bluuebunny/crossref_metadata_2025 huggingface dataset:
Is evolution faster at ecotones? A test using rates and tempo of diet transitions in Neotropical Sigmodontinae (Rodentia, Cricetidae)
Authors: Luza André , Maestri Renan , Debastiani Vanderlei , Patterson Bruce , Hartz Sandra , Duarte Leandro da Silva
Published: June 2021

We evaluated whether evolution is faster at ecotones as niche shifts may
be needed to persist under unstable environment. We mapped diet
evolution along the evolutionary history of 350 sigmodontine species.
Mapping was used in three new tip-based metrics of trait
evolution–Transition Rates, Stasis Time, and Last Transition
Time–which were spatialized at the assemblage level (aTR, aST, aTL).
Assemblages were obtained by superimposing range maps on points located
at core and ecotone of the 91 South American ecoregions. Using Linear
Mixed Models, we tested whether ecotones have species with more changes
from the ancestral diet (higher aTR), have maintained the current diet
for a shorter time (lower aST) and have more recent transitions to the
current diet (lower aLT) than cores. We found higher aTR, aST and aLT at
ecotones than at cores. Although ecotones are more heterogeneous, both
environmentally and in relation to selection pressures they exert on
organisms, ecotone species change little from the ancestral diet as
generalist habits are necessary toward feeding in ephemeral
environments. The need to incorporate phylogenetic uncertainty in
tip-based metrics was evident from large uncertainty detected. Our study
integrates ecology and evolution by analyzing how fast trait evolution
is across space.
Hydrological alteration: the missing dimension of water in wastewater treatment plants. The case of the Manzanares River in Madrid (Spain)
Authors: Pérez-Andrés Natalia , Martínez-Santamaría Carolina , Magdaleno Fernando , Martínez-Romero Roberto , Fernández José
Published: June 2021

The effects of the discharge of wastewater treatment plants (WWTP) on
the status of rivers have most commonly been focused on water quality. A
very limited number of works have characterised the ability of treatment
plants to modify flow patterns in the receiving rivers. This paper
presents a methodology for the assessment of the hydrologic alteration
caused by WWTP discharges, over a two-fold sequence. The first phase
comprises the application of indicators derived from accessible data and
informative of the capacity of treatment plants to produce significant
flow alterations. The second phase, which may only be carried out when
flow data in the receiving river is available, is based on the
indicators of hydrologic alteration provided by the free software IAHRIS
(6 indicators) and IHA (2 indicators), and on a new indicator proposed
in this paper to obtain information of flow alteration at seasonal and
monthly time scales. The procedure suggested in this work is applied to
the Manzanares River (Central Spain), allowing the quantification of the
flow alteration generated by the 12 WWTP which give service to Madrid
city (3.8 million inhabitants): Large increases of annual water volumes
(from 108 hm3 to 410 hm3); at a monthly scale (increase from 246% to
1516%); variability in flow decreases in wet years by up to 47% and
increases in dry years by up to 380%; seasonal patterns is altered
within an altered regime. Results of the analysis show: (i) the ability
of the proposed methodology to characterise the modification of flow
patterns due to WWTP discharges; (ii) the importance of assessing such
changes when evaluating the environmental impact of treatment plants;
(iii) the importance of designing preventive and mitigation measures
which maintain the ecological integrity of river ecosystems in the
receiving channels.
EVALUATION OF THE SHORT TERM HOST RESPONSE AND BIOMECHANICS OF AN ABSORBABLE POLY-4-HYDROXYBUTYRATE SCAFFOLD IN A SHEEP MODEL FOLLOWING VAGINAL IMPLANTATION
Authors: Diedrich Chantal , Guler Zeliha , Hympanova Lucie Hajkova , Vodegel Eva , Zundel Manuel , Mazza Edoardo , Deprest Jan , Roovers Jan-Paul
Published: June 2021

Objective: To compare the host and biomechanical response to a fully
absorbable poly-4-hydroxybutyrate (P4HB) scaffold to the response to PP
mesh in an animal model of vaginal POP surgery. Design: A study
employing a sheep model Setting: KU Leuven Center for Surgical
Technologies Population: 14 parous female Mule sheep Methods: P4HB
scaffolds were surgically implanted in the posterior vaginal wall of
sheep. The comparative PP mesh data were obtained from an identical
protocol. Main outcome measures: Gross necropsy, histological and
biomechanical evaluation of explants, and the in vivo P4HB scaffold
degradation were evaluated at 60- and 180-days post-implantation.
Results: Gross necropsy revealed no implant related adverse events using
P4HB scaffolds. The tensile stiffness of the P4HB explants increased at
180-days (12.498 ± 2.66 N/mm (P=0.019)) as compared to 60-days (4.585 ±
1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB
scaffolds exhibited excellent tissue integration with dense connective
tissue and a moderate initial host response. P4HB scaffolds induced a
significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as
compared to PP mesh (0.99 ± 0.78 SEM, score 0-4) at 180-days.
Conclusions: P4HB scaffold facilitated a gradual load transfer to
vaginal tissue over time. The fully absorbable P4HB scaffold, in
comparison to PP mesh, has a favorable host response with comparable
load bearing capacity. If these results are also observed at longer
follow-up, a clinical study for vaginal POP surgery may be warranted to
demonstrate efficacy. Key words: Pelvic organ prolapse, vaginal surgery,
Poly-4-hydroxybutyrate, degradable scaffold, host response,
biomechanics.
A Case of Post-partum Chronic Subdural Hematoma.
Authors: Rajbhandari Suyasha , Gurung Pritam , Nepal Gopi , Acharya Samir , Pant Basant
Published: June 2021

Intracranial subdural hematoma following spinal anesthesia is an
infrequent occurrence and has variable presentation. Due to rarity, it
may often be misdiagnosed as post-dural puncture headache. In this
report, we describe a case of a 25-year-old woman who presented with a
headache following lower segment cesarean section after spinal
anesthesia.
Incandescent combustion synthesis of nanomagnetic Ni/NiO composites
Authors: Deraz Nasrallah
Published: June 2021

This study is the first attempt to large-scale energy-efficient production of
nanomagnetic Ni/NiO composites by using the autocombustion based on leaves
or extract of corchorus olitorius. The as synthesized product can be
characterized by using XRD, SEM, TEM and EDX techniques. The results confirm
that the as synthesized materials consisted entirely of well crystalline Ni
and NiO phases. The crystallinity of both Ni and NiO enhanced by increasing
amount of the corchorus olitorius. However, the corchorus olitorius -
treatment resulted in an increase in the crystallite size and lattice
constant. The SEM analysis confirms formation of fragile, fluffy and spongy
networks. The average of grain size for the as prepared particles was found
to be 45 nm in agreement with the trend of the crystallite size calculated
by using XRD technique. Furthermore, changing of nature and content of the
corchorus olitorius brought about progressive modifications in the magnetic
properties, namely, Ms, Mr, Mr/Ms, Hc and Ka, of the fabricated Ni/NiO
nanocomposite according to the structural, morphological as well as
microstructural variation. The saturation magnetization (Ms) of the sample
with corchorus olitorius leaves was found to be 0.2383 emu/g while the Ms
with corchorus olitorius extract was found to 6.977 emu/g. This was
discussed in the light of finite size, surface and interface effects. Thus,
we unveil a new approach for incandescent combustion synthesis via an innate
approach for corchorus olitorius leaves in the directly fabrication for
different nanocomposites.
Structural and optical properties of HDPE implanted with medium fluences silver ions
Authors: Nenadovic Milos , Kisic Danilo , Mirkovic Miljana , Nenadovic Snezana , Kljajevic Ljiljana
Published: June 2021

The implantation of high-density polyethylene (HDPE) has been conducted using
Ag+ ions with energy of 60 keV, achieved fluences 1.5 and 10?1015 ions/cm2.
Transmission electron microscopy (STEM) and field emission gun - scanning
electron microscopy (FEG-SEM) showed the existence of nanoparticle clusters.
X ray photoelectron spectroscopy (XPS) revealed the presence of silver in
the sample surface region. The surface topography was studied by atomic
force microscopy (AFM), while the surface composition uniformity was
analyzed using phase imaging AFM. Optical characterization obtained by
spectroscopic ellipsometry (SE) showed changes in refractive index,
extinction coefficient and the optical band gap with the fluence of
implanted ions.
Between desires and reality: Investigating the return intentions among the second generation members of migrants from Serbia in Switzerland
Authors: Santic Danica , Todorovic Milica
Published: June 2021

Return migration is an under-explored area of population mobility studies.
Although the return intention does not represent a guarantee for its
realization, migrants who express the intention to return have a better
chance of achieving it compared to those who do not even think about it.
Return migration can have great importance for the country of origin?s
overall development, especially when it comes to return of young people. The
paper presents the results of a survey carried out among the second
generation members of migrants from Serbia in canton of Lucerne
(Switzerland) with the aim of determining their return intentions. The
research excludes the possibility of short-term (temporary) return, and the
respondents answered about the intentions related exclusively to permanent
return. For the purposes of the paper, an online questionnaire was conducted
as well as interviews. The results indicated the complexity and
indissolubility of migrants? ties with the Republic of Serbia on different
levels. However, the return intention has been shown to be influenced by a
number of factors that are primarily related to life satisfaction in the
country of destination. In that context, it is not surprising that most of
the respondents (48.4%) do not plan to return to Serbia, some of them
(30.3%) might return, while the smallest number of respondents (21.2%)
intend to return. In contrast to the intentions of the respondents
themselves, it was found that the respondents? parents (the first generation
of migrants) have a greater intention to return to Serbia (66.7%). By
crossing the data, it was determined that the return intention is most
express among employedmen who are married, who send remittances and visit
Serbia two to five times a year. The intention to stay in the country of
destination is most express among women aged 20-24 who are employed,
unmarried and have no children. In addition, the results showed that
respondents who plan to return are more likely to make contact with friends
and relatives in Serbia than respondents who do not plan to return.
The challenges of marital life: Factors of marital life decline
Authors: Micanovic-Cvejic Zivka , Simonji-Cernak Ruzenka
Published: June 2021

A human is a social being, who wants to achieve relations with other people.
The most common form of close emotional relationships in adulthood is
marriage. A married relationship can be implied in various ways and,
although marriage lasts as a constant form of emotional attachment,
contemporary marriage is in crisis. Actual social circumstances place
various challenges before married life. In this work we have focused on some
aspects which we recognized as potential factors of marriage
destabilization. These include various empirical researches both in Serbia
and abroad: the role of age in marriage, cohabitation, importance of primary
family, children, economic stress, mechanisms of coping with stress,
affective attachments between partners, solving conflicts, communication
competence, distribution of house chores. Those are the factors that experts
face in counseling and therapy works, solving marriage crisis. We see the
quality of a married relationship as a multidimensional phenomena consisting
of marriage satisfaction, marriage stability, marriage cohesion, marriage
compliance. In this paper, we tried to show the complexity of marriage
relationships in a nutshell and present the current research directions in
this area of psychology.
10-LB: The Apelinergic System Improves Angiogenesis and Blood Flow Reperfusion in Diabetic Mouse Model of Lower Limb Ischemia
Authors: ROBILLARD STEPHANIE , GERALDES PEDRO
Published: June 2021

Introduction: Peripheral vascular disease is a major risk factor for lower-extremity amputation in patients with diabetes due to an abnormal angiogenic response. The apelinergic system is known to improve cardiac function after ischemia by promoting angiogenesis.

The objective: is to study the effects of Apelin-13 (Ape-13) and Elabela (Ela) on blood flow (BF) reperfusion following limb ischemia in diabetic mice as well as on endothelial cell (EC) function.

Method: Primary EC were exposed to normal (5.6 mM; NG) or high (25 mM; HG) glucose concentrations for 24h and hypoxia (1% O2) for the last 16h. EC were stimulated or not with Ape-13 or Ela. Proliferation and migration assays were performed and apelin signaling pathway was evaluated by immunoblot and qPCR. In vivo, nondiabetic (NDM) and diabetic (DM) underwent femoral artery ligation to induce lower limb ischemia. DM mice received Ape-13 or Ela by subcutaneous osmotic pump. BF reperfusion was measured for 4 weeks post-surgery and exercise willingness was assessed in individual cages with voluntary wheel. The ischemic abductor muscles were collected for protein, genes and vascular density analyses.

Results: Inhibitory effects of HG exposure on EC migration and proliferation were prevented with Ape-13 and Ela treatment under hypoxia condition through activation of Akt, AMPK and Rock2. In vivo, our results indicated that BF reperfusion was recovered at 75% in NDM as compared to 37% in DM whereas Ape-13 and Ela treatment in DM mice improved BF reperfusion by 65% and 69%, respectively. Similar results were observed using voluntary wheel as Ape-13 and Ela enhanced distance run as compared to untreated DM mice. Finally, the expression of proangiogenic factors (VEGF-A, PDGF-B) was increased in the ischemic muscle of DM+Ape-13 or Ela as compared to DM mice.

Conclusion: We believe that stimulation of apelinergic system improved BF recovery in DM by increasing proangiogenic pathways and EC migration and proliferation.

Disclosure

S. Robillard: None. P. Geraldes: None.

Funding

Canadian Institutes of Health Research (PJT159627)
1007-P: Risk Factor for COVID-19 Infection-Related Hospitalization in Patients with Type 2 Diabetes
Authors: HORII TAKESHI , ANDO WATARU , OTORI KATSUYA , ATSUDA KOICHIRO
Published: June 2021

Objective: Coronavirus disease (COVID-19) in 2019 is highly prevalent among patients with type 2 diabetes (T2D). Several factors, such as the older and obesity have been reported to be risks of COVID-19 infection, but little is known about the clinical factors limited to patients with T2D. Here, we aimed to identify clinical factors linked to hospitalization with COVID-19 infection in T2D.

Research Design and Methods: We used data from Electronic Medical Record (EHR) registered in the Healthjump database provided by the COVID-19 Research Database consortium. Primary outcomes were to determine clinical factors linked to COVID-19 infection-associated hospitalization.

Results: Of 4,445 T2D patients with COVID-19, hospitalization occurred in 228 (5.1%). The risk of Covid-19 infection-related hospitalization was higher with ≥65years old (hazard ratio [HR] 1.45; 95% confidence interval [CI], 1.30-1.63), high in patients with a body-mass index (BMI) ≥30 kg/m2 (HR 1.59; 95% CI, 1.10-2.31), and Blacks than in Caucasians (HR 1.39; 95% CI, 1.04-1.85). The risk was lower in Metformin users (HR 0.56; 95% CI, 0.34-1394) and SGLT2inhibitors users (HR 0.45; 95% CI, 0.22-0.91). Asians tended to be at increased risk, but there was no significant difference due to the small number of cases (HR 1.88; 95% CI, 0.59-5.96).

Conclusions: We revealed that the risk of hospitalization may be higher with older, obesity and blacks. Furthermore, we discovered a low risk of hospitalization in patients with treated SGLT2 inhibitors and/or metformin. These findings can help inform patient-centered care decision making for people with T2D at risk for COVID-19.

Disclosure

T. Horii: None. W. Ando: None. K. Otori: None. K. Atsuda: None.
1025-P: Rate, Reasons, and Predictors of 30-Day Readmissions among Patients with Type 2 Diabetes Admitted for Hyperglycemic Hyperosmolar State: A Nationwide Analysis
Authors: SHAKA HAFEEZ , AGUILERA MARIA C. , YAP SARA ELIZABETH T. , RAMIREZ MARCELO , CORPUZ CARLOS GABRIEL D. , EDIGIN EHIZOGIE , OJEMOLON PIUS E. , ASEMOTA IRIAGBONSE R. , AKUNA EMMANUEL
Published: June 2021

Introduction: Hyperglycemic hyperosmolar state is an endocrinological emergency associated with type 2 diabetes (T2DM) patients. HHS is associated with significant morbidity and mortality. The burden of HHS, however, does not end with the index admission. This study sought to determine the rate, reasons and predictors of 30-day readmissions (30DR) in T2DM patients with index admission for HHS with the goal of identifying potentially modifiable factors to decrease the burden of readmissions.

Methods: The US Readmission database for 2018 was searched for index hospitalizations involving adult patients with T2DM who had HHS in 2018. Outcomes assessed included 30DR rates, top principal diagnosis for readmitted patients, comparison of mortality, length of stay (LOS), and hospitalization costs (THC), and predictors of 30DR.

Results: A total of 21,721 hospitalizations involved adults with T2DM with HHS during the index admissions. The 30DR rate was 13.77%. The most common reasons for readmission was DM type 2 with hyperglycemia (8.6%), DKA (8.1%), HHS (8.0%), sepsis unspecified (7.9%), and acute renal failure (4.2%). Readmission was associated with higher odds of mortality (2.55% vs. 0.65%, OR: 4.00, 95% CI: 2.63 - 6.07), longer LOS (5.8 vs. 3.9 days, p<0.001), higher THC (12,700 vs. 8,300 USD, p<0.001). In T2DM patients with HHS, readmissions accounted for a cumulative 17,189 days of hospitalization, costing over $38 million within the study period. Discharges against medical advice, protein energy malnutrition, COPD and overall higher Charlson Comorbidity index was associated with higher odds for readmission.

Conclusion: HHS is associated with significant complications following the index admission. 30DR is associated with increased mortality and healthcare utilization in this population. Proper discharge planning and addressing factors associated with readmissions would likely improve outcome in this population.

Disclosure

H. Shaka: None. M. C. Aguilera: None. S. T. Yap: None. M. Ramirez: None. C. D. Corpuz: None. E. Edigin: None. P. E. Ojemolon: None. I. R. Asemota: None. E. Akuna: None.
1047-P: Genetic Risk of Insulin Resistance Is Associated with Kidney Disease in Type 2 Diabetics and Nondiabetics
Authors: GARDUNO ALEXIS C. , RICHARD ERIN L. , CAO STEVEN , THAKER VIDHU , SALEM RANY
Published: June 2021

Background: Diabetic kidney disease (DKD) is a microvascular complication of type 2 diabetes (T2D) with significant variability in disease onset and progression. The objective of this study is to evaluate the role of genetic propensity to insulin resistance with kidney disease (KD) in individuals with and without T2D.

Methods: A total of 373,487 unrelated European subjects (5.7% T2D) were selected from the UK Biobank. An insulin resistance polygenic risk score (IR-PRS) was constructed using 18 genome-wide significant SNPs from the latest GWAS for insulin resistance. A T2D-PRS was derived using 277 SNPs. Each PRS was categorized into high (>90thpercentile), mid (10th-90th), and low (< 10th) genetic risk groups. Ten KD phenotypes were constructed using eGFR and/or urine albumin cutoffs. T2D-stratified logistic regression models were run for IR-PRS and KD outcomes, adjusting for principal components, age, sex, education, Townsend Deprivation Index, BMI, hypertension, and statin use; similar models were run for T2D-PRS.

Results: Among T2D, higher IR-PRS was associated with higher odds of DKD (Mid PRS: OR=5.20, 95% CI: 1.28-21.09; High PRS: OR = 4.17, 95% CI: 0.94-18.52; overall p=0.007) and macroalbuminuria (Mid PRS: OR = 2.05, 95% CI:1.12-3.77; High PRS: OR = 1.62, 95% CI: 0.80-3.27; overall p=0.02). Among nondiabetics, higher IR-PRS was associated with higher odds of microalbuminuria (Mid PRS: OR = 1.08, 95% CI: 1.02-1.15; High Risk: OR = 1.15, 95% CI: 1.06-1.25; overall p=0.006) and albuminuria groups (Mid Risk, OR=1.08, 95% CI: 1.01-1.14; High Risk, OR = 1.15, 95% CI: 1.06-1.24; overall p=0.004). No associations were observed with T2D-PRS.

Conclusion: Genetic propensity for insulin resistance is associated with KD or its predisposition among subjects with and without T2D. In contrast, genetic risk of T2D is not associated with KD. Future work will focus on the replication of these results in independent cohorts.

Disclosure

A. C. Garduno: None. E. L. Richard: None. S. Cao: None. V. Thaker: None. R. Salem: None.

Funding

National Heart, Lung, and Blood Institute (1R00HL122515)
1066-P: Association of Food Security with Cardiometabolic Health during Young Adulthood: Comparison by Race and Ethnicity
Authors: NIKOLAUS CASSANDRA J. , HEBERT LUCIANA E. , ZAMORA-KAPOOR ANNA , SINCLAIR KAIMI
Published: June 2021

Food insecurity, defined as insufficient access to nutritious foods, poses a significant public health problem in the U.S. In the general population, food insecurity is related to poor cardiometabolic health. American Indians (AIs) have some of the greatest burdens of food insecurity and cardiometabolic disease in comparison to other racial/ethnic groups. However, few studies have established how food insecurity is related to cardiometabolic health with data disaggregated for AIs. The objective of this study was to assess the cross-sectional association of food insecurity and cardiometabolic risk factors among AI adults during young adulthood in comparison with non-Hispanic white, non-Hispanic Black, and Hispanic respondents. Data from the fourth wave of the National Longitudinal Study of Adolescent to Adult Health (Add Health) was used. Measures included one survey item on risk of food insecurity, objective measures of cardiometabolic health (body mass index, hemoglobin A1c, fasting blood glucose), and sociodemographic items. Multivariable regression models were used to assess the association of food insecurity with cardiometabolic health, while controlling for sociodemographic variables. All analyses were weighted and accounted for complex sampling survey design. In models inclusive of all adults, AI and non-Hispanic Black adults had significantly higher odds of reporting risk of food insecurity than non-Hispanic white adults. In models stratified by race, measures of cardiometabolic health were not significantly associated with risk of food insecurity among AI adults. Results suggest that AIs’ elevated risk of food insecurity is present in young adulthood, but its relationship with cardiometabolic health is unclear. Study implications are limited by the cross-sectional design, age of respondents, and reliance on a single-item measure of food insecurity. Future work should capitalize on longitudinal data and the USDA food security surveys.

Disclosure

C. J. Nikolaus: None. L. E. Hebert: None. A. Zamora-kapoor: None. K. Sinclair: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (P30DK092923)
107-LB: Relative Contribution of Fasting Plasma and Postprandial Glucose to HbA1c and TIR in People with T1D on Basal-Bolus Insulin Therapy
Authors: PIRAS DE OLIVEIRA CAROLINA , DELLVA MARY A. , BUE-VALLESKEY JULIANA M. , CHANG ANNETTE M. , CHIGUTSA FARAI B. , LIAO BIRONG
Published: June 2021

Background: A recent report was published on the contribution of fasting plasma glucose (FPG) and postprandial glucose (PPG) to HbA1c and time in range (%TIR) in people with type 2 diabetes on multiple daily injection regimens using prandial Humalog® (Lispro). We extended this analysis to type 1 diabetes (T1D) using data from people randomized to 26 weeks of mealtime ultra rapid lispro (URLi; N=451), postmeal URLi (N=329) or mealtime Humalog (N=442) in the phase 3 trial, PRONTO-T1D, and its continuous glucose monitoring (CGM) substudy.

Methods: A multivariate regression model was used to quantify the contribution of FPG and PPG change to the change in HbA1c and %TIR. The contribution of PPG relative to FPG was determined. %TIR was derived from 10-point self-monitored blood glucose (SMBG) and CGM data from the CGM substudy. Only results for the mealtime groups are presented here.

Results: With URLi treatment, a 1 mmol/L reduction in FPG and PPG was associated with a 0.11% ± standard error 0.02% and 0.09% ± 0.01% reduction in HbA1c, respectively, both p<0.0001, with a contribution of PPG relative to FPG of 82%. Similar results were obtained with Humalog: A 1 mmol/L reduction in FPG and PPG was associated with reduction in HbA1c of 0.12% ± 0.02% and 0.07% ± 0.02%, respectively, both p<0.0001, but the contribution of PPG relative to FPG was 58%. For SMBG-derived %TIR, with URLi treatment, a 1 mmol/L reduction in FPG and PPG was associated with an increase in %TIR of 10.0% ± 0.53% and 8.6% ± 0.47%, respectively, all p<0.0001. Similarly, with Humalog, a 1 mmol/L reduction in FPG and PPG was associated with an increase in %TIR of 9.8% ± 0.56% and 8.6% ± 0.52%, respectively, all p<0.0001 A similar trend was observed with CGM data, although the absolute values of contributions of FPG and PPG differed.

Conclusions: Changes in FPG and PPG significantly impacted HbA1c and %TIR in people with T1D, reinforcing the need to manage both FPG and PPG to achieve optimal glycemic control.

Disclosure

C. Piras de oliveira: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. A. Dellva: Employee; Self; Eli Lilly and Company. J. M. Bue-valleskey: Employee; Self; Eli Lilly and Company. A. M. Chang: Employee; Self; Eli Lilly and Company. F. B. Chigutsa: None. B. Liao: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
1079-P: Maternal Gestational Diabetes and Childhood Hyperlipidemia
Authors: HU GANG
Published: June 2021

Very few studies have assessed the impact of maternal gestational diabetes mellitus (GDM) on lipid profiles in the offspring in China. We aim to compare the lipid profile between children exposed to maternal GDM and those not exposed, and assess association between maternal GDM and offspring’s dyslipidemia risk. We recruited 1144 mother-child pairs (572 GDM and 572 non-GDM women matched by their offspring’s age and sex). We used general linear models to compare mean values of different lipid profiles among children born to mothers with and without GDM. Logistic regression models were used to assess associations of GDM with abnormal lipid profiles in offspring. After adjustment for maternal and children’s characteristics, children born to mothers with GDM had lower mean values of high-density-lipoprotein (HDL) cholesterol (1.40±0.01 vs. 1.50±0.01; P <0.05) and higher mean levels of triglycerides/HDL cholesterol ratio (0.37±0.01 vs. 0.35±0.01; P <0.05) in comparison with their counterparts born to mothers without GDM. Multivariate-adjusted odds ratios among children exposed to mothers with GDM compared with the counterparts were 2.07 (95% confidence interval [CI 1.13-3.79]) for low HDL cholesterol and 1.36 (95% CI 1.01-1.82) for high triglycerides/HDL cholesterol ratio, respectively. Exposure to GDM mothers was an independent risk factor for the abnormal lipid profile among children, which can emerge as early as in the preschool period.

Disclosure

G. Hu: None.

Funding

Tianjin Women’s and Children’s Health Center; Tianjin Public Health Bureau; European Foundation for the Study of Diabetes/Chinese Diabetes Society/Lilly Programme for Collaborative Research; National Institute of Diabetes and Digestive and Kidney Diseases
1080-P: Trends in Clinical Inertia in Diabetes Treatment Intensification in the U.S. Veterans Affairs Health Care System (VA)
Authors: RAGHAVAN SRIDHARAN , PHILLIPS LAWRENCE S. , CAPLAN LIRON , REUSCH JANE E.
Published: June 2021

Despite mounting clinical trial evidence to guide second-line diabetes treatment, clinical inertia could be a persistent barrier to improved care. We analyzed secular trends in second-line diabetes prescribing and timing of intensification in the largest integrated healthcare system in the US. We studied 93,317 Veterans in VA primary care with type 2 diabetes incidence and initial metformin monotherapy from 2004-2015 who were subsequently newly started on add-on therapy from 2010-2015 with a sulfonylurea (SU, n=78,924), insulin (INS, n=10,251), thiazolidinedione (TZD, n=737), or dipeptidyl peptidase 4 inhibitor (DPP4i, n=3405). We used linear and logistic regression to analyze temporal trends of second-line drug choice, of hemoglobin A1c (HbA1c) at metformin initiation and at initiation of add-on therapy, and of the time to initiating second-line therapy. Over the 6 years, SU use declined (86 to 78%, p=0.003), and INS (9 to 14%, p<0.001) and DPP4i (1.8 to 7.2%, p=0.02) use increased. In the full sample, mean HbA1c remained 7.6% at metformin initiation from 2010-2015 (p=0.2 for trend), but time to add a second drug rose (2.6 to 3.7 years) as did HbA1c at the time of add-on therapy (7.8 to 8.1%) (both p<0.001). Mean HbA1c at initiation of add-on therapy was higher in SU (7.9%) and INS (8.9%) users than in TZD (7.1%) and DPP4i (7.2%) users (p<0.001 for difference between groups). HbA1c at initiation of add-on therapy increased from 2010-2015 among SU (7.8 to 8.0%, p<0.001), INS (8.7 to 8.9%, p<0.001), and DPP4i users (6.8 to 7.4%, p<0.001). The time to treatment intensification increased from 2010 to 2015 for users of each medication class (2.5 to 3.7 years for SU; 2.5 to 3.5 years for INS; 2.9 to 4.0 years for TZD; 3.1 to 4.1 years for DPP4i; all p<0.001).

Conclusions: Inertia in diabetes treatment intensification may be worsening in real-world care potentially blunting the impact of accumulating clinical trial evidence to guide optimal second-line diabetes treatment.

Disclosure

S. Raghavan: None. L. S. Phillips: Other Relationship; Self; Diasyst Inc., Research Support; Self; AbbVie Inc., Eli Lilly and Company, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Kowa Pharmaceuticals America, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Pharma Ltd., Pfizer Inc., Sanofi-Aventis. L. Caplan: None. J. E. Reusch: Advisory Panel; Self; Medtronic.

Funding

U.S. Department of Veterans Affairs (IK2-CX001907-01)
1099-P: Association between Variability in Body Mass Index and Development of Type 2 Diabetes: Panasonic Cohort Study
Authors: OKADA HIROSHI , HAMAGUCHI MASAHIDE , FUKUI MICHIAKI
Published: June 2021

Objective: Contrasting results have been reported for the association between the variability in body weight and development of diabetes. No study has elucidated the association between the variability in body weight and the development of type 2 diabetes in a population without obesity and without body weight gain or loss during the study period. In the present study, we evaluated the association between the variability in body mass index (BMI) and development of type 2 diabetes in 19,412 Japanese participants without obesity and without body weight gain or loss during the study period.

Methods: We recorded body weight of the participants consecutively each year in Panasonic Corporation, Osaka, Japan from 2008 to 2014 to evaluate the variability of BMI. The participants with obesity (BMI ≥ 25 kg/m2) at baseline and body weight gain or loss from 2008 to 2014 (delta BMI ≥ ± 1 kg/m2) were excluded from the study. We used coefficient of variation (CV) to represent the variability in BMI during 6 years of the study period.

Results: In total, 416 participants among all participants (315 participants among those without IFG at baseline) developed type 2 diabetes from 2015 to 2018. The risk of developing type 2 diabetes was higher in the fourth quartile of CV of BMI than that in the lowest quartile (first quartile; reference) of CV of BMI in all participants and in those without IFG at baseline (hazard ratio, 1.33; 95% CI, 1.01-1.75 and hazard ratio, 1.51; 95% CI, 1.10-2.08, respectively). The risk for developing diabetes increased by 11.1% and 15.0% per 1% increase in CV of BMI in all participants and in those without IFG at baseline, respectively. Age, BMI at baseline, HDL cholesterol, glucose, current smoking habit, and fast eaters were also associated with the increased odds of developing type 2 diabetes.

Conclusions: In conclusion, the variability in BMI is a risk factor for the development of diabetes in the Japanese population.

Disclosure

H. Okada: None. M. Hamaguchi: Research Support; Spouse/Partner; AstraZeneca K. K. M. Fukui: None.
110-OR: MDA5-Dependent Responses Can Influence Spontaneous and Virus-Accelerated T1D Onset
Authors: BLUM SAMUEL I. , CHEN YI-GUANG , TSE HUBERT M.
Published: June 2021

Coxsackievirus B3 (CVB3) infection promotes the activation of proinflammatory immune cells and is associated with triggering type 1 diabetes (T1D). We previously demonstrated that CVB3 infection of Non-Obese Diabetic (NOD) mice accelerates T1D, partly due to the activation of melanoma differentiation-associated protein 5 (MDA5)-dependent antiviral responses including IFN-α/β synthesis. Mutations within human IFIH1, the gene encoding MDA5, are correlated with T1D risk. Yet, the role of MDA5 on immune cells during T1D remains unknown. By utilizing mice that lack (KO) or contain an in-frame deletion within the helicase 1 domain of MDA5 (ΔHel1), we can test the hypothesis that reduced MDA5 responses delay T1D by decreasing IFN-α/β synthesis and immune cell activation. NOD and KO mice develop T1D similarly, but ΔHel1 mice have delayed spontaneous and CVB3-accelerated T1D. At 12 weeks of age during spontaneous T1D, ΔHel1 mice have a significant reduction in IFNγ+ CD4+ T cells (6.2-fold), perforin+ CD8+ T cells (13.2-fold), and TNF+ F4/80+ macrophages (MΦ) (1.7-fold) compared to NOD and KO mice. CVB3-infected ΔHel1 mice at day 3 exhibited a significant decrease in pancreatic IFN-α (2.2-fold) and IFN-β (3.1-fold) synthesis compared to NOD mice. At day 7 post-infection, ΔHel1 mice had a significant reduction in pancreatic TNF+ F4/80+ MΦ (2-fold) compared to NOD and KO mice. ΔHel1 and KO mice had reduced pancreatic IFNγ+ CD4+ T cells (1.9-fold) and perforin+ CD8+ T cells (2.6-fold) compared to NOD mice following CVB3 infection. This data demonstrated that the ΔHel1 mutation elicits a decrease in basal and CVB3-responsive MΦ and T cells within the pancreata to delay T1D. However, KO mice have impaired T cell responses to CVB3 and failed to delay spontaneous and CVB3-accelerated T1D indicating MDA5-dependent responses may be necessary for tolerance induction. Future studies will examine the mechanism of ΔHel1 T1D protection and whether MDA5 ATPase activity and/or dsRNA binding can modulate T1D development.

Disclosure

S. I. Blum: None. Y. Chen: None. H. M. Tse: None.

Funding

DK099550, DK127497, DK1264565, T32GM1097805, T32AI007051
1101-P: Association between Insulin Utilization and Average Out-of-Pocket Cost in Commercially Insured Patients with Diabetes
Authors: RUIZ-NEGRON NATALIA , SULLIVAN JANE , TUCKER JAMIE , MCADAM-MARX CARRIE
Published: June 2021

Introduction: Concerns over cost-related non-adherence and high patient out-of-pocket (OOP) costs for insulin has prompted policies limiting insulin copays. This study examines the associations of insulin OOP cost by policy-relevant groupings, with gaps in therapy and insulin dose, expanding on current cost-related non-adherence data.

Methods: This retrospective cohort study included patients from the OptumLabs® Data Warehouse, a longitudinal, real-world data asset with de-identified administrative claims and electronic health record data, with commercial insurance, type 1 (T1D) or 2 diabetes (T2D), and insulin claims between 2006 and 2018. Index date was January 1 following two insulin claims at least 30 days apart in the prior year. Patients were grouped by average insulin OOP cost per 30-day supply over 1-year of follow-up: $0, >$0-$20, >$20-$35, >$35-$50, and >$50. Descriptive statistics were used to assess the proportion of patients with a >/=90 continuous-day gap in insulin therapy and insulin daily average consumption (DACON) by OOP group.

Results: A total of 21,085 and 72,512 patients with T1D and T2D, respectively, were included. Mean age was 40.6 and 53.9 years. More patients with T2D in OOP groups $35-$50 (29.7%) and >$50 (34.2%) experienced a 90-day gap in therapy vs. >$0-$20 (28.3%, p ≤0.02 for both). These groups also had a significantly lower mean (SD) DACON at 67.2 (136.1) and 63.9 (159.3) units/day vs. >$0-$20 at 72.8 (133.7) units/day, p <0.001 for both. In the T1D OOP groups, DACON did not differ by OOP group, and only the >$50 OOP group had significantly more patients with a gap in therapy vs. >$0-$20 (22.7% vs. 19.6%, p =0.003).

Conclusions: In commercial patients, insulin OOP costs >$35 were associated with gaps in therapy, and a decrease in average daily insulin dose in those with T2D. However, those with T1D may exhibit an inelastic demand to insulin in this patient population, as it is life-saving medication.

Disclosure

N. Ruiz-negron: Research Support; Self; Genentech, Inc., Novartis Pharmaceuticals Corporation. J. Sullivan: None. J. Tucker: None. C. Mcadam-marx: None.

Funding

Robert Wood Johnson Foundation; Health Data for Action Research Program (ID77105)
1104-P: Normative Fasting C-Peptide Values in Adolescents in the National Health and Nutrition Examination Surveys (NHANES)
Authors: SONI PRIYA Y. , WANG YUMIN , ECKERT GEORGE J. , ISMAIL HEBA M.
Published: June 2021

Background: C-peptide values are used for evaluation of residual β-cell function as well as endpoints in clinical trials. Therefore, it is crucial to have normative standards as a reference. This study aims to report normative fasting C-peptide values and variations across demographics in healthy adolescents included in the NHANES dataset.

Materials and Methods: In this analysis, we used fasting C-peptide data (n=2063) from the 1999-2004 NHANES dataset for participants ages 12 to < 18 yrs old.

Results: The mean ± SE age of participants was 14.99 ± 0.06; 992 were females and 1071 were males. The majority (>80%) of females and males had a BMI percentile (%ile) <85%. Among males, geometric mean C-peptide levels increased from 0.52 nmol/L at age 12, to 0.66 nmol/L at age 15 yrs. Mean values decreased slightly at age 16 and increased back to 0.66 nmol/L at age 17 yrs. Among females, C-peptide levels fluctuated around a geometric mean of 0.67 nmol/L and age did not have a significant effect on C-peptide (p=0.15). Females had significantly higher mean log-transformed C-peptide concentrations than males (p<0.0001) after adjusting for age, race, and BMI %ile category. After adjusting for age and BMI %ile category, we found that in males, non-Hispanic blacks had significantly lower C-peptide levels than non-Hispanic whites (p=0.0026), Mexican Americans (p<0.0001) and other races including multiracial (p=0.0186). Similarly, in females, non-Hispanic blacks had significantly lower concentrations than non-Hispanic whites (p=0.0093), Mexican Americans (p<0.0001), and other Hispanics (p=0.0187). BMI %ile category was positively correlated with C-peptide levels in both males and females after adjusting for age and race.

Conclusions: Here we describe normative fasting C-peptide in a healthy adolescent population. These data will provide novel information which can be used in assessing residual β-cell function and response to intervention therapy.

Disclosure

P. Y. Soni: None. Y. Wang: None. G. J. Eckert: None. H. M. Ismail: None.
111-LB: Preadmission Insulin Treatment Was Associated with Increased In-Hospital Mortality among Critically Ill Patients with Type 2 Diabetes
Authors: FAN RONGPING
Published: June 2021

Introduction: Insulin treatment was associated with enhanced systemic inflammation that may lead to adverse clinical outcomes of critical illness, but clinical data are limited. We examined the impact of pre-admission insulin use on in-hospital mortality among critically ill patients with type 2 diabetes (T2D). Methods: This retrospective study investigated 372 critically ill patients with T2D from 3500 cases admitted to an ICU between March 2011 and April 2020 at Tongji Hospital (Wuhan). Clinical characteristics and outcomes were compared among those treated with or without insulin before admission.

Results: Among the 372 critically ill patients with T2D, 249(59%) had pre-admission insulin prescriptions for > 3 months. A total of 246 patients were 1:1 matched by age and diabetic complications, among whom the median age was 62 (IQR, 54.0-70.0) years, and 155(63.0% ) were male and 91(37.0%) were female. Compared with critically ill patients with T2D treated without insulin before admission, patients with pre-admission insulin treatment had increased in-hospital mortality(22.8%(28/123)vs.(12.2%(15/123); P=0.029) and longer length of ICU stay(6(4~10)vs. 5(3~8); P=0.025). Logistic regression analysis showed that pre-admission insulin treatment was associated with a 2.122-fold higher risk for mortality in critically ill patients with T2D (OR=2.122, 95% CI (1.07-4.21) P=0.031), and the risk was higher after adjustment for age, gender, chronic kidney disease, hemoglobin, creatinine, eGFR, CRRT (OR=2.487, 95% CI (1.190-5.197) P=0.015).

Conclusions: Pre-admission insulin treatment might be associated with increased in-hospital mortality and longer length of ICU stay among critically ill patients with T2D. This association warrants further investigation.

Disclosure

R. Fan: None.
1132-P: Genetic Relationships between Birth Weight and Type 2 Diabetes
Authors: WEDEKIND LAUREN E. , HSUEH WEN-CHI , OLAIYA MUIDEEN , KOBES SAYUKO , BAIER LESLIE , KNOWLER WILLIAM C. , MAHAJAN ANUBHA , MCCARTHY MARK , HANSON ROBERT L.
Published: June 2021

There is considerable evidence that birth weight is associated with increased risk of type 2 diabetes (T2D) in adulthood. However, evidence from populations with high prevalence of T2D on the genetic relationships between birth weight and T2D is limited.

Data were obtained from a genome-wide association study (GWAS) in an Indigenous population from the Southwest US with high prevalence of T2D in which the relationship of T2D with birth weight is “U-shaped." Weighted polygenic scores (PSs) were constructed using imputed genotypes for genome-wide significant single-nucleotide polymorphisms (SNPs) from GWAS meta-analyses for birth weight (EGG Consortium, 126 SNPs) and T2D (DIAGRAM Consortium, 293 SNPs). Associations of birth weight PS and T2D PS with T2D and birth weight were calculated, accounting for participants’ pairwise relationships, using linear mixed models. Birth weight data (n=3700) were normalized separately by sex and analyzed for associations, adjusted for birth year, gestational age and the first 5 genetic principal components (PCs). T2D (n=7659) data were analyzed for associations, adjusted for age, sex, birth year and the first 5 genetic PCs.

Birth weight PS had a significant, positive association with birth weight (β=0.134 SD birth weight per SD PS (95% CI 0.101, 0.168); p=4.1×10-15). The T2D PS was likewise significantly, positively associated with T2D (OR=1.48 per SD (1.38, 1.58); p=8.1×10-31). The birth weight PS was significantly, inversely associated with T2D (OR=0.91 (0.85, 0.97); p=0.0043); we found no evidence for a non-linear relationship between birth weight PS and T2D (p=0.80). The T2D PS was not significantly associated with birth weight (β=-0.005 (-0.040, 0.030); p=0.80).

Results indicate that genetic variants that associate with birth weight and T2D from larger European GWAS largely also influence these traits in this Indigenous population. Current findings also support the notion that many variants conferring susceptibility to low birth weight also confer susceptibility to T2D.

Disclosure

L. E. Wedekind: None. W. Hsueh: None. M. Olaiya: None. S. Kobes: None. L. Baier: None. W. C. Knowler: None. A. Mahajan: Employee; Self; Genentech, Inc. M. Mccarthy: Employee; Self; Genentech, Inc. R. L. Hanson: None.
1157-P: Brainstem Neurons Regulating Energy Homeostasis
Authors: BHAVE VARUN M. , HILL-OLIVA MICHAEL J. , KAMATKAR NACHIKET , CHOWDHURY SRIKANTA , NECTOW ALEXANDER R.
Published: June 2021

The central nervous system (CNS) plays a key role in the sense-and-respond system which maintains proper energy stores. However, the molecular, cellular, and circuit mechanisms through which the CNS achieves this goal is poorly understood. We have recently identified the dorsal raphe nucleus (DRN) as a key node in the CNS, responsible for regulating numerous aspects of energy balance. Neurons within the DRN can potently regulate feeding, thermogenesis, and locomotor activity, and prolonged changes in their activity can ultimately drive changes in body weight. Despite playing a key role in regulating energy homeostasis, the molecular heterogeneity of the DRN had, until recently, hindered further progress in understanding it’s intricate role in the regulation of body weight. Here, we use a combination of nuclear labeling, sorting, and single-nuclear RNA-sequencing to identify the component cell types of key DRN populations, themselves known to regulate the various facets of energy balance. In particular, we identify over twenty candidate subpopulations of DRN neurons, principally defined by the neurotransmitters serotonin, glutamate, and GABA. Many of the subpopulations of these ‘principal’ cell types differentially express peptides, receptors, and signaling molecules that are directly implicated in the regulation of energy balance. We have begun to validate the expression and neuroanatomy of these molecules, including such neuropeptides as thyrotropin-releasing hormone and neuropeptide Y, and we have leveraged available recombinase-driver lines to modulate the activity of neurons expressing these genes to effectively assay their function. Together, this work represents important progress towards identifying the key cell subtypes that regulate the various aspects of energy balance.

Disclosure

V. M. Bhave: None. M. J. Hill-oliva: None. N. Kamatkar: None. S. Chowdhury: None. A. R. Nectow: None.

Funding

American Diabetes Association/Pathway to Stop Diabetes (1-18-ACE-49 to A.R.N.)