A J‐shaped relationship between ketones and the risk of diabetic kidney disease in patients with type 2 diabetes: New insights from a cross‐sectional study

Abstract Aim To investigate the association between circulating β‐hydroxybutyric acid (βOHB) and diabetic kidney disease (DKD) risk in patients with type 2 diabetes (T2D). Materials and Methods A total of 1388 patients with T2D were recruited. Participants were divided into high and normal βOHB groups. Participants in the normal βOHB group were divided into four subgroups according to βOHB quartile (Q). The relationships of βOHB with DKD and DKD subtype were analysed using chi‐square and binary logistic regression. Restricted cubic splines were used to explore the non‐linear correlation between βOHB concentration and DKD risk in the total population. Results A higher prevalence of DKD was detected in the high compared with the normal βOHB group (43.3% vs. 33.3%, P = .041). Participants in the Q4 group (βOHB, 0.12‐0.30 mM) had the lowest prevalence of DKD ( P = .001). In the binary logistic regression model, the multivariable‐adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for DKD risk were 2.30 (1.62‐3.26) for Q1, 1.80 (1.23‐2.62) for Q2 and 1.63 (1.10‐2.41) for Q3 relative to Q4 ( P < .001). Restricted cubic spline analyses suggested a J‐shaped association of circulating βOHB concentration with DKD risk. DKD risk was lowest at a serum βOHB concentration of 0.183 mM (OR, 0.63; 95% CI, 0.52‐0.77). Conclusions A J‐shaped relationship between circulating ketone level and DKD risk in patients with T2D was determined. Circulating βOHB in the range of 0.12‐0.30 mM was associated with a lower risk of DKD. Further studies are warranted to verify the causality and to elucidate the underlying mechanisms.