Evidence mapPaperPMID 42330299Full record

Trial reportDiabetes2026

Global and Partitioned Polygenic Risk Scores: Associations With Pathophysiology and Incidence of Type 2 Diabetes in People With Prediabetes.

Elsa Vazquez Arreola, William C Knowler, Robert L Hanson

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

3 authors.

Elsa Vazquez ArreolaPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.ORCID 0000-0003-1960-1159
William C KnowlerPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Robert L HansonPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.ORCID 0000-0002-4252-7068

Funding

Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases
6 · The paper itself

Abstract

Type 2 diabetes partitioned polygenic risk scores (pPRS) are related to their physiological impact on insulin secretion and sensitivity. We investigated associations of two pPRS sets obtained from multiancestry cohorts with the relationship between insulin secretion and sensitivity and diabetes incidence in the Diabetes Prevention Program (DPP). We generated 12 and 8 pPRS from soft- and hard-clustering approaches, respectively, in 2,052 DPP participants randomized to intensive lifestyle intervention, metformin, or placebo. Baseline insulin secretion demand and compensation were estimated through the relationship between secretion and sensitivity. Most expected associations of pPRS with insulin secretion and sensitivity were replicated. Some pPRS associated with lower secretion compensation. Global PRS associations with diabetes incidence were stronger than those of any pPRS in both sets. When insulin secretion compensation and demand modified pPRS associations with diabetes incidence, modification occurred only for demand: higher compensation associated with decreased diabetes incidence regardless of pPRS level. A β-cell dysfunction pPRS interacted with DPP treatments in a way that suggested that these treatments may be less effective in those genetically predisposed to diabetes due to insulin deficiency. Regardless of genetic risk as measured by pPRS, inadequate compensatory insulin secretion contributes to progression to diabetes in people with prediabetes. ARTICLE HIGHLIGHTS: The extent to which partitioned polygenic risk scores (pPRS) for type 2 diabetes influence the relationship between insulin secretion and sensitivity has not been examined in people with prediabetes. We investigated whether insulin secretion compensation and demand, estimated through the relationship between insulin secretion and sensitivity, mediated or modified the associations of two sets of pPRS with diabetes incidence in Diabetes Prevention Program participants. Several pPRS modified the effects of insulin demand on diabetes incidence, but none modified the effect of compensation. In people with prediabetes, inadequate compensatory insulin secretion contributes to progression to diabetes regardless of genetic risk as measured by pPRS.

Indexed as

Diabetes Mellitus, Type 2Prediabetic StateFemaleGenetic Risk ScoreHumansIncidenceInsulinInsulin ResistanceInsulin SecretionMaleMetforminMiddle AgedMultifactorial InheritanceInsulinMetformin

Identifiers

PMID42330299
PMCPMC13468951

What Socratic holds

Texttitle and abstract
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 Socratic graph.