Abstract
The role of the triglyceride-glucose (TyG) index in the progression of diabetic microvascular complication (DMC) multimorbidity remains unclear. Moreover, its interaction with genetic susceptibility to type 2 diabetes (T2D) has not been fully elucidated. This study included T2D patients from the UK Biobank. Primary outcomes were the incidence of first DMC and DMC multimorbidity (including retinopathy, neuropathy, and nephropathy). Multivariable Cox regression and multistate models were used to assess associations between the TyG index and DMC progression. Interaction analyses examined the joint association of the TyG index and T2D genetic risk. A total of 19,512 T2D patients were included, with a median follow-up of 12.9 years. Among them, 5,875 (30.11%) developed a first DMC, and 1,314 (22.37%) progressed to multimorbidity. Each 1-SD increase in TyG was associated with a 19% increased risk of first DMC and a 38% higher risk of multimorbidity. Multistate models showed TyG was a significant predictor of progression from first DMC to multimorbidity (HR = 1.25; 95% CI: 1.15–1.37; P < 0.001), particularly among those with retinopathy (HR = 1.39) or nephropathy (HR = 1.14). A combined association was observed between high TyG index and elevated genetic risk, demonstrating a stepwise increase in risk for DMC onset and progression. In this large, population-based cohort of T2D patients, an elevated TyG index independently predicted both the onset and progression of DMC multimorbidity. This association was particularly evident in patients with retinopathy or nephropathy, with the highest risk observed among individuals with higher genetic risk, highlighting the potential utility of TyG for risk stratification and precision prevention strategies.
Data availability
The datasets generated and/or analyzed during the current study are available in the UK Biobank repository, [https://www.ukbiobank.ac.uk/]
Abbreviations
- T2D:
-
Type 2 diabetes
- DMC:
-
Diabetic microvascular complication
- DMCs:
-
Diabetic microvascular complications
- TyG:
-
Triglyceride-glucose
- IR:
-
Insulin resistance
- FBG:
-
Fasting blood glucose
- TG:
-
Triglyceride
- PRS:
-
Polygenic risk scores
- SD:
-
Standard deviation
- HR:
-
Hazard ratio
- HbA1c:
-
Hyperglycemia
- BMI:
-
Body mass index
- HDL-C:
-
High density lipoprotein cholesterol
- TDI:
-
Townsend deprivation index
- LDL-C:
-
Low-density lipoprotein cholesterol
- DBP:
-
Diastolic blood pressure
- SBP:
-
Systolic blood pressure
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Acknowledgements
The authors would like to thank the UK Biobank team for their support and contribution to this study (Project ID: 540121).
Funding
The study was supported by Shenzhen High-level Hospital Construction Foundation of No.4004013.
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XY and MP conceived and designed the study. XY performed the data analysis and drafted the manuscript. XY, MP, XS, DY, FW and CH provided statistical and methodological support. GX and CH contributed to data interpretation and manuscript revision. All authors read and approved the final manuscript.
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This study was conducted using data from the UK Biobank under application number 540121. Ethical approval was obtained from the North West Multi-Centre Research Ethics Committee.
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Yuan, X., Peng, M., Shi, X. et al. Triglyceride-glucose index, genetic susceptibility, and trajectory of microvascular multimorbidity in type 2 diabetes. Sci Rep (2026). https://doi.org/10.1038/s41598-026-39777-w
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DOI: https://doi.org/10.1038/s41598-026-39777-w
