Evidence map›Paper›PMID 40108650›Full record

ArticleClinical epigenetics2025

Type 2 diabetes impacts DNA methylation in human sperm.

Lei Su, Jonathan M Dreyfuss, Rafael Ferraz Bannitz, Danielle Wolfs, Georgia Hansbury, Lauren Richardson, Charnice Charmant, Jay Patel, Elizabeth S Ginsburg, Catherine Racowsky and 9 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03860558 (Impact of Metabolic Health on Sperm Epigenetic Marks in Humans), 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.

NCT03860558 naactive not recruitingnot on this map

Impact of Metabolic Health on Sperm Epigenetic Marks in Humans

TypeinterventionalSponsorJoslin Diabetes CenterRan2018 to 2026Enrolled40ConditionsOverweight, Type 2 Diabetes Mellitus, Type 1 Diabetes MellitusArmsLifestyle Intervention, No Intervention
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
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

19 authors.

Lei Su *Research Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Jonathan M Dreyfuss *Bioinformatics and Biostatistics Core, Research Division, Harvard Medical School, Joslin Diabetes Center, Boston, MA, USA.
Rafael Ferraz BannitzResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Danielle WolfsResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Georgia HansburyResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Lauren RichardsonResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Charnice CharmantResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Jay PatelDepartment of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Elizabeth S GinsburgDepartment of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Catherine RacowskyDepartment of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.
Ruby ForeDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School , Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Vissarion EfthymiouResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Jessica DesmondResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Allison GoldfineResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA.
Anne Ferguson-SmithDepartment of Genetics, University of Cambridge, Cambridge, CB2 3EH, UK.
Hui PanBioinformatics and Biostatistics Core, Research Division, Harvard Medical School, Joslin Diabetes Center, Boston, MA, USA.
Marie-France HivertDivision of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School , Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Elvira IsganaitisResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA. elvira.isganaitis@joslin.harvard.edu.
Mary Elizabeth PattiResearch Division, Harvard Medical School, Joslin Diabetes Center, 1 Joslin Place, Boston, MA, 02215, USA. Mary.elizabeth.patti@joslin.harvard.edu.

Funding

SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
Impact of Metabolic Health in Type 2 Diabetes on Sperm Epigenetic Marks in Humans: A Novel Intergenerational Mechanism for Metabolic Disease Risk TransmissionR21HD091974 · NICHD · JOSLIN DIABETES CENTER · PI ISGANAITIS, ELVIRA MARIE, PATTI, MARY E · 2018 to 2019
$462k
NICHD NIH HHS R21 HD091974NIDDK NIH HHS P30 DK036836NIH HHS R21HD091974
6 · The paper itself

Abstract

aims/hypothesisDisorders of the reproductive system, including hypogonadism and reduced fertility, are an under-recognized complication of diabetes. Based on experimental data in mice, hyperglycemia and obesity may modify epigenetic marks in sperm and impact health and development of offspring, but data are more limited in humans. Thus, we sought to study the impact of type 2 diabetes and glycemic control on sperm quality and DNA methylation.

methodsIn this prospective cohort study, we recruited 40 men with BMI greater than 25 kg/m

resultsMen with type 2 diabetes had higher levels of follicle-stimulating hormone (FSH), but similar testosterone levels and sperm quality as controls. Sperm DNA methylation was stable with repeat sampling at 3 months in men with and without type 2 diabetes. We identified differential methylation at 655 of 745,804 CpG sites in men with type 2 diabetes versus controls (FDR < 0.05). Of these, 96.5% showed higher methylation in type 2 diabetes, with a mean difference in DNA methylation (beta value, β) of 0.16 ± 0.004 (16 ± 0.4%). Ontology analysis of differentially methylated loci revealed annotation to genes regulating synaptic signaling, actin, cAMP-dependent pathways, and G protein-coupled receptor pathways. 24% of probes differentially regulated in men with type 2 diabetes versus control overlapped with probes associated with HbA1c, suggesting additional factors beyond glycemic control contributed to diabetes-associated differences in DNA methylation. CONCLUSIONS/

interpretationMen with type 2 diabetes showed higher DNA methylation levels in sperm relative to normoglycemic controls with similar BMI. Whether these differences are reversible with glucose-lowering treatment or may contribute to post-fertilization transcriptional regulation warrants further investigation.

trial registrationNCT03860558.

Indexed as

Diabetes Mellitus, Type 2DNA MethylationSpermatozoaAdultCohort StudiesCpG IslandsEpigenesis, GeneticFollicle Stimulating HormoneHumansMaleMiddle AgedProspective StudiesSemen AnalysisSperm MotilityFollicle Stimulating HormoneDNA methylationEpigeneticsSemen qualitySpermatozoaType 2 diabetes

Identifiers

PMID40108650
PMCPMC11924665

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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 OpenQuestion graph.