Introduction: Hyperglycemic emergencies in children with diabetes traditionally include diabetic ketoacidosis (DKA) predominantly associated with T1DM, whereas hyperosmolar hyperglycemic state (HHS) that is associated with relative insulin deficiency in T2DM, rarely occurs (2%). There have been increasing reports of mixed DKA-HHS affecting up to 27%. The purpose of this study is to identify clinical features, risk factors, complications and outcomes among minority children presenting with hyperglycemic emergencies at our center. Methods: This is a retrospective chart review of children and adolescents (ages 1-21 years) admitted for hyperglycemic emergencies including DKA [defined as glucose >200 mg/dL, metabolic acidosis (pH <7.3 or serum bicarbonate <15 mmol/L) and ketonemia (ß-hydroxybuyrate ≥3 mmol/L) or moderate to large ketonuria], or HHS [defined as glucose >600 mg/dL, effective serum osmolality >320 mOsm/kg, venous pH >7.25 or arterial pH >7.30 or serum bicarbonate >15 mmol/L, absent to mild ketonemia] or mixed DKA-HHS between 2004 and 2019. Descriptive statistics, chi-squared analysis and t-tests were used. Results: Of 322 patients, 92% were African American with mean age 13.6 ± 3.5 years, 39% males, consisting of 266 (83%) with DKA, 52 (16%) mixed DKA-HHS, and 4 (1%) HHS. Ninety-eight of the DKA and DKA-HHS groups had T1DM. All 4 patients with HHS had T2DM. Compared to the DKA group, the mixed DKA-HHS group required higher IV fluids rates (p<0.0001), 4.3-fold greater odds of acute kidney injury (AKI, mean serum creatinine of 1.6 mg/dl vs 1.1 mg/dl; ref 0.5-1.0 mg/dL) and 3.3-fold greater odds of developing altered mental status (AMS). Risk factors such as insulin adherence, and precipitating factors like infection or stress were not different between both groups (p=0.06). There was no significant difference in insulin rates or time to resolution (p=0.4) in both groups. Among the HHS group, 50% presented with AMS and AKI (mean Cr 1.1 mg/dl ± 0.31) due to severe dehydration and required higher IV fluids rates (≥2 x maintenance). Creatinine kinase in 2 patients were slightly elevated (mean 1643 units/L, ± 77; ref 39-309). Insulin drip at 0.05 u/kg/hour was started in all 4 patients. None had venous thrombosis, rhabdomyolysis, cerebral edema, or death. Average time of resolution was 10 ±1.63 hours. Conclusion: In this study, 16% of patients with hyperglycemic emergencies presented with mixed DKA-HHS which was associated with more complications compared to the DKA group. Serum osmolality should be calculated and checked at diagnosis. Identification of hyperosmolality whether with or without DKA in the emergency setting is important because treatment should be focused on the degree of dehydration (usually moderate to severe) and other complications such as AKI and mental status changes.

Elevated serum IgA occurs in ~20% of children with new onset T1D, although its potential role in T1D pathogenesis is not understood. Gut dysbiosis is present at onset of T1D and is strongly associated with its pathogenesis. Mucosal IgA is well known to influence the microbiome and vice versa. In animal models, serum IgA responds to microbiome changes, thereby inducing a protective response to gut invasion by pathogens. However, the relationship between gut microbiome and serum IgA in humans with T1D is unknown. Thus, we aimed to assess if elevated serum IgA is associated with gut dysbiosis at T1D onset. We enrolled 47 children between 7/2021 and 9/2022: New onset T1D with elevated serum IgA (T1D-Hi-IgA, n=14), new onset T1D with normal serum IgA (T1D-Nl-IgA, n=18) and controls (siblings of new onset T1D, n=15). Exclusions: <2 yrs age; antibiotics; probiotics; inflammatory bowel disease; celiac disease; or acute illness <10 days of stool collection. Demographic and clinical variables, diet questionnaires and stool were collected. Stool microbiome was determined via 16Sv4 rDNA sequencing. Differences in alpha and beta diversity along with taxa abundance were assessed. We found that the relative abundance of members of families Oscillospiraceae and Lachnospiraceae, both of which contain butyrate producers, were significantly associated with elevated IgA irrespective of T1D status (p<0.05); higher in T1D-Hi-IgA vs T1D-Nl-IgA (p<0.05); yet similar in T1D-Hi-IgA vs controls. Measures of alpha diversity, including richness and evenness, were also increased in T1D-Hi-IgA vs T1D-Nl-IgA, though these differences did not reach significance (richness: p=0.074; evenness: p=0.135). Similar results were observed for beta diversity. In sum, in children with new onset T1D, elevated serum IgA is associated with beneficial microbial taxa such as butyrate producers, with a trend towards increased diversity, similar to healthy siblings. Further studies are needed to understand its involvement in T1D pathogenesis. Disclosure A.Thakkar: None. M.J.Redondo: None. J.Hajjar: None. J.Petrosino: None. K.L.Hoffman: Consultant; Cooper Surgical. J.Cormier: None. M.Ahmed: None. X.C.Huang: None.

IgA is the most produced antibody in the body. There are two major forms of IgA, monomeric serum IgA and dimeric mucosal (secretory) IgA. During infection or inflammation, IgA binding to its antigen induces crosslinking of FcaRI, which activates immune effector cells to carry out their functions and can thus induce pro-inflammatory responses, which is hypothesized to occur when IgA titers are high. (1,2) Elevated serum IgA has been associated with autoimmune diseases (3) including type 1 diabetes (T1D) but its role in disease pathogenesis is not well known. To address this gap in knowledge, we aimed to test the hypothesis that at diagnosis of T1D, children and adolescents with elevated serum IgA have different demographic, clinical and laboratory characteristics than those with normal serum IgA. We analyzed 612 children 9.7 [4.2] (mean [SD]) years old (59% Non-Hispanic White, 20% Hispanic, 16% Black, 5% Other) with new onset T1D diagnosed between 1/2008-2/2012 at a large, academic pediatric hospital. Serum IgA values above age-adjusted normal ranges were defined as elevated serum IgA. Patients with low IgA were excluded because of known association between IgA deficiency and autoimmune disease. Demographic and clinical variables were compared between youth with and without elevated serum IgA. Univariable and multivariable regression models were used to compare baseline characteristics that were associated with elevated serum IgA. A significance level of 0.05 was used. We found that elevated serum IgA was present in 21% (128/612) of the children at T1D onset. By multivariate analysis, compared to children with normal IgA, those with elevated IgA were more likely to be of Hispanic ethnicity (Odds Ratio (OR)=3.27, 95% Confidence Interval (CI)=2.00, 5.35) and had a higher hemoglobin A1c (A1c) (OR=1.13, 95% CI=1.01, 1.26). They also had higher odds of having insulin autoantibody (IAA) positivity at diagnosis (OR=1.65, 95% CI=1.10, 2.45) and lower odds of GAD autoantibody (GADA) positivity (OR= 0.57, 95% CI=0.36, 0.93) (all, p<0.05), while there were no significant associations with age, glucose level or presence of DKA. In sum, at diagnosis of T1D, 21% of youth have elevated serum IgA and this was associated with Hispanic ethnicity, higher A1C and positivity for IAA. Our findings suggest that elevated serum IgA may help identify youth with T1D, islet autoimmunity and insulin deficiency. Further studies are warranted to investigate potential pathogenic correlates and persistence over time. This knowledge may lead to new targeted strategies to preserve or improve beta-cell function in individuals with clinical or pre-clinical T1D. References (1) Hansen IS et al. Cell Mol Life Sci. 2019 Mar;76(6): 1041-1055. PMID: 30498997 (2) Leong KW et al. DNA Cell Biol. 2014 Dec;33(12): 823-9. PMID: 25188736 (3) Kerr MA. Biochem J. 1990 Oct 15;271(2): 285-96. PMID: 2241915 Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Introduction: Hypoglycemia is a common manifestation of Growth Hormone (GH) deficiency in infancy, but is rarely seen beyond 1 year of age. Here, we describe the case of a 5 year 6- month- old child with recurrent episodes of hypoglycemia due to GH deficiency in the setting of malnutrition. Experimental Methods / Case Presentation: Case report and literature review Results: A 5y6m girl with history of atypical teratoid rhabdoid tumor, status-post surgical resection and adjuvant therapy with CNS irradiation (50.4 gray), presented with recurrent hypoglycemia despite continuous G-tube feedings. Child had undergone surgery and irradiation approximately 3 years prior to presentation. She was initially followed at the cancer survivor clinic but had been lost to follow up for 2 years. At presentation, whole blood glucose was 51mg/dL. Height was 93.5cm (-4 SDS) and BMI 10.6 kg/m2 (- 7.75 SDS); she appeared malnourished on exam with minimal subcutaneous fat. She was admitted to the hospital where blood glucoses ranged from 59-68 mg/dL, despite continuous enteral feeds. On evaluation, blood ketones were mildly elevated at 0.67 mmol/L (ref range < 0.3mmol/L), growth factors were low: IGF1 15 ng/mL (ref range 37 - 272 ng/mL); IGF-BP3 1.1 mg/L (ref range 1.1 - 5.2 mg/L), and other pituitary hormones were within normal range [stimulation test cortisol peak 31.9 mcg/dL, TSH 2.4 mIU/mL(Ref range: 0.700 - 4.100 uIU/ML), Free T4 1.2 ng/dL (Ref range 1.0-2.4 ng/dL)]. Hypoglycemia resolved within 48 hours of initiating empiric treatment with GH (0.2mg/kg/week) and patient’s feeds were successfully compressed to 16 hours. Child was discharged home after passing an overnight 8-hour safety fast. Conclusion: Growth hormone deficiency can present as recurrent hypoglycemia outside the infantile period in the setting of malnutrition and needs to be considered in the differential diagnosis and evaluation of childhood hypoglycemia. ​