYR01DK127083 · EMORY UNIVERSITY · 2025 to 2025
$296k
The Role of Tuberculosis Disease on Non-Communicable Disease Risk: Comparative Analysis of Large Healthcare DatabasesR21AI156161 · NIAID · EMORY UNIVERSITY · PI Julia Alison Critchley, Matthew James Magee · 2022 to 2022
$132k
American Diabetes Association 7-22-ICTSPM-23BLRD VA I01 BX005831BLRD VA I01 BX006417Boettcher Foundation Webb Waring Biomedical Research AwardCSRD VA I01 CX001737CSRD VA IK2 CX001907Cystic Fibrosis Foundation PHILLI12A0Doris Duke Foundation 2020096NCATS NIH HHS UL1 TR002378NIAID NIH HHS R03 AI133172NIAID NIH HHS R21 AI156161NIDDK NIH HHS R01 DK127083NIDDK NIH HHS U01 DK098246NIH HHS R01 DK127083NIH HHS R03 AI133172NIH HHS R21 AI156161NIH HHS U01 DK098246NIH HHS UL1 TR002378U.S. Department of Veterans Affairs CSP #2008U.S. Department of Veterans Affairs I01-BX005831U.S. Department of Veterans Affairs I01-BX006417U.S. Department of Veterans Affairs I01 CX001899U.S. Department of Veterans Affairs IK2-CX001907
6 · The paper itself

Abstract

Hypoglycemia is a preventable adverse treatment effect in diabetes patients, but genetic markers to identify those with increased susceptibility are lacking. We performed a case/control genome-wide association study (GWAS) of hypoglycemia in U.S. Million Veteran Program (MVP) participants with medication-treated diabetes. Case participants had an outpatient random serum/plasma glucose <70 mg/dL or an emergency department visit for hypoglycemia. GWAS was stratified by race/ethnicity, adjusted for age at MVP enrollment, sex, and top 10 population-specific principal components, followed by multipopulation meta-analysis. Secondary analyses examined genetic associations with hypoglycemia stratified by diabetes medication exposure as well as replication in UK Biobank and the Action to Control Cardiovascular Risk in Diabetes clinical trial. The study included 72,244 (22,045 case participants) non-Hispanic White participants, 24,162 (10,441 case participants) non-Hispanic Black participants, and 9,196 (2,800 case participants) Hispanic participants. Four loci had genome-wide significant associations with hypoglycemia in multipopulation meta-analysis: rs12712928 (chromosome 2, SIX2/SIX3 locus), rs1064173 (chromosome 6, HLA-DQB1/DQA2 locus), rs35198068 (chromosome 10, TCF7L2 locus), and rs113748381 (chromosome 17, SCL16A11 locus). All four loci replicated in at least one independent cohort, and the magnitude of associations with hypoglycemia varied by diabetes type. Genome-wide analyses may complement candidate pharmacogenetic studies to identify risk markers of adverse drug effects. ARTICLE HIGHLIGHTS: Genetic variants associated with hypoglycemia risk in individuals with medication-treated diabetes have not been evaluated genome-wide. The specific question we asked was whether common genetic variants are associated with hypoglycemia among individuals with diabetes treated with glucose-lowering medications. We found four genomic loci were associated with hypoglycemia in a genome-wide association study. One locus-on chromosome 6-was associated with hypoglycemia only in individuals with likely type 1 diabetes, and two loci-on chromosome 2 and chromosome 6-were associated with hypoglycemia only in the context of treatment with sulfonylureas (chromosome 2) or with insulin (chromosome 6). Genetic variants may help identify individuals with diabetes at increased hypoglycemia risk, but additional study is needed to address the clinical utility of genetic data to inform hypoglycemia risk.

Indexed as

Diabetes MellitusHypoglycemiaHypoglycemic AgentsAdultAgedCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleMiddle AgedPolymorphism, Single NucleotideTranscription Factor 7-Like 2 ProteinUnited StatesVeteransHypoglycemic AgentsTranscription Factor 7-Like 2 Protein

Identifiers

PMID40971195
PMCPMC12645173

What Socratic holds

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Registered trials

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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.