# High predicted cardiac event risk in youth with obesity and type 2 diabetes: a pooled cohort analysis

## TL;DR

Youth with obesity and type 2 diabetes face significantly higher predicted risk of future heart events compared to lean or overweight peers.

## Contribution

A novel pooled cohort analysis using the i3C combined-risk z-score reveals heightened cardiovascular risk in youth with type 2 diabetes.

## Key findings

- Youth with type 2 diabetes had a 4.25 hazard ratio for predicted CVD events compared to lean peers.
- Lipoprotein and inflammatory factors like ApoB, LDL-P, and hsCRP significantly increase predicted CVD risk.
- Youth with type 2 diabetes had 4.5 times higher predicted CVD risk than lean peers and 1.4 times higher than overweight/obese peers.

## Abstract

Despite the growing burden of youth-onset type 2 diabetes (Y-T2D), the long-term risk for fatal/non-fatal cardiovascular disease (CVD) in Y-T2D compared to peers is unknown. The International Childhood Cardiovascular Cohort (i3C) combined-risk z-score is a novel tool for predicting 35-year risk of adult CVD events. In Y-T2D compared to peers (Lean and overweight/obesity [OW/OB]), we estimated predicted CVD events and evaluated the relationship of the i3C z-score with risk-enhancing factors.

In a pooled cohort cross-sectional analysis of 1547 adolescents and young adults (AYA) aged 10–25 years [627 Lean, 803 OW/OB, 117 Y-T2D], i3C combined-risk z-scores and estimated hazard ratios (HR) were obtained from the published i3C equation using risk z-scores of systolic blood pressure, body mass index (BMI), smoking history, total cholesterol, and triglycerides. ANCOVA regression models were used: 1) to compare i3C z-scores and HR in AYA with Y-T2D, OW/OB and Lean peers, and 2) to measure associations between i3C estimated HR and risk-enhancing factors including apolipoprotein B (ApoB), total low density lipoprotein particle number (LDL-P), and high sensitivity C reactive protein (hsCRP). Models were adjusted for diagnosis group, race, study center and multiple comparisons with Bonferroni.

Y-T2D had the highest i3C z-score (Y-T2D: 1.23 [1.10, 1.36] vs. OW/OB: 0.84 [0.80, 0.88] vs. Lean: -0.11 [-0.15, -0.06], mean[95%CI]) and estimated HR for predicted CVD events (Y-T2D: 4.25 [3.65–4.86] vs. OW/OB: 3.04 [2.85–3.22] vs. Lean: 0.95 [0.74–1.17], HR [95% CI]). Risk-enhancing factors increased the HR for predicted CVD risk by 0.3 for each 10 mg/dL increase in ApoB, 0.1 for each 100 nmol/L increase in LDL-P, and 0.16 for each 2 mg/L increase in hsCRP, all P < 0.001.

Y-T2D had an estimated 4.5- and 1.4-times higher risk for predicted CVD events compared to Lean and OW/OB peers, respectively. Lipoprotein and inflammatory risk-enhancing factors may help stratify and guide primary prevention strategies in high-risk AYA.

The online version contains supplementary material available at 10.1186/s12933-025-02951-x.