bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-Centered Outcomes of a Randomized Trial of Blood Glucose Monitoring Technology and Family-Centered Goal Setting
Authors: HALPER JILLIAN B. , HANNON TAMARA , YAZEL-SMITH LISA
Published: June 2018

Adequate frequency of self-monitoring of blood glucose (SMBG) is important to maintain glycemic control. Real-time sharing of adolescent SMBG data with parents and providers is possible, however, adolescents may be reluctant to adopt this technology. The objective of this research was to determine patient-centered outcomes of adolescent-parent research participant pairs who were randomized to utilize: (1) a glucometer that shared blood glucose data among patients, parent, and providers, and allowed for communication; (2) family-centered goal setting; and (3) a combination of (1) and (2). We evaluated data from 97 adolescent-parent pairs in the form of 10 validated surveys; we modeled longitudinal changes in survey responses from baseline to 6 months. Differences between treatment groups were evaluated using ANOVAs and changes within patients over time were evaluated using paired t-tests. Patient and parent satisfaction was high at the onset of the intervention; 4.31 out of 5 and 4.55 out of 5, respectively. Parent Satisfaction Survey (p = 0.04) and Parental Environment Questionnaire (p = 0.006) results decreased over time; there was no significant change for any other surveys. Our data suggest that it is important to individualize therapy to meet patient-centered goals and acknowledge this when designing interventions to improve health outcomes in adolescents with T1D.

Disclosure

J.B. Halper: None. T. Hannon: Consultant; Self; Eli Lilly and Company. L. Yazel-Smith: None.
Does Initiation of Basal Insulin Analogs in Patients with Type 2 Diabetes Mellitus Confer Advantages over Neutral Protamine Hagedorn (NPH) for Severe Hypoglycemia and Glycemic Control?
Authors: LIPSKA KASIA J. , PARKER MELISSA M. , MOFFET HOWARD H. , HUANG ELBERT , KARTER ANDREW J.
Published: June 2018

In clinical trial populations, long-acting insulin analogs modestly reduce the risk of nocturnal hypoglycemia compared with neutral protamine Hagedorn (NPH) in type 2 diabetes, but cost 2-4 times more. In real-world clinical practice, insulin performance may vary due to greater heterogeneity of patient characteristics and behaviors.

To compare rates of severe hypoglycemia and changes in glycemic control associated with insulin analogs vs. NPH, we conducted a propensity-score matched cohort analysis using data from Kaiser Permanente Northern California (20to 2015). We included patients with type 2 diabetes if they started a long-acting insulin analog or NPH, and we censored follow-up at death, loss of health plan coverage, change in type of insulin used, change in sulfonylurea treatment, or end of follow-up. Main outcomes were time to hypoglycemia-related utilization (emergency department visit or hospitalization with a primary or principal discharge diagnosis of hypoglycemia) and change in hemoglobin A1c within 1 year of insulin initiation.

Among 1,928 patients with type 2 diabetes who started insulin analogs and 23,561 who started NPH, there were 31 and 319 hypoglycemic events, respectively. After propensity score matching, the hazard ratio for severe hypoglycemia associated with insulin analog use was 0.95 (95% CI, 0.57, 1.46) and did not change significantly after additional adjustment for prior severe hypoglycemia and time-dependent diabetes medication use (HR 0.97, 95% CI 0.58, 1.54). Hemoglobin A1c decreased from 9.4% to 8.1% after initiation of insulin analogs and from 9.4% to 7.9% after initiation of NPH (difference-in-difference -0.19% (95% CI, -0.06, -0.34)).

In real-world clinical practice, the use of basal insulin analogs is not associated with a substantial reduction in hypoglycemia-related utilization or improvement in glycemic control compared with NPH insulin.

Disclosure

K.J. Lipska: Other Relationship; Self; Centers for Medicare and Medicaid Services. Research Support; Self; National Institutes of Health. M.M. Parker: Research Support; Self; Eli Lilly and Company. H.H. Moffet: Research Support; Self; Regeneron Pharmaceuticals, Inc., AstraZeneca. E. Huang: None. A.J. Karter: None.
Economic Evaluation of Dapagliflozin vs. Other Oral Hypoglycemic Drugs in China via Idealized Model
Authors: ZHENG JUAN , LONG LU , YE ZI , CHEN LULU
Published: June 2018

Objective: To analyze and compare economic values of cardiovascular benefits from dapagliflozin to the ones from other oral hypoglycemic drugs in China using the idealized model.

Methods: An idealized model for type 2 diabetes in China with an assumed number of cases (n=2000) was established. Half of cases (Dapa group; n=1000) are treated with 10 mg of dapagliflozin and another half (Other hypoglycemic drug group; n=1000) are treated with other oral hypoglycemic drugs as monotherapy. Cardiovascular benefits resulting from the CVD-REAL study were used as the evaluation criteria for predictions of cardiovascular events. Information about the direct economic loss brought by cardiovascular events reported in relevant literatures from 20to the present (Data source including the Web of Science, PubMed, Google scholar, Wanfangdata, CNKI and Cqvip) was collected as the standard for cost calculation.

Results: Compared with other oral hypoglycemic drugs, the application of dapagliflozin allows each type 2 diabetic patient to save an average of 14279.57 CNY on cardiovascular events annually in China. The annual per capita treatment cost for patients receiving dapagliflozin in the control of blood glucose and cardiovascular events was 66.98% of that of patients in the first and second-line treatment regimens, and was 65.83% of that of patients in the second-line treatment regimen.

Conclusions: Based on this idealized model, dapagliflozin is expected to save 33.02% of annual cost on hyperglycemia control and cardiovascular complications in patients with type 2 diabetes compared to patients treated with the first and second-line treatment regimens and to save 34.17% of annual cost compared to patients treated with the second-line treatment regimen in China.

Disclosure

J. Zheng: None. L. Long: Employee; Self; AstraZeneca. Z. Ye: Employee; Self; AstraZeneca. L. Chen: None.
An Assessment of Protocol Utilization and Efficacy when Transitioning from Infusion to Subcutaneous Insulin at an Academic Medical Center
Authors: VINCENT LAUREN , BOX KEVIN , KULASA KRISTEN
Published: June 2018

Background: The transition from intravenous to subcutaneous insulin is a complicated process often associated with poor glycemic control. Our academic medical center has protocols for guiding providers through this transition. Our protocols have previously been shown to improve glycemic control. We sought to assess protocol utilization and whether it continues to produce successful insulin transitions.

Methods: Data was collected through retrospective chart review of all transitions from intravenous to subcutaneous insulin completed at our medical center from April 2015 through June 2015. A successful transition was defined as one in which the insulin drip was not restarted, mean blood glucose was less than 180 mg/dL for the first 48 hours after transition, and there was no hypoglycemia (blood glucose less than 70 mg/dL).

Results: In total, 267 transitions from intravenous to subcutaneous insulin occurred at our medical center over the study period, and 211 were included in the analysis. For the group of patients with diabetes and transitioned to long acting subcutaneous insulin, 25 out of 1(23.1%) were transitioned using either our paper or computer protocol, and 82 out of 1(75.9%) were not transitioned via protocol. Of the 25 patients transitioned via protocol, 15 (60%) were successfully transitioned from intravenous to subcutaneous insulin. Of the 82 patients transitioned without using the protocol, 39 (47.6%) were successful. Among patients without a history of diabetes, 62 out of 65 patients (95.4%) were successfully transitioned from intravenous to subcutaneous insulin. The majority of these patients maintained good glycemic control with correctional insulin only.

Conclusions: Our protocol is effective in producing successful transitions from intravenous to subcutaneous insulin, however it is underutilized in our academic medical center.

Disclosure

L. Vincent: None. K. Box: None. K. Kulasa: None.
Predictors of Achieving Glycemic Targets among People with Type 2 Diabetes—The CARRS Trial
Authors: MASOOD MUHAMMAD Q. , SINGH KAVITA , MAWANI MINAZ Z. , ALI MOHAMMED K. , DEVARAJAN RAJI , KONDAL DIMPLE , SHIVASHANKAR ROOPA , AJAY VAMADEVAN S. , VARTHAKAVI PREMLATA K. , DHARMALINGAM MALA , SAHAY RAKESH , MENON USHA , VISWANATHAN VIJAY , BANTWAL GANAPATHI , KHADGAWAT RAJESH , DESAI ANKUSH , SETHI BIPIN , KADIR MUHAMMAD M. , VENKAT NARAYAN K.M. , PRABHAKARAN DORAIRAJ , TANDON NIKHIL
Published: June 2018

While poor glycemic (A1c), blood pressure (BP), and lipid control are common in patients with diabetes, the CARRS Trial among 1,146 type 2 diabetes patients showed the effectiveness of a multicomponent intervention (care coordinators and decision-support electronic health records). Compared to usual care, the intervention was associated with twice the probability of achieving glycemic and combined diabetes care goals (A1c<7% and BP<130/80 mmHg or LDLc<100 mg/dl). In absolute terms, however, only 20% of the intervention participants achieved glycemic targets. In this analysis, we evaluated the predictors of achieving good (A1c<7%) and avoiding poor glycemic control (A1c>9%) among CARRS participants (mean age: 54.2 years, median diabetes duration: 7 years and mean A1c:9.9%). Using generalized estimating equations, we analyzed four regression models (demographics, disease-related, self-care and other risk factors) to identify predictors of glycemic control, adjusting for intervention. We found income, education, diabetes duration, adherence to prescribed medication/diet/exercise, and diabetic retinopathy to be significantly associated with glycemic control (Table 1). Our data highlight the importance of tailoring treatments based on patients’ socioeconomic status (SES) and disease severity and also further research into innovations to facilitate better self-care in lower SES groups.

Disclosure

M.Q. Masood: None. K. Singh: None. M.Z. Mawani: None. M.K. Ali: None. R. Devarajan: None. D. Kondal: None. R. Shivashankar: None. V.S. Ajay: None. P.K. Varthakavi: None. M. Dharmalingam: None. R. Sahay: Advisory Panel; Self; Boehringer Ingelheim, Sanofi, Eli Lilly and Company, Novo Nordisk A/S. Advisory Panel; Spouse/Partner; Intas Pharmaceuticals Ltd., Pfizer Inc.. Speaker's Bureau; Self; Sanofi, Eli Lilly and Company, Boehringer Ingelheim, Dr. Reddys Laboratories, USV Private Limited, Glenmark. Speaker's Bureau; Spouse/Partner; Boehringer Ingelheim. U. Menon: None. V. Viswanathan: None. G. Bantwal: Speaker's Bureau; Self; Abbott. Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. R. Khadgawat: None. A. Desai: None. B. Sethi: None. M.M. Kadir: None. K. Narayan: None. D. Prabhakaran: None. N. Tandon: None.
A Novel Economic Analysis Applied to Innovative Diabetes Digital Health Intervention Demonstrates Significant Financial Benefits
Authors: SHOMALI MANSUR , IYER ANAND K. , GRIFFIN BRIAN T. , PEEPLES MALINDA
Published: June 2018

The healthcare industry has had limited success in translating the value of innovative diabetes interventions into true economic return on investment. Our objective was to determine the value of improving diabetes outcomes and then to apply those values to the utilization of a digital health tool, BlueStar™. The analysis was conducted using the MarketScan® Research Databases owned by Truven Health Analytics®, part of IBM Watson Health™. These research data sets fully integrate de-identified patient-level health data, productivity, laboratory results, health risk assessments, hospital discharges, electronic medical records (EMR) and morbidity data into data available for research. Data are contributed by large employers, managed care organizations, hospitals, EMR providers, and Medicare and Medicaid programs. A complex algorithm was applied to the MarketScan data, resulting in quantified total costs broken down by A1C. We examined two population segments: commercial (age 40-64, n=2,320) and Medicare (age 65+, n=821). Cost estimates could thus directly be applied from the tables derived from the database to the A1C reductions associated with the BlueStar population of users, demonstrating significant cost savings associated with the use of BlueStar™.Healthcare Costs by A1C Band for Commercial and Medicare PopulationsCommercial PopulationMedicare PopulationA1C BandPercentage in BandAnnual Cost Per PatientPercentage in BandAnnual Cost Per Patient<7%30%$13,08042%$11,6537%-8%34%$14,29835%$13,7868%-9%16%$15,03614%$16,726>9%20%$19,9809%$17,036

Disclosure

M. Shomali: Consultant; Self; WellDoc, Inc. A.K. Iyer: Employee; Self; WellDoc, Inc. B.T. Griffin: Other Relationship; Self; WellDoc, Inc. M. Peeples: Employee; Self; WellDoc, Inc..
Establishment of the Type 1 Diabetes Exchange QI Learning Collaborative (T1DX-LC)
Authors: SHAH AVNI , CORATHERS SARAH , ALONSO GUY T. , BUCKINGHAM DON A. , CABRERA ALYSSA B. , CLEMENTS MARK A. , DESALVO DANIEL J. , KAMBOJ MANMOHAN K. , LAMBERT KATHRYN L. , MEHTA SANJEEV N. , OHMER AMY L. , RIOLES NICOLE , SONABEND RONA , LEE JOYCE
Published: June 2018

Background: The proportion of patients with type 1 diabetes (T1D) who meet recommended HbA1c targets remains suboptimal, with little improvement over the last two decades. A Learning Collaborative (LC) is a multi-clinic learning and sharing quality improvement (QI) process known to accelerate improvement in chronic conditions. We created the T1DX-LC to spread learning to improve health outcomes of individuals living with T1D.

Methods: In 2014, a design process engaged clinicians, researchers, patient advocates, and QI leaders to develop a roadmap for improvement, based on the Chronic Care Model. The T1DX-LC launched in 2016 with 7 pediatric and 3 adult diabetes practices, coordinated by the T1D Exchange (Boston, MA). Over 18 months, we established a LC foundation: teams representing each clinic, governance, QI training and capability, online collaboration space, standard measures, and population data systems. Teams selected clinical tests of change to pilot for depression screening, pre-visit planning, and patient-centered clinic design.

Results: Teams completed formal QI coursework and collaborated via monthly calls, emails, an online collaboration space, and 3 in-person learning sessions. Six teams increased depression screening, 5 teams adopted multiple change ideas for pre-visit-planning, and 5 teams shared patient-centered tools and practices. A QI capability assessment survey was established and showed proficiency for all teams. We established a HIPAA-compliant data repository, data formatting specifications, data extraction/transmission standards, and a prototype data visualization dashboard. Two sites demonstrated the ability to extract and transmit EHR data to the central database.

Conclusions: The T1DX-LC demonstrated broad engagement, improved QI capability, advanced 3 focus areas, and developed a data exchange infrastructure. Our next steps are to build upon these efforts to accelerate improvement of outcomes in high-risk patients with T1D defined by HbA1c >9%.

Disclosure

A. Shah: None. S. Corathers: None. G.T. Alonso: None. D.A. Buckingham: None. A.B. Cabrera: None. M.A. Clements: Speaker's Bureau; Self; Medtronic. Advisory Panel; Self; Glooko, Inc. D.J. DeSalvo: Consultant; Self; Dexcom, Inc.. Speaker's Bureau; Self; Insulet Corporation. M.K. Kamboj: None. K.L. Lambert: None. S.N. Mehta: None. A.L. Ohmer: None. N. Rioles: None. R. Sonabend: None. J. Lee: Consultant; Self; Unitio.
Cost Savings Associated with Digitally Enhanced Insulin Therapy
Authors: HODISH ISRAEL , BISGAIER STANLEY G. , UNGER EMILY , AUSTIN MARY M.
Published: June 2018

Improved glycemic control in patients with type 2 diabetes (T2D) is associated with avoidance of complications and reduced healthcare costs. Yet for decades, most patients have not achieved treatment goals and a third have A1>9%. The d-Nav® Insulin Guidance Service facilitates scalable attainment and maintenance of therapy goals without increasing provider burden. d-Nav is a handheld device that automatically titrates insulin dosage based on the patient’s glucose readings obtained using the d-Nav device. Additionally, the service includes dedicated support of care specialists and pharmacological optimization if A1c improves. This 9-month study assessed the financial impact of the d-Nav service on diabetes related costs in sub-optimally control patients with T2D. We enrolled 218 insulin-treated patients, 193 of whom completed the 3-month follow-up. Thus far, 156 have completed the study. See Figure for A1c changes and patient satisfaction. Furthermore, 88% have chosen to enroll in a 12-month extension. Direct savings was estimated at $6,172 per patient per year (PPPY) for patients using branded medications and $1,736 PPPY across the entire cohort (p<0.001). Given the simplicity of use for the patient and no added provider burden, expansion of such a service may lead to a sizable reduction in cost.

Disclosure

I. Hodish: Stock/Shareholder; Self; Hygieia. S.G. Bisgaier: Employee; Self; Hygieia. E. Unger: Employee; Self; Hygieia. M.M. Austin: None.
Blue Index—The Diabetes Health Score
Authors: PANCHAL DHARMENDRA , PHATAK SANJEEV , ZINZUWADIA PADMANABH , SABOO BANSHI D. , HASNANI DHRUVI , KALRA SANJAY , DAS A. K. , DWIVEDI SHIVANGI
Published: June 2018

Aim: To evaluate and monitor quality of diabetes care in a single risk score format BLUE INDEX (BI).

Design and Method: We assessed overall health of patients with T2DM based on 10 parameters - 3 goals (A1c, BP, lipids), 4 self-care parameters (diet, exercise, follow-up, habits), and 3 health parameters (general health, infection, hypoglycemia). We categorized each parameter into six grades and formulated BI with minimum score 0 and maximum 50. BI > 45 = excellent and > 40 is considered as favorable. BI < 35 = undesirable. We calculated BI for 100 patients with T2DM > 1 year and repeated it at 2nd visit (3 months) and 3rd visit (6 months). Patients were educated for importance of each parameter and their overall health score was discussed. At the end of 3rd visit improvement in each parameter was studied.

Result: 100 patients with T2DM > 1 year were studied and divided into 3 groups as per BI. Group A= BI < 35, Group B = BI 35-45 and Group C = BI > 45. At baseline there were 76, 17 and 7 patients in Group A, B and C respectively with mean BI =26 ±2. After 3 month - 33, 44 and 23 patients in Group A, B and C respectively with mean BI = 37±3 and after 6 months there were 21, 41 and 38 patients in Group A, B and C respectively with mean BI = 42±2. There was 61% improvement in BI over the 6 months.

Conclusion: The BI provides comprehensive, pragmatic and patient centered mean of assessing care in persons with diabetes. The main role is in clinical triage, helping identify high risk persons who need intensive clinical intervention.

Disclosure

D. Panchal: None. S. Phatak: None. P. Zinzuwadia: None. B.D. Saboo: None. D. Hasnani: None. S. Kalra: None. A.K. Das: None. S. Dwivedi: None.
Cost Savings Associated with Usage and Blood Glucose Control for Members of the Livongo for Diabetes Program
Authors: BOLLYKY JENNIFER , LU WEI , SCHNEIDER JENNIFER , WHALEY CHRISTOPHER
Published: June 2018

Background: Novel technologies to support real-time self-management of chronic conditions are of interest to entities bearing financial risk for healthcare costs. The Livongo Diabetes Program offers patients with diabetes (1) a cellular-enabled, two-way messaging device that measures blood glucose, (2) free unlimited BG test strips; and (3) access to Certified Diabetes Educators for real-time support and goal setting. Previous work has shown decreased medical costs of $83pmpm for Livongo members vs. matched controls during first year of program. This study uses biometric and claims data to investigate the association between use of the Livongo program, BG control and medical spending among a commercially insured population of diabetes patients.

Methods: We compared medical spending and clinical outcomes for Livongo users (n =2027) with matched non-Livongo users (n=8385) for 12 months before and after the launch of the Livongo program using multivariate instrumental variable regression models that included controls for patient demographics (e.g., age, gender) and risk characteristics (e.g., comorbidity index, prior-period medical spending and program usage).

Results: Following launch of Livongo, risk-adjusted total spending for users and non-users decreased by 15.9%. Launch of Livongo led to a risk-adjusted 76.2% increase in the monthly use rate of Livongo. A 10% increase in the monthly Livongo usage rate is associated with a 2.1% decrease in medical spending associated (p<0.01), which was driven by a 2.9% reduction in spending on office-based services. Mean monthly medical spending for users with mean BG<154mg/dL was significantly lower than for users with mean BG>154mg/dL ($505.86 vs. $681.01, p=0.02).

Conclusion: Patients with diabetes enrolled in the Livongo program for 12 months experience medical cost savings associated with improved BG control. Cost savings for Livongo program users are primarily due to decreased spending on outpatient visits.

Disclosure

J. Bollyky: Employee; Self; Livongo Health. Stock/Shareholder; Self; Livongo Health. W. Lu: None. J. Schneider: Employee; Self; Livongo Health. Stock/Shareholder; Self; Livongo Health. C. Whaley: Consultant; Self; Livongo Health.
Impact of Hyperglycemia on 30-Day Readmission Rates
Authors: GAINES MARY , PRATLEY RICHARD E.
Published: June 2018

Background: The Centers for Medicare and Medicaid (CMS) Hospital Readmissions Reduction Program (HRRP) aims to reduce 30-day readmission rates for patients with acute myocardial infarction, heart failure, pneumonia, chronic obstructive pulmonary disease and hip/knee arthroplasty. The impact of hyperglycemia on readmission rates for these diagnoses is not known.

Methods: We analyzed 30-day readmission rates for patients discharged from Florida Hospital Orlando with CMS HRRP diagnoses from July 1, 2014 through June 30, 2017. Subjects were grouped according to eligibility (2 point-of-care glucoses within 24 hours) for our glycemic monitoring program (GMP) or not (non-GMP). The GMP group was further divided into controlled (C-GMP, mean blood glucose during hospitalization 70-180 mg/dL) and hyperglycemic (H-GMP, mean blood glucose > 180 mg/dL) groups.

Results: The GMP group had significantly higher readmission rates than the non-GMP group, as did the H-GMP group relative to the C-GMP group (Table). These differences remained significant after adjusting for difference in age, sex, diagnosis, case mix index and other factors in logistic regression analyses.

Conclusion: Hyperglycemic patients discharged with a CMS HRRP diagnosis have higher 30-day readmission rates. Strategies to prevent readmission should target glycemic control during and after hospitalization.VariableNon-GMPGMPC-GMPH-GMPN1767517008111205888Female %53.9%49.8%49.7%49.9%White %78.5%71.8%71.0%73.3%Age (years)67686967Weight (kg)80.28885.592.7Case Mix Index1.492.072.311.6130-Day Readmission Rate (%)14.421.5**21.122.3* * P < 0.05, ** P < 0.01 in risk-adjusted logistic regression analyses.

Disclosure

M. Gaines: None. R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc..
Impact of Diabetes Mellitus on Outcomes of Patients Undergoing Autologous Stem Cell Transplantation for Multiple Myeloma in the U.S.
Authors: SIWAKOTI KRISHMITA , GIRI SMITH , BHATT VIJAY
Published: June 2018

High dose chemotherapy followed by Autologous Stem Cell Transplant (Auto-SCT) is considered standard of care for most patients with Multiple Myeloma (MM) in the U.S. However, recent evidence suggests that diabetic patients with MM are less likely to receive Auto-SCT due to concerns for higher toxicity. We sought to determine the impact of diabetes on in-hospital outcomes of MM patients undergoing autoSCT. We queried the Nationwide Inpatient Sample (NIS) from the years 2009-2011 to identify all adult hospitalizations with MM and auto-SCT. Diabetic status was ascertained using ICD-9 diagnostic codes. Primary and secondary outcomes were in-hospital mortality and length of stay (LOS) or costs of hospitalization (COH) respectively. Univariate methods included chi-square test and t-test where appropriate. Multivariate analysis was done using Generalized Linear Mixed Models (GLMM) to account for clustering in the dataset. All p values were two sided and level of significance was chosen at 0.05. A total of 2868 (14,153 estimated) hospitalizations for MM related auto-SCT was identified, out of which 13% had diabetes. The mean age was 58 ± 8.7 years, 43% females and 67% whites. The overall in-patient mortality rate was 1.78% whereas mean LOS and COH was 17 days and $160,720 respectively. Diabetes did not impact inpatient mortality (1.31% vs. 1.85%; p 0.45), LOS (18 vs. 17.6 days; p 0.33) or COH ($160,665 vs. $160,728; p 0.99). Similar results were seen on GLMM for in-hospital mortality (adjusted Odds Ratio, aOR 0.67; 95% CI 0.26-1.75; p 0.42) after adjusting for patient (age, sex, race, comorbidity, insurance status) and hospital characteristics (bedsize, location, teaching status). Our large U.S. population-based study suggests that diabetic patients with MM undergoing Auto-SCT have similar in-hospital outcomes compared to their nondiabetic counterparts. Future studies should explore the incidence of other treatment related complications in this population.

Disclosure

K. Siwakoti: None. S. Giri: None. V. Bhatt: None.
Childhood Habitual Sleep Duration Modifies the Polygenic Risk for Obesity through Leptin Pathway—A Longitudinal Study
Authors: LI MING , FU JUNLING , HAN LANWEN , LI GE , GAO SHAN , GRANT STRUAN F. ,   BCAMS GROUP
Published: June 2018

Sleep disruption is known to be an obesity risk factor, however, little is known about its interplay with genetic predisposition and pathways involved in obesity pathogenesis, especially in the longitudinal setting. Leveraging a large cohort from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study, we aimed to examine a possible sleep-gene interaction for childhood obesity risk, including longitudinal assessment in a 10-year follow-up and further test if there is any mediation through the leptin pathway. A total of 3,211 children (6-18 years) were recruited from this cohort study. Baseline leptin levels and twelve established adult BMI loci were examined for the associations with habitual sleep duration. After adjusting for pubertal stages, diet score and activity, short sleep duration at baseline was significantly associated with increased overweight/obesity risk at both baseline and follow-up. Genetic predisposition scores, particularly consisting of the central nervous system (CNS) gene variation (GPSCNS), were robustly correlated with baseline overweight/obesity in children who slept ≤8h/day (P<0.001), whereas the association was ablated in those who slept ≥10h/day (P>0.05). Comparable observations were made at follow-up. Mediation analysis revealed a modest direct effect of the GPSCNS-sleep interaction on BMI at baseline, while an indirect effect of this interaction was found to be mediated principally through elevated leptin (52.6%); moreover, the mediation effect via leptin remained stable over 10 years. This study provides longitudinal evidence that short sleep duration in children has a long-term impact on the association of polygenic risk for obesity from childhood to young adulthood and leptin pathway explains a key mechanism via a modification effect. Therefore, adequate sleep duration during childhood is important for the early prevention of obesity, especially if there is a genetic predisposition to this trait.

Disclosure

M. Li: None. J. Fu: None. L. Han: None. G. Li: None. S. Gao: None. S.F. Grant: None.
Association of Intensive Lifestyle Intervention and Metformin with Frailty in the Diabetes Prevention Program (DPP) Outcomes Study (DPPOS)
Authors: HAZUDA HELEN P. , PAN QING , CRANDALL JILL P. , FLOREZ HERMES , LUCHSINGER JOSE A. , VENDITTI ELIZABETH M. , KRISKA ANDREA , GOLDEN SHERITA , BRAY GEORGE ,   DPP RESEARCH GROUP
Published: June 2018

Objective: To examine whether odds of frailty differ by DPP intervention arms (intensive lifestyle intervention [ILS], metformin [MET], placebo [PLB] after long-term follow-up in the DPPOS.

Methods: DPP, a randomized trial of individuals at high risk of diabetes, lasted 2.8 years, after which there was a 13-month bridge period in which 16 sessions of group ILS was offered to all participants. During DPPOS, ILS was offered lifestyle reinforcement semi-annually and MET received unmasked metformin. Frailty was measured initially in DPPOS Year 8 in 2385 participants and repeated in 2264 of these in Year 10 (12 and 14 years after randomization). Using Fried criteria, presence of 3 of 5 characteristics (slow walking speed, weak grip strength, unintentional weight loss, low physical activity, and exhaustion) was classified as frail, 1 or 2 pre-frail, and 0 non-frail.: GEE models adjusting for visit year were employed with repeated measures pooled from Years 8 and 10 to estimate pairwise odds ratios between ILS, MET and PLB for the outcomes of frail and pre-frail vs. non-frail.

Results: Odds of frailty vs. non-frailty were 37% lower in ILS compared to PLB (Table) and MET (OR=0.629, CI= 0.420-0.942, p=0.024). There were no significant treatment group differences in odds of pre-frailty.

Conclusion: ILS intervention in persons at high risk of diabetes may reduce frailty in later life.12 years Post-randomization14 years post-randomizationOdds of Frailty vs. Non-Frailty Pooled over both examsTreatment GroupPrevalencePrevalence OR (95% CI) compared with placeboP-valuePre-FrailtyFrailtyPre-FrailtyFrailtyPlacebo42.8%5.7%43.7%5.4%1 (referent)n/aMetformin45.8%5.4%42.5%5.3%0.994 (0.694-1.424)0.976Lifestyle46.8%3.0%46.3%3.6%0.625 (0.419-0.934)0.022

Disclosure

H.P. Hazuda: None. Q. Pan: None. J.P. Crandall: None. H. Florez: Advisory Panel; Self; Sanofi. J.A. Luchsinger: None. E.M. Venditti: None. A. Kriska: None. S. Golden: None. G. Bray: Advisory Panel; Self; Herbalife International of America, Inc., Novo Nordisk A/S. D. Research Group: None.
Transforming Pediatric T2D Clinical Research—A Network Model
Authors: GAL ROBIN L. , BEAULIEU LINDSEY C. , KEELIN KIMBERLY D. , LESS JOANE E. , NELSON BRYCE A. , WINTERGERST KUPPER A. , KLINGENSMITH GEORGEANNA J. , TAMBORLANE WILLIAM V.
Published: June 2018

Background: Treatment options for youth with type 2 diabetes (T2D) are limited compared to those for adults with T2D. As pediatric clinical trials in T2D are difficult to complete, due to lower prevalence and population related recruitment challenges, clinical sites are often reluctant to participate. Protocol design, often not appropriate for pediatrics, administrative and financial burden related to study participation further reduce site interest.

Methods: The Pediatric Diabetes Consortium (PDC) is a network of 49 U.S. diabetes centers working together to improve care for children with diabetes. Recognizing challenges associated with pediatric T2D clinical trial participation, the PDC developed a network model to improve efficiency for both sites and sponsors.

Innovations: A consulting group was formed to assist with protocol design appropriate for T2D pediatric studies. A PDC master agreement with sites eliminates need for negotiation of standard contract language between sponsor and each site, allowing for a single contract between the PDC and sponsor. A single budget, based upon a clinical trial budget template, reflecting actual site costs, is negotiated by the PDC for all sites. Central archiving of site metrics eliminates need for a feasibility survey before site selection occurs. Monthly site calls led by an investigator oversight committee provide opportunities to discuss enrollment strategies, study challenges and best practices, and provide real-time feedback to sponsor.

Conclusion: Efficiencies established by the PDC network model reduce workload for sites and start-up timeline for sponsors. Population-appropriate trial design improves recruitment opportunities. Ongoing site engagement helps to identify and mitigate protocol issues in real-time. The network model improves likelihood of successful trial operations. To date, 26 PDC sites have participated in at least 1 of 3 studies, enrolling 137 across studies so far, contributing to successful recruitment ahead of projected schedule.

Disclosure

R.L. Gal: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Development Center Americas, Inc., Novo Nordisk Inc. L.C. Beaulieu: Research Support; Self; Novo Nordisk Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Development Center Americas, Inc.. K.D. Keelin: None. J.E. Less: None. B.A. Nelson: Speaker's Bureau; Self; Dexcom, Inc.. K.A. Wintergerst: None. G.J. Klingensmith: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Foundation. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceuticals U.S.A., Inc..
The Acute Effect of Empagliflozin on Fractional Excretion of Sodium and eGFR in Youth with Type 2 Diabetes
Authors: BJORNSTAD PETTER , LAFFEL LORI M. , TAMBORLANE WILLIAM V. , SIMONS GUDRUN , HANTEL STEFAN , EYNATTEN MAXIMILIAN VON , GEORGE JYOTHIS T. , MARQUARD JAN , CHERNEY DAVID
Published: June 2018

Sodium-glucose cotransporter-2 (SGLT2) inhibition reduces hyperfiltration in adults with T1D, likely by inducing natriuresis, which stimulates tubuloglomerular feedback. This exploratory analysis aimed to examine whether these renal effects occur acutely within 24 hours of SGLT2 inhibition following a single exposure to empagliflozin (EMPA) in youth with T2D. In this single-administration, open-label, randomized, parallel-group study (NCT02121483), 27 patients with T2D (mean age 14.1 years, 67% girls, mean BMI 35.5 kg/m2) received EMPA 5, 10 or 25 mg. The effects of EMPA on fractional sodium excretion (FENa+) and estimated GFR (eGFR as assessed by Zappitelli-combined creatinine and cystatin C equation) were investigated by pooling the three doses of EMPA for analyses. At baseline, mean (SD) baseline FENa+ was 0.55% (0.46), and eGFR was 123.4 ml/min/1.73m2 (15.6). After a single dose of EMPA, the adjusted mean change from baseline in FENa+ was +0.81% (95% CI 0.27, 1.36; p=0.006). The adjusted mean change from baseline in eGFR was -5.5 ml/min/1.73m2 (95% CI -8.3, -2.7; p=0.0006). In eGFR subgroups of interest, eGFR decreased by -6.7 (9.7) ml/min/1.73m2 in patients with hyperfiltration (n=8, eGFR >119.1 ml/min/1.73m2, [95th percentile of eGFR for obese youth in NHANES]) and by -5.0 (6.0) ml/min/1.73m2 in patients with normofiltration (n=19). SGLT2 inhibition following a single dose of EMPA was associated with acute natriuresis and attenuation of elevated GFR in youth with T2D, suggesting a reduction in intraglomerular pressure. Further mechanistic studies are required to define changes in renal function, and longer-term trials examining renal protective effects in youth with diabetes are needed.

Disclosure

P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. L.M. Laffel: Consultant; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi US, MannKind Corporation, Roche Diagnostics Corporation, Dexcom, Inc., Insulet Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Johnson & Johnson Diabetes Institute, LLC. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceuticals U.S.A., Inc. G. Simons: Employee; Self; Boehringer Ingelheim GmbH. S. Hantel: Employee; Self; Boehringer Ingelheim GmbH. M. von Eynatten: Employee; Self; Boehringer Ingelheim GmbH. J.T. George: Employee; Self; Boehringer Ingelheim GmbH. J. Marquard: Employee; Self; Boehringer Ingelheim GmbH. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..
Identification of Gastric Mucosa Key Pathways and Genes in Obesity and Obesity-Related Diabetes via Gene Microarray Analysis
Authors: WEN XIN , ZHANG YI , WU RUI J. , ZHU CUILING , CUI RAN , HUI YOU , MEI FANG Y. , GAO JINGYANG , QU SHEN , BU LE
Published: June 2018

Background: Gut uses variety of pathways to establish closely contact with obesity and obesity related diabetes, including gut-brain cross-talk, gut microbiota, immune pathway and gastrointestinal hormones. In this study, we aimed to identify the key pathways and genes of gastric mucosa in obesity patients with or without type 2 diabetes.

Methods: Our study was divided into three groups, healthy control group with normal BMI, patients with simple obesity(OB) and obesity with type 2 diabetes mellitus(OD), three cases in each groups. Gastric mucosal tissues were isolated then analyzed by gene microarray. The differentially expressed genes were screened by functional enrichment analysis and pathway analysis.

Results: 262 up-regulated genes and 265 down-regulated genes were differentially expressed between OB and normal-BMI patients. Besides, 1756 up-regulated genes and 1053 down-regulated genes were differentially expressed between OD and control subjects (fold change>2 p < 0.05). For DEGs comparisons in each group, 13 genes were co-up regulated, 10 genes were co-down regulated, and an additional 12 genes showed different trends. After analyzing the biological process and molecule function of differential expression genes, these genes were found to play crucial roles mainly in cellular metabolic, protein binding and other biological process. The analysis of KEGG showed that the relevant genes participate in Citrate cycle, NF-kappa B and PI3K-Akt signaling pathway.

Conclusions: During the process of obesity and obesity related diabetes, in gut there is not only one specific gene or pathway, but multiple genes and pathways that change. The effects of genes expressed in gastric mucosa mainly influence cellular metabolic processes, NF-kappa B and other proinflammatory signaling pathway.

Disclosure

X. Wen: None. Y. Zhang: None. R.J. Wu: None. C. Zhu: None. R. Cui: None. Y. Hui: None. F.Y. Mei: None. J. Gao: None. S. Qu: None. L. Bu: None.
Adolescents at High-Risk for Developing Type 2 Diabetes and/or Polycystic Ovary Syndrome Can Be Identified Using a Simple Questionnaire while in High School
Authors: KARAKAS SIDIKA
Published: June 2018

Introduction: Family history of type 2 diabetes (T2DM), obesity, acanthosis nigricans, skin tags, hirsutism and/or menstrual irregularities are associated with increased risk for developing T2DM, metabolic syndrome and polycystic ovary syndrome (PCOS). Early identification of adolescents at risk can provide opportunities for timely preventive interventions.

Methods: We created a simple questionnaire (UCD-QUES) which includes 5 sections: 1) Anthropometrics; 2) Signs of insulin resistance (pictures of acanthosis nigricans and skin tags); 3) Family history of DM; 4) Menstrual history; 5) Hirsutism (Figure of an adolescent female marking the areas susceptible to hirsutism). The UCD-QUES for male students included only the first 3 sections. We administered the UCD-QUES to 232 students (163 F, 69 M), attending grades 9-12 in 5 Sacramento, California high schools.

Results: Self-reported ethnic distribution of the students was: 35% Hispanic, 20% Asian, 17% white and 15% black. Weight distribution was: 39% were overweight (26%, BMI: 25-29.9) or obese (13%, BMI>30). Family history indicated: 22% had one or more 1st degree relative, and 51% had at least one 2nd degree relative with DM. Acanthosis nigricans or skin tags were reported by 14%, hirsutism by 15%, and irregular periods by 38%. One out of 8 female adolescents (13%) fulfilled the clinical criteria for PCOS, but only 2 students had ever heard of PCOS.

Conclusion: Adolescents who are at risk for developing DM, metabolic syndrome or PCOS can be identified by high-school-based screening using a simple questionnaire. Further research is required to determine 1) whether focusing preventive efforts to these high-metabolic risk adolescents can increase the success of the interventions while cutting cost, and 2) whether identification of high-risk adolescents can provide multi-generational benefits by creating access to their high-risk families and protecting their offspring.

Disclosure

S. Karakas: None.
Late Reactive Hypoglycemia (RHG) as a Common Early Sign of Glycemic Dysfunction in Obese Adolescent Girls
Authors: CARREAU ANNE-MARIE , RAHAT HASEEB , REYES YESENIA GARCIA , PYLE LAURA , NADEAU KRISTEN J. , CREE-GREEN MELANIE
Published: June 2018

Many obese adolescent girls describe symptoms of hypoglycemia, but this has not been systematically assessed. Due to pubertal insulin resistance (IR), hormonal responses to an oral glucose tolerance test (OGTT) may occur beyond the typical 2h sampling interval. We sought to determine how often reactive hypoglycemia (RHG) occurs in these girls. 56 girls aged 12-20 years, BMI percentile ≥ 90th, were enrolled in a study including fasting metabolic labs and a 6h OGTT with frequently sampled glucose, C-peptide, insulin, GLP-1 and glucagon. RHG was defined as a blood glucose (BG) < 70 mg/dL with a ≥ 20 mg/dL drop from the previous sample. Comparisons between those with and without RHG were performed with a Student’s t-test. 50% of girls had BG <70mg/dL (mean nadir was 62 mg/dL); 18% were <65 mg/dL and 12% < 60 mg/dL. The median time for lowest BG was 240 min (range 210-360 min) after the glucose load. Girls with RHG were slightly younger (15.1±1.8 vs. 16.2±1.5 years; p=0.02). The groups had similar BMI percentile (97.8 vs. 96.8) and percent fat mass, but tended to have more visceral fat (10.1% vs. 8.1%; p=0.08). Fasting glucose and insulin were not different between groups, but HOMA-IR tended to be higher in RHG (7.0±5.4 vs. 4.9±2.2, p=0.07). The area under the curve of insulin and glucose for the first 180 min of the OGTT was higher in RHG (p=0.01 and p=0.04, respectively), with impaired glucose tolerance tending to be more frequent in RHG (63% vs. 40%; p=0.08). The mean insulin peak for the RHG was at 150 min, vs. 30 min post-drink in the normal group. At 240 min, glucagon tended to be higher in RHG (81 vs. 67 pg/ml; p=0.06). RHG defined as a BG <70 mg/dL following a rapid drop, is common in girls with obesity in response to liquid sugar, and occurs later than detectable with a standard 2h OGTT. RHG appears to be secondary to an overly robust, late insulin response. This pattern is likely related to IR, may precede further dysglycemia and may be severe enough to cause a counter regulatory response, arguing to avoid consuming liquid sugar in isolation.

Disclosure

A. Carreau: None. H. Rahat: None. Y. Garcia Reyes: None. L. Pyle: None. K.J. Nadeau: None. M. Cree-Green: None.
Alterations in Novel Signals in the Gut–Adipose Axis–A Pilot Study in Insulin-Resistant Children with Obesity and Biopsy-Proven Nonalcoholic Steatohepatitis
Authors: DI GUGLIELMO MATTHEW D. , MANSOOR SANA , UPPAL VIKAS , FURUYA KATRYN N. , KUMAR SEEMA , BALAGOPAL P. BABU
Published: June 2018

Background: Body weight homeostasis and the progression of obesity to comorbidities such as nonalcoholic steatohepatitis (NASH), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) involve the gut-brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. Data on the role of a gut-adipose axis in children with obesity-related comorbidities are sparse. We determined novel signals in the gut-adipose axis such as pro-uroguanylin (PUG) produced in the gut and spexin, predominantly produced in white adipose tissue along with traditional appetite/satiety hormones in insulin-resistant children with (NASH) and simple obesity.

Method: A total of 29 children (age: 8-17 years) in three groups, normal weight (NW; n=11; BMI<85th%), obese (n=9; BMI>95th%) and biopsy-proven NASH (n=9; NAS-score>2) were studied. Spexin, PUG, leptin, total (T)- and high molecular weight (HMW)-adiponectin and insulin were measured.

Results: Spexin, PUG and both T and HMW adiponectins were lower in children with NASH compared to both children with simple obesity and their NW counterparts, while leptin and insulin were higher (p<0.05). Spexin/leptin ratio and concentration of PUG were significantly lower (p<0.05) in children with NASH vs. simple obesity, whereas leptin and insulin were higher (p<0.05).

Conclusions: Lower concentrations of novel signals such as PUG and spexin in the current study suggest that perturbations in the gut-brain axis occur at an early age in the clinical course of obesity and NASH. The potential role of these novel gut-adipose axis signals, by themselves or in unison with other factors, in diagnosing and/or monitoring the development and/or progression of obesity-related comorbidities such as NASH, T2DM and CVD as well as the potential development of more directed therapies appears to be promising and warrants further studies.

Disclosure

M.D. Di Guglielmo: None. S. Mansoor: None. V. Uppal: None. K.N. Furuya: None. S. Kumar: None. P. Balagopal: None.
Vitamin D Levels Are Associated with Risk Factors for Type 2 Diabetes and Metabolic Syndrome in Chinese Youths
Authors: GAO SHAN , HAN LANWEN , FU JUNLING , LI GE , LI MING , WILLI STEVEN M.
Published: June 2018

Evidence regarding association between vitamin D deficiency and metabolic syndrome (MS) remains controversial and relatively sparse among youth. We aimed to explore the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and risk factors for type 2 diabetes and MS in Chinese adolescents and young adults. A total of 559 subjects aged 14-28 years with high risk of MS were recruited from the Beijing Child and Adolescent Metabolic Syndrome Study cohort in 2012. All subjects underwent a 2h-oral glucose tolerance test. The concentrations of 25(OH)D, glucose, insulin and lipids were determined. MS was defined by the 2009 harmonized definition. The prevalence of vitamin D deficiency (< 20 ng/ml) was 78.3%. After adjusting for age, gender and visiting season, 25(OH)D levels were negatively correlated with percent body fat, LDL-C, fasting and 2h-glucose levels (all p < 0.05). 25(OH)D levels were significantly lower in subjects with obesity, high TG, type 2 diabetes, or MS, compared to their counterparts, respectively (all p < 0.05). After adjustment for potential confounders including body mass index, subjects in the lowest vs. highest tertile of 25(OH)D levels was 2.5 times more likely to have MS (Odds 95% CI: 1.13-5.45, p < 0.05). Vitamin D deficiency was very common in this young Chinese population with risk for MS. Given the negative association between vitamin D level and cardiometabolic risk factors, effective sun exposure and vitamin D supplementation should be encouraged in youths, particular in those with high MS risk.

Disclosure

S. Gao: None. L. Han: None. J. Fu: None. G. Li: None. M. Li: None. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim GmbH. Other Relationship; Self; Caladrius Biosciences, Inc.. Consultant; Self; GlaxoSmithKline plc., JAEB Center For Health Research.