bluuebunny/crossref_metadata_2025 huggingface dataset:
330-OR: Geographic Disparities and Community Context: Associations of Abandoned Coal Mine Lands with New-Onset Type 2 Diabetes in Pennsylvania
Authors: BROWN EVANS , POLLAK JONATHAN S. , HIRSCH ANNEMARIE G. , SCHWARTZ BRIAN S.
Published: June 2021

Differences in community features could help explain the geographic disparities found in type 2 diabetes (T2D). A growing literature documents that communities with abandoned industrial infrastructure, including coal mine lands with hazards such as spoil piles, open pits, and acid mine drainage, can adversely affect health through impacts on health-related behaviors and stress. We investigated the association between living near abandoned coal mine lands (AML) and new onset T2D through a case-control analysis using electronic health records from a health system in Pennsylvania. We identified cases as persons with new onset T2D (n = 15,888) and frequency-matched controls (5:1, n = 79,435) on sex, age and year of encounter. Residential addresses were geocoded using ArcGIS. We used the Abandoned Mine Land Inventory System database to obtain AML data in Pennsylvania and created variables to represent metrics of AML type and density. We performed logistic regression for each AML variable, adjusting for age, sex, race (white vs. non-white), ethnicity (Hispanic vs. non-Hispanic), and Medical Assistance (≥ 50% of time). The highest quartile (vs. the lowest) of multiple AML variables were associated (odds ratio, 95% confidence interval) with new onset T2D, including the density of physical hazards (1.20, 1.11-1.29), toxic contamination sites (1.17, 1.09-1.26), acid mine drainage impacted streams (1.12, 1.04-1.22), and the density of total mined area (1.18, 1.11-1.25). These findings contribute to the growing literature on geographic disparities in T2D. Further research is needed to investigate the physiologic mechanisms through which these associations may occur.

Disclosure

E. Brown: None. J. S. Pollak: None. A. G. Hirsch: None. B. S. Schwartz: None.

Funding

Centers for Disease Control and Prevention (DP006299); National Institutes of Health (T32HP10025)
347-P: Why Some Americans Use Health Care following Severe Hypoglycemia, and Why Some Do Not: Baseline Results of the iNPHORM Study
Authors: RATZKI-LEEWING ALEXANDRIA , BLACK JASON E. , RYAN BRIDGET L. , ZOU GUANGYONG , HARRIS STEWART B.
Published: June 2021

Background: Individual and societal determinants can affect the need and propensity for healthcare utilization (HCU) following diabetes-related severe hypoglycemia (SH). This is the first US study to explore the real-world risk factors of HCU- versus non HCU-based SH.

Methods: Data were collected online from a generalized cohort of Americans (≥18 years old) with type 1 or type 2 diabetes (T1D, T2D) on insulin and/or secretagogues. Multivariable logistic regression using backward selection was performed to identify the socio-demographic/clinical risk factors of past-year HCU- versus non HCU-based SH (daytime/nocturnal SH resulting in hospital or paramedical services).

Results: Results are based on 642 (T1D: 22.7%; female: 46.3%) of 1694 baseline respondents who experienced ≥1 SH events (past year). People with T1D were 40.9 (SD:12.5) years old, while those with T2D were 45.4 (SD: 13.3) years old. Among T2D respondents, 42.5% were on insulin and secretagogues, 31.1% were on insulin alone, and 26.4% on secretagogues alone. Almost half (44.6%) of participants (T1D: 29.9%; T2D: 49.0%) reported ≥1 HCU-based SH events (past year). In the final backward logistic model, the odds of past-year HCU-based SH decreased significantly with female sex, increasing age, decreasing income, and suburban or rural (versus urban) living. Diabetes type did not have an independent effect. However, for individuals on combination insulin-secretagogue therapy, the adjusted odds of HCU-based SH were 2- and 3-times that of those on insulin alone and secretagogues alone, respectively. High A1C (versus <7%) also positively correlated with HCU-based SH; though, this association was marginally insignificant (p=0.065).

Conclusion: Our study reveals several factors that can promote or reduce the odds of HCU-based SH. Therapeutic optimizations to mitigate non-essential HCU should prioritize patients on combination insulin-secretagogue therapy and those with poor glycemic control.

Disclosure

A. Ratzki-leewing: Consultant; Self; Eli Lilly and Company, Novo Nordisk, Other Relationship; Self; Sanofi. J. E. Black: None. B. L. Ryan: None. G. Zou: None. S. B. Harris: Advisory Panel; Self; Abbott Diabetes, Abvance Therapeutics, HLS Therapeutics Inc., Lilly Diabetes, Novo Nordisk A/S, Consultant; Self; Boehringer Ingelheim (Canada) Ltd., mdBriefCase, Other Relationship; Self; American Diabetes Association, AstraZeneca, Novo Nordisk Canada Inc., Sanofi.

Funding

Sanofi Global
349-P: Hospital Utilization for Hypoglycemia among Patients with Type 2 Diabetes Using Pooled Data from Six Health Systems
Authors: PILLA SCOTT J. , KRASCHNEWSKI JENNIFER L. , LEHMAN ERIK , KONG LAN , FRANCIS ERICA , POGER JENNIFER M. , BRYCE CINDY L. , MARUTHUR NISA M. , YEH HSIN-CHIEH
Published: June 2021

Hypoglycemia is the most common serious adverse effect of diabetes treatment and a major cause of medication-related hospitalization. This study aimed to identify trends and predictors of hospital utilization for hypoglycemia among adults with type 2 diabetes. Using electronic health record data from six academic health systems, we performed a retrospective open cohort study including 532,323 patients aged ≥18 years with type 2 diabetes receiving regular care between 2009 and 2019. The primary outcome was the yearly event rate for hypoglycemia hospital utilization: emergency department visits, observation visits, or inpatient admissions for hypoglycemia identified using a validated ICD-9 algorithm. After the transition to ICD-10 in 2015, we used two ICD-10 code sets for hypoglycemia (limited and expanded) that were used in prior studies. We identified independent predictors of hypoglycemia hospital utilization using multivariable logistic regression analysis with data from 2014. We found that yearly rates of hypoglycemia hospital utilization decreased non-significantly from 3.4 to 2.6 events per 1,000 patients from 2009 to 2014. From 2016 to 2019, yearly event rates ranged from 15.5 to 16.5, or 21.1 to 21.8, using the limited and expanded ICD-10 code sets, respectively. The strongest independent risk factors for hypoglycemia hospital utilization were chronic kidney disease (OR 3.13, 95% CI 2.63-3.70), age 18-39 years (OR 3.00 vs. age 40-64 years, 95% CI 2.42-3.73), and insulin use (OR 2.61 vs. no diabetes medications, 95% CI 2.16-3.15). In this multicenter open cohort study, we found that rates of hypoglycemia hospital utilization were stable from 2009 to 2014 and varied considerably by clinical risk factors such that younger adults, insulin users, and those with chronic kidney disease were at especially high risk. There is a need to validate hypoglycemia ascertainment using ICD-10 codes, which detect a substantially higher number of events compared to ICD-9.

Disclosure

S. J. Pilla: None. J. L. Kraschnewski: None. E. Lehman: None. L. Kong: None. E. Francis: None. J. M. Poger: None. C. L. Bryce: None. N. M. Maruthur: Other Relationship; Self; Johns Hopkins HealthCare Solutions. H. Yeh: None.

Funding

National Institutes of Health (KL2TR003099); Patient-Centered Outcomes Research Institute (1306-04912)
350-P: The Importance of Professional CGM Use in Clinical Care of Older Adults with Type 2 Diabetes on Insulin
Authors: SLYNE CHRISTINE , TOSCHI ELENA , MICHALS AMY , ATAKOV-CASTILLO ASTRID , SIFRE KAYLA , DEWAR RACHEL , DAVIS DAI’QUANN J. , MUNSHI MEDHA
Published: June 2021

Background: In recent years, professional continuous glucose monitoring (CGM) has become a beneficial tool in pattern management in older adults with type 2 diabetes (T2D) on insulin, however the need for use of professional CGM in this population had not been shown.

Methods: We evaluated electronic health record (EHR) data of a tertiary diabetes center to identify the use of professional CGM in patients over the age of 65 years with T2D using insulin. Professional CGM data from this cohort were analyzed when a minimum of 70% of data was available (≥10 days).

Results: A total of 2,481 patients over the age of 65 years with type 2 diabetes using insulin were seen at the Joslin Diabetes Center from January 2017-March 2020. Average age of the total cohort was 72±7 yrs, A1c was 8.2±1.5% and diabetes duration was 21±10 years. Professional CGM was used in 169 older adults with T2D using insulin (7% of the total patients seen). CGM data from 139/169 was sufficient for analysis. The average age of this cohort (139 patients) was 77±8 yrs, A1c 8.0±1.5%, duration of diabetes 21±12 yrs. The mean duration of hypoglycemia was 80±92 min/day <70 mg/dL and 32±51 min/day ≤54 mg/dL. A total of 86% of the cohort had ≥1 episode of hypoglycemia. The measure of high glycemic variability (CV >36%) was seen in 59 (42%) of the cohort, with a high A1c (8.2±1.2%). When comparing those people with and without hypoglycemia on CGM, there was no difference in age, A1c, or duration of diabetes.

Conclusion: In the real world, a small percentage of older adults with T2D on insulin therapy received professional CGM. Our data shows a high burden of hypoglycemia in this population, despite suboptimal A1c. Broader use of professional CGM would be beneficial in recognizing hypoglycemia in this vulnerable population.

Disclosure

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

Funding

National Institutes of Health (1DP3DK112214-01)
389-P: Pathological Significance of Renal Tubular ROCK2 in Chronic Kidney Disease
Authors: SEKIGUCHI KENSUKE , MATOBA KEIICHIRO , UKICHI RIKAKO , NAGAI YOSUKE , TAKEDA YUSUKE , AKAMINE TOMOYO , KANAZAWA YASUSHI , UTSUNOMIYA KAZUNORI , NISHIMURA RIMEI
Published: June 2021

The small GTPase Rho and its effector Rho-kinase (ROCK) are implicated in the pathogenesis of diabetic kidney disease. In chronic kidney diseases including diabetic nephropathy, progressive tubulointerstitial fibrosis is the final common pathway to end-stage renal disease and deeply related to renal prognosis. We have previously reported that a chemical ROCK inhibitor suppressed the progression of diabetic nephropathy. ROCK has two isoforms, ROCK1 and ROCK2. ROCK1 is known to be involved in the endocytosis of albumin in tubular epithelial cells via megalin/cubilin-dependent mechanism. On the other hand, the role of renal ROCK2 remains unclear. In the present study, we investigated the role of renal tubular ROCK2 in the pathogenesis of chronic kidney disease using an established model to cause renal fibrosis, unilateral ureteral obstruction (UUO). Masson’s trichrome staining revealed that the collagen deposition was significantly increased in the kidneys of UUO group compared with Sham-operated group. We detected upregulation of ROCK2 at both mRNA and protein levels in UUO group, relative to sham operated group. The kinase activity of ROCK2 was also elevated in UUO group. Based on our research, we suggest that ROCK2 may have an important role in tubulointerstitial fibrosis. ROCK2 may be a potential therapeutic target for the treatment of diabetic nephropathy.

Disclosure

K. Sekiguchi: None. K. Matoba: Research Support; Self; Eli Lilly Japan K. K. R. Ukichi: None. Y. Nagai: None. Y. Takeda: None. T. Akamine: None. Y. Kanazawa: None. K. Utsunomiya: None. R. Nishimura: Speaker’s Bureau; Self; Abbott Japan Co., Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K. K., Kissei Pharmaceutical Co., Ltd., Medtronic, MSD Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.
394-P: ROCK1/AMPK Axis Regulates the Development of Diabetic Kidney Disease via Modulation of Fatty Acid Metabolism
Authors: NAGAI YOSUKE , MATOBA KEIICHIRO , SEKIGUCHI KENSUKE , UKICHI RIKAKO , TAKEDA YUSUKE , AKAMINE TOMOYO , KANAZAWA YASUSHI , UTSUNOMIYA KAZUNORI , NISHIMURA RIMEI
Published: June 2021

The small GTPase Rho and its effector Rho-kinase (ROCK) are involved in the pathogenesis of diabetic kidney disease. Accumulating evidence shows that renal dysfunction in diabetic patient is associated with abnormal fatty acid oxidation in the kidney. However, the interaction of ROCK and fatty acid oxidation in diabetic kidneys remains unclear. Extracellular flux analyzer demonstrated that deficiency of ROCK1, one of the ROCK isoforms, improves TGF-β-induced mitochondrial dysfunction of cultured mesangial cells. ROCK1 deficiency rescued TGF-β-induced downregulation of fatty acid oxidation mediators such as peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1A (CPT1A). An investigation of mechanisms underlying this observation revealed activated ROCK1 functions through the phosphorylation of AMPK and increased expression of PGC-1α. Furthermore, fluorescence histochemistry showed that ROCK1 deficiency suppresses ROS production as a result of mitochondrial damage due to abnormal fatty acid metabolism. Consistent with this result, ROCK1 knockout mice exhibited reduced albuminuria and histological abnormalities along with the recovery of impaired fatty acid utilization and mitochondrial fragmentation. These observations indicate that ROCK1 is a key player in the development of diabetic renal injury. Glomerular ROCK1 may be a potential therapeutic target for the treatment of diabetic kidney disease.

Disclosure

Y. Nagai: None. K. Matoba: Research Support; Self; Eli Lilly Japan K. K. K. Sekiguchi: None. R. Ukichi: None. Y. Takeda: None. T. Akamine: None. Y. Kanazawa: None. K. Utsunomiya: None. R. Nishimura: Speaker’s Bureau; Self; Abbott Japan Co., Ltd., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly Japan K. K., Kissei Pharmaceutical Co., Ltd., Medtronic, MSD Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited.
395-P: Identification of Key Genes and Transcriptional Factors Associated with Podocyte Functions in Human Diabetic Nephropathy
Authors: AKIL AMMIRA S. , PADMAJEYA SUJITHA SUBASH , FAKHRO KHALID , HABIB TANWIR
Published: June 2021

Background: Direct podocyte injury in Diabetic nephropathy (DN) leads to proteinuria, glomerular hypertrophy, and accumulation of extra cellular matrix. By using six publicly available gene expression profiles from early DN, DN, advanced DN, and healthy controls. We have analyzed each of the DN stages against healthy controls and also analyzed the datasets using network inference technique to identify genes playing key role in DN pathogenesis.

Methodology: We performed modular repertoire analysis for each dataset separately, then, we performed meta-analysis by merging the datasets to obtain robust differentially expressed genes (DEG). Network inference technique was used to explore and detect novel associations between the DEG and to infer the interaction between the set of genes using mutual information (MI) measure. Statistically significant interactions were selected using a threshold p < 10-7 and visualized using force-directed layout in Cytoscape. MCODE tool was used to find densely connected regions in the network. STRING database utilized for functional enrichment of the clusters in the network and for in silico validation of the gene interactions.

Results: A total of 193 samples from the gene expression datasets of human kidney tissues were used, where 79 samples from DN, 21 of advanced DN, 10 early DN, 10 DKD, and 73 from controls. Several key genes have been identified in addition to a highly connected small cluster of genes enriched for podocyte differentiation. Two transcription factors, DACH1 and WT1, are important for podocyte differentiation and proper kidney function have been identified. Also, the expression level of TYRO3 which is a podocyte protective factor increased in early DN but was decreased as the disease progressed, per our analysis.

Conclusion: This meta-analysis found some of the key genes associated with DN. The level of contribution and relevance of the identified genes in the pathogenesis of DN should be functionally analyzed.

Disclosure

A. S. Akil: None. S. Subash padmajeya: None. K. Fakhro: None. T. Habib: None.

Funding

Qatar National Research Fund (NPRP9-229-3-041)
403-P: Plasma Renin Level and Aldosterone-to-Renin Ratio Are Associated with Diabetic Kidney Disease
Authors: HIGA MARIKO , SUZUKI TAKAYUKI , KIDO TAKASHI , ZENRI MARIKO , NAO KEIKO , HIJIKATA MAI , YAMASHITA KAORU , IKEHARA KAYOKO , ICHIJO TAKAMASA
Published: June 2021

Aim: A close association between primary aldosteronism (PA) and atherosclerosis has been well established. We aimed to determine the association between plasma renin activity (PRA) and aldosterone levels (PAC) as well as their ratios (PAC-to-PRA ratio: ARR) with urinary albumin excretion (UAE) in type 2 diabetic patients who did not fulfill PA confirmatory criteria.

Methods: The subjects were 70 type2 diabetic patients (age: 53.3±11.0 years, male: 51, female: 19) with UAE ≤100 mg/gCr. They did not take ACE inhibitors, angiotensin receptor blockers (ARB) or diuretic agents. Patients were selected for this study based on various criteria: PRA level ˂10 ng/ml/hr, PAC ˂20 ng/dl, and ARR ˂20 (ng/dl per ng/ml/hr). They were divided into three groups according to UAE levels: NL group (N=33) ˂ 10mg/gCr, N group (N=22) 10-29 mg/gCr, and M group (N=15) 30-100 mg/gCr.

Results: There were no significant differences in age, BMI, HbA1c, and eGFR levels among the three groups. The systolic blood pressure in the M group was significantly higher than those in the NL and N groups. The ARR in the M group was 10.1±4.6, which was significantly higher than those in NL (6.5±0.3) or N (7.0±2.7) groups. In the M group, the levels of PRA and PAC were significantly lower than those in NL or N groups. Log UAE was positively correlated with ARR (r=0.34, p<0.0001) and negatively correlated with PRA (r=-0.32, p<0.001). Systolic blood pressure showed a significant positive correlation with ARR and negative correlation with PRA.

Conclusion: These results suggest that a high ARR level, which did not fulfill confirmatory criteria for PA, was associated with diabetic nephropathy. The relative increase in PAC to PRA might contribute to the development of diabetic nephropathy, even if PAC remains normal level.

Disclosure

M. Higa: None. T. Suzuki: None. T. Kido: None. M. Zenri: None. K. Nao: None. M. Hijikata: None. K. Yamashita: None. K. Ikehara: None. T. Ichijo: None.
424-P: Autoantibodies to Glutamic Acid Decarboxylase in Type 1 Diabetes Are Not a Marker of Asymptomatic Cardiac Autonomic Neuropathy
Authors: NATTERO-CHÁVEZ LÍA , SILVA JHONATAN QUIÑONES , MONTANEZ LAURA , DURÁN ELENA FERNÁNDEZ , AVENDAÑO BEATRIZ DORADO , RODRÍGUEZ CRISTINA SÁNCHEZ , LORENZO MAR , ARGÜESO MARÍA FERNÁNDEZ , ROJANO NURIA BENGOA , LECUMBERRI EDURNE , ESCOBAR-MORREALE HÉCTOR F. , LUQUE-RAMÍREZ MANUEL
Published: June 2021

Aim: To clarify whether autoantibodies against glutamic acid decarboxylase (GAD-ab) are associated with cardiac autonomic neuropathy (CAN).

Methods: 319 consecutive patients with type 1 diabetes (DM1) were included. We assessed CAN by responses of heart rate variability to deep breathing (E/I index), Valsalva maneuver, standing (30:15 ratio), low-frequency activity (LFa), and high-frequency activity (HFa). We assayed GAD-ab by immunoprecipitation radioligand.

Results: Mean age was of 40 ± 14 years, with 20 ± 12 years as mean duration of diabetes. Mean A1c was 7.2 ± 1.0%. We confirmed CAN in 66 patients resulting in a 21% (95% CI 17-25) prevalence of asymptomatic CAN. GAD-ab were present in 199 individuals (62%), with no significant differences as a function of the presence of CAN or not [44 (70%) vs. 144 (66%), respectively; P = 0.544]. GAD-ab titles were similar between both groups (431 ± 695 U/mL in CAN subjects vs. 390 ± 662 U/mL in subjects without CAN, P = 0.688). Considering all patients as a whole, GAD-ab titles only correlated with duration of DM1 (r = -0.346, P < 0.001). HFa correlated with age (r = -0.523, P < 0.001), duration of DM1 (r = -0.374, P < 0.001), and A1c (r = -0.261, P < 0.001), but not with GAD-ab. Similarly, LFa correlated with age (r = -0.473, P < 0.001), duration of DM1 (r = -0.223, P < 0.001), and A1c (r = -0.294, P < 0.001). Age, sex, A1c, duration of DM1, GAD-ab, and systolic blood pressure were introduced as independent variables into a binary regression analysis. The stepwise model (R2: 0.106, P < 0.001) retained only age (β: -0.933, 95% CI: 0.933-0.976) as the significant predictor of the presence of CAN.

Conclusion: GAD-ab unlikely have a role as a CAN marker in patients with DM1.

Disclosure

L. Nattero-chávez: None. E. Lecumberri: None. H. F. Escobar-morreale: Consultant; Self; InsudPharma. M. Luque-ramírez: None. J. Quiñones silva: None. L. Montanez: None. E. Fernández durán: None. B. Dorado avendaño: None. C. Sánchez rodríguez: None. M. Lorenzo: None. M. Fernández argüeso: None. N. Bengoa rojano: None.

Funding

Menarini International Foundation
431-P: Gaps in Retinal Screening among Medicaid Patients with Diabetes: A Natural Experiment for Translation in Diabetes (NEXT-D) 2 Study
Authors: MOIN TANNAZ , HARWOOD JESSICA , DASKIVICH LAUREN , QUINTON JACOB , VASILYEV ARSENIY , TURK NORMAN , DURU O. KENRIK , MANGIONE CAROL
Published: June 2021

Background: Medicaid patients face many challenges in diabetes treatment and have higher rates of complications, including diabetic retinopathy (DR). We evaluated eye exam rates over a seven year period among Medicaid patients with diabetes and assessed variation by state, Medicaid eligibility category, and race/ethnicity.

Methods: Using United Healthcare claims (eligibility, medical, pharmacy) and lab data, we identified Medicaid patients with diabetes >21 years of age who received care in practices with >1000 Medicaid patients between 2010-2016. Diabetes was defined by diagnostic codes, AIC > 6.5% and/or anti-glycemic medication prescriptions. DR was defined by diagnostic codes. We used serial cross sections to calculate annual eye exam frequencies and our logistic regression covariates included age group, gender, race/ethnicity, language, Medicaid program, common comorbidities, indicators for type 1 vs. type 2 DM, indicators for chronic eye disease, state and and state by year fixed effects. We also adjusted for clustering at the 3-digit zip code level and excluded states with vision care carve-outs.

Results: Among 160,108 Medicaid person-years with diabetes, overall unadjusted rates of annual eye exams ranged between 23-36% per year. Adjusted annual eye exam rates varied significantly between states (range: TN at 24%, NV at 44%,). Adjusted rates were also significantly higher in 2014-2016 (30-33%) as compared to the baseline rate in 2010 (26%) and among patients with chronic eye disease as compared to those without (53% vs. 22%). There were no significant differences in eye exam rates by race/ethnicity or Medicaid program.

Conclusions: The majority of Medicaid patients with diabetes in our study did not receive annual eye exams between 2010-2016. These findings highlight significant gaps in care and interventions are needed to increase adherence to DR screening for underserved Medicaid patients with diabetes.

Disclosure

T. Moin: None. J. Harwood: None. L. Daskivich: None. J. Quinton: None. A. Vasilyev: None. N. Turk: None. O. Duru: None. C. Mangione: None.

Funding

Centers for Disease Control and Prevention; National Institute of Diabetes and Digestive and Kidney Diseases (U18DP006128)
439-P: A Promising Regulatory Role for MicroRNA-133b in Controlling Lipid Metabolism and Dyslipidemia Gene Expression in Diabetic Retinopathy: The 1000 Qataromics Cohort
Authors: AKIL AMMIRA S. , PADMAJEYA SUJITHA SUBASH , JERMAN LAILA A. , HABIB TANWIR , AL-KURBI ALYA , ALIYEV ELBAY E. , ANBARI MOHAMMED EL , FAKHRO KHALID
Published: June 2021

A number of hyperglycemia- and dyslipidemia- triggered pathways, and numerous protein-encoding genes boosting the diabetic retinopathy (DR) progression. Evolving data suggests vast number of microRNAs(miRNAs) which exhibit no protein-coding capacity, are expressed and play key roles in DR pathogenesis.

Purpose: of this pilot is to identify the miRNAs involved in pathways altered in lipid metabolism and dyslipidemia and to explore the association of dyslipidemia with the progression of DR.

Methodology: 460 patients with diabetes type 2 (T2D) aged 23-77 years including 37 with DR and 490 matched healthy controls age range 18-74, from Qatar biobank cohort. The circulating miRNA profile was assessed in this pilot study. Logistic regression analysis was performed on the phenotypic data to investigate the level of association between A1C, low-density lipoproteins (LDL) and Triglycerides (TG) covariants and the miRNA expression profile in T2D with and without DR.

Results: The most broadly characterized miRNAs in lipid metabolism are miR-33a/b; however, we identified another three miRNAs (miR-133b, miR-142-3p and miR-483-5p) shared between LDL and TG phenotypes. In particular, miR-133b appeared to be directly linked to retinal degeneration identified through our miRNA-target disease interaction network analysis. Our results indicated that all three miRNAs are significantly associated with VEGFR2 mediated vascular permeability, insulin signaling, apoptosis, EGFR, TGF-Beta signaling, cellular senescence and degradation pathways leading to the DR initiation than development.

Conclusions: miRNAs are not only small regulators of lipid metabolism, but vital influencers in lipid homeostasis and lipoproteins formation and secretion. Dysregulation of these regulatory elements most likely augment the underlying metabolic flaws perceived in lipid disorders and related microvascular complications.

Disclosure

A. S. Akil: None. S. Subash padmajeya: None. L. A. Jerman: None. T. Habib: None. A. Al-kurbi: None. E. E. Aliyev: None. M. El anbari: None. K. Fakhro: None.

Funding

Qatar National Research Fund (NPRP9-229-3-041)
45-LB: Improving Resiliency in Children with Type 1 Diabetes
Authors: PUFFENBERGER SYNTHIA S. , HOEKSTRA FRANCINE , KAPADIA CHIRAG R. , SHAIBI GABRIEL Q. , CHAMBERS MELISSA
Published: June 2021

Type 1 diabetes (T1D) is a chronic medical condition that can negatively impact both physical and psychological health. Diabetes resilience can be protective against the physical and social/emotional consequences among children with T1D yet few studies have examined the ability to increase resiliency in the pediatric population. Forty children with T1D (Age 14.1±2.3 years, 48% female, Hba1c 12.0±1.6%) were enrolled in a 4-month multi-disciplinary intervention that included medical management, Psychology-led motivational interviewing, and frequent support from a Certified Diabetes Care and Education Specialist (CDCES). Participants completed the Diabetes Strengths and Resilience (DSTAR) measure at baseline and post-intervention. The DSTAR is a validated assessment tool aimed to assess both self and parent reported measures of general and diabetes-related child self-efficacy and level of perceived support, as well as diabetes distress. HbA1c was assessed at baseline and 4 months. At baseline, higher DSTAR scores were associated with lower HbA1c (r=-0.34, p=0.03). DSTAR scores increased significantly in response to the intervention from 43.9±6.4 to 47.2±6.9 at 4 months (p<0.001). Additionally, HbA1c significantly improved from baseline to post-intervention (12.0±1.6% to 11.0±1.9%, p<0.001). A multifaceted approach to children with diabetes can improve levels of resilience, a factor involved in improving and maintaining both physical and psychological health.

Disclosure

S. S. Puffenberger: None. F. Hoekstra: None. C. R. Kapadia: None. G. Q. Shaibi: None. M. Chambers: None.

Funding

Thomas J. Beatson Jr. Foundation
458-P: The Current Status and Influencing Factors of In-Home Handling of Disposable Needles among Diabetic Patients in Beijing
Authors: YANG YUMO , ZHOU LIXIN
Published: June 2021

Objective: Diabetes mellitus is a chronic progressive disease that requires insulin injection to control blood glucose at a certain stage of development, and the used needles are a high-risk medical waste. This study was to understand the current situation and influencing factors of disposable needles handling among diabetic patients treated by injection in Beijing.

Methods: From October to November 2020, 420 diabetic patients were recruited from 3 tertiary hospitals and 3 community healthcare centers in Beijing. A questionnaire was conducted on disposal methods of injection needles at home. SPSS statistical software was used to establish the data set and to carry out data analysis.

Results: 405 complete questionnaires were retrieved in this survey(the response rate 96.4%). The mean age of patients was 60.3±13.2 years. The average number of injections per day was 2.1±1.1. 73.3% of the patients were aware that needles may transmit diseases, and 71.6% believed that needles need harmless treatment, but only 37.0% of the patients had received education and training in needle treatment, of which 15.1% had used sharps disposal containers. The ways of patient’s disposal of needles were as follows: 64.2% of patients discarded to household waste, 31.6% of patients collected needles in bottles or other containers before discarded to household waste bins, only 3.7% of patients collected them in sharps containers and sent back to the hospital for harmless treatment. Multivariate binary logistic regression analysis showed that only “having received education in needle handling” was independently and positively associated with “needle properly disposed of” (OR = 7.317).

Conclusion: Most of the patients did not properly handle the needles used in daily life. It is necessary to strengthen education on patients’ knowledge of correct disposal of medical waste, and relevant government authorities should take actions to strengthen the waste classification as soon as possible.

Disclosure

Y. Yang: None. L. Zhou: None.
46-OR: Hypoglycemia Increases the Left Ventricular Ejection Fraction in People with Diabetes and Healthy Controls
Authors: FABRICIUS THERESE W. , VERHULST CLEMENTINE E. , WIENBERG MALENE , DUIJNHOUWER ANTHONIE L. , KRISTENSEN PETER L. , DE GALAN BASTIAAN E. , PEDERSEN-BJERGAARD ULRIK
Published: June 2021

Background: Insulin-induced hypoglycemia, the most common adverse event in people with diabetes treated with insulin, is associated with increased risk of cardiovascular events. The effect of hypoglycemia on cardiac function has not yet been fully clarified. Our aim was to investigate the effect of hypoglycemia on left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) in people with type 1 diabetes (T1DM) and in healthy controls (HC).

Methods: We enrolled 15 adults with T1DM (M/F 9/6, age 47±19 years, HbA1c 7.9±2.9%, diabetes duration 22.5±12.6 years) and 14 HCs (M/F 7/7, age 39±17 years). All participants underwent a hyperinsulinemic normoglycemic (5.3±0.4 mmol/L, 30 min) hypoglycemic (2.8±0.5 mmol/L, 60 min) glucose clamp. At baseline and approximately 30 min into the hypoglycemic phase (steady-state), a cardiac ultrasound was performed (by the same person), for later analysis.

Results: All participants had sinus rhythm at baseline and none developed arrhythmias during hypoglycemia. We found no difference between T1DM and HC for LVEF measured at baseline. In response to hypoglycemia, LVEF increased from 58.1±2.6% at baseline to 63.7±4.0% in the T1DM group (p<0.0005) and from 58.0±3.8% to 64.7±2.4%, (p<0.005) in the HC group. GLS was unchanged (-20.9±1.5% to -21.3±3.5% (p=0.800)) in the T1DM group, but a numerical decrease from -19.6±3.0% to -22.0±2.7% (p=0.084) was seen in the HC. Age did not modulate the effect of hypoglycemia on LVEF or GLS.

Conclusion: An event of hypoglycemia increases the LVEF significantly in people with diabetes. Presumably due to the catecholamines chronotropic, inotropic and peripheral contracting effect. The result of this would be increased cardiac output, increased oxygen consumption and metabolism and thereby increased load on the heart. This may contribute to explain the link between hypoglycemia and cardiovascular disease.

Disclosure

T. W. Fabricius: None. C. E. Verhulst: None. M. Wienberg: None. A. L. Duijnhouwer: None. P. L. Kristensen: Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company. B. E. De galan: Research Support; Self; Novo Nordisk. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker’s Bureau; Self; Novo Nordisk A/S.

Funding

Innovative Medicines Initiative 2 Joint Undertaking (777460); European Union Horizon 2020 Research and Innovation Program; European Federation of Pharmaceutical Industries and Associations; T1D Exchange; JDRF; International Diabetes Federation; The Leona M. and Harry B. Helmsley Charitable Trust
461-P: A Day in the Life of a Person with Diabetes Mellitus: An Experiential Learning Initiative
Authors: GOLTZ JOSEPH D. , MORSI AMR , LIBMAN INGRID , ISMAIL HEBA M.
Published: June 2021

Background: Despite the increased use of diabetes related technology, patient outcomes remain suboptimal and there remains a gap in the understanding of these devices among medical trainees as well as a gap in relating to patients’ experiences. We aimed to improve understanding of diabetes technology as well as increase empathy for patients among trainees. In this pilot study, we proposed a novel model of diabetes teaching through experiential learning to address these deficits.

Methods: Participants (medical trainees) followed simulated type 1 diabetes (T1D) clinical management scenarios for 2 days designed to replicate the typical daily life of individuals with T1D. They wore and used insulin pumps (using saline) and continuous glucose monitors (CGMs). We evaluated their understanding of diabetes technologies and empathy for patients via mixed-method surveys (on a Likert scale) administered before and after following these scenarios.

Results: Pediatric endocrine fellows (n=7), pediatric residents (n=2), and 1 medical student participated. Trainees’ confidence in diabetes management and self-perceived capability of answering questions pertaining to insulin pumps were enhanced following participation [(3.10±0.99 vs. 3.90±0.57) and (2.80±0.92 vs. 3.80±0.92), respectively]. Trainees’ knowledge of diabetes management and self-perceived capability of answering CGM questions increased marginally [(3.30±0.82 vs. 3.80±0.42) and (3.14±1.07 vs. 3.57±0.98), respectively]. Participation positively changed their understanding, empathy, and overall perspective of patients’ daily challenges in 90% of participants.

Conclusions: Our experiential learning model provides an effective template and basis to address deficits in understanding of diabetes care and enhance empathy for those living with T1D. Future research could integrate this learning model into medical training programs across multiple centers in order to further assess its feasibility among a larger cohort.

Disclosure

J. D. Goltz: None. A. Morsi: None. I. Libman: Advisory Panel; Self; Novo Nordisk. H. M. Ismail: None.

Funding

National Institutes of Health (T32DK06446, KL2TR002530, UL1TR002529); National Center for Advancing Translational Sciences; University of Pittsburgh
463-P: Fuel Expenditure and Deposition in Tissues after Exercise or Low-Fat Diet in Obese Female and Male Mice
Authors: AN JULIA , ZHU LIN , YU SOPHIA , EDINGTON EMERY , LITTS BRIDGET , STAFFORD JOHN M.
Published: June 2021

We hypothesized that a healthy diet and exercise improve energy metabolism through different pathways in males and females. Understanding the mechanism for a how healthy diet vs. exercise improves metabolic outcomes is important for intervention through lifestyle change to target risk factors for obesity-associated diseases in specific populations. Mice were fed a high-fat diet (HFD) for 12 weeks, then divided into 4 groups, followed for 6 weeks: a. HFD; b. HFD + exercise; c. the diet was switched to chow; d. diet-switch + exercise. Instead of acute metabolic effects, we investigated sustained effects of exercise by examining tissue glucose uptake and metabolism 48 hours after the last exercise session. Diet-switch and exercise reduced obesity and fat contents in tissues in both sexes. Muscle glucose uptake was higher in males than females and not different between treatments 48 hours after exercise session. Liver glucose uptake was higher in males than females. Exercise, but not diet-switch, lowered liver glucose uptake, which effect was greater in males than females. Glucose uptake in subcutaneous, visceral, and brown adipose tissues was higher in females than males. Diet-switch, but not exercise, reduced glucose uptake in brown fat, which effect was greater in females than males. Furthermore, Diet-switch decreased the pathways for adipocyte differentiation (PPARγ) and lipogenesis (DGAT1/2) in subcutaneous adipose tissues in females. Muscle protein levels of CPT1β and pACC were increased by diet-switch in both sexes, and by exercise in males only. Our data indicate: 1) adipose tissue nutrient storage is the major energy reservoir that protects against obesity-related metabolic changes in females; 2) with regard to improving metabolic outcomes, diet-switch benefits females more and exercise benefits males more; for both sexes 3) exercise training is more effective in preventing fatty liver than diet-switch, and 4) both diet-switch and exercise promote fat oxidation in muscles.

Disclosure

J. An: None. L. Zhu: None. S. Yu: None. E. Edington: None. B. Litts: None. J. M. Stafford: None.

Funding

National Institutes of Health (R01HL144846)
464-P: Does the Referral Source Influence Retention in Community Diabetes Prevention Programs
Authors: KOEPPEN HALLIE , TYSK SONJA , HOUSE MELISSA , FERNANDES JESSIE , HARWELL TODD S. , HELGERSON STEVEN D. , GOHDES DOROTHY M.
Published: June 2021

The Montana Diabetes Prevention Program (DPP), with over 20 community sites, has tracked participants in a statewide registry since the inception of the program in 2008. Montana’s DPP sites conduct the standard lifestyle intervention in the fall and the spring of each year, recruiting group participants who have been referred from the surrounding community. Because retention in the program is key for success, we used data from the registry to ascertain if the referral source influenced the hazard of dropout among DPP participants. From the 2015 fall cohort through the fall cohort of 2019, 3,030 participants were eligible for analyses and referral information was available for 75.2% (2,280). The three primary referral methods were: physician referral (n=914), referral by a former DPP participant (n=422), and referral by a friend or family member (n=393). We conducted a survival analysis using the last DPP session attended as a measure for dropout. Backwards selection was used to identify significant covariates for inclusion in the adjusted model. A significant difference in time to dropout by type of referral was observed (p=0.0045). When compared to participants referred by a friend or family member and after adjusting for age, income, and distance traveled, the hazard of dropout was 17.4% higher for participants who were referred by a physician (HR: 1.174, 95% CI: 1.014, 1.395, p=0.0321) and 26.5% higher for participants who were referred by a former DPP participant (HR: 1.265, 95% CI: 1.057, 1.513, p=0.0103). These findings suggest that enlisting support from friends and family members may be helpful in retaining participants referred by physicians or former DPP participants.

Disclosure

H. Koeppen: None. S. Tysk: None. M. House: None. J. Fernandes: None. T. S. Harwell: None. S. D. Helgerson: None. D. M. Gohdes: None.

Funding

Centers for Disease Control and Prevention (NU58DP006517)
47-LB: Patient Factors Associated with Diabetes Distress among Veterans with Poorly Controlled Type 2 Diabetes
Authors: GERMAN JASHALYNN , KOBE ELIZABETH A. , SOLIMAN DIANA , LEWINSKI ALLISON , JEFFREYS AMY S. , COFFMAN CYNTHIA , EDELMAN DAVID , CROWLEY MATTHEW J.
Published: June 2021

Diabetes distress (DD), the psychological distress specific to living with diabetes, is associated with poor glycemic control. This study sought to examine the association of diabetes distress with demographic, clinical, and psychosocial factors in a vulnerable population. The Diabetes Distress Scale (DDS), a validated patient questionnaire that assesses perceived problems and burdens associated with diabetes management, yields a total diabetes stress score plus 4 subscale scores: emotional burden (EB), physician distress (PD), regimen distress (RD) and interpersonal distress (ID). We conducted a cross-sectional analysis of baseline data from a randomized telehealth trial in a population of Veterans with persistently poor T2DM control (HbA1c ≥8.5) (N= 248). Multivariable linear regression models were used with baseline patient characteristics as independent variables and DD score as the dependent variable, and separate models for the 4 subscales of the DDS were created. Mean age of the cohort was 58 years (SD 8.3); 21% of patients were female, 79% non-white with 14 being Latinx/Hispanic. Prevalence of moderate to severe DD was 37.5% (mean DDS 1.19 (SD 0.82). In the multivariable model, Latinx/Hispanic ethnicity β 0.4 (95% CI: .01, 0.8) and higher HbA1c 0.1 (.01, 1.3) were associated with higher total DD. With respect to the DDS subscales, higher HbA1c 0.14 (0.1, 0.2) was associated with higher RD. Latinx/Hispanic ethnicity 0.8 (0.2, 1.3) was associated with higher ID. Use of basal insulin was associated with higher PD 0.3 (.001, 0.6). Depression was associated with higher total DD 0.1 (0.1, 0.1), EB 0.1 (0.1, 0.1), PD .02 (.001, 0.1), RD 0.1 (0.1, 0.1) and ID .05 (0.03, 0.1). The knowledge gained from this study has implications for practice, particularly in developing interventions targeting modifiable barriers, including patient attitudes and beliefs regarding treatment regimens and diagnoses and treatment of depression.

Disclosure

J. German: None. E. A. Kobe: None. D. Soliman: None. A. Lewinski: Consultant; Self; Otsuka America Pharmaceutical, Inc., Other Relationship; Self; PhRMA Foundation. A. S. Jeffreys: None. C. Coffman: None. D. Edelman: None. M. J. Crowley: None.
475-P: School Nurses Report Low Confidence in Many Skills with Diabetes Devices
Authors: MARCH CHRISTINE , HILL AMBER L. , KAZMERSKI TRACI M. , SWITZER GALEN E. , WALLACE EILEEN , SIMINERIO LINDA M. , MILLER ELIZABETH , LIBMAN INGRID
Published: June 2021

New diabetes devices are increasingly standard of care for pediatric type 1 diabetes management. Youth often need caregiver assistance to use these devices, including at school. The aim of this study was to assess school nurse confidence with devices, which, to our knowledge, no study has previously evaluated. School nurses in Pennsylvania were recruited to complete a questionnaire, designed by our group and demonstrating content validity, evaluating confidence in specific skills. Each item was scored on a 5-point scale with low confidence considered a response of 1-2, moderate confidence 3, and high confidence 4-5. Respondents (n=269) were 99% female, 96% white, and mean age was 52 years. The majority had experience with insulin pumps (95%) and continuous glucose monitors (CGM, 92%), but not sensor-augmented pumps (34%). Primary forms of device training were informal learning from parents (68%), other nurses (49%), or web searches (49%); fewer (37%) received formal training from a medical center. Median response for insulin pump-related items was 3.1/5 and for CGM items 3.5/5, suggesting moderate confidence overall. We found a moderate positive correlation between confidence with pumps (0.47, p<0.001) or CGM (0.48, p<0.001) with confidence in general nursing skills; we did not find a significant association (p>0.05) between device confidence and years of experience as a school nurse, grades covered, or geographic region. A high proportion of nurses reported low confidence with certain skills, including operating a sensor-augmented pump (63%), setting a temporary basal rate (58%), changing the pump site (54%), knowing when CGM calibration is appropriate (48%), overriding pump calculations (42%), monitoring a CGM tracing (42%), or suspending insulin delivery (40%). Our findings suggest that school nurse confidence with diabetes devices varies by type of skill. Further validation of this questionnaire may help identify gaps in skills and tailor education as newer technology continues to emerge.

Disclosure

C. March: None. A. L. Hill: None. T. M. Kazmerski: None. G. E. Switzer: None. E. Wallace: None. L. M. Siminerio: Advisory Panel; Self; Abbott Diabetes, Bayer U. S., Research Support; Self; Becton, Dickinson and Company. E. Miller: None. I. Libman: Advisory Panel; Self; Novo Nordisk.

Funding

Cochrane Weber Endowment Award
477-P: The National Diabetes Prevention Program (National DPP): What the New Variables Are Telling Us about Outcomes
Authors: ELY ELIZABETH , BELL MIRIAM
Published: June 2021

In 2018, the Centers for Disease Control and Prevention (CDC) began requiring organizations recognized through the National DPP Diabetes Prevention Recognition Program (DPRP) to collect new information from participants at the time of enrollment: referral source (ENROLL), payer source (PAYER), and highest level of completed education (EDU). Of the 354,616 participants who enrolled in, and had the opportunity to complete, the National DPP lifestyle change program as of October 2020, analyses were restricted to the 63,598 who enrolled from March 2018 through February 2019 to ensure that information was complete. With respect to referral source, participants who decided on their own to enroll (option of “self”), or who reported the option of “primary care provider/office or specialist”, attended the most sessions on average (17.6 and 17.5 sessions, respectively). The least number of sessions attended (mean of 13.7) was associated with those who reported the option of “employer or employer’s wellness program.” While most participants reported a PAYER option of “private insurer”, they attended a mean of 14.2 sessions. The mean number of sessions attended by those reporting a PAYER of “Medicare” was 19.2. College graduates reported attending the most sessions, on average, 15.1, yet 50% attended at least 12. Fifty percent of those with less than a high school education attended at least 15 sessions. With respect to mean weight loss % and referral source, the highest (5.6%) was achieved by those who chose the ENROLL option of “media.” Those who chose “employer or employer’s wellness program” lost the least, 3.7%. When stratified by PAYER, those who chose “Medicare” lost the most weight (6.9% on average). Level of education did not have much impact on mean weight loss with a range of 4% to 4.5% across the four options. The collection of this additional information provides important insights into who is currently meeting programmatic goals.

Disclosure

E. Ely: None. M. Bell: None.