bluuebunny/crossref_metadata_2025 huggingface dataset:
1190-P: Oral Health Status among U.S. Adults with and without Diabetes, 2020
Authors: CHO PYONE , HORA ISRAEL A. , BULLARD KAI M. , BENOIT STEPHEN R.
Published: May 2022

To reduce the risk of gum disease, the American Diabetes Association recommends that people with diabetes brush twice and floss once daily and see the dentist twice a year. But only about two-thirds of all US adults seek dental care within a year. Regular dental checkups are more important for those with diabetes. Thus, we studied the current oral health status (visiting a dentist or a dental clinic in the past year and the number with permanent tooth loss) in US adults aged ≥ 18 years with and without diagnosed diabetes using data from the 2020 Behavioral Risk Factor Surveillance System. Both diabetes and oral health-related information were self-reported. We computed overall and state-specific age-adjusted estimates by diabetes status. In 2020, 64.4% (95% CI 64.0%-64.8%) of US adults had a dental visit within the past year. Annual dental checkups were more common among women, older people, non-Hispanic White persons, and those having higher education, better income, and health insurance. The proportion of US adults with diabetes seeing a dentist in the past year was significantly lower compared to those without diabetes (56.7% [95% CI 54.8%-58.5%] vs. 65.4% [95% CI 65.0%-65.8%]) . Both men (56.3% [95% CI 53.6%-58.9%] vs. 62.4% [95% CI 61.9%-63.0%]) and women (57.1% [95% CI 54.6%-59.6%] vs. 68.2% [95% CI 67.7%-68.8%]) with diabetes were also significantly less likely to get dental care than their counterparts. The frequency of annual dental visits among adults with diabetes also varied by state; Texas had the lowest percentage (39.8% [95% CI 32.5%-47.6%]) while Alaska had the highest (77.1% [95% CI 68.8%-83.7%]) . Adults with diabetes (34.1% [95% CI 32.4%-35.9%]) were also more likely to have a history of one or more permanent teeth removed due to tooth decay or gum disease than those without diabetes (26.5% [95% CI 26.1%-26.8%]) . Without having regular dental checkup and adequate oral hygiene, adults with diabetes are at increased risk for gum disease. These findings highlight a gap in preventive oral care among adults with diabetes.

Disclosure

P. Cho: None. I.A. Hora: None. K.M. Bullard: None.
1197-P: The Demographic and Geographic Distribution of Diabetes and Prediabetes Risk in Rural Settings
Authors: LEE DAVID C. , ARIAS CAROLINA QUINTERO , RONY MELISSA , PATEL RAHI , JENSEN ERICA , PETCU ROBERT , IMAS DANIEL M. , ELBEL BRIAN , ANTHOPOLOS REBECCCA , MCGRAW NANCY A. , THORPE LORNA
Published: May 2022

Introduction: Evaluating diabetes prevalence and prediabetes risk in rural settings can be difficult due to sparse population coverage and limited data.

Objective: To evaluate diabetes burden and prediabetes risk in a rural county with documented poor health outcomes.

Methods: In 2021, we mailed health surveys to all households in Sullivan County, a rural county with the second-worst health outcomes of all counties in New York State. We included questions on demographics, medical history, and the American Diabetes Association’s Prediabetes Risk Test in our survey. A score of 5 points or higher on this test is considered high risk for having prediabetes. To help mitigate non-response bias, statistical raking was performed using age, sex, race/ethnicity, and health insurance strata. We analyzed diabetes prevalence and prediabetes risk by demographic characteristics. We also used geospatial analysis within the county to assess for clustering of diagnosed diabetes cases and elevated prediabetes risk scores.

Results: Of 4,725 survey responses analyzed, the adjusted diabetes prevalence in our sample was 14% compared to the 20BRFSS estimate of 8.6% for Sullivan County. In this rural area, diabetes prevalence was notably higher among non-Hispanic Black (23%) and Hispanic (16%) residents compared to non-Hispanic White (13%) residents. Prediabetes risk scores were elevated among 41% of respondents without a history of diabetes. Nearest neighbor analyses revealed that hotspots of diagnosed diabetes and high prediabetes risk scores were primarily located in more urban areas of this rural county.

Conclusion: Our mailed health survey to all residents in Sullivan county demonstrated higher diabetes prevalence compared to modelled BRFSS estimates that are based on a small telephone sample. Our results suggest the need for better diabetes surveillance in rural communities, which may benefit from interventions specifically tailored for improving glycemic control among rural residents.

Disclosure

D.C.Lee: None. N.A.Mcgraw: None. L.Thorpe: None. C.Quintero arias: None. M.Rony: None. R.Patel: None. E.Jensen: None. R.Petcu: None. D.M.Imas: None. B.Elbel: None. R.Anthopolos: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK124400)
1214-P: Use of American Heart Association’s “Life's Simple 7” as a Predictor for Initiation of Dialysis
Authors: OSAWA TAEKO , FUJIHARA KAZUYA , YAMADA MAYUKO H. , YAGUCHI YUTA , SATO TAKAAKI , KITAZAWA MASARU , MATSUBAYASHI YASUHIRO , YAMADA TAKAHO , SONE HIROHITO
Published: May 2022

In 2016, to help achieve the goal of avoiding heart failure and preserving cardiac structure and function, the American Heart Association (AHA) designated Life’s Simple 7 as risk factors that can be addressed through lifestyle changes: smoking, weight, physical activity, diet, cholesterol, blood pressure (BP) , and blood glucose. Although most of these factors are also risk factors for the progression of kidney disease, the association between Life’s Simple 7 and risk of dialysis is unknown. We investigated the impact of 6 factors on the initiation of dialysis based on the AHA’s 7 factors using a nationwide claims database involving 294,647 participants during 2008-16. Multivariate Cox regression model identified risks of starting dialysis. Hazard ratios (HRs) were compared among 7 groups who had 0 to 6 of the following risk factors adjusted by age and sex: BMI ≥25, systolic BP (SBP) ≥140 mmHg, LDL-cholesterol ≥140 mg/dl, diabetes mellitus (DM) , no regular exercise, and smoking. Compared with SBP <140 mmHg, HR for starting dialysis in those with SBP ≥140 mmHg was 3.30 (2.49-4.34) . Compared with DM-, HR for starting dialysis in those with DM+ was 6.50 (4.89-8.65) . In comparison with no risk factors, HRs for starting dialysis for those who had 3, 4, 5, or 6 risk factors were 2.20 (1.17-4.09) , 5.30 (2.80-10.0) , 11.2 (5.47-23.1) , and 32.5 (11.4-92.6) , respectively.

In summary, the risk of dialysis increased with worsening of risk factors derived from AHA’s Life’s Simple 7. These results indicated that factors similar to those used to predict cardiovascular disease might also be useful to predict initiation of dialysis. Use of these approaches might be helpful in clinical practice, especially in patient education.

Disclosure

T.Osawa: None. K.Fujihara: None. M.H.Yamada: None. Y.Yaguchi: None. T.Sato: None. M.Kitazawa: None. Y.Matsubayashi: None. T.Yamada: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding

Japan Society for the Promotion of Science (18K17897) .
1218-P: Immigrant Density and Prevalence of Diabetes in American Neighborhoods
Authors: NGUYEN NGAN , BAKAL ETHAN , WANG NATALIE
Published: May 2022

Background: The “healthy immigrant effect” suggests that despite immigrants generally demonstrating lower socioeconomic status than non-immigrants, they have lower age-related disease prevalence and mortality compared to non-immigrants. Recent evidence suggests immigrants may have higher levels of physical activity and may also influence their neighbors to decrease sedentary behavior. Drawing from the literature, we investigated the association between immigrant density with the prevalence of diabetes in neighborhoods and of both foreign-born and U.S.-born populations by ZIP code level.

Methods: In this retrospective, cross-sectional ecological study, we used data from the American Community Survey (ACS) and the CDC Behavioral Risk Factor Surveillance System (BRFSS) for 2018. We performed multiple regression to test our predictive model that appointed obesity and physical activity as possible mediators between immigrant density and diabetes.

Participants: ZIP codes with more than 16 foreign-born individuals (324out of 41692 total ZCTAs)

Results: Higher immigrant density in a neighborhood is associated with lower prevalence of diabetes (beta estimate = −0.056657; r-squared = 0.02709) ; this remains true even after adjusting for prevalence of obesity (0.038646; 0.5356) , physical activity (-0.014093; 0.7097) , and both (−0.001015; 0.7168) , with all p-values < 0.001. We concluded that immigrant density is a potential protective factor of diabetes, and the relationship is mediated by the prevalence of obesity and physical activity.

Discussion: The effects may differ depending on the racial/ethnic composition of the neighborhood. A previous study has shown that living in communities with a high Hispanic concentration (>=25%) was associated with an increase in body mass index (BMI) and higher odds for obesity in non-Hispanic Whites, respectively; meanwhile, the opposite effect is observed for communities with high Asian concentration. As a next step, we will disaggregate our results by race.
1223-P: CRP-Mediated Associations of the Individual and Neighborhood Stressors with T2D in the MESA Cohort
Authors: TAMURA KOSUKE , JAGANNATHAN RAM , HU LU , NEALLY SAM , BAUMER YVONNE , NARAYAN K.M. VENKAT , VACCARINO VIOLA , POWELL-WILEY TIFFANY
Published: May 2022

There has been growing interest in examining the link between individual/neighborhood stressors with T2D. Prior studies have not tested if inflammation (CRP) may mediate the associations between multi-level stressors and T2D. This study included baseline data from the Multi-Ethnic Study of Atherosclerosis (MESA; n=5405; age=61.9±10.1y; 52% female) . T2D was defined as FPG ≥126 mg/dL or the use of diabetes drugs. Individual stressors included perceived lifetime discrimination, chronic burden, and personal safety. Neighborhood stressors included perceived problems, social cohesion, and physical activity facility density. Log transformed CRP (mg/L) was tested as the potential mediator. Linear regression models were used to test for significant indirect effects, adjusting for covariates. Twelve percent of participants (n=650) had T2D. Chronic burden and physical activity facility density were indirectly related to T2D via CRP (Table) . That is, higher chronic burden and lower density of physical activity facilities were linked to higher CRP. In turn, higher CRP was positively associated with T2D. Other stressors were neither directly nor indirectly associated with T2D. The associations between these stressors and T2D appear to be mediated by higher CRP in the MESA cohort. Future research should test the longitudinal mediating role of inflammation on the associations of stressors on T2D.

Disclosure

K.Tamura: None. R.Jagannathan: None. L.Hu: None. S.Neally: None. Y.Baumer: None. K.Narayan: n/a. V.Vaccarino: None. T.Powell-wiley: None.
1229-P: Participation of Hispanic (Hisp) and African-American (AA) Youth in an Observational Study in Diabetes
Authors: REDONDO MARIA J. , TOSUR MUSTAFA , UYSAL SERIFE , MUIR ANDREW B. , IFTEKHAR SANIA , DEEN SAIMA , PERRY DANIEL J. , HARRALL KYLIE K. , GLUECK DEBORAH H. , VEHIK KENDRA , ORAM RICHARD A. , HAGOPIAN WILLIAM , DABELEA DANA , ATKINSON MARK A. ,   RACE (DISCOVER) DIABETES STUDY IN CHILDREN OF DIVERSE ETHNICITY
Published: May 2022

Background and Aim: Suboptimal representation of race/ethnic minorities in clinical research contributes to critical gaps in our knowledge of diabetes in these populations. We aimed to evaluate the participation of AA and Hisp youth in an observational study in diabetes to assess factors impacting participation.

Methods: We studied 92 participants in the Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) that is currently enrolling youth (age 0-yrs) with non-secondary diabetes for collection of data and blood samples. We compared racial/ethnic distribution of actual vs. target enrollment and refusal rates by race/ethnicity. We analyzed qualitative data on reasons for study refusal.

Results: The racial/ethnic distribution of participants was 60.9% Hisp, 27.2% AA, 12.0% non-Hispanic white [NHW] and 0% other, vs. enrollment targets of 35.3% Hisp, 31.8% AA, 29.9% NHW and 3% other (p=0.001) . In the population of eligible candidates, 31.1% of the children were Hisp, 18.8% AA, 42.2% NHW and 7.9% other. Refusal rates were 20.0%, 16.7%, 38.9% and 100%, respectively, for Hisp, AA, NHW and other (p=0.072) . Among those who refused, the reasons noted were no interest in research (44.4% overall, 80% in AA youth) , blood draw (29.6% overall, 42.6% in Hisp youth) , no direct benefit to the participant (11.1%) , and being too busy (18.5%) or overwhelmed by the recent diabetes diagnosis (11.1%) . NHW youth cited the first 3 reasons, with similar frequency, for refusal.

Conclusions: Refusal rates were not elevated in AA and Hisp children compared with NHW. Actual enrollment was statistically different from the target, with over-representation of Hisp youth and underrepresentation of NHW youth. Facilitators of racial/ethnic minority participation in research studies may include diverse racial/ethnic distribution in the population where the study is conducted, a trusted environment, race/ethnicity concordance with research team members, and a minimally invasive study protocol.

Disclosure

M.J. Redondo: Advisory Panel; Provention Bio, Inc. M. Tosur: Advisory Panel; Provention Bio, Inc. A.B. Muir: None. S. Iftekhar: None. S. Deen: None. D.J. Perry: None. D.H. Glueck: None. K. Vehik: None. R.A. Oram: Consultant; Janssen Research & Development, LLC. Research Support; Randox R & D. W. Hagopian: Research Support; Janssen Research & Development, LLC. D. Dabelea: None. M.A. Atkinson: None.

Funding

NIH NIDDK RDK124395
1235-P: A Prospective Characterization of Metabolic and Metabolomic Profiles of COVID-19–Associated New-Onset Diabetes Patients Presenting with DKA from India
Authors: DASGUPTA RIDDHI , MONDAL S , GARAI R , CHOWDHURY B , HAZRA A , LODH M , GANGULY A
Published: May 2022

Background: Recent evidence suggests a bidirectional relationship between COVID-infection and new-onset diabetes (NOD) presenting with DKA.

Methodology: This one-year prospective study comprised of 29 COVID-negative DKA (controls) and 52 COVID-positive-DKA patients (18 NOD, 15 T1DM ,T2DM) . NOD were previously normoglycemic and negative for GAD/IA-2/ZnT8 autoantibodies. After 75g- OGTT with estimation of glucose, C-peptide, FFA and insulin at 0,15, 30,45, 60,90 ,120, 150 and 180minutes, Insulin secretion rate (ISR) [C-peptide-deconvolution] , Hepatic insulin sensitivity [AUC-glucose × AUC-insulin during first 30-minutes of OGTT ], Peripheral insulin sensitivity [ dG/dt ÷ mean plasma insulin concentration; dG/dt rate of decline in plasma glucose concentration]were calculated alongwith Metabolomics and Adipose tissue gene expression. All tests were performed at admission and 4, 8, and 12-months of followup.

Results: At baseline, ISR in NOD was significantly reduced than controls (p=0.001) but similar to T1DM (p=0.15) . Nearly 83% (n=17) of NOD with DKA had near-complete recovery of ISR on follow-up compared to T1DM (all p<0.01) ,with non-remitters (n=3) having significantly worse admission Hba1c and IL-6 (all p<0.01) . NOD had significantly increased hepatic and peripheral insulin resistance compared to T1DM (all p<0.05) ,but similar to T2DM (all p>0.05) . Their Metabolomics revealed increased inflammatory phosphatidylcholines, that correlated with peripheral glucose uptake (p<0.01) ,while RNA sequencing showed significantly enhanced WNT5A , TLR4 (Toll-like Receptor-4) and RETN (resistin) than T1DM and T2DM (both p=0.001) .

Conclusion: Our study provides novel insights into COVID-associated NOD with DKA. Majority have near-complete recovery of insulin secretion while simultaneous multi-tissue insulin resistance and inflammatory adipose tissue profiles persist as drivers of hyperglycemia .

Disclosure

R.Dasgupta: None. S.Mondal: None. R.Garai: None. B.Chowdhury: None. A.Hazra: None. M.Lodh: None. A.Ganguly: None.
1249-P: How Can Serum Adiponectin Levels Be Evaluated in Clinical Settings?
Authors: ONO SHOMA , DAIMON MAKOTO , KAMBA AYA , MIZUSHIRI SATORU , MURABAYASHI MASAYA , NISHIYA YUKI , ITO RYOMA , TAMURA AYUMI
Published: May 2022

Objective: Adiponectin, an adipocytokine, effects on various metabolic process including glucose regulation, and its decreased levels in serum have been reported as a risk for incident diabetes (DM) . However, cross-sectional studies often reported serum adiponectin levels (Ap) as increased in DM. We hypothesized that such inconsistency can be explained as abnormalities other than DM per se resided in the study subjects to be responsible for the increased Ap. Therefore, we here examined the effects of various conditions such as age, hypertension, dyslipidemia, and factors representing microangiopathies on association between DM and Ap in a general population.

Research Design and Methods: Among 1816 participants of the population-based Iwaki study of Japanese held in 2014-2017, 1771 subjects with complete data set including Ap were included, and the association between Ap and the above factors was analyzed by regression analysis and ANOVA with multiple factors adjustment.

Results: Ap showed positive correlation (p < 0.each) with age, HDL-cholesterol, and urinary albumin excretion (uACR) , and negative correlation (p < 0.each) with neutral fat, BMI, HbA1c, and waist circumference. As a whole, DM group had lower Ap than non-DM group (p < 0.01) . However, when the subjects were stratified based on uACR (<30 (normal) and >30 mg/gCr) , DM group had significantly lower Ap than non-DM group (p<0.01) in the normal group, but not in the other group (p=0.55) , indicated that increased uACR may be responsible for the increase in Ap in DM.

Conclusion: We here showed uACR, an indicator of microangiopathy, as a factor linking such inconsistency. Namely, although Ap is decreased in subjects prone to be diabetic and, thus, patients with DM should have lower Ap accordingly, patients with DM may have increased Ap depending on status of their complication such as microangiopathy. To strengthen this hypothesis, we now conducting analyses with stratification based on various other conditions and, longitudinal analyses as well.

Disclosure

S.Ono: None. M.Daimon: None. A.Kamba: None. S.Mizushiri: None. M.Murabayashi: None. Y.Nishiya: None. R.Ito: None. A.Tamura: None.
125-LB: Individualized Cost-Effectiveness Assessment of Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i) vs. Sulfonylureas as Add-On Therapy in People with Inadequately Controlled Type 2 Diabetes (T2D) Under Metformin Monotherapy
Authors: GUAN DAWEI , NIU SHU , FONSECA VIVIAN , SHI LIZHENG , LAITEERAPONG NEDA , GUO JINGCHUAN , SHAO HUI
Published: May 2022

The cost-effectiveness of SGLT2i can be modulated by patients’ characteristics, such as cardiovascular risks. We performed an individualized cost-effectiveness assessment of SGLT2i when added to metformin in people with inadequately controlled T2D to quantify the modulating effect of patients’ characteristics on the cost-effectiveness of SGLT2i. We identified survey participants with T2D receiving metformin monotherapy who had an A1c level above 7.0% from the National Health and Nutrition Examination Survey (2013-2018) . We applied a simulation-based smoothing method to populate the survey sample to its represented national population. We used the BRAVO diabetes model to simulate the lifetime cost and QALYs associated with SGLT2i or sulfonylureas. Treatment escalations were governed by the A1c level at 7% and 8% consequentially. Both costs and QALYs were discounted at 3% annually, and the incremental cost-effectiveness ratio (ICER) threshold was set at $100,000/QALYs. The study sample included 2.89 million individuals. Compared with sulfonylureas, the use of SGLT2i was associated with an average of $9,400 higher medical cost and 0.10 additional QALY, leading to an ICER of $94,000/QALY in the overall population. SGLT2i was cost-effective in people with a history of heart failure (ICER: $67,000/QALY) and myocardial infarction (ICER: $94,000/QALY) , and marginally cost-effective in stroke patients (ICER: $100,000/QALY) . Among individuals without CVD, SGLT2i was cost-effective only in subgroups with HbA1c > 7.5%, age > 60, and diabetes duration > 10 years. Overall, SGLT2i was only cost-effective in individuals with a baseline 10-year CVD risk over 16%, constituting 51.6% of the overall population. Our results align closely with the ADA guideline on the recommended population for SGLT2i use. Out-of-pocket payment subsidy or cost-sharing reduction of SGLT2i should be prioritized in patient subgroups in which SGLT2i has high economic values.

Disclosure

D. Guan: None. S. Niu: None. V. Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. L. Shi: None. N. Laiteerapong: None. J. Guo: None. H. Shao: Board Member; BRAVO4HEALTH, LLC.
1256-P: Lower Diabetes Technology Adoption and Worse Glycemic Control in Minorities with Type 1 Diabetes
Authors: CONWAY BAQIYYAH , SHAH VIRAL , RASMUSSEN CRISTY GENO , GONZALEZ ANDREA GERARD , SNELL-BERGEON JANET K.
Published: May 2022

Introduction: Poorer outcomes in acute and late complications of type 1 diabetes (T1D) persist among racial/ethnic minorities, and technology adoption may be lower in these groups. Technologies such as continuous glucose monitors (CGM) and insulin pumps (CSII) enhance diabetes management and improve glycemic control. We examined differences in use of diabetes technology by race/ethnicity among patients 12 and older followed at the Barbara Davis Center who had T1D for at least 1 year.

Methods: Use of CGM and/or CSII vs. neither was examined in 5,539 patients by racial/ethnic groups: Non-Hispanic White (NHW, n=3,945) , Black (n=161) , Hispanic (n=719) and Other racial groups (OR, n=714) . General liner models compared HbA1c and technology use by race/ethnicity.

Results: Black, Hispanic and OR patients were younger, had shorter T1D duration, higher HbA1c and less use of technology. In linear models adjusted for age, diabetes duration and visits over the past year, use of technology was associated with lower HbA1c in each race/ethnic group. However, among technology users, minority patients had higher HbA1c compared to NHW patients.

Conclusion: HbA1c was highest and diabetes technology use lowest among Blacks and Hispanics. Efforts to increase technology use for diabetes management in these populations may result in greater glycemic control and ultimately the reduction of acute and late complications of diabetes.

Disclosure

B.Conway: None. V.Shah: Advisory Panel; Medscape, Sanofi, Consultant; Dexcom, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. C.Geno rasmussen: None. A.Gerard gonzalez: n/a. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc.

Funding

NIH grant P30-DK116073
1264-P: Racial and Ethnic Inequities in Use of Diabetes Technology among Medicare Advantage Beneficiaries with Type 1 Diabetes
Authors: KOMMAREDDI MALLIKA , WHERRY KAEL , VIGERSKY ROBERT A.
Published: May 2022

Objective: Recent research highlighted racial and ethnic inequities in the use of diabetes technology among Medicare Fee-For-Service beneficiaries with type 1 diabetes. This study considers inequities among Medicare Advantage beneficiaries.

Methods: We assessed use of continuous glucose monitoring (CGM) and insulin pump technologies among beneficiaries with type 1 diabetes using a national database of health care claims between 2018 and 2020. The prevalence of CGM, pump, and combined technology was assessed annually (N = 17231 in 2018; N = 16298 in 2019; N = 15877 in 2020) by race and ethnicity. Within each year and type of technology, chi-square tests assessed differences in use between racial and ethnic groups.

Results: Prevalence of diabetes technology increased within each racial and ethnic group over the study period. There were significant differences in technology use between groups by year (p < 0.001) . In 2020, 37.1% of White beneficiaries used CGM devices, compared to 27.8% of Asian, 25.8% of Black, and 21.0% of Hispanic beneficiaries. The absolute difference in CGM use between White beneficiaries and those in other groups was stable or increased from 2018 to 2020. Similar trends were observed in pump use alone or with CGM.

Conclusion: While prevalence of diabetes technology increased across all racial and ethnic groups from 2018 to 2020, racial and ethnic inequities have persisted.

Disclosure

M.Kommareddi: Employee; Medtronic. K.Wherry: Employee; Medtronic. R.A.Vigersky: Employee; Medtronic.
1269-P: The Type 1 Diabetes Knowledge Portal: An Open-Access Resource for Insights into the Genetic and Genomic Basis of Type 1 Diabetes
Authors: COSTANZO MARIA C. , KUDTARKAR PARUL V. , NAYAK UMA , ONENGUT-GUMUSCU SUNA , SUN YING , RICH STEPHEN S. , FLANNICK JASON , GAULTON KYLE J. , BURTT NOËL
Published: May 2022

Type 1 diabetes (T1D) is a complex disease and more than 100 genetic loci influencing T1D risk have been identified to date. Discovering the genes and biological mechanisms through which these variants impact T1D requires the integration of multiple data types. We have created the T1D Knowledge Portal (T1DKP; type1diabetesgenetics.org) to help researchers utilize genetic and functional genomic data to generate hypotheses about the genes involved in T1D and its complications. The T1DKP aggregates genetic association data from the T1D community along with relevant functional genomics (e.g., accessible chromatin, 3D conformation, gene expression, gene perturbation) data, which are loaded via a sister resource, the Common Metabolic Diseases Genome Atlas (cmdga.org) . Using the HuGeAMP software platform developed for the Common Metabolic Diseases Knowledge Portal (CMDKP; cmdkp.org) within the Accelerating Medicines Partnership for Common Metabolic Diseases, the T1DKP integrates data by applying bioinformatic methods such as meta-analysis of genetic association results to generate “bottom-line” p-values, enrichment of genetic association within tissue-specific genomic annotations, and more. Interactive visualizations allow the user to explore results and to perform custom, on-the-fly analyses. The T1DKP also includes expert-curated lists of predicted effector genes of T1D loci, displaying the supporting evidence behind each prediction. Since the T1DKP is nested within and built upon the same framework as the CMDKP, users may navigate seamlessly to see results relevant to other metabolic disorders. In total the T1DKP project aims to accelerate our understanding and treatment of T1D by providing decision support for researchers as they prioritize loci, variants, and genes for experimental study.

Disclosure

M.C.Costanzo: Other Relationship; Pfizer Inc. P.V.Kudtarkar: None. U.Nayak: None. S.Onengut-gumuscu: None. Y.Sun: None. S.S.Rich: None. J.Flannick: None. K.J.Gaulton: Consultant; Genentech, Inc., Stock/Shareholder; Neurocrine Biosciences, Inc., Vertex Pharmaceuticals Incorporated. N.Burtt: n/a.

Funding

National Institutes of Health (5UM1DK105554-07)
127-LB: Real-World A1C Changes and Prescribing Provider Types among T2DM Patients Initiating Treatment with Oral Semaglutide
Authors: FRAZER MONICA S. , SWIFT CAROLINE , LESZKO MICHAEL , SARGENT ANDREW , BUYSMAN ERIN , ALVAREZ SARA B. , NOONE JOSHUA , GUEVARRA MICO
Published: May 2022

Purpose: To describe A1c changes and characteristics of patients with type 2 diabetes mellitus (T2DM) initiating oral semaglutide (sema) , by baseline A1c ≥9% and <9%.

Methods: Retrospective analysis using medical and pharmacy claims data from 11/01/2018-12/31/2020 from commercial and Medicare Advantage with Part D enrollees, aged 18+. Patients had ≥1 claim for oral sema (first claim=index date) , ≥1 T2DM diagnosis, continuous enrollment for 12 months before and including index (baseline) , and 6 months post-index (follow-up) , pregnant females excluded. Results were stratified by patient’s last baseline A1c (< or ≥9%) .

Results: Patients initiating oral sema who had ≥1 baseline A1c (n=994) had a mean age of 59 years, 50.4% were male, and 63.1% had commercial coverage. Among patients with baseline and follow-up A1c values (n=652) , mean A1c change was -0.8% (1.49) . Among a subset with ≥90 days of continuous oral sema treatment and ≥1 A1c after ≥90 days of treatment (n=200) , the A1c ≥9% group had a mean A1c change of -2.7% (2.1) . While half of index treatments were prescribed by primary care and internal medicine providers (50.6% overall) , a higher percentage of patients with A1c <9% had oral sema prescribed by an endocrinologist (24.4% vs. 16.1%; p=0.006) .

Conclusions: Results suggest that oral sema is an effective T2DM treatment in the real-world, especially among patients with A1c values ≥9% prior to treatment initiation. Patients with T2DM in this population are more often prescribed oral sema by primary care physicians than endocrinologists.

Disclosure

M. S. Frazer: None. C. Swift: Employee; Novo Nordisk. M. Leszko: None. A. Sargent: None. E. Buysman: None. S. B. Alvarez: Employee; Novo Nordisk, UnitedHealth Group. J. Noone: Employee; Novo Nordisk. M. Guevarra: None.
1271-P: The Gut Microbiota Related Genetic Variant at ABO Locus, Circulating Metabolome, and Type 2 Diabetes Risk: Prospective Study in UK Biobank
Authors: TANG RUI , WANG XUAN , MA HAO , LI XIANG , HEIANZA YORIKO , QI LU
Published: May 2022

Background: Gut microbiota has been implicated in the development of type 2 diabetes (T2D) . A recent genome-metagenome-wide study identified that genetic variants at the ABO locus (SNPs rs3758348, rs8176632, rs602662, and rs601338) were associated with the abundance of the gut microbiome. This study aimed to investigate whether the gut microbiota-related genetic variants at the ABO locus were associated with T2D and blood metabolome. We also analyzed the associations of the gut microbiota-related Metabolomic Risk Score (MRS) with incident T2D.

Methods: A total of 456,274 participants who are free of T2D at baseline and have available data on genetic variants from the UK Biobank population were included in this study. Plasma metabolome was profiled by a high-throughput NMR-based metabolic biomarker profiling platform among 109,0 participants. The MRS score was constructed with genetic variant-associated metabolites.

Results: We observed that the gut microbiota-related variant rs3758348 was significantly associated with T2D in the fully adjusted model (hazard ratio [HR] per copy of the C allele 1.06; [95% CI, 1.02-1.10]; P=0.0012 for trend) . We found that a total of 91 metabolites were significantly associated with rs3758348 (false discovery rate < 0.05) . Using elastic net regularized regressions, we generated a weighted MRS applying the 91 metabolites to predict the incidence risk of T2D. In multivariable Cox regressions, the weighted MRS showed a significant association with T2D incidence after adjusting for age, sex, BMI, alcohol status, smoking status, physical activity, and diet quality score (HR=1.49 [95% CI, 1.41-1.59], P<0.0001) .

Conclusion: Our study indicates that the gut microbiota-related genetic variant and metabolomic profile significantly predict T2D risk, independent of traditional risk factors.

Disclosure

R.Tang: None. X.Wang: None. H.Ma: None. X.Li: None. Y.Heianza: None. L.Qi: None.

Funding

National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024) , the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383) , the Fogarty International Center (TW010790) , and Tulane Research Centers of Excellence Awards.
1283-P: Paired Box 4 R192H (rs2233580) Variant Associated with Type 2 Diabetes Influenced the Response to the Treatment with Hypoglycemic Agents
Authors: TEERAWATTANAPONG NIPAPORN , TANGJITTIPOKIN WATIP , SRISAWAT LANRAPHAT , NARKDONTRI TASSANEE , YENCHITSOMANUS PA-THAI , PLENGVIDHYA NATTACHET
Published: May 2022

Paired Box 4 (PAX4) variants increase the risk of type 2 diabetes (T2D) and influence response to the treatment with hypoglycemic agents (HAs) in certain Asian populations. However, the influence of PAX4 variants associated with T2D on response to the treatment with different HAs and their combinations is unclear. This study aims to investigate the effects of the PAX4 R192H (rs2233580) variant associated with T2D on the therapeutic efficacy of antidiabetic medications in Thai T2D after following up for 3 years. A total of 526 patients who were followed up at the Diabetic Clinic of Siriraj Hospital during 2016 - 20 were enrolled. The rs2233580 variant was genotyped by rhAmp analysis and assessed the associations between genotypes and glycemic control by treatment with different HAs combinations by Generalized Estimating Equations (GEE) analysis. The average age at diabetes diagnosis of the patients was 54.9±9.59 years and the average diabetes duration was 9.7±6.55 years. The patients who carried GA+AA genotypes and were treated with a combination of sulfonylurea (SU) , biguanide (Bi) , thiazolidinediones (TZD) , and insulin (Ins) had lower fasting plasma glucose (FPG) compared with that of the patients who carried GG genotype (p=0.02) but FPG levels were significantly higher in the patients who received SU monotherapy (p=0.04) . Lower HbA1c was observed in the patients who carried GA+AA genotype and SU-Bi-Ins treatment compared with that of the patients who carried wildtype (p=0.002) . A treatment of Bi-TZD-Ins yielded higher HbA1c levels in the patients who carried GA+AA genotype compared with that of the patients who carried GG genotype (p<0.001) . Therefore, different genotypes might distinctively impact therapeutic effect of HA combinations on FPG and HbA1c. Taken together, genotypes of the PAX4 R192H (rs2233580) variant associated with T2D influence the response to HA combinations, providing evidence of pharmacogenetics in diabetes treatment.

Disclosure

N.Teerawattanapong: None. W.Tangjittipokin: None. L.Srisawat: None. T.Narkdontri: None. P.Yenchitsomanus: None. N.Plengvidhya: None.
1289-P: Role of Metformin and Lifestyle Modification in Management of Latent Autoimmune Diabetes in Adults
Authors: VELAYATI SARA , SHANIK MICHAEL , ROMAO ISABELA J.
Published: May 2022

Introduction: Latent autoimmune diabetes in adults (LADA) is atypical heterogenic diabetes that is frequently misdiagnosed as type 2 diabetes (T2DM) . LADA can demonstrate features of type 1 or T2DM.1 The diagnosis of LADA is well established, however, there are no universally accepted treatment guidelines. Few studies report the impact of metformin on long-term management in LADA. Most LADA cases will ultimately require insulin treatment.2 This case highlights the importance of early diagnosis of LADA and the potential benefit of using metformin with lifestyle changes to help maintain glycemic control.

Case presentation: A 27-year-old man with no past medical history presented with unintentional weight loss (30 lbs.) , frequent urination, blurry vision and dry mouth for 3 months. Physical exam was unremarkable, body mass index (BMI) : 24.5. Blood sugar: 381 mg/dL, HbA1c: 14% and C peptide: 0.97 ng/ml. He was diagnosed with T2DM and started on metformin 500 mg twice a day. Due to high clinical suspicion for atypical diabetes (young age, normal BMI and profound hyperglycemia) , immunological tests were done (reference ranges in parentheses) . GAD 65 antibody: 37.5 IU/mL (< 5 IU/mL) , Islet cell antibody 1:16 (<1:4) and Zinc Transporter 8 antibody: 97.2 U/mL (< 15.0 U/mL) . The results were suggestive of LADA. The patient continued treatment with metformin, regular exercise and low carbohydrate/sugar intake. After a year of adherence with treatment, results showed normal C peptide, controlled fasting and post-prandial blood sugars demonstrated by continuous glucose monitoring, 1,5 anhydroglucitol:13ug/mL (10.7-32.0 ug/mL) and HbA1c: 5.3%.

Conclusion: Treatment with metformin combined with lifestyle changes appears to be beneficial in patients with LADA. This management has so far been able to preserve adequate beta-cell function, providing optimal glycemic control. Future studies are warranted to further evaluate the therapeutic mechanism of metformin in this patient population.

Disclosure

S.Velayati: None. M.Shanik: Consultant; Bigfoot Biomedical, Inc., Proteomics International, Research Support; Better Therapeutics, Speaker's Bureau; Abbott, Boehringer Ingelheim International GmbH, Novo Nordisk, Xeris Pharmaceuticals, Inc. I.J.Romao: None.
1298-P: Metabolic Clearance of Insulin Is Altered after Gastric Bypass and Sleeve Gastrectomy
Authors: RAYAS MARIA S. , DEFRONZO RALPH A. , GASTALDELLI AMALIA , SALEHI MARZIEH
Published: May 2022

Roux-en-Y gastric bypass (GB) surgery and sleeve gastrectomy (SG) improve glucose tolerance, in part, by enhancing prandial insulin levels. Post-meal hyperinsulinemia after GB is caused by larger insulin secretion and lower metabolic clearance rate of insulin (MCRI) . Reduced prandial MCRI after GB is exaggerated in those with post-GB complication of hypoglycemia, suggesting that altered MCRI is a pathogenic factor. We investigated the role of GB or SG on insulin kinetics in fasting and fed states.

The MCRI were measured during a mixed meal text (MMT) in 9 GB and 7 SG subjects: and during MMT combined with hyperinsulinemic hypoglycemic clamp in 9 GB, 7 SG, and 5 CN. Three groups were matched for age and BMI and surgical groups for time and weight loss since surgery; none had diabetes or liver disease.

Fasting MCRI was greater in GB and SC than CN (p<0.05) . Meal ingestion diminished MCRI to a larger extent in GB subjects compared to SG reaching nadir values in 20-50 min (relative reduction in GB vs. SG: 82±3% vs. 74±3%, p<0.05) . The relative postprandial reduction in MCRI was inversely associated with the glycemic excursion and insulin response. During the clamp hepatic insulin clearance was larger in GB and SG compared to CN (p<0.05) . There was no association between hepatic insulin clearance and peripheral insulin sensitivity (M/I) . Induced hyperinsulinemia approximating 300 µU/ml reduced MCRI in 3 groups despite a larger M/I in surgical subjects. Meal ingestion during hyperinsulinemic hypoglycemia clamp raised MCRI in 3 groups (p<0.05) returning to pre-meal values in an hour. These findings demonstrate that the differences in basal MCRI among GB, SG and CN are mainly attributed to variations in insulin clearance in the liver and independent on peripheral insulin sensitivity. Further, prandial reduction in MCRI is greater after GB than SG in proportion to the rates of nutrient influx.; the effect of nutrient ingestion on insulin kinetics is altered during hyperinsulinemic hypoglycemia.

Disclosure

M.S.Rayas: None. R.A.Defronzo: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Intarcia Therapeutics, Inc., Novo Nordisk, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Speaker's Bureau; AstraZeneca. A.Gastaldelli: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Boehringer Ingelheim International GmbH, Inventiva Pharma, Other Relationship; Eli Lilly and Company, Gilead Sciences, Inc., Pfizer Inc., Speaker's Bureau; Novo Nordisk. M.Salehi: None.

Funding

National Institute of Diabetes, Digestive, and Kidney Diseases (DK105379)
1301-P: The Effect of Insulin on α-Aminoadipic Acid Metabolism in Polycystic Ovary Syndrome (PCOS) Patients with Insulin Resistance
Authors: CHANG ALICE Y. , ASOKAN ANEESH K. , SAKRIKAR DHANANJAY , LALIA ANTIGONI , PETTERSON MAI , NAIR K. SREEKUMARAN
Published: May 2022

Population studies have shown that the α-Aminoadipic Acid (AAA) , a lysine metabolite, predicts future type 2 diabetes and AAA concentrations decrease following administration of insulin sensitizers. To determine whether women with PCOS and insulin resistance have altered lysine and AAA kinetics we compared age-matched 18 women with PCOS to 12 women without PCOS using stable isotopes labeled [α-15N1]-lysine and [13C1]-AAA to measure lysine and AAA kinetics. Baseline levels of AAA flux and lysine concentrations were higher in PCOS compared to women without PCOS. Insulin decreased the concentrations and flux values of lysine and AAA. The conversion of lysine to AAA and AAA-metabolic clearance rates were increased on insulin infusion in both groups (Table) . Insulin sensitivity was negatively correlated with lysine concentration (r = - 0.547, p < 0.05) and AAA flux (r= - 0.587, p < 0.05) . In conclusion, our results indicate that insulin sensitivity is a determinant of AAA metabolism and insulin administration modulate the kinetics thus reducing AAA concentration indicating that altered AAA and lysine metabolism may result from insulin resistance.

Disclosure

A.Y.Chang: None. A.K.Asokan: None. D.Sakrikar: Employee; The Binding Site. A.Lalia: None. M.Petterson: None. K.Nair: None.

Funding

National Institutes of Health (RAG62859)
1320-P: Insulin Receptors and Their Signal Transduction Pathways in Choroid Plexus
Authors: MAZUCANTI CAIO , KENNEDY VERNON L. , CHO ANDREW , LIU QING-RONG , O’CONNELL JENNIFER F. , CAMANDOLA SIMONETTA , EGAN JOSEPHINE M.
Published: May 2022

The insulin receptor (IR) is a tyrosine kinase receptor present in cell membranes. It is highly expressed in hepatocytes (where it promotes glycogenesis and inhibits gluconeogenesis) , and skeletal muscle and fat (where it facilitates glucose uptake by translocation of the glucose transporter GLUT4) . IR expression is also found throughout the brain, both in neurons and all glial cell types, and for decades impaired insulin signaling has been implicated in the onset and development of Alzheimer’s disease. IR expression pattern in the brain parenchyma is heterogeneous, with highest levels of expression found in olfactory bulb, hypothalamus, and hippocampus. However, the choroid plexus (CP) , a structure present in all 4 ventricles of the brain and responsible for the secretion of cerebrospinal fluid, has the highest affinity for insulin binding compared to any other brain region. This work aims to characterize the insulin signaling in the epithelial cells of the choroid plexus (EChP) and its possible implications in diseases of the brain. Relative expression levels of specific splicing variants of the Insr gene in dissected CP of adult mice were evaluated by qPCR and revealed predominant expression of the variant coding for isoform IR-A when compared to isoform IR-B. In vitro stimulation of EChP with insulin elicits a classical tyrosine kinase cascade, with activation of both the mitogenic (ERK) and metabolic (Akt) arms of the insulin signaling pathway, in a time-and concentration-dependent manner. Using pharmacological (S961, an insulin receptor antagonist) and genetic (insulin receptor shRNA, and Insr cre-loxP) approaches, we show that downregulation of IR in these cells not only impairs insulin signaling, but it also decreases IGF2’s ability to activate ERK and Akt, even when IGF1R levels are unaltered. Finally, using a viral vector coding for an IR shRNA, we show that downregulation of Insr expression in CP of adult mice has a profound effect on its structure, as demonstrated by MRI and histological technique.

Disclosure

C.Mazucanti: None. V.L.Kennedy: None. A.Cho: None. Q.Liu: None. J.F.O’connell: None. S.Camandola: None. J.M.Egan: None.
1322-P: Role of Macrophage NOD1 in Fat-Induced ß-Cell Dysfunction
Authors: RAHMAN S.M. NIAZUR , YUNG JUSTIN HOU MING , ZHANG YIHE , GIACCA ADRIA
Published: May 2022

In individuals with obesity, free fatty acids (FFA) are chronically raised resulting in ß-cell dysfunction, leading to type 2 diabetes (T2D) . Recent data implicate the role of inflammation in developing ß-cell dysfunction, which is in part mediated by nucleotide-oligomerization domain 1 (NOD1) , an intracellular pattern recognition receptor. NOD1 is activated by peptidoglycans of bacterial cell walls; however, in vitro studies have documented that NOD1 can also be activated by saturated FFA.

Previous data from our lab have shown that palmitate-induced ß-cell dysfunction was prevented in whole body and ß-cell specific NOD1 null mice. We have seen earlier reports on increased macrophage infiltration in islets after elevation in circulating palmitate, and much higher expression of NOD1 in macrophages than ß-cells. Hence, we hypothesized that macrophage NOD1 receptors play a pivotal role in FFA-induced ß-cell dysfunction.

We have generated myeloid specific NOD1 null mice to target macrophage NOD1 receptors by crossing NOD1 floxed mice with Lyz2 Cre+ mice. Both knockouts and their controls (floxed and Cre) were infused for 48 h with ethylpalmitate (hydrolyzed to palmitate and ethanol in plasma) , to achieve elevated circulating FFA in a non-toxic manner. Ethanol vehicle was infused as control treatment. To assess in vivo ß-cell function, hyperglycemic clamp was performed following the 48 h infusion, and the disposition index (DI) was calculated.

Ethylpalmitate resulted in elevated plasma FFA compared to vehicle infusion. Ethylpalmitate caused marked reduction in DI in control mice, while knockout mice displayed no significant changes in DI between ethylpalmitate and vehicle infused groups. These results suggest that macrophage NOD1 plays a causal role in palmitate-induced ß-cell dysfunction in vivo. Overall, our data reveal NOD1 as a key factor and a potential therapeutic target for obesity-associated diabetes.

Disclosure

S.Rahman: None. J.Yung: None. Y.Zhang: None. A.Giacca: None.
1341-P: Dietary Fat and Fructose Impair Glucagon-Stimulated Liver Glucose Metabolism
Authors: EDGERTON DALE S. , KRAFT GUILLAUME , COATE KATIE C. , FARMER BEN , SMITH MARTA S. , SCOTT MELANIE , HASTINGS JON R. , MOORE MARY C. , CHERRINGTON ALAN D.
Published: May 2022

High fat and fructose diets (HFFD) disrupt glucose metabolism. The aim of this study was to determine the effect of HFFD on glucagon (GGN) effectiveness. Dogs were fed either chow or HFFD for one month. After a basal sampling period, somatostatin and basal portal vein infusions of insulin and GGN were given for 4h, with the exception of GGN, which was either maintained at basal or increased 6-fold. Glucose was infused in the basal GGN groups (CHOW+GLC & HFFD+GLC) to match the 3-fold increase in plasma glucose that occurred with 6x-GGN (CHOW+GGN & HFFD+GGN) . There were no differences in plasma insulin or glucose and GGN levels were proportional to GGN infusion rates in all groups. 6x-GGN caused an identical increase in net hepatic glucose balance (NHGB) in the chow and HFFD groups (Fig 1A) after which NHGB declined. During the last hour NHGB was 1.8-fold greater in HFHF+GGN compared to Chow+GGN (A) . However, hyperglycemia per se caused a switch from net hepatic glucose output to uptake in Chow+GLC but not HFHF+GLC (there was a 3.7±0.4 vs. 0.3±0.4 mg/kg/min decrease in NHGB over time in the two groups, respectively) (B) . Thus, when expressed relative to each group’s respective glucose control group, the AUC for GGN stimulated NHGB was 1.9-fold greater in the Chow (C) compared to HFHF (D) groups (P<0.05) .

In summary, HFHF feeding reduced hepatic glucagon action indirectly by impairing hepatic glucose effectiveness.

Disclosure

D.S.Edgerton: None. G.Kraft: None. K.C.Coate: None. B.Farmer: None. M.S.Smith: None. M.Scott: None. J.R.Hastings: None. M.C.Moore: None. A.D.Cherrington: Advisory Panel; Biocon, Diakard, Metavention, Sekkei Bio, Sensulin Labs, LLC, vTv Therapeutics, Consultant; Abvance, Fractyl Health, Inc., Novo Nordisk, Research Support; Bristol-Myers Squibb Company.

Funding

NIH R01DK18243