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TOPLINE
Among patients with type 2 diabetes (T2D) who were not on insulin or thiazolidinedione therapy, having higher levels of total ketone bodies within a mild hyperketonemic range was associated with a lower risk for adverse kidney events.
METHODOLOGY
- Researchers analyzed data from a prospective cohort of 1392 clinically stable patients with T2D (mean age, 64.6 years; 41.8% women) who were not receiving insulin or thiazolidinedione therapy at baseline.
- Blood levels of total ketone bodies (beta-hydroxybutyrate and acetoacetate) were measured once after an overnight fast when feasible using an automated enzymatic test. Patients were grouped into tertiles based on ketone levels — lowest (0.08-92.3 μmol/L), middle (92.7-170.8 μmol/L), and highest (171.0-1629.6 μmol/L).
- Outcomes included a composite major adverse kidney event (MAKE), defined as the first occurrence of any of the following: macroalbuminuria (urine albumin‑to‑creatinine ratio ≥ 300 mg/g), a sustained ≥ 40% decline in the estimated glomerular filtration rate, or end‑stage kidney disease.
- The composite major adverse cardiovascular event (MACE) was defined as the first occurrence of myocardial infarction, coronary revascularization, ischemic stroke, hospitalization for heart failure, or cardiovascular death.
- The median follow-up duration was 23.2 months.
TAKEAWAY
- During follow up, 158 patients experienced at least one MAKE and 64 experienced a MACE.
- Compared with patients in the lowest ketone tertile, those in the highest tertile were 37% less likely to develop a major adverse kidney event (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.41-0.98). The strongest association was for a ≥ 40% decline in the eGFR (aHR, 0.46; 95% CI, 0.26-0.84).
- In a separate analysis of patients with a baseline eGFR ≥ 60 mL/min/1.73 m2, those in the highest ketone tertile had a 50% lower risk of developing chronic kidney disease (aHR, 0.50; 95% CI, 0.31-0.79).
- The highest vs lowest ketone tertile showed a favorable but statistically nonsignificant association with MACE. Further statistical analyses revealed a nonlinear relationship between blood ketone levels and kidney risk, with lowest risk seen when total ketone body levels were around 300-400 µmol/L.
IN PRACTICE
“These findings suggest that circulating ketone body levels may have prognostic value as biomarkers of kidney risk, although they do not establish a causal or mediating role of ketone bodies in kidney protection,” the authors of the study wrote.
SOURCE
The study was led by Soo Myoung Shin, Korea University College of Medicine, Seoul, Republic of Korea. It was published online in Diabetes Research and Clinical Practice.
LIMITATIONS
Serum ketone levels were measured only once at baseline. Patients with higher ketone levels generally had a more favorable clinical profile, including younger age and better kidney function. Dietary intake before blood test was not standardized or recorded. Because the study excluded patients taking insulin or thiazolidinediones, the findings may not apply to patients on those therapies.
DISCLOSURES
This study was supported by the Ministry of Trade Industry & Energy (MOTIE, Korea) and the Korean Diabetes Association. The authors reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
