PP078 - METABOLIC VULNERABILITY INDICES, GENETIC SUSCEPTIBILITY AND RISK OF TYPE 2 DIABETES: A PROSPECTIVE COHORT STUDY IN THE UK BIOBANK

PP078

METABOLIC VULNERABILITY INDICES, GENETIC SUSCEPTIBILITY AND RISK OF TYPE 2 DIABETES: A PROSPECTIVE COHORT STUDY IN THE UK BIOBANK

G. Ding¹, X. Liu^1,*, W. yang¹, Y. Li¹, J. cui¹

¹Center of Cancer, The First Hospital of Jilin University, Changchun, China

Rationale: Type 2 diabetes (T2D) involves complex interactions between inflammatory and metabolic dysregulation. We investigated associations between the Metabolic Vulnerability Index (MVX) and its components—Inflammation Vulnerability Index (IVX) and Metabolic Malnutrition Index (MMX)—with incident T2D and potential effect modifications.

Methods: This prospective cohort included 204,485 UK Biobank participants without baseline diabetes. MVX was calculated from NMR metabolomics data integrating inflammatory markers (glycoprotein acetyls, small HDL particles) and metabolic biomarkers (branched-chain amino acids, citrate). Cox proportional hazards models assessed associations with incident T2D across demographic, clinical, and genetic subgroups.

Results: During median 13.4-year follow-up, 14,533 T2D cases were identified. The highest vs. lowest MVX quartile conferred 46% higher T2D risk (HR=1.46, 95% CI: 1.39–1.54). IVX showed a strong positive association (HR=1.79, 95% CI: 1.69–1.89), while MMX demonstrated a protective effect (HR=0.63, 95% CI: 0.60–0.67). Significant interactions were observed with sex (stronger in females: HR=1.30 vs. males: HR=1.11), BMI (attenuated in obese individuals), education, and ethnicity. The protective effect of MMX was strongest in high genetic susceptibility individuals (HR=0.83 vs. low-PRS: 0.89).

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Conclusion: MVX demonstrates strong T2D associations, with contrasting contributions from inflammatory and metabolic components. These findings highlight complex metabolic-inflammatory interplay in T2D pathogenesis, offering potential for enhanced risk stratification and targeted prevention.

Disclosure of Interest: None declared