bluuebunny/crossref_metadata_2025 huggingface dataset:
1231-P: Impact of Obesity on Patients Admitted for Diastolic Heart Failure: Insights from the National Inpatient Sample
Authors: ASEMOTA IRIAGBONSE R. , SHAKA HAFEEZ , ALMANI MUHAMMAD USMAN , AKUNA EMMANUEL , EDIGIN EHIZOGIE
Published: June 2021

Background: Obesity is one of the common comorbidities in patients with diastolic heart failure(HF). Though recognized as a risk factor for incidence of diastolic HF, the relationship of obesity to outcomes in patient with this diagnosis of is not clear and the obesity paradox has been suggested in the literature. Purpose The aim of this study was to compare the outcome of patient admitted for diastolic HF with and without obesity.

Method: Data were obtained from The National Inpatient Sample (NIS) 2016 and 2017 Database. The NIS was searched for hospitalization for diastolic HF as principal diagnosis with and without a secondary diagnosis of obesity using International Classification of Diseases, Tenth Revision (ICD-10) codes. Multivariate logistic and linear regression analysis was used accordingly to adjust for possible confounders.

Results: The combined 2016 and 2017 NIS database contained 367,395 hospitalizations for adult patients (aged ≥ 18 years) with a principal ICD-10 diagnosis for diastolic HF. Among this group, 107,790 (29%) had co-existing obesity. Of note, diastolic heart failure with obesity had decreased inpatient mortality that reached statistical significance (2.8% vs. 1.4%, AOR:0.71, 95% CI 0.62-0.81, p<0.0001) compared to those without obesity. The adjusted mean LOS in patients with diastolic HF and coexisting obesity was 0.68 days longer than those without obesity(5.65 days vs. 4.92 days, 95% CI 0.60-0.77, p<0.0001). Patient hospitalized with diastolic HF and obesity also had higher adjusted mean total hospital charge of $3,257 ($45,660 vs. $39,815, CI 2,134-4,379, p<0.0001) compared to diastolic HF patient without obesity.

Conclusion: Patients admitted for diastolic heart failure with co-existing obesity have reduced inpatient mortality compared to those without obesity. However, Total hospital charges and LOS were increased in the obesity group compared to the patient without obesity. Further prospective studies on this topic are needed.

Disclosure

I. R. Asemota: None. H. Shaka: None. M. Almani: None. E. Akuna: None. E. Edigin: None.
1236-P: Association between Body Mass Index (BMI) and Brachial-Ankle Pulse Wave Velocity (BAPWV) in Women with Type 2 Diabetes
Authors: CHEN YAO , MA BINGWEI , QU SHEN , WANG XINGCHUN , WEI DONG
Published: June 2021

Abstract Aims: The aim of this study was to investigate the association between body mass index (BMI) and brachial-ankle pulse wave velocity (baPWV) in Chinese woman with type 2 diabetes (T2DM).

Methods: We identified 1148 diabetes patients between 1 November 2017 and 1 November 2019 from Shanghai Tenth People’s Hospital. 407 women over were enrolled in this cross-sectional study. BaPWV was assessed as a marker of subclinical atherosclerosis. According to baPWV values, arteriosclerosis (AS) was set as 3 degrees: mild AS (baPWV ≥ 1400 cm/s), moderate AS (baPWV ≥ 1700 cm/s) and severe AS (baPWV ≥ 2000 cm/s). The multivariate linear regression analysis was used to explore the relationship between BMI and baPWV.

Results: Compared with the mild AS group, BMI was significantly lower in the moderate AS and severe AS groups (25.63±4.15 kg/m2 vs. 24.59±4.12 kg/m2 p=0.030; 25.63±4.15 kg/m2 vs. 24.49±3.60 kg/m2 p=0.025) There were no statistical difference between the moderate AS and the severe AS groups (p=0.838). BMI was significantly negatively associated with baPWV (r=-0.118, P=0.018). The associations were still significant after age and blood pressure adjustment (r=-0.160, P=0.001). Using multiple linear regression, BMI was negatively associated with baPWV (β=-0.152, P=0.001).

Conclusion: Arterial stiffness, as measured by baPWV, is lower in overweight and obesity Chinese woman with type 2 diabetes. High BMI was found to be a protective factor for AS. These findings may contribute to the explanation of the “obesity paradox” in T2DM.

Disclosure

Y. Chen: None. B. Ma: None. S. Qu: None. X. Wang: None. D. Wei: None.

Funding

Cheng du Committee of Health, China (20PJ201)
125-OR: Synaptotagmin 9 Regulates Tomosyn-2 Protein Abundance to Affect Early Phase of Insulin Secretion
Authors: PATHAK ASMITA , ALSHARIF HAIFA , TROMBLEY JOHN E. , RAHMAN MD MOSTAFIZUR , BHATNAGAR SUSHANT
Published: June 2021

Insulin secretion from pancreatic β-cells occurs in a biphasic manner. The loss of the early phase of insulin secretion, which occurs due to the inability of insulin granules to fuse with the plasma membrane (PM) via the formation of the SNARE complex, acts as a key determinant in impaired glucose tolerance and development of type 2 diabetes (T2D). Thus, it is critical to elucidate molecular mechanisms underlying early-phase insulin secretion. Tomosyn-2 binds to Stx1A, a key component of the SNARE complex, and functions as an endogenous inhibitor of insulin secretion. The mechanism by which Tomosyn-2 regulates the fusion of insulin granules is not completely understood. Our preliminary data show that Tomosyn-2 binds, colocalizes, and co-fractionates with synaptotagmin-9 (Syt9) at high glucose; Syt9 protein is present in the insulin granule membrane, and its role in insulin secretion remains poorly defined. Our data show that mice lacking Syt9 (Syt9-/-) have improved glucose clearance, increased in vivo early-phase insulin secretion at 5 min and 15 min post-glucose challenge with no change in insulin tolerance vs. the wild type control mice, suggesting that Syt9 regulates the early phase of insulin secretion from β-cells. Strikingly, Syt9-/- mouse islets have reduced Tomosyn-2 levels (∼50%) without altering the levels of other key SNARE proteins. The knockdown of Tomosyn in INS1 β-cells treated with KCL prevents the localization of Syt9 with Stx1A. These results show that Syt9 binding stabilizes Tomosyn-2 protein in a non-fusogenic complex by potentially blocking insulin granules’ access to the PM-Stx1A for membrane fusion and insulin secretion.

In summary, our data reveal a novel molecular complex in Stx1A-Tomosyn-2-Syt-9 to regulate the early-phase insulin secretion.

Disclosure

A. Pathak: None. H. Alsharif: None. J. E. Trombley: None. M. Rahman: None. S. Bhatnagar: None.

Funding

National Institutes of Health (R01DK120684-01)
1256-P: Insights into Acetyl-Coa-Carboxylase (ACC1) Phospho-Regulation in Pancreatic Beta Cells
Authors: BAKAR RULA BANY , LIBERATORI SABRINA , VEPRIK ANNA , TEBEKA NCHIMUNYA N. , KEMP BRUCE E. , MOHAMMED SHABAZ , CANTLEY JAMES
Published: June 2021

Aims: ACC1 couples glucose metabolism with de novo lipogenesis in lipogenic tissues, by converting acetyl-CoA to malonyl-CoA. In β-cells, ACC1 plays a critical role in β-cell growth and insulin secretion. However, very little is known about ACC1 regulation in β-cell. The aims of this study were to 1) assess the role of ACC1S79 in β-cell function and whole body glucose homeostasis; and 2) screen for novel phosphosites that may regulate ACC1 activity in β-cell.

Methods: 1) ACC1 single knock-in mouse model, with ACC1S79 mutated to alanine ACC1S79A, was obtained by crossing ACC1 double knock-in mice with wild type mice to isolate the ACC1S79A point mutation. 2) ACC1 protein was purified from INS1 β-cell following culture with different glucose concentrations. Quantitative phosphoproteomics was performed to characterise ACC1 phosphosites using a Q-Executive MS. Data analysed using MaxQuant and Perseus.

Results: 1) Female ACC1S79A mice exhibited no alternations in glucose homeostasis. In male mice we found no differences in serum insulin, GTT or ITT, although a small but significant reduction in fasting blood glucose was recorded in ACC1S79A mice compared to littermate controls. There was no significant change in GSIS from isolated ACC1S79A islets at 2mM glucose or in response to 7.5 and 20mM glucose, suggesting that ACC1S79 phosphorylation does not play a role in insulin secretion under physiological conditions.2) Using phosphoproteomics, we identified twenty phosphosites on ACC1 protein in β-cells. ACC1S1215 was highly phosphorylated at 2mM glucose, and showed a significant reduction in phosphorylation in response to 15mM glucose. In contrast, phosphorylation of ACC1S25 was lower at basal glucose and increased upon glucose stimulation.

Conclusions: Our data show that ACC1S79 phosphorylation does not play a major role as a glucose-regulated phosphosite in β-cells. However, other phosphosites show greater dynamic regulation by glucose and may play a role in regulating β-cell ACC1 activity.

Disclosure

R. Bany bakar: None. S. Liberatori: Employee; Self; LONZA. A. Veprik: None. N. N. Tebeka: None. B. E. Kemp: None. S. Mohammed: None. J. Cantley: Other Relationship; Self; Oxstem Beta.
1269-PUB: Evaluating the Response to GLP-1 Agonists in Veterans with Type 2 Diabetes Mellitus
Authors: BEGLEY BRETT A. , DESOUZA CYRUS , SHIVASWAMY VIJAY , SAMSON KAELI , SILVERMAN EMILY
Published: June 2021

Purpose: To delineate which factors help predict whether a patient is likely to respond or not respond to treatment with a glucagon-like peptide-1 (GLP-1) agonist.

Methods: The medical records for veterans with type 2 diabetes mellitus who began treatment with any GLP-1 agonist at the Veterans Affairs Nebraska-Western Iowa Health Care system from January 1, 2015, to December 31, 2019, were retrospectively reviewed. Patient demographics and baseline objective data were collected at treatment onset. Defined decreases in hemoglobin A1C (HbA1c), body weight, and insulin dose over a minimum 6-month period were used to identify responders and nonresponders. Associations between categorical variables and response status were assessed using Chi-Square tests or Fisher’s exact tests, and Wilcoxon Rank Sum tests were used to examine differences in distributions of variables of interest between response status groups.

Results: Of the 55 veterans evaluated during the study period, forty-two subjects (78%) responded to treatment with a GLP-1 agonist whereas twelve subjects (22%) did not respond. The median baseline HbA1c of those who responded was 8.7 (IQR: 8.3, 10.0) compared to 8.1 (IQR: 7.6, 8.8) for those who did not respond (p = 0.03). Among patients with peripheral neuropathy, 88.5% responded while only 65.5% of those without peripheral neuropathy responded (p = 0.046).

Conclusion: We demonstrate that a response to GLP-1 agonist treatment was associated with a higher baseline HbA1C and the presence of peripheral neuropathy. These findings warrant future multivariate analyses of a larger cohort to determine the ideal candidates for GLP-1 agonist therapy.

Disclosure

B. A. Begley: None. C. Desouza: Advisory Panel; Self; Bayer AG, Novo Nordisk, Consultant; Self; AstraZeneca. V. Shivaswamy: Research Support; Self; Eli Lilly and Company, Kowa Pharmaceuticals, Novo Nordisk. K. Samson: None. E. Silverman: None.
1274-PUB: Clinical Comparison of Hospitalized Patients with Diabetic Ketoacidosis Admitted to Intensive Care Unit (ICU) vs. Non-ICU Areas
Authors: LIU AIQUN , CARMICHAEL KIM , SCHALLOM MARILYN , ARROYO CASSANDRA
Published: June 2021

Many patients with DKA are admitted to Intensive Care Units (ICUs) due to restriction of insulin infusions outside of ICU areas. Our previous retrospective study showed that 37.0% of patients did not require admission to ICUs. Notably, reduced ICU admissions decrease costs and preserve bed availability for critical patients.

Aim: To compare the clinical characteristics and hospital care among patients with DKA admitted to the ICU to those admitted to the non-ICU areas.

Methods: A secondary analysis of collected data from the previous DKA study included 170 patients admitted from April-December 2017.

Results: Of 170 emergency department (ED) patients, 96 (56.5%) were admitted to an ICU and 74 (43.5%) to non-ICUs; 72 (42.4%) had T1D, 82 (48.2%) had T2D, and 16 (9.4%) had other types of DM. Mean age was 46.9±16.0 years old. The length of ED stay was significantly shorter (4.68±2.4 vs. 9.5±4.4 hours, p<0.001) and the length of hospital stay significantly longer (6.2±11.2 vs. 3.1±3.9 days, p=0.03) in the ICU group than in the non-ICU group. Acute kidney injury (p=0.01), stroke and deep vein thrombosis (p=0.05), and substance abuse (p=0.03) were more common in the ICU group. Mean blood glucose, pH, anion gap, ketone, potassium, and lactate levels were significantly higher, while bicarbonate levels were significantly lower in the ICU group. Insulin (96.9%) and fluid (97.9%) infusions were more commonly used in the ICU group. Patients in the ICU group received more endocrine (p<0.001) and dietitian (p<0.006) consultations than those in the non-ICU group.

Conclusions: Patients in the ICU group had more severe metabolic acidosis and other critical illnesses. Patients with uncomplicated DKA can be safely treated in the ED. Insulin drips should not be the criteria for ICU admission. Further study along with these data can help with the development of a severity scoring tool to identify the appropriate patients for ICU admissions.

Disclosure

A. Liu: None. K. Carmichael: None. M. Schallom: None. C. Arroyo: None.
1276-PUB: Diagnosis and Management of Inpatient Corticosteroid-Induced Hyperglycaemia in an Acute Respiratory Cohort in a Tertiary Centre
Authors: LONERGAN EIBHLÍN M. , CROWLEY MAIREAD , O’HALLORAN DOMHNALL J.
Published: June 2021

Corticosteroid-induced hyperglycaemia (CIH) is commonly encountered among acute respiratory inpatients, particularly those with diabetes mellitus (DM). Guidelines dictate frequency of inpatient capillary blood glucose (CBG) monitoring and treatment modification in the context of exogenous corticosteroid administration. Patients admitted with acute respiratory illness requiring corticosteroids were reviewed to evaluate monitoring, diagnosis and treatment of CIH. A re-audit was performed at a 3-month interval. Twenty patients were treated acutely with corticosteroids; median age 68 years (range 40-88); 13 male. Seven of these patients were diabetic; 6 type 2 DM; 1 type 1 DM. The most common conditions requiring admission included COPD, IPF, pneumonia, asthma, covid-19 and lung cancer. Of the twenty patients included, 13/20 (65%) had CBG monitoring. Within the monitored group, 6/13 (46%) showed readings consistent with hyperglycaemia (>12mmol/L) on more than one reading, of whom all were diabetic. Patients who exhibited hyperglycaemia had appropriate escalation of CBG checks in 3/6 (50%) cases. One patient of six (17%) with persistent CIH was treated appropriately with oral hypoglycaemics. The remaining five patients remained untreated. After education of respiratory medical staff, re-audit revealed persistently infrequent CBG checks (8/15 monitored - 53%). However, of those monitored, escalation of treatment was undertaken in 2/3 cases (67%) in cases of CIH. A high proportion of respiratory inpatients require treatment acutely with corticosteroids. Co-existent DM indicates a higher likelihood of developing CIH. Overall, CBG checks are sporadically performed despite hyperglycaemia. Appropriate treatment escalation of CIH is inadequate. Further education of medical and nursing staff regarding CIH guidelines is required for optimal glycaemic control in this cohort.

Disclosure

E. M. Lonergan: None. M. Crowley: None. D. J. O’halloran: None.
128-OR: DOC2b Boosts Insulin Secretion via a Yes Kinase-Dependent Mechanism
Authors: BHOWMICK DITI CHATTERJEE , ASLAMY ARIANNE , BHATTACHARYA SUPRIYO , OH EUNJIN , AHN MIWON , THURMOND DEBBIE C.
Published: June 2021

Exocytosis regulatory protein DOC2b is a crucial regulator of SNARE assembly in β-cells and enrichment of DOC2b enhances glucose-stimulated insulin secretion (GSIS). However, the underlying mechanism of how DOC2b boosts GSIS remains to be explored. We hypothesize that tyrosine-phosphorylation of DOC2b’s functionally indispensable C2AB domain is required for DOC2b’s beneficial function on GSIS. Biochemical analysis revealed that DOC2b is tyrosine-phosphorylated specifically by glucose within 1-2 min of stimulation in MIN6 β-cells and human islets. Pervanadate (pV) treatment, which inhibits tyrosine-specific phosphatases, validated the phosphorylation event to be tyrosine-specific. Further, the Src family kinases (SFKs) were implicated in this phosphorylation event, based upon the ability of SFK inhibitor SU-6656 to markedly attenuate the level of tyrosine-phosphorylated DOC2b under pV treated conditions. Phosphorylated/activated SFKY416 co-immunoprecipitated with DOC2b from pV treated β-cells; SU-6656 abrogated the interaction. YES kinase, an SFK, was also co-immunoprecipitated with DOC2b following glucose stimulation or pV treatment, suggesting YES kinase to be the specific SFK that phosphorylates DOC2b in β-cells. All-atom molecular dynamics simulations identified a specific tyrosine residue present in DOC2b’s C2B domain, Y301, as solvent-exposed and available for modification. Our results using phosphodeficient and phosphomimetic point mutants validated the involvement of the Y301 phosphorylation in for the boosting effect of DOC2b on GSIS. Taken together, these results resolve the first glucose-induced post-translational modification of DOC2b in β-cells, pinpointing the kinase and the site of action. These findings support a new model for DOC2b in GSIS: 1) glucose stimulation of the β-cell rapidly phosphorylates DOC2b on residue Y301 via YES kinase at the plasma membrane, yielding 2) an activated form of DOC2b that regulates insulin release.

Disclosure

D. Chatterjee bhowmick: None. A. Aslamy: None. S. Bhattacharya: None. E. Oh: None. M. Ahn: None. D. C. Thurmond: Consultant; Self; Immutics.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (DK067912, DK112917, DK102233 to D.C.T.); JDRF (3-PDF-2020-934-A-N to D.C.B.)
130-OR: Statin Exposure Increases Star (Steroidogenic Acute Regulatory Protein) Expression in Islets: A Novel Mechanism for ß-Cell Dysfunction and Increased Diabetes Risk?
Authors: HOGAN MEGHAN F. , ESSER NATHALIE , TEMPLIN ANDREW T. , CASTILLO JOSEPH J. , AKTER REHANA , HULL REBECCA L. , KAHN STEVEN E. , ZRAIKA SAKENEH
Published: June 2021

While statin therapy reduces plasma cholesterol, it also impairs β-cell function and increases the risk of developing diabetes. We have shown that the cholesterol transport protein STAR is synthesized in β cells and its upregulation results in increased β-cell mitochondrial cholesterol content, producing β-cell dysfunction. Given statins’ role in cholesterol metabolism, we determined whether statin exposure increased expression of islet STAR, decreased expression of the downstream cholesterol metabolizing enzyme CYP27A1 and inhibited β-cell function.

Atorvastatin treatment of C57Bl/6 islets increased Star gene (4.51±1.12 vs. 1.00±0.19, n=5, p<0.05) and a 3.3-fold increase in relative protein levels (n=2, p<0.005) while decreasing expression of Cyp27a1 (0.55±0.14 vs. 1.00±0.18, n=5, p<0.05). As expected, inhibition of the enzyme HMG-CoA reductase (Hmgcr) with atorvastatin resulted in compensatory increases in expression of Hmgcr and the LDL receptor (Ldlr); (Hmgcr: 5.88±0.65 vs. 1.00±0.05; Ldlr: 3.22±0.58 vs. 1.00±0.12; n=5, p<0.05), and a 5.1-fold increase in relative LDLR protein (n=2, p<0.05). Atorvastatin decreased glucose-stimulated insulin secretion (fold insulin response to 20 mM over 2.8 mM glucose: 28.6±5.86 vs. 52.0±8.25, n=5, p<0.05), but did not change insulin content (51.0±5.64 vs. 47.2±3.51 pmol insulin/5 islets, n=5, p=0.90).

In summary, exposure of islets to atorvastatin increased Star expression, decreased Cyp27a1 expression and reduced β-cell secretory function. These findings suggest that increased Star and impaired cholesterol metabolism, leading to increased cholesterol accumulation and mitochondrial dysfunction, may be a novel mechanism mediating the effects of statins to impair β-cell function and increase risk of type 2 diabetes.

Disclosure

M. F. Hogan: None. N. Esser: None. A. T. Templin: None. J. J. Castillo: None. R. Akter: None. R. L. Hull: None. S. E. Kahn: Advisory Panel; Self; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Pfizer Inc. S. Zraika: None.

Funding

American Diabetes Association (1-18-PDF-174 to M.F.H.); U.S. Department of Veterans Affairs (BX001060)
135-OR: Impaired Awareness of Hypoglycemia Is Associated with Residual Beta-Cell Function and Glucose Variability Parameters in Patients with Type 1 Diabetes
Authors: KLIMONTOV VADIM , SEMENOVA JULIA F. , KORBUT ANTON I.
Published: June 2021

The Aim: to evaluate the relationships between impaired awareness of hypoglycemia (IAH), residual beta cell function and short-term glucose variability (GV) in patients with type 1 diabetes (T1D).

Materials and Methods: We observed 400 patients, 145 M/255 F, age 18-85 years (median - 36 years), diabetes duration 0.5-52 years (median - 16 years), HbA1c 4.7-15.1% (median - 8%). The Clarke's questionnaire was used for IAH recognition. Beta cell function was estimated by fasting and 2-h postprandial C-peptide levels. Day-time (6.00-23.59), nocturnal (0.00-5.59) and 24-h Time In target Range (TIR), Time Above target Range (TAR), Time Below target Range (TBR), and GV parameters, including Standard Deviation (SD), Coefficient of Variation (CV), Mean Amplitude of Glucose Excursions (MAGE), 2-h Continuous Overlapping Net Glycemic Action (CONGA), Lability Index (LI), J-index, Low Blood Glucose Index (LBGI), High Blood Glucose Index (HBGI), M-value and Mean Absolute Glucose (MAG), were calculated from short-term (3-7 days) continuous glucose monitoring (CGM).

Results: In our cohort, IAH was recognized in 163 (40.8%) individuals. Patients with IAH, as compared to those without, demonstrated longer diabetes duration (P<0.0001), lower C-peptide postprandial level and increment (p=0.02 and p=0.0003 respectively) and increased day-time and nocturnal mean glucose, SD, CONGA, J-index, HBGI and M-value (all P≤0.02). Nocturnal MAGE, LI and LBGI, as well as 24-h mean glucose, SD, CV, MAGE, CONGA, J-index, HBGI, and M-value were also higher in patients with IAH (all P≤0.01). No differences in HbA1c, TIR, TAR and TBR were found between the groups. Day-time, nocturnal and 24-h SD, CV, LI, J-index, and HBGI, as well as day-time and 24-h MAGE, correlated negatively with postprandial C-peptide.

Conclusion: In patients with T1D, IAH is associated with low (or zero) residual beta cell function. This relationship could be mediated via enhanced GV.

Disclosure

V. Klimontov: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Sanofi, Research Support; Self; Boehringer Ingelheim International GmbH, Speaker’s Bureau; Self; AstraZeneca, Medtronic. J. F. Semenova: None. A. I. Korbut: None.

Funding

Russian Science Foundation (20-15-00057)
136-OR: Nocturnal Hypoglycemia Prevention Strategies Used by People with Type 1 Diabetes According to Their Insulin Delivery and Blood Glucose Monitoring Technology
Authors: TALBO MERYEM K. , MESSIER VIRGINIE , DESJARDINS KATHERINE , RABASA-LHORET RÉMI , BRAZEAU ANNE-SOPHIE , PETERS TRICIA
Published: June 2021

People with T1D (PWT1D) use many strategies to avoid nocturnal hypoglycemia (NH), however, the current evidence on these strategies is limited. Technologies such as continuous subcutaneous insulin infusion (CSII) or continuous glucose monitors (CGM) could help reduce NH and possibly alter PWT1D’ management behaviors.

Aim: To describe PWT1D’ preferred NH prevention strategies according to their use of technology.

Methods: Self-reported data from an online registry of PWT1D were analyzed. To describe which NH prevention strategies are most often used, we ran a χ2 test with a post hoc pairwise comparison of the groups based on their mode of insulin delivery and glucose monitoring (CSII + self-monitoring of blood glucose (SMBG); CSII + CGM; multiple daily injections (MDI) + CGM; MDI + SMBG).

Results: Among 767 adults (64% female, mean age 45 ± 15 years, T1D duration 25 ± 14 years) 42% used MDI + CGM, 40% CSII + CGM, 5% CSII + SMBG, and 13% MDI + SMBG. About 67% reported waking up ≥1 time in the past month due to NH symptoms. The most widely used strategies were verifying bedtime glycemia (71%), having an evening/bedtime snack (60%), and/or reducing nocturnal basal insulin (30%). PWT1D using CSII + CGM or CSII + SMBG relied more on basal insulin reduction (36% and 33.3%, respectively) compared to those using MDI + CGM (26%) or MDI + SMBG (19%). Less PWT1D using CSII + CGM reported having a snack to prevent NH (51%), compared to CSII + SBMG (61%), MDI + CGM (66%), and MDI + SBGM (67%) groups (p<0.001).

Conclusion: Results suggest that PWT1D using technology choose different strategies to avoid NH than non-users. CSII users relying on basal insulin adjustment was expected as CSII offers more flexibility for insulin delivery. Snacks remain a popular strategy to prevent NH but are less used by PWT1D on CSII + CGM. While our findings provide some real-life insight into the methods PWT1D use to avoid NH, the efficacy of these strategies still needs further investigation.

Disclosure

M. K. Talbo: None. V. Messier: Other Relationship; Self; Eli Lilly and Company. K. Desjardins: None. R. Rabasa-lhoret: Advisory Panel; Self; Bayer Inc., Covance Inc., Insulet Corporation, Pfizer Inc., Other Relationship; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Novo Nordisk, Sanofi-Aventis, Research Support; Self; Canadian Institutes of Health Research, Cystic Fibrosis Canada, Diabetes Canada, JDRF, National Institutes of Health, Prometic, Société Francophone du Diabète, Speaker’s Bureau; Self; CMS Canadian Medical&Surgical Knowledge Translation Research Group, CPD Network. A. Brazeau: None. T. Peters: None.

Funding

Canadian Institutes of Health Research (JT1-157204); JDRF (4-SRA-2018-651-Q-R)
138-OR: Indirect Treatment Comparison of Ready-to-Use Glucagon Rescue Treatments for Severe Hypoglycemia: Nasal Glucagon vs. Liquid Stable Glucagon
Authors: YAN YU , CHILD CHRISTOPHER J. , SYRING KRISTEN , WANG QIANQIAN , THRELKELD REBECCA J.
Published: June 2021

Objective: An indirect treatment comparison (ITC) evaluated the efficacy and safety differences between 2 ready-to-use severe hypoglycemia rescue treatments, nasal glucagon (NG, Eli Lilly and Company) and liquid stable glucagon rescue pen (GRP, Xeris Pharmaceuticals), in adults with type 1 or type 2 diabetes.

Methods: Systematic literature reviews identified 3 randomized clinical trials assessing the efficacy and safety of NG versus reconstituted injectable glucagon (IG), and 3 trials of GRP versus IG. No head-to-head trials of NG versus GRP were identified. The Bayesian fixed-effect network meta-analysis was used to perform the ITC. Endpoints included the proportion of participants achieving treatment success (defined as increase in blood glucose to ≥70 mg/dL or an increase of ≥20 mg/dL from nadir blood glucose within 30 mins), maximum blood glucose, and treatment-emergent adverse events (TEAE). In order to more closely match the study populations, participants with a nadir blood glucose value of ≤54 mg/dL were analyzed.

Results: A similar proportion of GRP (98.9% [279/282]) and NG participants (99.4% [155/156]) achieved treatment success (Wald method p=0.63). The mean max blood glucose values were 220 mg/dL for GRP and 168 mg/dL for NG, with a significant treatment difference between GRP and NG, while adjusting IG as a comparator (17.32 mg/dL, 95% credible interval: [3.94, 30.97]). Proportions of participants experiencing ≥1 TEAE were 48.8% for GRP and 38.5% for NG (odds ratio: 1.31 [0.67, 2.31]). Subgroup analyses showed consistent results.

Conclusion: NG and GRP had comparable efficacy in reversing insulin-induced hypoglycemia in adults with diabetes. NG had a mean max blood glucose below 180 mg/dL, which may have implications on the re-establishment of euglycemia after severe hypoglycemia rescue.

Disclosure

Y. Yan: Employee; Self; Eli Lilly and Company. C. J. Child: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. K. Syring: Employee; Self; Eli Lilly and Company. Q. Wang: Employee; Self; Eli Lilly and Company. R. J. Threlkeld: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
139-LB: Understanding Attitudes towards Influenza Vaccination among Children with Diabetes in a NYC Hospital
Authors: APSAN JENNIFER , COPPEDGE EMILY , ANTAL ZOLTAN
Published: June 2021

Background: It is well established that diabetes serves as a risk factor for morbidity and mortality of Influenza infections in the US. The AAP recommends Influenza vaccinations in all children over 6 months of age with a noted emphasis on ensuring that children in high risk groups are vaccinated. We sought to better understand patient and family attitudes towards Influenza vaccination in our diabetes clinic as the first step in trying to improve vaccination rates in our clinics.

Methods: 64 patients, ages 2 to 20 years, of a NYC diabetes clinics were surveyed between 12/2019 and 3/2020. If responses indicated they had refused a vaccine, patients were asked why they had refused. Regardless of their vaccination status, all patients were asked if they would obtain vaccination if one were available at their diabetes clinic appointment.

Results: Overall, 57% of our patients responded that they had received an influenza vaccine in the 2019-2020 season. Further, 13% of patients indicated that they would be receiving a vaccination while 27% of them responded that they did not wish to receive a vaccination. When viewed by age, the 10-15 year old age group had the highest vaccination rate at 70%. While attitudes varied from family to family, the most the most common reasons for refusal included patient preference (31%), disbelief in efficacy (21%), concerns for side effects of vaccination (21%) and ’too busy’ (10.5%). 70% of all patients surveyed expressed that if a vaccination was offered in their diabetes clinic, they would be interested in receiving it.

Conclusions: Focus should be placed on educating our youngest and oldest patients with diabetes to obtain an annual Influenza vaccine. Understanding the most common hesitations among our patients will allow us to improve communication about the vaccine and access to care.

Disclosure

J. Apsan: None. E. Coppedge: None. Z. Antal: None.
148-LB: Demographic Factors Predict Successful Transition to Adult Care in Adolescents and Emerging Adults with Type 1 Diabetes
Authors: TILDEN DANIEL R. , JASER SARAH S.
Published: June 2021

Background: Adolescents and emerging adults with T1D are a particularly vulnerable group among those with this chronic disease. Previous work has shown that this group has the highest HgbA1c of any age cohort with the disease. While it has been shown that maintaining engagement with care can help improve disease control, there is limited evidence to identify those at most risk of being lost to follow up at this care transition. The current study used visit-level EHR data to analyze demographic and visit data to determine predictors of successful pediatric to adult transition.

Methods: This is a retrospective cohort study of 4,185 patients with T1D who were seen in the pediatric diabetes clinic at least once in three consecutive calendar years between 2004 and 2020. The primary outcome of interest was completion of at least 1 adult endocrinology clinic visit for T1D care. Patients were compared using descriptive statistics and logistic regression to analyze demographic factors and key disease metrics including HgbA1c and hospital admission.

Results: Among study subjects, 730 completed transition to adult care within our health system. Those completing transition has about one fifth the odds (aOR 0.22 95%CI: 0.15 - 0.32) of having private insurance compared to patients who did not transition. No other significant demographic differences were found between the two groups. Among those who did transition, the median time from last pediatric to the first adult visit was 190 days (IQR 100 - 542) with only 53.2% completing their first adult visit within 6 months.

Discussion: Our data suggest that insurance is the most significant barrier to transition from our pediatric to adult clinics for patients with T1D. Importantly, even among those who do ultimately receive care from our adult clinics, we identified significant gaps in care. Improving our processes for transitions should focus on closing these gaps to help emerging adults maintain engagement in their T1D care.

Disclosure

D. R. Tilden: None. S. S. Jaser: None.

Funding

National Institutes of Health (DK007061CTSA); National Center for Advancing Translational Sciences (UL1TR002243)
148-OR: Usefulness of CGM Metrics to Assess Glycemic Control in Non-White Subjects with Diabetes
Authors: TOSCHI ELENA , SLYNE CHRISTINE , MICHALS AMY , SIFRE KAYLA , DEWAR RACHEL , ATAKOV-CASTILLO ASTRID , DAVIS DAI’QUANN J. , MUNSHI MEDHA
Published: June 2021

Introduction: Glucose management indicator (GMI), a CGM-based metric, of mean glucose is thought to give more information on glycemic excursion than laboratory measured A1c. We have shown differences in relationship between A1c and GMI in different age groups, however it is not known whether racial differences affect the relationship between A1c and GMI.

Methods: We analyzed data from patients with diabetes undergoing professional CGM (proCGM) at a tertiary care diabetes center between year 2017 and 2020, who had at least 10 days of CGM data. Medical records were queried to obtain demographic information and laboratory A1c results from within 1 month of CGM wear. GMI was calculated as Formula =3.31 + (0.02392 × mean glucose in mg/dL).

Results: We evaluated 316 patients (mean age 60 ±18, 51% female, duration of diabetes 24±15 years, T1D 45% and T2D 55%, 78% white and 22% non-white). Subjects were identified by race as non-white (T1D 22%; T2D 78%) or white (T1D 45%; T2D 55%). CGM metrics in the non-white and white cohort were similar; time in range (728 ± 342 vs. 722 ± 307 min/day; p=ns), time <70 mg/dL (90 ± 98 vs. 97 ± 108 min/day; p=ns ), and time >180 mg/dL (568 ± 324 vs. 569 ± 346 min/day; p=ns). While GMI was not different in the nonwhite vs. white cohort (7.6 ± 1.3 vs. 7.7 ± 1.5; p=ns), A1c was higher in non-whites (8.7 ± 1.6 vs. 8.1 ±1.3; p=0.004). An absolute difference between A1c and GMI was higher in nonwhite vs. white (1.5 ± 0.88 vs. 1.1 ± 0.82 vs; p=0.006) and the absolute difference of 0.5% was observed in higher proportion of nonwhite patients (50 [75%] vs. 165 [68%]).

Conclusions: In our study cohort, the relationship between GMI and A1c is different in non-white versus white population despite similar CGM metrics. This difference might be important to consider when assessing glycemic control and goals in diverse patient population.

Disclosure

E. Toschi: Consultant; Self; Medtronic. C. Slyne: None. A. Michals: None. K. Sifre: None. R. Dewar: None. A. Atakov-castillo: None. D. J. Davis: None. M. Munshi: Consultant; Self; Sanofi.

Funding

National Institutes of Health (1DP3DK112214-01)
154-LB: Impact of Maternal Diabetes Exposure on Soluble Adhesion Molecules
Authors: LANDRETH SAMANTHA B. , TEAGUE APRIL M. , JENSEN MARY ELLEN , GULATI SHELLY , TRYGGESTAD JEANIE B.
Published: June 2021

Soluble adhesion molecules are associated with cardiovascular disease and increased in individuals with diabetes. The current study assesses the impact of diabetes exposure in utero on the abundance of circulating adhesion molecules in cord serum as well as soluble adhesion molecules released from human umbilical vein endothelial cells (HUVEC) upon exposure to high levels of glucose. Women with and without diabetes (DM; gestational or type 2) were recruited at delivery. DM was diagnosed based on the criteria by the American Diabetes Association. Primary cultures of HUVEC were established in M199 medium with growth supplements. For the high glucose treatment, medium was adjusted to a final glucose concentration of 25mM with media collected 48 hours post treatment. The soluble adhesion molecules intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and E-selectin were measured by ELISA in the cord blood serum and the conditioned HUVEC media. Serum adhesion molecules were measured in 42 infants born to mothers with normal glycemia and 35 infants of mothers with DM. The mothers with DM were older with higher BMI (p=0.027 and 0.008, respectively). In a fully adjusted model, VCAM was significantly increased in the cord serum of infants born to mothers with diabetes (p=0.046), but ICAM and E-selectin were not different. ICAM was significantly correlated with E-selectin (r2=0.25, p<0.001), but not VCAM. ICAM was also significantly correlated with maternal HbA1c (r2=0.16, p=0.004) and cord serum non-esterified fatty acids (r2=0.08, p=0.013). From the HUVEC, the abundance of adhesion molecules was not different based on DM or high glucose exposure; however, VCAM abundance in the HUVEC supernatant was significantly correlated with ICAM (r2=0.27, p=0.010) and cord serum insulin (r2=0.19, p=0.042). Alterations in soluble adhesion molecule abundance in infants exposed to the diabetic milieu of pregnancy may reflect early alterations in vascular function predicting future cardiovascular disease.

Disclosure

S. B. Landreth: None. A. M. Teague: None. M. Jensen: None. S. Gulati: None. J. B. Tryggestad: None.

Funding

National Institutes of Health (1K23DK106533)
159-LB: High-Affinity ZnT8 Autoantibodies by Electrochemiluminescence Assay Improve the Risk Prediction for Type 1 Diabetes
Authors: JIA XIAOFAN , HE LING , MIAO DONGMEI , WAUGH KATHLEEN , RASMUSSEN CRISTY GENO , DONG FRAN , REWERS MARIAN , YU LIPING
Published: June 2021

Background: A cohort of children with single ZnT8 autoantibody (ZnT8A) positivity were identified in two large clinical trials, Autoimmunity Screening for Kids (ASK) and Diabetes Autoimmunity Study in the Young (DAISY), and their risk of type 1 diabetes (T1D) have never been studied.

Methods: Three cohorts were analyzed using a high-affinity electrochemiluminescence (ECL) ZnT8A assay including 302 new onset T1D patients, 135 children positive for ZnT8A by standard radio-binding assay (RBA) from 23400 children screened in ASK study, and 123 children with multiple autoantibodies or single ZnT8A by RBA from 2547 children in DAISY study.

Results: ECL-ZnT8A had a similar sensitivity with RBA-ZnT8A in the cohort of 302 new onset T1D patients (62.3% vs. 61.9%). In ASK, 135/23400 of general population children were positive for RBA-ZnT8A and 64/135 were found as single ZnT8A only without other islet autoantibodies. Of 64 children with single ZnT8A, only 14.1% (9/64) were detectable by ECL-ZnT8A. Antibody-affinity analysis revealed that the ZnT8A in RBA but not confirmed by ECL were of low affinity and they were easily disappeared during the follow-up behaving as ‘transient’ positivity. In terms of T1D classification from stage 1 to stage 3, positive predictive value (PPV) of ECL-ZnT8A (61/70 [87.1%]) was significantly higher than that of RBA-ZnT8A (73/137 [53.3%]; P<0.0001). The cumulative risk of clinical T1D development with ZnT8A confirmed by ECL (16/66) was significantly enhanced during a short time of follow-up, compared with ZnT8A not confirmed by ECL (1/43; p=0.023). Similarly in DAISY participants, 11/2547 children were identified as single ZnT8A by RBA while only three who developed T1D were detected ECL-ZnT8A.

Conclusions: Large proportion of ZnT8A by current standard RBA are single ZnT8A with majority at low risk in population-based screening while ECL-ZnT8A can discriminate high risk from low risk and are highly predictive for T1D development.

Disclosure

X. Jia: None. L. He: None. D. Miao: None. K. Waugh: None. C. Geno rasmussen: None. F. Dong: None. M. Rewers: Advisory Panel; Self; Provention Bio, Inc., Consultant; Self; RTI, Research Support; Self; Janssen Research & Development, LLC, JDRF. L. Yu: None.

Funding

Diabetes Research Center (P30DK116073); JDRF (2-SRA-2018-533-S-B, 2-SRA-2020-965-S-B, 1-SRA-2016-208-S-B); National Institutes of Health (DK32083)
160-OR: Increased Adiposity and Low Height-for-Age in Early Childhood Is Associated with Later Metabolic Risk in American Indian Children and Adolescents
Authors: RAMIREZ-LUZURIAGA MARIA J. , KOBES SAYUKO , SINHA MADHUMITA , KNOWLER WILLIAM C. , HANSON ROBERT L.
Published: June 2021

Background: Growth abnormalities in early childhood have been related to later metabolic risk, but little is known about these associations in populations at high risk of diabetes.

Methods: We linked anthropometric data collected at ages 0-<5 y from 2928 routine clinical examinations conducted 1990-2000 to metabolic data from a longitudinal study in a southwestern American Indian population at high risk of diabetes. A total of 701 participants with ≥1 follow-up examination at ages 5-16 y were included. We derived age and sex-specific z-scores (from WHO Child Growth Standards) of weight-for-height (WHZ) and height-for-age (HAZ) at ages 0-<5 y. We selected the highest observed WHZ and the lowest HAZ and analyzed associations of categories of WHZ and HAZ with metabolic data at ages 5-9 y and 10-16 y. Linear mixed effects models were used to account for repeated measures.

Results: In age and sex-adjusted models, overweight and obesity (WHZ > 2) at ages 0-<5 y was significantly associated with higher BMI and with greater height at ages 5-16 y relative to normal weight (WHZ ≤ 1). It was also associated with increased fasting glucose, 2-h glucose, fasting insulin, 2-hr insulin, total cholesterol, triglycerides, SBP, DPB and decreased HDL. For example, at ages 5-9 y 2-h glucose was 10.4 mg/dl higher (95% CI: 5.6, 15.3) and fasting insulin was 1.88 times higher (95% CI: 1.58, 2.24). Associations were attenuated and no longer significant when adjusted for BMI. Low height-for-age (HAZ< -2) at ages 0-<5 y was associated with lower BMI and lower height at ages 5-16 y relative to normal height (HAZ ≥ 0). With adjustment for BMI, low height-for-age was associated with 1.40 times higher 2-h insulin (95% CI: 1.05, 1.87) and 5.47 mg/dL lower HDL (95% CI: 2.68, 8.62) at ages 10-16 y.

Conclusion: These analyses suggest that both overweight/obesity and low height-for-age in early childhood can influence subsequent metabolic risk in American Indian children and adolescents.

Disclosure

M. J. Ramirez-luzuriaga: None. S. Kobes: None. M. Sinha: None. W. C. Knowler: None. R. L. Hanson: None.
161-LB: Role of Child Physical Activity and Sleep Efficiency in Relation to Prenatal Exposure to Gestational Diabetes on Adiposity
Authors: ALVES JASMIN M. , DEFENDIS ALEXIS W. , CHOW TING , NGUYEN-RODRIGUEZ SELENA T. , XIANG ANNY , PAGE KATHLEEN A.
Published: June 2021

Introduction: Little is known on the role of child physical activity (PA) and sleep in relation to maternal gestational diabetes mellitus (GDM) and child adiposity. We explored these relationships using data collected from the BrainChild Study.

Method: Data included 88 children (mean ± SD, age 9.5 ± 1.7 years; 52% GDM exposed; 56% female) born at Kaiser Permanente Southern California. GDM exposure was obtained from electronic medical records. Anthropometric measurements, time spent in moderate and vigorous PA and actigraphy-based sleep parameters were measured during daily life for 7 days using wrist-worn accelerometers.

Results: GDM exposed vs. unexposed children had higher BMI z-scores (1.3 ± 1.0 vs. 0.7 ± 1.1, p=0.015), total body fat (29.7 ± 9.6 vs. 25.0 ± 8.3%, p=0.017) and waist to height ratios (WHR) (0.52 ± 0.08 vs. 0.47 ± 0.07, p=0.002). Linear regression showed that children who engaged in more VPA had lower measures of adiposity, independent of age and sex (BMI z-score: β=-0.39, p=0.033; body fat%: β=-3.25, p=0.037; WHR: β=-0.23, p=0.068). Further adjusting for sleep efficiency did not affect the results. Similar patterns were observed for MVPA but were not significant. There was no interaction between GDM exposure and PA on adiposity. Sleep efficiency was not associated with adiposity, but there was a significant interaction between GDM exposure and sleep efficiency on child adiposity (p=0.042). GDM exposed children who had better sleep efficiency had marginally lower body fat (β=-0.56, p=0.098), while this relationship was not observed in unexposed children (β=0.50, p=0.14).

Conclusion: Our findings demonstrate that VPA is associated with lower child adiposity measures regardless of GDM exposure, and sleep efficiency is associated with lower adiposity among GDM exposed children. These findings suggest that strategies to increase VPA and improve sleep efficiency may be beneficial for ameliorating the adverse effects of GDM exposure on child adiposity.

Disclosure

J. M. Alves: None. A. W. Defendis: None. T. Chow: None. S. T. Nguyen-rodriguez: None. A. Xiang: None. K. A. Page: None.

Funding

American Diabetes Association (1-14-ACE-36 to K.A.P.); National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116858)
165-OR: Antioxidant-Based Encapsulation Strategies to Enhance Islet Allotransplantation
Authors: BARRA JESSIE , KOZLOVSKAYA VERONIKA , KHARLAMPIEVA EUGENIA , TSE HUBERT M.
Published: June 2021

The destruction of insulin-producing cells is a hallmark of type 1 diabetes (T1D) and results in a loss of glycemic control. Islet transplantation can restore glucose homeostasis and prevent hypoglycemic events; however, long-term graft survival is low. Oxidative stress mediates islet transplant rejection. Therefore, suppressing oxidative stress with nanothin encapsulation materials comprised of alternating layers of tannic acid (TA), an immunomodulatory antioxidant, and poly(N-vinylpyrrolidone) (PVPON), a scaffold polymer, may allow for improved graft survival. We hypothesize that (PVPON/TA)-encapsulation of islets will prolong graft function and delay allotransplantation rejection in the absence of systemic immunosuppression. We recently published that allogeneic transplantation of encapsulated C57BL/6 islets into NOD mice significantly delayed graft failure, decreased free radical-adduct formation, and reduced infiltrating immune cell effector responses. These data suggest local immunosuppression with (PVPON/TA)-encapsulation may be a promising technique to prolong islet graft function in islet allotransplants. To enhance immunosuppression, we conjugated CTLA-4-Ig to the outer surface of (PVPON/TA) layers. (PVPON/TA/CTLA-4)-encapsulated islets display significantly delayed allograft rejection compared to (PVPON/TA) controls. Flow cytometry analysis demonstrated reduced CD80/CD86 costimulatory receptor and MHC-II expression on innate immune populations, enhanced FOXP3+ regulatory T cells, and enhanced PD1+ CD8 T cells within (PVPON/TA/CTLA-4)-encapsulated grafts. To monitor graft integrity in vivo, we conjugated (PVPON/TA) layers with the fluorophore Cy5.5. Transplantation of (PVPON/TA/Cy5.5)-encapsulated islets restored glucose tolerance and was detected in vivo for up to eight weeks post-transplant. The ability to modify our (PVPON/TA) coatings opens the door for endless possibilities to improve clinical islet transplantation.

Disclosure

J. Barra: None. V. Kozlovskaya: None. E. Kharlampieva: None. H. M. Tse: None.

Funding

National Science Foundation (1608728); National Institute of Diabetes and Digestive and Kidney Diseases (DK-099550); JDRF (SRA-2016-270-S-B, 2-SRA-2019-692-S-B)