Fasting insulin genetic clusters were significantly associated with distinct patterns of T2D medication use, hypertension, and chronic kidney disease in an East Asian population (all P<0.05).
Observational (n=70,694)
No
Do fasting insulin genetic clusters associate with T2D treatment intensity and cardiometabolic complication risk in an East Asian population?
Fasting insulin genetic clusters capture reproducible clinical heterogeneity in East Asian populations, supporting their potential utility for risk stratification and precision diabetes care.
p-value: p=<.05
Introduction and Objective: Recent multi-ancestry studies indicate that fasting insulin (FI)-associated variants form distinct mechanistic clusters with heterogeneous risks for type 2 diabetes (T2D) and cardiometabolic outcomes. Given the specific clinical and pathophysiological features of diabetes in East Asian populations, the generalizability of these cluster-specific effects remains uncertain. Methods: Using genetic data from the Taiwan Precision Medicine Initiative (TPMI) integrated with electronic medical records from a Taiwanese medical center, we constructed partitioned polygenic risk scores for previously defined 7 fasting insulin genetic clusters (4 diabetogenic and 3 nondiabetogenic) and examined associations with T2D medication use and cardiometabolic complications stratified by T2D status (19,734 T2D vs. 50,960 non-T2D). Results: Several clusters demonstrated consistent clinical epidemiological patterns in the East Asian population (all with p.05). Among diabetogenic clusters, the adiposity-driven hyperinsulinemia cluster was associated with higher risks of intensive T2D treatment, hypertension (HTN), and chronic kidney disease (CKD) in individuals with T2D, and was additionally associated with oral antidiabetic therapy use. The FI-Lipodystrophy cluster showed greater injectable therapy use in T2D and higher HTN risk in non-T2D individuals. The FI-Liver/Lipid cluster was linked to higher injectable use in T2D, alongside protective associations with CVD in T2D and HTN in non-T2D individuals. Notably, the non-diabetogenic preserved insulin secretion cluster was also associated with increased CKD risk in T2D and higher HTN risk in both T2D and non-T2D individuals. Conclusion: These findings demonstrate that fasting insulin genetic clusters capture reproducible clinical heterogeneity in East Asian populations and support their potential utility for risk stratification and treatment-related phenotyping in precision diabetes care. Disclosure W.H. Sheu: None. J.I. Rotter: None. Funding This work was supported by the grants MG-112-PP-18, MG-112-SP-09 and MG-113-GP-03 from the National Health Research Institutes in Taiwan and National Science and Technology Council, Taiwan (NSTC 114-2314-B-400-014). The authors thank all the participants from Taiwan Biobank (TWB).
SHEU et al. (Fri,) conducted a observational in Type 2 Diabetes and cardiometabolic complications (n=70,694). Fasting insulin genetic clusters was evaluated on T2D medication use and cardiometabolic complications (p=<.05). Fasting insulin genetic clusters were significantly associated with distinct patterns of T2D medication use, hypertension, and chronic kidney disease in an East Asian population (all P<0.05).