bluuebunny/crossref_metadata_2025 huggingface dataset:
121-LB: Prescribing Patterns of Sodium–Glucose Cotransporter 2 Inhibitors in Patients with Heart Failure With or Without Type 2 Diabetes
Authors: BERMUDEZ SARAH R. , ANDERSON JOE R. , RAY GRETCHEN
Published: May 2022

The goal of heart failure (HF) pharmacotherapy is to improve disease-related morbidity and mortality. Recent clinical trials demonstrated a reduction in cardiovascular death and HF-related hospitalizations with the addition of sodium glucose co-transporter 2 inhibitors (SGLT2i) in patients with HF with reduced ejection fraction (HFrEF) , as well as HF with preserved ejection fraction (HFpEF) with or without type 2 diabetes (T2D) . The objective of this study was to identify SGLT2i prescribing rates in these patients and to identify predictors of drug class utilization. The University of New Mexico (UNM) Health Sciences Center IRB approved this retrospective, single-center, descriptive study. Individuals ≥ 18 years with a diagnosis of HF, an eGFR of ≥ 20 ml/min/1.73m2, and a visit to the UNM Hospital system between August 17, 2020 to August 16, 2021 were included. Patients were excluded if they were diagnosed with type 1 diabetes or had no documented EF in their patient chart. A total of 2,905 patients with HF were identified, of which 1,101 were randomly reviewed. After exclusion, the study sample included: 377 with HFrEF, 335 with HFpEF, and 88 with HF with mid-range ejection fraction. The mean age was 65 years; 60% were female; 76% were white; 47% were Hispanic; and 49% had established atherosclerotic cardiovascular disease. Overall, 42% (n = 339) had T2D with a mean A1C of 8.0%. SGLT2is were prescribed in 6.5% of patients overall, 14.7% of patients with T2D, and 0.4% of patients without T2D. Predictors of SGLT2i prescribing were: T2D (OR = 38.4; 95% CI, 8.9 - 165.58) , HFrEF (OR = 3.7; 95% CI, 1.79 - 7.47) , having a cardiology provider (OR = 2.2; 95% CI, 1.79 - 7.47) , being seen by a pharmacist with prescriptive authority (OR = 4.1; 95% CI, 2.01 - 8.26) , and enrollment in UNM’s patient assistance program (OR = 2.3; 95% CI, 1.08 - 4.97) . Despite guideline recommendations, SGLT2is are underutilized in patients with HF with or without T2D. Future studies are needed to determine the barriers to utilization.

Disclosure

S. R. Bermudez: None. J. R. Anderson: None. G. Ray: None.
1212-P: Cost-Related Medication Nonadherence in Alabama's Medicaid Population with Diabetes
Authors: NESS EMILY C. , JUAREZ LUCIA , HOWELL CARRIE R. , HOHMANN LINDSEY , CHERRINGTON ANDREA , PRESLEY CAROLINE A.
Published: May 2022

Background: Cost-related medication nonadherence (CRMN) occurs when an individual takes less medication than what is prescribed due to difficulty affording their medications. In adults with diabetes, medication nonadherence is associated with worse glycemic control and increased healthcare costs. The goal of this study was to determine what proportion of Alabama’s Medicaid population with diabetes experiences CRMN and to evaluate for potential risk factors for CRMN in this financially-at-risk population.

Methods: We conducted a cross-sectional study surveying a population-based sample of adults (ages 19-64) with diabetes covered by Alabama Medicaid. We classified participants as experiencing CRMN if they responded yes to “Not including over the counter medications, was there a time in the past 12 months when you didn't take your medication as prescribed because of cost?” Using multivariable logistic regression, we examined what variables were associated with CRMN adjusting for demographic and clinical factors (insulin use, diabetes duration, receipt of care coordination, and self-rated health) .

Results: We included 1893 of 2235 (84.7%) participants who completed the survey and had complete data for the variables of interest in the analysis. This sample was predominantly nonwhite (60.7%) , female (73.9%) with a mean age of 52 ±10.1 years. Overall, 23.7% of participants reported CRMN. In the fully adjusted model, insulin use (OR 1.41, 95% CI 1.11, 1.79) , use of a discount prescription plan (OR 1.55, 95% CI 1.20, 2.00) , and self-report of poor health (OR 1.67, 95% CI 1.33, 2.09) were significantly associated with CRMN.

Conclusion: We found that almost a quarter of a population-based sample of adults with diabetes covered by Alabama Medicaid experienced cost-related medication nonadherence. More research is needed to determine how to address this among this vulnerable population.

Disclosure

E.C.Ness: None. L.Juarez: None. C.R.Howell: None. L.Hohmann: None. A.Cherrington: Consultant; Bayer AG, Other Relationship; Novo Nordisk. C.A.Presley: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R18DK109501) UAB Diabetes Research Center (P30 DK079626)
122-OR: Association between Annual Wellness Visits and Major Amputations among Medicare Beneficiaries in the Diabetes Belt
Authors: LOBO JENNIFER M. , KIM SOYOUN , KANG HYOJUNG , SOHN MIN-WOONG
Published: May 2022

Objective: Annual Wellness Visits (AWVs) are yearly visits for Medicare beneficiaries that include discussing preventive care needs and scheduling future preventive care services. Our prior work found that AWVs are associated with increased utilization of preventive care for diabetes patients, including uptake of foot exams. Our objective is to determine whether AWVs are associated with a reduced risk of major lower-extremity amputations (MLEAs) for patients in the Diabetes Belt.

Methods: Our analysis used a sample of approximately 900,000 Medicare Fee-for-Service beneficiaries from 2015 that lived in the Diabetes Belt and surrounding areas. The Diabetes Belt is a region of 644 counties in the Appalachian and deep south areas of the US identified by the CDC in 20 that continues to have a high prevalence. We used multivariable logistic regression to examine the association between AWVs and MLEAs in 2015, adjusting for demographic factors, comorbidities, major risk factors including diabetic foot ulcers, neuropathy, peripheral vascular disease, and access to care factors.

Results: The rate of MLEAs was significantly lower among patients in the Diabetes Belt who had an AWV in the last year. The odds of MLEAs were 36% lower in patients who used AWVs in the same year compared to those who did not, adjusting for all covariates. We also found that patients in the Diabetes Belt had about 27% higher odds of having an MLEA compared to those residing in the surrounding areas.

Discussion: Patients who used AWVs may have had their diabetic foot examined sooner to prevent a major adverse outcome than those who did not. Policy makers should prioritize incentives for having patients participate in AWVs to help reduce MLEAs.

Disclosure

J.M.Lobo: n/a. S.Kim: None. H.Kang: None. M.Sohn: None.

Funding

NIH/NIDDK R01DK113295
1230-P: Patient-Reported Outcomes (PROs) to Treatment in Type 2 Diabetes (T2D) from the International Diabetes Management Practices Study (IDMPS)
Authors: ASCHNER PABLO , GAGLIARDINO JUAN J. , ILKOVA HASAN M. , RAMACHANDRAN AMBADY , MBANYA JEAN CLAUDE , SHESTAKOVA MARINA V. , PILORGET VALERIE , MELAS-MELT LYDIE , CHANTELOT JEAN-MARC , CHAN JULIANA C.
Published: May 2022

Introduction: Treatment acceptance and self-management are essential for achieving better HbA1c in people with diabetes.

Methods: IDMPS is an international, observational study investigating care practices and clinical profiles of people with diabetes in developing countries. This analysis of Wave 8 evaluated PROs in people with T2D and their associations with glycemic control using 1) the chronic treatment acceptance questionnaire (ACCEPT) to assess acceptance of long-term medication advantages/disadvantages, and 2) the diabetes self-management questionnaire (DSMQ) to assess health-related behaviors.

Results: Of 2475 people with T2D (mean ± SD age 58 ± 12 years, 51% women, diabetes duration ± 8 years, BMI 31 ± 6 kg/m2, HbA1c 8.0 ± 1.8 %, 43% on insulin, HbA1c <7 % 31%) from 13 countries, most completed ACCEPT (99%) and DSMQ (99%) . Acceptance was high for medication effectiveness and side effects, but low for number of medications and their duration (Figure A) . Scores for self-management were low, especially physical activity (Figure B) . Multivariate analyses did not show association of HbA1c <7 % with higher ACCEPT scores (bar effectiveness score) , regardless of treatment.

Conclusions: Despite high medication acceptance in developing countries, low self-management calls for further education to improve medication effectiveness.

Disclosure

P.Aschner: Advisory Panel; Merck & Co., Inc., Sanofi, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. J.J.Gagliardino: None. H.M.Ilkova: Advisory Panel; Novo Nordisk. A.Ramachandran: None. J.Mbanya: Advisory Panel; Novo Nordisk, Sanofi, Servier Laboratories. M.V.Shestakova: None. V.Pilorget: None. L.Melas-melt: None. J.Chantelot: Employee; Sanofi, Stock/Shareholder; Sanofi.

Funding

Sanofi
1232-P: Beta-Cell Function and Type 2 Diabetes in Africans and Asian Indians
Authors: STAIMEZ LISA R. , SHAH ROHAN , DEEPA MOHAN , MATSHA TANDI E. , ANJANA RANJIT MOHAN , ERASMUS RAJIV T. , MOHAN VISWANATHAN , MABUNDO LILIAN , DUBOSE CHRISTOPHER , NARAYAN K.M. VENKAT , DAGOGO-JACK SAMUEL , KENGNE ANDRE PASCAL , SUMNER ANNE E.
Published: May 2022

The role of β cell dysfunction in the development of type 2 diabetes (DM) is not understood across populations with different levels of insulin resistance. We examined β-cell function in two cohorts of Africans and compared them to Asian Indians. Adults without known DM were examined in 3 cohorts: (1) Mixed Ancestry Africans (MAA, n=1112) living in South Africa, (2) African-born Black immigrants living in United States (A-US, n=529) and born in West, Central or East Africa and (3) Asian Indians (n=1751) living in Chennai, India. OGTT were performed with fasting and 2h glucose and insulin levels obtained. Insulin resistance was defined as HOMA-IR above cohort-specific upper quartile. Beta-cell failure was defined as hyperglycemia without insulin resistance. Beta-cell secretion (HOMA-β) and insulin resistance between ethnicities by ANOVA were compared. MAA were older than A-US or Asians [ (MAA: mean 46y SD 14) , A-US) (39y, SD 10) , Asians (39y, SD 11) with more % female (MA: 73%, A-US 36%, Asians 64%) . Newly diagnosed DM was similar across cohorts (MAA: 6.4%, A-US 7.0%, and Asians 8.1%) . When pooled, 54% total had β-cell failure as the predominant etiology of DM. Fasting glucose, adjusted for age, sex, and BMI, was highest in AI (MAA: 90 mg/dL, SE 0.8; A-US 92, SE 1.1; Asians 101, SE 0.6) . However, A-US had highest 2h glucose (MAA: 97 mg/dL, SE 2.5; A-US 128, SE 4.0; Asians 107, SE 1.8) . In the normal weight BMI group (BMI:18.5-25.0 kg/m2) adjusted for age and sex, HOMA-β was lowest in Asians [97.7, SE 14.6] and 3 times higher in MAA vs. A-US (MAA 151.6, SE 88.3; A-US 48.5, SE 143.6) , despite similar HOMA-IR [MAA: 1.1, SE 0.1; A-US: 1.1 SE 0.1]. The difference in HOMA-β between overweight and obesity strata was modest in Asians and A-US vs. MAA (MAA: 90.9, A-US: 21.6, Asians: 0.9) . Overall, β-cell function was heterogeneous across African cohorts and lowest in Asians. Differences in average β-cell function between overweight and obese participants suggest insulin secretion may be less available to A-US and Asians compared to the MAA.

Disclosure

L.R.Staimez: None. K.Narayan: n/a. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi. A.Kengne: None. A.E.Sumner: None. R.Shah: None. M.Deepa: None. T.E.Matsha: None. R.Anjana: None. R.T.Erasmus: Speaker's Bureau; Abbott. V.Mohan: None. L.Mabundo: None. C.Dubose: None.
1233-P: Racial/Ethnic Differences in the Prevalence of Diagnosed Anemia in Adults with Type 2 Diabetes
Authors: BOARD CHRISTINE , GOPALAN ANJALI , KARTER ANDREW J. , GRANT RICHARD W. , SOFRYGIN OLEG
Published: May 2022

Individuals with anemias are often excluded from diabetes research when the population or outcome of interest is defined by HbA1c, as abnormal red blood cell turnover rates raise concern about the accuracy of measured HbA1c values. While racial/ethnic differences in the prevalence of certain anemias are well-known, the potential bias introduced by excluding individuals with anemias from research samples is less studied. We examined the prevalence of diagnosed anemias by race/ethnicity in a population of adults diagnosed with diabetes. Using data from a large healthcare system, we identified adults (≥21 years) diagnosed with type 2 diabetes from 2010-2016. We used ICD-9/codes to identify individuals diagnosed with anemia in the year prior to diabetes diagnosis and inherited hemoglobinopathies through follow-up. We used chi-square tests to compare the prevalence of these diagnoses by race/ethnicity. Among 78,2individuals, 5,434 (6.9%) had an anemia diagnosis in the 12 months prior to their diabetes diagnosis, with the most common being unspecified anemia (3.3%) and iron deficiency anemia (2.3%) . Black adults had the highest prevalence of any anemia (11% vs. Other race/ethnicity 8.8% vs. White 7% vs. Latino 6.1% vs. Asian 5.9%, p≤.0001) , unspecified anemia (5.4% vs. Other race/ethnicity 3.8% vs. White 3.5% vs. Latino 2.8% vs. Asian 2.4%, p≤.0001) , and iron deficiency anemia (3.6% vs. Other race/ethnicity 2.9% vs. White 2.2% vs. Latino 2.4% vs. Asian 1.9%, p≤.0001) . Black and Asian adults had the highest prevalence of inherited hemoglobinopathies (Asian 2.3% vs. Black 1.9% vs. Other race/ethnicity 1.3% vs. White 0.3% vs. Latino 0.3%, p≤.0001) .

In conclusion, among adults diagnosed with diabetes, Black adults had the highest prevalence of diagnosed anemias (>1 in Black adults had a diagnosis) . Excluding individuals from diabetes research based on diagnosis of anemia may disproportionately impact the relevance of the findings to Black adults.

Disclosure

C.Board: None. A.Gopalan: None. A.J.Karter: Research Support; Dexcom, Inc. R.W.Grant: None. O.Sofrygin: None.

Funding

National Institutes of Health (1R21DK130018-01)
1242-P: Prevalence of Newly Detected Diabetes and Glycemic Status of People with Diabetes Already on Treatment: Results from a Nationwide Community Screening Program by RSSDI.
Authors: PARIKH RAKESH M. , GUPTA AMIT , SABOO BANSHI D. , CH VASANTH K. , AGARWAL SANJAY , MAKKAR BRIJ M. , BHATTACHARYYA SUPRATIK , CHITTAWAR SACHIN , NANDITHA ARUN , KOVIL RAJIV R. , CHAWLA SR., PURVI M.
Published: May 2022

Background: Several studies have suggested that prevalence of diabetes in India is increasing, a large number of people remain undiagnosed, and overall glycemic control is poor among patients with diabetes. Although there is paucity of data from large population studies. Current study was aimed at analyzing the data collected during the One Nation, One Day, One Million Tests campaign by the Research Society for the Study of Diabetes in India (RSSDI)

Methodology: Data collected from the One Nation, One Day, One Million Tests campaign by the Research Society for the Study of Diabetes in India (RSSDI) was retrospectively analyzed. A total data of 225955 adults was included in the analysis out of which 142391 (63%) were males while 83564 (37%) were females.

Results: 78694 (34.8%) subjects reported to have preexisting diabetes while 21380 (9.5%) were detected to have diabetes for the first-time during the screening program. Total prevalence of diabetes in the cohort was 100074 (44.3%) .

Among people with preexisting diabetes, 68669 (87.3%) reported to be on treatment for diabetes. 17646 of them presented in fasting state and 14834 (21.6%) of them had fasting sugar above 130 mg/dl. Random blood sugar was tested for 423diabetic subjects on treatment, out of which 28335 (41.3%) had random blood sugar more than 180 mg/dl. Overall, 62.9% (43169) of diabetes patients on treatment had their blood sugar values beyond target range.

Conclusions: High prevalence of newly detected diabetes in the cohort re-emphasizes the need for aggressive screening for early detection of diabetes in the Indian population. Although the number of people who reported to be on treatment for diabetes was better in this cohort compared to earlier studies, only one third of these subjects had their sugar levels under control.

Disclosure

R.M.Parikh: None. R.R.Kovil: None. P.M.Chawla: Speaker's Bureau; Biocon, Boehringer Ingelheim International GmbH, Eris Lifesciences Ltd., Novo Nordisk, Sanofi. A.Gupta: Speaker's Bureau; Lupin Pharmaceuticals, Inc., Medtronic, Novartis AG, Novo Nordisk, Sanofi. B.D.Saboo: None. V.K.Ch: None. S.Agarwal: Speaker's Bureau; Novo Nordisk, Roche Diabetes Care, Sanofi, USV Private Limited. B.M.Makkar: None. S.Bhattacharyya: None. S.Chittawar: None. A.Nanditha: None.
1261-P: Is Glycemic Control Better in Adults with Type 1 Diabetes When Office Visits are Supplemented with Telehealth Visits?
Authors: TOSCHI ELENA , ADAM ATIF , SLYNE CHRISTINE , LAFFEL LORI M. , MUNSHI MEDHA
Published: May 2022

Objective: Since the COVID-pandemic began, instead of in-office care alone, many institutions implemented hybrid care (in-office + telemedicine) . It is not known if hybrid care is as effective as in-office visits in regards to achieving glycemic goals.

Methods: Clinical characteristics of adults with type 1 diabetes (T1D) (age ≥40 years) were retrieved from electronic health records from two periods: in-office model before the pandemic (April 2019-March 2020) and hybrid-care model during the pandemic (September 20pril 2021) . Patients were stratified by age.

Results: Overall, 1,820 patients were evaluated, 66% younger (40-64 years: mean age 52±7yrs, 52% female, 53% CGM users, 56% pump users) and 34% older (≥65 years: mean age 72±5yrs, 55% female, 53% CGM users, 38% pump users) . A1c using hybrid-care improved in both younger (7.8±1.2 vs. 7.6±1.2%; p=0.005) and older adults (7.6±0.9 vs. 7.4±1%; p=0.02) , compared to in-office care. Within the hybrid-care model period, poor glycemic control was associated with a higher number of hybrid visits, and more in-office missed appointments, while pump use was associated with lower A1c.

Conclusion: Compared with in-office care, hybrid care was effective at maintaining glycemic control in both younger and older adults with T1D. Prospective studies are needed to understand the use of hybrid-care for the management of adults with T1D.

Disclosure

E.Toschi: Consultant; Medtronic. A.Adam: None. C.Slyne: None. L.M.Laffel: Advisory Panel; Medtronic, Roche Diabetes Care, Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. M.Munshi: Consultant; Sanofi.
1265-P: The Role of Health System Penetration Rate in Estimating Prevalence of Type 1 Diabetes (T1D) in Children and Adolescents Using Electronic Health Records (EHR)
Authors: LI PIAOPIAO , LYU TIANCHEN , BIAN JIANG , GUO YI , SHENKMAN ELIZABETH , DONAHOO WILLIAM T. , GUO JINGCHUAN , SHAO HUI
Published: May 2022

This study aimed to develop a novel method that can accurately estimate the prevalence of T1D in children and adolescents using EHR data. T1D cases among individuals <= 18 years old were identified from the OneFlorida EHR (2018-2020) using a computable phenotype algorithm we have developed. The T1D prevalence was estimated at the zip code level, with numerator being the total T1D cases and the denominator being the number of residents in each zip code area extracted from the census data. The observed health system penetration rates (HSPR) in 20 were estimated as a ratio of total patients who visited the healthcare systems in the OneFlorida network (2018-2020) to the total number of residents in each zip code area in 2019. We applied a joint-point regression to determine the cutoff thresholded where the observed HSPR can produce accurate prevalence estimation. The cutpoint value of 72.0% for the observed HSPR was identified, and the trend line between prevalence and HSPR plateaued in areas with HSPR>72% (slope=0.002, figure) . The estimated T1D prevalence in 20 was 0.243%, which is similar to that of estimated by SEARCH (0.255%) . Our algorithm provides a critical tool for developing a EHR-based diabetes surveillance system in the US.

Disclosure

P.Li: None. T.Lyu: None. J.Bian: None. Y.Guo: None. E.Shenkman: None. W.T.Donahoo: None. J.Guo: None. H.Shao: Board Member; BRAVO4HEALTH, LLC.

Funding

U18DP006512 CDC/NIDDK
127-OR: Diabetic Foot Ulcers in Remission: Cyclical-Pressure Topical Wound Oxygen Therapy Significantly Reduces DFU Related Hospitalizations and Amputations over a 12-Month Period
Authors: GAROUFALIS MATTHEW G.
Published: May 2022

Purpose: The purpose of this real-world evidence (RWE) cohort study was to evaluate whether utilization of Cyclical-Pressure Topical Wound Oxygen (TWO2) therapy had any impact on the incidence of Diabetic Foot Ulcer (DFU) related hospitalizations and amputations over a 12-month period in patients with hard to heal Diabetic Foot Ulcers (DFU)

Methods: An IRB approved retrospective review of deidentified DFU patient medical records was conducted at 2 US Veterans Affairs Medical Centers in Illinois and Virginia, which included demographic information on wound characteristics, clinical characteristics, neuropathy, cardiovascular disease (CVD) , peripheral vascular disease (PVD) , pain level and kidney disease etc.

Results: Within the unmatched cohorts of 202 DFU patients (91 TWO2, 1NO TWO2) there was an 88% reduction in hospitalizations and 71% reduction in amputations over the 12-month period for the patients treated with TWO2 therapy compared to those that did not receive TWO2 therapy. After propensity score matching was conducted, which minimizes the effects of confounding by achieving more balanced covariates in the absence of a randomized study, resulting in matched cohorts of 140 DFU patients (70 TWO2, 70 NO TWO2) , 82% fewer TWO2 patients were hospitalized) and 73% fewer TWO2 patients had amputations, compared to those who did not receive TWO2 therapy (p < 0.0001, p = 0.00 respectively) .

Conclusions: This large RWE study demonstrates that TWO2 therapy positively impacts patient’s quality-of-life and the costs associated with treating their DFU by forcing them into remission, resulting in significantly reduced rates of amputations and hospitalizations.

Disclosure

M.G.Garoufalis: None.
128-OR: Income-Related Disparities in Medical Expenditures in U.S. Adults with Diabetes
Authors: WANG YU , SHAO HUI , IMPERATORE GIUSEPPINA , HOLLIDAY CHRISTOPHER S. , ZHANG PING
Published: May 2022

Relatively little is known about diabetes-related medical costs across income groups, yet such information can assist efforts to reduce income-related diabetes disparities. Using data from the 2017-20 Medical Expenditure Panel Survey, we estimated medical expenditures (total and by service category [inpatient, outpatient, and drug]) in adults with diabetes, overall and by income level (<125% of federal poverty level (FPL) , ≥125% and <200% FPL, ≥200% and <400% FPL, ≥400% FPL) . We also identified factors that contribute to the differences (education, health insurance, marital status, physical and mental health) by constructing a concentration index (CI) (an inequality measure with values ranging from -1 to 1 with 0 indicating no disparity) and conducting a decomposition analysis which quantifies the contribution to CI by factor. We estimated crude and adjusted medical expenditures by income group, controlling for age, sex, and race/ethnicity. All expenditures were adjusted to 20 US dollars. Persons with incomes <125% FPL had significantly higher health medical expenditures in total and across all service categories than the other three income groups (P<0.05) . After adjustments, the lowest income group spent $2828 more per person per year than the other three income groups (P<0.05) while no significant differences in expenditures were found among the other three groups. The estimated CI value was -0.022, indicating expenditures more concentrated in the lower income group About a half (49.1%) of the disparity was explained by higher public insurance coverage (28.6%) and poorer physical (13.3%) and mental (7.2%) health status. Diabetes-related medical expenditures are disproportionately concentrated among low-income group. Improving physical and mental health for low-income populations may help to reduce the disparity in medical expenditures of diabetes.

Disclosure

Y.Wang: None. H.Shao: Board Member; BRAVO4HEALTH, LLC. G.Imperatore: None. C.S.Holliday: None. P.Zhang: None.
1292-P: Differential Glycaemic Effects of Recombinant IL-9 across Species Highlight Translational Challenges for Immunometabolic Phenotypes
Authors: GUO TINGQING , STRAARUP ELLEN MARIE , CHRISTENSEN JOSEFINE LINDROOS , BOLT GERT , NØRBY PEDER LISBY , ZHE WANG , PEDERSEN THOMAS A. , FERRERAS MERCEDES , SASS-ØRUM KRISTIAN , FREDERIKSEN KLAUS S.
Published: May 2022

In the present study, IL-9 was initially identified as a strong regulator of blood glucose in diabetic db/db mice through a hydrodynamic gene delivery screening effort. IL-9 belongs to the common gamma-chain binding cytokine family and has classically been linked to asthma and type 2 immune responses. Alongside the very clear dosing effects of mouse IL-9 on fasting blood glucose, the more classical effects of IL-9, including IL-5 plasma increases and eosinophilia, were also observed in the db/db mice. An expansion of epididymal white adipose tissue macrophages was shown with IL-9-, but not IL-5 dosing. Inhibition of endogenous IL-5, with an anti-IL5 mAb, attenuated the IL-9 effects on eosinophils but not macrophages. Interestingly, suppression of glucagon levels following IL-9 dosing was a general observation in several diabetic mouse studies. The addition of anti-IL-5 mAb to IL-9 dosing did not affect glucagon levels in the db/db mouse model, and an association between eosinophil/macrophage changes and blood glucose could not be established. To examine the translation of these interesting IL-9 effects to higher species, a recombinant protracted human IL-9 dosed to low streptozotocin induced diabetic mini-pigs (2-week study) , showed increased numbers of circulating eosinophils, but no significantly reduced levels of glucagon or plasma glucose. Finally, an 11-week treatment study in type 2 diabetic cynomolgus monkeys was performed. Eosinophilia was observed as an indicator of IL-9 receptor engagement, but several glycaemic parameters and glucagon levels were unaffected throughout the study. Conclusion: The pronounced glycaemic effects observed for IL-9 in a diabetic mouse model was not found in diabetic minipigs and non-human primates highlighting the complexity and need for further studies of the translation of immuno-metabolic phenotypes.

Disclosure

T.Guo: Employee; Novo Nordisk A/S. K.S.Frederiksen: Employee; Novo Nordisk A/S. E.Straarup: Employee; Novo Nordisk A/S. J.Lindroos christensen: Employee; Novo Nordisk A/S. G.Bolt: Employee; Novo Nordisk A/S. P.Lisby nørby: Employee; Novo Nordisk A/S. W.Zhe: Employee; Novo Nordisk A/S. T.A.Pedersen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. M.Ferreras: Employee; Novo Nordisk A/S. K.Sass-ørum: Employee; Novo Nordisk A/S.
1293-P: Diabetes Management at the Time of Renal Transplantation
Authors: GRIFF MEGAN , CRAWLEY SVITLANA , ROWLAND ANN , SEGGELKE STACEY A. , HAWKINS R. MATTHEW , WANG CECILIA C. LOW
Published: May 2022

The goal of this retrospective review was to characterize the glycemic status and antihyperglycemic treatments in persons with diabetes (PwD) undergoing renal transplant and to determine whether use of intravenous insulin infusion (IVI) is associated with clinical outcomes. A retrospective review of all adult patients undergoing renal transplantation at a single tertiary referral center from January 1 - December 31, 20 was performed.

Results: Of the 292 patients who underwent renal transplantation, 1 (34.6%) had a diagnosis of diabetes. Pre-transplant treatment for diabetes included insulin in 61 (60.4%) , non-insulin medications in (10.9%) , and both insulin and non-insulin medications in 5 PwD (4.9%) . Twenty-four PwD (23.8%) were not taking medications for diabetes. While hospitalized 65 (64.4%) PwD received IVI while the remainder received SC insulin (SCI) . The pooled daily mean point of care (POC) glucose on postoperative day (POD) 0 through POD 3 was not significantly different between IVI vs. SCI (164.5 vs. 165.3mg/dL, p=0.91) . ICU admission occurred in 7 (10.8%) IVI and 8 (22.5%) SCI (OR 0.42, 95% CI 0.14-1.28) . Fourteen (21.5%) IVI and 5 (13.9%) SCI underwent dialysis during hospitalization (OR 1.70, 95%CI 0.56-5.19) . Readmission within 30 days occurred for 17 (26.6%) IVI and 12 (33.3%) SCI (OR 0.53, 95% CI 0.22-1.27) .

Discussion: While pre-transplant treatment of diabetes varied, most PwD undergoing renal transplantation were placed on IV insulin for management of hyperglycemia post-transplant. Insulin infusion was not associated with significant differences in pooled daily mean blood glucose. Significant differences in clinical outcomes were not identified between those treated vs. not treated with insulin infusion, but this could be due to the relatively small sample size. More research is needed to understand how diabetes care can be improved in hospitalized PwD undergoing renal transplantation.

Disclosure

M.Griff: None. S.Crawley: None. A.Rowland: None. S.A.Seggelke: None. R.Hawkins: None. C.C.Low wang: Employee; CPC Clinical Research, Research Support; CellResearch Corporation, Virta Health Corp.
1300-P: Novel Insulin Modified Oral Glucose Tolerance Test Improves the Estimation of Insulin Sensitivity and Glucose Effectiveness
Authors: STEFANOVSKI DARKO , PICCININI FRANCESCA , ADER MARILYN , KABIR MORVARID , BERGMAN RICHARD N.
Published: May 2022

Estimating insulin resistance from the oral glucose tolerance test (OGTT) has long been a challenge in diabetes research and practice. Because the time courses of glucose and insulin during the OGTT are similar in shape, the estimates of insulin sensitivity per se may be corrupted by other metabolic responses such as insulin release or glucose absorption. We have previously shown insulin injection during the intravenous test yields accurate values of insulin sensitivity (SI) and glucose effectiveness (SG) . Here we examine an analogous approach during the OGTT - in which exogenous insulin is administered during the test. Methods: For 100 simulated subjects (NGT: n=25, IGT: n=25, T2D: n=25, T1D: n=25) , glucose and insulin data were calculated using Dalla Man Mixed Meal Simulator. For each simulated subject, several protocols were examined by varying the time of insulin bolus (30, 60, or 90 min) and the dose of the bolus (0, 0.01, 0.02, or 0.03 IU/kg) . The resulting 3600 simulated datasets were analyzed with Dalla Man’s OGTT model to estimate SI. Results: When adjusted for the dose of insulin, the time of the dose did not significantly impact the estimation of SI. The 0.IU/kg insulin dose resulted in significantly (P<0.001) better estimates of SI when compared to the three other doses. Unique estimates of SG were obtained only without and with insulin dose of 0.IU/kg. There was no difference (P=NS) between the quality of SG estimates with these two doses. Conclusions: An intravenous insulin bolus of 0.IU/kg given at 60 min during the OGTT will enable accurate and precise estimations of both SI and SG.

Disclosure

D.Stefanovski: None. F.Piccinini: Employee; Medtronic. M.Ader: None. M.Kabir: None. R.N.Bergman: Consultant; Fractyl Health, Inc., Novo Nordisk, Research Support; AstraZeneca, Janssen Research & Development, LLC.
1307-P: Leptin Action in the Nucleus of the Solitary Tract
Authors: BRUCE KYLA , LI ROSA J.W. , LIM YUMI , YUE JESSICA T. , LAM TONY K.
Published: May 2022

Obesity and diabetes are characterized by a disruption in energy balance and glucose homeostasis in association with leptin resistance. Leptin action in the hypothalamus regulates glucose levels and body weight, but whether other brain regions facilitate leptin action remain unclear. Here, we investigate whether the nucleus of the solitary tract (NTS) of the brainstem is a crucial site for leptin action in regulating glucose homeostasis in 3d high-fat (HF) -fed male rats, as recent studies report leptin activates leptin receptor in the NTS to regulate feeding. In this study, we performed brain stereotaxic bilateral surgery targeting the NTS followed one week later by catheterization of the left carotid artery and right internal jugular vein for infusion/sampling purposes. Rats that attained >90% of presurgical weight received 3d of Lard oil enriched HF diet and were fasted 4-6 hr before undergoing a 2min pancreatic (basal insulin) -euglycemic clamp studies together with tracer glucose infusion to assess glucose metabolism independent of changes in plasma insulin and glucagon levels. Leptin (91.7 ng/uL at 0.33 ul/hr) or saline was infused into the NTS throughout the duration of the clamp studies. Correct placement of the NTS catheter was verified by infusion of bromophenol blue dye through the brain cannula. For the first time, we found that leptin vs. saline infusion into the NTS markedly increased the exogenous glucose infusion [lep: 4.6±0.2 vs. sal: 1.3±0.4 mg/kg/min; p<0.005; n=12, 5] required to maintain euglycemia [lep: 137.5±2.2 vs. sal: 145±3.1 mg/dl; p>0.05; n=12, 5], during the clamps. The drop in plasma glucose levels was due to an inhibition of glucose production [lep: 4.9±0.1 vs. sal: 8.4±0.7 mg/kg/min; p<0.01; n=12, 5], but not an increase in glucose uptake [lep: 10.4±0.5 vs. sal: 9.7±0.3 mg/kg/min; p>0.05; n=12, 5]. These findings demonstrate that the NTS mediates leptin action on glucose homeostasis. Future studies are needed to investigate the NTS leptin signaling cascade in glucose homeostasis in obesity and diabetes.

Disclosure

K.Bruce: None. R.Li: None. Y.Lim: None. J.T.Yue: None. T.K.Lam: None.

Funding

Canadian Institutes of Health Research Foundation Grant (FDN-143204)
1309-P: Central Mechanisms of Pollution-Induced Metabolic Disease
Authors: DEBARBA LUCAS K. , KOSHKO LISA , JAYARATHNE HASHAN M. , YI ZHENGPING , KLUEH ULRIKE , SADAGURSKI MARIANNA
Published: May 2022

There is growing evidence linking exposure to volatile organic compounds (VOC) in ambient air with metabolic disease in humans. Benzene is a prominent VOC present in water, food, detergents, vehicle exhaust, tobacco smoke, and e-cigarettes. However, a direct link between exposure to VOC and metabolic homeostasis is not yet established. We performed a meta-analysis and found a positive association between exposure to VOC and metabolic impairments. Using a highly controlled mouse exposure system, we have recently demonstrated that chronic exposure of mice to VOC induces neuroinflammation and insulin resistance predisposing to T2D. To establish a timeline for the onset of VOC-triggered metabolic effects, we monitored glucose changes of exposed mice using continuous glucose monitoring (CGM) system. Surprisingly, we detected significant changes in glycemic control of male mice starting at day 4 of exposure. Further, mice exhibited impaired parameters of energy homeostasis within 6h of exposure. This was associated with activation of hypothalamic gliosis via stimulation of the NF-κB signaling and dysregulation of hypothalamic insulin signaling, contributing to blunted responses to glucose stimulation in glucose-sensing neurons. To determine the role of the central inflammatory mechanism in VOC-induced metabolic imbalance, we genetically ablated NF-κB signaling in microglia using Cx3cr1creERΔIKK mice. Selective inhibition of microglial NF-κB signaling completely restored hypothalamic insulin signaling, astrocytes activation, and hypothalamic glucose-sensing, consequently protecting from whole-body metabolic imbalance induced by VOC exposure. Importantly, this effect was mediated via hypothalamic ER stress response. Collectively, our data provide evidence that neuroinflammatory responses precede and mechanistically contribute to whole-body metabolic imbalance and identify air pollution-induced cellular and molecular targets in the hypothalamus that lead to metabolic disease.

Disclosure

L.K.Debarba: n/a. L.Koshko: None. H.M.Jayarathne: None. Z.Yi: None. U.Klueh: Research Support; Dexcom, Inc. M.Sadagurski: None.

Funding

American Diabetes Association (1-18-JDF-063)
1311-P: Glucokinase in AGRP Neurons Is Required for Normal Insulin Secretion and Action in Female Mice
Authors: JOSIPOVIC MASA , STARICOFF EMILY O. , RICHES CHRISTINE H. , SHEPPARD LAURA , EVANS MARK
Published: May 2022

Discrete brain areas, including hypothalamic nuclei, have been implicated in glucose homeostasis. Some contain molecular machinery capable of detecting changes in blood glucose such as glucokinase (GK) , a low affinity hexokinase important for pancreatic beta cell glucose-sensing. A subset of arcuate nucleus AGRP neurons express GK. We created GKAGRP knockout (KO) mice by crossing AGRP Cre with GK floxed mice, hypothesizing that they would display impaired gluco-regulation. Despite established sex differences in metabolic neurocircuitry, female mice are not always studied. In pilots, we found impaired glucose handling in i.p. glucose tolerance tests in older GKAGRP KO females, but not younger female, nor male mice. Here, we perform detailed phenotyping, using sequential euglycemic (with stable glucose isotope tracers) and hyperglycemic clamp studies in conscious, free moving, 19-23 week old female mice with implanted carotid artery and jugular vein catheters. As shown below, we found that GKAGRP KO females were insulin resistant with a lower dextrose infusion rate and reduced suppression of hepatic glucose production during euglycemic clamps. They also displayed reduced insulin secretory responses during hyperglycemic clamps. Our data support a sexually-dimorphic central gluco-regulatory role for AGRP neurons which requires the presence of GK to facilitate normal insulin release and action.

Disclosure

M.Josipovic: Research Support; Novo Nordisk A/S. E.O.Staricoff: Research Support; Novo Nordisk A/S. C.H.Riches: Research Support; Novo Nordisk. L.Sheppard: None. M.Evans: Advisory Panel; Pila Pharma, Zucara Therapeutics, Other Relationship; Abbott Diabetes, Dexcom, Inc., Medtronic, Novo Nordisk, Research Support; AstraZeneca, Sanofi, Speaker’s Bureau; Lilly Diabetes.

Funding

European Union’s Innovative Medicines Initiative 2 Joint Undertaking (grant agreement 777460) also supported by EFPIA, T1D Exchange, JDRF, International Diabetes Federation (IDF) , The Leona M. and Harry B. Helmsley Charitable Trust, Wellcome Trust, Medical Research Council UK and Gates Cambridge Trust.
1314-P: Activating GABAergic Neurons in the Caudal Preoptic Area Promote Energy Expenditure in Diet-Induced Obesity
Authors: BASU RASHMITA , ELMENDORF ANDREW J. , MAHLER CONNOR A. , FLAK JONATHAN
Published: May 2022

Obesity results from the imbalance between energy intake and energy expenditure, which are tightly regulated by dynamic hypothalamic circuits. Our goal is to identify and leverage hypothalamic components that promote energy expenditure for successful weight loss. Vesicular communication by ventromedial hypothalamic nucleus (VMN) steroidogenic factor 1 (Sf1) neurons is required for maintaining body weight, due at least in part to stimulating metabolic activity in adipose tissue, but the mechanistic details are unclear. VMNSf1 neurons efferently communicate with relatively few places in the brain but the most prominent projections are in the most caudal regions of the preoptic area (cPOA) (+0.1 to -0.3mm bregma, lateral to the suprachiasmatic nucleus) . We tested the hypothesis that GABAergic cPOA neurons promote energy expenditure and weight loss by activating either GABAergic or glutamatergic neurons via hM3dq, using vGATCre (vesicular GABAergic transporter) or vGLUT2Cre (vesicular glutamatergic transporter 2) in diet-induced obese male mice. Activating vGATcPOA neurons reduced body weight and adiposity without altering food intake. Activating vGLUT2cPOA neurons reduced body weight and food intake but did not reduce adiposity. Activating vGLUT2cPOA neurons reduced core body temperature, but not vGATcPOA neurons. We are currently investigating the mechanisms for how vGATcPOA neurons reduce adiposity. Weight loss is not likely mediated by direct inhibition of vGLUT2cPOA neurons because diet induced obese male mice with CNO-initiated signaling of hM4di in vglut2cPOA neurons does not reduce adiposity or body weight. Alternatively, vGATcPOA neurons may communicate with a distinct efferent system. Indeed, vGATcPOA, but not vGLUT2cPOA, neurons project to the lateral hypothalamus and medial raphe. Future studies will reveal the functional connection between VMNSf1 neurons and vGATcPOA neurons, and the descending circuitry that promotes energy expenditure.

Disclosure

R.Basu: None. A.J.Elmendorf: Research Support; Eli Lilly and Company. C.A.Mahler: Stock/Shareholder; AstraZeneca, Pfizer Inc. J.Flak: Research Support; Eli Lilly and Company.

Funding

American Diabetes Association (17-INI-15) ; IU CDMD NIH/NIDDK (P30 DK097512)
1325-P: Modulation of Overnight Free Fatty Acid and Glucose Concentrations and Their Effect on Postprandial Islet Function and Glucose Metabolism
Authors: WELCH ANDREW A. , SCHEMBRI WISMAYER DANIEL , EGAN AOIFE M. , FARAHANI RAHELE A. , LAURENTI MARCELLO C. , COBELLI CLAUDIO , DALLA MAN CHIARA , VELLA ADRIAN
Published: May 2022

Individuals with prediabetes can be classified by fasting and glucose tolerance status. Previously we observed that elevated fasting Free Fatty Acids (FFA) are associated with Impaired Glucose Tolerance (IGT) and decreased β-cell function (quantified as Disposition Index (DI)) . Impaired Fasting glucose (IFG) is associated with further decreases in DI. To examine how changes in fasting FFA and glucose alter islet function, we studied subjects with Normal Fasting Glucose (NFG) and Normal Glucose Tolerance (NGT) on 2 occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG / IGT. In addition, we studied 7 subjects with IFG / IGT on 2 occasions. On one occasion insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG / NGT. The 2 groups were matched for Body Mass Index (BMI: 32±3 vs. 31±2 kg/m2, NFG / NGT vs. IFG / IGT respectively, p = 0.87) . The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and β-cell function. Elevation of overnight fasting FFA and glucose in NFG / NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 hrs, Saline vs. Intralipid / glucose, p = 0.55) . In people with IFG / IGT, insulin also did not alter peak and integrated glucose concentrations (2.5 ± 0.1 vs. 2.5 ± 0.2 Mol per 5 hrs, Saline vs. Insulin, p = 0.39) . Changing overnight concentrations of glucose and FFA did not alter postprandial concentrations of insulin and C-peptide in either group. While fasting Endogenous Glucose Production (EGP) differed between groups (14 ± 1 vs. 18 ± 1 μmol/kg/min, NFG / NGT vs. IFG / IGT, p < 0.01) , intervention did not change fasting and nadir EGP. Peak and integrated meal appearance and DI were also unchanged by intervention in either group. We conclude that acute, overnight changes in FFA and glucose concentrations do not alter islet function or glucose metabolism in prediabetes.

Disclosure

A.A.Welch: None. D.Schembri wismayer: None. A.M.Egan: None. R.A.Farahani: None. M.C.Laurenti: None. C.Cobelli: None. C.Dalla man: Research Support; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. A.Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S, Other Relationship; Novo Nordisk.

Funding

NIH DK 078646
1356-P: Investigating the Metabolic Function of an Orphan G Protein–Coupled Receptor in the Intestinal Epithelium
Authors: REN HONGXIA
Published: May 2022

G protein-coupled receptors (GPCRs) in the gastrointestinal tract are involved in maintaining glucose and energy homeostasis by regulating the release of gut hormones in response to luminal dietary nutrients as well as microbial metabolites. We recently identified that an orphan GPCR, Gpr17, was co-expressed in glucagon-like peptide-1 (GLP-1) -expressing EECs in human and rodent intestinal epithelium. However, it is unknown how Gpr17 ablation in the intestinal epithelium affects feeding behavior and satiety regulation. To address this question, we used genetic knockout approach to generate intestinal Gpr17-deficient mice and analyzed their glucose metabolism and feeding behavior. We showed that intestinal Gpr17-deficient mice had similar growth curve, body composition, and ad libitum food intake compared with littermate controls. We found that acute genetic ablation of Gpr17 in intestinal epithelium (iKO) improved oral glucose tolerance and glucose-stimulated insulin secretion (GSIS) in female and male mice. iKO mice responded to glucose or lipid ingestion with increased secretion of GLP-1, but not the other incretin glucose-dependent insulinotropic polypeptide (GIP) . Intestinal Gpr17-deficient mice responded to fasting-refeeding challenge with reduced fasting locomotor activity and less food intake after refeeding, suggesting increased satiety during the phase of rebound hyperphagia. Furthermore, comprehensive studies including gut morphology, gut epithelium heterogeneity by scRNA-seq, and microbiome analysis were examined but none of them was changed because of intestinal Gpr17 ablation. In addition, male Gpr17 whole body knockout mice have improved intraperitoneal glucose tolerance, and increased insulin sensitivity in hyperinsulinemic-euglycemic clamp studies.

In conclusion, our work showed that ablation of intestinal Gpr17 signaling led to improved neurohormonal regulation to maintain metabolic homeostasis.

Disclosure

H.Ren: None.

Funding

National Institute of Health (R01DK120772)