bluuebunny/crossref_metadata_2025 huggingface dataset:
87-OR: Vitreous Retinol Binding Protein 3 Is Increased in Patients without Advanced Diabetic Retinopathy in Type 1 and Type 2 Diabetes
Authors: FICKWEILER WARD , PARK HYUNSEOK , PARK KYOUNGMIN , BOUMENNA TAHANI , GAUTHIER JOHN , WU I-HSIEN , CAVALLERANO JERRY D. , AIELLO LLOYD P. , SUN JENNIFER , KING GEORGE L.
Published: June 2021

Retinol Binding Protein 3 (RBP3), a retinol transport protein secreted mainly by photoreceptors, may inhibit progression of diabetic retinopathy (DR) by decreasing glucose uptake and inflammation in the retina. In people with type 1 diabetes with duration of ≥50yrs (Joslin Medalist Study), >40% of Medalists exhibited no to mild non-proliferative diabetic retinopathy (NPDR) and increased expression of RBP3 compared to those with severe DR. We examined 213 vitreous samples from a larger population of Medalists and patients with type 1 and type 2 diabetes with shorter diabetes duration (mean±SD 26.5±12.7 years) from the Joslin Beetham Eye Institute to determine whether vitreous RBP3 levels are correlated with DR severity and progression in a broad population with diabetes. RBP3 was increased in vitreous from people with no diabetes compared to subjects with type 1 and type 2 diabetes (p<0.0001). Type of diabetes (type 1 vs. type 2, p=0.44) and A1c (p=0.68) were not associated with RBP3. In patients with both type 1 and 2 diabetes, vitreous RBP3 levels gradually decreased from the highest concentration in no to mild NPDR (15.7 nM) to the lowest concentrations in advanced DR (moderate-severe: 8.2 nM, p=0.01 vs. no-mild NPDR; active proliferative DR: 8.4 nM, p=0.0003 vs. no-mild NPDR; quiescent proliferative DR: 3.5 nM, p<0.0001 vs. no-mild NPDR). RBP3 was higher in moderate-severe NPDR compared to quiescent PDR (p=0.03). RBP3 concentrations in surgical samples from living donors were lower than those from post-mortem Medalists (p<0.01), but were associated with DR severity in both groups (p=0.03 and p<0.0001, respectively). Increased RBP3 concentrations were associated with reduced risk of PDR development over time (n=34, p<0.001). These findings indicate that elevated vitreous RBP3 is associated with decreased DR severity and decreased risk of PDR development, supporting the postulate that RBP3 is a protective factor and therapeutic target for the progression of DR.

Disclosure

W. Fickweiler: None. G. L. King: Consultant; Self; Agios, Inc., Medtronic, Other Relationship; Self; Janssen Pharmaceuticals, Inc. H. Park: None. K. Park: None. T. Boumenna: None. J. Gauthier: None. I. Wu: None. J. D. Cavallerano: None. L. P. Aiello: Consultant; Self; KalVista Pharmaceuticals, Novo Nordisk, Regeneron Pharmaceuticals Inc., Stock/Shareholder; Self; KalVista Pharmaceuticals. J. Sun: Other Relationship; Self; Novo Nordisk, Roche Pharma, Research Support; Self; Adaptive Sensory Technology, Boehringer Ingelheim Pharmaceuticals, Inc., KalVista Pharmaceuticals, Optovue, Roche Pharma.

Funding

National Eye Institute (R01EY026080-01); National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK094333-01); JDRF (17-2013-310); Beatson Foundation; Dianne Nunnally Hoppes Fund
871-P: Integrating the PHQ-A Depression Screening Tool within the Electronic Health Record Increases Detection of Depression Symptoms
Authors: GETTINGS JULIE , PATIL OONA , VAJRAVELU MARY ELLEN , HAWKES COLIN P. , TUTTLE ALAN , BUZBY MARIANNE , CREAN STEPHANIE , DEVER MAUREEN B. , MULLIGAN LIAM , WILLI STEVEN M.
Published: June 2021

Depression symptoms are common for youth with diabetes and may negatively affect quality of life and health outcomes. In our large, urban, pediatric diabetes clinic, depression screening with a condensed, verbally-administered measure, the Patient Health Questionnaire-2 (PHQ-2), had a positivity rate of only 2%, which is far below anticipated rates. We developed a quality improvement project to increase the sensitivity of depression screening for youth with diabetes. The primary test of change was electronically administering the Patient Health Questionnaire for Adolescents (PHQ-A), a 13-question survey validated for use in pediatrics. Youths ≥ 12 years of age were asked to privately complete the PHQ-A on a laptop at a diabetes visit annually. Responses populated within the electronic health record, and medical providers were trained to respond to positive screens with the support of a social worker or psychologist. A run chart was used to assess screen-positivity rate over time; ≥6 points above the baseline was considered a significant change. During the study period (August 2018—February 2020), 740 PHQ-A screens were completed by 618 patients. The majority of patients (n = 489; 79%) had type 1 diabetes, 50% were female, and the median age (IQR) at screening was 16.2 (14.0-18.0) years. On average, 38.9 screens/month were completed (range: 16-70), and 6.8 screens/month were positive (range: 0-16). Of all completed screens, 129 (17.4%) were positive. The positivity rate was greater than baseline for all 7 quarters evaluated after implementation of PHQ-A. Of the positive screens, 55 (43%) were positive due only to SI or SA history. Using a standardized and easily administered approach, the detection of depression symptoms increased to a range comparable to previous reports. The number of completed screens per month was manageable, allowing us to promptly address depression symptoms within our interdisciplinary clinic workflow.

Disclosure

J. Gettings: None. S. M. Willi: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Medtronic, Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases. O. Patil: None. M. Vajravelu: None. C. P. Hawkes: None. A. Tuttle: None. M. Buzby: None. S. Crean: None. M. B. Dever: None. L. Mulligan: None.
889-P: Prescriber Perceptions of the Implementation of Liraglutide into Pediatric Type 2 Diabetes Care
Authors: HITT TALIA A. , DIAZ SANDRA VAZQUEZ , SANCHEZ-KLEINBERG YESENIA , SHEA JUDY A. , KATZ LORRAINE E. , VAJRAVELU MARY ELLEN
Published: June 2021

Background: In 2019, nearly two decades after metformin approval, liraglutide became the third medication approved by the U.S. FDA for pediatric type 2 diabetes (T2D). However, successful uptake of liraglutide in practice depends on prescribers’ perceptions of acceptability and appropriateness of use in this population.

Objective: We explored pediatric diabetes prescribers’ perceptions on ordering liraglutide, including facilitators and barriers, for youth with T2D at a single, large academic center.

Methods: We conducted semi-structured interviews with diabetes attending physicians (A), fellow physicians (F), and nurse practitioners (NP) supplemented with a patient vignette, chart-stimulated recall (CSR), and review of a clinical practice guideline (CPG). Interviews were audio-recorded, transcribed, and analyzed using modified grounded theory by three coders with constant comparison techniques.

Results: Nineteen physicians (15 A, 4 F) and 6 NPs with a median experience of 7 years (1.5- 40) participated. Themes identified included 1) primary drivers of use: desire to promote weight loss/maintenance or to avoid/reduce insulin use; 2) acceptance by patients and families: highest for those with familiarity with the medication class and interest in weight benefits; and 3) primary barriers to prescribing: patients’ dislike of injections or prescriber hesitancy due to lack of experience with the drug, concerns about adherence, or issues with insurance coverage. Although most responders recommended liraglutide when presented with a patient vignette, they recalled prescribing barriers in actual practice during CSR. The CPG was endorsed as a facilitator to prescribing, but additional dissemination and use strategies were recommended.

Conclusions: Although liraglutide adds to the toolbox for pediatric T2D, our findings highlight the challenges of introducing new therapeutics and provide insights that may guide implementation efforts in pediatric diabetes clinics.

Disclosure

T. A. Hitt: None. S. Vazquez diaz: None. Y. Sanchez-kleinberg: None. J. A. Shea: None. L. E. Katz: None. M. Vajravelu: None.

Funding

National Institutes of Health (5T32DK063688-17, K23DK125719-01); University of Pennsylvania
9-LB: Effects of Hyperglycemia-Induced Stress in a Human Cardiomyocyte Cell Line
Authors: WAGHELA HIRAL , THAKUR VIKRAM , CHATTOPADHYAY MUNMUN
Published: June 2021

The prevalence of diabetes in America has continued to increase over the past years, affecting 10.5% of the US population. Cardiomyopathy is one of the major complications of long-term diabetes. Diabetic cardiomyopathy is characterized by an increase in the thickness and rigidity of the heart wall resulting in contractile dysfunction that can ultimately result in heart failure. Hyperglycemia has been also associated with an increase in the production of reactive oxygen species and inflammatory mediators. In the current study, we investigated the role of hyperglycemic exposure to cardiomyocyte in altering the epigenetic markers such as histone deacetylases (HDACs) and inflammatory mediators (such as TLR4 and RAGE) in the progression of cardiomyocyte remodeling and hypertrophy. Cardiac damage was assessed by analyzing the expression of cardiac structural proteins such as Troponin I&T and Connexin43 (Cx43). AC16 cardiomyocyte cell line derived from adult ventricular heart tissue was subjected to high glucose conditions (25 mM) for 24 hours and stress mediated markers were assessed by Western Blot and immunocytochemistry. The statistical significance of the difference between groups was determined by ANOVA (systat 13 software, SPSS Inc., Chicago, IL, USA), using Bonferroni correction for the multiple post hoc analyses for each control and hyperglycemic conditions. An increase in class I HDAC expression (HDAC2) was observed, with no changes seen in the expression of class II HDACs (HDAC 4 and 6). A downregulation of CXCR4 was observed, suggestive of its role as a cardioprotective agent. Increased levels of oxidative stress markers such as RAGE and TLR4 were seen, along with increased expression of markers of cardiac injury such as Cx43 and Troponin I&T. These findings suggest that epigenetic mechanisms and oxidative stress-mediated inflammatory markers can alter the functionality of cardiomyocytes exposed to high glucose conditions.

Disclosure

H. Waghela: None. V. Thakur: None. M. Chattopadhyay: None.

Funding

Texas Tech University Health Sciences Center El Paso (183381SEED)
9-OR: Personalized Diets by Prediction of Glycemic Responses Improve Glycemic Control in Subjects with Newly Diagnosed T2D
Authors: REIN MICHAL S. , BEN-YACOV ORLY , GODNEVA ANASTASIA , SHILO SMADAR , ZELBER-SAGI SHIRA , ELINAV ERAN , SEGAL ERAN
Published: June 2021

Dietary modifications are crucial for the management of newly-diagnosed type-2 diabetes (T2D) and prevention of its health complications, but many patients fail to achieve clinical goals with diet alone. We previously developed a machine-learning algorithm for predicting personalized postprandial glucose responses (PPGR) to meals using clinical and gut microbiome features, and showed that dietary interventions based on this algorithm successfully lowered PPGRs in adults with prediabetes. Here, we sought to evaluate the clinical efficacy of our algorithm-based diet in subjects with newly-diagnosed T2D. We performed a short-term randomized controlled crossover trial and compared the effects of an algorithm-based personalized postprandial-targeting (PPT) diet, to those of a commonly used Mediterranean (MED) diet on glucose levels in 23 subjects with newly-diagnosed T2D. Average PPGR, glucose fluctuations, daily time of glucose levels >140 mg/dl and fructosamine levels decreased significantly more during the PPT intervention compared to the MED intervention. We further evaluated the long-term clinical effects of the PPT diet in 16 of the participants by an additional 6-month PPT intervention, and found significant improvements in multiple clinical parameters, including HbA1c (mean±SD, -0.39±0.48%, p<0.001), fasting glucose (-16.4±24.2 mg/dl, p=0.02), fasting insulin (-2.3±4.0 MCU/ml, p=0.04), triglycerides (-49±46 mg/dl, p<0.001), body weight (-3±3.5 kg, p=0.005), body fat% (-2.5±3%, p=0.005) and waist circumference (-4.7±3.7 cm, p=0.001). Importantly, 61% of the participants exhibited diabetes remission at the end of the intervention, as measured by HbA1c. Finally, some of the improvements in clinical outcomes were accompanied by significant alterations to the gut microbiome composition. These findings may be valuable for the design of future studies in larger cohorts and may have implications for dietary advice in clinical practice.

Disclosure

M. S. Rein: None. O. Ben-yacov: None. A. Godneva: None. S. Shilo: None. S. Zelber-sagi: None. E. Elinav: Consultant; Self; BiomX, DayTwo. E. Segal: Consultant; Self; DayTwo.
901-P: COVID-19 and Type 2 Diabetes: Children Spared from Severe Disease Course
Authors: CYMBALUK ANNA , ASTUDILLO MARCELA , DESALVO DANIEL , BACHA FIDA , MCKAY SIRIPOOM , REDONDO MARIA J.
Published: June 2021

Diabetes and hyperglycemia are risk factors for severe COVID-19 course and/or death in adult patients. While most cases in children remain mild, studies in pediatric T2D are limited.

Our study aim was to describe the clinical characteristics of COVID-19 course in youth with T2D. We conducted a retrospective review of electronic medical records of patients with T2D and positive SARS-CoV-2 PCR testing performed at Texas Children’s Hospital between 3/1/2020 and 10/31/2020. Demographics, diabetes treatment regimen, metrics of glycemic control, and variables of COVID-19 course were recorded and analyzed.

We identified 14 youth with active T2D and positive SARS-CoV-2 testing. All individuals had established diabetes; none were concurrently diagnosed with new onset T2D and SARS-CoV-2. Of them, 43% [n=6] were African-American, 57% [n=8] Hispanic, and none were Non-Hispanic Whites. All individuals had public medical insurance and were obese, with mean BMI Z score =+2.22 [SD =0.48]. Median last hemoglobin A1C within 3 months prior to testing positive for SARS-CoV-2 was 13.2% [IQR= 2.50%], with 27% [n=3] patients’ last A1C above the limit of detection [>14.0%] and 91% [n=10] above the American Diabetes Association Standards of Care goal of 7.0%. Twelve (85.7%) children were on insulin and 36% [n=5] on Metformin. Admission was required in 42.8% [n=6] children, 1 prior and 2 after having SARS-CoV-2 detected, and 3 at the time of SARS-CoV-2 detection for diabetic ketoacidosis [DKA]. Mean pH for those admitted for DKA [n=3] was 7.12 [SD = 0.09]. Median length of all admissions was 1.5 days [IQR = 1.23 days]. One patient required brief supplemental oxygen for comfort, but no patients had documented hypoxia. No patients required intubation and no patients expired.

In sum, T2D in youth did not appear to be a risk factor for severe SARS-CoV-2 related illness. However, prevalence of DKA was higher than expected, suggesting that COVID-19 may adversely affect diabetes course; this will require further investigation.

Disclosure

A. Cymbaluk: None. M. Astudillo: None. D. Desalvo: Consultant; Self; Insulet Corporation, Research Support; Self; Insulet Corporation, Speaker’s Bureau; Self; Dexcom, Inc. F. Bacha: None. S. Mckay: None. M. J. Redondo: Advisory Panel; Self; Provention Bio, Inc.
923-P: Tolerability and Time-Action Profile of Technosphere Insulin in Pediatric Subjects
Authors: JONES MARISA C. , HALLER MICHAEL J. , NG SAVANNAH E. , BHAVSAR SUNIL , KAISERMAN KEVIN B. , KRUEGER JOHN A.
Published: June 2021

Introduction: Technosphere Insulin (TI) is an inhaled ultra-rapid-acting dry powder prandial insulin. Reported are the results of the first study of TI in pediatric patients.

Methods: PK/PD and safety of TI was evaluated in a single-arm, 4-week study in 30, 8-17 years old subjects with T1DM on a stable MDI regimen, meeting pre-defined pulmonary function testing criteria. On day 1, subjects received an individualized single prandial dose of TI (4-16 U, in 4U increments) based on their usual meal-time dose and meal content. Serum insulin and blood glucose were measured -30 to 250 minutes relative to dosing. Over the next 4 weeks, each subject’s dose of TI was titrated, targeting a 120-150 minute post-prandial glucose level of 110-180 mg/dL. Safety and tolerability were assessed over the course of the study. Severe hypoglycemia was defined as an event associated with coma, loss of consciousness, or seizure.

Results: Mean age of subjects was 12.7 years (60% Female; 83.3% White). Serum insulin rapidly increased post-dose and returned to baseline by 120 minutes. Mean serum insulin Cmax was 77.3 µU/ml, 119.15 µU/ml, 101.29 µU/ml and 104.86 µU/ml for doses of 4, 8, 12 and 16U respectively. Tmax occurred at 10.5, 13.9, 14.6, and 20.0 minutes post-dose for 4, 8, 12 and 16U respectively. Glucose lowering during 30-60 minutes post-dose was consistent with the PK profile. Over 4 weeks of study, 23 subjects (76.7%) reported 41 TEAEs. One subject had an SAE of diabetic ketoacidosis that was considered possibly related to TI. The most common AEs were hypoglycemia (none severe) and cough. No subjects had a clinically relevant decline in pulmonary function.

Conclusion: Inhaled TI demonstrated an ultra-rapid time-action profile similar to that observed in adults. These data suggest TI can be safely administered to children and adolescents ages 8-17 with T1DM.

Disclosure

M. C. Jones: Employee; Self; MannKind Corporation, Stock/Shareholder; Self; MannKind Corporation. M. J. Haller: Board Member; Self; SAB Biotherapeutics, Inc., Consultant; Self; MannKind Corporation, Other Relationship; Self; Janssen Pharmaceuticals, Inc., Sanofi. S. E. Ng: Employee; Self; MannKind Corporation. S. Bhavsar: Employee; Self; MannKind Corporation. K. B. Kaiserman: Advisory Panel; Self; Medtronic, Consultant; Self; Medtronic, Employee; Self; MannKind Corporation, Research Support; Self; Medtronic, Speaker’s Bureau; Self; Medtronic, Stock/Shareholder; Self; MannKind Corporation. J. A. Krueger: Employee; Self; MannKind Corporation, Stock/Shareholder; Self; Eli Lilly and Company.

Funding

MannKind Corporation
926-P: HbA1c Monitoring among Adolescents and Young Adults with Type 1 Diabetes: Impact of Diabetes Care Provider Type
Authors: WISK LAUREN E. , LANDRUM MARY BETH , FU CHRISTINA , CHIEN ALYNA
Published: June 2021

Adolescents and young adults with type 1 diabetes (T1D) are at-risk of not receiving the recommended levels of annual HbA1c testing, but extent to which this occurs and the degree to which this may due to not accessing care or changes in physicians is poorly understood. This is an observational study of 9,916 unique 13-26 year olds with T1D who were continuously insured by a large US health insurer for 12 months or more during 2012-2016. We evaluate the frequency at which this population does not receive twice yearly HbA1c tests and the degree to which such rates are associated with age, not accessing care at all, and types of physicians of delivering diabetes care descriptively and using multivariable regression. The percent of those with T1D not receiving twice yearly HbA1c tests rose from 17% to 40% between the ages of 13 to 26 (peaked at 45% at age 24). The percent not making any diabetes visit within a year rose from 12% to 17% between those same ages. Pediatric endocrinologists and general pediatricians were the dominant providers at age 13 (62% and 26%, respectively), while adult endocrinologists and adult primary care physicians were the dominant providers at age 26 (48% and 44%, respectively). The age at which care transfers from pediatric to adult physicians appears to be at age 18 for primary care and at age 19 for endocrinologists. Receiving the twice yearly HbA1c tests was associated with endocrinologists after adjusting for sex, age, rurality, and neighborhood poverty. HbA1c monitoring declines substantially as adolescents grow into adults and appears to be related to not accessing healthcare despite being insured and also be due to transferring from pediatric to adult primary care physicians and endocrinologists.

Disclosure

L. E. Wisk: None. M. Landrum: None. C. Fu: None. A. Chien: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (K01DK116932 to L.E.W.); Agency for Healthcare Research and Quality (U19HS024072 to A.C.)
933-P: Impact of Sleep and Activity on Glycemic Control and Quality of Life in Haitian Youth with Type 1 Diabetes
Authors: BABINSKI MELANIE , DUPERVAL REGINA , VON OETTINGEN JULIA E. , ALTENOR KETLY
Published: June 2021

Background: Sleep and exercise affect overall health. In youth with type 1 diabetes (T1DM), physical activity and adequate sleep reportedly improve glycemic control. Data from low-income countries is lacking.

Objective: To describe sleep and activity in Haitian youth with T1DM and examine their impact on glycemic control, health-related quality of life (HRQL) and Life Satisfaction (LS).

Methods: Single-center cross-sectional study in Haiti, including youth diagnosed with T1DM between 0-25 years old. Wristbands tracked activity and sleep for 10 days. Diabetes Quality of Life in Youth (DQoLY) questionnaire was used to evaluate HRQL and LS. Point-of-care hemoglobin A1c (A1C) values (max. measure 14%) were recorded. Linear regression was used to assess sleep and activity as predictors of A1C, HRQL and LS.

Results: We included 66 participants (59% female, mean age 17.8±4.8 years, mean diabetes duration 3.7±3.4 years, mean BMI Z-score -0.86±1.1). Mean HRQL was 63/100 and mean LS 65/100. Mean A1C was 11.3%, and 22 patients (34%) had A1C >14%. Mean daily step count was 9448±8431 and mean sleep duration 7h31±1h17. Higher A1C was predicted by younger age (p=0.005) and lower BMI Z-score (p=0.0016), but not sex or diabetes duration. Better HRQL was predicted by younger age (p=0.029), and marginally by male sex (p=0.07). None predicted LS. Sleep duration and step count did not predict either outcome. When excluding patients with A1C>14% (to eliminate a possible ceiling effect), shorter sleep duration was a significant predictor of higher A1C (p=0.03) in uni- and multivariate models adjusted for age, sex, BMI and diabetes duration.

Conclusions: Youth with T1DM in Haiti have poor glycemic control, and low HRQL and LS. Their average sleep duration and daily activity is similar to reported values in peers. While activity level did not affect A1C, HRQL or LS, shorter sleep duration predicted higher A1C in youth with A1C<14%. Prospective studies with larger sample sizes are needed to validate our findings.

Disclosure

M. Babinski: None. R. Duperval: None. J. E. Von oettingen: None. K. Altenor: None.
936-P: Nutrition Experiences among Caregivers of Youth with Type 1 Diabetes
Authors: GORDON ERIN N. , DYKEMAN BLAIR S. , GRECO KIMBERLY , RHODES ERINN , GARVEY KATHARINE
Published: June 2021

Many children with type 1 diabetes (T1D) do not meet nutritional guidelines. Little is known about how caregivers perceive the necessity of appointments with a dietitian (RD) or how satisfied they are with their nutrition care. To better understand caregiver nutrition experiences and perceptions, we surveyed 838 families of children <18 years old receiving T1D care at Boston Children’s Hospital (BCH). Of 184 (22%) responses, 159 with complete data were analyzed. Using multivariable logistic regression, we assessed factors associated with caregiver (1) perception of the necessity for annual nutrition visits; (2) satisfaction with nutrition care and (3) encouragement from a nurse or doctor to meet with an RD. Covariates included child’s age, diabetes duration, gender, race and ethnicity, and diabetes technology use. Age and diabetes duration were categorized as <13 and ≥ 13 years old and ≤ 3 and > 3 years, respectively. Among children in the analysis, 55% were ≥ 13 years old and 51% had T1D for ≤ 3 years. Over half (56.6%) of respondents considered it necessary to see a RD every year. Older age (aOR=2.06, 95% CI [1.01, 4.20]) and shorter disease duration (aOR=2.50, 95% CI [1.22, 5.12]) were associated with this perception. Less than half (47.8%) reported satisfaction with their nutrition care, with shorter disease duration associated with a higher likelihood of satisfaction (aOR=2.24, 95% CI [1.13, 4.42]). Only 61.4% of respondents reported encouragement from a nurse or doctor to meet with a RD. No demographic or clinical characteristics were associated with this finding. Our findings suggest that caregiver satisfaction with nutrition care and its perceived need for children with T1D may wane with longer disease duration. However, the perceived need for nutrition services is also higher in parents of teens. Future work should delineate strategies for engaging families in nutrition education that is more tailored to later stages of the T1D journey. In addition, there is a need for teen-focused T1D nutrition care curricula.

Disclosure

E. N. Gordon: None. B. S. Dykeman: None. K. Greco: None. E. Rhodes: Other Relationship; Self; AstraZeneca. K. Garvey: None.
947-P: Racial/Ethnic Differences in Type 2 Diabetes Diagnosis among Women with Gestational Diabetes: Creation of a Diverse Population-Based Eight-Year Postpartum Diabetes Cohort
Authors: JANEVIC TERESA , MCCARTHY KATHARINE J. , KENNEDY JOSEPH J. , CHAN HIU TAI , VAN WYE GRETCHEN , MAYER VICTORIA L. , LIU SHELLEY H. , HUYNH MARY
Published: June 2021

Background: Women with gestational diabetes (GDM) are at increased risk of developing type 2 diabetes, a leading cause of premature morality. While data suggest racial/ethnic minority women bear the disproportionate burden of gestational diabetes, current postpartum GDM cohorts lack adequate diversity to examine whether racial/ethnic disparities persist in the transition to type 2 diabetes. To address this gap, we make use of two NYC public health surveillance databases to construct a novel population-based cohort of women with gestational diabetes and their progression to diabetes diagnosis.

Methods: We used a systematic matching process to identify unique cases of women who gave birth between 2009 and 2011 and diabetes diagnosis (two A1c results6.5%) in the following 8 years using linked NYC vital statistics and HbA1c registry data.

Results: Of 16,231 women with gestational diabetes, the cumulative incidence of diabetes in 8 years of follow-up was 14.4% (N=2,333 cases) in the overall cohort, 21.1% among non-Hispanic Black women, 15.9% among Hispanic women, 12.3% among Asian women, and 6.1% among non-Hispanic white women. Using this diverse cohort, future analyses will examine racial/ethnic differences in disease progression (e.g., from diabetes to glycemic control) among women with gestational diabetes, which has not been well studied in prior cohorts.

Conclusions: This study makes use of diverse public health surveillance data to construct a population-based postpartum cohort of pregnant women to produce pioneering evidence of diabetes disease progression (using HbA1c levels) following pregnancies complicated by GDM. Future research will leverage this novel cohort to investigate how social determinants influence lifecourse racial-ethnic disparities in diabetes.

Disclosure

T. Janevic: None. K. J. Mccarthy: None. J. J. Kennedy: None. H. Chan: None. G. Van wye: None. V. L. Mayer: None. S. H. Liu: None. M. Huynh: None.

Funding

National Institutes of Health (R21DK122266)
951-P: Diabetes Management Delivery and Pregnancy Outcomes in Women with Gestational Diabetes Mellitus during the First Wave of the 2020 COVID-19 Pandemic: A Single Reference Centre Report
Authors: WILK MAGDALENA , SUROWIEC PAULINA , MATEJKO BARTłOMIEJ , CYGANEK KATARZYNA , HURAS HUBERT , MALECKI MACIEJ
Published: June 2021

The COVID-19 pandemic has forced a rapid adaptation of healthcare services to secure medical care for many patients’ groups. This includes women with Gestational diabetes mellitus (GDM). We evaluated the impacts of the first COVID-19 wave on parameters such as the GDM treatment, glycemic control and pregnancy outcomes. In this retrospective study from a reference diabetes centre (Krakow, Poland), we compared patient data from two different time periods: the first wave of COVID-19 pandemic (March 2020 - June 2020) and the preceding five months (October 2019 - February 2020). Data was collected from the medical records and telephone surveys. No patient was diagnosed with concomitant COVID-19. We included 155 women - Group 1 N=73 and Group 2 N= 82 from the COVID-19 pandemic period and non-COVID-19 period, respectively. During the COVID-19 pandemic, almost half of all GDM women (N1=36, 49.3%) used telemedicine as a method of contacting their diabetic specialist while this tool was not utilized in the earlier period. Moreover, these patients reported difficulties in performing blood glucose self-control more often (N1=20, 27.4% vs. N2=7, 8.5% p=0.002) and spent less time on diabetes education and training than the control group on average (N1=39, 53.4% vs. N2=9, 9.8% below 2 hours of training; p≤0.001). Glycemic control parameters were very similar and most analysed pregnancy outcomes occurred with comparable frequencies. Differences were found with respect to the incidence of prolonged labour which was more frequent in the COVID-19 period Group 1 (N1=12, 16.4% vs. N2=3, 3.7% p=0.007) whereas no episodes of pre-eclampsia were observed in this group (N1=0 vs. N2=7, 8.5% p=0.01) during this same time period. We report that the first wave of the COVID-19 pandemic did not seem to have a negative impact on glycemic control and pregnancy outcomes in GDM women, in spite of difficulties in diabetes management delivery.

Disclosure

M. Wilk: None. P. Surowiec: None. B. Matejko: Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care. K. Cyganek: Advisory Panel; Self; Medtronic, Speaker’s Bureau; Self; Lilly Diabetes, Novo Nordisk. H. Huras: None. M. Malecki: Advisory Panel; Self; Abbott Diabetes, Medtronic, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck & Co., Inc., Mundipharma International, Novo Nordisk, Sanofi-Aventis, Servier Laboratories.
953-P: Glycated Albumin Is Not an Accurate Marker of Glycemia in Pregnancy or Postpartum
Authors: SOFFER MARTI D. , JAMES KAITLYN , CALLAHAN MICHAEL J. , BARTH WILLIAM H. , POWE CAMILLE E.
Published: June 2021

Objective: Assessments for diabetes are vital to pregnancy and postpartum (PP) care, but screening, conducted with oral glucose tolerance tests (OGTTs), is cumbersome. Outside of pregnancy, percent glycated albumin (%GAlb) reflects average glycemia over a period of weeks. %GAlb may not be subject to the same limitations as hemoglobin A1c in pregnancy, as it does not rely on stable red blood cell kinetics. We studied %GAlb as a potential glycemic marker during gestation and PP.

Study Design: Pregnant women (N=50) in the Study of Pregnancy Regulation of Insulin and Glucose cohort underwent 75g OGTTs at a mean of 13 weeks (SD 1.6, V1) and 26 weeks (SD 1.4, V2) of gestation and 11 weeks (SD 4.9) PP. Non-pregnant controls had a single OGTT. We measured GAlb on frozen plasma samples.

Results: Serum total GAlb and total albumin decreased from V1 to V2 and increased PP to levels higher than at V1. %GAlb declined between V1 and V2 (β= -0.64 95% CI [-0.8, -0.4] p<0.001) and remained stable between V2 and PP (β= -0.04 [-0.3, 0.2] p=0.66). Age-adjusted comparisons to non-pregnant controls showed that %GAlb values were similar to controls at V1 (β=0.05 [-0.5, 0.6] p=0.84), and were lower at V2 (β= -0.53 [-1.1, 0.0] p=0.05) and PP (β= -0.62 [-1.1, -0.1] p=0.02). Neither glucose levels nor hemoglobin A1c were associated with %GAlb at V1, V2, or PP. BMI was inversely related to %GAlb in pregnancy (V1: rho= -0.5, p=0.0001; V2 rho= -0.4, p=0.006), but not PP (rho= -0.2, p=0.31). BMI was higher at both V2 (β=2.05 [1.5, 2.6] p<0.001) and PP (β=0.65 [0.1, 1.2] p=0.01 compared to V1. However, BMI-adjusted longitudinal changes in %GAlb were similar to those in unadjusted analyses. Adjustment for BMI also did not reveal associations between %GAlb and glucose levels or A1c.

Conclusions: %GAlb decreases during gestation and remains decreased PP, despite a return of total albumin and total GAlb to baseline. Given the lack of correlation with OGTT glucose levels or hemoglobin A1c, %GAlb is unlikely to be useful in assessing glycemia in pregnant or PP women.

Disclosure

M. D. Soffer: None. K. James: None. M. J. Callahan: None. W. H. Barth: None. C. E. Powe: None.
954-P: In Gestational Diabetes, Patient-Led Insulin Titration Is Rapidly Effective without Detrimental Hypoglycaemia
Authors: MAYNE ISABELLE K. , THOMAS NICHOLAS , HATTERSLEY ANDREW T. , MCGOVERN ANDREW P.
Published: June 2021

Introduction: Elevated fasting blood glucose in gestational diabetes (GDM) is the strongest predictor of adverse pregnancy outcomes but is difficult to treat. We assessed the effectiveness and safety of a novel patient-led insulin dose titration algorithm, targeting rapid reduction in fasting glucose.

Research Design and Methods: In women with GDM commenced on insulin, we initiated a patient-led approach to basal dose titration. Women were asked to increase their basal insulin dose by 4 units after every elevated fasting blood glucose (>90 mg/dL). We retrospectively reviewed the records of 50 women with GDM, after initiating this approach. Daily fasting capillary glucose measurements and insulin dose were collected from GDM diagnosis to delivery.

Results: Basal insulin was commenced at a median 30+4 weeks gestation in 28 (56%) women. At insulin initiation median fasting glucose was 104.4 mg/dL. Fasting glucose control (defined as the first of three consecutive readings <95 mg/dL) was achieved by all women after a median 4 days (IQR: 1-13). This was successfully maintained for the remainder of pregnancy with additional patient-led titrations. Basal insulin dose at delivery (median 38+2 weeks gestation) was a median 34 units (IQR 18-62; 0.31 units/kg; IQR 0.23-0.71) with a birthweight less than half a standard deviation above normal (birthweight z-score 0.47 vs. 0.81 [n=34 insulin treated prior to implementation]). Hypoglycaemia <63 mg/dL was uncommon in those on basal insulin (1.86% of all fasting glucose readings) with just five values <54 mg/dL (0.34% of all readings). By comparison, in women never started on basal insulin (n=22), 0.45% of fasting readings were <63 mg/dL with just one value <54 mg/dL (0.09% of all readings). No patients experienced hypoglycaemia requiring assistance.

Conclusions: In GDM, fasting glycaemic control is achieved within a week by using intensive patient-led insulin titration and is not at the expense of detrimental hypoglycaemia.

Disclosure

I. K. Mayne: None. N. Thomas: None. A. T. Hattersley: None. A. P. Mcgovern: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.
971-P: Prevalence of Diabetic Cardiomyopathy in Real-World Practice: A Longitudinal Cohort Study
Authors: SWIATKIEWICZ IWONA , PATEL NEEJA T. , TAUB PAM R.
Published: June 2021

Background: Diabetic Cardiomyopathy (DbCM) is a form of Stage B heart failure (HF) which results from diabetes-associated metabolic alterations. The prevalence of DbCM in patients with type 2 diabetes (T2D) is not well established. This study aims to evaluate prevalence of DbCM in T2D patients that have had transthoracic echocardiograms (TTE) at the UC San Diego Medical Center.

Methods: Retrospective review of medical records of patients with confirmed T2D who had TTE within 2010-2015 performed. DbCM was diagnosed in patients without overt HF based on echocardiographic demonstration of left ventricular (LV) dysfunction (LVD) defined as LV ejection fraction (LVEF) ≥45% and left atrial volume index (LAVI) ≥34 mL/m2, while excluding other medical conditions which can contribute to LVD and TTE findings.

Results: In total, 6570 T2D patients with TTE were identified and 5959 (91%) had LVEF≥45%. Of them, 1868 patients (31%) had LAVI≥34 mL/m2, thus met criteria for LVD suggesting diagnosis of DbCM. After excluding patients with comorbidities such as hypertension (42% of excluded patients), coronary artery disease (38%), and valvular heart disease (24%), 165 patients (9% of patients with LVD; 3% of T2D patients with TTE) met criteria for DbCM associated solely with T2D. LV hypertrophy was found in 70% of patients with DbCM.

Conclusion: The majority of T2D patients (~91%) had preserved LV systolic function, of which at least ~31% had initial diagnosis of DbCM. The conservative estimation of the prevalence of DbCM indicates that at least ~9% of patients from this group had DbCM associated solely with T2D. However, this is an underestimation as only patients who had TTE were included and LAVI was the only initial criteria used to stratify the patients. If other criteria such as elevated E/E’ or LV hypertrophy were included we estimate the prevalence to be significantly higher. Therapies that target metabolic derangement responsible for DbCM can be useful in treating T2D patients to prevent progression to overt HF.

Disclosure

I. Swiatkiewicz: None. N. T. Patel: None. P. R. Taub: Consultant; Self; Amgen Inc., Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Other Relationship; Self; Applied Therapeutics.

Funding

Applied Therapeutics
98-LB: Diabeloop DBL4K Hybrid Closed-Loop System Improves Time-in-Range without Increasing Time-in-Hypoglycemia in Children Aged 6–12 Years
Authors: KARIYAWASAM DULANJALEE , MORIN CAROLE , CASTEELS KRISTINA , TALLEC CLAIRE LE , GODOT CECILE , SFEZ ANNIE , GARREC NATHALIE , POLAK MICHEL , CHARPENTIER GUILLAUME , FRANC SYLVIA , BELTRAND JACQUES
Published: June 2021

Introduction: The DBLG1 Hybrid Closed-Loop system improves time in range and glycemic control in adults. However, the efficacy and safety of the system had not yet been evaluated in children.

Objective: of this study is to evaluate the non-inferiority of the DBL4K (Diabeloop for Kids) hybrid closed-loop system (Kaleido pump + Dexcom G6 = CL) compared to a Dexcom G6 sensor augmented pump (open loop = OL) in prepubescent children.

Materials and Methods: Multicenter open-label randomized controlled trial in 3 pediatric diabetology centers, 2 of which are French. The CL and OL are allocated for 4 days in hospital, followed by 6 weeks at home for the French centers.

Results: Seventeen patients (mean age: 8.3+/- 1.6 years) were included for evaluation at 6 weeks at home between March and December 2019. The percentage of time spent in range (0.7-1.8 g/L) was significantly higher in the CL group during the 6 weeks at home (66.19% in CL vs. 58.68% in OL, p<0.001). The percentage of time spent in hypoglycemia (<0.7 g/L) was significantly lower in the CL group (2.62% in CL vs. 5.24% in OL, p<0.0001) as well as the number of hypoglycemic episodes (25.51 in CL vs. 48.16 in OL, p<0.0001). The coefficient of variation of blood glucose is significantly lower in CL group (31.85% in CL vs. 36.36% in OL, p<0.001). No events of ketoacidosis or severe hypoglycemia were recorded.

Conclusions: The DBL4K Closed-Loop System is suitable for prepubescent children. It is not inferior to sensor augmented pump therapy in children. Just as in adults it improves the time in range while decreasing the time spent in hypoglycemia. It could allow for better long-term glucose control in children with diabetes.

Disclosure

D. Kariyawasam: None. C. Morin: None. K. Casteels: None. C. Le Tallec: None. C. Godot: None. A. Sfez: None. N. Garrec: None. M. Polak: Other Relationship; Self; AMMTeK. G. Charpentier: Other Relationship; Self; Diabeloop. S. Franc: Advisory Panel; Self; Diabeloop SA. Board Member; Self; Novo Nordisk. Research Support; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Self; Diabeloop SA. Other Relationship; Self; Abbott Diabetes. J. Beltrand: None.
98-OR: Gestational Glucose Intolerance without Gestational Diabetes Is a Risk Factor for Type 2 Diabetes
Authors: SELEN DARYL J. , THAWEETHAI TANAYOTT , HSU SARAH , JAMES KAITLYN , KAIMAL ANJALI , MEIGS JAMES B. , POWE CAMILLE E.
Published: June 2021

Background: Women with gestational diabetes (GDM) have an increased risk of adverse perinatal outcomes and future type 2 diabetes (T2D). Gestational glucose intolerance (GGI, abnormal initial GDM screen) without GDM has been linked to adverse perinatal outcomes but is not a recognized T2D risk factor. We tested whether GGI without GDM is associated with incident T2D.

Methods: Using clinical data from women seen at our US medical center for prenatal and primary care (1998-2018), we assessed risk of T2D (defined using validated laboratory and outpatient diagnoses) according to GGI/GDM status during pregnancy. We defined GGI as 1-hr glucose loading test (GLT) ≥ 140 mg/dl at ≥ 24 weeks gestation. We subcategorized GGI by 3-hr oral glucose tolerance test (OGTT) result. We used Cox proportional-hazard models with time-varying exposures/covariates to assess T2D risk after delivery, adjusting for age, race/ethnicity, parity, insurance type, marital status, BMI, and blood pressure. Women were followed from 1st delivery until diagnosed with T2D or censored at time of last primary care visit.

Results: Among 13988 women, 17109 pregnancies had normal glucose tolerance (NGT, GLT < 140mg/dL). Among 3619 GGI pregnancies (GLT ≥ 140 mg/dl), 2076 had a normal OGTT, 699 had 1 abnormal OGTT value, and 844 had GDM (≥ 2 abnormal OGTT values). Over a median of 8.3 years of follow-up, 2.2% (N=304 women) developed T2D. In our primary comparison, women with GGI without GDM (16% of pregnancies) had increased T2D risk compared to women with NGT (HR 2.1 [1.5-2.9], p<0.001). Among women with GGI, T2D risk increased with the number of abnormal OGTT values (normal OGTT: HR 1.8; 1 abnormal OGTT value: HR 2.8; GDM: HR 11.7; p≤0.01 for all compared to NGT).

Conclusions: Pregnant women with GGI without GDM have a two-fold increased risk of future T2D compared to those with NGT. Clinical data universally available during pregnancy identifies a large, previously unrecognized group of women who may benefit from T2D screening and prevention.

Disclosure

D. J. Selen: None. T. Thaweethai: None. S. Hsu: None. K. James: None. A. Kaimal: None. J. B. Meigs: Consultant; Self; Quest Diagnostics. C. E. Powe: None.

Funding

National Institutes of Health (2T32DK007028-46, K23DK113218); Robert Wood Johnson Foundation; Massachusetts General Hospital
996-P: Prevalence of Functional Hyperandrogenism in Young Women with Type 1 Diabetes: A Preliminary Analysis from a Cross-Sectional Study of a Spanish Cohort
Authors: BAYONA ANE , NATTERO-CHÁVEZ LÍA , DURÁN ELENA FERNÁNDEZ , AVENDAÑO BEATRIZ DORADO , ESCOBAR-MORREALE HÉCTOR F. , LUQUE-RAMÍREZ MANUEL
Published: June 2021

Introduction: Increased prevalence of functional hyperandrogenism/polycystic ovary syndrome (PCOS) has been previously described in type 1 diabetes (T1DM) patients. However, the reported prevalence rates vary depending on different diagnostic criteria. Our study aim was to determine the prevalence of PCOS and hyperandrogenic traits in premeopausal women with T1DM.

Methods: A cross-sectional study was conducted at a diabetes outpatient clinic in a tertiary Hospital from Madrid, Spain. We recruited consecutive premenopausal woman with T1DM, and menarche at least 2 years before the study. For this preliminary report, we included 40 patients. History data collection, physical exam, a complete hormonal analysis in follicular phase (including d4-androstenedione, DHEA-S, total testosterone, SHBG, 17-OH-progesterone, FSH, LH, prolactin, and TSH), and ovarian ultrasound were performed.

Results: Mean age of patients was of 28 ± 8 yr; mean duration of T1DM was of 13 ± 8 yr-old. Twenty-seven patients were on multiple daily insulin therapy, while 13 of them were on continuous subcutaneous insulin infusion. Mean BMI was of 23.8 ± 3.7 Kg/m2. Mean daily insulin dose was 0.64 ± 0.2 U/kg and mean A1C was 7.5 ± 1.8%. PCOS was diagnosed in 7 patients resulting in a 18% (95% CI: 8; 32) prevalence of PCOS according to NIH-Rotterdam, and in 6 patients resulting in a 15% (95% CI: 7; 29) prevalence of PCOS according to AES-PCOS criteria. Three patients [7% (95% CI: 3; 20)] had isolated polycystic ovarian morphology (PCOM), and 7 patients [18% (95% CI: 8; 32)] presented with oligo-amenorrhea (ovulatory dysfunction-WHO class 2).

Conclusion: Our preliminary data show a significant increase in prevalence of PCOS in premenopausal women with T1DM with respect to the general population.

Disclosure

A. Bayona: None. L. Nattero-chávez: None. E. Fernández durán: None. B. Dorado avendaño: None. H. F. Escobar-morreale: Consultant; Self; InsudPharma. M. Luque-ramírez: None.
NATOs rolle i norsk forsvarsreform, 1998‒2002
Authors: Heier Tormod
Published: June 2021

På begynnelsen av 2000-tallet ble det norske invasjonsforsvaret nedlagt. Men hvilke årsaker var viktigst for denne beslutningen? Var det økonomiske, institusjonelle eller kulturelle årsaksforhold? I denne artikkelen legges hovedvekten på institusjonelle årsaker, særlig den norske frykten for at NATO skulle bli irrelevant for USA. Dermed var det bare en ting å gjøre: å avvikle invasjonsforsvaret slik at det kunne frigjøres friske penger. For slik kunne et lite allianseavhengig land, i utkanten av Europa, utenfor EU, og med felles grense til Russland, bidra med ekspedisjonære styrker. Ikke minst for å holde liv i et NATO som strevde med å gjøre seg relevante for USA, først på Balkan og senere i Afghanistan. Med kildemateriale fra Washington D.C., Brussel og Oslo mellom 1998 og 2002 tolkes Norges politiske kontekst inn i et institusjonelt perspektiv. Forhold som resiprositet, norsk omdømme og lojalitet i NATO, blir viktig for å forstå invasjonsforsvarets endelikt.
Abstract in English:NATO’s Role in Norway’s Defence Reforms, 1998–2002At the turn of the new milennium, Norway’s anti-invasion defence concept vanished. What was the rationale for this decision? Was it economc, institutional or cultural reasons? The findings in this article emphasise institutional perspectives. Norwegian apprehensions over a possibly irrelevant NATO in the eyes of the United States stirred a fundamental post-Cold War defence reform. To preclude a future marginalisation of NATO, decision-makers in Oslo needed to free scarce resources from a static, territorial defence that had lost its political and military relevance in the High North. By forging a smaller but more professional force, with improved deployability, survivability and usability abroad, Norway could more effectively contribute to allied cohesiveness. Not least through improved risk- and burdensharing in NATO’s out-of-area operations on the Balkans and in Afghanistan. By using primary sources from Washington, DC, Brussels and Oslo between 1998 and 2002, the data is interpretated though the lense of liberal institutionalism. Explanatory mechanisms such as Norwegian reciprocity in the High North, US expectations towards dependent allies abroad, and Norway’s collective solidarity may explain why the anti-invasion concept died.