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Background <p>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.</p> Methods <p>In a pooled cohort cross-sectional analysis of 1547 adolescents and young adults (AYA) aged 10–25&#xa0;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.</p> Results <p>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&#xa0;mg/dL increase in ApoB, 0.1 for each 100&#xa0;nmol/L increase in LDL-P, and 0.16 for each 2&#xa0;mg/L increase in hsCRP, all<i> P</i> &lt; 0.001.</p> Conclusions <p>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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月24日

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  • Noemi Malandrino,
  • Faith S. Davis,
  • Sophia B. Glaros,
  • Ila N. Kacker,
  • Samson L. Cantor,
  • Natalie A. Macheret,
  • Geethika Thota,
  • Lilian Mabundo,
  • Maureen Sampson,
  • Alan Remaley,
  • Marissa Lightbourne,
  • Sheela N. Magge,
  • Jack A. Yanovski,
  • Stephanie T. Chung

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Graphical Abstract