Endocrine Abstracts

Objective: A potential role for the ketone body beta-hydroxybutyrate (β-OHB) has received increasing interest in the study of metabolic disease, but the association of β-OHB with Type 2 Diabetes (T2D) risk remains unclear. The present study aimed to explore the association of β-OHB with incident T2D in a prospective population-based cohort.

Methods: We measured plasma concentrations of β-OHB using nuclear magnetic resonance spectroscopy in 6095 participants followed for a median of 8.1 years. We estimated the risk of incident T2D using multivariable-adjusted Cox regression models.

Results: Cox regression analyses revealed a significant association between β-OHB and incident T2D. The hazard ratio (HR) per one standard deviation of β-OHB was 1.17 (95% confidence interval (CI): 1.08–1.26, P<0.001) after adjustment for age, sex, BMI, family history of T2D, smoking and alcohol consumption, systolic blood pressure, fasting plasma glucose, insulin, total cholesterol/HDL cholesterol ratio, triglycerides, eGFR and urinary albumin excretion. Likewise, the association remained significant after full adjustment when β-OHB was evaluated by quartiles (HR for the highest vs. lowest quartile =2.63, 95% CI: 1.67–4.14, P<0.001). Furthermore, the Net Reclassification Improvement index was enhanced after addition of β-OHB to a traditional risk model (P<0.01), improving the reclassification of 20% of participants.

Conclusions: This prospective study revealed that high plasma concentrations of β-OHB are prospectively associated with an increased risk of T2D. The association remained independent after adjusting for several traditional risk factors. Our results shows that plasma β-OHB is a strong biomarker for developing T2D and improves the risk classification for T2D.