Evidence map›Paper›PMID 42376493›Full record

ArticleEClinicalMedicine2026

Predominantly genetic, intrauterine, and lifestyle aetiologies of type 2 diabetes are associated with distinct clinical presentations and risk of complications: a Danish cross-sectional and follow-up study.

Aleksander Lühr Hansen, Charlotte Brøns, Leonie Mieke Engelhard, Mette K Andersen, Jens Steen Nielsen, Peter Vestergaard, Kurt Højlund, Michael Hecht Olsen, Henrik Toft Sørensen, Reimar W Thomsen and 1 more

Abstract read
In one paragraph

Article in EClinicalMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

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

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.

Aleksander Lühr HansenSteno Diabetes Center Copenhagen, Herlev, Denmark.
Charlotte BrønsSteno Diabetes Center Copenhagen, Herlev, Denmark.
Leonie Mieke EngelhardSteno Diabetes Center Copenhagen, Herlev, Denmark.
Mette K AndersenNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Jens Steen NielsenSteno Diabetes Center Odense, Odense University Hospital, Odense, Denmark.
Peter VestergaardSteno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark.
Kurt HøjlundSteno Diabetes Center Odense, Odense University Hospital, Odense, Denmark.
Michael Hecht OlsenDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Henrik Toft SørensenDepartment of Clinical Epidemiology and Center for Population Medicine, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Reimar W ThomsenDepartment of Clinical Epidemiology and Center for Population Medicine, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Allan VaagSteno Diabetes Center Copenhagen, Herlev, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: We investigated whether individuals who likely developed type 2 diabetes (T2D) through predominantly genetic, adverse intrauterine, or lifestyle aetiologies have different clinical presentations and complications. Methods: In this Danish nationwide combined cross-sectional and registry-based follow-up study, we included 7867 individuals with newly diagnosed T2D from the DD2 cohort, enrolled during 2010-2023 through general practices and hospital outpatient clinics across Denmark. Participants were required to have available genotyping and birthweight data; those with GAD antibody levels >30 were excluded. Individuals were grouped by presumed predominant aetiologies: genetic (highest-quartile T2D genetic risk score (GRS), birthweight above lowest quartile; n = 1435); intrauterine (lowest-quartile birthweight, GRS below highest quartile; n = 1195); and lifestyle (birthweight above lowest quartile, GRS below highest quartile; n = 4380). Baseline characteristics at diagnosis were examined using linear and log-binomial or robust Poisson regression. The main follow-up outcomes were standardised 10-year risks of major adverse cardiovascular events and microvascular complications after DD2 enrolment, estimated using the Aalen-Johansen method. Findings: Compared with the genetic group (18%), intrauterine (15%) and lifestyle (56%) aetiologies both showed -6.9% lower Homeostatic Model Assessment-2 (HOMA2) insulin sensitivity, higher triglycerides (+6.6% and +5.3%), higher HOMA2 beta-cell function (+8.9% and +9.6%), and higher high-sensitivity C-reactive protein (+14.8% and +24.1%). Age at T2D diagnosis was 1.2 years lower (intrauterine) and 2.3 year higher (lifestyle). The 10-year risk of major adverse cardiovascular events was 14.8% (intrauterine), 13.2% (lifestyle), and 11.5% (genetic), corresponding to absolute risk differences (RDs) of +3.3% (95% confidence interval [CI] 0.6, 6.0) for intrauterine, and +1.7% (95% CI -0.3, 3.6) for lifestyle, Interpretation: Individuals who developed T2D with predominant intrauterine or lifestyle rather than genetic aetiology exhibited distinct characteristics including higher long-term complication risks. Future studies should validate this framework in more diverse populations and assess whether these proxy-based aetiological domains can improve risk stratification and guide treatment. Funding: This work was funded by Danish Agency for Science, the Danish Health and Medicines Authority, the Danish Diabetes Association, the Region of Southern Denmark, the Swedish Research Council, the Novo Nordisk Foundation, the Swedish ALF for Region Skåne, the Crafoord Foundation, and the Swedish Diabetes Association.

Indexed as

BirthweightDisease heterogeneityGenetic risk scoreInsulin resistanceIntrauterine environmentLife-course epidemiologyLifestyle-related riskMacrovascular complicationsMicrovascular complicationsType 2 diabetesVascular complications

Identifiers

PMID42376493
PMCPMC13312026

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.