Beta-hydroxybutyrate: An Early Predictor of Success in Type 2 Diabetes Remission During Dietary Intervention

Year Submitted: 2025
Published Date: 13 January 2026

Tags: Care Continuum, Specialist Outpatient Care, Care Process ＆ Redesign, Value Based Care, Safe Care

About this Content

Aims

To investigate the relationship between BHB levels and T2DM remission outcomes in patients undertaking 12 weeks of total diet replacement (TDR)

Background

Serum-hydroxybutyrate (BHB) is the predominant ketone body produced during carbohydrate restriction. It represents a metabolic shift from glucose to fat utilization. Serum BHB level is measured in patients following a Very Low-Calorie Diet (VLCD) to assess for dietary adherence and to distinguish nutritional ketosis from diabetic ketoacidosis. Recent studies suggest modest increase in ketone bodies reduced risk of type 2 diabetes (T2D) in patients with impaired fasting glucose and had greater HbA1c reduction in new-onset T2D patients after 6 months of treatment. Proposed mechanism behind was BHB acts as a signaling substance, reducing oxidative stress, regulating gluconeogenic gene expression and modulating pathways that improve insulin resistance. However, the association of modestly increased serum BHB
during early phase of VLCD and outcomes in T2D remission is underexplored. We hypothesized that early BHB elevation during dietary intervention would predict T2D remission success.

Methods

We analysed 36 T2D participants (age:4210 years, 61.1% male, BMI:33.93.9 kg/m) who completed Phase 1 of the programme consisting of 12-week total diet replacement (TDR). BHB measurements were obtained at week 2 of TDR following withdrawal of medications that may affect BHB production. The primary outcome was T2D remission, defined as HbA1c6.5% without glucose-lowering medications, while secondary outcome was absolute HbA1c change from baseline to end of TDR.

Results

Following TDR, T2D remission was achieved in 28 (77.8%) participants. Remitters exhibited higher BHB levels compared to non-remitters (median 0.85 vs 0.15 mmol/L, p=0.005). Modified Poisson regression analysis revealed that one-unit increase in natural-log transformed BHB levels elevated likelihood of remission by 26% (95% CI:1.031.52, p=0.021) in the unadjusted model. The relationship persisted after controlling for age, sex, and baseline HbA1c (risk ratio:1.29, 95% CI:1.111.50, p=0.001). Linear regression confirmed an independent association between higher BHB levels and greater HbA1c reduction (coefficient:0.36, 95% CI:0.200.52, p0.001).

Conclusion

Early elevated BHB levels during TDR significantly predict successful T2D remission. Hence, monitoring BHB may help to identify individuals who are more likely to respond favorably to dietary intervention.

Lessons Learnt

This study showed that elevated BHB levels detected at week 2 of TDR significantly predict successful T2D remission and greater reduction in HbA1c after 12 weeks of TDR. This result showed that BHB level potentially serving as a useful early biomarker representing enhanced fat metabolism and therapeutic response, as well as serving as a source of motivation for participants to adhere to dietary intervention.

Additional Information

Award: SHBC Best Poster (Allied Health) (Merit Award). This study is supported by the Alexandra Health Fund Ltd through the Science Translational and Applied Research Grants STAR22103 & STAR24204

Keywords

Beta-hydroxybutyrate, T2DM remission, Very Low-Calorie Diet

Innovators' Details

Connect with this contributor!

Kang Ru PANG - pang.kang.ru@nhghealth.com.sg

Project Attachment

KR SHBC Poster 2025 BP AH 04.pdf