bluuebunny/crossref_metadata_2025 huggingface dataset:
1033-P: An Interactive Capacity Planning Dashboard for Algorithm-Enabled Telemedicine-Based Diabetes Care
Authors: CHANG ANNETTE , GAO MICHAEL Z. , FERSTAD JOHANNES , MAAHS DAVID M. , PRAHALAD PRIYA , JOHARI RAMESH , SCHEINKER DAVID
Published: May 2022

We previously showed that the use of a tool for remote analysis of continuous glucose monitor data, Timely Interventions for Diabetes Excellence (TIDE) , was associated with improved glucose management for patients with type 1 diabetes. To facilitate the deployment of TIDE at two partner institutions, we developed an operational planning tool.

We designed an interactive dashboard to match capacity and demand with a variety of operational, population, and workforce parameters. To improve the dashboard’s accessibility, simplicity, and interpretability, we performed iterative design based on feedback from users and two partner institutions. We set parameter values based on the first deployment of TIDE and conducted sensitivity analyses of the capacity-demand match.

The dashboard (Figure 1) contains seven modifiable parameters; generates a table illustrating the match between capacity and demand; displays a timeseries plot of capacity and demand; and calculates three alternative capacity plans that satisfy annual patient demand. It is available online (www.bit.ly/surf-tide) . Small absolute reductions in per-patient review time produced the most significant changes in clinic capacity.

We developed an interactive dashboard that facilitates data-driven operational planning for clinics seeking to deploy algorithm-enabled telemedicine-based diabetes care.

Figure 1. Capacity Planning Dashboard

Disclosure

A.Chang: None. M.Z.Gao: None. J.Ferstad: None. D.M.Maahs: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Sanofi, Consultant; Aditx Therapeutics, Inc., Biospex. P.Prahalad: None. R.Johari: None. D.Scheinker: None.

Funding

NIH R18DK122422
104-OR: Association of Neighborhood Deprivation and Gestational Diabetes Mellitus
Authors: LIU EMILY F. , SRIDHAR SNEHA B. , FERRARA ASSIAMIRA , GREENBERG MARA , HEDDERSON MONIQUE M.
Published: May 2022

A more comprehensive understanding of gestational diabetes mellitus (GDM) risk factors is needed given its increasing incidence and association with adverse maternal and fetal outcomes. Physical and social environments may play an important role in GDM because of their relationship to known risk factors such as physical activity, diet, and other lifestyle behaviors. We used logistic regression to examine the relationship between neighborhood deprivation index (NDI) , a composite score employing US Census indicators of education, income and poverty, employment, housing, and occupation, and GDM in a large and racially diverse cohort of livebirths between 20 and 2018 (n = 167,287) in Kaiser Permanente Northern California. GDM was defined by the Carpenter and Coustan criteria. Overall, 12,238 (7.4%) of pregnancies had GDM. When stratified by quartiles of NDI, GDM prevalence increased with neighborhood deprivation -- from 2,674 (6.5%) in the least deprived quartile to 3,432 (8.3%) in the most deprived quartile. Adjusted model results showed increased GDM risk as higher neighborhood deprivation quartiles were compared to the least deprived quartile (Table 1) . The test for linear trend was statistically significant (p≤0.05) .

In conclusion, additional emphasis should be placed on social determinants of health prior and during pregnancy when evaluating GDM risk and working towards health equity in maternal and fetal outcomes.

Disclosure

E.F.Liu: None. S.B.Sridhar: None. A.Ferrara: n/a. M.Greenberg: None. M.M.Hedderson: None.

Funding

Kaiser Permanente Health Policy and Disparities Research Program grant
1047-P: To Assess the Physiological Changes of Glucose Metabolism Associated with Increased BMI in Pregnancy
Authors: LINDER TINA , EPPEL DANIEL , MONOD CÉCILE , KOTZAERIDI GRAMMATA , TURA ANDREA , GÖBL CHRISTIAN S.
Published: May 2022

Background: Maternal overweight is a risk factor for Gestational Diabetes Mellitus (GDM) . However, there is emerging evidence that increased maternal BMI has considerable impact on the development of large for gestational age (LGA) offspring even in women who do not develop GDM, possibly related to subtle impairments in glucose metabolism. This study aims to assess physiological changes associated with increased BMI.

Methods: 21 women with overweight and 21 normal weight controls were included in this explorative study and received a metabolic assessment at early pregnancy (13.3 weeks) (Visit 1) , including a 60 min frequently sampled intravenous glucose tolerance test (FSIGT) . An OGTT was performed between 24 and 28 weeks of gestation (Visit 2) in women who remained normal glucose tolerant.

Results: At V1 mothers with overweight showed significantly elevated fasting glucose and HbA1c values, a well as impaired insulin sensitivity at fasting condition and dynamically assessed during the FSIGT, whereby the Calculated Insulin Sensitivity index (CSI) was lower in the overweight group as compared to normal weight controls (3.5 vs. 6.7 10-4⋅[μU/mL]-1⋅min-1, p=0.025) . The Disposition Index (DI) as a parameter of β-cell function was significantly decreased in mothers with overweight. Likewise, maternal BMI was inversely related to fasting (rho=0.56, p=0.005) and dynamically assessed insulin sensitivity (rho=0.51, p=0.014) as well as the DI (rho=0.51, p=0.014) and the AUC of glucose (rho=0.66, p<0.001) and C-Peptide (rho=0.46, p=0.020) during the OGTT in mothers who remained normal glucose tolerant during pregnancy at V2.

Conclusions: Increased maternal BMI is associated to insulin resistance and impaired β-cell function already at early pregnancy. We also observed that maternal BMI was associated with impaired glucose metabolism and especially elevated glucose levels during the OGTT at mid gestation in women who did not develop GDM and remained normal glucose tolerant.

Disclosure

T.Linder: None. D.Eppel: None. C.Monod: None. G.Kotzaeridi: None. A.Tura: None. C.S.Göbl: Research Support; Dexcom, Inc., Sanofi.
1049-P: Outcomes for Macrosomic Births by Maternal Diabetes Status
Authors: FITCH KATHERINE , HERSH ALYSSA R. , GARG BHARTI , VALENT AMY M.
Published: May 2022

Objective: To determine obstetric outcomes by birthweight (BW) among individuals with and without diabetes mellitus (gestational or pre-existing diabetes) in pregnancy.

Study Design: Retrospective cohort study of singleton, non-anomalous, live births in the U.S. from 2012-2018 registered in the National Vital Statistics System. Infants weighing > 3,000g at 37-42 week gestation were included. BW was stratified into four categories: 3,000-3,999g, 4,000-4,499g, 4,500-4,999g and ≥5,000g. Association of BW with outcomes was examined among women with and without diabetes mellitus (DM) . Chi-squared and multivariable logistic regression analyses were performed for statistical comparisons.

Results: Of 18,397,3deliveries included in this analysis, 6.3% had DM. Higher BW were associated with higher odds of cesarean delivery, maternal blood transfusion, anal sphincter injury, APGAR <7 at 5 minutes, NICU admission, and assisted ventilation. At ≥5,000g, there were higher odds of neonatal seizures and death. Although findings among pregnant persons without DM were similar, the strength of association for most adverse perinatal outcomes was greater among persons with DM.

Conclusion: Fetal macrosomia is associated with significant adverse perinatal outcomes, with even greater odds among deliveries impacted by maternal DM. Prenatal intervention studies to optimize pregnancy health are necessary to improve perinatal outcomes.

Disclosure

K.Fitch: None. A.R.Hersh: None. B.Garg: None. A.M.Valent: None.
1054-P: Dietary Fat Intake Is Not Associated with Increased Insulin Resistance among Pregnant Women
Authors: ROSENBERG EMILY A. , SEELY ELLEN W. , THAWEETHAI TANAYOTT , JAMES KAITLYN , YU CHU , CALLAHAN MICHAEL J. , NELSON STACEY , POWE CAMILLE E.
Published: May 2022

Background: Dietary modification in gestational diabetes (GDM) has focused on restricting carbohydrates. Some research suggests that increased dietary fat intake, which often occurs with carbohydrate restriction, may worsen insulin resistance in women with GDM. We tested for a relationship between dietary fat intake and insulin sensitivity in pregnant women.

Methods: Pregnant women in the late 2nd trimester, (median [IQR] =26 [25-27] weeks’ gestation) completed a 75 g oral glucose tolerance test (OGTT) and a validated self-administered 24-hr dietary recall. We tested for an association between fat intake the day before the OGTT and insulin sensitivity (inverse of insulin resistance, measured using Matsuda index) using linear regression, adjusting for age, race, education, parity, BMI, gestational age, carbohydrate intake, and caloric intake. We also tested for associations with insulin secretion (measured using Stumvoll 1st phase estimate, with adjustment for insulin sensitivity) , and fasting, 1-hr and 2-hr OGTT glucose (mg/dl) .

Results: Pregnant women (N=120, age 34 [31-36]) consumed 82 g of fat [62-101], 235 g of carbohydrate [195-298] and 78 g of protein [61-100] during a 24-hr period. Carbohydrate and fat intake were inversely related after adjusting for total caloric intake (0.3 fewer g of carbohydrate per additional g of fat, P <0.001) . We found no association between fat intake and insulin sensitivity (β=0.07, P=0.14) . There was no association between fat intake and insulin secretion (β=2.21, P=0.62) or OGTT glucose (fasting: β=0.03, P=0.67, 1-hr: β=-0.36, P=0.26, 2-hr: β=0.01, P=0.98) .

Conclusion: Our results suggest that dietary fat intake does not increase insulin resistance in pregnant women. This may have implications for dietary recommendations in women with GDM.

Disclosure

E.A.Rosenberg: None. E.W.Seely: None. T.Thaweethai: None. K.James: None. C.Yu: None. M.J.Callahan: None. S.Nelson: None. C.E.Powe: None.

Funding

National Institutes of Health (1F32DK126343-01A1) ,Nation Institutes of Health (K23DK113218) , and the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Program
1055-P: Low Rate of Preconception Counseling and Near Absence of Contraception Provision by Endocrinologists for Women with Diabetes
Authors: JEFFERS REBECCA , SAYRES LAUREN , ABUSHAMAT LAYLA , NIELSEN CHLOE , ZAMAN ADNIN , BARBOUR LINDA (LYNN) A.
Published: May 2022

Preconception counseling for reproductive-age women with type 1 and type 2 DM improves maternal-fetal outcomes. Endocrinologists are in a unique position to provide such important counseling and contraception or applicable referrals. In response to an increasing number of women referred to our prenatal clinic with poor glycemic control and unplanned pregnancies, we instituted a quality improvement initiative to improve preconception care at our academic center. We conducted a chart review of 96 women of reproductive age with at least one in-person visit for DM from July 2020-Oct 2021. Patients who were pregnant or had undergone sterilization were excluded. Fifty patients (mean age 34.5+/-6.7 yrs) met inclusion criteria. Of these, 66% had T1DM, 32% had T2DM and 26% had a HgbA1c ≤6.5%, recommended for pregnancy. Each woman had a mean of 2.1+/-1.2 visits with an endocrinology provider during these 15 mos. Only 4% had contraception specifically documented during a visit, although medical staff or other providers had documented contraception use in 56% of cases. No women received a contraception prescription. Endocrinologists did not document provision of preconception counseling to any of these women, although 14% had previously undergone counseling with a maternal fetal medicine provider. No women were referred to an OB-Gyn provider. Our data suggest that endocrinology providers infrequently provide preconception or contraception counseling or referrals for women with diabetes and underscores the striking need for a QI initiative. To this end, we are implementing a multifaceted intervention to educate providers on key aspects of preconception counseling and contraception provision, facilitate specialist referrals, simplify documentation, and provide patient education materials. We will assess the efficacy of our intervention with the ultimate goal of improving outcomes for this rapidly growing population of women with diabetes and their offspring.

Disclosure

R.Jeffers: None. L.Sayres: None. L.Abushamat: None. C.Nielsen: None. A.Zaman: None. L.A.Barbour: None.
1056-P: Reported Pregnancy Outcomes with Insulin Glargine 100 U/mL (Gla-100) and 300 U/mL (Gla-300) : Post-Marketing Survey of Pharmacovigilance Data
Authors: WESTERBACKA JUKKA , BASSOLE CAROLINE , DUVERNE MARIELLE , DODER ZORAN , SCHOEPPER HEIKE
Published: May 2022

Background: Good metabolic control during pregnancy is crucial for people with diabetes to prevent adverse events associated with hyperglycemia. Gla-300, a long-acting basal insulin (BI) analog, provides similar glycemic control and less hypoglycemia versus the first-generation BI Gla-100. We examined real-life safety of insulin glargine use in pregnancy.

Methods: Cumulative searches of the Sanofi global pharmacovigilance database for Gla-100/Gla-300 exposures in pregnancy were performed using Medical Dictionary for Regulatory Activities terms, from database initiation to March 9, 2021.

Results: Searches found 4936 (2370 solicited, 2566 unsolicited; 71 countries) exposures to Gla-100 and 246 (66 solicited, 180 unsolicited; 44 countries) for Gla-300 (Table) . Cumulative exposure was 89 million and 7.9 million person-years for Gla-100 and Gla-300, respectively. Congenital, familial, and genetic anomalies were rare (2.6% Gla-100; 2.0% Gla-300) , in line with general population rates (3-5%) . Spontaneous abortion rates were low (3.0% Gla-100; 2.8% Gla-300) , which is also in line with the general population (˜10%) .

Conclusion: Rates of congenital anomalies and spontaneous abortions for Gla-100 and Gla-300 were consistent with the general population. The results indicate no safety issues with insulin glargine use during pregnancy.

Disclosure

J.Westerbacka: Employee; Sanofi, Stock/Shareholder; Sanofi. C.Bassole: Employee; Sanofi. M.Duverne: Employee; Sanofi. Z.Doder: None. H.Schoepper: None.

Funding

Sanofi
1063-P: Social Risks and Health-Related Quality of Life in Women Who Have Experienced Gestational Diabetes
Authors: WALKER SHANNON L. , WALKER REBEKAH J. , HAWKS LAURA , MOSLEY-JOHNSON ELISE , NAGAVALLY SNEHA , EGEDE LEONARD E.
Published: May 2022

Objective: To examine the relationship between social risk factors (housing instability and food insecurity) on health-related quality of life (HRQoL) in women with a previous diagnosis of gestational diabetes mellitus (GDM) .

Methods: Cross-sectional data on women aged 18 and older from the Behavioral Risk Factor Surveillance System (2014, 2015, 2017) were analyzed. GDM was defined by self-reported diagnosis of diabetes only during pregnancy. Social risks were defined by experiences of housing instability or food insecurity within the previous year. Linear regression was run to evaluate the association between social risks and HRQoL controlling for sociodemographic confounders. Interaction terms between each social risk factor and race/ethnicity were tested for each outcome but were not significant, thus the analysis was not stratified.

Results: Among the total study sample (weighted N=3,080,442) of adult women with a prior GDM diagnosis, 14.8% and 12.6% reported recent housing instability and food insecurity, respectively. Among women with prior GDM, housing instability was associated with reduced self-rated general health status (-0.36; 95%CI -0.53, -0.19) and increased days of poor mental health (4.81; 95%CI 1.23, 8.39) . Food insecurity was associated with reduced self-rated general health status (-0.43, 95%CI -0.59, -0.27) and increased days of poor mental health (5.29; 95%CI 1.95, 8.64) .

Conclusion: Our findings indicate an inverse association between food insecurity and housing instability and self-rated general health status and mental health functioning among women with a prior GDM diagnosis. There was no differential relationship by race/ethnicity. These findings highlight the importance of interventions which address social risks to improve quality of life in women with a prior GDM diagnosis.

Disclosure

S.L.Walker: None. R.J.Walker: None. L.Hawks: None. E.Mosley-johnson: None. S.Nagavally: None. L.E.Egede: None.

Funding

American Diabetes Association (1-19-JDF-075) ; National Institute of Diabetes and Digestive Kidney Disease (K24DK093699, R01DK118038, R01DK120861, PI: Egede) , the National Institute for Minority Health and Health Disparities (R01MD013826, PI: Egede/Walker)
1066-P: Association of T2D Subgroups with MCI/Dementia
Authors: BANCKS MICHAEL , LOVATO JAMES , BALASUBRAMANYAM ASHOK , CODAY MACE , JOHNSON KAREN C. , MUNSHI MEDHA , REBELLO CANDIDA J. , WAGENKNECHT LYNNE E. , ESPELAND MARK
Published: May 2022

Objectives: To assess whether T2D subgroups are associated with MCI/dementia, and whether the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) differs in prevention of MCI/dementia by T2D subgroup.

Methods: Included 3760 participants (73% of original cohort after death and attrition) with T2D and overweight/obesity randomized to years of ILI or diabetes support and education. We characterized T2D subgroups at randomization using k-means clustering methods and data on age of T2D diagnosis, BMI, waist circumference, and HbA1c. We estimated marginal probabilities for prevalent MCI/dementia 10-13 years post-randomization by T2D subgroup with adjustment for cohort attrition and covariates (Table) and assessed for differential effects of ILI on MCI/dementia by T2D subgroup.

Results: T2D subgroups were characterized by (1) older and (2) younger age at T2D onset, (3) high HbA1c, and (4) severe obesity (Table) . Prevalence of MCI/dementia was 8.4% and differed by T2D subgroup. After adjustment, rate of MCI/dementia was highest for the severe obesity and lowest for the younger onset subgroups. There were no differences in MCI/dementia rates between intervention arms for any T2D subgroup (interaction p-value=0.84) .

Conclusions: T2D subgroups differ in rate of MCI/dementia, with the highest rate for a subgroup of participants with severe obesity. Lifestyle intervention did not modify rate of MCI/dementia in any T2D subgroup.

Disclosure

M.Bancks: None. J.Lovato: None. A.Balasubramanyam: None. M.Coday: None. K.C.Johnson: None. M.Munshi: Consultant; Sanofi. C.J.Rebello: None. L.E.Wagenknecht: None. M.Espeland: None.
1067-P: A National Physician Survey Examining Clinical Scenarios for Deintensifying Diabetes Medications
Authors: PILLA SCOTT J. , SCHOENBORN NANCY , BOYD CYNTHIA , GOLDEN SHERITA , MATHIOUDAKIS NESTORAS N. , MARUTHUR NISA M.
Published: May 2022

Many older adults with type 2 diabetes (T2D) are tightly controlled with high hypoglycemia risk medications and may benefit from deintensifying (stopping/reducing) or switching to newer medications. As deintensifying rarely occurs in practice, we aimed to determine how physicians make these decisions. We conducted a national survey of a random sample of US physicians in general medicine, geriatrics, and endocrinology. The survey was designed by a team of patients, caregivers, and physicians, and distributed in 3 mailing waves. Physicians were asked what action they would take in three scenarios of patients with T2D treated below individualized targets: 1) a healthy 79F with HbA1c 6.3% on a sulfonylurea; 2) a 77M with stage 4 kidney disease with HbA1c 7.3% on basal insulin; 3) a 78F with advanced dementia with HbA1c 7.7% on a sulfonylurea. Scenarios started with a base case of the patient reporting no medication issues, then varied hypoglycemia history, health, and patient preferences. Statistical comparisons used multinomial logistic regression accounting for clustering. We received 427 responses to date, response rate 27%. In the base case, 57% of physicians made no change to the high-risk medication, 16% switched, 12% decreased, 12% stopped, and 3% increased. Decreasing/stopping occurred over twice as often in scenario 1 than other scenarios (p<0.001) . In scenario variations, hypoglycemia of any severity led >95% of physicians to decrease, stop or switch the high-risk medication. Worsening health status also caused substantially more deintensification, but polypharmacy, financial barriers, and patient preference did not. Endocrinologists were 3-5 times as likely to switch medications compared to other specialties (p<0.001) . Overall, we found clinical inertia to deintensify high-risk diabetes medications, especially in medically complex patients with HbA1c >7.0%. Hypoglycemia and worsening health were strong motivators to deintensify or switch to newer medications.

Disclosure

S.J.Pilla: None. N.Schoenborn: None. C.Boyd: Other Relationship; Dynamed, UpToDate. S.Golden: Advisory Panel; Abbott Diabetes, Medtronic. N.N.Mathioudakis: None. N.M.Maruthur: Other Relationship; Johns Hopkins HealthCare Solutions.

Funding

National Institutes of Health (1R24AG064025 and 1K23DK128572)
1069-P: A National Physician Survey of Perspectives on Deintensifying Diabetes Medications
Authors: PILLA SCOTT J. , WANG ISABELLE J. , SCHOENBORN NANCY , BOYD CYNTHIA , GOLDEN SHERITA , MATHIOUDAKIS NESTORAS N. , MARUTHUR NISA M.
Published: May 2022

Deintensifying diabetes medications rarely occurs for older adults with type 2 diabetes (T2D) despite many being tightly controlled with hypoglycemia-inducing medications. We conducted a national survey of US physicians to understand their perspectives on deintensification for older adults with T2D. The survey was designed by a team of patients, caregivers, and physicians, and distributed to a random sample of physicians in general medicine, geriatrics, and endocrinology in three mailing waves. Respondents rated the importance of deintensifying, and of switching to a medication with a better risk/benefit profile, on 5-point Likert scales; the frequency of these actions in the past 3 months; and barriers/facilitators. We received 427 completed surveys to date, response rate 27%. The Figure shows physicians’ responses. Our findings show that the vast majority of US physicians view deintensifying diabetes medications as important to the care of older adults, although they accomplish this infrequently. Major barriers were physicians’ views that patients were reluctant to change medications or to allow their glucose to be higher. Adverse events, especially hypoglycemia, were strong facilitators, as was reducing cost of therapy. Geriatricians reported deintensifying more often than other specialties. Endocrinologists switched medications more often and were more concerned about short-term hyperglycemia.

Disclosure

S.J.Pilla: None. I.J.Wang: None. N.Schoenborn: None. C.Boyd: Other Relationship; Dynamed, UpToDate. S.Golden: Advisory Panel; Abbott Diabetes, Medtronic. N.N.Mathioudakis: None. N.M.Maruthur: Other Relationship; Johns Hopkins HealthCare Solutions.

Funding

National Institutes of Health (1R24AG064025 and 1K23DK128572)
1077-P: Assessing the Relationship among Multimorbidity, Psychosocial Factors, and Clinical Outcomes in Older Adults Living in Rural Appalachia
Authors: SMALLS BRITTANY L. , ADEGBOYEGA ADEBOLA , SIMON-OKUBE PATIENCE , WESTGATE PHILIP , SCHOENBERG NANCY
Published: May 2022

Type 2 diabetes (T2DM) is a significant public health burden in rural Appalachian Kentucky, with an estimated one in four older adults diagnosed with T2DM. To determine factors associated with T2DM, we assessed the relationship between multimorbidity (MM) , psychosocial factors, and clinical outcomes among 148 older adults with T2DM along with one or more comorbid conditions, living in rural Appalachian Kentucky. A community-based sample of Appalachian residents provided data on diabetes knowledge, chronic conditions in addition to T2DM, demographics, and clinical measures (HbA1c, blood pressure) using point-of-care methods.The sample population (N=148) had an average age of 72.2 years (± 5.4) and were mostly women (66%) and White (98%) , reflecting the region’s demographics. The average HbA1c was 7.6 (±1.3) and systolic and diastolic blood pressure were 145.2 (±20.8) mmHg and 81.9 (±12.6) mmHg, respectively. Participants reported having 2.3 (±1) chronic conditions in addition to T2DM. As for psychosocial factors, participants reported average score stress 20.7 (±9.1) , distress 26.7 (±10.7) , and social support 115.0 (±15.9) . There was a significant relationship between MM and HbA1c (β=0.27, SE=0.13, p=0.04) and stress (β=0.23, SE=0.08, p=0.004) . However, distress, social support, disability, and depression did not have significant relationships with MM in this sample.These findings elucidate the burden of MM in older adults who are living with T2DM in a rural environment. Though MM is not unique to the aging population, understanding how MM effects clinical outcomes and T2DM related psychosocial factors is important. In most cases, properly managing T2DM could reduce (or prevent) severity and complications of comorbid conditions. Thus, identifying psychosocial factors that are associated with clinical outcomes provides a pathway for targeted interventions to improve health outcomes for this vulnerable population.

Disclosure

B.L.Smalls: None. A.Adegboyega: None. P.Simon-okube: None. P.Westgate: None. N.Schoenberg: n/a.

Funding

NIDDK RDK112136NIDDK K01DK116923
1079-P: Effectiveness and Safety of Empagliflozin in Routine Care: Results from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study
Authors: HTOO PHYO T. , TESFAYE HELEN , PAIK JULIE M. , WEXLER DEBORAH J. , NAJAFZADEH MEHDI , GLYNN ROBERT , DERUAZ-LUYET ANOUK , FARSANI SOULMAZ F. FAZELI , KOENEMAN LISETTE , SCHNEEWEISS SEBASTIAN , PATORNO ELISABETTA
Published: May 2022

EMPRISE is a 5-year monitoring program that evaluates the effectiveness and safety of empagliflozin (EMPA) using Medicare and 2 U.S. commercial claims [2014-20 (2018 for Medicare) ]. We identified 190,226 patients ≥18 years with type 2 diabetes initiating EMPA or a dipeptidyl peptidase-4 inhibitors (DPP-4i) , and followed them up for heart failure hospitalization in primary (HHF-Specific) or any discharge positions (HHF-Broad) , a composite of myocardial infarction (MI) and stroke, and all-cause mortality (ACM) (Medicare only) . Safety outcomes were lower-limb amputations (LLA) , non-vertebral fractures, diabetic ketoacidosis (DKA) , acute kidney injury (AKI) , renal and bladder cancers (CA) . We estimated pooled HR (95% CI) after propensity score matching, adjusting for 143 baseline covariates. Compared to DPP4i, EMPA was associated with a reduced risk of HHF [HHF-Specific: 0.47 (0.41, 0.55) ; HHF-Broad: 0.67 (0.62, 0.72) ], a similar risk of the composite of MI or stroke [0.92 (0.84, 1.02) ], and a reduced risk of ACM [0.56 (0.46, 0.68) ]. EMPA was associated with a reduced risk of AKI [0.73 (0.68, 0.78) ], an increased risk of DKA [1.88 (1.51, 2.34) ], and a similar risk of LLA, fractures, and renal and bladder CA. Our findings support the cardiovascular effectiveness of EMPA in routine care with a safety profile in line with documented information.

Disclosure

P.T.Htoo: Employee; Johnson & Johnson. S.Schneeweiss: Consultant; Aetion, Inc., Research Support; Boehringer Ingelheim International GmbH. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. H.Tesfaye: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. M.Najafzadeh: None. R.Glynn: Research Support; Amarin Corporation, AstraZeneca, Kowa Pharmaceuticals America, Inc., Novartis AG, Pfizer Inc. A.Deruaz-luyet: Employee; Boehringer Ingelheim International GmbH, Other Relationship; IQVIA Inc., Sanofi. S.F.Fazeli farsani: Employee; Boehringer Ingelheim International GmbH. L.Koeneman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.
108-OR: The Effect of Human Pregnancy on Morphology of the Endocrine Pancreas
Authors: EGAN AOIFE M. , HER TRACY K. , VELLA ADRIAN , MATVEYENKO ALEKSEY
Published: May 2022

In animal models, pregnancy is associated with distinct morphological and functional adaptations in the endocrine pancreas, particularly characterized by β cell hyperplasia and hypertrophy. Failed islet adaptation to increased metabolic demands in pregnancy contributes to the development of gestational diabetes. However, the effects of pregnancy on the remodeling of human endocrine pancreas remain largely unknown. To address this, we used human pancreatic autopsy specimens from 8 women who died during pregnancy or within 6 weeks postpartum (P/PP) , and 16 women who were matched by age and body mass index (BMI) to serve as controls (CON) who were not pregnant at death. Subjects had a complete autopsy with pancreatic tissue of adequate quality/quantity stored and a corresponding medical record. Consecutive pancreatic sections were co-immunostained for key islet cell markers including Insulin, Glucagon and Glucagon-Like Peptide-1 (GLP-1) as well as a marker of cell proliferation (Ki-67) . Although the pancreatic fractional insulin area (β cell area) was comparable between P/PP and CON groups, the glucagon and the GLP-1 positive areas were substantially increased ∼2-fold in the P/PP group (p<0.05) . Our analysis also revealed an increase in the proportion of GLP-1/glucagon double positive islet cells (p<0.05) in PP/P subjects, suggesting a modulatory effect of pregnancy in favor of increased islet GLP-1 production in α cells. Consistently, P/PP subjects demonstrated an increase in α cell expression of prohormone convertase 1/3 (PC1/3) (p<0.05) , an enzyme responsible for the proteolytic cleavage of GLP-1 from proglucagon. Finally, the frequency of both β and α cell proliferation was comparable between groups (p>0.05) . While prior pre-clinical studies have focused solely on functional and morphological changes in pancreatic β cells, our data suggest that proglucagon gene products (glucagon and GLP-1) may play an underappreciated role in (or serve as markers of) the metabolic changes impacting human pregnancy.

Disclosure

A.M.Egan: None. T.K.Her: None. A.Vella: Advisory Panel; Crinetics Pharmaceuticals, Inc., Rezolute, Inc., vTv Therapeutics, Zealand Pharma A/S, Other Relationship; Novo Nordisk. A.Matveyenko: None.

Funding

National Institutes of Health (K12 HD065987/HD/NICHD)
1080-P: Sex-Specific Associations between Risk-Factor Control and Incident CVD in Diabetic Patients
Authors: WANG XUAN , MA HAO , FONSECA VIVIAN , QI LU
Published: May 2022

Background: Women with diabetes are at higher risk of CVDs than men. We investigated the associations between the degree of risk factor control and CVD in women and men with diabetes.

Methods: A total of 16,760 diabetes patients from UK Biobank were included. The exposure was the number of optimized risk factors including HbA1c level <53 mol/mol (7%) , blood pressure <140/90 mm/Hg, and non-HDL-cholesterol <130 mg/dl.

Results: During a mean follow-up of 8.4 years, 2000 incident CVD were documented, including 1685 IHD and 412 stroke. Number of risk-factor control was inversely associated with the risks of IHD, stroke and total CVD, and such associations were stronger in women than men (P for interaction with sex=0.012, 0.018 and 0.017, respectively) . The two most important risk factors for men were blood pressure and non-HDL-cholesterol, while for women were HbA1c and non-HDL-cholesterol. In addition, as compared with non-diabetic controls, the diabetes-related risk of CVD was theoretically eliminated when 2 or more risk-factors were under control in women, and 3 risk-factors were under control in men.

Conclusion: Among diabetes patients, to control the risk factors within the target range benefit more in women than men in preventing subsequent risk of CVD. Our findings highlight the importance of raising awareness of control of risk factors and provide evidence for the sex-specific priority of control strategies.

Disclosure

X.Wang: None. H.Ma: None. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. L.Qi: None.

Funding

National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024) , the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383, DK078616)
1081-P: Blood Pressure Variability Is Associated with Risk of Heart Failure, Elevated NT-proBNP, and High-Sensitivity Troponin: Results from MESA
Authors: NUYUJUKIAN DANIEL S. , ZHOU JIN , KOSKA JURAJ , NWABUO CHIKE , BERTONI ALAIN , SHEA STEVEN , REAVEN PETER
Published: May 2022

The association between blood pressure variability (BPv) and heart failure (HF) is incompletely studied. This association, and its links with biomarkers of HF and cardiac injury, were examined in the community-based Multi-Ethnic Study of Atherosclerosis (MESA) . Resting seated BP was measured thrice; the average of the last two measures was used for analysis, and visit-to-visit BPv (coefficient of variation-CV) was assessed over 5 visits. Biomarkers of HF (N-terminal B-type natriuretic peptide: NT-proBNP) and cardiac injury (high-sensitivity troponin-T: hs-cTnT) , respectively, at exams 1, 3 and 5 were ascertained. With 9.4 years median follow-up in 6,785 individuals, 385 HF events occurred. In adjusted time-dependent models including CVD risk factors, BMI, BP medications, and cumulative mean BP, BPv (CV-SBP and CV-DBP) was associated with risk of clinical HF (e.g., CV-SBP HR=1.16, p=0.03) . Similar patterns were seen regardless of T2D status. The associations were stronger for HF with reduced ejection fraction (EF) vs. preserved EF. When excluding those with baseline NT-proBNP >450 pg/mL or hs-cTnT >14 ng/L, the association between BPv and HF became stronger. CV-SBP and CV-DBP were also associated with elevated exam 5 NT-proBNP (>450 pg/mL: OR=1.74, and OR = 1.32, p<0.001) . We saw a positive relationship between CV-SBP and exam 1 to exam 5 changes in NT-proBNP (p=0.001) and hs-cTnT (p<0.001) as well as elevated hs-cTnT (>14 ng/L; OR=1.18, p<0.001) . Our data strongly support an association between BPv and both clinical HF and elevated NT-proBNP, and the association was greater in those with reduced vs. preserved EF. The association between BPv and clinical HF was related to deleterious changes in subclinical markers of myocardial injury and heart failure.

Disclosure

D.S.Nuyujukian: None. J.Zhou: Research Support; Dexcom, Inc. J.Koska: None. C.Nwabuo: None. A.Bertoni: None. S.Shea: Research Support; National Heart, Lung, and Blood Institute. P.Reaven: Research Support; AstraZeneca, Dexcom, Inc.

Funding

NIH/NHLBI (F32HL156626) NIH/NHLBI (R21HL150374) NIH/NHLBI (R21HL150268) NIH/NHLBI (R01HL138969)
1086-P: Cardiovascular Effectiveness of SGLT2 Inhibitors: Head-to-Head Comparisons
Authors: ABRAHAMI DEVIN , D’ANDREA ELVIRA , PAIK JULIE M. , WEXLER DEBORAH J. , EVERETT BRENDAN M. , KIM SEOYOUNG C. , PATORNO ELISABETTA
Published: May 2022

In placebo-controlled cardiovascular (CV) outcome trials, SGLT2 inhibitors (SGLT2i) reduced the risk of CV events in patients with T2D and CV disease. However, not all trials showed consistent CV benefits across individual SGLT2i. We assembled a cohort of adults with T2D (median age 62, 57% male) , newly treated with an SGLT2i (canagliflozin, dapagliflozin, empagliflozin) from Medicare and two US commercial healthcare claims databases (4/2012 - 12/2020) . We assessed the risk of a composite event of myocardial infarction (MI) or stroke (MI/stroke) , its individual components, hospitalization for heart failure (HHF) , and mortality. To account for differences between initiators of different SGLT2i, we reweighed each group using inverse probability of treatment weights, adjusting for >130 baseline characteristics. In each database, hazard ratios (HRs) and 95% CI were estimated using Cox proportional hazards models and results were pooled using random-effects models. Compared to canagliflozin, the most frequently used SGLT2i during the study period, dapagliflozin and empagliflozin had a similar risk of MI/stroke, though empagliflozin was associated with a reduced risk of HHF [HR (95% CI) = 0.73 (0.57-0.94) ], over a median 0.65 years of follow-up. Individual SGLT2i showed a similar risk of other outcomes (Table) . This study suggests that SGLT2i have similar effectiveness on most CV outcomes and mortality in patients with T2D.

Disclosure

D.Abrahami: None. E.D’andrea: None. J.M.Paik: None. D.J.Wexler: Other Relationship; Elsevier, Novo Nordisk, UpToDate. B.M.Everett: Consultant; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Lilly, Provention Bio, Inc., UpToDate, Other Relationship; American Heart Association, Research Support; Novo Nordisk. S.C.Kim: Research Support; AbbVie Inc., Bristol-Myers Squibb Company, Pfizer Inc., Roche Pharmaceuticals. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute.

Funding

Patient-Centered Outcomes Research Institute (DB-2020C2-20326)
1089-P: Importance of Cardiorenal Complications for Prognosis in Persons with Type 1 Diabetes and Controls
Authors: HALLSTRÖM SARA , WIJKMAN MAGNUS O. , LUDVIGSSON JOHNNY , EKMAN PER , PFEFFER MARC A. , WEDEL HANS , ROSENGREN ANNIKA , LIND MARCUS
Published: May 2022

Background: Historically, life expectancy in persons with type 1 diabetes (T1D) has been shorter than the general population, but earlier studies did not stratify patients according to cardiorenal complications.

Methods: T1D persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141) . Mortality rates from 2002 to 20were estimated in persons with T1D overall and after stratification for prevalent cardiovascular and renal disease.

Results: In persons with T1D, mean age was 32.4 years and 44.9% were women. Age- and sex- adjusted mortality rates decreased over time in both groups but remained significantly higher in those with T1D during 2017 to 2019. In T1D persons ≥45 years without previous renal or cardiovascular complications (approximately 50% of persons in this age group) similar standardized mortality rates were observed, over time compared with controls, with slightly lower mortality in T1D persons during the last period, 5.55 (95% CI 4.51-6.60) vs. 7. (95% CI 6.75-7.40) deaths per 1,000 person years (Figure) .

Conclusion: Excess mortality persisted over time in persons with T1D, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on differentiated treatment is needed to close the gap in mortality for persons with T1D.

Disclosure

S. Hallström: None. M.O. Wijkman: None. J. Ludvigsson: Advisory Panel; Dompé. Research Support; Diamyd Medical. M.A. Pfeffer: Consultant; AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Corvidia Therapeutics, GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Peerbridge, Sanofi. Research Support; Novartis Pharmaceuticals Corporation. Other Relationship; DalCor Pharmaceuticals, National Heart, Lung, and Blood Institute. A. Rosengren: None. M. Lind: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. Research Support; Eli Lilly and Company, Novo Nordisk.

Funding

ALF [ALFGBG-717211] and [ALFGBG-966173], grants from the Novo Nordisk foundation, Swedish Heart and Lung Foundation [20180589], [20210679], Swedish Research Council [2018-02527] [VRREG 2019-00193], and the Gothenburg Society of Medicine.
1090-P: Prevalence of Diabetic Cardiomyopathy in an Electronic Health Record–Based Cohort
Authors: SEGAR MATTHEW W. , PATEL KERSHAW , VADUGANATHAN MUTHIAH , CHANDRA ALVIN , WILLETT DUWAYNE L. , PANDEY AMBARISH
Published: May 2022

Introduction: Diabetic cardiomyopathy (DbCM) is characterized by abnormal cardiac structure/function, associated with incident HF, and has a 67% prevalence in the community. However, the prevalence of DbCM in a real-world, electronic health record (EHR) system is not known.

Methods: Adult patients with DM in a single center EHR free of CVD with available data on HF risk factors were included. The presence of DbCM was defined using different definitions (Figure) . DbCM prevalence was compared across subgroups with differences assessed using the chi-squared test. Adjusted logistic regression models were constructed to evaluate significant predictors of DbCM.

Results: Among 1,921 individuals with DM, prevalence of DbCM in the overall cohort was 8.7% and 64.4% in the most and least restrictive definitions, respectively. Across all definitions, increasing age and Hispanic ethnicity was associated with higher proportion of DbCM (Figure A,D) . No consistent differences in DbCM prevalence were observed across sex and race-based subgroups across definitions (Figure B-C) . In multivariable-adjusted logistic regression, higher creatinine and longer QRS duration were associated with higher risk of DbCM across all definitions.

Conclusions: In a single-center, EHR cohort, the prevalence of DbCM was up to 64.4%. Increasing age and Hispanic ethnicity had a higher prevalence of DbCM.

Disclosure

M.W.Segar: None. K.Patel: None. M.Vaduganathan: Advisory Panel; American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Pharmacosmos, Relypsa, Roche Diagnostics, and Sanofi, Other Relationship; Novartis and Galmed , Research Support; Amgen, AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics, and Sanofi, Speaker's Bureau; Novartis and Roche Diagnostics. A.Chandra: None. D.L.Willett: None. A.Pandey: Advisory Panel; Lilly, Consultant; Tricog, Research Support; Applied Therapeutics, Gilead Sciences, Inc.
1091-P: Impact of Metabolic Syndrome and Metabolic Dysfunction-Associated Fatty Liver Disease on Cardiovascular Risk in People with and without Type 2 Diabetes
Authors: MATSUBAYASHI YASUHIRO , FUJIHARA KAZUYA , YAMADA MAYUKO H. , YAGUCHI YUTA , YAMAMOTO MASAHIKO , ISHIGURO HAJIME , KITAZAWA MASARU , IWANAGA MIDORI , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO
Published: May 2022

This study aims to examine the impact of the association between metabolic syndrome (MetS) and metabolic dysfunction-associated fatty liver disease (MAFLD) , which both have insulin resistance and are pathophysiologically similar, on the development of new-onset cardiovascular disease, with and without type 2 diabetes mellitus (T2DM) A total of 570,426 participants without a history of cardiovascular disease who were enrolled in the nationwide claims database from 2008-2016 were included in this study. Participants were classified according to the presence or absence of MetS and/or MAFLD, and the risk of developing coronary artery disease (CAD) and/or cerebrovascular disease (CVD) in each category was analyzed using a multivariate Cox proportional hazard model. The same analysis was performed with stratification by the presence or absence of T2DM. During a median follow-up of 5.2 years, 2,252 CAD and 3,128 CVD events occurred. The hazard ratio (HR) (95% CI) for CAD, compared with the group with neither MAFLD nor MetS, was 1.46 (1.32-1.62) for MAFLD only (without MetS) , 2.02 (1.51-2.70) for MetS only (without MAFLD) , and 2.33 (2.10-2. 58) for MAFLD + MetS. For CVD, The HR was 1.41 (1.28-1.55) for MAFLD only, 1.67 (1.38-2.02) for MetS only, and 1.89 (1.72-2.08) for MAFLD + MetS. These results were similar for non-T2DM participants but different for T2DM participants, with no significant increased risk for CAD in MetS only and a significant increased risk for CVD only when both MAFLD and MetS coexisted. The predictive ability for cardiovascular disease development in patients with MetS and MAFLD differed depending on the presence or absence of T2DM. These results suggest that distinguishing between the diagnosis of MetS and MAFLD, taking into account the presence or absence of T2DM, may lead to more accurate identification of patients at high risk of developing cardiovascular disease.

Disclosure

K. Fujihara: None. M.H. Yamada: None. M. Yamamoto: None. H. Ishiguro: None. M. Kitazawa: None. M. Iwanaga: None. S. Kodama: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding

The Japan Society for Promotion of Science (JSPS) KAKENHI Grant Number JP 20K19706)
1093-P: Vascular Health across the Lifespan in Women with and without Type 1 Diabetes (TID)
Authors: CHARTIER-LOGAN CATHERINE J. , ALMAN AMY C. , SHAH VIRAL , SNELL-BERGEON JANET K.
Published: May 2022

Introduction: Cardiovascular disease (CVD) is the leading cause of death in people with T1D, and women with T1D are disproportionately affected. However, few studies have examined how T1D affects vascular health in women across the lifespan.

Methods: Women ages 18-79 with (N=309) and without T1D (n=351) were examined cross-sectionally for markers of CVD: pulse wave velocity (PWV) , augmentation index (AiX) , pulse height (PH) , brachial artery distensibility (BrachD) , subendocardial viability index (SVI) , and carotid intima thickness (cIMT) . Menopausal status was self-reported. Body composition was measured by Dual Xray Absorptiometry. CVD markers were examined by diabetes status and age using linear regression models adjusted for menopausal status.

Results: Age did not differ in women with and without diabetes (49 ± 12 vs. 50±14 years, p=0.32) . Women with T1D had higher systolic blood pressure (SBP) , cIMT, PWV and PH, and lower BrachD and SVI than non-diabetic women (Table 1) . Changes in blood pressure, cIMT, AiX, and SVI with age differed by diabetes status, as demonstrated by a significant interaction. While SBP and Aix were increased more in women with T1D at younger ages, cIMT and SVI worsened with age to a greater extent in T1D.

Conclusions: Women with T1D have worse CVD markers than women without diabetes across the lifespan, with more arterial stiffness at younger ages and more atherosclerosis and lower SVI later in life.

Disclosure

C.J.Chartier-logan: None. A.C.Alman: None. V.Shah: Advisory Panel; Medscape, Sanofi, Consultant; Dexcom, Inc., Research Support; Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Novo Nordisk. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc.