Spontaneous ketonuria and risk of incident diabetes: a 12 year prospective study

Abstract

Aims/hypothesis Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic variables in a large population-based observational study. Methods We analysed 8703 individuals free of diabetes at baseline enrolled in the Korean Genome and Epidemiology Study, a community-based 12 year prospective study. Individuals with (n = 195) or without fasting ketonuria were matched 1:4 by propensity score. Incident diabetes was defined as fasting plasma glucose ≥7.0 mmol/l, post-load 2 h glucose ≥11.1 mmol/l on biennial OGTTs, or current use of glucose-lowering medication. Using Cox regression models, HRs for developing diabetes associated with the presence of ketonuria at baseline were analysed. Results Over 12 years, of the 925 participants in the propensity score-matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in participants with spontaneous ketonuria compared with those without ketonuria (HR 0.63; 95% CI 0.41, 0.97). Results were virtually identical when participants with fasting ketonuria were compared against all participants without ketonuria (after multivariate adjustment, HR 0.66; 95% CI 0.45, 0.96). During follow-up, participants with baseline ketonuria maintained lower post-load 1 h and 2 h glucose levels and a higher insulinogenic index despite comparable baseline values. Conclusions/interpretation The presence of spontaneous fasting ketonuria was significantly associated with a reduced risk of diabetes, independently of metabolic variables. Our findings suggest that spontaneous fasting ketonuria may have a potential preventive role in the development of diabetes.

The mystery of the ketogenic diet: benevolent pseudo-diabetes

“…In a remarkable study of healthy people, ketonuria after spontaneous (overnight) fasting was associated with a reduced risk of diabetes. Indeed, Kim et al suggested that spontaneous ketosis may prevent the development of diabetes [100]. Ketogenesis is suppressed in aged mice and rapamycin increases ketone production [101].…”

Association between Fasting Ketonuria and Advanced Liver Fibrosis in Non-Alcoholic Fatty Liver Disease Patients without Prediabetes and Diabetes Mellitus

“…Pathological ketosis occurs in uncontrolled DM and hyperglycemia due to insufficient insulin production, and is associated with life threatening conditions, such as diabetic ketoacidosis [12]. However, nutritional ketosis, associated with prolonged fasting and low carbohydrate or ketogenic diets (KD), has been shown to be metabolically favorable in recent studies [13][14][15][16]. In a recent study, KD was shown to have hepatic antisteatotic effects by the activation of mitochondrial beta oxidation in patients with NAFLD [17].…”

The Presence of Urinary Ketones according to Metabolic Status and Obesity

“…In a 12 year longitudinal study in Korea, the relationship between the presence of spontaneous fasting ketonuria was associated with a low risk of DM (HR, 0.63; 95% CI, 0.41–0.97) and subjects with ketonuria show lower glucose level after loading of glucose. 23 We already have reported the results that the healthy obese group with the presence of ketonuria get more reduction in body weight, BMI, and waist circumference compared to the non-ketonuria group. 24 In one study conducted during the Muslim fasting period, most of the obese individuals did not show ketonuria after more than 20 days of fasting, on the other hand, the normal weight group showed ketonuria after 3–6 days of fasting.…”