bluuebunny/crossref_metadata_2025 huggingface dataset:
1501-P: Patients with Diabetes Mellitus Hospitalized with Pancreatitis Have Reduced Mortality but Higher Overall Cost Compared with Patients without Diabetes
Authors: CHOI NICOLE , GARCIA MONIKA E. , ZAKHARY BISHOY L. , FIREK MATTHEW A. , KIM DANIEL I. , JACKSON CHRISTIAN S. , FIREK ANTHONY
Published: June 2020

Introduction: Acute pancreatitis (AP) is the leading cause of admissions for gastrointestinal disorders in the United States with annual costs of nearly $2.6 billion. The identification of modifiable risk factors may help lower AP-related hospitalizations. Diabetes mellitus (DM) increases the risk of AP. To date, there have been limited single and multi-center studies with varying results on mortality difference in patients with AP and DM. Our primary aim was to evaluate trends in hospitalizations, mortality and costs in patients with DM and AP using a large national database.

Method: We extracted data from Healthcare Cost and Utilization Project Nationwide Inpatient Sample database from 2012-2014. International Classification of Diseases 9th Version, Clinical Modification codes for adult patients hospitalized with primary diagnosis of AP were used.

Result: Between 2012 and 2014, 1,310,385 patients were admitted with a primary diagnosis of AP. 27.4% were diagnosed with AP-DM. Length of stay was four days for all patients. Cost of stay was $7467 for AP without DM, $7560 and $8482 for AP-DM without and with complications, respectively. Regression analysis for mortality controlling for age, gender, DM, and race showed AP-DM had less odds of mortality than patients without DM (p<0.05). The AP patients who were older than age 65 had 2.5 greater odds of mortality (p<0.05). The AP patients with greater Charlson score were at 1.5 greater odds of mortality (p<0.05).

Conclusion: All patients had the same length of stay. The total mortality was lower in AP-DM but higher overall costs compared to patients without DM. The explanation for these differences is unclear but may relate to higher inpatient services for DM, modifying effects of DM on the course of AP, or the type of care patient received in different types of hospitals. Further studies are needed to determine the effects of DM on inpatient mortality, costs and outcomes in patients with AP.

Disclosure

N. Choi: None. M.E. Garcia: None. B.L. Zakhary: None. M.A. Firek: None. D.I. Kim: None. C.S. Jackson: None. A. Firek: None.
1510-P: Age at Menarche, Type 2 Diabetes, and Cardiovascular Disease Complications in U.S. Women Under 65 Years: NHANES, 1999-2016
Authors: LEY SYLVIA H. , LI YALING , REXRODE KATHRYN M. , ELIASSEN A. HEATHER , BUNDY JOSHUA D. , HE JIANG , BAZZANO LYDIA A.
Published: June 2020

Background: Diabetes and diabetes complications are on the rise in U.S. adults under 65 years, while younger onset of menarche is also increasing. We examined the associations of menarche age with type 2 diabetes and with cardiovascular disease (CVD) complications among women with diabetes.

Methods: In the cross-sectional National Health and Nutrition Examination Survey (NHANES) 1999-2016, women aged 20-65 years free of cancer were included. CVD was defined as coronary heart disease and stroke.

Results: Of 15,619 participants, 1,545 (9.9%) reported having type 2 diabetes. Earlier age at menarche was associated with type 2 diabetes, compared to median menarche age 13 years, after multiple adjustment (Table). Among women with diabetes, earlier age at menarche was associated with CVD (Table). The association of earlier age at menarche was more pronounced with stroke among women with diabetes (table). When race stratified, the association between extremely early age at menarche (≤10 years) remained significantly associated with CVD among non-white women with diabetes (OR 2.27 [95% CI 1.11-4.62]), while the association among white women was attenuated (1.95 [0.88-4.30]).

Conclusion: Earlier age at menarche was associated with type 2 diabetes and with CVD among young and middle-aged women living with diabetes in the U.S.

Disclosure

S.H. Ley: None. Y. Li: None. K.M. Rexrode: None. A. Eliassen: None. J.D. Bundy: None. J. He: None. L.A. Bazzano: None.

Funding

National Institutes of Health (P20GM109036)
1515-P: Epidemiology and Treatment of Chronic Kidney Disease among Commercially-Insured Patients in the U.S.
Authors: KAUF TERESA , WANG WEIYING , DILLON ALLISON , SINGH INDERJIT , ODEGARD JOHN T. , RINGEMANN CHRISTIAN , HALDRUP STEFFEN
Published: June 2020

Objectives: Early diagnosis and treatment of chronic kidney disease (CKD) may delay disease progression and reduce the burden of disease. This study examined the epidemiology and treatment of CKD among commercially-insured patients in the U.S.

Methods: A retrospective cohort study was conducted using January 2010-December 2018 MarketScan® data. Patients with ≥2 outpatient (≥ 30 days apart) and/or ≥1 inpatient claims containing a diagnosis code for CKD were eligible for analysis. The earliest CKD diagnosis date served as the index date. Continuous enrollment for ≥6 months pre- and post-index was required. Baseline characteristics and use of ACE inhibitors and/or ARBs pre/post-index were analyzed for the overall CKD population and patients with pre-existing diabetes (Types 1 and 2). Annual CKD prevalence and incidence were calculated from the total enrollee population in a given year.

Results: Of 753,097 CKD patients identified, 310,837 (41.3%) had pre-existing diabetes. More CKD patients with pre-existing diabetes had hypertension (81.7% vs. 75.7% for overall CKD). Approximately 45% of patients in both cohorts were diagnosed at Stage 3. Overall CKD prevalence per 1,000 enrollees increased from 11.7 in 2011 to a high of 16.7 in 2016 before decreasing to 13 in 2018. Among persons with pre-existing diabetes, prevalence was 2.0 per 1,000 enrollees in 2011, falling to 1.6 in 2018, with a high of 2.83 in 2015. In the pre-index period, 55.3% of CKD patients overall and 66.2% of CKD patients with pre-existing diabetes received an ACE/ARB. Following CKD diagnosis, use of ACE/ARBs increased to 63.2% and 73.7% for the overall CKD and diabetes populations, respectively.

Conclusions: On a population basis, the annual incidence of new CKD patients enrolled in commercial plans is not inconsequential. Greater efforts are needed to identify patients at earlier stages of disease and ensure that treatment guidelines are being followed.

Disclosure

T. Kauf: Consultant; Self; Roche Diabetes Care. W. Wang: Consultant; Self; Roche Diabetes Care. A. Dillon: Consultant; Self; Roche Diabetes Care. I. Singh: Employee; Self; Roche Diabetes Care. J.T. Odegard: None. C. Ringemann: Employee; Self; Roche Diabetes Care. S. Haldrup: Employee; Self; F. Hoffmann-La Roche Ltd.
1518-P: Worsening of Microvascular Reactivity and Markers of Endothelial Activation and Oxidative Stress in Patients with Stabilized Type 1 Diabetes: 3-Year Follow-Up
Authors: SKRHA JAN , SOUPAL JAN , FLEKAC MILAN , PRAZNY MARTIN , SKRHA JAN
Published: June 2020

Endothelial activation accelerated by oxidative stress (OxS) is believed to be the major step in development of diabetes angiopathy. The aim of this follow-up study was to measure microvascular reactivity (MVR) and markers of OxS.

Our study involved 87 patients with type 1 diabetes (aged 37 ± 15 yrs, HbA1C 7.8 ± 1.5 % DCCT, DM duration 18 ± 11 yrs). MVR was evaluated from post-occlusive reactive hyperemia (PORH) by Laser-Doppler fluxmetry (Perimed) and skin autofluorescence (SAF), reflecting advanced glycation endproducts (AGEs) accumulation, was assessed by AGE-Reader (Diagnoptics). OxS was evaluated by malondialdehyde (MDA), derivatives of reactive oxygen metabolites (d-ROMs) test and plasma antioxidant test (PAT) (FRAS4). Markers of endothelial activation (ICAM-1, VCAM-1, vWF) and routine biochemical and biometrical parameters were evaluated in all patients during 3 years of follow-up.

Diabetes control slightly improved during the study period (HbA1c 7.8 ± 1.5 vs. 7.5 ± 1.4 % DCCT, p<0.05), while SAF remained almost unchanged (2.1 ± 0.5 vs. 2.3 ± 0.5 AU, ns). Worsening of MVR was observed (Time to max PORH 12.7 vs. 17.5 s, p<0.05). Significant increase in VCAM-1 was present (718 ± 186 vs. 918 ± 550 pg/L, p<0.005), while ICAM-1 and vWF did not change significantly. Both higher MDA (0.70 ± 0.26 vs. 0.81 ± 0.23 µmol/L, p<0.05) and PAT (2431 ± 645 vs. 2944 ± 466 U Cor, p<0.0001) were observed. Skin autofluorescence was positively associated with vibration perception threshold (r=0.45, p<0.0001) and HbA1c (r=0.24, p<0.005).

Although diabetes control slightly improved, we observed further progression of endothelial dysfunction and oxidative stress in our T1D patients. Higher AGEs accumulation in patients with worse glucose control was associated with impaired vibration perception threshold. It is questionable whether boosted human antioxidant capacity in subject with increased OxS could be considered protective and beneficial.

Disclosure

J. Skrha: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. J. Soupal: Advisory Panel; Self; Abbott. Consultant; Self; Medtronic, Roche Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc. M. Prazny: Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Roche Diabetes Care. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd.

Funding

RVO VFN64165, Progres Q25
153-LB: Physician Well-being Related to Diabetes Technology and Clinic Workflow
Authors: SHAH VRUSHALI , PINKHASOVA DIANA , FRENCH ESRA KARSLIOGLU
Published: June 2020

Background: Endocrinology physicians and clinic staff are burdened by workload created during the download of diabetes devices (insulin pumps, glucometers, and sensors). Inefficiencies caused by data interoperability can impact physician well-being and clinic workflow. The aim of this study is to identify physician wellbeing related to Diabetes Technology (DT) and determine whether the use of a single software platform to upload and view diabetes data improves efficiency.

Methods: Physician satisfaction survey related to DT was sent to providers at a single academic endocrinology office. Tidepool®, a free software, was implemented to enable data upload from multiple devices onto a single platform. The time required to have this data available to the provider was recorded pre and post-implementation. The provider was then able to view this data in the patients’ electronic chart.

Results: All providers (n=14) completed the survey. Only 7% felt that pumps were always downloaded on time. Related to DT, 21% felt a sense of dread at work, 36% experienced a lack of enthusiasm, and 43% experienced emotional exhaustion. Almost 80% felt that clinic workflow due to DT contributed to spending less time with patients. Data from a total of 90 devices pre and 144 devices post-Tidepool® were included in the study. There was a significant improvement in the average time of sensor and glucometer data availability; 4.95 vs. 3.2 minutes (CI -2.48 to -1.01, p-value <0.0001). There was no significant change in average time for insulin pump data availability; 8.8 vs. 8.46 minutes (CI -2.6 to 2.1, p-value 0.7) post Tidepool®. Time and resources related to printing the data were saved as well. 100% of staff at the download station felt that Tidepool® was an easier software to use.

Conclusion: Our study shows a high prevalence of physician dissatisfaction and symptoms of burnout related to DT among the providers even at a university academic office with access to the best resources. The use of Tidepool® could potentially improve clinic workflow.

Disclosure

V. Shah: None. D. Pinkhasova: None. E. Karslioglu French: None.

Funding

University of Pittsburgh Medical Center
1537-P: Lifetime Risk of Diabetes in Metropolitan India: Striking in All BMI Groups
Authors: LUHAR SHAMMI , KINRA SANJAY , MOHAN VISWANATHAN , KONDAL DIMPLE , ANJANA RANJIT MOHAN , PATEL SHIVANI A. , ALI MOHAMMED K. , PRABHAKARAN DORAIRAJ , TANDON NIKHIL , T NARAYAN K.M. VENKA
Published: June 2020

Background: To our knowledge, no estimates of lifetime risk of diabetes have been produced for India, a country with a high propensity to developing diabetes and a low overall body weight compared to high-income countries.

Data: We estimated the lifetime risk of diabetes in metropolitan India, and its variation by sex, age and BMI. We used government mortality statistics, diabetes prevalence from the Indian Council for Medical Research INdia DIABetes study (2008-15) and incidence from the Centre for Cardiometabolic Risk Reduction in South Asia (2010-2018). We limited estimates Indians aged 20 or more years.

Results: Overall lifetime risk of diabetes in women in metropolitan cities aged 20 was 74.7% (95%CI: 65.4-83.3%), and 69.0% (95%CI: 58.9-78.7%) in men. Remaining risk is highest among the obese (92.9% (95%CI: 88.0-96.0%) in women and 92.4% (95%CI: 86.6-96.1%) in men aged 20) and is lowest among underweight/normal weight people (56.4% (95%CI: 46.9-66.3%) in women and 54.2% (95%CI: 44.5-64.6%) in men). Lifetime risk declines with age (to 67.3% (95%CI: 57.4-77.1%) in women aged 40 to 42.5% (95%CI: 33.8-52.9%) at age 60).

Conclusion: In metropolitan India, 1 in 2 underweight/normal weight, and 9 in 10 obese, people aged 20 are projected to develop diabetes during their life. This portends a serious epidemic and indicates what may develop elsewhere in India in the absence of urgent action.

Table. Lifetime risk of diabetes by sex, age and BMI

Disclosure

S. Luhar: None. S. Kinra: None. V. Mohan: None. D. Kondal: None. R. Anjana: None. S.A. Patel: None. M.K. Ali: Research Support; Self; Merck & Co., Inc. D. Prabhakaran: None. N. Tandon: None. K. Narayan: None.

Funding

Economic and Social Research Council (ES/J500021/1)
1542-P: Associations of Dietary Patterns with Glycemia in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study
Authors: BASU ARPITA , ALMAN AMY C. , SNELL-BERGEON JANET K.
Published: June 2020

Background: Among the modifiable risk factors, diet plays an important role in the risks and progression of poor glycemic control in diabetes. However, few studies have examined this association in people who have type 1 diabetes (T1D), who are at a greater risk of developing cardiovascular diseases than people without diabetes.

Methods: We conducted cross-sectional and longitudinal analyses of data from CACTI study [n=1257; T1D: n=568; nondiabetic controls: n=689] collected between March 2000 and April 2002. Participants completed a validated food frequency questionnaire, a physical examination and fasting biochemical analyses (12h fast). At baseline, dietary patterns based on variations in food group intake were created with principal components analysis (PCA). Linear regression was used to examine associations of dietary patterns with HbA1c in a model adjusted for age and sex and stratified by diabetes status.

Results: Three dietary patterns were identified using PCA as follows: ’fruits, veggies, meats, cereal’, ’baked desserts’ and ’convenience foods and alcohol’ patterns. At baseline, higher intake of ’baked dessert’ pattern was significantly associated with higher HbA1c in T1D (β±SE: 0.10±0.05, p=0.03), but not in nondiabetic controls (0.06±0.04, p=0.21) when adjusted for age, sex and baseline total calories, as well as diabetes duration for T1D. At year-6, baseline higher intake of ’baked dessert’ pattern tended to be associated with increasing HbA1c in T1D (β±SE: 0.11±0.06, p=0.06), but not in nondiabetic controls (0.01±0.04, p=0.68) when adjusted for the same covariates.

Conclusions: Habitual intake of a dietary pattern that is characterized by an increased intake of added sugar and saturated fats, such as in baked desserts may increase risks of poor glycemic control in T1D.

Disclosure

A. Basu: None. A.C. Alman: None. J.K. Snell-Bergeon: Stock/Shareholder; Self; GlaxoSmithKline plc.

Funding

American Diabetes Association (7-13-CD-10 to J.K.S-B.)
155-LB: Understanding Determinants of Caffeinated Sugar-Sweetened Beverage Consumption among Children: A Concept-Mapping Approach
Authors: HALBERG SABRINA E. , VISEK AMANDA J. , BLAKE EMILY F. , SACHECK JENNIFER M. , SYLVETSKY ALLISON
Published: June 2020

Background: Excess sugar-sweetened beverage (SSB) consumption is associated with type 2 diabetes, obesity, and cardiometabolic disease. In addition to having high added sugar content, caffeinated sugar-sweetened beverages (CSSBs) are the predominant source of caffeine among children. However, the extent to which the caffeine and sugar in CSSBs promote continued CSSB intake among children has not been rigorously studied.

Aim: To develop a conceptual framework of children’s CSSB consumption using group concept mapping.

Methods: Children, ages 8-14, recruited from the Washington, D.C. area who reported consuming ≥ 12 ounces of CSSBs per day participated in concept mapping, an applied social research multimethodology. Concept mapping involved 3 participant-driven activities, including: (1) brainstorming (n=51), during which children reported reasons or determinants for their CSSB consumption, from which 58 unique determinants were identified, (2) sorting (n=72), during which children categorized each of the determinants and named each category, and (3) rating (n=74), during which children rated the influence of each determinant on their own consumption (Likert scale, 1-5). Similarity matrices, multidimensional scaling, and hierarchical cluster analysis were applied to generate concept maps.

Results: The concept maps generated from this study displayed the 58 determinants in a 9-cluster solution, reflective of 3 overarching motives: Perceived Mental and Physical Benefits, Energy and Function, and Preference and Palatability. Among the 58 determinants, the greatest drivers of consumption related to Energy and Function and Preference and Palatability.

Conclusions: The use of concept maps to illuminate the importance of certain determinants, such as energy improvements or taste preferences related to caffeine and/or sugar, as drivers of consumption will inform the development of tailored interventions to reduce CSSB consumption.

Disclosure

S.E. Halberg: None. A.J. Visek: None. E.F. Blake: None. J.M. Sacheck: None. A. Sylvetsky: None.
1574-P: Insulin Resistance, but Not Impaired Beta-Cell Function, at Type 2 Diabetes Diagnosis Is Associated with Mortality
Authors: OTTEN JULIA , TAVELIN BJÖRN , SÖDERBERG STEFAN , ROLANDSSON OLOV
Published: June 2020

We hypothesized that individuals with type 2 diabetes and low insulin resistance in combination with impaired beta cell function at diabetes diagnosis have lower mortality compared to those with high insulin resistance in combination with preserved beta cell function.

In this prospective cohort study, 864 individuals with type 2 diabetes (median age 60 years) had fasting glucose and fasting C-peptide measured at the time of diabetes diagnosis or up to five years before diagnosis. Insulin resistance was estimated with HOMA-%S and beta cell function with HOMA-%B. Four groups based on the median of HOMA-%S and HOMA-%B were formed: 1) low HOMA-%S and high HOMA-%B, 2) low HOMA-%S and low HOMA-%B, 3) high HOMA-%S and high HOMA-%B, and 4) high HOMA-%S and low HOMA-%B (reference group). Mortality was registered during a median follow up of 15 years after diabetes diagnosis, and the associations between the four groups and mortality was estimated with Cox regression adjusted for gender and age at diabetes diagnosis (model 1) and adjusted for gender, age at diabetes diagnosis, smoking, hypertension, BMI and total cholesterol (model 2).

Group 1 had higher total mortality (model 2: HR 1.58, 95% CI 1.06−2.36) compared to the reference group 4. Group 1 was also associated with higher cardiovascular mortality (model 1: HR 2.24, 95% CI 1.08−4.66), but this difference was no longer significant in model 2.

Insulin resistance in combination with preserved beta cell function at the time of diabetes diagnosis is an independent risk factor for total mortality. Insulin resistance in combination with preserved beta cell function increases the risk for cardiovascular mortality but not independent of conventional risk factors. Thus, treatment of type 2 diabetes should focus not only on normalizing blood glucose levels but also improve insulin resistance.

Disclosure

J. Otten: None. B. Tavelin: None. S. Söderberg: None. O. Rolandsson: None.
1584-P: Lack of Prescription Medication Coverage and Poor Glycemic Control among U.S. Adults with Diagnosed Diabetes, 2005-2016
Authors: BULLARD KAI M. , BENOIT STEPHEN R. , SAYDAH SHARON , MERCADO CARLA , IMPERATORE GIUSEPPINA
Published: June 2020

About 20 million U.S. adults with diabetes (DM) used glucose-lowering medications in 2016. We examined insurance coverage for prescription medications and its association with glycemic control in this population, overall and by age group. We used data from 3,311 adults aged ≥18y with self-reported diagnosed DM and treated with oral hypoglycemic agents or insulin in the 2005-2016 National Health and Nutrition Examination Survey. Participants reported on having health insurance that covered any part of prescription costs. Poor glycemic control (poor A1C) was defined as A1C >9%. During 2005-2016, 15.3% (95%CI 13.7-17.1) of treated U.S. adults with DM lacked prescription coverage, including 8.9% (7.9-10.1) who were uninsured and 6.4% (5.2-7.8) who were insured without any prescription coverage. Compared to treated adults ≥65y, the percentage without prescription coverage was 55% higher for treated adults 18-44y (20.3%, 16.3-25.0 vs. 13.1%, 10.7-16.0) and similar for those 45-64y (15.9%, 13.7-18.4). Overall, 21.4% (17.6-25.7) of treated adults without prescription coverage and 13.5% (11.9-15.3) with prescription coverage had poor A1C (prevalence ratio 1.58 [1.25-2.00]). By age group, % poor A1C differed by coverage status for treated adults 18-44y (covered: 24.9% [18.8-32.1]; not covered: 38.9% [28.2-50.8], p=0.034) and those 45-64y (covered: 15.2% [12.8-18.1]; not covered: 25.5% [19.8-32.3], p=0.005) but not for those ≥65y (covered: 7.5% [6.1-9.1]; not covered: 6.4% [4.0-9.9], p=0.29). For those insulin-treated, % poor A1C differed by coverage status only among adults 18-44y (covered: 31.9% [23.4-41.8]; not covered: 70.0% [53.1-82.8], p<0.001). Despite the high usage of medication among U.S. adults with diabetes, about 15% of the treated population has no prescription coverage. Most young adults under 45y without prescription coverage who use insulin have poor glycemic control, signifying a major public health concern.

Disclosure

K.M. Bullard: None. S.R. Benoit: None. S. Saydah: None. C. Mercado: None. G. Imperatore: None.
1589-P: Testosterone (T) in Early Puberty Predicts Visceral (VAT) and Subcutaneous Adipose Tissue (SAT) in the EPOCH (Exploring Perinatal Outcomes among Children) Cohort
Authors: KIM CATHERINE , HARRALL KYLIE K. , GLUECK DEBORAH H. , DABELEA DANA
Published: June 2020

Among adults, higher T predicts lower VAT in men and higher VAT in women, and higher E2 predicts greater SAT in women. The degree to which the association between adiposity and sex steroids is bidirectional is controversial. Using data from a cohort of adolescents, we examined whether sex steroid levels in early puberty influenced VAT and SAT deposition in adolescents. EPOCH participants (n=418, 209 girls and 209 boys) underwent sex steroid measures at visit 1 (mean age 10 years) and magnetic resonance imaging (MRI) assessments of VAT and SAT at visit 1 and visit 2 (mean age 17 years). Using mixed models, we examined whether T and E2 at visit 1 were associated with overall VAT and SAT levels from visit 1 to visit 2. Models adjusted for maternal education and income as well as children’s race, pubertal status, caloric intake, physical activity levels, insulin, leptin, and MRI-measured hepatic fat fraction. Among girls, each unit increase in T was associated with a higher overall VAT (0.16, 95% confidence interval [CI] 0.04, 0.28) and SAT (0.33, 95% CI 0.33, 1.52) levels. Each unit increase in E2 was associated with overall higher SAT (0.56, 95% CI 0.28, 0.83) levels. Among boys, undetectable T was associated with higher VAT (5.12, 95% CI 1.90, 8.36) and lower SAT (-18.85, 95% CI -36.23, -1.46) levels. We conclude that endogenous T and E2 during the pubertal transition significantly influence adolescent adipose tissue deposition in both boys and girls. Future investigations should examine how the use of exogenous sex hormones impacts adipose tissue deposition during this critical period. Additional follow-up is needed to determine how adolescent fat deposition impacts subsequent glucose tolerance in early adulthood.

Disclosure

C. Kim: Research Support; Spouse/Partner; Apple. K.K. Harrall: None. D.H. Glueck: None. D. Dabelea: None.

Funding

National Institutes of Health (R01DK068001)
1591-P: Associations of Referral to Wellness Counseling and Diabetes in Midlife Women
Authors: BADON SYLVIA E. , NANCE NERISSA , HEDDERSON MONIQUE M. , AVALOS LYNDSAY
Published: June 2020

Wellness counseling resources have the potential to decrease diabetes risk in high risk populations. Midlife women are at high risk for diabetes because of menopause and aging, and diabetes risk is further increased in women with low levels of physical activity (PA). We determined whether referral to wellness counseling was associated with diabetes risk among midlife women with low PA levels. We identified 64,350 women members of Kaiser Permanente Northern California who were 45-55 years old, did not have diabetes, and reported <10 minutes of PA on PA screening during an appointment with their primary care provider in 2015. We identified referrals to wellness counseling resources within 30 days of the index visit and diabetes diagnoses 2 years after the visit using the electronic health record. Relative risk of diabetes associated with wellness counseling referral was estimated using modified Poisson regression, adjusting for age, race/ethnicity, smoking, and comorbidities. In 2015, 1.6% (n=1029) of midlife women reporting low PA levels were referred to wellness counseling resources. Women who were referred were more likely to be Hispanic (32% vs. 24%) or non-Hispanic Black (14% vs. 9%) and have prediabetes (16% vs. 7%), hypertension (39% vs. 24%), or a cholesterol disorder (26% vs. 20%) than women who were not referred. Our preliminary analysis suggests that referral to lifestyle-related wellness counseling was associated with 2.94 times greater risk of diabetes (95% CI: 2.64, 3.27). Referral to wellness counseling resources among midlife women with low levels of PA at Kaiser Permanente Northern California is low; however, women with diabetes risk factors (minority women and women with comorbidities) were more likely to be referred, which is likely why we observed associations of referral with greater risk of diabetes. Future research should examine whether participation in lifestyle-related wellness counseling resources after referral is effective in decreasing diabetes risk in midlife women.

Disclosure

S.E. Badon: None. N. Nance: None. M.M. Hedderson: None. L. Avalos: None.

Funding

Kaiser Permanente; National Institutes of Health (T32DK116684)
1630-P: Receipt of Type 1 Diabetes Care by Physician Specialty during Adolescence and Young Adulthood
Authors: WISK LAUREN E. , LANDRUM MARY BETH , FU CHRISTINA , CHIEN ALYNA
Published: June 2020

For a sample of continuously-insured adolescents/young adults (AYA, ages 13-26) with T1D enrolled in a national managed care plan from 2013-2016 (16,500 person-years among 8,694 AYA), we describe frequency of medical visits, types of physicians (specialist vs. primary care; pediatric vs. adult) delivering care, and receipt of recommended diabetes monitoring tests. Over 75% of all outpatient visits for 13 year olds (yo) were to pediatric physicians, declining to 2.5% of visits for 26yo; access to specialty care declined from 82% of 13yo to 68% of 26yo. Those receiving ≥twice yearly A1c tests declined from 83% of 13yo to 60% of 26yo, while receiving annual LDL or microalbumin tests rose from 51% of 13yo to 60% of 26yo. Those not accessing specialty care were the least likely to receive recommended tests (A1c odds ratio [OR]:0.26, 95%CI:0.23-0.29; LDL OR:0.61, 95%CI:0.55-0.67; microalbumin OR:0.50, 95%CI:0.46-0.56). Those receiving the majority of care from adult specialists had lower odds of receiving recommended tests (A1c OR:0.61, 95%CI:0.54-0.69; microalbumin OR:0.90, 95%CI:0.82-0.99) compared to those receiving care from pediatric specialists. Despite continuous insurance, many AYA don’t access any specialty care and are less likely to receive routine diabetes monitoring tests as a result. There is large variation in physician types visited by AYA and measurable differences in testing by specialty type.

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.)
1642-P: Colocalization Analyses of Genetic Associations of Type 2 Diabetes with DNA Methylation on Chromosome 11p in American Indians
Authors: HANSON ROBERT L. , KOBES SAYUKO , HSUEH WEN-CHI , MULLER YUNHUA L. , KNOWLER WILLIAM C. , BAIER LESLIE
Published: June 2020

Our recent genome-wide association study (GWAS) identified variants strongly associated with type 2 diabetes (T2D) on chromosome 11p15 in American Indians at KCNQ1 (index variant rs2237895, P=2.5×10-8) and TH (rs11564707, P=3.8×10-8). To assess whether these variants influence epigenetic variation we analyzed associations with DNA methylation. Participants included 7659 American Indians (33% with T2D) who had participated in the GWAS, 842 of whom had DNA methylation measured in peripheral blood. Methylation was measured with the Infinium 450k array (Illumina, San Diego, CA). To identify local CpG sites associated with index variants, we analyzed associations for sites within 1 Mb of each gene (2162 sites for KCNQ1, 2325 for TH). Strong associations were identified: the diabetes risk allele at rs2237895 associated with decreased methylation at cg14637411 (β= 1.35 SD per copy, P=2.6×10-169), and the risk allele at rs11564707 associated with increased methylation at cg19878200 (β=0.46 SD, P=1.1×10-21). We further conducted Bayesian functional fine-mapping association of T2D and statistical colocalization of association of methylation at these sites with T2D using CAVIAR- including 1943 variants for KCNQ1 and 2954 variants for TH. Potentially causal variants for T2D were identified for each gene (30 for KCNQ1 and 33 for TH with posterior probability of causality >0.01); all were in strong linkage disequilibrium with the index variant. Strong evidence for colocalization of the association of T2D with methylation at cg14637411 (colocalization posterior probability >0.01, suggesting both traits are influenced by the same causal variants) was seen with 4 KCNQ1 variants: rs60808706, rs2299620, rs2237896 and rs2237897. Evidence for colocalization was weak for cg19878200 and T2D at TH variants. These results support the notion that KCNQ1 variants may influence T2D risk via an epigenetic effect, and they identify candidate functional variants.

Disclosure

R.L. Hanson: None. S. Kobes: None. W. Hsueh: None. Y.L. Muller: None. W.C. Knowler: None. L. Baier: None.

Funding

American Diabetes Association (1-12-DNP-01 to R.L.H.)
1657-P: Patatin-Like Phospholipase Domain-Containing 3 Gene Indirectly Modulates Hepatocellular Lipid Content in Severe Insulin Resistant Diabetes
Authors: ZAHARIA OANA P. , STRASSBURGER KLAUS , KNEBEL BIRGIT , KUPRIYANOVA YULIYA , KARUSHEVA YANISLAVA , BODIS KALMAN , WOLKERSDORFER MARTIN , MARKGRAF DANIEL F. , BURKART VOLKER , HWANG JONG-HEE , KOTZKA JÖRG , AL-HASANI HADI , SZENDROEDI JULIA , RODEN MICHAEL ,   GDS GROUP
Published: June 2020

The G-allele in the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase domain containing 3 (PNPLA3) gene associates with increased risk of nonalcoholic fatty liver disease (NAFLD) and its progression. As the recently-described severe insulin resistant diabetes (SIRD) cluster specifically relates to NAFLD, the present study examined whether this SNP differently associates with insulin sensitivity and hepatic lipid content (HCL) in clusters of new-onset diabetes patients. Participants (n=917) of the prospective German Diabetes Study underwent genotyping, hyperinsulinemic-euglycemic clamps and magnetic resonance spectroscopy. SIRD had the lowest whole-body insulin sensitivity compared to severe insulin deficient (SIDD), moderate obesity-related (MOD), moderate age-related (MARD) and severe autoimmune diabetes clusters (SAID; all p<0.001). Interestingly, SIRD presented with higher prevalence of the G-allele compared to other clusters and the glucose tolerant controls (p<0.05). Also, HCL was higher in SIRD [13.6 (5.8;19.1)%] compared to MOD [6.4 (2.1;12.4)%], MARD [3.0 (1.0;7.9)%], SAID [0.4 (0.0;1.5)%] and the glucose tolerant group [0.9 (0.4;4.9)%] (all p<0.05). Although the PNPLA3 polymorphism did not directly associate with whole-body insulin sensitivity or HCL in SIRD, G-allele carriers of this cluster had higher free fatty acids and greater adipose-tissue insulin resistance than non-carriers.

In conclusion, SIRD patients are more frequently carriers of the G-allele which is associated with adipose-tissue insulin resistance and lipolysis. Together, these alterations may mutually accelerate NAFLD and progression of SIRD.

Disclosure

O.P. Zaharia: None. K. Strassburger: None. B. Knebel: None. Y. Kupriyanova: None. Y. Karusheva: None. K. Bodis: None. M. Wolkersdorfer: None. D.F. Markgraf: None. V. Burkart: None. J. Hwang: None. J. Kotzka: None. H. Al-Hasani: Consultant; Self; Bayer AG. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S.

Funding

German Federal Ministry of Health; Ministry of Culture and Science of North Rhine-Westphalia; German Federal Ministry of Education and Research; German Center for Diabetes Research
1665-P: Uncovering the Cell-Type Specificity in Human T1D Immune Activation Using iPSC-ß-Cells
Authors: LEITE NAYARA
Published: June 2020

It is known that T1D involves a complex interaction between pancreatic β-cells and cells of both the innate and adaptive immune systems. Innate immune signaling is involved in the initiation of the autoimmune process, which results in the destruction of β cells by cytotoxic T cells during T1D pathogenesis. Here, we show that exposing human induced pluripotent stem cells derived β cells (hiPSC-β cells) to autologous peripheral immune cells in vitro reveals an activation signature of T1D β cell rejection across multiple immune cell types. We profiled innate and adaptive immune activated populations and identified relevant populations to T1D autoimmunity. After co-culture of donor-matched target and effector cells, we performed mass cytometry (CyTOF). We used an immunophenotyping CyTOF panel containing 32 markers to identify activation in different immune populations. As a negative control, we used unstimulated effector peripheral immune cells. As a positive control, we used unmatched β cells from other donors. Finally, all experiments were performed with hiPSC-α cells and donor-matched peripheral immune cells, and we did not observe the activation of immune cells in the hiPSC-α cells donor-matched coculture. Exposing T1D hiPSC-β cells to donor-matched peripheral immune cells in vitro revealed the activation of distinct immune cell populations that participate in T1D β cell rejection. We observed differences within T1D patient samples, we anticipate that we can use this model to study T1D patient heterogeneity.

Disclosure

N. Leite: None.

Funding

American Diabetes Association (1-19-PMF-024)
1669-P: Immune Checkpoint Inhibitor Induced Diabetes and Diabetic Ketoacidosis
Authors: HAFEEZ SHAHZEENA , VELLANKI PRIYATHAMA , XING MINZHI , UMPIERREZ GUILLERMO E.
Published: June 2020

Immune checkpoint inhibitors (CPI) are increasingly used to improve survival rates in cancer patients. CPI therapy has been associated with new onset diabetes due to immune-mediated damage of beta-cells, with many patients presenting with diabetic ketoacidosis (DKA). We used Emory University’s Clinical Data Warehouse to examine clinical characteristics and outcomes of adult patients with new onset diabetes and DKA after CPI therapy from 01/01/2014 to 08/01/19. Comparisons of covariates were made with analysis of variance, χ2 and Fisher’s exact tests; log-rank test was used to analyze survival.

A total of 2279 patients received CPIs during the study period. Of these, 1622 had no DM, 540 had a previous history of DM, and 117 patients (5.1%) developed new onset DM after CPI treatment. Pembrolizumab, Nivolumab and Ipilimumab were the most common CPIs associated with DM. A total of 13 patients developed DKA, on average at 140 days from CPI initiation. Compared to no-DM group, patients with new-onset DM and DKA had higher DM-related hospitalization (p<0.01), mortality (p=0.02), and reduced survival from CPI initiation, p=0.03.

In summary, incidence of new-onset DM is 5.1% and is associated with higher DM-related hospitalizations. DKA patients have reduced survival compared to no-DM after CPI treatment. Healthcare professionals caring for patients undergoing CPI therapy need to be aware of this potential complication.

Disclosure

S. Hafeez: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Xing: None. G.E. Umpierrez: None.
167-OR: Exercise Training Alters Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha (PGC-1 Alpha) DNA Methylation in Human Skeletal Muscle
Authors: LEE SUNG , GARCIA LUIS , LEON ALMA D. , BUSTOS ROCIO ZAPATA , CAMPOS BALTAZAR , KRENTZEL JUDY A. , MANDARINO LAWRENCE , COLETTA DAWN K.
Published: June 2020

Exercise training improves insulin sensitivity in skeletal muscle and increases mitochondrial function. These improvements are due, in part, to an increase in expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha). The effect of exercise training on epigenetic factors, such as DNA methylation remains elusive. The aim of this study was to determine whether an 8-week exercise training alters DNA methylation of PGC-1 alpha. Fourteen participants (5M/9F; age 34.2±3.0 years) were studied before and after 8-weeks of supervised exercise training (60% of VO2peak for 20 minutes, 3 times per week; gradually increased to 70% of VO2peak for 45 minutes, 4 times per week). Euglycemic hyperinsulinemic clamps in combination with vastus lateralis muscle biopsies were obtained before and after the exercise training. Training increased peak aerobic capacity (VO2peak) from 31.9±1.0 to 36.5±1.4 ml∙min-1∙kg FFM-1 (P = 0.013) and improved insulin sensitivity from 7.0±2.1 to 9.2±2.3 ml·kg FFM−1·min−1. Genomic DNA was extracted and pyrosequencing methylation analysis was performed on CpG -816 and -783 bp upstream transcription start site (TSS). Methylation analysis revealed a significantly decreased methylation at CpG -816 bp following exercise (pre = 16.8±0.9 % versus post = 14.2±0.5 %, P = 0.035). For CpG -783 bp, methylation did not change following exercise (pre = 11±0.6 % versus post = 11.5±0.7 %, P = NS). Our results showed that exercise training improved insulin sensitivity and peak aerobic capacity. In addition, we provide evidence that exercise training alters PGC-1 alpha methylation at CpG -816 bp. We propose that the increased response of insulin action in muscle following exercise training is due, in part, to epigenetic modifications.

Disclosure

S. Lee: None. L. Garcia: None. A.D. Leon: None. R. Zapata Bustos: None. B. Campos: None. J.A. Krentzel: None. L. Mandarino: None. D.K. Coletta: None.

Funding

National Institutes of Health (R01DK094013)
1679-P: Islet Autoimmunity in Adults with Impaired Glucose Tolerance (IGT) and Newly Diagnosed, Treatment-Naïve Type 2 Diabetes (NDX T2D) in the Restoring Insulin Secretion (RISE) Study
Authors: BROOKS-WORRELL BARBARA , TJADEN ASHLEY H. , EDELSTEIN SHARON , PALOMINO BRENDA M. , UTZSCHNEIDER KRISTINA , ARSLANIAN SILVA A. , MATHER KIEREN J. , BUCHANAN THOMAS A. , NADEAU KRISTEN J. , ATKINSON KAREN M. , BARENGOLTS ELENA , KAHN STEVEN E. , PALMER JERRY P. ,   RISE CONSORTIUM
Published: June 2020

In obesity, immune cells establish a systemic inflammatory state associated with development of insulin resistance and T2D. Previous studies have shown that peripheral blood mononuclear cell (PBMC) responses to islet proteins (IPs) in adults with established T2D on glucose-lowering therapies identify those patients with more severe β-cell dysfunction. Moreover, attenuation of PBMC responses to IPs in adults with established T2D improves β-cell function. However, the presence of IP reactive PBMCs, glutamic acid decarboxylase autoantibodies (GADA), and their relationship to insulin sensitivity and β-cell function has never been evaluated in IGT or Ndx T2D. We measured at baseline and after 12 months of RISE medication interventions (12 months with either metformin or liraglutide plus metformin or for 3 months with insulin glargine followed by 9 months of metformin), PBMC responses to IPs, GADA, insulin sensitivity, and β-cell function in 258 RISE participants (mean ± SD) 53.3 ± 9.2 years of age, BMI 35.1 ± 5.4 kg/m2, with IGT (n=180) or Ndx T2D (<12 months duration, n=78). At baseline, IP reactive PBMCs were present in 46% of participants with IGT and 40% of participants with Ndx T2D. However, 97% of IGT and 98% of Ndx T2D were GADA negative. There were no significant relationships between the presence of PBMC reactivity to IPs, GADA positivity and insulin sensitivity or β-cell function. RISE treatments did not alter PBMC responses to IPs, GADA, or the relationship between IP reactive PBMCs or GADA with glycemic responses.

In summary, IP reactive PBMCs are present in a large percentage of adults with very early dysglycemia, However, the presence of IP reactive PBMCs did not correlate with insulin sensitivity or early β-cell dysfunction. Further studies are needed to unravel the pathogenesis of IP reactive PBMCs and GADA and their effects on β-cell function during progression of T2D.

Disclosure

B. Brooks-Worrell: None. A.H. Tjaden: None. S. Edelstein: None. B.M. Palomino: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. K.J. Mather: Research Support; Self; Abbott, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. T.A. Buchanan: None. K.J. Nadeau: None. K.M. Atkinson: None. E. Barengolts: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc. J.P. Palmer: None.

Funding

National Institutes of Health (R01DK107560)
1689-P: Perioperative Hyperglycemia around Renal Transplantation Surgery and the Development of New-Onset Diabetes Mellitus after Transplantation
Authors: FERREIRA MARÍA LETICIA MÉNDEZ , BUENO ELVIO D. , BENITEZ ALDO , PALACIOS CONCEPCION M. , JIMENEZ JORGE T. , AMARILLA ALEJANDRA , PONTE FERNANDO DA , STANLEY IDALINA
Published: June 2020

Background: New onset of diabetes after transplantation (NODAT) is an important problem as it increases infectious and cardiovascular complications reducing patient and graft survival.

Aim: To establish the impact of perioperative hyperglycemia on the development of NODAT and the other known risk factors for its development in patients who go to renal transplant surgery, in a renal transplant unit dependent on an academic center.

Methods: Study of cases and controls of patients with renal transplantation who developed or not NODAT within the year of follow-up, with more than 18 years of age, with the same immunosuppressive scheme (prednisone, tacrolimus, mycophenolate mofetil).

Results: Of 71 transplanted patients, 14 (19.7%) developed NODAT per year, with an average age of 37.57 ± 15.02 years vs. 36.08 ± 12.43 years for those who did not develop it (p: 0, 73) respectively; those who developed NODAT were male in 57.14% vs. 70.18% of those who did not develop it respectively. Patients whose preoperative laboratory evaluation showed blood glucose equal to or greater than 100 mg/dl and less than 126 mg/dl had a NODAT frequency of 21.3% vs. 5.26% (OR 4.9 p: 0.005) in those who they had values ​​lower than 100 mg/dl at the same time of the evaluation. In addition, if the blood glucose prior to hospital discharge was ≥140 mg/dl, the frequency of NODAT was 35.71% vs. 1.75% (OR 31.11 p: 0.0003) if the blood glucose was lower than 140 mg/dl at the same time of the evaluation. None of the other risk factors considered: age >40 years, female sex, overweight, obesity, hypertriglyceridemia, family history of diabetes had significant statistical differences between the two groups.

Conclusion: In our experience, poor glycemic controls, especially before surgery and prior to hospital discharge, marked a higher frequency trend of NODAT one year after follow-up. The patients presenting with this phenomenon should be observed with special attention in the follow up.

Disclosure

M. Méndez Ferreira: None. E.D. Bueno: None. A. Benitez: None. C.M. Palacios: None. J.T. Jimenez: None. A. Amarilla: None. F. Da Ponte: None. I. Stanley: None.
171-LB: Evaluation of Universal Diabetes Diagnostic Testing at First Prenatal Visit
Authors: LARCO PHILIPPE , BAPTISTE EDDY JEAN , MOISE KEDDY , LARCO MARIE-NANCY CHARLES , JEROME BELLO S. , VON OETTINGEN JULIA E. , CHARLES RENE
Published: June 2020

Diabetes mellitus (DM) in pregnancy is not routinely screened for in Haiti. If done, screening relies on OGTT at 24-28 weeks (w) of gestation. It is unclear whether this is an optimal approach in Haiti. We aimed to evaluate the implications of a universal DM diagnostic testing before 24 w.

All consecutive pregnant women aged ≥18 y without known DM attending their first pregnancy visit in 4 prenatal clinics of Port-au-Prince and surroundings were invited to participate. Using a Contour NextR glucometer, eligible subjects underwent: Fasting blood glucose (FBG) test at 1-23 w and ≥36 w, 75g 2-h OGTT at 24-28 w for FBG <126 mg/dL before 24 w or at 24-35 w-first visit. We used WHO/IADPSG diagnostic criteria for DM in pregnancy (DIP) (FBG ≥126 mg/dL and/or 2h ≥200 mg/dL) and for gestational DM (GDM) (1 or more: FBG 92-125 mg/dL, 1-h BG ≥180 mg/dL, 2-h BG 153-199 mg/dL).

A total of 945 women (mean age 29.78 ± 5.77 y, parity 2.04 ± 1.29, pre-eclampsia: 3.80%, caesarian section: 18.75%, preterm birth: 7.13%, single or living alone: 10.13%, family history of DM: 10.11%) were studied. Women with first visit at < and ≥24 w were 332 and 613, respectively. Prevalence of DIP and GDM by first screening period was: 7.20% and 13.02% overall, 12.35% and 13.86% at <24 w, and 4.40% and 12.56% at ≥24 w. Median FBG progressively decreased from 83 mg/dL at ≤5 w to 73 mg/dL at ≥36 w, p=0.0000. Of the 40 women with GDM at <24 w, 20 had GDM confirmed and 20 were normal on OGTT. A cut-off value of FBG >100 mg/dL at <24 w for DM (DIP and GDM) diagnosis on OGTT had: specificity (SP) 98.8%, sensitivity (SE) 19.3%, and positive predictive value (PPV) 78.6%. A cut-off value of FBG <72 mg/dL at <24 w to rule out DM on OGTT had: SP 12.2%, SE 98.3%, and NPV 96.8%. Women with these cut-offs represented 14.9% of those undergoing OGTT after the <24 w screening.

Our findings suggest that universal screening for DM before 24 w of gestation leads to diagnosis of DM in about 20% of pregnant women. A rule in/rule out approach using FBG <72 mg/dL and >100 mg/dL values at <24 w can help reduce the number of OGTT at ≥24 w.

Disclosure

P. Larco: None. E. Jean Baptiste: None. K. Moise: None. M. Charles Larco: None. B.S. Jerome: None. J.E. von Oettingen: None. R. Charles: None.