| Title: | Comprehensive risk factor control and its biomarker-mediated association with diabetic microvascular complications |
| Journal: | Diabetes Obesity and Metabolism |
| Published: | 25 Dec 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41448960/ |
| DOI: | https://doi.org/10.1111/dom.70403 |
Publication 17031
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
AIMS: Type 2 diabetes (T2D) confers a high risk of diabetic microvascular complications (DMCs). While multifactorial risk factor control is recommended, its associations with DMC risk, DMC-free survival, and mediating biomarkers remain unclear. We investigated these associations in an early-stage T2D subgroup with preserved kidney function and no prior cardiovascular or microvascular disease.</p>
MATERIALS AND METHODS: This prospective cohort study utilized data from the UK Biobank. Control of seven modifiable factors (blood pressure, adiposity, lipid profile, HbA1c, smoking, diet, physical activity) was assessed. DMCs were ascertained from hospital inpatient and death records, capturing severe or clinically overt events. Cox proportional hazard and flexible parametric survival models were used to estimate DMC risk and the DMC-free survival, respectively. Mediation analysis quantified the contribution of biomarkers related to inflammation, metabolism, and organ function.</p>
RESULTS: Among 11 083 participants with T2D (mean age: 59.26 years; 61.08% men), 1716 (15.48%) developed DMCs over a median follow-up of 11.26 years. Optimal control (≥6 factors) was associated with a hazard ratio of 0.55 (95% confidence interval 0.41-0.76) for DMCs and an additional 5.51 years (95% confidence interval 3.10-7.91) of DMC-free survival from age 45. Biomarkers of inflammation (e.g., leukocytes, monocyte counts, neutrophil counts, C-reactive protein), liver function (gamma-glutamyltransferase), and energy metabolism (glycoprotein acetyls) significantly mediated these associations, explaining 1.79%-30.31% of the observed associations.</p>
CONCLUSIONS: In this apparently healthy T2D population, comprehensive risk factor control is associated with a substantially lower incidence of DMCs and longer DMC-free survival, effects partly mediated through improvements in inflammatory, metabolic, and hepatic biomarkers.</p>
12 Authors
- Jing-Wei Gao
- Yu-Biao Wu
- Ze-Gui Huang
- Qing-Rong Deng
- Zhi-Teng Chen
- Qing-Yuan Gao
- Xu-Hui Wu
- Zhao-Yu Liu
- Jing-Feng Wang
- Hai-Feng Zhang
- Pin-Ming Liu
- Shao-Ling Zhang
1 Application
| Application ID | Title |
|---|---|
| 91090 | Predictors of coronary artery calcification (CAC) progression in the UKB population |
Enabling scientific discoveries that improve human health