bluuebunny/crossref_metadata_2025 huggingface dataset:
1176-P: A Population Shift in Meeting Glycemic Targets Following Five Years of a Very-Low-Carbohydrate Intervention (VLCI) and Continuous Remote Care (CRC)
Authors: VOLK BRITTANIE M. , MCKENZIE AMY L. , ATHINARAYANAN SHAMINIE J. , VANTIEGHEM MICHELLE , ADAMS REBECCA N. , ROBERTS CAROLINE G.P. , RATNER ROBERT E. , VOLEK JEFF , PHINNEY STEPHEN , HALLBERG SARAH
Published: May 2022

Background: We previously reported 1- and 2-year effectiveness of a VLCI via CRC. Here we assess the long term effectiveness of the treatment via achievement of A1c ≤6.5%, <7%, and <8% with and without antidiabetes medications at 5 years.

Research Design and Methods: Patients with T2D who initially enrolled in a 2-year non-randomized, controlled clinical trial and received a VLCI via CRC were offered 3 additional years of prospective follow-up. Of the 200 patients completing 2 years, 169 (84.5%) consented to extend; 122 (72.2%) were retained at 5 years. Among those who extended, McNemar's test was used to assess the change in percent of patients meeting glycemic targets from baseline to 5 years among completers and on an intent-to-treat basis.

Results: At 5 years, the percent of completing patients meeting glycemic goals improved across all defined targets (Table 1) . Of completing patients, 20% achieved diabetes remission, while 32.5% achieved an A1c <6.5% without the use of antidiabetes medications with the exception of metformin.

Conclusions: One fifth of completing patients achieved the international consensus criteria for diabetes remission at 5 years, which is unique among lifestyle interventions. The proportion of people at A1c goal increased, suggesting the VLCI delivered via CRC may be an effective, long-term strategy to improve population health.

Disclosure

B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.Hallberg: Advisory Panel; Atkins Nutritionals Inc., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.J.Athinarayanan: Employee; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. C.G.P.Roberts: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp. J.Volek: Advisory Panel; Abbott Diagnostics, Simply Good Foods, Stock/Shareholder; Virta Health Corp. S.Phinney: Employee; Virta Health Corp.
1181-P: Influence of Nutrients Consumed on Associations between the Gut Microbiota Composition and Type 2 Diabetes
Authors: TAMURA AYUMI , DAIMON MAKOTO , KAMBA AYA , MIZUSHIRI SATORU , MURABAYASHI MASAYA , NISHIYA YUKI , ITO RYOMA , ONO SHOMA
Published: May 2022

Objective: Upon food digestion, the gut microbiota plays a pivotal role in energy metabolism, affecting the development of type 2 diabetes (DM) . We aimed to examine the influence of nutrients consumed on the association between the gut microbiota and DM.

Research Design and Methods: Among participants of the population-based Iwaki study of Japanese held in 2016, those with information of gut microbiota (n=1148) were included. The following individuals were also excluded: over 77 years of age (excluded to minimize age-related diversity in gut microbiota as previously reported) , and were the 55 individuals with an incomplete data set. After these exclusions, 10individuals (403 men, 616 women) aged 52.4 ± 14.1 years were included in the present study.

Results: Compared with non diabetic subjects, diabetic subjects had larger proportions of the genera Bifidobacterium and Streptococcus but smaller proportions of the genera Roseburia and Blautia in their gut microbiotas. The genera Streptococcus and Roseburia were positively correlated with the amounts of energy (β= 0.064, p=0.0297) and of carbohydrate and fiber (β= 0.079, p=0.0069, and β=0.069, p=0.0129, respectively) consumed, respectively. In contrast, the genera Bifidobacterium and Blautia were not correlated with any nutrients consumed. Cluster analyses of these four genera revealed that the Blautia-dominant cluster was most protective against DM, whereas the Bifidobacterium-dominant cluster was a risk for DM, after adjustment for multiple factors including nutrients consumed (vs. the Blautia-dominant cluster; odd ratio 3.97, 95% confidence interval 1.68-9.36) .

Conclusions: Positive correlations of the genera Streptococcus and Roseburia indicate the possible involvement of nutrient factors in the association between the gut microbiota and DM. Furthermore, having a Bifidobacterium-dominant gut microbiota may be a risk for DM whereas having a Blautia-dominant gut microbiota may be protective against DM.

Disclosure

A.Tamura: None. M.Daimon: None. A.Kamba: None. S.Mizushiri: None. M.Murabayashi: None. Y.Nishiya: None. R.Ito: None. S.Ono: None.
1184-P: Adolescent Growth Spurt and Type 2 Diabetes Risk in an American Indian Population
Authors: RAMIREZ-LUZURIAGA MARIA J. , KOBES SAYUKO , SINHA MADHUMITA , KNOWLER WILLIAM C. , HANSON ROBERT L.
Published: May 2022

Background: Some studies suggest that earlier pubertal development is associated with obesity and metabolic disorders in adulthood, but whether accelerated adolescent linear growth spurt influences type 2 diabetes (T2D) in populations at high risk of diabetes is unclear.

Aim: To examine associations of age at initiation of the adolescent growth spurt (i.e., take-off) (ATO) , velocity at take-off (VTO) , and age at peak velocity (APV) with T2D incidence.

Methods: Height measurements obtained from a longitudinal study of diabetes in American Indians were used to estimate biological growth parameters using the Preece-Baines growth model I, a parametric model of the human growth curve. Diabetes incidence was analyzed among individuals who had ≥ 4 height examinations at ages 5-17 years and who remained nondiabetic at first examination after age 18. Participants were followed until diabetes developed or last examination. Associations of growth parameters with diabetes incidence were analyzed by Poisson regression.

Results: Among 649 originally nondiabetic participants, 135 females and 82 males developed diabetes in a median follow-up of years. With adjustment for age, birth date and maternal diabetes, younger ATO and APV were associated with T2D incidence in males (incidence rate ratio (IRR) =1.75 per year, 95% CI, 1.23, 2.50; and IRR=1.33, 95% CI, 1.01, 1.75, respectively) but not in females (IRR=0.93, 95% CI, 0.75, 1.16; and IRR=1.04, 95% CI, 0.86, 1.26, respectively) . Higher VTO was associated with T2D incidence in males (IRR=1.80 per cm/y, 95% CI, 1.15, 2.81) but not in females (IRR=1.15, 95% CI, 0.88, 1.50) . With further adjustment for adult and childhood BMI and fasting insulin, the associations were attenuated for APV and VTO but remained significant for ATO in males.

Conclusion: Our findings suggest that an early and accelerated adolescent growth spurt is a risk factor for T2D, at least in males. These associations are only partially explained by measures of adiposity and insulinemia.

Disclosure

M.J.Ramirez-luzuriaga: n/a. S.Kobes: None. M.Sinha: None. W.C.Knowler: None. R.L.Hanson: None.
1186-P: The Effect of Age on the Risk Relationship between Prediabetes and Mortality and Major Adverse Clinical Events
Authors: ZHANG XINGE , WU HONGJIANG , LAU ERIC S.H. , SHI MAI , FAN BAOQI , YANG AIMIN , CHOW ELAINE , KONG ALICE P. , CHAN JULIANA C. , MA RONALD C. , LUK ANDREA
Published: May 2022

Background: Prediabetes is associated with increased risk of cardiovascular disease (CVD) , kidney disease and death but the extent to which the risk associations between prediabetes and clinical events are modified by age is not known.

Methods: We conducted a retrospective analysis of a territory-wide diabetes surveillance dataset from the Hong Kong Hospital Authority including 2,692,880 individuals with at least one glycaemic measurement between 2000 and 2019. Prediabetes was defined according to the American Diabetes Association criteria. Proportional Cox regression was used to derive hazard ratios (HR) and 95% CI of prediabetes vs. normoglycaemic for incident CVD, end-stage kidney disease (ESKD) , all-site infection and all-cause death, stratified by baseline age categories (20-39, 40-59, 60-79 and ≥80 years) .

Results: Compared with people with normoglycaemia, people with prediabetes had greater hazards for clinical events in all age groups but the effect size attenuated with ascending age. In the youngest and in the oldest age categories, the respective HRs (95% CI) of prediabetes vs. normoglycaemia were 1.93 (1.71-2.17) and 1. (1.01-1.12) for CVD, 1.72 (1.42-2.08) and 1. (1.03-1.17) for ESKD, 1.48 (1.36-1.62) and 1. (1.00-1.08) for all-site infection, and, 1.52 (1.33-1.73) and 1. (1.04-1.10) for all-cause death. The associations remained after excluding people who later developed diabetes and after adjusting for metabolic factors.

Conclusion: Prediabetes increases the risk of major clinical events and death independent of subsequent development of diabetes and metabolic factors. The risk relationships between prediabetes and clinical events are stronger in young than older people.

Disclosure

X.Zhang: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. A.Luk: None. H.Wu: None. E.S.H.Lau: None. M.Shi: None. B.Fan: None. A.Yang: None. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. 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.
119-LB: Targeted IL-22 Improves Glucose Tolerance and Reduces Hepatic Steatosis and Hepatic Fibrosis in Murine Models of Diabetes and Liver Disease
Authors: PRINS JOHN B. , SAJIIR HARESSH , KESHVARI SAHAR , WONG KUAN YAU , LOCKETT JACK , MCGUCKIN MICHAEL , HASNAIN SUMAIRA Z.
Published: May 2022

The cytokine interleukin-22 (IL-22) is an inhibitor of cellular stress. In HFD murine models, systemic IL-22 is efficacious to restore glucose tolerance, reduce circulating triglycerides and hepatic steatosis, and improve AST:ALT ratio, but is also associated with gut and skin toxicity. As an approach to maintain efficacy without skin/gut adverse effects we have developed a prototype IL-22-based bispecific biologic drug candidate (IL-22-ScFv) which is targeted towards the pancreas and liver. In mouse models of T2D and NAFLD/NASH twice-weekly subcutaneous administration of IL-22-ScFv provides numerous therapeutic and metabolic benefits. After IL-22-ScFv administration for four weeks in HFD mice random glucose, glucose tolerance and insulin tolerance were normalised (c.f. chow fed controls) . Significant reduction in hepatic steatosis was also seen, evidenced by liver weight, histology, oil-red-O, and (normalisation of) key lipogenic gene expression patterns. In both Thioacetamide/HFD and Choline Deficient L-Amino acid defined/HFD mice IL-22-ScFv administration significantly reduced hepatic fibrosis (Masson’s trichrome, picrosirius red, and normalisation of hepatic expression of Col1a1&2, Col3a1, Timp2, Mmp2 and Cd68) . Effective targeting of IL-22 to liver and pancreas was observed with minimal IL-22 exposure to gut and skin. Following four weeks administration of a range of doses of IL-22-ScFv no adverse effects were observed. Histological analysis of gut and skin showed no features of hyperproliferation, consistent with effective targeting of IL-22 to liver and pancreas. Mechanism of action of IL-22-ScFv was again shown to be reduction in cellular stress via IL-22 receptor mediated STAT3 phosphorylation.

In conclusion, liver/pancreas targeted IL-22 shows promise as a therapeutic approach to metabolic liver disease, with concomitant improvement in disorders of glucose homeostasis.

Disclosure

J. B. Prins: None. H. Sajiir: None. S. Keshvari: None. K. Wong: None. J. Lockett: Advisory Panel; Lilly Diabetes. M. Mcguckin: None. S. Z. Hasnain: None.
119-OR: Metabolic Abnormalities across the Liver Fat Continuum: How Much Liver Fat Is “Normal”?
Authors: LE MINHDA , WU ELAINE (YILING) , BERRY JARETT , BROWNING JEFFREY , DELEMOS JAMES , NEELAND IAN , LINGVAY ILDIKO
Published: May 2022

Proton magnetic resonance spectroscopy (MRS) provides an accurate quantification of liver fat, but the threshold of 5.5% for “normal” is challenged. We evaluated the relationship between liver fat content and metabolic parameters to explore what might be a metabolically healthy liver fat content. We analyzed data from adult participants in the Dallas Heart Study who underwent clinical evaluation and liver fat quantification by MRS. We compared metabolic characteristics across groups stratified by liver fat quintiles using ANOVA for normal continuous variables, Kruskal-Wallis test for non-normal continuous variables, and Chi-square test for categorical variables. Mean age of the entire cohort was 44 years and 47% were men. Metabolic abnormalities were more prevalent across liver fat quintiles (p<0.0001) : BMI, weight, waist circumference, HTN, diabetes, cholesterol, triglycerides, CRP, leptin, fasting glucose, HOMA-IR, coronary artery calcium score, visceral fat, abdominal subcutaneous adipose tissue, and lower body subcutaneous adipose tissue (table) . Increase in these metabolic abnormalities was noticeable even between the lowest two quintiles. Clinically relevant metabolic abnormalities increased across all quintiles of liver fat, with increment occurring at well below what is currently considered “normal.” Our findings suggest that the presence of any liver fat may be abnormal.

Disclosure

M.Le: None. E.Wu: None. J.Berry: Consultant; Cooper Institute, Roche Diagnostics, Research Support; Abbott Diagnostics. J.Browning: None. J.Delemos: Advisory Panel; Eli Lilly and Company, Novo Nordisk. I.Neeland: Advisory Panel; Boehringer Ingelheim International GmbH, Merck & Co., Inc., Consultant; Nestlé Health Science. I.Lingvay: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Mannkind, TARGET PharmaSolutions; Valeritas;; Altimmune; DataRevive; Click; Medscape Duke CRI; Janssen Pharma; Bayer; Intercept, Novo Nordisk, Sanofi, Zealand Pharma A/S, Consultant; Novo Nordisk, Research Support; NovoNordisk; Mylan; Merck, Sanofi.
1191-P: Predictors of Hemoglobin A1c Testing in Adults with Type 2 Diabetes Covered by Alabama Medicaid
Authors: PRESLEY CAROLINE A. , HOWELL CARRIE R. , KHODNEVA YULIA , RIGGS KEVIN R. , HUANG LEI , LEVITAN EMILY B. , CHERRINGTON ANDREA
Published: May 2022

Background: ADA Standards of Care recommend A1C tests at least twice per year for patients with diabetes. We evaluated predictors of A1C testing among adults with type 2 diabetes covered by Alabama Medicaid.

Methods: We conducted a retrospective analysis of Medicaid claims data between 2011-2020 using person-year observations as the unit of analysis. Inclusion criteria were ages 19-64 years, type 2 diabetes diagnosis, continuous Medicaid enrollment for the full calendar year and the year prior. The primary outcomes were receiving ≥1 and ≥2 A1C test (s) during a calendar year. We conducted multivariable Poisson regression stratified by eligibility (i.e. disability, poverty) to evaluate the relationships of study year, demographics, clinical factors, and healthcare utilization with A1C tests using generalized estimating equations to account for individuals contributing >1 observations.

Results: We analyzed 288,379 person-year observations; 69% were female; 49% were Black; 47% were 35-54 years old, 44% 55-64 years old; 51% were eligible based on disability, 49% based on poverty. Overall, 57% observations had ≥1 A1C test per year, 35% had ≥2 A1C tests. More observations eligible by disability had ≥1 A1C test (76% vs. 38%) and ≥2 A1C tests (49% vs. 20%) than those eligible by poverty. For observations eligible by disability, Black race and older age were associated with higher likelihood of having ≥1 A1C test. For observations eligible by poverty, year after 2011, female sex, and younger age were associated with higher likelihood of having ≥1 A1C test. For both groups, rurality, insulin use, endocrinology care, diabetes complications, and ambulatory care visits were associated with higher likelihood of having ≥1 A1C test.

Conclusions: Just over one-third of adults with diabetes covered by Alabama Medicaid had at least 2 A1C tests per year. A1C testing frequency differed by Medicaid eligibility; poverty-based eligibility was associated with lower likelihood of having recommended A1C testing.

Disclosure

C.A.Presley: None. C.R.Howell: None. Y.Khodneva: None. K.R.Riggs: n/a. L.Huang: None. E.B.Levitan: Research Support; Amgen Inc. A.Cherrington: Consultant; Bayer AG, Other Relationship; Novo Nordisk.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases R18DK109501PI: CherringtonUAB Diabetes Research Center P30 DK079626PI: Cherrington
1192-P: Diabetes-Related Proteomic Alterations: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: ECHOUFFO TCHEUGUI JUSTIN B. , CHEN JINGSHA , ROONEY MARY R. , TANG OLIVE , BALLANTYNE CHRISTIE M. , BOERWINKLE ERIC , NDUMELE CHIADI E. , PANKOW JAMES S. , DEMMER RYAN , LUTSEY PAMELA , GRAMS MORGAN , SELVIN ELIZABETH , CORESH JOSEF
Published: May 2022

Introduction: There is a paucity of large-scale data from multiethnic populations on proteomic alterations related to type 2 diabetes, which could help identify prognostic mediators.

Method: We analyzed 4,955 plasma proteins using SomaLogic v4.0 on 10,478 ARIC Study participants (Visit 2, 1990-92, mean age: 57±6 years, 56% women, 22% Black adults, 14% with diabetes) . We used logistic regression to quantify proteins associations with prevalent diabetes in a 2/3 discovery and 1/3 validation subset, with Bonferroni correction of P-values.

Results: After adjustment for demographics, clinical, and lifestyle risk factors (Figure) , 642 proteins were significantly associated with diabetes in the discovery sample (p<10−6) , with 3confirmed in the validation sample (p<0.05/642) . The top five findings were semaphorin-6A, plexin-B2, inactive tyrosine-protein kinase 7, cartilage intermediate layer protein 2, and semaphorin-6B. Proteins with known diabetes associations were also identified : insulin receptor, insulin-like growth factor-binding protein 2, growth differentiation factor-15, and adiponectin.

Conclusions: A large-scale proteomics approach identified numerous diabetes-related alterations. Pathway analysis and comparison to proteomic risk factors for diabetes incidence and complications will shed light on plasma proteomic consequences of diabetes and their relation to future risk.

Disclosure

J.B.Echouffo tcheugui: None. P.Lutsey: None. M.Grams: None. E.Selvin: Other Relationship; Wolters Kluwer. J.Coresh: Consultant; Healthy.io Ltd, Research Support; National Institutes of Health. J.Chen: None. M.R.Rooney: None. O.Tang: None. C.M.Ballantyne: Consultant; Abbott Diagnostics, Althera Pharmaceuticals, Amarin Corporation, Amgen Inc., Arrowhead Pharmaceuticals, Inc., AstraZeneca, Corvidia Therapeutics, Denka Seiken, ESPERION Therapeutics, Inc., Genentech, Inc., Gilead Sciences, Inc., Illumina, Matinas BioPharma Inc, Merck & Co., Inc., New Amsterdam, Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Regeneron Pharmaceuticals Inc., Roche Diagnostics, Sanofi, Research Support; Abbott Diagnostics, Akcea Therapeutics, Amgen Inc., Arrowhead Pharmaceuticals, Inc., ESPERION Therapeutics, Inc., Ionis Pharmaceuticals, Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals Inc., Roche Diagnostics. E.Boerwinkle: None. C.E.Ndumele: None. J.S.Pankow: None. R.Demmer: None.

Funding

National Institutes of Health (K23 HL153774)
1196-P: Sex Difference in the Progression of Metabolic Syndrome Severity from Normoglycemia, Prediabetes, to Diabetes
Authors: YOSHIDA YILIN , CHEN ZHIPENG , BAUDIER ROBIN L. , KROUSEL-WOOD MARIE , ANDERSON AMANDA H. , FONSECA VIVIAN , MAUVAIS-JARVIS FRANCK
Published: May 2022

Aim: Evaluate if cardiovascular (CV) risk factors increase at a greater rate during the prediabetes (preDM) stage rather than the diabetes (DM) stage by sex.

Methods: We pooled data from the Atherosclerosis Risk in Communities Study and the Multi-Ethnic Study of Atherosclerosis. The CV risk outcome was the metabolic syndrome (MetS) severity z-score derived from components of waist circumference, HDL, triglycerides, SBP, and fasting glucose accounting for the weight of each component. The score was calculated for participants at visits 1 to 4 (3-year interval between visits) . We used linear mixed regressions to model the MetS z-score over time in men and women by levels of glucose (normal <100, preDM 100-125, DM ≥126 mg/dL) , adjusting for age, race, education, smoking, medication & cohort. A sex interaction was added to assess if the magnitude of risk factor changes over time differs by sex in each glucose level.

Results: Men and women had a greater rate of change in MetS severity during the preDM than the DM stage. Women had a significantly greater increase of MetS severity than men during the preDM stage, while men had a significantly greater increase in the DM stage than women.

Conclusion: A more rapid increase in MetS severity occurred in preDM than in DM. Women exhibited a faster increase in MetS severity compared to men during the preDM stage. Greater attention should be given to CV risk in women with preDM.

Disclosure

Y.Yoshida: None. Z.Chen: n/a. R.L.Baudier: None. M.Krousel-wood: None. A.H.Anderson: 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. F.Mauvais-jarvis: Consultant; Mithra Pharmaceutical.

Funding

NIH K12HD043451
12-OR: Preventing ß-Cell Death under Glucotoxic Conditions: The Role of ChREBPb
Authors: KATZ LIORA S. , BRILL GABRIEL , HERMAN MARK A. , GARCIA-OCANA ADOLFO , SCOTT DONALD
Published: May 2022

Glucotoxicity is a major mediator of β-cell dysfunction derived from prolonged hyperglycemia. A better understanding of glucotoxicity and preservation of β-cell mass are urgently needed. Carbohydrate response element binding protein (ChREBP) is a glucose-responsive, lipogenic transcription factor with two splice isoforms, ChREBPα and ChREBPβ. We previously showed ChREBPβ is induced by glucose and is required for glucose-stimulated β-cell proliferation in both rodent and human β-cells. In addition, we identified ChREBPβ as a marker for hyperglycemia in β-cells, with its nuclear expression reflecting the progression and severity of the diabetic state. Here, we demonstrate that β-cell death due to glucolipotoxicity (20 mM glucose + 1 mM palmitate) can be prevented by silencing ChREBPβ (6.5±3.1% TUNEL+/Insulin+ in ChREBPβ knock-out islets compared with 47.2±13.6% in control islets, N=7) , most likely via inhibition of lipogenesis and prevention of ceramide-mediated β-cell death. Furthermore, we generated mice with β-cell specific overexpression of ChREBPβ. These mice exhibited increased non-fasting blood glucose levels, impaired glucose tolerance and a marked decrease in β-cell mass, all in a gene dose-dependent manner (OE of one or two alleles of ChREBPβ, N=5) . ChREBPβ overexpression in human beta cells also mimicked glucotoxicity (93.6±3.1% TUNEL+/Insulin+, N=3) . Importantly, we show that ChREBPβ-mediated rodent and human β-cell death was rescued by co-expression with ChREBPα, or by pharmacological activation of Nrf2, a downstream effector of ChREBPα (6.6±1.9 and 2.8±0.9%, respectively, TUNEL+/Insulin+, N=3) . Altogether, our data demonstrate that ChREBPβ is a marker and a causative effector of glucotoxicity, and that downregulating ChREBPβ levels or upregulating ChREBPα levels or its downstream effector (NRF2) rescues β-cells from glucotoxicity. These results position ChREBPβ as a therapeutic target for the prevention of β-cell loss in T2D, an important unmet need in diabetes research.

Disclosure

L.S.Katz: None. G.Brill: None. M.A.Herman: Research Support; Eli Lilly and Company. A.Garcia-ocana: Consultant; Sun Pharmaceutical Industries Ltd. D.Scott: None.

Funding

NIH, R01DK130300NIH, R01DK114338NIH, R01DK108905
1202-P: Disparities in Incidence of Diagnosed Diabetes in Rural United States, 2011–2018
Authors: DUGANI SAGAR , LAHR BRIAN , BAILEY KENT R. , MIELKE MICHELLE M. , VELLA ADRIAN
Published: May 2022

US rural, compared to non-rural, populations have diabetes health disparities. However, it is unknown if there are rural disparities in incident diabetes. We used CDC data on incidence of diagnosed diabetes in adults aged ≥20 years, available for 97.5% of US counties (n=3145/3226) . Trends in the annual age-adjusted incident diabetes rate per 1000 adults (AADR) were assessed by weighted least squares regression. Year was fitted nonlinearly with a spline function, and AADR fold-change was tested by a model-based contrast of 20vs. 2018. The average AADR of 8.7 (95% CI 8.6-8.7) ranged from 9.3 (in 2011) to 8.3 (in 2013) and 8.9 (in 2018) , and concealed subnational disparities based on rurality (Figure) . In 2018, compared with 2011, the AADR decreased for large central metro counties (most urban) with AADR fold-change of 0.92 (0.91-0.93) but increased for noncore counties (most rural) with AADR fold-change of 1. (1.01-1.08) (both P<.01) . The AADR declined in counties with intermediate rurality except for micropolitan counties (no change; P=.56) . When stratified by region, the largest rural disparity in AADR was observed in the South, with smaller disparities in other regions.

In summary, from 2011-2018, rural counties had the highest overall AADR. The overall disparity in trends based on county rurality and the disparity in incidence in the rural South and rural West highlight areas for diabetes primary prevention interventions.

Disclosure

K.R. Bailey: None. M.M. Mielke: Consultant; Biogen, LabCorp. A. Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S. Other Relationship; Novo Nordisk.

Funding

National Institute on Minority Health and Health Disparities (NIH K23 MD016230)
1203-P: Association of Bone Mineral Density (BMD) with Prediabetes in a Biracial Cohort
Authors: LIU ZHAO , PATEL AVNISHA A. , DAGOGO-JACK SAMUEL
Published: May 2022

Background: Type 2 Diabetes (T2D) is associated with alterations in BMD, but association between prediabetes and BMD is less clear.

Subjects and Methods: We analyzed BMD in relation to demographic and metabolic parameters among the initially normoglycemic offspring of T2D parents in the POP-ABC (Pathobiology of Prediabetes in a Biracial Cohort) study. We further assessed the relationship between BMD and the risk of progression to prediabetes during 5 years of follow-up.

Results: A total of 376 participants underwent DEXA (Dual-energy X-ray absorptiometry) during Year 1 of POP-ABC and were followed quarterly for 5 years, the primary outcome being progression from normoglycemia to prediabetes. The mean age was 44.2 ± 10.6 years; BMI was 30.2 ± 7.23 kg/m2; 217 Black, 159 White, with 71% female. At baseline, the mean BMD was 1.176 ± 0.135 g/cm2 for the entire cohort; 1.230 ± 0.124 g/cm2 in men vs. 1.154 ± 0.134 g/cm2 in women (P<0.0001) ; 1.203 ± 0.114 g/cm2 in Black vs. 1.146 ± 0.150 g/cm2 in White participants (P=0.0003) . There was an inverse relationship between BMD and age (r= −0.254, P<0.0001) and a direct association with BMI (r=0.173, P=0.0028) and weight (r=0.315, P<0.0001) . The BMD showed no significant correlation with insulin secretion or insulin sensitivity. However, the BMD z score, which compares BMD to the average values for a person of same age and gender, was significantly correlated with risk of progression to prediabetes (r = 0.173, P=0.0029) and showed positive association with total body fat mass (r=0.208, p=0.0003) and trunk fat mass (r= 0.178, P= 0.0021) . BMD z score was not significantly correlated with either CRP or adiponectin level.

Conclusion: Among POP-ABC participants, BMD had the expected relationships with age, sex, and race. Higher BMD z score was predictive of progression to prediabetes among initially normoglycemic offspring of T2D parents during 5-year follow-up, an association that requires further mechanistic insights.

Disclosure

Z.Liu: None. A.A.Patel: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi.

Funding

American Diabetes Association (7-07-MN-13) ; National Institutes of Health (RDK067269)
1204-P: Evaluation of Mediation via the Physical Activity Environment of Neighborhood, Socioeconomic Environment, and Type 2 Diabetes Associations
Authors: MOON KATHERINE A. , NORDBERG CARA M. , ZHU AOWEN , UDDIN JALAL , LOPEZ PRISCILLA M. , ORSTAD STEPHANIE L. , SCHWARTZ MARK D. , RYAN VICTORIA , HIRSCH ANNEMARIE G. , SCHWARTZ BRIAN S. , CARSON APRIL P. , LONG D LEANN , MEEKER MELISSA A. , BROWN JANENE R. , LOVASI GINA S. , ADHIKARI SAMRACHANA , KANCHI RANIA , AVRAMOVIC SANJA , SIEGEL KAREN R. , POULSEN MELISSA N.
Published: May 2022

Inequitable access to neighborhood leisure-time physical activity (LTPA) resources may explain geographic disparities in type 2 diabetes (T2D) . We evaluated the LTPA environment as a potential mediating pathway through which the neighborhood socioeconomic environment (NSEE) affects T2D. We used harmonized measures and analytic approaches in three independent study samples in the Diabetes Location, Environmental Attributes, and Disparities Network: the national Veterans Administration Diabetes Risk (VADR) cohort, comprising electronic health records (EHR) of 4.1 million T2D-free veterans; Reasons for Geographic and Racial Differences in Stroke (REGARDS) , a national prospective cohort (n=11,2T2D-free) ; and a case-control study in the Geisinger EHR in Pennsylvania (15,888 T2D cases) . We measured NSEE with an index of census tract-level Census metrics (higher indicates disadvantage) . The LTPA environment was evaluated by PA facility density within street network buffers and population-weighted distance to parks. In models stratified by levels of community urbanicity, we estimated natural direct effects and indirect effects for each mediator. PA facility density mediated NSEE-T2D effects, but the magnitude and direction of the indirect effects differed by urbanicity and study sample. In rural communities, we found positive indirect effects via PA facility density (incidence rate difference [95% confidence interval] of NSEE quartile 4 vs. 1: 0.0[0.0038, 0.0099] in VADR; 1.53 [0.25, 3.05] in REGARDS) , representing a proportion mediated of 3% (VADR) and 51% (REGARDS) . We found small indirect effects for all other community types in VADR but none in the Geisinger sample. Distance to parks mediated NSEE-T2D effects only in VADR rural communities. Results suggest regional or population-specific differences in how and whether the LTPA environment mediates NSEE-T2D relations, which could support local T2D prevention efforts.

Disclosure

K.A. Moon: None. C.M. Nordberg: None. A. Zhu: Research Support; Amgen Inc. J. Uddin: None. P.M. Lopez: None. S.L. Orstad: None. M.D. Schwartz: None. V. Ryan: None. B.S. Schwartz: None. A.P. Carson: Research Support; Amgen Inc. D. Long: Research Support; Amgen Inc. J.R. Brown: None. G.S. Lovasi: None. S. Adhikari: Research Support; Johnson & Johnson. R. Kanchi: None. S. Avramovic: None. K.R. Siegel: None. M.N. Poulsen: None.

Funding

Centers for Disease Control (U01DP006293, Drexel University; U01DP006296, Geisinger-Johns Hopkins University; U01DP006299, New York University School of Medicine; U01DP006302, University of Alabama at Birmingham) .
1207-P: Hepatic Steatosis Index and Fibrosis-4 Scores in Relation to Cardiometabolic Risk in Healthy Offspring of Parents with Type 2 Diabetes
Authors: BARRETO BRIGIDA COLON , SIWAKOTI KRISHMITA , EDEOGA CHIMAROKE , EBENIBO SOTONTE , DAGOGO-JACK SAMUEL
Published: May 2022

We explored the association between nonalcoholic fatty liver disease and cardiometabolic risk and the impact of race/ethnicity among healthy offspring of parents with type 2 diabetes (T2D) . These post hoc analyses were conducted on baseline data from the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC study) . Participants (N 376) were normoglycemic (NGT) White (N159) and Black (N 217) adults, aged 18-75 years, with at least 1 parent with T2D. The presence of hepatic steatosis was estimated by hepatic steatosis index (HSI; 8 × ALT/AST + BMI + 2 if female) ; and for hepatic fibrosis, fibrosis-4 score (FIB-4; [age × AST]/[platelets count × √ALT]) . We determined the association between HSI and Fib-4 vs. markers of the metabolic syndrome (MetS) , using a modified definition in our NGT cohort (waist≥100cm in men, ≥88 cm in women; BP ≥ 120/80mmHg, triglycerides ≥150mg/dl, HDL ≤40 in men, ≤50 in women) . HSI did not differ by sex or race, showed no correlation with age, but correlated significantly with MetS components: waist (r= 0.77, P<0.0001; systolic BP (r= 0.246, P <0.0001;) ; HDL (r= −0.224, P<0.0001; triglycerides (r= 0.11, P= 0.0009) . HSI increased cumulatively with MetS markers. FIB-4 score showed no sex or ethnic disparities, and correlated with BMI (r= −0.17, P= 0.0015) , total fat mass (r= −0.13, P= 0.02) and HDL (r=0.11, P=0.044) but not waist, BP or triglycerides. Unlike HSI, Fib-4 showed no cumulative association with MetS markers. These findings were similar in Black and White participants. Our data from POPABC study indicate that HSI is an informative early marker of the link between hepatic steatosis and cardiometabolic risk in normoglycemic Black and White offspring of parents withT2D.

Disclosure

B.Colon barreto: None. K.Siwakoti: None. C.Edeoga: None. S.Ebenibo: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck & Co., Inc., Sanofi.

Funding

American Diabetes Association (7-07-MN-13) ; National Institutes of Health (R01 DK067269)
1210-P: Associations between HbA1c, Area Level Social Vulnerability, and Poor COVID-Outcomes
Authors: HOWELL CARRIE R. , ZHANG LI , WILLIAMS SHANQUELA , YI NENGJUN , GARVEY W. TIMOTHY , CHERRINGTON ANDREA
Published: May 2022

Background: HbA1c has been associated with COVID-poor outcomes in diabetic and non-diabetic populations, while patients living in census tracts with high levels of social vulnerability [measured using the CDC’s Social Vulnerability Index (SVI) ] have experienced poorer outcomes.

Objective: To examine associations between HbA1c, area level social vulnerability and poor COVID outcomes in patients who tested positive for COVID and were captured in the electronic medical record (EMR) at a large academic institution in the Southeastern United States.

Methods: HbA1c and SVI, collected up to 3 years prior to a positive COVID test, were extracted from the EMR. HbA1c and SVI were compared by poor outcome status [hospitalization, intensive care unit (ICU) admission, and mortality]. Bayesian logistic regression was used to examine associations between HbA1c [≤5.7%; 5.7%-<6.5%; and ≥6.5%], SVI [living in high SVI census tract vs low SVI tract] and each COVID outcome separately. Multivariable models were adjusted for sex, age, race, body mass index and diabetes status. Results presented as odds ratios (OR) and 95% confidence intervals (95% CI) .

Results: N=3,7patients were identified [mean age: 54 years (SD 16.3) , 60% female, 47% Black]. Patients with HbA1c ≥ 6.5% and those living in a high SVI census tract were more likely to experience a poor COVID outcome (p’s<0.0001) . In multivariable models, patients with HbA1c ≥ 6.5% had higher odds of hospitalization (OR 1.79, 95% CI 1.44-2.22) ; ICU admission (OR 2.13, 95% CI 1.78-2.55) ; and mortality (OR 1.60, 95% CI 1.12-2.28) . Patients living in a high SVI census tract had higher odds of hospitalization (OR 2.47, 95% CI 1.94-3.15) ; ICU admission (OR 2.58, 95% CI 2.12-3.14) ; and mortality (OR 2.07, 95% CI 1.39-3.09) .

Conclusion: HbA1c ≥6.5% and living in a census tract with high social vulnerability were independently associated with poor COVID-outcomes. Findings highlight the need to assess HbA1c and area level social determinants in the context of COVID.

Disclosure

C.R.Howell: None. L.Zhang: None. S.Williams: None. N.Yi: None. W.Garvey: Other Relationship; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Epitomee, JAZZ Pharmaceuticals, Novo Nordisk, Novo Nordisk, Pfizer Inc., Pfizer Inc. A.Cherrington: Consultant; Bayer AG, Other Relationship; Novo Nordisk.

Funding

This work was supported by funding from the National Institute on Minority Health and Health Disparities (U54MD008176) .
1215-P: Evaluating Alternate Bias Correction Methods in Estimating Diabetes Prevalence with Electronic Health Records
Authors: CONDERINO SARAH , ANTHOPOLOS REBECCCA , THORPE LORNA , CAI BO , SHAO HUI , ONG TOAN C. , CRUME TESSA L. , SCHWARTZ BRIAN S. , KIRCHNER H. LESTER , ROSENMAN MARC , ZHONG VICTOR W. , REYNOLDS KRISTI , PARK SEHO , UTIDJIAN LEVON H. , DIVERS JASMIN
Published: May 2022

Background: The Assessing the Burden of Diabetes by Type in Children, Adolescents and Young Adults (DiCAYA) Network aims to provide timely estimates of diabetes prevalence and incidence using large scale electronic health record (EHR) data. However, patients who self-select into health systems are likely to differ demographically and by health status than the overall source population of interest, which could limit the generalizability of surveillance estimates.

Methods: Using simulations, we evaluated the potential of established bias correction methods (inverse probability weighting, post stratification, raking and multilevel regression with post stratification (MRP)) to mitigate selection biases within EHR data. The EHR sample was assumed to have overrepresentation of younger, higher socioeconomic status (SES) and white individuals than the source. Simulations varied the selection processes (e.g. dependent on diabetes status) and misspecification in the adjustment methods. The performance of each method was assessed as the absolute difference between the estimated prevalence in the sample and true prevalence in the simulated source.

Results: When selection was dependent on demographics alone, the mean bias in the crude prevalence estimate was -0.7 percentage points (pp) . Each method performed well in removing this bias when demographics that affected selection were adequately accounted for. Biases remained when SES was misclassified in the adjustment process, with best performance seen for MRP (-0.5 pp) . When selection was dependent on diabetes status, the mean bias in the crude prevalence estimate was 1.3 pp and each method similarly worsened this bias (2.3 pp) .

Conclusions: These methods are easy to implement and can provide reliable surveillance estimates if factors that are associated with selection into the EHR can be accounted for. However, novel methods may be needed when selection is dependent on diabetes status or other unmeasured factors.

Disclosure

S.Conderino: None. M.Rosenman: None. V.W.Zhong: None. K.Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. S.Park: None. L.H.Utidjian: None. J.Divers: None. R.Anthopolos: None. L.Thorpe: None. B.Cai: None. H.Shao: Board Member; BRAVO4HEALTH, LLC. T.C.Ong: None. T.L.Crume: None. B.S.Schwartz: None. H.Kirchner: None.

Funding

Centers for Disease Control and Prevention (1 U18DP006633-01-00)
1216-P: Prevalence of SGLT2i and GLP1RA Use among U.S. Adults with Type 2 Diabetes
Authors: LIMONTE CHRISTINE , HALL YOSHIO , TRIKUDANATHAN SUBBULAXMI , TUTTLE KATHERINE R. , HIRSCH IRL B. , DE BOER IAN , ZELNICK LEILA
Published: May 2022

Objective: To determine the prevalence of sodium-glucose contransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP1RA) use among adults with type 2 diabetes (T2D) in the United States.

Methods: We studied adults with T2D and eGFR ≥30mL/min/1.73m2 who participated in the National Health and Nutrition Examination Survey (NHANES) , focusing on the 2017-2020 examination cycle. We tested prevalence of SGLT2i and GLP1RA use among subgroups based on demographic variables and relevant comorbidities, including chronic kidney disease (CKD) , congestive heart failure (CHF) , and atherosclerotic cardiovascular disease (ASCVD) . We compared use of SGLT2i and GLP1RA to other glucose-lowering medications and assessed trends from prior NHANES cycles.

Results: Among 1,375 participants studied in 2017-2020, mean age was 60 years, 46% were women, 13% self-identified as non-Hispanic Black, 10% self-identified as Mexican American, 37% had CKD, 8.5% had CHF, and 23% had ASCVD. The prevalence of SGLT2i and GLP1RA use was 5.8% and 4.4%, respectively. SGLT2i were used by 7.2% of adults with CKD or CHF, and GLP1RA were used by 3.5% of adults with ASCVD. Differences in SGLT2i or GLP1RA use were observed by age, race, ethnicity, and health insurance status. Biguanides, sulfonylureas, DPP-4 inhibitors, and insulin were used more frequently than SGLT2i or GLP1RA. Overall, prevalence of SGLT2i but not GLP1RA use increased significantly from 2013-2014 to 2017-2020.

Conclusions: SGLT2i and GLP1RA use is low among adults with T2D, including among those with strong indications. Enhanced implementation of these agents is crucial to improving kidney and cardiovascular outcomes and mitigating health disparities in T2D.

Disclosure

C.Limonte: None. Y.Hall: None. S.Trikudanathan: Research Support; Bionic pancreas, Bionic pancreas , Insulet Corporation, Insulet Corporation. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. I.De boer: Advisory Panel; AstraZeneca, Bayer AG, Cyclerion Therapeutics, Inc., George Clinical, Goldfinch Bio, Inc., Other Relationship; American Society of Nephrology, Research Support; Dexcom, Inc. L.Zelnick: None.

Funding

This work was supported by an unrestricted fund from the Northwest Kidney Centers. CPL was funded by NIDDK grant T32DK007467 and the American Kidney Fund Clinical Scientist in Nephrology grant program. Additional funding was provided by R01DK126373, R01DK125084, R01DK088762.
1217-P: The Impact of Diabetes on Mortality and Clinical Outcomes in Hospitalized Patients with COVID-in the Capital Region of Denmark
Authors: KLIIM-HANSEN VIVIAN , NYELAND MARTIN E. , GASBJERG LÆRKE S. , JIMENEZ-SOLEM ESPEN , PETERSEN TONNY S. , ELLEGAARD ANNE-MARIE , KNOP FILIP K. , CHRISTENSEN MIKKEL B.
Published: May 2022

During the COVID-pandemic, patients diagnosed with diabetes have been overrepresented among patients admitted to hospital with COVID-19. We explored the impact of diabetes on mortality and clinical outcomes in hospitalized patients with COVID-in the Capital Region of Denmark. All patients from the Capital Region of Denmark admitted to hospital with COVID-in the period from February 2020 to March 2021 were included. Patients with a diabetes diagnosis were compared to patients without a diabetes diagnosis in multivariable adjusted analyses. The primary outcome was death within 30 days from hospitalization. Secondary outcomes included time to discharge, use of oxygen treatment, referral to intensive care unit, and use of respirator. Among 3,997 hospital admitted patients, 1,186 had diabetes (1,090 type 2 diabetes; 96 type 1 diabetes) . The patients with diabetes were 59% men, 72±13 years (mean±standard deviation) with BMI 28±6.4 kg/m2, while patients without diabetes were 51% men, 67±years with BMI 26±5.8 kg/m2. Within 30 days, 292 (24.6%) patients with diabetes died compared to 521 (18.5%) without diabetes (adjusted odds ratio (aOR) 1.28 (95% CI 1.02-1.6) for death) . Patients with diabetes were 24% less likely to be discharged alive at any given time compared to patients without diabetes with a hazard ratio of 0.76 (0.70-0.81) . aOR for oxygen treatment was 1. (0.97-1.47) , for referral to intensive care unit 1.37 (1.01-1.85) , and for use of respirator 1. (0.86-1.65) . We found that hospitalized COVID-patients with diabetes had a 28% higher risk of dying within 30 days and were 19% more likely to receive intensive care treatment than hospitalized COVID-patients without diabetes.

Disclosure

V.Kliim-hansen: None. M.E.Nyeland: None. L.S.Gasbjerg: Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; Antag Therapeutics. E.Jimenez-solem: None. T.S.Petersen: None. A.Ellegaard: n/a. F.K.Knop: Advisory Panel; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Sanofi, ShouTi, Zucara Therapeutics, Consultant; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pharmacosmos A/S, Sanofi, ShouTi, Zealand Pharma A/S, Zucara Therapeutics, Research Support; AstraZeneca, Novo Nordisk, Sanofi, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Stock/Shareholder; Antag Therapeutics. M.B.Christensen: None.

Funding

Novo Nordisk Foundation (NNF20SA0062873)