Evidence map›Paper›PMID 41074977›Full record

ArticleDiabetologia2026

Shared and distinct metabolomics profiles associated with microvascular complications in the Diabetes Prevention Program Outcomes Study.

Wei Perng, Shiyu Shu, David M Nathan, Jose A Luchsinger, Robert E Gerszten, Roeland J W Middelbeek, Steven E Kahn, William C Knowler, Dana Dabelea, Marinella Temprosa and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetologia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Lifestyles, metabolome and diabetic kidney disease: a cohort study.QJM : monthly journal of the Association of Physicians · 2026
    Article
  4. Review
  5. Review
  6. 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

11 authors.

Wei PerngLifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Department of Epidemiology at the Colorado School of Public Health and the University of Colorado Anschutz Medical Campus, Aurora, CO, USA. dppmail@bsc.gwu.edu.ORCID 0000-0001-8552-6850
Shiyu ShuDepartment of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Rockville, MD, USA.
David M NathanDiabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Jose A LuchsingerDepartments of Medicine and Epidemiology, Columbia University Irving Medical Center, New York, NY, USA.
Robert E GersztenBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Roeland J W MiddelbeekJoslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
Steven E KahnDivision of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA.
William C KnowlerConsultant, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Rockville, MD, USA.
Dana DabeleaLifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Department of Epidemiology at the Colorado School of Public Health and the University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Marinella TemprosaDepartment of Biostatistics and Bioinformatics, Milken Institute School of Public Health, George Washington University, Rockville, MD, USA.
DPP Research Group

Funding

PRIMARY PREVENTION TRIAL--DATA COORDINATING CENTERU01DK048489 · NIDDK · GEORGE WASHINGTON UNIVERSITY · PI JABLONSKI, KATHLEEN ANN, TEMPROSA, MARINELLA · 1994 to 2021
$84.8M
Physical activity, physical function, and frailty in relation to cognitive impairment and AD/ADRD biomarkers in DPPOSU19AG078558 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Jose Alejandro Luchsinger, DAVID M NATHAN · 2022 to 2026
$82.5M
SPECIAL ASSAY COREP30DK036836 · NIDDK · JOSLIN DIABETES CENTER · PI ROHIT N. KULKARNI · 1986 to 2026
$50.5M
ROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Elizabeth Austen Lawson, Takara Leah Stanley · 1994 to 2026
$31.6M
Post-DDP Follow-up StudyU01DK048413 · NIDDK · UNIVERSITY OF WASHINGTON · PI KAHN, STEVEN EMANUEL · 1994 to 2021
$13.7M
PRIMARY PREVENTION TRIAL (DPT-2)U01DK048397 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI NATHAN, DAVID M · 1994 to 2021
$12.0M
NIDDM PRIMARY PREVENTION TRIAL (DPT 2)U01DK048404 · NIDDK · ST. LUKE'S-ROOSEVELT INST FOR HLTH SCIS · PI LAFERRERE, BLANDINE B · 1994 to 2021
$11.6M
PRIMARY PREVENTION TRIAL (DPT-2)U01DK048339 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ARANETA, MARIA ROSARIO GORREZ, MUDALIAR, SUNDER · 1994 to 2022
$11.4M
NIDDM PRIMARY PREVENTION TRIALU01DK048412 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VENDITTI, ELIZABETH MARY · 1994 to 2021
$11.4M
PRIMARY PREVENTION TRIALU01DK048387 · NIDDK · MEDSTAR RESEARCH INSTITUTE · PI MAGEE, MICHELLE FISCHMANN · 1994 to 2022
$11.1M
TITLE OMITTEDU01DK048349 · NIDDK · YESHIVA UNIVERSITY · PI CRANDALL, JILL P · 1994 to 2021
$11.0M
PRIMARY PREVENTION TRIALU01DK048443 · NIDDK · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WATSON, KAROL E · 1994 to 2021
$10.2M
NIA NIH HHS 5 U19 AG078558NIA NIH HHS U19 AG078558NIDDK NIH HHS P30 DK036836NIDDK NIH HHS P30 DK040561NIDDK NIH HHS U01 DK048339NIDDK NIH HHS U01 DK048349NIDDK NIH HHS U01 DK048375NIDDK NIH HHS U01 DK048377NIDDK NIH HHS U01 DK048380NIDDK NIH HHS U01 DK048381NIDDK NIH HHS U01 DK048387NIDDK NIH HHS U01 DK048397NIDDK NIH HHS U01 DK048400NIDDK NIH HHS U01 DK048404NIDDK NIH HHS U01 DK048406NIDDK NIH HHS U01 DK048407NIDDK NIH HHS U01 DK048411NIDDK NIH HHS U01 DK048412NIDDK NIH HHS U01 DK048413NIDDK NIH HHS U01 DK048434NIDDK NIH HHS U01 DK048437NIDDK NIH HHS U01 DK048443NIDDK NIH HHS U01 DK048468NIDDK NIH HHS U01 DK048485NIDDK NIH HHS U01 DK048489NIDDK NIH HHS U01 DK048514
6 · The paper itself

Abstract

aims/hypothesisThe aim of this study was to identify shared and distinct metabolite profiles prospectively associated with nephropathy, retinopathy and neuropathy at 15 years' follow-up among 1947 participants in the Diabetes Prevention Program Outcomes Study, the long-term follow-up of the Diabetes Prevention Program (DPP).

methodsWe applied bootstrapped LASSO to 353 annotated metabolites to identify metabolites associated with one or more complication. For these metabolite hits, we tested for an interaction with DPP treatment arm, and ran multivariable models for the pooled sample or within treatment group as appropriate.

resultsAt follow-up, 572 participants had one or more complication (n=277 nephropathy, n=194 retinopathy, n=212 neuropathy). Of 105 metabolites that predicted any complication, 74 predicted one, 27 predicted two, and four predicted all three. In a pooled analysis of 69 metabolites without treatment arm interactions, histidine predicted lower odds of nephropathy (OR 0.75; 95% CI 0.69, 0.88), and serine predicted lower odds of nephropathy (OR 0.69; 95% CI 0.58, 0.82) and neuropathy (OR 0.68; 95% CI 0.56, 0.84). Of 36 metabolites that interacted with treatment arm, higher N-carbamoyl-β-alanine predicted greater odds of nephropathy (OR 1.99; 95% CI 1.38, 2.99) and C22:0-sphingomyelin predicted lower odds of neuropathy (OR 0.54; 95% CI 0.37, 0.77) in the metformin arm. In the lifestyle intervention arm, quinolinic acid predicted greater odds of neuropathy (OR 1.64; 95% CI 1.24, 2.19). These estimates accounted for sex, race, baseline age, BMI and smoking, and time elapsed during follow-up. Further adjustment for HbA CONCLUSIONS/

interpretationThe existence of distinct metabolite profiles associated with single microvascular complications highlights the importance of characterising pathophysiological mechanisms specific to each complication, in addition to studying shared mechanisms across multiple complications.

Indexed as

Diabetes Mellitus, Type 2Diabetic AngiopathiesDiabetic NephropathiesDiabetic NeuropathiesMetabolomicsAgedDiabetic RetinopathyFemaleFollow-Up StudiesHumansMaleMetabolomeMiddle AgedProspective StudiesCohort studyMetabolomicsMicrovascular complicationsNeuropathyRetinopathy

Identifiers

PMID41074977
PMCPMC12685977

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