β-hydroxybutyrate as an early predictive biomarker of diabetes remission following intensive dietary intervention.

PURPOSE: Although intensive weight management achieves considerable success in diabetes remission, individual response varies substantially. We aimed to evaluate the predictive ability of early β-hydroxybutyrate (BHB) for type 2 diabetes (T2D) remission following an intensive dietary intervention in Southeast Asian individuals, and explore the metabolomic signatures associated with remission. METHODS: We analysed 45 adults with obesity and T2D (age:42 ± 10 years, 66.7% male, body mass index:33.7 ± 4.2 kg/m²) who completed 12 weeks of total diet replacement (TDR; ~800 kcal/day) in a secondary care setting. Blood BHB levels were measured at week 2 of TDR using point-of-care testing (POCT). Metabolomic analysis was performed on baseline and post-TDR plasma samples from 33 participants using nuclear magnetic resonance spectroscopy. Remission was defined as HbA1c < 6.5% and fasting plasma glucose<7 mmol/L without glucose-lowering medications. RESULTS: Following TDR, 64.4% of participants achieved remission with 8.2% mean weight loss. Increasing remission rates were observed across POCT-BHB tertiles (p-trend=0.001), with the highest tertile independently associated with remission (risk ratio:3.11, 95% CI:1.63-5.94, p < 0.001). Addition of POCT-BHB to a base model (baseline age, sex, weight, and HbA1c) increased the area under the receiver operating characteristic curve from 0.72-0.94. The optimal POCT-BHB cut-off value was 0.575 mmol/L, yielding 72.4% sensitivity and 93.8% specificity. Metabolomic analysis revealed that remitters exhibited enhanced ketone metabolism and distinct lipoprotein remodelling. CONCLUSION: In this real-world implementation of an intensive weight management programme, our preliminary findings identified week 2 POCT-BHB as a potentially useful biomarker for predicting diabetes remission in clinical practice.