bluuebunny/crossref_metadata_2025 huggingface dataset:
235-OR: Sphingosine Kinase 2-Mediated Pyroptosis of Renal Tubular Epithelial Cells Contributes to the Progression of Diabetic Nephropathy
Authors: YAN SISHAN , LIANG LANMEI , LIU WENWEN , CHEUNG WAI WILSON , DING WEI , LAN TIAN
Published: June 2019

Pyroptosis of renal tubular epithelial cells and deposition of interstitial matrix proteins leads to chronic diabetic nephropathy. Recent data suggest that deficiency of sphingosine kinase 2 (SphK2) attenuates acute kidney injury and renal fibrosis. We aim to investigate the role of SphK2 signaling in the pathogenesis of diabetic nephropathy. The protein expression of SphK2 in kidney, especially in renal tubular, was significantly increased in STZ-induced diabetic mice and Leprdb/db mice, compared with control mice. Renal injury and fibrosis, as demonstrated by albumin-to-creatinine ratio, histology and fibronectin deposition, were significantly ameliorated in STZ-induced SphK2-/- or Leprdb/dbSphK2-/- double KO mice relative to control mice. Moreover, administration of ABC294640, the specific inhibitor of SphK2, significantly prevented renal injury and fibrosis in STZ-induced diabetic mice. SphK2 siRNA significantly downregulated fibronectin in renal tubular epithelial cells (NRK52E) cultured by high glucose. Furthermore, the activation of NLRP3 inflammasome and caspase 1, as well as subsequent pyroptosis were significantly inhibited in NRK52E cells transfected with SphK2 siRNA under high glucose condition.

In conclusion, SphK2 deficiency attenuates diabetic nephropathy by preventing pyroptosis in renal tubular epithelial cells.

Disclosure

L. Liang: None. W. Liu: None. W. Cheung: None. W. Ding: None. T. Lan: None.

Funding

National Natural Science Foundation of China (81870420); Science and Technology Planning Project of Guangdong Province (2017A020211007)
2356-PUB: The Relationship between Hypoglycaemia, Weight, and Quality of Life among Patients with Type 1 Diabetes: Observations from the DEPICT-2 Trial
Authors: GORDON JASON , BERESFORD-HULME LEE M. , BENNETT HAYLEY , TANK AMARJEET , EDMONDS CHRISTOPHER , MCEWAN PHILIP
Published: June 2019

Insulin-treatment in type 1 diabetes mellitus (T1DM) is associated with elevated risk of hypoglycaemia and weight gain, which may act as a barrier to achieving optimal glycaemic control. For patients inadequately controlled by insulin alone, adjunct dapagliflozin can reduce body weight and improve glycaemic control without increased risk of hypoglycaemia. This study aimed to empirically quantify the inter-relationships between hypoglycaemia, body mass index (BMI) and quality of life using DEPICT-2 trial data. A two-stage linear regression framework evaluated (1) the relationship between hypoglycaemic fear score (HFS) and the occurrence of severe hypoglycaemia, the number of documented symptomatic events and patient age, and (2) the relationship between health-related utility (EQ-5D) and prognostic factors for utility, including HFS and BMI. Model selection was based on clinically-relevant factors. A linked evidence approach correlated the relationship between treatment, hypoglycaemia incidence and HbA1c over 52-weeks, to the relationships captured within the regression models. HFS increased as a function of incidence of severe hypoglycaemia (coefficient estimate (CE): 14.62, p=0.004) and frequency of symptomatic events (log transposed, CE: 1.32, p=0.0026). In turn, increased HFS and increased BMI were both independently associated with a significant reduction in utility (CE 0.0024, p<0.001 and 0.0026, p=0.0016 respectively). In DAPA-treated patients, attainment of target glycaemic control was not associated with an increased rate of hypoglycaemic events. This study demonstrates that fear of hypoglycaemia, driven by increased incidence of hypoglycaemia, and BMI are significant determinants of quality of life for people with T1DM. These findings support the role of dapagliflozin in T1DM management, which was associated with achievement of glycaemic control targets and weight loss, without increased hypoglycaemia.

Disclosure

J. Gordon: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, GlaxoSmithKline plc., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Takeda Canada, Takeda Pharmaceutical Company Limited. L.M. Beresford-Hulme: None. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. A. Tank: Employee; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd.
237-OR: Beneficial Impact of Intensified Multifactorial Intervention on Stroke—The Steno-2 Study
Authors: GÆDE PETER , OELLGAARD JENS , KRUUSE CHRISTINA , ROSSING PETER , PARVING HANS-HENRIK D. , PEDERSEN OLUF
Published: June 2019

Epidemiological studies have shown that diabetes is a well-established independent but modifiable risk factor for stroke. In the Steno-2 Study 160 patients with T2DM and microalbuminuria were randomised to intensified or conventional multiple risk factor intervention targeting classical CVD risk factors for a mean of 7.8 years and then followed for up to 21.9 years. The primary endpoint in this post hoc analysis was time to first stroke (Cox regression adjusted for age and sex). Baseline predictors were examined using backwards regression elimination (threshold of α = 0.10) of the following variables: age, sex, known diabetes duration, smoking status, left ventricular ejection fraction, heart rate variability, atrial fibrillation, BMI, systolic BP, GFR, retinopathy, HbA1c, proBNP and total cholesterol, and urinary albumin excretion rate. During follow-up 30 participants experienced a total of 39 strokes. More patients randomised to conventional therapy experienced a stroke with 21 participants (26%) with 29 strokes in the conventional-therapy group vs. 9 participants (11%) with a total of 10 strokes in the intensive therapy group. Baseline systolic BP and GFR were significant risk factors for stroke.

In conclusion, intensified multiple risk factor intervention in patients with type 2 diabetes and microalbuminuria reduces the risk for strokes as well as the number of recurrent cerebrovascular events.

Disclosure

P. Gæde: None. J. Oellgaard: Employee; Self; Novo Nordisk A/S. C. Kruuse: Speaker's Bureau; Self; Novo Nordisk A/S. P. Rossing: Advisory Panel; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. Other Relationship; Self; Novartis AG, Novo Nordisk A/S. H.D. Parving: None. O. Pedersen: None.
2371-PUB: Addition of a GLP-1 Agonist to Safety Net Hospital System Formulary to Improve Glycemic Control
Authors: GUNASEKARAN UMA
Published: June 2019

Parkland Health and Hospital System (PHHS) is one of the largest safety net health systems in the United States serving the indigent population of Dallas County. The majority of patients with diabetes seen in the PHHS Primary Care clinics receive their medications through PHHS pharmacies which offer subsidized prices for medications on the PHHS formulary. The GLP-1 agonist, liraglutide, was added to the formulary at the end of 2016. To improve glycemic control in the primary care clinics, bi-monthly webinars providing diabetes education, in conjunction with e-consultations between primary care providers and diabetes specialists, were begun in early 2017 with an emphasis on using GLP-1 agonists. GLP-1 agonist prescriptions in the PHHS primary care clinics increased 435% (34 to 148) between 2016-2017 and 168% (148 to 248) from 2017-2018, an overall increase in prescribing of 729%. Of the 469 patients who were prescribed GLP-1 agonists from 2015-2018, 316 patients had baseline and post-prescription Hba1c values available. The average baseline Hba1c at time of prescription was 9.0% with an average final Hba1c value of 8.4% (p=0.0005). This data shows how an institutional formulary can be used as an agent of change to improve glycemic control. Of note, 90% of prescriptions were written for liraglutide with the other 10% including other GLP-1 agonists such as exenatide, albiglutide, and dulaglutide, showing the effect of diabetes education in prescribing practices.

Disclosure

U. Gunasekaran: None.
2374-PUB: Early Diabetes Intervention for High-Risk Cardiology Inpatients
Authors: FOURLANOS SPIROS , MINGOS NICHOLAS D. , ROWAN LOIS M. , BARMANRAY RAHUL , KYI MERVYN
Published: June 2019

Adverse glycaemia in hospital is associated with worse clinical outcomes. Given the high prevalence of diabetes in the cardiology wards, we introduced an early intervention model of diabetes care in high-risk inpatients aiming to decrease adverse glycaemia. A prospective pre- and post-intervention study was conducted in a tertiary referral hospital cardiology ward. It consisted of an initial 6-month baseline phase of standard care (a ‘reactive’ referral-based diabetes consultation service), followed by an 9-month intervention phase, comprising a ‘proactive’ multidisciplinary inpatient diabetes team (IDT) assisted by networked blood glucose (BG) meter technology. The proactive IDT performed electronic surveillance of capillary BG measurements and provided an early consultation service (within 24 hours of admission), without waiting for referral from the parent team. Consecutive inpatients admitted to the cardiology ward (length of stay >48 hours) at high risk of adverse glycaemia (insulin treatment prior to hospital; or BG <4, >15 or two BG >10 mmol/L in the first 48 hours) were recruited. BG data from day 2 until discharge, along with demographic and clinical features, was collected. The primary outcome was the incidence of adverse glycaemic days (AGD) (rate per 1000 patient-days with any capillary BG measure <4 or >15 mmol/L). Overall, we observed 332 patients (1320patient-days and 4887 BG measurements). Compared to usual care, the incidence of AGD decreased from 405 to 320 per 1000 patient-days (21% decrease, p=0.002) which remained significant after MVA adjustment. During the intervention phase, there was decreased mean (±SD) patient-day BG (10.8 ±3.3 vs. 10.1 ±2.8, p<0.001), decreased patient-days with hyperglycaemia (BG >15 mmol/L) (10.4% vs. 6.1%, p=0.044) with no significant difference in patient-days with hypoglycaemia. Analysis of clinical outcomes is pending. An early intervention model of diabetes care decreased adverse glycaemia in cardiology in patients with diabetes.

Disclosure

S. Fourlanos: None. N.D. Mingos: None. L.M. Rowan: None. R. Barmanray: None. M. Kyi: None.
2381-PUB: Shared Medical Appointments: An Academic-Community Partnership to Improve Metabolic Outcomes among People with Type 2 Diabetes in the Central Valley of California
Authors: NOYA CAROLINA E. , GATEWOOD ELIZABETH , ALKON ABBEY , CASTILLO ELIZABETH , KUO ANGEL C.
Published: June 2019

Diabetes has reached epidemic proportions in the United States. Shared medical appointments are an increasingly popular model to provide access to DSMES and primary care services.

The purpose of the study was to evaluate the effectiveness of a Shared Medical Appointment (SMA) intervention, compared to usual primary care (UPC), for the treatment of adults with type 2 diabetes over a 6-month period in two rural Federally Qualified Health Centers (FQHC) in the central valley of California.

This study was a quasi-experimental design with a non-randomized matched control group that followed participants prospectively for 6 months. All adults living with type 2 diabetes receiving primary care at 2 FQHC clinics were eligible for inclusion. Participants in the control group were matched retrospectively on baseline A1C and age.

To test the effect of group membership on A1C change, differences in change scores were compared between the ALDEA SMA intervention group and the UPC control group. Linear regression analysis was computed to assess if mean A1C change at 6 months post-intervention was greater among SMA intervention group participants compared to the UPC control group participants.

The reductions in A1C were greater in the intervention group relative to the control group at 6 months. Results of the linear regression analysis revealed a net reduction A1C difference of -1.12% from baseline to 6 months (p≤0.05) in FQHC #1, and -1.06% from baseline to 6 months (p≤0.05) in FQHC #2.

This study demonstrated that patients in the ALDEA program were able to achieve a significant reduction in A1C compared to those who received UPC. Despite its limitations, the ALDEA SMA program was successful in empowering patients and improving glycemic control.

Disclosure

C.E. Noya: None. E. Gatewood: None. A. Alkon: None. E. Castillo: None. A.C. Kuo: None.

Funding

Health Resources and Services Administration
2382-PUB: Socioeconomic Disparities in the Management of Glycemic Control among Adults with Type 2 Diabetes in the United States
Authors: PAWASKAR MANJIRI , NGUYEN JENNIFER , HUYNH STEPHANIE , HASKELL TOM , LEE LULU , RAJPATHAK SWAPNIL
Published: June 2019

Optimal management of glycemic control is important to delay and prevent the onset of long-term complications in patients with type 2 diabetes (T2D). While health disparities in diabetes burden and complications are well-documented, limited data exist on socioeconomic status (SES) as a determinant of glycemic control. We conducted a study linking the National Health and Wellness Survey (NHWS), a nationally-representative, self-administered annual internet survey of about 75,000 adults (≥18), and two electronic health record (EHR) systems: Veradigm, which contains data for 46+ million unique patients, and Healthverity, a nationally-representative database with 60+ million unique patients. The study population consisted of T2D adults who responded to the NHWS between 2015-2018 and had clinical measurements in the EHR database for at least 6 months from NHWS response (i.e., at least 6 months of follow-up). Glycemic control was treated as a binary variable (HbA1c <7% or ≥7%) and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated adjusting for age and gender. Of 2,380 total T2D patients [mean age = 61.5 (standard deviation = 12.0), 54% males, 85% White, 32% employed, 84% living in an urban area], 501 (21%) had at least one HbA1c test taken within 6 months of NHWS participation. Of these 501 patients, 197 (39%) had uncontrolled HbA1c (≥7%). Black/African American patients were significantly more likely to have uncontrolled HbA1c compared with White patients (OR = 2.0; 95% CI: 1.02, 3.92; p = 0.04). Further, Medicaid and uninsured patients were significantly more likely to have uncontrolled HbA1c compared to those with commercial health insurance (OR = 2.81; 95% CI: 1.46, 5.4; p < 0.005). There were no differences by geographic regions. The observed associations of glycemic control with race and health insurance may possibly be related to disparity in diabetes management. Future studies are needed further investigating the role of SES in diabetes management.

Disclosure

M. Pawaskar: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. J. Nguyen: Other Relationship; Self; Merck & Co., Inc. S. Huynh: Other Relationship; Self; Merck & Co., Inc. T. Haskell: Other Relationship; Self; Merck & Co., Inc. L. Lee: Other Relationship; Self; Merck & Co., Inc. S. Rajpathak: None.
2384-PUB: Implementation of Interdisciplinary Panel Management (PM) Teams in Urban Primary Care Settings to Improve Care for High-Risk Patients with T2DM
Authors: WITTMAN DEBORAH , ABIA CASELY-HAYFORD SOPHIA NAA , YOUNG EDWIN , ALBU JEANINE
Published: June 2019

Purpose: Mount Sinai St. Luke’s Hospital located in NYC, received a DSRIP (Delivery System Reform Incentive Program) grant to improve population health in the Medicaid population. Divisions of Endocrine and General Medicine collaborated to improve care for high-risk patients with T2DM in three urban primary care practices by implementing PM to reduce percentage (%) of patients with HbA1c >9.

Methods: A team of six CDEs was formed; two CDEs were embedded in the practices and each CDE was assigned to a PCP(s). Teams received quarterly reports of patients (HbA1c >9) and met monthly to discuss care management (PM). Eligibility criteria: HbA1c >9 taken within 12 months. Patients were excluded if receiving care by a CDE/endocrinologist. We calculated % of patients who reached HbA1c <9 using the first HbA1c from time of PM until their last repeated HbA1c over one year. We also evaluated % of patients who reached HbA1c <9 based on visits with: PCP only, CDE-PCP, CDE-endocrine or endocrine only. Lastly, we calculated % of patients seen by a CDE who attained HbA1c <9 with or without PM.

Results: A total of 549 patients were identified; 257 patients were eligible and received PM where 34% (n=87) improved, achieving HbA1c <9. Out of the 87 patients, 10.5%, 12.5%, 8.2% and 2.7% showed improvement, based on visits with: PCP only, CDE-PCP, CDE-endocrine or endocrine only, respectively. A total of 292 patients did not receive PM; 153 patients were eligible where 44% (n=67) improved, achieving HbA1c<9. Overall improvement in HBA1c <9 was found in 45% of patients seen by a CDE vs. in 35% of those not seen by a CDE, regardless of PM or endocrine involvement.

Conclusion: While use of PM for patients with T2DM identified as high-risk (HbA1c >9) was not impactful, visits with CDEs had the greatest impact on improving HbA1c to <9, regardless whether the patient was part of PM or not. We therefore recommend all patients with T2DM identified as high-risk (HbA1c >9) receive CDE support services.

Disclosure

D. Wittman: None. S.N. Casely-Hayford: None. E. Young: None. J. Albu: None.
2391-PUB: Determinants of Poor Glycemic Control among Adolescents with Type 1 Diabetes
Authors: ALADSANI AFAF M.S.A.
Published: June 2019

Objective: The majority of adolescents with type 1 diabetes have poor glycemic control, calling for an action to be taken. The aim of this study was to identify the determinants of poor glycemic control among adolescents with type 1 diabetes.

Methods: Data were collected for all adolescents with type 1 diabetes (age < 20 years), who attended diabetes clinics at one hospital, and had at least one result of HbA1c performed during the study year. The average level of HbA1c was calculated from all the HbA1c results collected over one year. Glycemic control was defined as poor if the HbA1c was >8%. Variables studied were gender, age, age at diagnosis, diabetes duration, annual clinic attendance, frequency of blood glucose monitoring, healthy eating, medication adherence, and frequency of HbA1c performance over one year.

Results: The study included 78 adolescents with type 1 diabetes (47.4% males). Mean age was 15.4+2.0 years, mean age at diagnosis was 9.0+3.6 years, and mean duration of diabetes was 6.6+3.8 years. The mean of the average level of HbA1c was 10.2+1.9%, and 84.6% had HbA1c >8%. Mean frequency of HbA1c performance was twice per year, and mean annual clinic attendance was three visits. Poor glycemic control was significantly associated with female gender (p<0.05). Healthy eating, medication adherence, and frequent HbA1c performance (> 3 per year) were significantly associated (p<0.001) with better glycemic control (HbA1c<8%). With regression analysis, healthy eating, medication adherence and HbA1c performance remained as the major determinants of the glycemic control.

Conclusions: The overall glycemic control in adolescents with type 1 diabetes was poor, putting them at high risk of developing diabetes complications at an early stage of life. Healthy behavior was a major determinant of glycemic control. Behavioral healthy intervention strategies should be integrated in the management plan of diabetes care to improve glycemic control and reduce diabetes complications in this vulnerable group.

Disclosure

A.M.A. Aladsani: None.
2392-PUB: Health-Care Cost Avoidance in Indian Participants with Type 2 Diabetes Initiating Second-Line Treatment: The DISCOVER Study, India Subset
Authors: KALRA SANJAY , SRINIVASAN BHARATH
Published: June 2019

Aim: DISCOVER is a 3 year-global, observational study of patients with type 2 diabetes (T2D) initiating second-line glucose lowering treatment in 37 countries. Here we report healthcare cost avoidance pattern of 3139 participants from India.

Methods: Participants were recruited from 28 centers in India from both primary and specialist healthcare settings. Data were collected using a standardized case report form. This is a 3-year prospective ongoing observational study and here we analyze the healthcare cost avoidance patterns at baseline, 6 months and 12 months. Healthcare cost avoidance was measured through a patient questionnaire.

Results: Majority of the participants had no health insurance coverage. More than 90% of the participants in this study didn’t avoid any healthcare services due to cost reason and most of them didn’t avoid a medication prescribed for cost reasons.

Conclusions: Though majority of the participants enrolled were self-paying, and not covered by insurance or government schemes, the majority rarely or never missed to follow the physician’s advice. This reflects on health care adherence related patient behavior in India. Majority of the participants had completed secondary education which might have added some bias to the results.

Disclosure

S. Kalra: None. B. Srinivasan: None.

Funding

AstraZeneca
2397-PUB: PowerHouse: A Lifestyle Intervention for Youth at Risk for Type 2 Diabetes (T2D)
Authors: EL MIKATI HALA K. , PIKE JULIE , HABERLIN-PITTZ KATIE , YAZEL-SMITH LISA , MCKINNEY BRETT M. , HANNON TAMARA S.
Published: June 2019

The prevalence of T2D is increasing in youth partly because of the lack of effective prevention strategies. Lifestyle intervention is established for adult T2D prevention and family-based lifestyle intervention is the most efficacious non-surgical treatment of obesity in youth. We developed a 16-wk family-based program modeled after the U.S. Diabetes Prevention Program, using Expert Committee Recommendations Regarding the Prevention, Assessment and Treatment of Child and Adolescent Overweight and Obesity. Sessions included physical activity, separate adult/youth nutrition education and goal setting, and a shared meal. Youth inclusion criteria were age 7-18 y, BMI > 85th %ile, a caregiver to participate, and ≥ 2 risk factors: family history of T2D, maternal history of gestational diabetes, minority race/ethnicity. Paired t-tests were used to compare BMI and HbA1c at baseline (BL) and 4 months (M4) and at BL and 12 months (M12, data set currently incomplete). Between Feb 2017 and Nov 2018, 79 eligible youth enrolled (Table) the majority of whom had government-issued health insurance. Youth HbA1c was maintained at M4 (p = 1.0) and M12 (p = 0.45). Similarly, BMI SDS were stable at M4 (p = 0.67) and M12 (p = 0.12) while BMI scores increased at M4 (p = 0.007), but not at M12 (p = 0.23). As excessive weight-gain is correlated with T2D development, programs that maintain BMI could have significant impact on preventing or delaying T2D in youth.

Disclosure

H.K. El Mikati: None. J. Pike: None. K. Haberlin-Pittz: None. L. Yazel-Smith: None. B.M. McKinney: None. T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company.

Funding

Indiana University School of Medicine; Indiana University
2402-PUB: Clinical and Demographic Factors Associated with Morbidity in Adolescents and Young Adults with Type 1 Diabetes
Authors: CYMBALUK ANNA L. , CORATHERS SARAH , YAYAH JONES NANA-HAWA
Published: June 2019

Purpose: This study investigates clinical and demographic variables associated with youth who died of type 1 diabetes mellitus [T1D] complications between the years 2011-2018.

Methods: Retrospective chart review was performed on patients with T1D who died between the years 2011 to 2018 at a single center. Deceased youth autopsy reports were reviewed for causation of death.

Results: In the deceased cohort, 57% were female, 71% were non-Hispanic white, median age at death 19 years (range 15-22), 40% Medicaid. One case was excluded in analysis as youth transitioned T1D care to adult provider prior to death. Median duration between T1D diagnoses and death was 9.9 years. Median/mean hemoglobin A1c (A1c) year prior to death was 9.65/9.71%. Majority of patients (71%) were on basal bolus insulin regimen at time of death. Causation of death was determined as diabetic ketoacidosis in 85% of patients; unclear in others, although one case review documented precedent hypoglycemia. At the time of death, 71% of patients had transitioned out of the care of their primary caregiver (i.e., parent/guardian) into either state custody, college, or living independently. Notably, one patient had a history of 14 (known) addresses, with cohort mean/median # of lifetime addresses 5.57/3.

Conclusions: Although T1D providers clinically suspect the psychosocial factors that predispose to T1D complications, little is known about the contextual characteristics of youth who die of T1D. Given the low volume but extreme risk of T1D death in youth, it is prudent to investigate clinical and demographic variables to develop predictive models by which to inform interventions. Study findings indicate that A1C is not a predictor of mortality, but address history and transition of care out of the primary caregiver may be. Future direction includes comparing data between living and deceased patients to determine a predictive risk factor score for early death; and thus institute targeted interventions.

Disclosure

A.L. Cymbaluk: None. S. Corathers: None. N.Y. Jones: None.
2404-PUB: Evaluating a Multidisciplinary Chronic Illness Management Program for Children and Adolescents
Authors: MARCHETTA CLAIRE M. , MARUYAMA RYO , O'REILLY COLIN R.
Published: June 2019

Objective: Among youth with type 1 diabetes mellitus (T1DM), older adolescents have demonstrated decreased compliance to treatment adherence, resulting in unfavorable disease control. Poor disease management established in this population can continue into adulthood, perpetuating the health and economic burden to the individual and society. This study aims to evaluate the effectiveness and sustainability of an inpatient multidisciplinary approach to treating children and adolescents with T1DM.

Methods: Patients with a diagnosis of T1DM admitted to the Chronic Illness Management Program (CIMP) between 1/1/2016 and 12/31/2017 were eligible for inclusion. Data related to physiological and psychosocial outcomes were compared between admission and discharge. Outpatient providers were contacted following a patient’s discharge from the CIMP for A1C and health care utilization data.

Results: During the 2-year study period, 57 inpatient admissions of children and adolescents with T1DM were included in the analysis sample. On average, there was a significant (p < 0.0001) reduction in A1C values from admission (11.1%) to discharge (9.1%). Patients improved significantly (p < 0.01) in all psychosocial outcome measures during their inpatient stay. While patient’s A1C values increased 3 months after discharge, they still sustained clinically significant improvements from admission values. Among outpatient providers successfully contacted, none reported any patient hospitalizations or diabetic ketoacidosis episodes in the 3 months following discharge from the CIMP.

Conclusion: The inpatient setting allows for an intensive multidisciplinary treatment model for T1DM management that demonstrates sustainable clinical improvements post discharge. This program model should be considered for adolescents who have been unable to successfully manage their T1DM with outpatient treatment alone. Evaluation of successful long-term management after the CIMP is currently underway.

Disclosure

C.M. Marchetta: None. R. Maruyama: None. C.R. O'Reilly: None.
241-OR: Restenosis after Percutaneous Transluminal Coronary Angioplasty in Patients with Different Categories of Glucose Tolerance: A 2-Year Follow-Up Study
Authors: ZHANG LEI , GU YAN , YIN XIAOYAN , WANG JUN , WANG NA , YANG YUXIU , DONG YANHU
Published: June 2019

Patients with diabetes (DM) are at high risk for restenosis after coronary stenting. Information relating the outcome of percutaneous transluminal coronary angioplasty (PTCA) to prediabetes is, however, limited. The study objective was to investigate the relationship between restenosis after PTCA and baseline glucose categories. We retrospectively analyzed data of 1003 patients (mean age 58.5±4.2 years, 61.5% of men, mean history of coronary heart disease 9.5±1.1 years) who undertook PTCA at Emergency Department between Jan 2008 and Dec 2011. Baseline measures included blood pressure (BP), fasting plasma glucose, lipid profile, HbA1c, C-reactive protein (C-RP), and 2-hour capillary glucose. All patients had follow-up coronary angiography 2 year after PTCA. Restenosis was defined as ≧ 50% stenosis in stent or within 5 mm adjacent to stent. The rate of restenosis was compared among patients with normal glucose tolerance (NGT, n=436), impaired glucose regulation (IGR, n=275), and DM (n=292) according to their baseline glucose levels or prior history of DM. Patients with DM had highest levels of body mass index (BMI), BP, triglycerides (TG), and C-RP, followed by those with IGR and NGT (P<0.01).The number of lesion was 1.6, 1.8, and 2.5 in patients with NGT, IGR, and DM, respectively (p<0.05). At year 2, the rate of restenosis were 4.2%, 5.3%, and 12.0% in patients with NGT, IGT, and DM, respectively (P<0.05). Among DM subgroup, compared with patients with A1c<8%, those with A1c>8% had increased rate of restenosis (14.6% vs. 11.2%, P<0.05). In the logistic regression model, the odd ratio (OR) of having restenosis was 1.46 (95% CI: 1.05-1.87) for DM and 1.10 (95% CI: 1.01-1.25) for IGR, after adjusting for age, history of coronary heart disease, BMI, BP, LDL-C, TG, and C-RP. Restenosis is more frequent in patients with compared those without DM. Prediabetes is associated with increased risk of restenosis after PTCA.

Disclosure

L. Zhang: None. Y. Gu: None. X. Yin: None. J. Wang: None. N. Wang: None. Y. Yang: None. Y. Dong: None.
2416-PUB: Healthy Lifestyle to Prevent Obesity-Adiposity and Diabetes in Young Offspring of Diabetic Mothers?
Authors: WAGLE SONALI S. , KUMARAN KALYANARAMAN , LADKAT RASIKA , BHAT DATTATRAY , KAMAT RAJASHREE , WADKE SAYALI , DESHMUKH MADHURA K. , YAJNIK PALLAVI C. , YAJNIK CHITTARANJAN S.
Published: June 2019

Background: It’s well known that maternal diabetes increases risk of obesity-adiposity and hyperglycemia in children. Few studies have explored the modifying influence of child’s lifestyle (nutrition and physical activity, PA). Intensive treatment of GDM have not shown any protection against adiposity in the child. We assessed the current lifestyle in offspring of diabetic mothers (ODM) 2-26 years after birth and investigated its association with obesity-adiposity and hyperglycemia.

Methods: We studied 200 ODM and 177 offspring of nondiabetic mothers (ONDM, age and gender matched). Anthropometry, body composition (DXA) and blood glucose (capillary in <10y, 1.75g/kg OGTT in >10y) were measured. Overweight + obesity was classified by international standards [IOTF (≤18y), WHO (>18y)], glucose intolerance (ADA 2014). Dietary intake was assessed using food frequency questionnaire (preceding 6 months) and PA by recording time and frequency of vigorous, moderate, and sedentary activities. We studied the influence of diet and activity on risks of obesity-adiposity and hyperglycemia.

Results: ODM consumed sweets, milk and milk products, vegetables and salads more frequently and cereals less frequently than ONDM. Frequent consumption of ‘healthy foods’ and infrequent consumption of ‘unhealthy foods’ were associated with decreased risk for obesity-adiposity. Higher level of moderate PA (>60min/day) and lower sedentary PA (<480 min/day) were associated with lower obesity-adiposity in both the groups. Hyperglycemia was not affected. These effects worked across both groups, there was no interaction with maternal diabetes.

Conclusions: Healthy lifestyle (food and activity) is protective against obesity-adiposity but not against hyperglycemia in young Indian children (both ODM and ONDM). Our results suggest a need for a formal lifestyle intervention in children born in diabetic pregnancies for reduction in obesity-adiposity and hyperglycemia.

Disclosure

S.S. Wagle: None. K. Kumaran: None. R. Ladkat: None. D. Bhat: None. R. Kamat: None. S. Wadke: None. M.K. Deshmukh: None. P.C. Yajnik: None. C.S. Yajnik: None.
242-OR: Do GLP-1RA and SGLT2i Reduce Cardiovascular Mortality in African-American Patients with Type 2 Diabetes? A Meta-analysis
Authors: MISHRIKY BASEM M. , POWELL JAMES R. , WITTWER JENNIFER A. , CHU JENNIFER X. , SEWELL KERRY , WU QIANG , CUMMINGS DOYLE M.
Published: June 2019

While patients enrolled in the cardiovascular safety trials (CVST) for GLP-1RA and SGLT2i were mostly whites, the ADA’s updated recommendations are being generalized to all races. This raises a controversial question regarding the ability to generalize CVST results to African American (AA) patients.

We searched MEDLINE, EMBASE, and CENTRAL looking for CVST comparing diabetic medications to placebo in type 2 diabetes and reporting a statistically significant lower incidence of either the primary outcome of MACE or any of the pre-specified secondary outcomes. We then extracted cardiovascular outcomes for AA patients. Sensitivity and subgroup analyses were performed according to the class of diabetic medications.

We included 6 trials (GLP-1RA in 4; SGLT2i in 2). While those trials enrolled 53,978 patients, only 2794 were AA. There was no significant difference in CV outcomes between diabetic medications (GLP-1RA or SGLT2i) and placebo in AA patients (RR [95% CI] = 0.97 [0.68, 1.39]). On restricting the analysis to GLP-1RA, then to SGLT2i, results for AA patients remained non-significant. On comparing results for GLP-1RA to those with SGLT2i, there was no difference between the groups.

We conclude that AA are not well represented in CVST. Because cardiovascular outcomes were not significantly improved for AA, it remains unclear whether GLP-1RA or SGLT2i would reduce cardiovascular risk in AA.

Disclosure

B.M. Mishriky: None. J.R. Powell: None. J.A. Wittwer: None. J.X. Chu: None. K. Sewell: None. Q. Wu: None. D.M. Cummings: None.
2429-PUB: Circulating microRNAs Are Associated with Glycemic Variability over a 12-Month Period
Authors: FLOWERS ELENA , ALLEN ISABEL D. , KANAYA ALKA M. , AOUIZERAT BRADLEY
Published: June 2019

Introduction: Circulating microRNAs (miRs) function as mediators of biological responses to the environment and may provide insights into mechanisms for type 2 diabetes (T2D). A limitation of prior studies is their cross-sectional design. We sought to characterize variability in fasting blood glucose (FBG) at 5 time-points over a 12-month period in order to determine whether FBG variability was associated with circulating miR expression and identify miR-associated biological pathways.

Methods: Participants were from a previously completed trial on restorative yoga for overweight/obese adults with prediabetes. FBG variability was defined using the standard deviation across 5 time-points. A subset of participants with high (n=10) vs. low (n=10) FBG variability, matched by age and sex, were evaluated. Expression of 336 miRs collected at baseline was measured with the Fireplex Circulating MicroRNA assay. False discovery rate (FDR) threshold of 0.2 was applied. The miRPathDB database was used to identify KEGG pathways.

Results: A total of 6 miRs (i.e., miR-192, miR-197, miR-206, miR-424, miR-486, miR-93) were differentially expressed between individuals with highly compared to low FBG variability. For the six miRs identified in both batches, 321 KEGG pathways were targeted. The Insulin signaling pathway was targeted by miR-197, miR-206, miR-424, and miR-486; the Insulin secretion pathway was targeted by miR-486; and the type 2 diabetes mellitus pathway was targeted by miR-197, miR-206, miR-424, and miR-486.

Conclusions: Circulating miRs are associated with variability in FBG and miRs target pathways that are known to underlie risk for T2D. The immediate next step is to perform longitudinal analysis of the relationships between FBG and circulating miRs to explore novel pathway targets to derive new insights about mechanisms for T2D.

Disclosure

E. Flowers: None. I.D. Allen: None. A.M. Kanaya: None. B. Aouizerat: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R21DK117346-01A1)
243-LB: Characterization and Genetic Validation of Gene Expression Changes across Diabetes Development
Authors: CHEN HUNG-HSIN , PETTY LAUREN E. , MCCORMICK JOSEPH , MCCORMICK SUSAN P. , GAMAZON ERIC , BELOW JENNIFER E.
Published: June 2019

Type 2 diabetes is a complex and heritable disease. Gene expression is influenced by a number of factors, including genetic and environmental factors as well as disease progression. Yet, the changes in genome-wide transcriptome profiles during diabetic development have not yet been studied. We recruited 58 subjects from Cameron County, Texas, whose fasting glucose was less than 126 mg/dl (mean 106.74 mg/dl). During the follow-up period, 24 subjects' fasting glucose elevated to the diabetes diagnostic level (≥126 mg/dl), and the other 34 subjects’ maintained healthy level (<126 mg/dl). To explore the effect of gene expression, we applied RNA-sequencing to profile the peripheral blood transcriptome at both baseline and follow-up visit for all individuals. We then performed an unsupervised network approach, weighted gene co-expression network analysis, to cluster genes into modules with correlated changes in expression pattern over time. Among 17 identified modules, one showed significant differences in gene expression pattern over time between convert and control groups. This module contains 822 genes, including WDFY3, which accounted for the most variance, and STX3, which exhibited the highest connectivity. In addition, change pattern over time of MIR3605, ASB9P1, NUDT16, and MKNK1-AS1 had the highest correlation with transition status. To validate the function of genes in this interesting module, we examined the association between these 822 genes and diabetes and related metabolism disease via genetically regulated expression in a large electronic health record linked biobank at Vanderbilt University. We found that the genes in this module were significantly enriched with significant association to diabetes mellitus, disorders of pancreatic internal secretion, and disorders of mineral metabolism. In sum, we present a set of genes expression change correlated with diabetes progression, and validated their function on diabetes related disorders in a large biobank.

Disclosure

H. Chen: None. L.E. Petty: None. J. Mccormick: None. S.P. McCormick: None. E. Gamazon: None. J.E. Below: None.
2436-PUB: Predicting Risk for New-Onset Type 2 Diabetes in Chinese People with Coronary Heart Disease and Impaired Glucose Tolerance
Authors: XU SHISHI , SCOTT CHARLES A. , COLEMAN RUTH L. , TUOMILEHTO JAAKKO , HOLMAN RURY R.
Published: June 2019

Background and Aims: Patients with cardiovascular disease are at high risk of type 2 diabetes (T2D), but little has been done to provide robust T2D risk estimates. We used Acarbose Cardiovascular Evaluation (ACE) trial data to develop a T2D risk calculator for Chinese people with coronary heart disease (CHD) and impaired glucose tolerance (IGT).

Methods: ACE recruited 6522 Chinese CHD patients with IGT, randomized 1:1 to acarbose or placebo, with prospective ascertainment of new-onset diabetes over median 5.0 years. Logistic regression was used to develop basic and full risk prediction models in the 6238 with the requisite baseline data. Clinically relevant variables and variables showing a univariate association (P<0.1) with incident diabetes were included.

Results: Overall 918 (15%) of 6238 participants developed diabetes. The basic model, using only clinical variables, was a poor fit with an area under the receiver-operating characteristic curve (AUC) of 0.60, whilst the full model including routinely-available laboratory results had an AUC of 0.76 with excellent goodness of fit (Table).

Conclusion: In Chinese people with IGT and CHD, lower age, male sex, obesity, prior hypertension, calcium channel blocker use, nondiabetic hyperglycaemia and dyslipidaemia were major determinants for new-onset diabetes. A model comprising these factors can be used to predict 5-year T2D risk.

Disclosure

S. Xu: None. C.A. Scott: None. R.L. Coleman: None. J. Tuomilehto: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; AstraZeneca. Research Support; Self; Bayer AG. R.R. Holman: Advisory Panel; Self; Bayer AG, Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. Other Relationship; Self; AstraZeneca, Bayer AG, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.
244-LB: Glutamate Is Associated with Type 2 Diabetes through PLG Regulation
Authors: LEE HYO JUNG , YUN JI HO , KIM HYO-JIN , JANG HAN BYUL , PARK SANG IK , LEE HYE-JA
Published: June 2019

Glutamate is a major excitatory neurotransmitter and is involved in the ER stress and β-cell dysfunction, which are important clinical features of diabetes mellitus. However, metabolic studies of diabetes in relation to glutamate are not well understood. In this regard, we tried to search for the function of glutamate in type 2 diabetes. We found that glutamate levels were significantly increased in both prediabetic and diabetic participants in 10 years follow-up study (Korean Genome and Epidemiology Study: Ansan-Ansung cohort). And also, we observed that glutamate is associated with FERM domain-containing protein 4B (FRMD4B), plasminogen (PLG) and partitioning-defective 3 (PARD3) by genome-wide association studies (GWAS). Among them, PLG levels were not only significantly increased by palmitate treatment, which is general model for induction of insulin resistance, but also increased by glutamate treatment. To demonstrate the association between PLG and type 2 diabetes, we treated thapsigargin (ER stress) or oligomysin (mitochondrial dysfunction) in Sk-Hep I cells, and observed that PLG levels were significantly increased in these conditions. Consistently, PLG overexpression increased expression of ER stress-related factors; however, repression of PLG expression by plg siRNA attenuated these changes. Our results demonstrate that high levels of glutamate are associated with development of diabetes, and are assumedly regulated by PLG.

Disclosure

H. Lee: None. J. Yun: None. H. Kim: None. H. Jang: None. S. Park: None. H. Lee: None.

Funding

Korea National Institute of Health (2017-NG64001-02)
2446-PUB: To What Extent Does Hyperglycemia Affect Bone Metabolism?
Authors: HAYASHI SEIKO , DESHPANDE GAUTAM , NOTO HIROSHI
Published: June 2019

Background: Chronic hyperglycemia has been previously reported to affect bone metabolism. However, this association may also be affected by other factors surrounding the hyperglycemic state, including physiologic complications of diabetes mellitus and its treatments. This study aims to assess to what extent hyperglycemia itself affects bone metabolism, using HbA1c as an indicator for chronic hyperglycemia.

Methods: We retrospectively examined data on all patients older than 20 years old who visited St. Luke’s Hospital for annual health checkup from April 2004 to March 2017. T scores were measured by forearm Dual-energy X-ray absorptiometry (DXA). Longitudinal analysis was used for statistical analyses, using multi-level mixed effect modeling treating T scores as a time-dependent variable to calculate beta coefficients, based on a T score range of HbA1c 5.5- 6.4. Data were adjusted for age, BMI, alcohol consumption, smoking, and exercise.

Results: 129,295 patients (mean age, 45.3 ±12.5 years; mean BMI, 22.3 ±3.39 kg/m2; male, 49.1%) were included over a median follow-up time of 744 days. Mean T score value was 99.1±12.3%. In longitudinal regression for men, T scores of HbA1c <=5.4 and HbA1c 6.5-8.4 were significantly low (βcoefficient -0.58- -0.14, P<0.05). In women under 50 years old, T scores in HbA1c range of 4.5-5.4 were significantly high (βcoefficient 0.19, P<0.05); T scores in a HbA1c range of 6.5-7.4 were significantly low (βcoefficient -0.60, P<0.05). In women >= 50 years, T scores in a HbA1c range of 4.5-5.4 were significantly high (βcoefficient 0.15, P<0.05), while T scores of HbA1c >=6.5 were significantly low (βcoefficient -1.80- -0.57, P<0.05).

Conclusion: Both men and women tend to have low bone mineral density at HbA1c values >= 6.5. Especially in women older than 50 years, bone mineral density significantly decreases as the value of HbA1c increases.

Disclosure

S. Hayashi: None. G. Deshpande: None. H. Noto: None.
2456-PUB: Cholesterol Uptake Capacity of High-Density Lipoprotein Predicts the Risk of Future Diabetes: The Hisayama Study
Authors: HIRAKAWA YOICHIRO , TOH RYUJI , HIGASHIOKA MAYU , YOSHINARI MASAHITO , HONDA TAKANORI , YOSHIDA DAIGO , HATA JUN , NAKAMURA UDAI , KITAZONO TAKANARI , NINOMIYA TOSHIHARU
Published: June 2019

Background: Cholesterol uptake capacity (CUC) is a novel index of the functionality of serum high-density lipoprotein (HDL), which has been reported to be associated with insulin resistance and the cardiovascular risk. However, only a few studies investigated the association of CUC with the development of diabetes. Herein, we assessed the association of CUC with incident type 2 diabetes in a general Japanese population.

Methods: A total of 2,162 subjects aged 40-79 years without diabetes underwent comprehensive health examination including 75g OGTT and were followed-up prospectively for a median of 6.0 years. The amount of HDL-contained cholesterol per apolipoprotein A1 levels after incubating the participants’ HDL with cholesterol as CUC were measured at baseline. CUC levels were categorized into quartiles (Q1:<0.303, Q2:0.303-0.325, Q3:0.326-0.351, Q4:≥0.352 a.u.). The hazard ratios (HRs) and their 95% confidence intervals (CIs) of CUC levels on the incident diabetes were estimated by using a Cox’s proportional hazard model with adjustment for confounding factors.

Results: During the follow-up period, 219 subjects experienced diabetes. The multivariable-adjusted HR (95% CI) was significantly decreased with elevating levels of CUC: 1.00 (reference) in Q1, 0.83 (0.57, 1.20) in Q2, 0.77 (0.52, 1.14) in Q3 and 0.64 (0.42, 0.98) in Q4 (p=0.04 for trend). In the analysis combined serum HDL cholesterol level (≤50mg/dl [25 percentile value] vs. >51 mg/dl) and CUC (Q1-Q3 vs. Q4), HRs (95% CIs) for the incident diabetes compared to both low group were 0.72 (0.36, 1.45) in isolated high CUC group, 0.73 (0.50, 1.06) in isolated high HDL cholesterol group, and 0.56 (0.34, 0.93) in both high group (p=0.88 for interaction).

Conclusion: Our findings suggest that the risk of diabetes decreased with elevating CUC levels independent of HDL cholesterol levels in the general Japanese population.

Disclosure

Y. Hirakawa: None. R. Toh: Other Relationship; Self; Sysmex Corporation. M. Higashioka: None. M. Yoshinari: None. T. Honda: None. D. Yoshida: None. J. Hata: None. U. Nakamura: None. T. Kitazono: None. T. Ninomiya: Research Support; Self; Asahi Kasei Corporation, Denka Company Limited, DeSC Healthcare, Inc, Mochida Pharmaceutical Co., Ltd., Suntory Beverage & Food Limited, Sysmex Corporation.

Funding

Japan Ministry of Education, Culture, Sports, Science and Technology; Japan Ministry of Health, Labour and Welfare; Japan Agency for Medical Research and Development