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α-Hydroxybutyrate Association With Incident Type 2 Diabetes Over 10 Years Across Different Glycemic States
Elena Fortin1,2,3, Anna Norhammar1,4, David Stadler5
1Division of Cardiology, Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden.
Diabetes, Obesity & Metabolism
|August 2, 2026
Summary
Plasma alpha-hydroxybutyrate (α-HB) is a strong, independent predictor of developing Type 2 diabetes (T2DM) within ten years. This marker identifies metabolic risk beyond traditional glucose measurements, aiding in early diabetes risk stratification.
Area of Science:
- Metabolic Health
- Diabetes Pathophysiology
- Biomarker Discovery
Background:
- Type 2 diabetes (T2DM) poses a significant global health challenge.
- Early identification of individuals at high risk for T2DM is crucial for timely intervention.
- Current risk assessment tools may not fully capture long-term metabolic risk.
Purpose of the Study:
- To assess the association between baseline plasma alpha-hydroxybutyrate (α-HB) levels and the incidence of T2DM over a 10-year period.
- To determine if α-HB can serve as an independent predictor of T2DM development.
- To evaluate the added value of α-HB in risk stratification models for T2DM.
Main Methods:
- Prospective cohort study of 1349 participants from the Swedish PAROKRANK study.
- Baseline oral glucose tolerance tests and plasma α-HB quantification.
- Median follow-up of 9.95 years with incident T2DM identified via national registries; Cox regression analysis used.
Main Results:
- Plasma α-HB levels increased progressively across the spectrum of glucose tolerance.
- Each unit increase in log-transformed α-HB was associated with a nearly twofold increased risk of T2DM (HR 1.99, P<0.001).
- This association remained significant after adjusting for clinical variables (HR 1.78, P<0.01), and α-HB improved risk reclassification (NRI 0.23, P=0.01).
Conclusions:
- Plasma α-HB is a robust, independent risk marker for incident T2DM over a decade.
- α-HB identifies long-term metabolic risk not fully captured by glycemic status alone.
- A single fasting α-HB measurement offers a practical tool for refining early T2DM risk stratification.
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