Catabolism of fats and branched-chain amino acids in children with Type 1 diabetes: Association with glycaemic control and total daily insulin dose.

OBJECTIVE: Hyperglycaemia in Type 1 diabetes (T1D) results from an absolute insulin deficiency. However, insulin resistance (IR) may exacerbate glycaemic instability in T1D and contribute to long-term cardiovascular complications. We previously showed that IR in teenagers with obesity is associated with sex-dependent derangements in the catabolism of branched-chain amino acids (BCAA) and fatty acids. Here we hypothesized that byproducts of BCAA and fatty acid metabolism may serve as biomarkers or determinants of glycaemic control and IR in prepubertal or early pubertal children with T1D. METHODS: Metabolites, hormones and cytokines from fasting blood samples were analysed in 28 children (15 females, 13 males; age 6-11 years) with T1D. Principal components analysis (PCA) and multiple linear regression models were used to correlate metabolites of interest with glycaemic control, total daily insulin dose (TDD, units/kg/d), adiponectin and the triglyceride (TG) to high-density lipoprotein (HDL) ratio. RESULTS: Males and females were comparable in age, BMI-z, insulin sensitivity, glycaemic control, inflammatory markers, BCAAs and C2/C3/C5-acylcarnitines. The majority of components retained in PCA were related to fatty acid oxidation (FAO) and BCAA catabolism. HbA1c correlated positively with Factor 2 (acylcarnitines, incomplete FAO) and Factor 9 (fasting glucose). TDD correlated negatively with C3 and C5 and Factor 10 (BCAA catabolism) and positively with the ratio of C2 to C3 + C5 and Factor 9 (fasting glucose). CONCLUSIONS: These findings suggest that glucose intolerance in prepubertal or early pubertal children with T1D is accompanied by incomplete FAO while TDD is associated with preferential catabolism of fats relative to amino acids.

The Perfect Storm: Rapid Progression of Diabetic Ketoacidosis in Pediatric Diabetes in the Setting of COVID-19.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has introduced countless challenges to the medical field. Although pediatric patients have been reported to have lower rates of COVID-19 mortality, the presence of pre-existing conditions can heighten the severity of their clinical presentation. This report discusses the potential influence COVID-19 might have on diabetic ketoacidosis. METHODS: Our patient, a 6-year-old girl with known type 1 diabetes, presented with acute onset of abnormal breathing and altered mental status. The day prior, she had 1 episode of emesis, diarrhea, and abdominal pain but no fever. She presented to an outside hospital and was reported to have agonal breathing with a Glasgow Coma Scale score of 8 (eyes open to pain, no verbal response to stimuli, and localized pain). She was promptly intubated, and the initial laboratory tests revealed severe diabetic ketoacidosis (DKA). A family member had COVID-19, and she also tested positive for COVID-19. RESULTS: Our patient's rapid progression and severity of illness require a discussion of how COVID-19 might affect diabetes and indicate opportunities for improving clinical practice in children with pre-existing diabetes. We discussed how COVID-19 might change the underlying pathophysiology of DKA and cause metabolic complications. Possible mechanisms include binding to angiotensin-converting enzyme 2 receptors and enabling a proinflammatory "cytokine storm." Additionally, ketoacidosis and altered mental status have been present in patients with COVID-19 without diabetes, which might potentiate the symptoms in developing DKA. CONCLUSION: Prompt recognition of DKA is warranted, as caregivers may attribute the symptoms to COVID-19 rather than to DKA, resulting in an increased severity of illness on presentation with acute symptom onset, as described in this report.