Protective Role of Serum β-Hydroxybutyrate in Early Diabetic Kidney Disease: A Longitudinal Study

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INTRODUCTION: β-Hydroxybutyrate (βHB), the most stable form of ketone bodies, has exhibited protective effects in metabolic and chronic diseases. This study aimed to assess the association between fasting serum βHB levels, measured at baseline in drug-naïve state, and the risk of proteinuria in patients with newly diagnosed type 2 diabetes. METHODS: In this longitudinal study involving 280 patients, baseline fasting serum βHB levels, urine protein parameters, and metabolic parameters were evaluated. To monitor the development of albuminuria (spot urine albumin-to-creatinine ratio ≥ 30.0 mg/gCr) or proteinuria (spot urine protein-to-creatinine ratio > 0.15 g/gCr), patients with normal baseline levels were followed for a mean of 2.40 ± 1.40 years. RESULTS: Patients were classified into the highest tertile of baseline serum βHB level group and two other lower tertiles. The highest tertile group (median fasting serum βHB: 0.30 mmol/l) had a significantly lower incidence of proteinuria (6.90% vs. 24.3%, p = 0.028) and nonalbumin proteinuria (6.67% vs. 22.9%, p = 0.031) compared to the lower two tertiles. Higher baseline βHB levels were associated with a reduced risk of proteinuria (hazard ratio 0.313, 95% confidence interval 0.110-0.891), adjusted for confounders. CONCLUSION: Higher baseline fasting serum βHB levels are linked to a lower risk of proteinuria in newly diagnosed type 2 diabetes, suggesting its potential as a protective metabolic marker in early diabetic kidney disease.

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