Introduction: Obesity and type 2 diabetes (T2D) increase severity of SARS-CoV2 in adults. In one review of DKA and COVID-19 in adults, 77% had pre-existing diabetes while 10% were newly diagnosed. We report an adolescent with severe DKA and new onset T2D in the setting of COVID-19 infection, who had a complex hospital course. Case: A 14-year old male with BMI of 43.7 kg/m2 and learning disabilities presented with decreased mental status and 4 day history of polydipsia, polyuria and emesis. Initial labs: glucose 546 mg/dl, BOHB 4.4 mmol/L, venous pH 6.94, HCO3 3mmol/L, serum osm 287 mOsm/kg, A1C 12.3%, pancreatic antibodies negative. C-reactive protein, d-dimer, ferritin, CPK, troponin, lipase (4,610 U/L), and amylase (839 U/L) were elevated. Patient received mannitol. No cerebral edema on head CT. Chest/Abd CT showed bilateral lower lobe consolidation of lungs and heterogeneous pancreas with no fluid collection. IV fluids and insulin were started. Nine hours after presentation, mental status declined further and patient required intubation for respiratory failure. At 19 hours, ketosis had resolved but acidosis persisted with arterial pH=7.05. SARS-CoV-2 nasopharyngeal swab PCR was positive. Course was complicated by multi-organ failure, rhabdomyolysis, and fluid refractory shock requiring vasopressors and renal replacement therapy (max creatinine 5.13 mg/dL). Patient started anticoagulant therapy, but on day 12 left femoral DVT was diagnosed. On hospital day 20 a retroperitoneal hemorrhage was noted. Inflammatory markers normalized by day 43. The patient had significant neurologic deficits and required prolonged rehabilitation after discharge on hospital day 46. Conclusion: To our knowledge, this case of a morbidly obese adolescent with neurocognitive delays, is the first report of an adolescent with COVID-19 presenting with new onset T2D and DKA, who had a hospital course similar in severity to those reported in adult patients. Adolescents with T2D and SARS-CoV2 infection should be monitored for severe disease. Disclosure M. Baby: None. M. S. Litao: None. H. R. Dapul: None. B. Franklin: None. M. Gallagher: None.

Background: Hyperosmolar diabetic ketoacidosis (H-DKA), a distinct clinical entity, is the overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Aim: We describe the clinical presentation, metabolic aberrations, and associated morbidity/mortality of these cases with H-DKA. We highlight the problem areas of medical care which require particular attention when caring for pediatric diabetes patients presenting with H-DKA. Methods: In our study we reviewed the literature back to 1963 and retrieved twenty-four cases meeting the criteria of H-DKA: glucose >600 mg/dL, pH < 7.3, bicarbonate <15 mEq/L, and serum osmolality >320 mOsm/kg, while adding three cases from our institution. Results: Average age of presentation of H-DKA was 10.2 years +/- 4.5 years in females and 13.3 years +/- 4 years in males, HbA1c was 13%. Biochemical parameters were consistent with severe dehydration: serum osmolality = 394.8 +/- 55 mOsm/kg, BUN = 48 +/- 22 mg/dL, creatinine = 2.81 +/- 1.03 mg/dL. Acute kidney injury, present in 12 cases, was the most frequent end-organ complication. Conclusion: Multi-organ involvement with AKI, rhabdomyolysis, pancreatitis, neurological and cardiac issues such as arrhythmias, are common in H-DKA. Aggressive fluid management, insulin therapy and supportive care can prevent acute and long term adverse outcomes in children and adolescents. (C) 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Background: Studies in adults with type 1 diabetes (T1D) show Continuous Glucose Monitoring (CGM) significantly lowers HbA1c however, the benefit of CGM use in adolescents has been elusive. We asked if short-term CGM use would have an effect on adolescents with poorly controlled T1D. Methods: In a randomized open label study we recruited 12 CGM naïve subjects with T1D, with an HbA1c >8% and ages 13-18 years. Visit 1 (V1) entailed consent, survey completion (Stage of Change (SOC), Diabetes Empowerment Scale (DES-SF), Pediatric Quality of Life (PedsQL), diabetes knowledge) and randomization to treatment (T), CGM Dexcom G4 for 1 week, or control (C). Both groups received daily diabetes care communication for the 1 week between V1 and Visit 2 (V2). Visit 3 (V3) was 1 month later and Visit 4 (V4) was at 3 months. Surveys were completed at all visits and HbA1c at V1 and V4. Results: Subjects (n=12) had an average age of 15.5 years and consisted of six Hispanic and five males. There were no significant (NS) differences between subject characteristics in the C (n=3) and T (n=9) groups. Compared to V1, there were NS changes in SOC and average number of boluses or blood glucoses (BGs) between the groups. The change in DES-SF from V1 to V4 was significant (p=0.04) for the T compared to the C. The decrease in HbA1c between V1 and V4 (-1.5%) in the T vs. an increase in the C (.4%) was NS (p=0.10) but clinically meaningful. Although NS, there was an increase in average BGs/day (+1.7) and a decrease in 7 day average BG (-81mg/dl) for T vs. the C (+0.1 BGs and -28mg/dl) from V1 to V2. Conclusions: Research on CGM use or its emotional effects in adolescents with poorly controlled T1D is limited. This study demonstrated a significant impact on diabetes empowerment with short-term use of CGM. Although NS, this was associated with an increased number of BG checks and a decreased average BG during CGM use plus a decreased HbA1c at 3 months. Use of more advanced CGM systems may hold promise for adolescents with T1D through greater empowerment. Disclosure J. Ilkowitz: None. M. Raisingani: None. F. Wu: None. Y. Chen: None. J. Gerson: None. M. Gallagher: None. B. Franklin: None.

Treatment to induce puberty in boys is indicated in those who do not undergo spontaneous development at a normal age. Stimulating development of the secondary sex characteristics is possible using gradually increasing doses of testosterone esters (TEs) via intramuscular (IM) administration, which is the most widely used method of testosterone (T) supplementation. When TEs are administered as monthly injection, serum T levels exhibit large fluctuations with supraphysiologic levels seen immediately after the injection followed by a decrease into the low range. Transdermal T (TT) has also been used for replacement therapy in adult males with hypogonadism and this provides steadier serum T levels. We report three adolescent boys with delayed puberty who were treated with TT gel for pubertal induction/continuation. This route was chosen as an alternative therapy due to their hepatic dysfunction, as is known that TT avoids the hepatic first- pass metabolism.

BACKGROUND:Increased prevalence of type 2 diabetes mellitus (T2DM) makes it important for pediatricians to use effective screening tools for risk assessment of prediabetes/T2DM in children.METHODS:Children (n = 149) who had an oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) were studied. American Diabetes Association recommended screening criteria-HbA1c ≥5.7% and fasting plasma glucose (FPG) ≥100 mg/dL-were compared against OGTT. The homeostatic model assessment of insulin resistance (HOMA-IR), a mathematical index derived from fasting insulin and glucose, was compared with OGTT. We studied whether combining screening tests (HbA1c and fasting glucose or HbA1c and HOMA-IR) improved accuracy of prediction of the OGTT.RESULTS:HbA1c of ≥5.7% had a sensitivity of 75% and specificity of 57% when compared with the OGTT. Combining screening tests (HbA1c ≥5.7% and FPG ≥100 mg/dL; HbA1c ≥5.7% and HOMA-IR ≥3.4) resulted in improved sensitivity (95.5% for each), with the HbA1c-FPG doing better than the HbA1c-HOMA-IR combination in terms of ability to rule out prediabetes (likelihood ratio [LR]) negative. 0.07 vs 0.14).CONCLUSIONS:HbA1c of ≥5.7% provided fair discrimination of glucose tolerance compared with the OGTT. The combination of HbA1c and FPG is a useful method for identifying children who require an OGTT.

BACKGROUND Acute lymphoblastic leukemia (ALL) maintenance therapy (MT) has been occasionally associated with symptomatic hypoglycemia (SH), attributed to purine analog (mercaptopurine [6-MP]). This hypoglycemia has been hypothesized to affect substrate utilization of gluconeogenic precursor alanine in the liver. CASE REPORT An overweight 5-year-old boy with ALL was evaluated for SH (lethargy and vomiting) that occurred 8-10 h after fasting while receiving daily 6-MP. Hypoglycemic episodes (>20 episodes per month) occurred predominantly around midmorning but not during the 5-day dexamethasone pulse. The adrenocorticotropic hormone test yielded a normal cortisol response, which ruled out pituitary adrenal suppression. A 12-h overnight fasting glucose was 49 mg/dL, with suppressed insulin response <2 IU/mL, low C-peptide of 0.5 ng/mL, high insulin-like growth factor-binding protein >160 ng/mL, high free fatty acid of 2.64 mmol/L, and negative glucagon stimulation test (change in blood glucose [BG] <5 mg/dL). These results ruled out hyperinsulinism. The patient was placed on cornstarch therapy 5 h prior to dosing with 6-MP. This treatment reduced the SH events to fewer than two episodes per month. To study the efficacy of cornstarch, the patient was fitted with the iPro™ professional continuous glucose monitoring system (CGMS) (Medtronic MiniMed, Northridge, CA) with a preset low alarm at 70 mg/dL, which was worn for a period of 5 days while the patient was on cornstarch. With 1,000 sensor reading the BG range was 65-158 mg/dL, and the percentage mean absolute difference between sensor and finger-stick BG readings (the parent monitored his BG four times a day) was 9.4%. There were no hypoglycemic episodes detected by the CGMS while the patient was on cornstarch. After the cessation of chemotherapy, a 15-h fasting study was performed, and the CGMS was placed. Results showed resolution of hypoglycemia. CONCLUSIONS The CGMS helped us devise an effective management plan for our patient. CGMS proved useful as an adjunct to characterize the pattern of hypoglycemia and to validate the benefit of cornstarch in hypoglycemia associated with 6-MP treatment of ALL.

Mutation of the Wilms tumor gene (WT1) is associated with two well-described syndromes called Denys-Drash (DDS) and Frasier (FS). Both are associated with nephropathy and ambiguous genitalia and have overlapping clinical and molecular features. The known risk of Wilms tumor in DDS and gonadoblastoma (GB) in FS patients requires tumor surveillance. The literature reports the occurrence of GB in DDS as lower than FS. This case highlights a very early presentation of bilateral GB in DDS and the consideration of early prophylactic gonadectomy at the time of diagnosis with DDS.

BACKGROUND:Activating mutations of the ABCC8 gene can lead to permanent neonatal diabetes mellitus (PNDM). Glucose variability in infants with NDM treated with insulin can be extreme. We report long-term glycemic control in a patient with PNDM on sulfonylurea therapy, despite initial allergic reaction.METHODS:A Chinese girl presented on the first day of life with persistent hyperglycemia. Despite treatment with various insulin regimens, hemoglobin (Hb)A1c (normal 4.8%-6.3%) increased from 5.0% at 14 days of age to a peak of 9.7% at 15 months of age. Her average insulin dose was 0.5 units/kg/day. Genetic analysis revealed two novel ABCC8 gene activating mutations encoding the beta-cell sulfonylurea-1 receptor of the ATP-sensitive potassium channel. At age 3 years 2 months, transition from insulin to the oral sulfonylurea glyburide was initiated. After 8 days, she developed urticaria, palmar erythema, and a diffuse maculopapular rash, which resolved when medication was discontinued. At age 3 years 11 months, glyburide was reintroduced at a very low dose and was increased with concomitant weaning of insulin over the following 6 months.RESULTS:Normoglycemia (HbA1c 5.6%) was achieved on glyburide without any further allergic reaction at the age of 4 years 5 months with improved metabolic control. For the next 3 years, HbA1c measurements, and glucose means and variability were significantly lower compared with values during insulin therapy.CONCLUSIONS:As compared with subcutaneous insulin, oral sulfonylureas improved long-term metabolic control in a patient with NDM caused by novel activating mutations in the ABCC8 gene. Desensitization permitted safe oral sulfonylurea therapy in our patient with NDM despite initial allergic reaction. Fewer episodes of hypoglycemia occurred on sulfonylurea than on insulin therapy, which is an advantage in a very young child.

BACKGROUND:The optimal dose and efficacy of ¹³¹I treatment of children and adolescents with well-differentiated thyroid carcinoma (WDTC) and pulmonary metastases are not well established. A therapeutic challenge is to achieve the maximum benefit of ¹³¹I to decrease disease-related morbidity and obtain disease-free survival while avoiding the potential complications of ¹³¹I therapy. SUMMARY:We systematically reviewed the published literature on children and adolescents with WDTC and pulmonary metastases treated with ¹³¹I to examine outcomes after ¹³¹I administration and the risks and benefits of therapy. After reviewing 14 published articles, 9 articles met our inclusion criteria encompassing 112 pediatric and adolescent patients with WDTC and pulmonary metastases 21 years of age or younger at diagnosis spanning a follow-up period of 0.6–45 years. ¹³¹I therapy after surgery and thyrotropin suppression resulted in complete, partial, and no disease response in 47.32%, 38.39%, and 14.29% of patients, respectively. Five studies provided data on disease response in relation to ¹³¹I dose. In general, nonresponders received the highest ¹³¹I doses and complete responders received a higher dose than partial responders. The disease-specific mortality rate was 2.68%. Survival was 97.32%. A second primary malignancy occurred in one patient. One out of 11 patients studied experienced radiation fibrosis. CONCLUSIONS:This review confirms that the majority of pediatric and adolescent patients with WDTC and pulmonary metastases treated with ¹³¹I do not achieve complete response to therapy, yet disease-specific morbidity and mortality appear to remain low. It is therefore prudent to use caution in the repeated administration of ¹³¹I to such patients to ensure that adverse effects of therapy do not cause more harm than good in a disease that has an overall favorable natural course. Long-term prospective studies are needed to analyze disease-specific morbidity and mortality, recurrence rate, dose-specific response, and dose-related adverse effects of ¹³¹I in this patient population.

Pituitary apoplexy is an acute clinical event usually caused by hemorrhage or infarction in a pituitary adenoma. We report the unusual case of hemorrhagic pituitary apoplexy in an 18 year-old male with previously undiagnosed type 2 diabetes mellitus who presented with unexplained hyperglycemia (glucose 49.2 mmol/l [887 mg/dl]) and obtundation and in whom an initial diagnosis of non-ketotic hyperglycemic coma (NKHC) was made. MRI revealed a heterogeneous mass arising from an expanded sella turcica into the suprasellar cistern. Despite well-controlled glucose levels on continuous insulin infusion, dexamethasone, and initiation of bromoergocriptine (parlodel) therapy, the patient's vision and pupillary responses deteriorated acutely. Following emergency transphenoidal surgery, the patient's vision and mental status improved. Data confirmed preoperative panhypopituitarism; serum prolactin was 396 ng/ml (microg/l). Immunostudies demonstrated tumoral labeling for prolactin, but not for ACTH, GH, TSH, LH, FSH, or P53.

Diabetes mellitus is a frequent transient or rare permanent complication of pregnancy. The role of autoimmune phenomena in this gestational form of diabetes is incompletely understood. We have examined sera from 312 pregnant women who had abnormal glucose tolerance (based on a screening examination during the second trimester) for the presence of islet cell surface antibodies or insulin autoantibodies. Fifty-eight of these women were lost to follow-up. Of the remaining subjects, 144 (57.1%) had gestational diabetes diagnosed by formal glucose tolerance testing and the others (42.9%) were normal. Sixty percent of the women with gestational diabetes eventually required insulin to control their blood glucose during pregnancy. One serum from the non-diabetic women was positive for insulin antibodies (0.9%); 8 of the sera from the patients with gestational diabetes were positive (5.6%). Subsequent analysis revealed that all nine of the women whose sera were positive for insulin autoantibodies had been treated with insulin previously. Islet cell surface antibodies were strongly correlated with gestational diabetes. Forty-five of 144 gestational diabetic sera were positive (31.3%) whereas only 9 of 108 suspect control sera (8.3%) and 7 of 60 unknown sera (11.7%) were positive. These data suggest that a high percentage of pregnant women who screen positive for glucose intolerance have serological evidence of an autoimmune response against the pancreatic islets, in spite of the state of relative immune tolerance during pregnancy. These data suggest that autoimmune phenomena may play a role in gestational diabetes and that the presence of islet cell antibodies can predict insulin-requiring gestational diabetes.

The effect of the stress of crowded housing conditions (10 mice/cage) on the onset of diabetes after multiple, sub-diabetogenic doses of streptozotocin (MSZ) in male C57BL/KsJ mice was investigated. Prior to MSZ treatment, the group-housed and individually-housed animals had similar plasma glucose levels, while the former group's plasma corticosterone (CS) levels were elevated (54 +/- 8 ng/ml, p less than 0.03; 166% of the latter group). The group-housed animals became hyperglycemic (253 +/- 23 mg/dl) 2 days after the MSZ (day 7), with maximum hyperglycemia (506 +/- 23 mg/dl) developing by day 10. The individually housed animals did not become hyperglycemic until day 10 (303 +/- 24 mg/dl, p less than 0.001), and did not reach maximal hyperglycemia until between days 31 and 46, when plasma glucose levels were no longer different from the group-housed mice (507 +/- 37 mg/dl). There was a significant and progressive rise in CS levels of the stressed animals, reaching 218 +/- 25 ng/ml at day 46. The rise in CS of the unstressed animals was not significant until day 46, when the mean value reached 96 +/- 19 ng/ml (p less than 0.001 vs. basal). However, even at the conclusion of the experiment, the mean CS in the stressed animals was still 227% of that in the unstressed group (p less than 0.001). These studies demonstrate that the effects of stress (biochemically documented as an increase in CS levels) act synergistically with streptozotocin to promote an earlier onset of diabetes mellitus in males of this murine strain.

An insulin-producing clone of rat insulinoma cells (RINm5F) has been used by several investigators as target cells for studies of both humoral and cell-mediated anti-islet immunity in diabetic animals and humans. We noted that the rate of proliferation of RINm5F cells obtained from different laboratories varied considerably, and, in the present study, we have compared the proliferation rates of RINm5F cells obtained from 3 laboratories (Uppsala, Sweden [UPP], Chicago [CHI] and New York [NY]). The cells were plated at 0.5 and 2.0 X 10(4)/cm2 and changes in cell number were measured over 5 days. Basal insulin release was also determined daily. In addition, binding of IgG from sera of human diabetics by each of the cell lines was also examined by a solid-phase, quantitative assay. Plating efficiency was significantly greater in the NY and CHI cells than UPP cells at both plating densities (p less than 0.025). When plated at 2 X 10(4)/cm2, the growth rate of the NY cells was faster than the others (NY: 100.1 +/- 7.8%/day, CHI: 72.2 +/- 8.1%/day, UPP: 78.3 +/- 14.0%/day, p less than 0.025). All growth rates were lower when cells were plated at 5 X 10(4)/cm2, and the differences in growth between the NY and the other cells was greater (NY: 94.1 +/- 12.2%/day, CHI: 61.8 +/- 5.8%/day, UPP: 58.1 +/- 5.6%/day). Insulin release also differed among the cells. More insulin was released by the NY cells than by the other cells on all days, and the CHI cells released more insulin than the UPP cells (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Two groups of 58 gestational diabetic women matched for age, prepregnancy weight, height, and parity were studied. The home glucose monitoring study group performed fasting and 1-hour postprandial capillary blood glucose testing after every meal. The control group was followed by conventional treatment. The incidence of macrosomia (birth weight of greater than or equal to 4000 gm) and large (greater than or equal to 90%) for gestational age infants was significantly reduced in the home glucose monitoring group. The mean birth weight of the study group was 3231 +/- 561 gm, while that of the control group was 3597 +/- 721 gm (p less than 0.002). Significantly more patients in the home glucose monitoring group were receiving insulin therapy (50% versus 21%). We believe that intensive home glucose monitoring will allow for the early identification of those gestational diabetic patients needing insulin and thus reduce the incidence of macrosomia and large for gestational age infants.

A longitudinal investigation was conducted from 1977 to 1984 on 178 families in which one or more of the children had insulin-dependent diabetes mellitus. Of 351 nondiabetic sibs followed up for an average of 54 months, ten have, thus far, become diabetic. Eight sibs were HLA identical to their diabetic proband and nine had HLA-DR3 and/or HLA-DR4. Islet cell surface antibody and islet cell cytoplasmic antibody were found from two to 74 months before the onset of clinical diabetes in 100% and 90%, respectively, of the children. A decrease in insulin secretion was observed in all of these children on entry into the study and was detected in the absence of elevated plasma glucose concentrations. The data suggest that the triad of HLA identity, pancreatic islet cell antibodies, and depressed insulin secretion identifies those sibs who are at high risk of developing insulin-dependent diabetes mellitus.

ICSA and ICA are present in more than 90% of children at the onset of IDDM and also prior to its development. In addition 6-25% of unaffected sibs of IDDM probands also have such antibodies but most never develop IDDM. In the present study we have measured complement-dependent cytotoxic ICSA by a simple microcytotoxicity assay using as targets the cloned rat, insulinoma line RIN-m Cytotoxicity was positive if 50% of cells were killed after incubation with diluted, heat inactivated, rat liver powder-adsorbed sera followed by complement with ethidium bromide added after 90'; dead cells were identified under epiillumination with an inverted Leitz microscope. The sera of all unaffected first degree relatives of 112 IDDM probands were examined and the results were divided with reference to sharing of HLA haplotypes by the sibs with their respective diabetic probands. 23/186 (12.4%) sibs were ICSA-positive and this was most common in sibs whose diabetic sib was also ICSA-positive(32.1 vs. 3.8%, p<.001).Furthermore, ICSA were found predominantly in those sibs HLA-identical (7/44) or haploidentical (14/105) to their diabetic sib and were rare in HLA-nonidentical sibs (2/37, p<.05).The results suggest that the tendency to produce ICSA may be inherited as a dominant trait, different from the inheritance of IDDM itself. Further studies are required to identify etiologic factors in the development of these ICSA.