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

Aim: To investigate the association between circulating beta-hydroxybutyric acid (beta OHB) 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 beta OHB groups. Participants in the normal beta OHB group were divided into four subgroups according to beta OHB quartile (Q). The relationships of beta OHB 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 beta OHB concentration and DKD risk in the total population. Results: A higher prevalence of DKD was detected in the high compared with the normal beta OHB group (43.3% vs. 33.3%, P =.041). Participants in the Q4 group (beta OHB, 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 ss OHB concentration with DKD risk. DKD risk was lowest at a serum beta OHB 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 beta OHB 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.