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May 19, 2026Cardiovascular Diabetology2 citationsOpen Access

Predicting cardiovascular death in overweight/obese people with prediabetes using machine learning—a proof-of-concept study

AAAmalie K. AndersenKFKristine FærchDVDorte Vistisen

Key Result

A 7-feature machine learning model predicted short-term cardiovascular death in overweight/obese individuals with prediabetes and prior cardiovascular disease with an acceptable ROC AUC of 0.730.

Key Points

  • The aim is to create a predictive model for cardiovascular death risk in overweight/obese individuals with prediabetes.
  • Developed a binary logistic regression model using data from 5636 participants (≥45 years) with prediabetes and established cardiovascular disease.
  • Performed stratified threefold cross-validation to evaluate model performance.
  • Calculated ROC AUC to examine the model's predictive capability.
  • The model achieved an acceptable discrimination with ROC AUC of 0.730 (95% CI 0.659–0.801).
  • Compared to existing models (SCORE2: 0.630, SCORE2-Diabetes: 0.643), our model showed superior performance for predicting cardiovascular death.
  • No existing prediction models are available for individuals with prediabetes and prior cardiovascular disease.

Study Design

Type

Cohort (n=5,636)

Multicenter

Yes

Structured PICO

Does a prediabetes-specific machine learning model accurately predict cardiovascular death in overweight/obese individuals with prediabetes and established CVD compared to existing benchmark models?

P
Population
5,636 participants ≥ 45 years with prediabetes (HbA1c 39–47 mmol/mol [5.7–6.4%]), established cardiovascular disease, and overweight/obesity.
I
Intervention
Prediabetes-specific machine learning prediction model (binary logistic regression) using seven demographic and clinical variables.
C
Comparator
Existing benchmark models (SCORE2 and SCORE2-Diabetes).
O
Outcome
Cardiovascular death.hard clinical

A prediabetes-specific machine learning model showed acceptable discrimination for predicting cardiovascular death in high-risk individuals, outperforming existing general models like SCORE2.

Main Result

Absolute Event Rate: 0.73% vs 0.63%

Limitations

  • External validation of the model is crucial before adoption to a real-world setting to clarify whether the model generalizes beyond the studied population.
  • The populations used in the benchmark models (SCORE2 and SCORE2-Diabetes) do not include people with a history of CVD and use a 10-year horizon.
  • 3-point MACE is the primary endpoint in SCORE2 and SCORE2-Diabetes, making evaluation on CV death difficult.
  • No publicly available CVD risk models specifically for prediabetes exist for direct comparison.
  • Lack of external validation to clarify generalizability beyond the studied population

Abstract

Individuals with prediabetes face an increased risk of cardiovascular (CV) complications, which can ultimately lead to premature mortality. However, existing risk stratification tools are not targeted for people with prediabetes. We aimed to develop a simple explainable model to predict if a person will develop a fatal CV outcome or not among people with prediabetes. Participants ≥ 45 years with prediabetes (HbA1c 39–47 mmol/mol (5.7–6.4%)) and established CV disease and overweight/obesity were included. A binary logistic regression model was trained to predict CV death using stratified threefold cross-validation. The model’s risk estimates were calibrated, and the predictive capability was evaluated using receiver operating characteristic (ROC) area under the curve (AUC), precision and recall. In total 5636 participants with 182 (3.2%) CV deaths (mean time-to-event of 2.0 years) and a mean trial duration of 3.3 years were included. Seven easily collected demographic and clinical variables were selected for the model. Discrimination (ROC AUC) was acceptable at 0.730 (95% CI 0.659–0.801). Applying our prediabetes cohort on existing benchmark models developed for major adverse cardiovascular events (MACE) in a general and type 2 diabetes population without prior CVD, demonstrated lower performance for CV death (ROC AUC: 0.630 (SCORE2) and 0.643 (SCORE2-Diabetes)) compared to our model. Lower performance was also observed for predicting MACE in our cohort (ROC AUC: 0.596 and 0.603) using the established models compared to the original populations (ROC AUC: 0.739 and 0.66–0.73). No comparative models for people with prediabetes and prior CVD exists. Thus, even with the limitations in different populations and outcome targets, this indicates that prediabetes-specific prediction models could potentially improve early prevention in this high-risk population. We have developed a prediabetes-specific proof-of-concept model that predicts whether a person is at high risk of cardiovascular death. External validation of the model is crucial before adoption to a real-world setting to clarify whether the model generalizes beyond the studied population.

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Cite This Study

Andersen et al. (2026) conducted a cohort in Prediabetes with overweight/obesity and established cardiovascular disease (n=5,636). 7-feature logistic regression prediction model vs. SCORE2 and SCORE2-Diabetes benchmark models was evaluated on Cardiovascular death prediction (ROC AUC) (95% CI 0.659-0.801). A 7-feature machine learning model predicted short-term cardiovascular death in overweight/obese individuals with prediabetes and prior cardiovascular disease with an acceptable ROC AUC of 0.730.

synapsesocial.com/papers/6a0bfe2d166b51b53d379751https://doi.org/10.1186/s12933-026-03210-3
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Predictive performance of established cardiovascular risk scores in the prediabetic population: external validation using the UK Biobank data set2023 · 4 citations
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  4. 4Developing a Simple Non–Laboratory-Based Machine Learning Tool for Prediabetes Screening in a Target Population: A Proof-of-Concept Study2025
  5. 5Development and validation of a prediction model based on machine learning algorithms for predicting the risk of heart failure in middle‐aged and older US people with prediabetes or diabetes2023 · 18 citations