Fasting ketone bodies strongly and independently associated with diabetes in general population: Study

There has been a rising incidence and prevalence of type 2 diabetes. Instead of this, the identification of prospective biomarkers that predict type 2 diabetes is increasingly relevant for personalized medicine strategies. Ketone bodies have recently received a renewed interest as potential biomarkers, but there is a lack of data linking these metabolites to diabetes risk. To address this knowledge gap, Tamas Szili-Torok, University Medical Center Groningen, Groningen, the Netherlands, and colleagues investigated a potential association between fasting ketone bodies and incident type 2 diabetes in the general population.

The study was undertaken from the PREVEND cohort and included 3,307 participants from the general population initially free of impaired fasting glucose or diabetes. Nuclear magnetic resonance spectroscopy was used to measure baseline fasting ketone body concentrations.

Type 2 diabetes was defined as self-report of type 2 diabetes diagnosis, nonfasting glucose of ≥11.1 mmol/L, fasting glucose of ≥7.0 mmol/L, or initiation of glucose-lowering medication. Impaired fasting glucose was defined according to the criteria of the WHO reflecting the standard of care in the Netherlands (6.1–7.0 mmol/L).

The authors reported the following findings:

• 3.8% of the participants developed type 2 diabetes during a median follow-up of 7.3 years.
• In Kaplan-Meier analysis, sex-stratified ketone body levels were strongly positively associated with incident type 2 diabetes, which was confirmed in Cox regression analyses adjusted for several potential confounders.
• There was no significant interaction by sex. Both 3-β-hydroxybutyrate and acetoacetate+acetone are individually associated with incident type 2 'diabetes.

"Our study demonstrates that fasting ketone bodies strongly and independently associate with incident type 2 diabetes in the general population," the researchers wrote. "These data may have important implications for the identification and potential stratification of subjects at risk for T2D development, and for considering intervention strategies against the obesity epidemic with its cardiometabolic sequelae."

Limitations of PREVEND were that free fatty acids were not determined, dietary habits were not recorded, and participants were from a relatively homogenous, predominantly White population. Also, HbA1c levels were not available to establish a type 2 diabetes diagnosis, and ketone body concentrations were only measured at baseline and not during follow-up.

Reference:

Tamas Szili-Torok, Martin H. de Borst, Erwin Garcia, Ron T. Gansevoort, Robin P.F. Dullaart, Margery A. Connelly, Stephan J.L. Bakker, Uwe J.F. Tietge; Fasting Ketone Bodies and Incident Type 2 Diabetes in the General Population. Diabetes 1 September 2023; 72 (9): 1187–1192. https://doi.org/10.2337/db22-0826