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Introduction: The COVID-19 pandemic has introduced countless challenges to the medical field and has brought increased attention to pediatric patients with pre-existing diagnoses such as diabetes. While pediatric patients have lower rates of COVID-19 mortality, the presence of pre-existing conditions can heighten the severity of their clinical presentation. Here we discuss how COVID-19 may contribute to the pathophysiology of DKA. Case Presentation: Our patient is a 6-year old female with known type 1 diabetes for 6 months, with positive GAD 0.25 nmol/L, c-peptide 0.3 ng/ml, blood glucose 555 mg/dl, HbA1c 10.9, beta hydroxybutyrate (βOHB) 3.21mmol/l, pH 7.35, HCO3 21 mEq/L at her initial presentation, and insulin requirement <0.5 IU/kg/day (in honeymoon). She presented to an outside hospital due to acute onset of abnormal breathing and altered mental status. The day prior, she had one episode of emesis, diarrhea, and abdominal pain, but no fever. She was reported to be agonal breathing with a GCS of 8 and unresponsive to physical or verbal stimuli. She was intubated shortly after arrival and given mannitol. Initial labs included a glucose 486 mg/dL, pH 6.88, bicarbonate 4 mEq/L, lactate 5.8 mmol/L, βOHB 11.9 mmol/L, and anion gap 29 mEq/L, all consistent with severe DKA. With a known family member with COVID-19, she was tested and found to be COVID-19 positive. She was transferred via flight to a higher level of care. Remarkably, she was appropriate for extubation the following day with return to her baseline mental status with improved acidosis. On day three of hospitalization, she developed further COVID-19 symptoms which included sore throat, productive cough, fatigue, headache, and high fever. These symptoms persisted four more days until she was afebrile and discharged home in good condition. Conclusion: Our patient’s rapid progression and severity of illness, including the need for intubation, requires the discussion of how COVID-19 might affect diabetes and suggests opportunities for improvement in clinical practice in children with preexisting diabetes. 1) COVID-19 might change the underlying pathophysiology and cause severe metabolic complications. Possible mechanisms might include a) binding to angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in key metabolic organs and tissues, including pancreatic beta cells, leading to insulin resistance and islet cell destruction b) enabling a proinflammatory “cytokine storm” in the setting of higher basal proinflammatory state from diabetes. Additionally, ketoacidosis and altered mental status have been discovered in patients with COVID-19 without diabetes, which could potentiate the symptoms of DKA. 2) Prompt recognition and treatment of DKA is warranted as caregivers may attribute the symptoms to COVID-19 rather than DKA and recognition could be too late if symptoms are as acute as described in this case report.

Introduction/Background Type 1 diabetes (T1D) is associated with decreased skeletal muscle mass (SMM) and impaired muscle function in adults. Despite the importance of skeletal muscle in insulin action and metabolic homeostasis, our understanding of skeletal muscle health in children with T1D is very limited. Here we used a novel, non-invasive methodology to compare muscle mass (MM) in children with T1D and sex and age-matched healthy children without diabetes. Objectives We hypothesized that: (a) children with T1D have lower MM than age, sex, and BMI-matched children without T1D; (b) MM in children with T1D correlates with insulin sensitivity and glycemic control. Methods Weight (BW), height, BMI%, body fat% (BF%), daily insulin requirement, CGM data, HbA1c, and total and HMW adiponectin were measured in 24 young children (15 females, 9 males; age 6-11 years) with T1D. BF% and fat-free-mass (FFM) was measured by bioelectrical impedance. Insulin sensitivity was assessed by total and HMW-adiponectin and daily insulin requirements. Glycemic control was assessed by glucose time in range, mean blood glucose, and HbA1c. MM was measured using the D3creatine dilution method in 22 of the children with T1D (14 females, 8 males) and, in a separate study, in 34 children without T1D (17 females and 17 males). This method involves an oral 10 mg dose of deuterated creatine (methyl-d3, D3Cr). Creatine is converted in vivo to creatinine, including D3Cr to D3creatinine, in muscle by an irreversible, nonenzymatic reaction and then excreted. A single fasting urine sample is collected to determine D3creatinine enrichment. MM/BW (%) was calculated to normalize for body weight. Results There were strong positive associations between MM and body weight (r=0.85, p<0.0001), BMI (r=0.61, p=0.0028), and FFM (r=0.72, p=0.0040). Although children with T1D were slightly older (9.2 ±1.3 vs 8.1± 1.2 yo, p=0.003) and had higher BMI (18± 2.3 vs16.0 ±2.0, p=0.001) than controls, they had lower %MM/BW than children without diabetes (37.8± 4.6 vs 43.1±4.5%, p<0.0001). The lower %MM/BW in T1D compared to controls was confirmed in sub-cohorts matched for age and in males and females analyzed separately. Mean daily insulin requirement and HbA1c in the children with T1D were 0.76±0.15 IU/kg/day and 7.1±1.1%, respectively. MM, FFM, %BF, FM, %MM/BW did not correlate with metrics of insulin sensitivity or glycemic control. Conclusions This is the first study to quantitate MM directly in young children with T1D. Our results demonstrate a lower %MM in 6–11-year-old pre-pubertal children with T1D with stable and reasonable glycemic control. The cause for the lower % MM in T1D is not clear; however future studies could examine the rates of muscle protein and fat synthesis and breakdown in healthy and diabetic children along with their relations to insulin administration, metabolic control, growth, and pubertal development. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

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