bluuebunny/crossref_metadata_2025 huggingface dataset:
1405-P: Reproducibility for the Diagnosis of Abnormal Glucose Tolerance Is Excellent for A1C and Glycated Albumin but Only Moderate for Fructosamine
Authors: DE DIEU GATETE JEAN , SCHENK BLAYNE R. , HURSTON JAMAIICA , DUBOSE CHRISTOPHER , MABUNDO LILIAN , WORTHY CHARLITA , JAGANNATHAN RAM , SACKS DAVID B. , SUMNER ANNE E.
Published: June 2023

A1C represents glycated hemoglobin A and is a non-fasting measure of average glycemia which has been used since 2010 to diagnose abnormal glucose tolerance (Abnl-GT) (a summary term for diabetes and prediabetes). However, A1C may not correlate with average glucose in the presence of anemia, G6PD deficiency and certain hemoglobinopathies. Two non-fasting markers of glycemia which have been proposed as alternatives to A1C are fructosamine (FA) and glycated albumin (GA). FA is a measure of all plasma glycated proteins. Whereas GA is a subfraction of FA. Emerging data suggests that in the diagnosis of Abnl-GT, GA is superior to FA. Critical to the value of a diagnostic test is assessing reproducibility. Therefore, we examined the reproducibility of A1C, FA and GA by performing all three tests 9±4d (mean±SD) apart in 209 African-born Blacks living in the Washington, DC area. Diagnostic sensitivity of A1C, FA and GA for the detection of Abnl-GT was determined by thresholds at the upper quartile of each, specifically ≥5.7%, 235 umol/L and 14.6%, respectively. A1C was assessed by high performance liquid chromatography, FA by colorimetric nitroblue tetrazolium assay and GA by enzymatic assay. Coefficients of variation (CV) were calculated. Kappa statistic (k-statistic) was used to measure diagnostic reproducibility. Strength of agreement by k-statistic is: slight: 0.0 to 0.20, fair: 0.21-0.40, moderate: 0.41-0.60, substantial: 0.61-0.80; excellent: 0.81-1.0. The CV for A1C, FA and GA were: 2%, 3% and 2% respectively, and the k-statistics were: 0.86, 0.59, 0.89 respectively. In short, the diagnostic agreement between A1C and GA on different days was excellent but only moderate for FA. This may explain why GA appears to be a better measure of Abnl-GT than FA. Variation in FA may be greater than the variation in GA because FA encompasses all plasma proteins rather than specifically albumin.

Disclosure

J.Gatete: None. B.R.Schenk: None. J.Hurston: None. C.Dubose: None. L.Mabundo: None. C.Worthy: None. R.Jagannathan: None. D.B.Sacks: Other Relationship; Sebia, Trinity. A.E.Sumner: None.
1406-P: Trends in All-Cause and Cause-Specific Mortality in Older Adults With and Without Diabetes—A Territory-Wide Analysis in One Million Older Adults in Hong Kong
Authors: YANG AIMIN , SHI MAI , LAU ERIC S.H. , CHOW ELAINE , CHAN JULIANA C.
Published: June 2023

Objective: Nationwide data on trends in mortality in older adults with and without diabetes in Asia are lacking. We described the recent trends of all-cause and cause-specific (pneumonia, cardiovascular [CV], and cancer) mortality in adults aged ≥65 years in Hong Kong in 2014-2018.

Methods: We performed a territory-wide analysis in 1,152,418 elderlies who had at least one in- or out-patient attendance in the Hospital Authority. We used the Joinpoint regression to assess patterns of mortality rate.

Results: In 2014-2018, 354,357 (31.7%) and 763,488 (68.3%) old adults with and without diabetes were included respectively. All-cause death rate has declined in older adults with (458.7 vs. 431.2 events/10,000 person-years, average annual percent change [AAPC]: -3.1% [95% CI -4.2%, -2.1%]) and without (337.0 vs. 294.6 events/10,000 person-years, AAPC: -1.6% [-2.7, -0.4%]) diabetes. In 2018, compared with adults without diabetes, those with diabetes had higher all-cause mortality (1.4-fold), CV- (1.9-fold), and pneumonia-cause (1.3-fold) mortality. Pneumonia was the leading cause of death. CV death has declined significantly in old adults with with (AAPC: -5.5% [-6.8, -4.1%]) and without (AAPC: -5.8% [-8.6, -2.9%]) diabetes. There were no declines in cancer death in older adults with (AAPC: -1.6% [-2.7, 0.4%]) and without (AAPC: -1.6% [-2.7, 3.9%]) diabetes, while cancer death has surpassed CV death in old adults with diabetes. Cancer death has increased markedly in men with diabetes versus those without diabetes (AAPC: 2.9% [1.1, 4.6%] vs. 1.8% [-5.0, 1.4%]), particularly in the youngest-older adults (65-74 years) with diabetes.

Conclusions: One in 3 elderlies had diabetes. Overall, cardiovascular-death had declined in these elderlies. Although elderly people with diabetes had a greater decline in all-cause death, they had substantially higher risk of cancer-death than those without diabetes, especially in younger men.

Disclosure

A.Yang: None. M.Shi: None. E.S.H.Lau: None. E.Chow: Research Support; Medtronic, Merck KGaA, Speaker's Bureau; Novartis, Bayer Inc., Sanofi. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer Inc., Celltrion, Boehringer Ingelheim and Eli Lilly Alliance, Sanofi, Research Support; AstraZeneca, Servier Laboratories, Viatris Inc., Hua Medicine, Merck KGaA, Applied Therapeutics Inc., Lee Powder, Pfizer Inc., Speaker's Bureau; Novartis, Stock/Shareholder; GemVCare Ltd.
1411-P: Serum Adipocyte Fatty Acid–Binding Protein Is Related to the Development of Prediabetes—Tokushima Cohort Study
Authors: HATA AKIKO , AKI NANAKO , ICHIHARA TAKAKO , MINAGAWA TAKAKO , TAMURA AYAKO , KUWAMURA YUMI , FUNAKI MAKOTO
Published: June 2023

Adipocyte fatty acid-binding protein (A-FABP/FABP4) is abundantly expressed in mature adipocytes and presumably secreted into the plasma from these cells. Emerging evidence suggests that FABP4 may be involved in the development of insulin resistance. However, prospective cohort studies to prove their causative relationship are still limited. The aim of the present study was to investigate the association between serum concentration of FABP4 and incidence of prediabetes. Here we analyzed data of a prospective cohort study, which was conducted during 2008-2019 in Japan. A total of 527 subjects without prediabetes aged 20 to 60 years were followed up prospectively. Prediabetes was defined as either: 1) fasting plasma glucose ≥ 100 mg/dl, 2) HbA1c ≥ 5.7% or 3) medication for hyperglycemia. The subjects were divided into three categories based on the tertiles of baseline serum FABP4 for each sex (male: < 7.8, 7.8-11.3 and > 11.3 ng/ml, female: <10.0, 10.0-13.0 and > 13.0 ng/ml). The age- and sex-adjusted incidence of prediabetes significantly increased with increasing tertile of serum FABP4 level at baseline (P for trend<0.001). In multivariate analysis after adjusting for age, sex, BMI, smoking habit, alcohol intake, regular exercise, HDL cholesterol, triglycerides, family history of diabetes, and hypertension, the hazard ratio of prediabetes was 1.65 [95% confidence interval:1.09 to 2.50, P=0.02] in the highest tertile of baseline serum FABP4, when compared with the lowest tertile. In addition, serum FABP4 at baseline was significantly higher in the subjects who developed diabetes, rather than prediabetes, during the follow-up period. Our findings suggest that increased serum concentration of FABP4 is an independent predictor of the incidence of prediabetes in Japanese and is related to the severity of future glucose intolerance. These results imply that altered FABP4 may associate with disorders of glucose metabolism from the early stages.

Disclosure

A.Hata: None. N.Aki: None. T.Ichihara: None. T.Minagawa: None. A.Tamura: None. Y.Kuwamura: None. M.Funaki: Board Member; Mechanogenic, Inc.

Funding

Grants-in-Aid for Scientific Research (to M.F.); Japan Society for the Promotion of Science (25860439 to A.H.)
1412-P: Sleep Patterns and Metabolic Syndrome Severity among African Americans in the Jackson Heart Study
Authors: DUAN DAISY , JUN JONATHAN , AHIMA REXFORD , BERTONI ALAIN , REDLINE SUSAN , ECHOUFFO TCHEUGUI JUSTIN
Published: June 2023

Objective: To elucidate the relationship between sleep and metabolic dysfunction among African Americans, who are disproportionally affected by cardiometabolic diseases.

Methods: This is a cross-sectional analysis of participants in the Jackson Heart Sleep Ancillary Study (2012-2016) who completed 7-day actigraphy and home sleep apnea studies. We used linear regression to assess the associations between metabolic syndrome (MetS) and actigraphy-derived parameters including: sleep timing, total sleep duration and regularity (night-to-night variation measured by within-individual standard deviation in sleep duration), and sleep continuity (sleep maintenance efficiency and fragmentation index). We assessed MetS severity, expressed as a validated sex- and race/ethnicity-specific z-score (MetS-Z), given the high prevalence of each of the MetS components in this cohort. Models were adjusted for age, socioeconomic factors, physical activity, smoking, alcohol use, and the presence of moderate to severe obstructive sleep apnea.

Results: Among 660 participants (mean age 63 ± 11 yrs, 66% women, mean BMI 31.8 ± 6.9 kg/m2), mean sleep onset was 23:09 ± 1.4h, mid-sleep time was 2:54 ± 1.2h, total sleep duration was 6.7 ± 1.2h, median night-to-night variation was 1.2h (IQR 0.8-1.5), median sleep maintenance efficiency was 88.9% (IQR 85.6-91.4), median sleep fragmentation index was 28.5% (IQR 23.3-34) and mean MetS-Z score was 0.33 ± 1.1. In adjusted models, later mid-sleep time (β 0.09, p<0.01), increased variation in sleep duration (β 0.004, p<0.01), lower sleep maintenance efficiency (β -0.02, p=0.03), and higher sleep fragmentation index (β 0.01, p=0.02) were associated with higher MetS-Z.

Conclusions: Later sleep timing, irregular sleep duration, and poor sleep continuity were associated with higher MetS severity scores among African Americans, highlighting the importance of sleep and circadian disruption as factors that influence metabolic health.

Disclosure

D.Duan: None. J.Jun: None. R.Ahima: None. A.Bertoni: None. S.Redline: Consultant; Eli Lilly and Company, JAZZ Pharmaceuticals, Apnimed. J.Echouffo tcheugui: None.

Funding

National Institutes of Health (K23DK133690)
1413-P: Associations of Age at Menarche with Biomarkers of Inflammation and Glucose Metabolism in U.S. Adult Women—NHANES 1999–2018
Authors: SANTOS MARIA P. , ROMRELL AMANDA M. , BAZZANO LYDIA A. , CARMICHAEL OWEN , HE JIANG , LEY SYLVIA H.
Published: June 2023

Background: Early age at menarche (AAM) is a risk factor for type 2 diabetes later in life, but the pathways involved remain unknown. We examined the associations of AAM with C-reactive protein, fasting glucose, and fasting insulin among U.S. adult women free of diabetes in adulthood.

Methods: Using the National Health and Nutrition Examination Survey (NHANES) 1999-2018, 19,228 women over 20 years old, free of cancer and diabetes were included in our cross-sectional analysis. AAM was self-reported age of first menstruation. Multiple linear regression was performed on biomarkers measured in adulthood.

Results: The median age was 44 years (IQR, 33-62). Age-adjusted least-square means for AAM categories ≤10, 11, 12, 13, 14, and ≥15 years were 1.42, 1.08, 1.05, 0.80, 0.84, and 0.91 mg/L for C-reactive protein (P-trend=0.006); 84.85, 69.19, 68.11, 67.27, 64.42, and 60.69 pmol/L for fasting glucose (P-trend<0.0001); and 5.54, 5.45, 5.40, 5.39, 5.35, and 5.36 mmol/L fasting insulin (P-trend <0.0001), respectively. When models were further adjusted for demographic, reproductive, and lifestyle variables, the associations remained significant [Table].

Conclusion: Earlier age at menarche is associated with higher levels of C-reactive protein and poorer glucose metabolism in U.S. adult women free of diabetes.

Disclosure

M.P.Santos: None. A.M.Romrell: None. L.A.Bazzano: None. O.Carmichael: Advisory Panel; Novo Nordisk, Research Support; Eli Lilly and Company, Nestlé Health Science. J.He: None. S.H.Ley: None.

Funding

National Institutes of Health (T32HL158290)
1414-P: Stalling of Trends in Glycemic and Risk Factors Control in People with Type 2 Diabetes in Hong Kong in 2000–2019
Authors: WU HONGJIANG , LAU ERIC S.H. , YANG AIMIN , ZHANG XINGE , FAN BAOQI , MA RONALD C. , KONG ALICE P. , CHOW ELAINE , CHAN JULIANA C. , LUK ANDREA
Published: June 2023

Background: We aimed to examine trends in diabetes control in Hong Kong between 2000 and 2019.

Methods: We conducted a retrospective analysis of data from 360,202 people aged 20 years or older with type 2 diabetes who underwent a territory-wide Risk Assessment and Management Programme-Diabetes Mellitus (RAMP-DM) in primary and secondary settings in Hong Kong between 2000 and 2019. We examined trends in proportion of people with type 2 diabetes achieving target of glycemic control (hemoglobin A1c [HbA1c] <7.0%), blood-pressure control (systolic/diastolic blood pressures [SBP/DBP] <140/90 mm Hg), and lipid control (low-density lipoprotein cholesterol [LDL-C] <130 mg/dl).

Results: The proportion of people with type 2 diabetes who achieved HbA1c <7.0% increased from 40.3% (95% CI: 35.6%, 50.0%) in 2000 to 55.2% (54.4%, 56.0%) in 2014 and then leveled off thereafter. After improvements in blood-pressure control from 2000 to 2014, the proportion of people in whom blood pressure was achieved to below 140/90 mm Hg declined from 71.0% (70.4%, 71.6%) in 2014 to 63.5% (62.8%, 64.2%) in 2019. From 2000 to 2019, the proportion of people with LDL-C <130 mg/dl continued to increase from 32.6% (27.6%, 37.6%) to 59.9% (59.2%, 60.6%). The proportion of people in whom all three targets were simultaneously achieved increased from 9.5% (3.8%, 15.3%) in 2000 to 23.1% (22.1%, 24.1%) in 2014 and plateaued from 2014 to 2019. Conclusions: After major improvements from 2000 to 2014, glycemic control stalled and blood-pressure control declined in people with type 2 diabetes in Hong Kong, while there was a continued encouraging trend in lipid control.

Disclosure

H.Wu: None. A.Luk: Research Support; Novo Nordisk, Boehringer-Ingelheim, Bayer Inc., Speaker's Bureau; Eli Lilly and Company. E.S.H.Lau: None. A.Yang: None. X.Zhang: None. B.Fan: None. R.C.Ma: Advisory Panel; AstraZeneca, Merck & Co., Inc., Other Relationship; Bayer Inc., Boehringer-Ingelheim, Research Support; Tricida, Inc., Roche Diagnostics, Novo Nordisk. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Speaker's Bureau; Abbott, AstraZeneca, Lilly, Bayer Inc., Boehringer Ingelheim Inc. E.Chow: Research Support; Medtronic, Merck KGaA, Speaker's Bureau; Novartis, Bayer Inc., Sanofi. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer Inc., Celltrion, Boehringer Ingelheim and Eli Lilly Alliance, Sanofi, Research Support; AstraZeneca, Servier Laboratories, Viatris Inc., Hua Medicine, Merck KGaA, Applied Therapeutics Inc., Lee Powder, Pfizer Inc., Speaker's Bureau; Novartis, Stock/Shareholder; GemVCare Ltd.
1416-P: Differences in Treatment and Metabolic Outcome between Males and Females Living with T2D—Results from the Multicenter DPV Registry
Authors: TITTEL SASCHA R. , HESS GREGOR , MUEHLDORFER STEFFEN , GILLESSEN ANTON , JUNG RALF , KARL MANUELA D. , LANZINGER STEFANIE
Published: June 2023

To explore sex differences in diabetes therapy, outcome, and complications of adults with T2D in Germany. We included 77,587 individuals ≥18 years and ≥1 year of T2D duration that were treated between January 2019 and June 2022. Data was aggregated over the most recent treatment year and most recent diabetes therapy was evaluated. Age and diabetes duration-adjusted regression models are presented as estimated means with standard error mean. Median age was 71.1 [61.3 - 80.0] years, diabetes duration 11.5 [6.3 - 19.7] years, 55% male. Male patients were more often treated with insulin or OADs (51.3% vs. 50.5%, 28.1% vs. 26.5%, resp.). There were no sex differences in GLP1-RA treatment (male: 9.8%, female: 9.4%). SGLT2i treatment was significantly more frequent in males (18.4% vs. 12.2%). Females had a lower HbA1c compared with males, but a higher BMI. Dyslipidemia was more frequent in females compared with males, while hypertension was higher in males. We observed sex differences in treatment, especially newer OADs and GLP1-RA, metabolic control, and complications in all analyzed age groups. While women seem to be more affected by higher BMI and dyslipidemia, their metabolic control is better compared with males, although they have less medical treatment. Sex differences in compliance, adherence or disease perception could be the cause of these differences.

Disclosure

S.R.Tittel: None. G.Hess: Other Relationship; Novo Nordisk. S.Muehldorfer: None. A.Gillessen: None. R.Jung: Advisory Panel; Boehringer Ingelheim Inc., Speaker's Bureau; Novo Nordisk. M.D.Karl: None. S.Lanzinger: None.
1420-P: Predictors of Readmission and Mortality in Adults with Diabetes or Stress Hyperglycemia after Initial Hospitalization for COVID-19
Authors: CHAUGULE AKSHATA S. , HOWARD KYRA , SIMONSON DONALD C. , MCDONNELL MARIE E. , GARG RAJESH K. , GOPALAKRISHNAN GEETHA , MITRI JOANNA , LEBASTCHI JASMIN , PALERMO NADINE E. , WESTCOTT GREGORY P. , WEINSTOCK RUTH S.
Published: June 2023

Our consortium previously reported that older age, elevated glycemic gap, higher BMI and DKA on admission predicted mortality in adults with diabetes or stress hyperglycemia (glucose >180 mg/dl twice in 24 hrs) admitted with COVID-19 from March 2020 - February 2021 to 5 university hospitals. Here we examine those from this cohort who were readmitted (19.4%) after their initial discharge (Table). Of those readmitted 90.3% were readmitted within 30 days [median (IQR) 4 (0, 14) days]. Older age, lower eGFR, comorbidities, ICU admission, mechanical ventilation, DKA and longer length of stay during the initial hospitalization were associated with readmission. Higher A1c and admission glucose, diagnosed diabetes, glycemic gap and BMI did not predict increased risk of readmission. Hispanics were less likely to be readmitted. Mortality during readmission was 8.0%. Those who died were older than those who survived (74.9±9.5 vs 65.2±14.4 yrs, p= 0.002) and were more likely to have had DKA during the first hospitalization (p< 0.001). Mortality analyses were limited by the small number of deaths (n=23). In conclusion, in adults with diabetes or stress hyperglycemia hospitalized with COVID-19, older age and non-glycemic comorbidities were associated with the risk of readmission, while glycemic gap and higher A1c were not. These results are important for guiding treatment strategies.

Disclosure

A.S.Chaugule: None. G.P.Westcott: None. R.S.Weinstock: Consultant; Jaeb Center for Health Research, Other Relationship; Wolters Kluwer Health, Research Support; Insulet Corporation, Medtronic, Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Inc., Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases, Tandem Diabetes Care, Inc., Kowa Pharmaceuticals America, Inc. K.Howard: None. D.C.Simonson: Stock/Shareholder; Phase V Technologies, Inc., GI Windows. M.E.Mcdonnell: None. R.K.Garg: None. G.Gopalakrishnan: Research Support; Spruce Biosciences, Sparrow Pharmaceuticals Inc, Medtronic. J.Mitri: Other Relationship; Novo Nordisk, Research Support; Kowa Company, Ltd. J.Lebastchi: None. N.E.Palermo: Research Support; Dexcom, Inc.
1424-P: Imprecise Diagnosis of Diabetes Type in Youth
Authors: TOSUR MUSTAFA , HUANG XIAOFAN C. , INGLIS AUDREY S. , SCHNEIDER AGUIRRE REBECCA , REDONDO MARIA J.
Published: June 2023

Identifying diabetes (DM) type at the time of onset is important to establish the correct management but is increasingly difficult due to overlaps in characteristics between the most frequent DM types. We aimed to evaluate the prevalence and characteristics of youth with imprecise DM type at onset. In a large, tertiary, USA pediatric hospital, we studied (1) 2073 youth with new onset DM (Cohort 1: median age [IQR]: 11.4 [6.2] years, 50% male, 75% White, 21% Black, 37% Hispanic) and compared characteristics of those with DM that was classified by their treating endocrinologists as “unknown type” versus others; and (2) 1019 youth followed for ≥3 years since DM diagnosis (Cohort 2: median age [IQR]: 10.7 [5.7] years, 51% male, 77% White, 19% Black, 34% Hispanic), and compared characteristics of youth whose DM type changed between diagnosis and 3 years later, versus children whose DM classification did not change. In Cohort 1, “unknown” DM type appeared in 62 youth (3%), associated with older age, negative IA-2 antibody, lower C-peptide, and absence of diabetic ketoacidosis after adjustment for confounding factors. In Cohort 2, “changed” DM type appeared in 35 youth (3.4%), and, after adjusting for confounders, was not associated with any single characteristic. Other results are summarized in Table 1. In sum, DM type at onset is unknown or changes 3 years later in 6.5% of youth with DM. These findings warrant further research to optimize DM care in youth.

Disclosure

M.Tosur: Advisory Panel; Provention Bio, Inc. X.C.Huang: None. A.S.Inglis: None. R.Schneider aguirre: None. M.J.Redondo: None.

Funding

National Institutes of Health (R01DK124395 to M.J.R.), (K23DK129821 to M.T.)
143-LB: Preconception Counseling and Reproductive Education Program for Persons with Diabetes (PREPPD)
Authors: FALLURIN RESHMITHA , ROUVIERE MADELEINE , O'MALLEY GRENYE , RODRIGUEZ ORTEGA SUSEL , WANG ALLY W. , OGYAADU SELASSIE J. , LEVISTER CAMILLA , LAM DAVID W. , SHAH NIRALI , LEVY CAROL J.
Published: June 2023

Objective: Pregnancy without preparation in people with diabetes (PWD) can lead to adverse maternal and fetal outcomes. Improved patient knowledge through effective preconception counseling can help reduce the rate of complications. We developed a quality improvement initiative to improve both patient and provider knowledge.

Methods: Interventions were implemented for PWD and providers (HCPs) at 2 underserved clinics. HCPs completed pre-intervention questionnaires (highest score of 10) about management of diabetes in pregnancy and preconception goals followed by a training lecture. PWD aged 18-50 with reproductive potential were identified to receive a survey (highest score of 6) about preconception preparation, contraceptive use, glycemic targets, and safer medications in pregnancy. HCPs used a standardized template to guide counseling during visit. PWD and HCPs completed a follow up survey 3- 6 months later.

Results: Pre-intervention surveys were completed by 75 PWD and 16 HCPs. Documentation of preconception counseling by HCPs increased from 38% to 83% post intervention. Counseling was perceived as satisfactory by 83% of PWD.

Conclusion: Process measures have improved with our pregnancy focused QI initiative. Continued enrollment and post-intervention assessment as well as expansion to include adolescent PWD will enable us to further evaluate outcome measures.

Disclosure

R. Fallurin: None. C. J. Levy: Advisory Panel; Dexcom, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc., T1D Exchange. M. Rouviere: None. G. O'malley: Research Support; Dexcom, Inc., Abbott Diabetes, Tandem Diabetes Care, Inc., Omnipod, Eli Lilly and Company. S. Rodriguez ortega: None. A. W. Wang: None. S. J. Ogyaadu: None. C. Levister: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Abbott Diabetes. D. W. Lam: None. N. Shah: Research Support; Dexcom, Inc.
1434-P: Smoking, All-Cause, and Cause-Specific Mortality in Individuals with Type 2 Diabetes in Mexico—An Analysis of the Mexico City Prospective Study (MCPS)
Authors: RAMÍREZ-GARCÍA DANIEL , FERMÍN-MARTÍNEZ CARLOS A. , EDUARDO ANTONIO VILLA NEFTALI , VARGAS-VÁZQUEZ ARSENIO , FERNÁNDEZ CHIRINO LUISA , SEIGLIE JACQUELINE A. , YAXMEHEN BELLO-CHAVOLLA OMAR
Published: June 2023

Background: Cigarette smoking increases the already elevated risk of mortality observed in adults with type 2 diabetes but prospective data on the association between smoking and mortality among Mexican adults with type 2 diabetes are lacking.

Methods: We analyzed data from the MCPS, which surveyed 150,000 adults between 1998-2004. We performed Cox proportional hazard models and Fine and Gray sub distribution hazard models to estimate adjusted relative risk for all-cause and cause-specific mortality, respectively.

Results: Among 25,141 individuals with diabetes, 50.7% were never smokers, 26% former smokers, and 23.2% active smokers. Compared to non-smokers (Fig 1A), former smokers had an increased risk of all cause-mortality at 7.5 years of follow-up (HR 1.15 [95% CI 1.05-1.26]), with this risk receding completely after 7.5 years. Compared to non-smokers (Fig 1B), active smokers had a significantly higher risk of death after 7.5 years of follow-up (HR 1.17 [95% CI 1.07-1.28]), but not in the preceding 7.5 years. For cause-specific mortality, active smokers had an increased risk of death due to myocardial infarction, lung cancer, and COPD.

Conclusions: The risk of death among Mexican adults with type 2 diabetes varies over time and according to smoking status. Strategies to support sustained smoking cessation in people with type 2 diabetes are needed.

Disclosure

D.Ramírez-garcía: None. C.A.Fermín-martínez: None. N.Antonio villa: None. A.Vargas-vázquez: None. L.Fernández chirino: None. J.A.Seiglie: Consultant; BDMT Global, Techspert Expert Network. O.Bello-chavolla: None.
1436-P: Glycemic Variability as a Risk Factor for In-Hospital Mortality among CKD, Type 2 DM Patients Admitted for COVID-19—Retrospective Cohort Study
Authors: MANGUGAN NOREEN ADA G.
Published: June 2023

Background: COVID-19 severity is affected by multiple factors and it is theorized that better glycemic control results in lower mortality. Also, the use of glycemic variability through Time In Range (TIR) may be a better indicator of glycemic control.

Objective: To determine the association of glycemic control (ie TIR and HbA1c) during admission with in-hospital mortality among patients with COVID-19, CKD, and T2DM

Methods: A single center retrospective study was conducted on admitted CKD T2DM COVID patients from September 2020 to December 2021. Participants were excluded with mild COVID-19, post kidney transplant, no CBG monitoring, admitted for < 24 hours. A survival analysis was used to determine the association of glycemic control & mortality.

Results: Among 148 patients, 42.0% (n = 63) had in-hospital mortality. Glycemic control within range was achieved in 4.7% (4 out of 85) of the survivor group and 1.6% (1 out of 63) of the non survivor group and no significant difference noted between the two groups (HR 0.41 95% CI 0.06 to 3.03). For HbA1c level on admission, no significant difference between the two groups (HR 1.22 95% CI 0.74 to 2.01).

Conclusion: This study concluded that glycemic control did not show association with in-hospital mortality among CKD T2DM patients with COVID-19 infection. Additionally, HBA1c on admission was not associated with mortality.

Disclosure

N.G.Mangugan: None.
1441-P: Index60 Stratification Enhances Current Staging for Type 1 Diabetes by Identifying At-Risk Single Islet Autoantibody Positive (Ab+) Individuals
Authors: SIMS EMILY K. , CUTHBERTSON DAVID D. , BOSI EMANUELE , EVANS-MOLINA CARMELLA , REDONDO MARIA J. , NATHAN BRANDON M. , ISMAIL HEBA M. , JACOBSEN LAURA M. , SOSENKO JAY
Published: June 2023

The current staging system for T1D development is used for participant selection in prevention trials. This system is based on multiple Ab+ and the presence or absence of dysglycemia, but does not address C-peptide measures or single Ab+ individuals. Since a limited number of Ab+ individuals are available for trials, we used TrialNet Pathway to Prevention (TNPTP) study data to assess whether a composite glucose and C-peptide measure, Index60, could identify single Ab+ individuals (designated as Stage 0) with comparable risk to those in Stages 1 or 2 for progression to Stage 3. Table 1A compares normoglycemic Stage 0 individuals with Index60 values above the median (>-0.045) of the full TNPTP cohort (n=6107) vs. those at Stage 1 with Index60 below the median (< -0.045). Table 1B compares those at Stage 0 with dysglycemia and higher Index60 vs. those at Stage 2 with lower Index60. In both comparisons, Index60 stratification identified Stage 0 individuals with metabolic features characteristic of T1D (e.g., lower C-peptide with higher glucose) and comparable 5-year risk to Stage 1 or Stage 2 individuals. Thus, by considering individuals with 1 Ab and C-peptide measures, the current staging system could be improved for risk discernment and to identify appropriate eligibility for prevention trials.

Disclosure

E.K.Sims: Speaker's Bureau; Medscape, American Diabetes Association. D.D.Cuthbertson: None. E.Bosi: None. C.Evans-molina: Advisory Panel; Provention Bio, Inc., DiogenX, Avotres Inc., Neurodon, MaiCell Therapeutics, Other Relationship; Isla Technology, Bristol-Myers Squibb Company, Nimbus Therapeutics, Research Support; Lilly, Astellas Pharma Inc. M.J.Redondo: None. B.M.Nathan: None. H.M.Ismail: Consultant; Rise Therapeutics. L.M.Jacobsen: None. J.Sosenko: None.
1446-P: Success of a Hybrid Care Model to Maintain Glycemic Control in Older Adults with Type 1 Diabetes (T1D)
Authors: ADAM ATIF , MUNSHI MEDHA , HURLBERT REBECCA , SLYNE CHRISTINE , LAFFEL LORI M. , TOSCHI ELENA
Published: June 2023

Aim: During the COVID-19 pandemic, a hybrid care (in-office and telemedicine) model was urgently implemented. Impact of this hybrid model on clinical visit frequency and glycemic outcomes in older adults with T1D warrants study.

Methods: Demographics, clinical characteristics, and clinical visits of older adults (aged ≥65 years) with T1D were retrieved from electronic medical records covering 2 time periods, before the pandemic (pre-pandemic: April 1, 2019-March 1, 2020) and during the pandemic (pandemic: September 1, 2020 to August 31, 2021) periods, with adjustment for length of follow-up.

Results: 661 (45% male) unique older adults with T1D received care and had HbA1c measurements in both periods at a tertiary diabetes center. Mean age was 72±5 years; 59% were CGM users, 38% were pump users. Clinic visits in the pre-pandemic period were almost all in-person, averaging 4.2 visits/person/year (CI 3.9-4.4), with <2% as phone visits. During the pandemic period, the mean number of visits was significantly greater than in the pre-pandemic period, at 6.3 visits/person/year (CI 5.7-6.9), with 30% in-office, 38% by video, and 32% by phone. HbA1c values were similar between periods (pre-pandemic: 7.6% (CI 7.5-7.8) vs pandemic: 7.4% (CI 7.3-7.6)). However, there was a significant, favorable shift in HbA1c distribution <7%, 7-8%, >8% when using hybrid care model: pre-pandemic period 21, 42, 37%, respectively; pandemic period 35, 36, 29%, respectively (pre-pandemic vs pandemic period p<.0.001).

Conclusion: Compared with the pre-pandemic care model, the hybrid care model during pandemic for older adults with T1D allowed for increased visit frequency and preserved HbA1c values while favorably increasing the proportion with HbA1c <7% and decreasing proportion at the higher end of the distribution. This data support ongoing use of a hybrid care model for older adults with T1D.

Disclosure

A.Adam: None. M.Munshi: Consultant; Sanofi. R.Hurlbert: None. C.Slyne: None. L.M.Laffel: Advisory Panel; Medtronic, Lilly Diabetes, Novo Nordisk, Vertex Pharmaceuticals Incorporated, Roche Diagnostics, Provention Bio, Inc., Consultant; Dexcom, Inc., Janssen Pharmaceuticals, Inc., Medscape. E.Toschi: Advisory Panel; Eli Lilly and Company.

Funding

Thomas J. Beatson, Jr. Foundation
1447-P: Young Children with T1D on Three Continents—An Especially Vulnerable Group in Need of Specialized Health Care
Authors: TITTEL SASCHA R. , SANDY JESSICA L. , ROMPICHERLA SAKETH , KARGES BEATE , JAMES STEVEN , NOOR NUDRAT , ZIMMERMANN ANTHONY , MAAHS DAVID M. , HOLL REINHARD W. , CRAIG MARIA E. , EBEKOZIEN OSAGIE , FRÖHLICH-REITERER ELKE
Published: June 2023

We aimed to identify differences in care and outcomes of very young children with T1D onset from 3 multicenter registries from three continents: T1DX-QI (US), DPV (Germany/Austria/Switzerland/Luxembourg), and ADDN (Australia/New Zealand). These results are an update of 2,011 children of this age-group treated in 2011/2012 in European/US centers (Diabetologia 57:1578-585, 2014). For treatment years 2019-2021, there were 8,004 children with T1D <6 years of age in the 3 registries. The most recent treatment year per child was analyzed. To ensure data protection, analyses were pre-defined and conducted separately by each group. Age at onset, median diabetes duration and gender ratio, as well as anthropometry, and insulin requirement were very similar between the three registries (Table). In DPV, the vast majority of children in this age-group used insulin pumps and glucose sensors, followed by ADDN and T1DX-QI. HbA1c was lowest in DPV, followed by ADDN. Severe hypoglycemia and DKA were rare. Celiac disease was reported most often in Europe, while thyroid disease was more prevalent in the US. Both T1DX-QI and DPV improved metabolic control in this age-group compared to an analysis 10 years ago. However, the majority of children still do not reach currently recommended A1C levels. This young group of subjects needs extensive resources in terms of education, insulin dose adjustment, and family support.

Disclosure

S.R.Tittel: None. M.E.Craig: None. O.Ebekozien: Advisory Panel; Medtronic, Research Support; Eli Lilly and Company, Dexcom, Inc. E.Fröhlich-reiterer: None. J.L.Sandy: None. S.Rompicherla: None. B.Karges: None. S.James: None. N.Noor: None. A.Zimmermann: None. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. R.W.Holl: None.
1448-P: Diabetes-Related Complications and Comorbid Conditions in Older Adults with Type 1 Diabetes (T1D) in a Large Geographically Diverse Health Care System
Authors: KAHKOSKA ANNA , WEINSTEIN JOSHUA M. , MUTHUKKUMAR RASHMI , YOUNG LAURA A.
Published: June 2023

Older adults (age 65+) with T1D are an understudied population. Though many older adults may have long-standing diabetes and the prevalence of multimorbidity accumulates over the lifespan, the prevalence of diabetes-related complications and comorbid conditions in older adults with T1D have not been well-characterized, though these factors can affect quality of life. We analyzed electronic health record (EHR) data from older adults with T1D within a large public hospital system (n=560). We used ICD-10 diagnostic codes and calculated the proportion of the sample with different comorbidities and diabetes-related complications, as well as the average number of total complications and the Charlson Comorbidity Index Score (Table). The mean number of T1D-related complications was 3.93 with 29.6% (n=166) having 6+ concurrent T1D complications. The most common T1D complication was retinopathy or other ophthalmic complication with (72%; n=402). The median Charlson Comorbidity index score was 3. Nearly half of the sample (n=282; 50.4%) had cardiovascular disease and more than one third (n=197; 35%) had renal disease. These data underscore a high burden of diabetes complications and comorbidities among older adults with T1D. Understanding the medical complexity of this population can inform future research and intervention.

Disclosure

A.Kahkoska: None. J.M.Weinstein: Research Support; Dexcom, Inc. R.Muthukkumar: None. L.A.Young: Research Support; Novo Nordisk, Rhythm Pharmaceuticals, Inc., Eli Lilly and Company, Jaeb Center for Health Research, Sanofi, Boehringer-Ingelheim.

Funding

National Institutes of Health (KL2TR002490, UL1TR002489)
145-OR: Counterregulatory Response to Hypoglycemia Is Improved with Serotonin and Norepinephrine Reuptake Inhibitors
Authors: MACON ERICA L. , DEVORE MICAH H. , ILES ASHLEY , SCHOEDER LILY A. , PATEL BANSI , MUSIC MEGAN B. , FISHER SIMON
Published: June 2023

We previously reported that serotonin and norepinephrine reuptake inhibitors, amitriptyline (AMT) and imipramine (IMP), restored hypoglycemia awareness in rodents. To test the hypothesis that AMT and IMP could prevent the development of an impaired counterregulatory response (CRR) to hypoglycemia, Sprague-Dawley rats (250-350 g) with pre-implanted arterial and jugular cannulae were randomly assigned to one of four treatment groups: 1) recurrent saline controls (RS, n=8); 2) recurrent insulin-induced hypoglycemia (RH, 30-50 mg/dl, n=8); 3) RH + AMT (10 mg/kg IP, n=8); or 4) RH + IMP (5 mg/kg IP, n=8). Following 3-days of RS/RH treatment, all groups underwent 90-minute hyperinsulinemic (50 mU.kg-1.min-1) hypoglycemic (40-45 mg/dL) clamps. Blood glucose was similar for all groups during the clamp. Glucose infusion rates during the last 30-minutes were significantly reduced for both RH+AMT (23.7 mg/kg/min) and RH+IMP (24.8 mg/kg/min) as compared to RH (40.4 mg/kg/min), indicating that both drugs improved the glucoregulatory response to hypoglycemia. In conclusion, these studies identify 1) the involvement of serotonin and norepinephrine neurotransmitter pathways in the development of blunted counterregulatory responses to hypoglycemia, 2) in subjects with blunted CRR, these drugs may be useful therapeutic agents to improve the glucoregulatory response to hypoglycemia.

Disclosure

E.L.Macon: None. M.H.Devore: None. A.Iles: None. L.A.Schoeder: None. B.Patel: None. M.B.Music: None. S.Fisher: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (DK118082)
1450-P: Profiles of Glycemic Control in People with Type 1 Diabetes Using CGM—A Clustering Approach in the SFDT1 Study
Authors: COSSON EMMANUEL , AGUAYO GLORIA A. , SABLONE LAURA , HUET MATHILDE , RIVELINE JEAN-PIERRE , FAGHERAZZI GUY ,   SFDT1STUDY TEAM
Published: June 2023

CGM-derived data are usually analyzed in silos, metric by metric, for diabetes care or therapeutic strategy. Simultaneous analysis of the various dimensions of glycemic control would allow a more comprehensive overview. We analyzed data of people with type 1 diabetes (PWT1D) in the SFDT1 cohort study. A K-means clustering model was developed with HbA1c, coefficient of variation (CV), time in range (TIR), time below 70 mg/dl (TBR), Gold score and Glycemic Risk Index (GRI). We included 618 participants (53% men, age 41±14 years) from 20 centres in France. The optimal model had 3 clusters. The “Euglycemia” cluster (n=280, 45%) was characterized by a high TIR (mean 69.3%); low TBR ​​(4.2%), TAR (time above 180 mg/dl: 26.5%), CV (35.7%), HbA1c (7.0%) and GRI (36.4) values. The “Hyperglycaemia" cluster (n=197, 32%) was characterized by high TAR (56.5%), GRI (71.8) and HbA1c (8.5%) and low TIR (40.3%), TBR (3.2%) and Gold score (2.3). The “Hypoglycemia” cluster (n=141, 23%) was characterized by high TBR (15.8%), CV (46.1%), GRI (69.2) and Gold score (3.0). Participants in the “Hyperglycemia” cluster were younger, socially vulnerable, and had more frequent hypertension than those in the “Euglycemia” cluster. To conclude, we identified three distinct, clinically relevant glycemic control profiles, enabling better characterization of PWT1D and, thus, more personalised management.

Disclosure

E.Cosson: Board Member; Abbott, Medtronic. G.A.Aguayo: None. L.Sablone: None. M.Huet: None. J.Riveline: Board Member; Abbott Diabetes, Medtronic, Dexcom, Inc., Novo Nordisk, Eli Lilly and Company, Sanofi. G.Fagherazzi: Advisory Panel; Roche Diabetes Care, Consultant; AbbVie Inc., Lilly. Sfdt1 study team: n/a.
1453-P: Remedy to Diabetes Distress (R2D2)—Identify the Relationship between HbA1c, Socioeconomic Status (SES), and Diabetes Distress (DD)
Authors: POMERANTZ RHIANNON , WILLIAMS DAVID D. , YEH HUNG-WEN , CLEMENTS MARK A. , PATTON SUSANA R.
Published: June 2023

Objective: DD among school-age children with Type 1 Diabetes (T1D) and their parents is associated with suboptimal glycemic control. We sought to determine if SES modulates the association between parent distress and child HbA1c.

Methods: Parents completed the Problem Areas in Diabetes-Child (P-PAID-C) and reported family demographics. We measured child HbA1c using a validated fingerstick homekit. We calculated a Hollingshead Score to quantify family SES. We developed a multivariable regression model with child HbA1c as the outcome and Hollingshead Tertiles (lowest = tertile 1) and P-PAID-C scores as predictors.

Results: The sample included N = 158 parent-child dyads,[M ± SD] child age 10.20±1.49 years, HbA1c 7.96±1.63%, 50% boys, 9.3% Black, 6.2% Hispanic; 88.8% of respondents were mothers. P-PAID-C score was 59.0±18.0. Simple correlations suggested higher child HbA1c associated with higher P-PAID-C scores and lower SES. Regression results showed P-PAID-C scores as the strongest predictor of child HbA1c even when including SES and an interaction variable. (Figure.1)

Conclusion: Child HbA1c increases as a function of parent DD, but family SES does not modify this association. Parent DD may represent a treatable, underscoring a need for research testing interventions to reduce parent DD levels.

Disclosure

R.Pomerantz: None. D.D.Williams: None. H.Yeh: None. M.A.Clements: Consultant; Glooko, Inc., Research Support; Dexcom, Inc., Abbott Diabetes. S.R.Patton: None.
1457-P: Analysis of Type 1 Diabetes Trends in Israel
Authors: DUSKIN-BITAN HADAR , TIROSH AMIR , BECKENSTEIN TANYA , NETZER DORON , ARBEL RONEN , PERETZ ALON
Published: June 2023

Background and Aim: With increased awareness of late-onset type 1 diabetes and the importance of accurate diabetes classification, there is a need to reassess the epidemiological and clinical characteristics of people with T1D (PwT1D). We report analyses of a novel population based cohort of PwT1D in Israel.

Methods: Using database of Clalit HMO in Israel, insuring 4.8M people (51.5% of the population) we established a registry of all PwT1D. Prevalence, annual incidence, assessment of anthropometric, metabolic parameters, complications, and comorbidities were analyzed.

Results: We recorded data of 13,167 PwT1D (0.27% of the population, 51.3% men), with an annual incidence of 1.05/10,000 people representing a 13% increase over the past decade. Median age at diagnosis is 22 years with 25% diagnosed at age ≥40 years. Median age of current PwT1D is 36 years with 25% are ≥55. Of note, 50% are either overweight or obese, with over 50% having metabolic abnormalities, traditionally associated with type 2 diabetes. Hypothyroidism (16.1%) and Celiac disease (4.5%) are the most prevalent autoimmune diseases in this cohort. Additional characteristics are depicted in table 1.

Conclusion: Currently, a significant proportion of PwT1D are middle aged or older, half are overweight or obese with the majority having additional characteristics of the metabolic syndrome. Efforts for accurate classification of PwT1D and addressing associated comorbidities are of key importance.

Disclosure

H.Duskin-bitan: None. A.Tirosh: Advisory Panel; Medtronic, Novo Nordisk, Sanofi, Eli Lilly and Company, Research Support; Medtronic, Sanofi, Speaker's Bureau; Medtronic, Novo Nordisk, Sanofi, Eli Lilly and Company. T.Beckenstein: None. D.Netzer: None. R.Arbel: None. A.Peretz: None.
1458-P: Challenges for the Diagnostic Classification of Type 1 Diabetes (T1D) among Older Adults in Electronic Health Record (EHR) Data
Authors: WEINSTEIN JOSHUA M. , MUTHUKKUMAR RASHMI , YOUNG LAURA A. , KAHKOSKA ANNA R.
Published: June 2023

As T1D treatments improve and the US population ages, there is a growing number of older adults (≥65 years) with T1D. This patient population is distinct from their T2D counterparts yet remains understudied. Analyzing routine health care may yield real-world evidence to augment trial data and inform best practices. Yet, it is essential to properly classify patients with T1D vs. T2D. We aimed to assess the extent to which codes for T1D versus T2D overlap in EHR data among older adults with diabetes and assess the implications for identifying older adults with T1D, specifically. We analyzed electronic health record (EHR) data from a large, public health care system in the southeast US, including 12 affiliated hospitals and over 200 academic and community-based practices. We included data from adults ages 65+ years that had at least one code for T1D or T2D. Of the 7,436 patients withT1D or T2D listed among their medical conditions, 7,253 (97.5%) had a diagnostic code for T2D and 895 (12.0%) had a diagnostic code for T1D. Of those with a T1D code, 787 (87.9%) also had at least one T2D code. Among those with a code for T1D, the mean percentage of codes that indicate T1D is 49.4%. There is a high degree of co-occurring T1D and T2D diagnosis codes in EHR profiles of older adults, with implications for clinical care and research. Cohort classification in diabetes-oriented RWE studies warrants further research.

Disclosure

J.M.Weinstein: Research Support; Dexcom, Inc. R.Muthukkumar: None. L.A.Young: Research Support; Novo Nordisk, Rhythm Pharmaceuticals, Inc., Eli Lilly and Company, Jaeb Center for Health Research, Sanofi, Boehringer-Ingelheim. A.R.Kahkoska: None.

Funding

National Institutes of Health (KL2TR002490, UL1TR002489)
1460-P: Prevalence of Chronic Kidney Disease Associated with Type 1 Diabetes in the U.S.
Authors: ROSSING PETER , GROOP PER-HENRIK , SINGH RAKESH , LAWATSCHECK ROBERT , TUTTLE KATHERINE R.
Published: June 2023

Background: Chronic kidney disease (CKD) is associated with an increased risk of kidney failure, cardiovascular events, and mortality in patients with type 1 diabetes (T1D). However, the prevalence of CKD associated with T1D in the US is unclear. The aim of this study was to estimate the prevalence of CKD in people with T1D in the US using data collected in the National Health Examinations Survey (NHANES).

Methods: People with T1D were identified from NHANES using an established algorithm (Mosslemi et al. Cardiovasc Endocrinol Metab. 2020). Adults aged ≥18 years with CKD in this group were identified by single measurements of estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. The NHANES data were used to create corresponding weighted variables to represent the US

Results: During 2015 to 2018, diabetes was identified in 1647 of 19,225 adults surveyed in NHANES. Among those with diabetes, CKD was present in 20 out of 47 people with T1D with evaluable eGFR and UACR, corresponding to an unweighted estimate of 43%. CKD status was uncertain in 7 patients with T1D as their eGFR and/or UACR measurements were not available (unweighted estimate). In the CKD and T1D group, 59% were male and 60% were non-Hispanic White (weighted characteristics). Mean eGFR (SD) was 57 (4) mL/min/1.73 m2 and median UACR (IQR) was 89 (8-875) mg/g (weighted characteristics). Since the weighted overall number of adult people with T1D in the US was estimated at 1,202,739 (95% CI: 681,820-1,723,657), the corresponding number with T1D and CKD with evaluable eGFR and UACR was 258,196 (95% CI: 71,189-445,203), corresponding to a weighted estimate of 21%.

Conclusions: CKD was common in people with T1D and evaluable eGFR and UACR based on recent US data. Since the absolute number in NHANES was small, these prevalence estimates should be interpreted cautiously and validated in other cohorts.

Disclosure

P.Rossing: Other Relationship; Abbott Diagnostics, AstraZeneca, Bayer Inc., Boehringer Ingelheim Inc., Novo Nordisk, Merck KGaA, Gilead Sciences, Inc., Sanofi. P.Groop: Advisory Panel; Boehringer-Ingelheim, Bayer Inc., Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Bayer Inc., Merck Sharp & Dohme Corp., Medscape, Nestlé Health Science. R.Singh: None. R.Lawatscheck: Employee; Bayer Inc. K.R.Tuttle: Consultant; Lilly, AstraZeneca, Gilead Sciences, Inc., Research Support; Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Novo Nordisk, Goldfinch Bio, Inc., Traveere Pharmaceuticals.

Funding

Bayer AG