bluuebunny/crossref_metadata_2025_split huggingface dataset:
1123-P: Analysis of Readmissions for Diabetic Ketoacidosis in Patients with Hidradenitis Suppurativa: A Nationwide Analysis
Authors: EDIGIN EHIZOGIE , SHAKA HAFEEZ , ESEATON PRECIOUS O. , ALMANI MUHAMMAD USMAN , KICHLOO ASIM , OJEMOLON PIUS E. , JAKHAR DEEPAK 
Published: June 2021

Hidradenitis suppurativa (HS) is known to increase the risk of diabetes mellitus. This study aims to compare rates and outcomes of 30-day readmissions following admissions for type 1 diabetic ketoacidosis (T1DKA) in patients with and without co-existing Hidradenitis Suppurative (HS) in the United States.
We analyzed the 2018 National Readmission Database. We included index hospitalizations for all patients (aged≥18 years) with a principal diagnosis of T1DKA using ICD-10 codes. We further sub-stratified this group into those with and with a secondary diagnosis of HS. Chi-square tests and regression analysis were used to compare rates and outcomes of 30-day readmissions between both groups. We excluded elective and traumatic readmissions.
A total of 94,461 index hospitalizations for T1DKA, that were discharged alive, were included in the analysis. 109 (0.2%) of these, had co-existing HS. A total of 15,614 (16.5%) readmissions occurred within 30 days. Readmission rates were similar between HS and non-HS group (21.8% vs. 16.5%, p=0.328). HS group had a similar mean hospital length of stay (3.0 days vs. 2.9 days, p=0.645) and mean total hospital costs ($6,878 vs. $7,236, p=0.691) compared to the non-HS group. Readmissions for T1DKA in HS patients were associated with a total of 331 hospital days and $747,976 in hospital costs. T1DKA without coma was the most common reason for readmission in both groups.
HS patients admitted for T1DKA have a greater, but statistically non-significant rate of 30-day readmission, and similar readmission outcomes compared to non-HS patients admitted for TIDKA.

Disclosure
E. Edigin: None. H. Shaka: None. P. O. Eseaton: None. M. Almani: None. A. Kichloo: None. P. E. Ojemolon: None. D. Jakhar: None.
1125-P: Do Non-HLA Genes Contribute to Age of Type 1 Diabetes Onset in Monozygotic Twins?
Authors: TRIOLO TAYLOR M. , DONG FRAN , BRONCUCIA HALI C. , ONENGUT-GUMUSCU SUNA , STECK ANDREA , RICH STEPHEN S. 
Published: June 2021

Development of islet autoimmunity (IA) and type 1 diabetes (T1D) are associated with high-risk HLA class II loci as well as non-HLA genes. Monozygotic (MZ) twins have a high rate of concordance to T1D progression after the first twin develops T1D, especially for those diagnosed at a young age. We analyzed 52 T1D-associated non-HLA SNPs from ImmunoChip data in 159 MZ twins from the Twin Family Study: 79 twin probands with T1D and their 80 unaffected cotwins/triplets (including one set of triplets). Subjects are enrolled into the Twin Study when the proband is diagnosed with T1D and cotwins are followed longitudinally for the development of IA and/or T1D. In the cotwins, we analyzed the association between each of the non-HLA SNPs and IA after adjusting for HLA DR3/4*0302. In the twin probands with T1D, we used a linear regression model to evaluate the association of non-HLA SNPs with diabetes age at onset after adjusting for HLA DR3/4*0302. Median (IQR) age of diagnosis of the twin probands was 9.9 (5.4-13.9) years and age of last visit for the cotwins was 17.5 (11.2-26.7) years. Of the 80 cotwins, 41 (51.3%) developed IA and 15 (18.8%) were diagnosed with T1D. After adjusting for HLA DR3/4*0302, SNPs in CTLA4 (rs3087243), IL2 (rs4505848), IKZF1 (rs62447205), and INS (rs7111341) were found to be associated with the development of IA in cotwin subjects (all p&lt;0.04). After adjusting for HLA DR3/4*0302, SNPs in CTSH (rs3825932) and TYK2 (rs34536443) were found to be associated with younger age of diabetes onset in the twin probands (p&lt;0.05). In this cohort of MZ twins, non-HLA SNPs in CTSH and TYK2, which function both in the immune system and in beta cells, were associated with younger age of onset in the twin probands. Further studies are needed to evaluate the specific role of these genes for immunity and T1D onset.

Disclosure
T. M. Triolo: None. F. Dong: None. H. C. Broncucia: None. S. Onengut-gumuscu: None. A. Steck: None. S. S. Rich: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (K12DK094712)
1127-P: Expression-Based Genome-Wide Association Study Links Osteopontin and Interleukin-1 Receptor Antagonist with Type 1 Diabetes
Authors: JIA XIAOFAN , TODA KYOKO , HE LING , MIAO DONGMEI , YAMADA SATORU , YU LIPING , KODAMA KEIICHI 
Published: June 2021

Type 1 diabetes (T1D) is caused by autoimmune destruction of insulin-producing β-cells in the pancreatic islets. Islet autoantibodies (IAbs) are indicators of islet autoimmunity. However, IAbs do not fully meet the need for the prediction of future hyperglycemia and the rate of disease progression. We assumed that functional proteins associated with autoimmune cellular process are great sources for biomarkers. In an attempt to identify additional biomarkers, we performed an expression-based genome-wide association study (eGWAS) using microarray data from 169 arrays of the pancreatic islets of T1D rodents. We ranked all 16,099 protein-coding genes by the likelihood of finding repeated differential expression in the pancreatic islets. Our top 20 secreted proteins were screened using the serum samples from newly diagnosed children with diabetes. First, we screened 20 selected candidates with 170 sera including 100 T1D, and 50 type 2 diabetes (T2D) and 20 age matched healthy children. With 7 proteins showing significance, we further did validation study using the second set of 400 samples from newly diagnosed children with diabetes and age matched controls including 200 T1D, 100 T2D, and 100 age-matched controls. We identified 2 serum proteins were significantly changed in T1D vs. both control and T2D and 5 serum proteins were significantly changed in both T1D and T2D vs. control. Serum Osteopontin (OPN) levels were uniquely higher in T1D (p&lt; 0.0001) with no difference between T2D and healthy control subjects. Serum Interleukin 1 receptor antagonist (IL-1RA) levels were lower in T1D compared with both T2D (p&lt;0.001) and healthy subjects (p&lt; 0.0001). Our results suggest that OPN and IL1RA could be the useful biomarkers of T1D in children.

Disclosure
X. Jia: None. K. Toda: None. L. He: None. D. Miao: None. S. Yamada: None. L. Yu: None. K. Kodama: None.

Funding
JDRF (2-SRA-2019-695-S-B)
114-LB: Metformin-Associated Lactic Acidosis Risk Assessment in Veterans on Continuous Oxygen Therapy
Authors: LUTZ-MCCAIN STACEY J. , DESANZO BETH E. , HERK BRANDON , MCLINDEN MEGHAN , DINARDO MONICA M. , CODARIO RONALD 
Published: June 2021

Metformin is the most prescribed oral medication for type 2 diabetes in the US due to its low cost, efficacy in reducing insulin resistance, and overall safety profile. However, literature shows that metformin can cause a rare but serious side effect of lactic acidosis (LA) with an incidence of 0.03-0.06 per 1000 patients. Persons requiring continuous oxygen therapy (COT) may be at risk for LA associated with hypoxia and decreased tissue perfusion, but the risk of metformin associated lactic acidosis (MALA) in persons requiring COT is unclear. Due to lack of evidence, some clinicians may empirically discontinue metformin in patients on COT, compromising glycemic stability. The objective of this drug utilization evaluation was to determine the frequency of metformin use and incidence of MALA in patients receiving COT.
A retrospective review was conducted at a large regional Veterans Affairs Medical Center for patients with active prescriptions of metformin and supplemental oxygen therapy from 4/2017-4/2020. Of 578 unique patients identified, manual medical-record review was conducted for 6 patients who had serum lactate levels &gt;4 mmol/L while using concomitant metformin and COT. All were white males with mean: age of 71, pH of 7.35, and eGFR of 56. No cases of LA or DKA were identified. In all cases, elevated lactate levels were attributed to advanced medical conditions including: COPD, sepsis, CHF, CKD, and liver disease. None had serum metformin levels drawn.
In conclusion, the association of elevated serum lactate among persons using concomitant metformin and COT was low and occurred in persons with advanced medical conditions. It could not be determined if metformin use was a contributing factor without metformin levels. These findings confirm the importance of clinical judgement when prescribing and continuing metformin for persons with advanced underlying medical conditions. Further study with serum metformin levels may help to better characterize the risk of MALA for persons on COT.

Disclosure
S. J. Lutz-mccain: None. B. E. Desanzo: None. B. Herk: None. M. Mclinden: None. M. M. Dinardo: None. R. Codario: None.
1140-P: Immune Dysregulation as a Consequence of Aberrant Glycemic Control in Diabetes Mellitus
Authors: SABAPATHY VIKRAM , DOGAN MURAT , VENKATADRI RAJKUMAR , ARBAB RAJIA , MA JENNIE Z. , BASU ANANDA , BASU RITA , SHARMA RAHUL 
Published: June 2021

People with diabetes mellitus are more vulnerable to viral infections including influenza and the ongoing COVID-19 pandemic. Fatal pneumonia and cytokine storm is a contributor to the mortality. We hypothesized that aberrant glycemic control induces an immune dysregulation, which compromises the anti-viral immunity and promotes inflammation by altering the balance of the protective T-regulatory cells (Tregs) and IL-17 responses. Indeed, comparison of the peripheral blood lymphocytes in a limited cohort of healthy controls (HC; n=4) and people with diabetes (n=9) showed profound immune dysregulation. As compared to HC (66±21 x10^3/ml), the number of circulating Tregs were significantly (p&lt;0.0001) reduced in diabetes group (15±2 x10^3/ml). Compared to HC, the proportion of IL-17 producing CD4 and CD8 T-cells was remarkably increased in the diabetes group at baseline as well as upon ex-vivo stimulation. A comparison of the ratio of IFNγ to IL-17 producing CD8 T-cells showed a significant bias towards reduced IFNγ and enhanced IL-17 production in the diabetes group (4.7±1.7) as compared to the HC (35±4). Similarly, comparison of the ratio of Tregs and Th1 to Th17 cells was also significantly biased towards reduced Treg and Th1 cells, and an exacerbated Th17 response in diabetes group as compared to the HC. Meta-analysis confirmed a significant positive correlation between HbA1c levels and the exacerbated IL-17 to IFNg ratios in CD4 (R2=0.7, p=0.0008) as well as CD8 (R2=0.6, p=0.002) cells.
In summary, altered glycemic control, as indicated by higher HbA1c levels, significantly correlates with compromised IFNg production in the CD8 and Th1 cells, which is important for anti-viral immunity, as well as a marked proinflammatory shift shown as reduced Tregs levels and enhanced IL-17 production by both CD4 and CD8 cells. This immune-dysregulation in diabetes may thus contribute to a greater susceptibility to viral infections and infection-induced pathology.

Disclosure
V. Sabapathy: Stock/Shareholder; Self; 10x Genomics, Apple, AstraZeneca, Bayer U. S., Gilead Sciences, Inc. M. Dogan: None. R. Venkatadri: None. R. Arbab: None. J. Z. Ma: None. A. Basu: None. R. Basu: None. R. Sharma: Other Relationship; Self; SlateBio Inc.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK104963); University of Virginia
1144-P: Chemical Assessment of Populations of Human Pancreatic Islets Isolated for Transplantation
Authors: RUBAKHIN STANISLAV , ROMANOVA ELENA V. , SWEEDLER JONATHAN V. 
Published: June 2021

Clinical transplantation of human cadaveric islets is an important therapy for the treatment of T1D. Such transplantation has demonstrated safety and efficacy in academic and clinical trials. Quality control during all stages of islet isolation, handling, and transplantation is critical for success of the therapy. A variety of tests are used to assess cellular integrity, islet population purity, and potency. Unfortunately, most of applied tests are not evaluating individual pancreatic islet chemical compositions which are indicative of overall islets functional and health state. Here we describe the results of mass spectrometric (MS) assessment of populations of individual pancreatic islets received from seven donors including four T2D cases. Random sampling and MS analysis of 232 islet-like structures detected 150 islets (based on size, morphology, and visual inspection). Our findings correlate (R2=0.9) with data on sample purity for different batches provided by the ADI IsletCore. The classic pancreatic islet hormones are observed in the majority of islets. Peptide profiles are mostly dominated by insulin, although we observe a greater variability of insulin peaks than somatostatin- and glucagon-related signals by mass spectrometry. No significant differences in our results are observed between healthy and T2D-affected islets. Fast mass-spectrometry-based assessment allowed selection of representative individual islets for liquid chromatography-MS (LC-MS), which provides an in-depth chemical coverage. Using LC-MS, a number of histone-related peptides are detected significantly expanding analyte coverage. To increase the throughput of direct MS analysis of islets, we use our optically guided mass spectrometry approach to automate the localization and analysis of larger islet populations. Using this technology and MS detection, hundreds of islets can be profiled for presence of a variety of metabolites, lipids, and peptides during a several-hour timespan.

Disclosure
S. Rubakhin: None. E. V. Romanova: None. J. V. Sweedler: None.

Funding
American Diabetes Association/Pathway to Stop Diabetes (1-18-VSN-19 to J.V.S.)
1145-P: Association of Muscle Mass Loss and Diabetes Development in Liver Allograft Recipients
Authors: LEE SEJEONG , KIM HAE KYUNG , KIM YOUNG-EUN , LEE MINYOUNG , JOO DONG JIN , KIM MYOUNG SOO , KANG EUN SEOK 
Published: June 2021

There has been increased recognition of the importance of post transplantation diabetes mellitus (PTDM), which is one of the most frequent complications after liver transplantation. Patients with end-stage liver diseases requiring transplantation are prone to be sarcopenic but the association between sarcopenia and PTDM remains inconclusive. We investigated the effect of postoperative muscle mass loss on the risk of PTDM development by measuring muscle area using computed tomography (CT) in Liver Allograft Recipients before and after transplantation. A total of five hundred patients who received liver transplantation between 2005 and 2020 were included from tertiary care hospital. Skeletal muscle area (cm2) at the level of vertebra L3-L5 was measured using CT scans performed before and 1 year after the transplantation, and the area was normalized to height squared (m2). Cox proportional hazard model was used to investigate the associations between the change in the muscle area after the transplantation (Δmuscle area) and the incidence of PTDM. Patients were divided into two groups (with muscle loss and without muscle loss). During the study follow-up period (median 4.9 years), PTDM occurred in 165 patients (33%). Muscle depletion was significantly associated with the increased risk of incident PTDM after adjustment for age, BMI, model for end-stage liver disease score and fasting blood glucose after liver transplantation (hazard ratio, 1.47; 95% confidence interval, 1.23-1.76; p&lt;0.001). Δmuscle area predicted PTDM development with a receiver operating characteristic area under the curve of 0.633 (95% confidence interval, 0.573-0.694). The cumulative incidence of PTDM was significantly higher in the patients with muscle loss than in the patients without muscle loss (P=0.026). The muscle depletion after liver transplantation is associated with the increased risk of PTDM development.

Disclosure
S. Lee: None. H. Kim: None. Y. Kim: None. M. Lee: None. D. Joo: None. M. Kim: None. E. Kang: None.
1150-P: A Hyperhomocysteinemia-Inducing Diet Alters Gut Microbiome and Glucose Homeostasis
Authors: CHENG CHAK KWONG , WANG CHENGUANG , HUANG YU 
Published: June 2021

Hyperhomocysteinemia (HHcy) is a risk factor for higher mortality in type 2 diabetic patients. A high methionine low folate (HMLF) diet chronically induces HHcy by causing homocysteine (Hcy) accumulation in systemic circulation. A higher systemic Hcy level is clinically associated with the incidence of diabetes mellitus. However, whether HHcy negatively impacts on glucose metabolism and insulin sensitivity remains inconclusive and contradictory. Meanwhile, very few studies have focused on the direct impact of HMLF diet on glucose homeostasis, and that on the gut flora. To understand the impact of HMLF diet, C57BL/6 mice were fed a HMLF diet for 8 consecutive weeks. HMLF diet feeding successfully induced HHcy, caused progressive body weight loss, and slightly impaired glucose homeostasis, as revealed by slight glucose intolerance and insulin resistance, in C57BL/6 mice. Of noted, HMLF diet feeding altered the gut microbiome profile that the relative abundance of porphyromonadaceae family of bacteria was enriched in diet-induced HHcy mice. Interestingly, a previous study correlated the higher frequency of porphyromonadaceae with the development of GLP-1 resistance, implying that HMLF diet might prompt the development of GLP-1 resistance. GLP-1 resistance results in the impairment on glucose-induced insulin secretion. These results provide novel insights into the roles of impaired glucose homeostasis and gut microbiome in the pathogenesis of HHcy-related complications. In short, an improper dietary pattern might impair glucose homeostasis by altering the gut microbiome profile.

Disclosure
C. Cheng: None. C. Wang: None. Y. Huang: None.

Funding
Chinese University of Hong Kong (4930709); Hong Kong Research Grants Council Senior Research Fellow Scheme 2020/21 (SRFS2021-4S04)
1155-P: Neurocircuits Controlling Adaptive Thermogenesis Rely on Skin Detection of External Temperatures through Calcitonin Gene-Related Peptide Expressing Spinal Neurons
Authors: RIERA CELINE 
Published: June 2021

Heat-sensory neurons arising from the dorsal root ganglia (DRG) play a pivotal role in the detection of cutaneous temperature and transmission of external signals to the brain, ensuring the maintenance of thermoregulation. However, whether these thermoreceptor neurons contribute to adaptive thermogenesis has remained elusive. We show that genetic ablation of heat sensing Calcitonin Gene-Related Peptide α (CGRPα) neurons promotes resistance to weight gain upon high fat diet (HFD) feeding and increases energy expenditure in mice. Mechanistically, we find that loss of CGRPα-expressing sensory neurons is associated with reduced lipid deposition in adipose tissue, enhanced expression of fatty-acid oxidation genes, higher ex-vivo lipolysis in primary white adipocytes and enhanced mitochondrial respiration from iBAT. Remarkably, mice lacking CGRPα sensory neurons manifest increased tail cutaneous vasoconstriction at room temperature. This exacerbated cold perception was not associated with reduced core temperature, suggesting that heat production and heat conservation mechanisms are engaged. Specific denervation of CGRPα neurons in intrascapular BAT did not contribute to the increased metabolic rate observed upon global sensory denervation. Taken together, these findings highlight an important role for cutaneous thermoreceptors in regulating energy metabolism, by triggering counter-regulatory responses involving energy dissipation processes including lipid fuel utilization and cutaneous vasodilation.

Disclosure
C. Riera: None.

Funding
American Diabetes Association/Pathway to Stop Diabetes (1-15-INI-12 to C.R.)
1171-P: HORMAD1, a Novel Hypoxia-Inducible Factor-1 Target, Is Upregulated in Maternal Overnutrition-Induced Nonalcoholic Steatohepatitis (NASH)/Hepatocellular Carcinoma
Authors: TAKIYAMA TAKAO , BESSHO RYOICHI , KITSUNAI HIROYA , TAKEDA YASUTAKA , SAKAGAMI HIDEMITSU , SERA TOSHIHIRO , NAKAMURA MASANORI , HORIKE SHIN-ICHI , NISHIKAWA YUJI , TAKIYAMA YUMI 
Published: June 2021

We investigated whether overnutrition during pregnancy were associated with the changes in gene expressions, oxygen metabolism, and vascular and hepatic parenchymal remodeling in fetal livers at mid gestational days E14.5 of dams fed a control diet (CD group) or a high-fat diet (HFD group) during pregnancy. Synchrotron-based phase-contrast micro-CT demonstrated embryos of HFD group showed hepatomegaly accompanied with the same size umbilical vein and less portal branching, which might result in liver hypoxia. Correspondingly, fetal livers of HFD group increased the expression of HIF-1alpha. To identify genes and pathways targeted by maternal overnutrition in fetal livers, we assayed mRNA levels with microarray. We identified 430 differentially expressed genes (DEGs) including 146 upregulated- and 284 downregulated genes in fetal livers of HFD group compared with those of CD group. The up-regulated DEGs were significantly enriched in DNA alkylation, bile secretion, and the down-regulated DEGs mainly enriched in neuronal system, cell maturation. Among upregulated DEGs, a cancer/testis antigen HORMAD1 was induced by hypoxia up to 30-fold compared with that in normoxia in primary mouse hepatocytes (PMH), and the genetic inhibition of HIF-1alpha by siRNAs abolished the stimulatory effect of hypoxia on Hormad1 expression. In addition, we found three putative hypoxia response elements within the mouse Hormad1gene. Interestingly, the tumor suppressor WW domain-containing oxidoreductase (WWOX), which inhibits the activity of HIF-1alpha, were remarkably decreased in hypoxia in PMH. Finally, HORMAD1 protein was upregulated in fetal livers and NASH-based HCC in offspring of HFD group at 15 weeks old. Our results suggest that WWOX-HIF-1alpha-HORMAD1 pathway might be involved in the development of NAFLD in offspring of obese and/or diabetic pregnant woman, and be an important therapeutic target of NASH/HCC.

Disclosure
T. Takiyama: None. Y. Takiyama: Other Relationship; Self; Gilead Sciences, Inc., Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Mochida Pharmaceutical Co., Ltd., Roche Diabetes Care, Taisho Pharmaceutical Co., Ltd. R. Bessho: None. H. Kitsunai: None. Y. Takeda: None. H. Sakagami: None. T. Sera: None. M. Nakamura: None. S. Horike: None. Y. Nishikawa: None.