Fasting ketone levels vary by age: implications for differentiating physiologic from pathologic ketotic hypoglycemia

Objectives: Ketone production is a physiological phenomenon that occurs during beta-oxidation of free fatty acids. Distinguishing physiologic ketosis from pathologic over-production/underutilization of ketones is critical as part of the diagnostic evaluation of disorders of carbohydrate metabolism, but there is limited literature on normal ketone production with fasting. Our aimis to measure fasting serum beta-hydroxybutyrate (BHB) concentrations in healthy children after an overnight fast. Methods: Children <= 18 years of age were prospectively recruited from elective procedures through our surgery centers. Exclusion criteria included a history of diabetes, hypopituitarism, adrenal, metabolic or inflammatory disorders, dietary restrictions, trauma, or use of medications that might affect blood glucose. Serum glucose, cortisol, and BHB were assessed after an overnight fast. Results: Data from 94 participants (mean 8.3 +/- 5.7 years, 54 % male, 46 % female, were analyzed. Children <= 3 years of age (19) have significantly higher mean (0.40 +/- 0.06 mmol/L) and median (0.4, IQR 0.2-0.6 mmol/L) BHB concentrations compared to children >3 years of age (75) with mean (0.21 +/- 0.02mmol/L) andmedianBHB (0.1, IQR 0.1-0.2mmol/L) (p<0.0001). Fasting BHB levels of >1.0 mmol/L was rare (2 %, N=2) and 74 % (N=70) of participants had BHB levels <0.3 mmol/ L. Conclusions: BHB concentrations are significantly higher in young children (=3 years of age) compared to older children. Fasting BHB levels >1.0 mmol/L are rare within our population and therefore may identify a value above which there may a greater concern for pathologic ketotic hypoglycemia. It is imperative to establish the normative range in children to differentiate physiological from pathological ketotic hypoglycemia.