bluuebunny/crossref_metadata_2025_split huggingface dataset:
153-LB: Initial Presentation of Children with Type 2 Diabetes during the COVID-19 Pandemic
Authors: HSIA DANIEL S. , LIM MARIA , BEYL ROBBIE A. , HASAN HIRA A. , GARDNER JAMES 
Published: June 2021

Stay at home orders due to the COVID-19 pandemic have exacerbated risk factors for type 2 diabetes. These orders have limited opportunities for daily physical activity, encouraged more screen time and sedentary behaviors, led to disturbed sleep, and promoted consumption of ultra-processed foods. Even modest weight gain over a short period of time can increase the risk for long-term consequences such as type 2 diabetes and cardiovascular disease. During the COVID-19 pandemic, there has been little data on the incidence or severity of new-onset type 2 diabetes in the pediatric population. We conducted a retrospective chart review of admissions for new onset type 2 diabetes from March to December 2019 and for the same period in 2020 at a tertiary care children’s hospital. Eligible patients were identified using ICD-10 codes for type 2 diabetes (E11.*); hyperglycemia (E72.51, E11.65, R73.9, R73.09); and hyperosmolar hyperglycemic syndrome (E13.*, E11.01). Each admission was carefully reviewed, and those with type 1 diabetes or hyperglycemia unrelated to diabetes were excluded. In 2019 the hospitalization rate for new onset type 2 diabetes was 0.27% (8 cases out of 2964 hospitalizations) compared to 0.62% (17 out of 2729) in 2020, p&lt;0.048. In total 23 of 25 children were African American and 19 children were male. Three children in 2019 versus 8 children in 2020 met criteria for DKA while 2 children met criteria for HHS in 2020. The mean admission HbA1c was 12.4% in 2019 vs. 13.1% in 2020; while the mean admission glucose was 441 mg/dL in 2019 vs. 669 mg/dL in 2020. Furthermore, the admission serum osmolality was 314 mmol/kg in 2019 compared to 335 mmol/kg in 2020. Our study found that the incidence of hospitalization for new onset type 2 diabetes was higher in 2020 during the COVID-19 pandemic compared to the same period in 2019. While the labs presented were not statistically different due to the limited number of participants, further studies are warranted to better understand the clinical implications of these findings.

Disclosure
D. S. Hsia: None. M. Lim: None. R. A. Beyl: None. H. A. Hasan: None. J. Gardner: None.

Funding
National Institute of General Medical Sciences (U54GM104940)
16-OR: Endocrine Manifestations of Pediatric HNF1B-MODY (MODY 5)
Authors: CRAVEN MEGHAN E. , BAMBA VANEETA , CALABRIA ANDREW C. , PINNEY SARA E. 
Published: June 2021

Objective: Mutations in hepatocyte nuclear factor 1B (HNF1B), are often identified based on a history of renal disease and diabetes mellitus, but other endocrine manifestations including dyslipidemia and hyperparathyroidism have not been well-defined in the literature. Given HNF1B-MODY is rare, there have been few case series defining the disease spectrum. This study analyzes the clinical characteristics of HNF1B-related endocrine disorders in 9 pediatric patients identified at a single pediatric tertiary care center.
Methods: Data was collected through the Atypical Diabetes Registry and Biorepository at the Children’s Hospital of Philadelphia.
Results: Of the 9 pediatric patients with HNF1B mutations or deletions, 7/9 (78%) have diabetes mellitus, 8/9 (89%) have renal disease, 8/9 (89%) have dyslipidemia, and 5/9 (55%) have hyperparathyroidism. Over half (55%) initially presented with diabetes mellitus, while the remaining 45% were diagnosed either based on family history or a genetic workup secondary to renal disease. No patients presented with diabetic ketoacidosis and only two presented with ketosis. Of the 4/9 with previously identified HNF1B-mutations, two have subsequently developed diabetes mellitus. Lipid profiles demonstrated: 7/9 with total cholesterol &gt;170 mg/dL, 8/9 with triglycerides &gt;100 mg/dL, 3/9 with LDL &gt; 110 mg/dL and 3/9 with HDL &lt; 40 mg/dL. In regards to calcium homeostasis, 55% have an elevated PTH (&gt;65 pg/mL) with high-normal calcium levels. Autism spectrum disorder was diagnosed in 3/9 patients (2 with 17q12 deletion and 1 with HNF1B mutation).
Conclusion: This study represents one of the largest series of pediatric patients with HNF1B-MODY at a single center. The majority of patients have had progressively declining beta-cell function resulting in diabetes mellitus. Nearly all had elevated lipids with hypertriglyceridemia predominating. Over half of the patients had elevated PTH levels preceding the decline in renal function concerning for primary hyperparathyroidism.

Disclosure
M. E. Craven: None. V. Bamba: None. A. C. Calabria: None. S. E. Pinney: None.
162-OR: Food Insecurity and Glycemic Control among Youth and Young Adults with Type 2 Diabetes
Authors: REID LAUREN A. , MENDOZA JASON A. , MERCHANT ANWAR , GERACI MARCO , REBOUSSIN BETH A. , ELLYSON ALICE M. , MALIK FAISAL , DABELEA DANA , MERJANEH LINA , MARCOVINA SANTICA M. , LUSTIGOVA EVA , LIESE ANGELA D. 
Published: June 2021

Screening for household food insecurity (HFI) is recommended because of its impact on diabetes management. While HFI has been shown to be associated with poor glycemic control in adults with type 2 diabetes (T2D) and youth and young adults (YYA) with type 1, the association between HFI and glycemic control in YYA with T2D is not known.
This cross-sectional study included T2D YYA (n=395) from the 2015-2020 SEARCH for Diabetes in Youth Study (14-35 yrs; median age: 25.2 yrs). HFI was defined as affirming ≥3 items on the US Household Food Security Survey Module. HbA1c values were available for 271 participants. It was measured in a sample of whole blood and analyzed as a continuous variable. Glycemic control was dichotomized into optimal/suboptimal (≤9 %) vs. high risk (&gt; 9.0%) based on HbA1c. Survey data on experiencing severe hypoglycemia or diabetic ketoacidosis (DKA) in the last 12 months was available for 292 participants. Logistic and linear regression were used for modeling the association of HFI with binary and continuous outcomes, respectively.
Approximately 34% of YYA with T2D reported HFI in the past 12 months. The mean HbA1c of the YYA with HFI was 9.2%, 54% had HbA1c &gt;9.0%, and 19% reported experiencing DKA or hypoglycemia. YYA who were food secure had a mean HbA1c of 9.5%, 54% had HbA1c &gt;9.0%, and 8% reported acute complications. No associations were observed between HFI and HbA1c or glycemic control. YYA with HFI had 2.3 (CI: 1.1-5.2) times the odds of experiencing DKA or hypoglycemia as those without HFI, after adjusting for age, gender, race, parent education, household income, insurance, clinic, diabetes duration, use of continuous glucose monitoring, and medication regimen. Our data suggests that HFI among YYA with T2D is a quite common, affecting more than a third of our sample and is associated with acute diabetes-related complications. These results warrant longitudinal studies in this particularly vulnerable group to establish if alleviating HFI reduces frequency of DKA and hypoglycemia episodes.

Disclosure
L. A. Reid: None. S. M. Marcovina: None. E. Lustigova: None. A. D. Liese: None. J. A. Mendoza: None. A. Merchant: None. M. Geraci: None. B. A. Reboussin: None. A. M. Ellyson: None. F. Malik: None. D. Dabelea: None. L. Merjaneh: None.

Funding
National Institutes of Health (R01DK117461, 1UC4DK108173)
167-OR: Long-Term Follow-up after Total Pancreatectomy and Islet Cell Autotransplantation in Patients with Chronic Pancreatitis Utilizing Off-Site Islet Isolation
Authors: LAD SALONI U. , ALI KHAWLA F. , JOHNSTON PHILIP C. , MARTIN VICENTE SAN , LIN YU KUEI , BOTTINO RITA , WALSH MATTHEW , STEVENS TYLER , HATIPOGLU BETUL 
Published: June 2021

Context: Total pancreatectomy (TP) with islet-cell auto transplantation (IAT) is an option for pain management for patients with chronic pancreatitis (CP). IAT allows the preservation of beta cell function to reduce or prevent long-term diabetes.
Objective: We performed a follow-up study up to 12 years after TPIAT surgery with an off-site isolation laboratory, to determine the efficacy and durability of the procedure.
Methods: Data (August 2008 to August 2020) were obtained from a TPIAT database which included information from medical records, clinic visits, questionnaires, and follow-up telephone calls. Patient demographics were collected. Additionally, each patient was assessed with a 4-hour mixed meal tolerance test for metabolic measurements, serial glycosylated hemoglobin (HbA1c), and insulin requirements prior to surgery and during their most recent follow-up appointment.
Results: Seventy-seven patients with a median age of 45.0 years underwent TP-IAT for CP due to different etiologies. At a median follow-up time of 422.5 days 12 patients were insulin independent and 65 patients were on at least one insulin injection a day. Post-operative C-peptide area under the curve (AUC) measurements (P=0.008) were a better indicator of procedure success compared to the number of islet cells transplanted (P=0.225). Patients who were insulin-dependent post-surgery demonstrated increased insulin resistance prior to surgery, by their median pre-surgery insulin AUC; insulin-independent, 626 (241, 3803); insulin-dependent, 1591 (325, 4803), HOMA-IR values 9.02.
Conclusions: TPIAT improves intractable pain for patients with CP. IAT decrease insulin requirement and improve blood glucose control after TP. Insulin resistance prior to surgery may be a predictor for insulin-dependence. Intervention studies using insulin sensitizer prior surgery may be considered in evaluating long-term outcomes for these patients.

Disclosure
S. U. Lad: None. K. F. Ali: None. P. C. Johnston: None. V. San martin: None. Y. Lin: None. R. Bottino: None. M. Walsh: None. T. Stevens: Speaker’s Bureau; Self; AbbVie Inc. B. Hatipoglu: None.
173-OR: Medial Amygdala Projections Regulate the Metabolic Responses to Internal and External Signals
Authors: DEVARAKONDA KAVYA , ALVARSSON ALEXANDRA , GONZALEZ MARIA JIMENEZ , LI ROSEMARY , LEHMANN VANESSA E. , STANLEY SARAH 
Published: June 2021

Medial amygdala projections regulate the metabolic responses to internal and external signals
The brain is a crucial part of the complex system that controls blood glucose in response to internal signals and external stressors. However, we do not know whether distinct CNS circuits regulate metabolism in response to internal state (fed vs. fasted) and environmental cues. Here we used detailed mapping of activated neurons, circuit tracing and projection-specific neural manipulation to determine the contribution of medial amygdala (MeA) neurons and circuits to the metabolic response to internal and external signals. Fasting, refeeding and stressors that increase blood glucose significantly activate MeA neurons. MeA neurons are synaptically connected to organs crucial to metabolic control and chemogenetic activation of MeA neurons significantly increased blood glucose, independent of pancreatic hormone release, and suppressed feeding. We identified the bed nucleus of the stria terminalis (BNST) and ventromedial hypothalamus (VMH) as major downstream projections from the MeA. MeA neurons projecting to BNST and to VMH are distinct neural populations activated by metabolic and emotional stress. Targeted activation of MeA neurons projecting to VMH but not to BNST MeA neurons mimicked the glycemic responses to fasting and stress with significantly impaired glucose tolerance, increased hepatic gluconeogenesis and a more rapid recovery from hypoglycemia, without increased corticosterone or epinephrine. Conversely, targeted ablation of MeA neurons projecting to VMH significantly reduced blood glucose and blunted the hyperglycemic response to stress. These data reveal a critical role for the MeA-VMH circuit in glucose regulation in response to internal and external signals. Future work will assess how this pathway is disrupted in diabetes and its contribution to the associations between diabetes and mental health disorders.

Disclosure
K. Devarakonda: None. A. Alvarsson: None. M. Jimenez gonzalez: None. R. Li: None. V. E. Lehmann: None. S. Stanley: None.

Funding
American Diabetes Association/Pathway to Stop Diabetes (1-17-ACE-31 to S.S.); National Institutes of Health (R01NS097184, OT2OD024912); U.S. Department of Defense (W81XWH-20-1-0345, W81XWH-20-1-0156); Charles H. Revson Foundation (18-25); Swedish Society
176-OR: STIM1 Deletion Leads to Loss of Beta-Cell Identity in High-Fat Diet-Fed Female Mice
Authors: SOHN PAUL , KRISHNAN PREETHI , LEE CHIH-CHUN , KONO TATSUYOSHI , EVANS-MOLINA CARMELLA 
Published: June 2021

STIM1 is an endoplasmic reticulum (ER) calcium (Ca2+) sensor that replenishes ER Ca2+ stores in a process known as store operated calcium entry (SOCE). Previously, we have shown that SOCE is impaired in the diabetic pancreatic β cell; however, the consequences of reduced β cell SOCE have not been well studied. To this end, mice with pancreatic β cell specific deletion of STIM1 (STIM1Δβ) were generated by crossing STIM1flox/flox with Ins-Cre mice and fed a high fat diet (HFD) beginning at 8 wk of age. Male STIM1Δβ mice did not show changes in glucose tolerance or body composition. In contrast, female HFD-fed STIM1Δβ mice were heavier (25.1 vs. 28.3 g, p&lt;0.05), had increased fat mass (4.9 vs. 8.2g, P&lt;0.01), and exhibited significant glucose intolerance (AUC IPGTT 22461 vs. 29245 mg/dL*min; p&lt;0.0001) with impaired insulin secretion by in-vivo GSIS (p&lt;0.05) without differences insulin tolerance, energy expenditure or food intake. Bulk RNA-sequencing of wild-type and STIM1Δβ female islets revealed reduced expression of MafA, UCN3, and Ins1 and Ins2 in STIM1Δβ islets, indicating potential loss of β cell identity. Pathway analysis showed modulation of pathways related to 17-beta estradiol (E2) signaling, with downregulation of a G-protein coupled estrogen receptor 1 (GPER), while differentially expressed genes were enriched for functions related to apoptosis, lipid metabolism, and epithelial cell differentiation. Consistently, STIM1Δβ female mice had lower β cell mass (2.984 mg vs. 1.349 mg, p&lt;0.05) and higher alpha cell mass (0.1822 mg vs. 0.4463 mg, p&lt;0.05). Proteomics analysis performed in STIM1-deficient INS-1 cells revealed significantly increased glucagon expression. Further, lower mobilization of intracellular cAMP levels was noted in response to treatment with E2 or G1, an agonist of GPER. These findings suggest a role for STIM1 in the maintenance of pancreatic β cell identity and indicate a potential interaction between SOCE and E2 signaling in female mice.

Disclosure
P. Sohn: None. P. Krishnan: None. C. Lee: None. T. Kono: None. C. Evans-molina: Advisory Panel; Self; Provention Bio, Inc., Consultant; Self; Dompe, Other Relationship; Self; Bristol-Myers Squibb Company, Nimbus Pharmaceuticals, Pfizer Inc.

Funding
National Institutes of Health (5T32DK064466-17, 5F30DK123996); U.S. Department of Veterans Affairs (2-I01BX001733); National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK093954-06A1); Indiana University School of Medicine; Gates Millennium Scholars Program
178-LB: Food Insecurity and Dietary Intake Adequacy in Youth and Young Adults with Type 1 and Type 2 Diabetes
Authors: BERCAW HOPE D. , REID LAUREN A. , MENDOZA JASON A. , FRONGILLO EDWARD A. , SAUDER KATHERINE A. , REBOUSSIN BETH A. , MAYER-DAVIS ELIZABETH J. , DABELEA DANA , MARCOVINA SANTICA M. , MERCADO CARLA , LIESE ANGELA D. 
Published: June 2021

Household food insecurity is associated with poor dietary intake in the general population, but little is known about persons with diabetes. We examined dietary intake among youth and young adults (YYA) with diabetes in relation to food security (FS) to identify differences in intake quantity and adherence to recommendations. The SEARCH for Diabetes in Youth cross-sectional study includes 1,134 YYA with type 1 diabetes (T1D, mean age: 21 years ± 5) and 274 YYA with type 2 diabetes (T2D, 25 years ± 4.2). Participants (or parents if &lt;18 years) completed the USDA Household FS Survey Module, wherein ≥3 affirmations indicate food insecurity. Diet was assessed via food frequency questionnaire and compared to age- and sex-specific 2020-25 Dietary Guidelines for Americans (DGA) nutritional goals for daily energy, added sugar, saturated fat, calcium, fiber, iron, magnesium, potassium, sodium, vitamins C, D, and E. Associations of FS with daily intake and meeting guidelines were assessed with sex-stratified multivariate linear regression. No intake differences by FS were observed, except females with T1D consumed more sodium (+155 mg, p = .01) and percent of kilocalories from saturated fat (+0.7%, p = .04) when FS was absent. Males with T2D consumed more vitamin E (+1 mg, p = .03) when FS was present. Crude guideline adherence was poor across the board (i.e. below 60%). After multivariate adjustment for demographic, socioeconomic, clinical and diabetes characteristics, females with T1D and T2D, regardless of FS, on average met vitamin C and males met iron guidelines. Males with T2D met percent of kilocalories from saturated fat guidelines in the absence of FS. DGA adherence among YYA with diabetes is of grave concern given that diet is crucial to diabetes management. FS reflects very little enhancement in diet quality. YYA with diabetes consume excessive sodium, added sugars, and inadequate micronutrients except for vitamin C and iron, increasing risk for deficiency, weight gain, heart attack and stroke.

Disclosure
H. D. Bercaw: None. C. Mercado: None. A. D. Liese: None. L. A. Reid: None. J. A. Mendoza: None. E. A. Frongillo: None. K. A. Sauder: None. B. A. Reboussin: None. E. J. Mayer-davis: None. D. Dabelea: None. S. M. Marcovina: None.
183-OR: Pyruvate Kinase M2 (PKM2) Enzymatic Activity Is Necessary to Improve Podocyte Mitochondrial Function and Glomerular Fuel Metabolism and Diabetic Nephropathy
Authors: FU JIALIN , SHINJO TAKANORI , LI QIAN , ST-LOUIS RONALD , PARK KYOUNGMIN , YOKOMIZO HISASHI , YU MARC GREGORY , SHAH HETAL , WU I-HSIEN , KING GEORGE L. 
Published: June 2021

Diabetic nephropathy (DN) is the result of abnormal systemic and local changes in metabolism and hemodynamics. We have reported that many glycolytic enzymes, such as pyruvate kinase M2 (PKM2), were elevated in the renal glomeruli of type 1 and type 2 diabetic patients who were protected from DN. TEPP46, a small-molecule which activates PKM2 by inducing oligomerization, reversed glomerular pathology in diabetic mice. After 7 months of STZ induced diabetes, mice with PKM2 specific overexpression in podocytes (PPKM2Tg) with podocin promoter, exhibited lower albumin-creatinine ratio (ACR), kidney-body weight ratio, mesangial expansion, basement membrane thickness and podocyte foot process effacement vs. WT diabetic littermates. PPKM2Tg mice exhibited lower expression of fibrotic (FN, TGFβ1 and Col4a) and oxidative stress (p47phox, NOX2 and NOX4) genes and improvement in endothelial function with increased eNOS and VEGF expressions in the glomeruli, compared to diabetic WT mice. Glycolytic and mitochondrial metabolisms as measured by oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using Seahorse showed striking improvement of impaired mitochondrial maximal respiration capacity and glycolytic rate in isolated glomeruli of diabetic PPKM2Tg mice, in concordance with elevated expressions of mitochondrial related-genes, such as PGC1α. Knocking-down PKM by shRNA in podocyte cell line (pPKMKD) replicated metabolic findings induced by diabetes with dramatic decline of both OCR and glycolytic rate. Re-expressing human PKM1 or PKM2 in pPKMKD cell line reversed impaired mitochondrial function and glycolysis, which were not improved in pPKMKD cells re-expressing with enzymatically inactive human PKM2 gene. These results indicate that PKM2 and its enzymatical function are both necessary in podocytes to improve glomerular mitochondrial abnormalities and delay the progression of DN.

Disclosure
J. Fu: None. G. L. King: Consultant; Self; Agios, Inc., Medtronic, Other Relationship; Self; Janssen Pharmaceuticals, Inc. T. Shinjo: None. Q. Li: None. R. St-louis: None. K. Park: None. H. Yokomizo: None. M. Yu: None. H. Shah: None. I. Wu: None.

Funding
Iacocca Family Foundation
186-OR: Risk Prediction of Early Decline in Renal Function in Diabetic Kidney Disease with Algorithm Including Fractional Excretion of Glycated Amino Acids
Authors: THORNALLEY PAUL , FUENTE ALBERTO DE LA , RABBANI NAILA 
Published: June 2021

Diabetic kidney disease occurs in ca. 40% patients with diabetes. Approximately 1 in 5 patients with type 1 diabetes mellitus (T1DM) develop early decline in renal function (EDRF), requiring renal dialysis after 5 - 20 years. Currently, it is uncertain which patients are at high risk of EDRF. With Joslin Kidney Study investigators, we found patients with T1DM with and without microalbuminuria who later develop EDRF (Decliners) have higher fractional excretion (FE) of 6 glycated amino acids - fructosyl-lysine and 5 advanced glycation endproducts (AGEs), compared to patients with stable renal function (Non-decliners) (Perkins et al., Sci Rep 10, 12709, 2020). No individual FE could classify patients. In this study, we applied artificial intelligence machine learning to develop diagnostic algorithms to classify Decliners and Non-decliners, exploring A1C, log(ACR), 14 glycated and oxidized amino acids in plasma, urine, related FEs and other features. Data from patients with T1DM with stable renal function (n = 52) and EDRF (n = 33) were available. Algorithms were trained and tested on 90%/10% data split, repeated 1000 times, using Extreme Gradient Boosting. Optimum classification required measurement of 3 AGEs: Nꞷ-carboxymethylarginine (CMA) and glyoxal-derived hydroimidazolone (G-H1) in plasma and urine, and N-carboxymethyl-lysine (CML) in plasma; measured in 15 min by liquid chromatography-tandem mass spectrometry. Optimum algorithm features were: A1C, log[ACR], FECMA, FEG-H1 and plasma CML free adduct. The diagnostic performance for risk prediction of future EDRF was (mean ± SD): sensitivity 0.74 ± 0.09, specificity 0.91 ± 0.04 and accuracy 87 ± 4%. The positive likelihood ratio LR+ of 11.0 indicates that this method gives strong, often conclusive evidence of future EDRF in patients with T1DM. With further validation, including in patients with type 2 diabetes mellitus, this method may markedly improve risk prediction of EDRF.

Disclosure
P. Thornalley: None. A. De la fuente: None. N. Rabbani: None.

Funding
Qatar Foundation; Qatar University