bluuebunny/crossref_metadata_2025 huggingface dataset:
13-LB: Nasal vs. Injected Glucagon: User Experience Results of a Simulated Severe Hypoglycemia Study
Authors: SETTLES JULIE , CHILD CHRISTOPHER J. , BAJPAI SANJAY K. , SPAEPEN ERIK , SUICO JEFFREY G.
Published: June 2019

Injectable glucagon (IG) is challenging to use for caregivers of a person with diabetes (PWD) in stressful severe hypoglycemia (SH) rescue. We evaluated user preference for nasal glucagon (NG) and IG devices after treating simulated SH. The PWD trained arm was adult PWDs trained to use NG or IG, then PWDs trained their caregivers how to use it; 1 week later, caregivers administered the device to a life-like manikin exhibiting SH in a simulated real life setting with distractions creating urgency. The untrained arm was adults not associated with a PWD, but willing to assist - not trained, but shown the device just presimulation. After 1 week, the process was repeated with the other device. We assessed perceptions of simulation participants and PWDs via comparative device questionnaires, completed after videos of both simulations were viewed after the 2nd simulation (no confirmation of success provided). NG was rated more preferred by those with successful doses of NG or IG. PWDs indicated that they felt safer with NG even with successful IG dosing (Table). Untrained users were as successful as PWD-trained in dosing NG, while there were no IG successes without training. None of the few who preferred IG gave a successful IG dose, whereas the few successful IG-users preferred NG or stated no preference. Being PWD-trained was not critical for success with NG, and ease of preparation and use likely contributed to overall preference.

Disclosure

J. Settles: Employee; Self; Eli Lilly and Company. C.J. Child: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. S.K. Bajpai: Employee; Self; Eli Lilly and Company. E. Spaepen: Consultant; Self; Eli Lilly and Company. J.G. Suico: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
130-OR: Does the Duration of Prediabetes Status Affect Reversibility with Lifestyle Intervention?
Authors: UMEKWE NKIRU A. , OWEI IBIYE , BREWER AMY A. , FRENCH LINDSEY , JAMES DEIRDRE J. , ARIGANJOYE FOLABI , DAGOGO-JACK SAMUEL
Published: June 2019

Background: Intensive lifestyle intervention (ILI) prevents progression from prediabetes (Predm) to type 2 diabetes (T2D). Here we assessed reversion to normal glucose regulation (NGR) following ILI.

Subjects and Methods: The PROP-ABC (Pathobiology and Reversibility of Prediabetes in a Biracial Cohort) study followed an established cohort of African Americans (AA) and European Americans (EA) with parental T2D for 5 years and initiated ILI in subjects with Predm and those with newly incident Predm. ILI was started after variable intervals from onset of Predm, targeting 10% weight loss through calorie restriction, physical activity, and meal replacements. Serial assessments included anthropometry, fasting plasma glucose (FPG) and lipid levels, OGTT, IVGTT and insulin sensitivity. The primary endpoint was reversion to NGR.

Results: We studied 210 PROP-ABC participants: mean (SD) age 53.3(9.28) y; BMI 30.6(6.70) kg/m2; 70% female, 52.4% AA, 47.6% EA. Predm subjects (N=138) initiated ILI after a latency of 4.08 (2.02) years (range 3 months-8 years), and were stratified into < 3 years (n=32), 3-5 years (n=59) or >5 years (n=47), between onset of Predm and initiation of ILI. Control (N=72) were NGR subjects not receiving ILI. After 5y, FPG (-6.91±1.13 mg/dl vs.1.23 ± 1.43 mg/dl, P=0.0008), 2hPG (-8.23 ±3.27 mg/dl vs.-4.90 ± 8.63 mg/dl, P=0.08) and weight (-2.64 ± 0.85 kg vs. 1.24±1.13 kg, P= 0.04) decreased among ILI participants vs. control. Reversion to NGR occurred in 43.5%, stable Predm in 50%, and T2D in 6.5%. These outcomes did not differ significantly by time to initiation of ILI (chi-square P=0.901). Reversion to NGT occurred within 12 months of ILI and was significantly predicted by BMI, waist size, insulin sensitivity, insulin secretion, and HDL-c (P= 0.04-0.001).

Conclusion: Starting ILI within 3 months to 8 years of occurrence of prediabetes prevented T2D in >90% and restored NGR in ~44% of AA and EA subjects with parental T2D, regardless of time to initiation of ILI.

Disclosure

N.A. Umekwe: None. I. Owei: None. A.A. Brewer: None. L. French: None. D.J. James: None. F. Ariganjoye: None. S. Dagogo-Jack: Board Member; Self; Jana Care Inc. Consultant; Self; Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Stock/Shareholder; Self; Dance Biopharm Holdings Inc.

Funding

National Institutes of Health (R01DK067269)
1301-P: An Analysis of Correlative Factors of HbA1c Achieving Rate in Follow-Up Cohort of Internet plus Diabetes Shared Care Clinic
Authors: LI ANG , YUAN XIAOYONG , LIN LIU , LU DIFEI , ZHANG DONGHUI , SUN YALAN , LI JUN , JING LULU , WANG YANNI , GUO XIAOHUI , ZHANG JUNQING
Published: June 2019

Objectives: Our study aimed to investigate the correlative factors of HbA1c achieving rate in diabetic patients followed-up in Internet plus Diabetes Shared Care Clinic (IDSCC) in General Hospital.

Methods: Patients who were regularly followed-up in IDSCC were enrolled in the study from Oct. 2016. Up to Dec. 2018, demographic data of patients, HbA1c of each follow-up, diabetic medication and education power during online and offline follow-ups were recorded. Patients were divided into two groups according to whether HbA1c achieve target (<7%) or not at the last follow-up. Logistic regression analysis was performed to analyze covariates of HbA1c at last follow-up, including age, diabetic duration (<5 years, 5-10 years, 10-15 years, >15 years), gender, baseline HbA1c, insulin usage, self-monitoring of pre-meal and postprandial glucose (none, <=1 pair per week, >1 pair per week), intensity of offline support and exposure of online support.

Results: 515 patients were enrolled. Shorter diabetic duration (OR=2.64, p=0.005), no usage of insulin (OR=3.83, p<0.0001), achieving HbA1c target at first visit (OR=7.94, p<0.0001) and higher exposure of online support (OR=1.84, p=0.009) were positively correlated to better HbA1c achieving rate.

Conclusions: Higher online self-management support (over 41.9 min/quarter) could bring better HbA1c achieving rate for diabetic patients in IDSCC.

Disclosure

A. Li: None. X. Yuan: None. L. Lin: None. D. Lu: None. D. Zhang: None. Y. Sun: None. J. Li: None. L. Jing: None. Y. Wang: Employee; Self; iHealth Labs Inc. X. Guo: None. J. Zhang: None.
1302-P: Availability and Affordability of WHO Essential Medicines for Diabetes in Low- and Middle-Income Countries—Assessing the Gap and Needs from a Systematic Review
Authors: DIALLO ALPHA MAMADOU , ALI MOHAMMED K. , VENKAT NARAYAN K.M.
Published: June 2019

Background: The burden of diabetes is overwhelming worldwide and more important in low- and middle-income countries (LMICs). Preventing cardiovascular morbidity and mortality by providing essential medicines for diabetes and its associated risk factors is a major concern in a context of scarcity of resources and weak health systems. We conducted a systematic review from the recent literature to assess and synthesize the gap and needs for access to essential diabetes medicines in LMICs.

Methods: We selected the recently published literature on essential medicines for diabetes in LMICs using the PubMed database. Articles were found using the following keywords: "Diabetes AND Essential Medicines" and "Diabetes AND Access to Insulin." Relevant studies conducted in one or more LMICs, as defined by the World Bank, were selected for analysis.

Results: Availability and affordability of essential medicines for diabetes is poor in LMICs. Availability of insulin was as low as 10.3% in low income countries while 63% of households could not afford insulin in the PURE study conducted in 22 countries (18 LMICs). In two national surveys conducted in Uganda and Zambia, none of the heathcare facilities was meeting the WHO Standards for essential tools and medicines in Uganda and few (6 out of 46) in Zambia, with only 11% availability of insulin in rural area.

Conclusions: The LMICs include a wide range of countries with varying levels of health care resources and quality. To meet the challenge of access to essential medicines for diabetes and other noncommunicable diseases, it is necessary to categorize needs by region and by country in order to prioritize interventions.

Disclosure

A.M. Diallo: None. M.K. Ali: None. K. Narayan: None.
1303-P: Improving Rate of Glucose Recheck after Hypoglycemia through the PDSA Model
Authors: YUNXIA LIU , YI LI , LI CHUNRUI , ZHENGGUO YANG , KAREN LAU KA HEI , POBER DAVID M. , ZHANG LINDA (YAN) , GABBAY ROBERT A. , HSU WILLIAM C.
Published: June 2019

Recent studies have linked severe hypoglycemic episodes with increased risk for adverse cardiovascular outcomes. The ADA guidelines recommend that hospitals implement a hypoglycemia management protocol that includes rechecking for hypoglycemia 15 minutes after each hypoglycemic episode.

Sunshine Union Hospital in China collaborated with Joslin Diabetes Center to implement an inpatient glucose management (IPGM) program. A steering committee was set up to oversee the implementation of inpatient protocols. As a quality improvement pilot to enhance patient safety, the committee focused effort on improving the rate of rechecking blood glucose within 15-30 minutes after a hypoglycemic episode (< 70mg/dL). Following the Plan-Do-Study-Act (PDSA) method, which is a four-step model that tests small changes to identify best practices, outcomes were tracked, analyzed, and communicated monthly with the nursing and medical staff.

Hypoglycemic events occurred 56.9 ± 22.1 times/month in the 1000-bed hospital. Hypoglycemic recheck frequency (15-30 minutes post a hypoglycemic event) steadily improved over the 12 month-period, from 0% in December of 2017 to over 95% in the last three months of 2018 (Figure 1). Most common reasons for missing hypo-recheck included patient refusal and busy nursing schedule.

PDSA model was helpful in improving outcomes in this IPGM pilot. Future efforts will leverage a similar approach to reduce inpatient hypoglycemia.

Disclosure

L. Yunxia: None. L. Yi: None. C. Li: None. Y. Zhengguo: None. K. Lau: None. D.M. Pober: None. L. Zhang: None. R.A. Gabbay: Advisory Panel; Self; HealthReveal, Hygieia, Lark, Onduo LLC. Consultant; Self; Sanofi. W.C. Hsu: Consultant; Self; Onduo LLC.
1304-P: “They Were All Together...Discussing the Best Options For Me”: Integrating Specialist Diabetes Care within Primary Care
Authors: KUZULUGIL DENIZ O. , HARRIS MELISSA L. , BYLES JULIE E. , PARSONS MARTHA E. , PHILCOX ANNALISE N. , ACHARYA SHAMASUNDER H.
Published: June 2019

Introduction: In Australia, over a third of encounters with health care providers for diabetic patients fail to provide clinical guideline appropriate care. The Diabetes Alliance, integrated care model implemented across a large healthcare district with a view to enhance diabetes care capacity at primary care through intensive case-conferencing with primary care team, patients and visiting specialist team; whole practice performance feedback, and; regular diabetes masterclasses. Here, we aimed to provide in-depth insight into the case-conferencing process and impact of the model of care for patients with diabetes.

Methods: Patients from 5 practices (including 2 with high and 3 with low proportions of patients with a recent HbA1c) provided the sampling frame. Patients were selected according to Patient Activation Measure scores to achieve maximum variation with 1 or 2 patients with high scores and 2 or 3 patients with low scores were selected from each practice. Participants were sampled until saturation was achieved. Thematic content analysis was applied to the 19 interviews.

Results: Patients largely found the model of care a positive experience, reporting a boost in confidence in diabetes self-management (particularly around nutrition), with the program providing an opportunity to refocus when “life gets in the way.” Other key aspects of the program that were viewed positively included the holistic approach to healthcare, reduced travel time and congestion, familiarity in environment and clinical care, top-down knowledge transfer as well as mutual learning by the patient and their primary care team. Patients however also described difficulties in coping with diabetes as a chronic illness and adherence to treatment recommendations.

Conclusion: Providing timely integrated specialist care within the primary care setting is an efficient means of enhancing the engagement of diabetic patients with their diabetes care and therefore their outcomes.

Disclosure

D.O. Kuzulugil: None. M.L. Harris: None. J.E. Byles: None. M.E. Parsons: None. A.N. Philcox: None. S.H. Acharya: None.
1305-P: Detection of Diabetes Status and Type in Youth Using EMRs
Authors: WELLS BRIAN J. , LENOIR KRISTIN M. , WAGENKNECHT LYNNE E. , MAYER-DAVIS ELIZABETH , DABELEA DANA , LAWRENCE JEAN M. , PIHOKER CATHERINE , SAYDAH SHARON , IMPERATORE GIUSEPPINA , CASANOVA RAMON , TURLEY CHRISTINE B. , LIESE ANGELA D. , STANDIFORD DEBRA , HAMMAN RICHARD F. , KAHN MICHAEL G. , DIVERS JASMIN
Published: June 2019

Diabetes surveillance often requires manual chart review to confirm status and type. This project aimed to derive and validate an EMR-based algorithm using structured data in the era of ICD-10 codes for improving screening efficiency. Youth (<20 years) with potential evidence of diabetes based on in- and out-patient visits were identified from EMRs at 3 Children’s Hospitals participating in the SEARCH Study. Charts were reviewed to determine presence and type of diabetes based on provider notes. Two methods were compared: a multinomial regression evaluating 29 predictors, and a deterministic approach based on ratios of ICD-10 codes (≥2 diabetes codes with the most frequently occurring type-specific codes to indicate type). To evaluate performance, data from two hospitals were used for model building and the third for testing. From 8,752 potential cases, 5,308 true cases were identified; T1D (89.2%), T2D (7.5%), Other types (3.3%). Age, race/ethnicity, ICD-10 codes, and medications were the strongest predictors in the multinomial regression. Performance metrics are shown. Both methods performed well for diabetes diagnosis and for classification of T1D (all metrics ≥0.95). For T2D, the regression model had substantially lower sensitivity (0.59 vs. 0.90), but higher positive predictive value (0.80 vs. 0.62). The ICD-10 ratio model is easier to implement and could be combined with targeted chart reviews to increase efficiency for surveillance efforts.

Disclosure

B.J. Wells: None. K.M. Lenoir: None. L.E. Wagenknecht: None. E. Mayer-Davis: None. D. Dabelea: None. J.M. Lawrence: None. C. Pihoker: None. S. Saydah: None. G. Imperatore: None. R. Casanova: None. C.B. Turley: Stock/Shareholder; Self; Abbott Laboratories, AbbVie Inc., CVS/Caremark, Edwards Lifesciences Corporation, Johnson & Johnson, Novartis AG, Pfizer Inc. A.D. Liese: None. D. Standiford: None. R.F. Hamman: None. M.G. Kahn: None. J. Divers: None.

Funding

Centers for Disease Control and Prevention
1318-P: Fructose Consumption Contributes to Hyperinsulinemia in Obese Adolescents through a GLP-1-Mediated Mechanism
Authors: GALDERISI ALFONSO , VAN NAME MICHELLE A. , GIANNINI COSIMO , SAVOYE MARY , CAPRIO SONIA
Published: June 2019

Background: The consumption of high-fructose beverages is associated with higher risk for T2D. Fructose can stimulate GLP-1 secretion in lean adults, in the absence of any inhibitory effect on appetite. We hypothesized that the ingestion of glucose (GLC) and fructose (FRU) may differentially stimulate GLP-1 and insulin response in lean and obese adolescents.

Methods: We studied 14 lean (4F, 15.9±1.6y, 21.8±2.2 kg/m2) and 23 obese (5F, 15.1±1.6y, 34.5±4.6 kg/m2) adolescents. Participants received, in a double blinded cross-over study, 75g of GLC or FRU. Plasma was obtained every 10min for 60 minutes GLC was determined by YSI Analyzer; insulin and GLP-1 were measured by Millipore RIA; data were expressed as incremental values from baseline and compared by linear mixed effect model between lean and obese.

Results: Obese adolescents exhibited greater insulin (p<0.001) and GLP-1 (p<0.001) rise after FRU than lean peers, at each time points (Figure), in the absence of a significant difference in plasma GLC (p0.699). After GLC ingestion, neither the rise in plasma GLC (p0.099), nor in insulin (p0.099) and GLP-1(p0.083) differed between lean and obese youths.

Conclusion: Fructose, but not glucose, ingestion elicits higher insulin and GLP-1 response in obese as compared to lean adolescents. High-fructose consumption may contribute to the hyperinsulinemic phenotype through a GLP-1 mediated mechanism.

Disclosure

A. Galderisi: None. M.A. Van Name: Research Support; Self; Novo Nordisk Inc. C. Giannini: None. M. Savoye: None. S. Caprio: None.

Funding

National Institutes of Health (1R01DK085577-01, R01HD40787, R01HD28016; P30DK045735, K12DK094714-02; R01DK111038-01A1; Pediatric Endocrine Society; Robert E. Leet and Clara Guthrie Patterson Trust; European Medical International Framework (EMIF115372)
1321-P: Reduced Heart Rate Variability (HRV) in Young Adults with Youth-Onset Type 2 Diabetes (T2D) Is Related to Glycemic Control: The TODAY Study
Authors: SHAH AMY SANGHAVI , GHORMLI LAURE EL , BACHA FIDA , FARRELL RYAN M. , GIDDING SAMUEL , KATZ L. E. , TRYGGESTAD JEANIE B. , VAJRAVELU MARY ELLEN , WHITE NEIL H. , URBINA ELAINE M.
Published: June 2019

Cardiovascular autonomic neuropathy (CAN), a complication of T2D, affects the autonomic nerves innervating the heart and can adversely affect cardiac performance. Reduction in HRV is an early manifestation of CAN with parasympathetic loss preceding sympathetic dysfunction. Whether HRV is influenced by prior diabetes treatment or glycemic control in young adults with youth-onset T2D is not known.

Heart beats over 10 minutes from an ECG were measured by Sphygmocor to derive the normal R-R intervals (NN intervals). HRV outcomes included: the standard deviation of the NN intervals (SDNN), the root mean square differences of the NN intervals (RMSSD), and the frequency domain low to high (LF:HF) power. TODAY participants (n=400) 7 y post-randomization (T2D duration 7.7±1.5 y) were compared to 133 obese controls without T2D. We assessed whether prior randomized treatment (metformin alone, metformin+ rosiglitazone or metformin+ intensive lifestyle) or glycemic control over time (time-weighted HbA1c) were associated with HRV.

Compared to obese controls, TODAY subjects were younger (mean age 20.7±2.5 vs. 22.6±3.7 y) but not different by sex or BMI (35% male, BMI 36.6±8.1 kg/m2). TODAY participants had reduced overall HRV (SDNN; 57.9±29.6 vs. controls 67.1±25.4, p<0.0001), including a pattern of parasympathetic loss (RMSSD; 53.0±36.6 vs. controls 67.9±35.2, p<0.0001) with sympathetic overdrive (LF:HF power; 1.4±1.7 vs. controls 1.0±1.1, p<0.0001). Among TODAY subjects, HRV did not differ by previously randomized treatment, but higher HbA1c over time was independently associated with lower SDNN and RMSSD and higher LF:HF power independent of age, race, sex, T2D duration and BMI.

Young adults with youth-onset T2D show early manifestations of CAN with both parasympathetic and sympathetic impairments that are associated with higher HbA1c.

Disclosure

A.S. Shah: None. L. El Ghormli: None. F. Bacha: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, Pediatric Diabetes Consortium. Other Relationship; Self; AstraZeneca, Jaeb Center for Health Research. R.M. Farrell: Stock/Shareholder; Self; Tandem Diabetes Care. S. Gidding: Research Support; Self; Color Genomics. L.E. Katz: None. J.B. Tryggestad: None. M. Vajravelu: None. N.H. White: None. E.M. Urbina: None.

Funding

National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases
1322-P: Early Environment and Genetic Predisposition to Metabolically Obese Normal-Weight Phenotype in Children: Findings from a Cohort Study
Authors: LI MING , LI GE , GAO SHAN , WILLI STEVEN M. ,   BCAMS STUDY GROUP
Published: June 2019

Some normal-weight individuals are predisposed to obesity-related cardiometabolic abnormalities, namely, metabolically obese normal weight (MONW). Studies of the MONW phenotype in youths are scarce. We aimed to identify early environmental and genetic factors associated with MONW in children. Overall, 1,484 normal-weight Chinese children aged 6-18, including 588 subjects with MONW phenotype, were recruited from the Beijing Children and Adolescents Metabolic Syndrome cohort. Birth weight (BW) childhood lifestyle and socio-economic factors, and 20 genetic variants which had been previously shown to be associated with BMI or T2D in East Asian adults were examined for the associations with pediatric MONW phenotype. Metabolically unhealthy was defined as having any metabolic syndrome component or HOMA-IR≥3.0. Independent risk factors for MONW phenotype were low BW, increased BMI, and lower levels of physical activity, maternal education and family income (all P<0.05), while amongst genetic variants, CDKAL1 rs2206734 shown the strongest association with MONW (OR per C allele=0.81, 95% CI=0.70-0.95; P=0.008). Moreover, rs2206734 interacted with BW on MONW phenotype (P interaction=0.005). Every C allele was associated with a 50% reduced risk of MONW in high (>75th percentile) BW (95% CI=0.34-0.72; P=0.0002), while the genetic associations were nonsignificant in intermediate and low (≤75th percentile) BW (P>0.1). The effect of high BW on the CDKAL1-MONW relationship could be further augmented by the combined impact of beneficial childhood environmental factors (physically active, high maternal education and family income) (Pinteraction=0.017).

In conclusion, both early environments, particularly BW, and genetic predisposition plus their interaction were associated with MONW in children. Our study provides new insights into MONW and suggests a long-term prevention strategy, especially in genetically susceptible individuals.

Disclosure

M. Li: None. G. Li: None. S. Gao: None. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Roche Diagnostic USA. Research Support; Self; Jaeb Center for Health Research, National Institute of Allergy and Infectious Diseases, Sanofi-Aventis. Other Relationship; Self; National Institute of Diabetes and Digestive and Kidney Diseases.

Funding

National Key Research Program of China (2016YFC1304801); Beijing Municipal Science & Technology Commission (D111100000611001, D111100000611002); Beijing Natural Science Foundation (7172169); Beijing Science & Technology Star Program (2004A027), Novo Nordisk (2011A002); National Key Program of Clinical Science (WBYZ 2011-873); Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT32020, 2018PT32001)
1323-P: Offspring Diet Quality Modifies the Effect of Gestational Diabetes Exposure on Adiposity Outcomes: The EPOCH Study
Authors: SAUDER KATHERINE A. , BEKELMAN TRACI A. , HARRALL KYLIE K. , GLUECK DEBORAH H. , DABELEA DANA
Published: June 2019

Intrauterine exposure to gestational diabetes (GDM) is associated with increased adiposity; however, not all exposed offspring exhibit excess adiposity, indicating that additional factors are involved. We examined whether higher diet quality in childhood and adolescence modifies the association between GDM exposure and adiposity outcomes. In 499 offspring (n=88 GDM-exposed), we assessed dietary intake (via food frequency questionnaire) and adiposity (BMI, waist-to-height ratio, visceral and subcutaneous adipose tissue [VAT, SAT], and subscapular-to-triceps skinfold ratio) at 6-12 and 12-19 years of age. Diet quality was estimated with the Healthy Eating Index (HEI). Linear mixed models were used to examine the association between GDM exposure and adiposity among those with higher (HEI≥60) versus lower (HEI<60) diet quality, adjusting for sex, race/ethnicity, age, and pubertal status. Among those with lower diet quality, exposure to GDM was associated with increased adiposity for all outcomes (all p<0.05; Table). Among those with higher diet quality, there was no association between GDM exposure and adiposity outcomes (all p>0.05). Our results suggest that higher diet quality in childhood and adolescence may be a potential postnatal strategy for reducing adiposity among offspring exposed to GDM.

Disclosure

K.A. Sauder: None. T.A. Bekelman: None. K.K. Harrall: None. D.H. Glueck: None. D. Dabelea: None.

Funding

National Institutes of Health
133-LB: High Hypoglycemia Risk Patients with T2D on First-Generation Basal Insulins (BI) in the U.S. Have a Lower Risk of Hypoglycemia after One Year following Switch to Insulin Glargine 300 U/mL (Gla-300) vs. First-Generation BIs (DELIVER - High Risk)
Authors: SULLIVAN SEAN D. , FREEMANTLE NICK , MENON ARJUN A. , GUPTA RISHAB , WU JASMANDA , NICHOLLS CHARLIE , WESTERBACKA JUKKA , BAILEY TIMOTHY S.
Published: June 2019

DELIVER - High Risk study compared long-term clinical outcomes for patients with T2D and high hypoglycemia risk on first-generation BIs who were switched to Gla-300 or other first-generation BIs (other switchers). Electronic medical record data from the PHIE database were used. Eligible patients (age >18 years) had ≥1 criterion for high hypoglycemia risk (age >64 years; basal-bolus insulin use; renal impairment; uncontrolled baseline A1C; sulfonylurea use; atherosclerotic cardiovascular disease; history indicating high risk, including ≥1 severe hypoglycemic episode (prior 12 months). Endpoints were A1C reduction from baseline to 9-12 months, attainment of A1C goals (<7.0%; <8.0%), and hypoglycemia (based on ICD-9-CM codes or blood glucose ≤70 mg/dL) at 12 months. In a propensity score-matched comparison of Gla-300 vs. other switchers (Table), mean A1C reduction from baseline and attainment of A1C goals were comparable. Significantly fewer Gla-300 vs. other switchers experienced inpatient/ED-related hypoglycemia. For T2D patients at high hypoglycemia risk in a real-world setting, Gla-300 was associated with a significantly lower risk of hypoglycemia than switching to other BIs, 1 year after switching, while delivering similar glycemic control.

Disclosure

S.D. Sullivan: Research Support; Self; Sanofi. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Sanofi. A.A. Menon: None. R. Gupta: None. J. Wu: Employee; Self; Sanofi US. C. Nicholls: Employee; Self; Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics.

Funding

Sanofi
1331-P: OGTT Glucose-Response-Curve (GRC) in Islet Cell Antibody-Positive (Ab+) vs. -Negative (Ab-) Obese Youth Clinically Diagnosed with Type 2 Diabetes (CDX-T2D)
Authors: KIM JOON YOUNG , GEBARA NOUR , TFAYLI HALA , BACHA FIDA , ARSLANIAN SILVA A.
Published: June 2019

The OGTT-GRCs [Incessant Increase (IIn), Monophasic (Mph), and Biphasic (Bph)] reflect insulin sensitivity (IS) and β-cell function (BCF), being worse in the former and best in the latter. Accordingly, the prevalence of these GRCs differ in diabetic and nondiabetic individuals (Table). While islet cell Ab- obese youth CDX-T2D have worse IS, Ab+ youth have severe impairment in BCF [Diabetes 58: 2009]. Here, we examined the prevalence of OGTT-GRC patterns, clamp-measured IS, and BCF in obese Ab+ (GAD65 and IA2) vs. Ab- youth CDX-T2D. The dominant GRC was IIn in Ab+ and Mph in Ab- youth while Bph was scarce in both (Table). In Ab+ youth, 1st- (32.5 ± 5.6 vs. 40.2 ± 8.0 µU/mL, p=0.13) and 2nd-phase insulin (39.6 ± 8.6 vs. 62.8 ± 12.2 µU/mL, p=0.04), were 20% and 40% lower in IIn vs. the other two combined. In Ab-, while 1st- (67.3 ± 19.1 vs. 122.4 ± 28.3 µU/mL, p=0.049) and 2nd-phase insulin (110.3 ± 31.4 vs. 171.6 ± 28.6 µU/mL, p=0.054) were lower in IIn vs. Mph, overall BCF was less impaired than in Ab+ youth. IS did not differ by GRC type in either group but was lower in Ab- vs. Ab+ irrespective of GRC type. The prevalence of IIn-GRC is 3-fold higher in Ab+ vs. Ab- obese youth CDX-T2D, and the prevalence in Ab- youth is similar to that in the TODAY study (Table). The higher prevalence of IIn-GRC in Ab+ obese youth signifies the severe insulin deficiency characteristic of type 1 diabetes.

Disclosure

J. Kim: None. N. Gebara: None. H. Tfayli: Other Relationship; Self; Sanofi. F. Bacha: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, Pediatric Diabetes Consortium. Other Relationship; Self; AstraZeneca, Jaeb Center for Health Research. S.A. Arslanian: None.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (K24-HD01357, R01HD27503 to S.A.A.); National Center for Advancing Translational Sciences (UL1TR000005); National Center for Research Resources (UL1RR024153)
1333-P: Increased Spare Respiratory Capacity in Circulating Cells and Decreased Serum Antioxidant Defense Mechanisms in Obese Children
Authors: CARVALHO EUGENIA , ROSE SHANNON , COTTER MATTHEW , BENNURI SIRISH C. , DELHEY LEANNA M. , GOODE GRACE A. , BEEBE ALEXANDRIA , BØRSHEIM ELISABET
Published: June 2019

With increasing rates of childhood obesity, diagnoses of insulin resistance and type 2 diabetes (DM) in children is on the rise. Mitochondrial dysfunction is associated with insulin resistance and DM, therefore bioenergetics profiling of circulating cells may serve as a marker for mitochondrial dysfunction in insulin resistant subjects. The advantage of this biomarker is that others currently in use may not exhibit alterations until symptoms are already present.

Mitochondrial bioenergetics (Seahorse XF96) was measured in peripheral blood mononuclear cells (PBMCs) and platelets. Levels of oxidative stress, post-translational modifications of protein tyrosine residues, 3-Nitrotyrosine and 3-Chlorotyrosine, reduced (GSH) and oxidized (GSSG) glutathione, as well as whole-body D31-palmitate oxidation were also assessed in healthy lean (HL; n=18), and overweight/obese (OW/OB; n=29) (BMI ≥85th percentile) 5-9 years old children.

While maximal respiration was not different, the reserve capacity (RC) was increased in OW/OB compared to HL subjects in PBMC (45,6±4,7 vs. 32,1±7.7; p=0.05) and platelet (65,3±3.7 vs. 31,2±6,7; p=0.001). Importantly, 20% of these children already presented HbA1c levels above 6.5%. Moreover, 3-Chlorotyrosine was elevated (52,0±3,1 vs. 40,7±1,8; p=0.05), while GSH/GSSG and cysteine/cysteine (intracellular, extracellular redox buffers, respectively) tended to be decreased. Palmitate oxidation is being quantified.

RC is a critical component of the cell’s bioenergetics and can be used during increases in energy demand. Our results suggest significant metabolic adjustments to an excess in substrate availability and already compromised antioxidant defenses in 5-9 year old OW/OB children. Oxidative stress and damage occur when antioxidant defense mechanisms fail to counter-balance and control reactive oxygen species generated from endogenous oxidative metabolism or from pro-oxidant environmental exposures.

Disclosure

E. Carvalho: None. S. Rose: None. M. Cotter: None. S.C. Bennuri: None. L.M. Delhey: None. G.A. Goode: None. A. Beebe: None. E. Børsheim: None.

Funding

National Institute of General Medical Sciences (P20GM109096)
1336-P: Health-Care Utilization in T2D Youth in the Pediatric Diabetes Consortium (PDC)
Authors: KLINGENSMITH GEORGEANNA J. , CHENG PEIYAO , GAL ROBIN L. , BEAULIEU LINDSEY C. , KOLLMAN CRAIG , ADAMS RAMON L. , HANNON TAMARA S. , LOOPER LISA M. , TAMBORLANE WILLIAM V.
Published: June 2019

Background: Youth with T2D experience barriers to obtaining diabetes care. We evaluated whether healthcare utilization (HCU) was associated with glycemic outcomes in youth with T2D.

Methods: We evaluated annual HCU in 1,324 T2D PDC youth by diabetes duration up to 13 years post diagnosis. Medical record and self-reported HCU data were collected at enrollment and annually. Frequency of diabetes related inpatient admissions, Emergency Department (ED), urgent care, Diabetes Management (DM), Registered Dietician (RD) visits, and 911 calls were collected.

Results: After adjusting for age, gender, diabetes duration, and annual visits, those with ≥1 admission/year, regardless of admission reason, (16%) had a higher A1c vs. those without admission, 8.8 vs. 8.4% (p=0.002). Those with ≥2 DM office visits/year (75%) had lower A1c vs. those with 0-1 visits, 8.4 vs. 8.8% (p=0.001). BMI and A1c did not differ by number of RD visits (p=0.63 and 0.39 respectively); RD visits/year decreased over time.

Conclusions: In T2D youth, hospitalizations and <2 DM office visits/year are associated with higher A1c. Frequencies of ED and inpatient admissions for T2D are stable following the first year of T2D diagnosis. Only 24-38% of T2D youth had 4 DM visits/year while ∼50% have ≥3 visits a year, even with long T2D duration. Methods to improve follow-up care are needed to improve outcomes in youth with T2D.

Disclosure

G.J. Klingensmith: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited. Research Support; Self; Novo Nordisk Foundation. Stock/Shareholder; Spouse/Partner; Dexcom, Inc. P. Cheng: None. R.L. Gal: None. L.C. Beaulieu: None. C. Kollman: None. R.L. Adams: None. T.S. Hannon: Advisory Panel; Self; Eli Lilly and Company. L.M. Looper: None. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited.

Funding

Boehringer Ingelheim; Novo Nordisk; Takeda Pharmaceutical Company Limited
1338-P: Lipoprotein Insulin Resistance Scores Decrease after a Lifestyle Intervention among Obese Adolescents with Prediabetes
Authors: RENTERIA-MEXIA ANA M. , OLSON MICAH , CONNELLY MARGERY A. , VEGA-LÓPEZ SONIA , WILLIAMS ALLISON , SHAIBI GABRIEL Q.
Published: June 2019

Introduction: Insulin resistance (IR) is associated with impaired lipid metabolism. The Lipoprotein Insulin Resistance Index (LP-IR) is a novel composite biomarker that estimates IR from lipoprotein particle size and concentration, and prospectively predicts type 2 diabetes (T2D) in adults. Less is known about LP-IR and T2D risk in youth. This study evaluated the effect of a lifestyle intervention on LP-IR scores in obese Latino youths with prediabetes.

Methods: Obese Latino adolescents (n=27, 15.5±1.1 years, 13 male/14 female) with prediabetes (defined as a 2-hour, post-challenge glucose ≥120 mg/dL) completed a 12-week intervention including nutrition education (one hour/week) and moderate-to-vigorous physical activity (three hours/week). Measurements at baseline and 12 weeks included anthropometrics, total, large, medium, and small lipoprotein particle concentrations (VLDL and chylomicron, LDL, and HDL), mean lipoprotein particle sizes (VLDL, LDL, HDL), lipid concentrations (total triglyceride, VLDL and chylomicron triglyceride, and HDL cholesterol), and LP-IR scores using nuclear magnetic resonance spectroscopy.

Results: After adjusting for body fat and sex, significant reductions in LP-IR scores (63.2±14.4 vs. 59.0±15.5 units, p=0.013), large VLDL and chylomicron particle concentration (9.1±7.8 vs. 7.3±6.2 nmol/L, p=0.004), total HDL particle concentration (30.2±4.3 vs. 28.3±3.9 μmol/L, p=0.013), total triglyceride concentration (144.5±91.9 vs. 122.9±77.9 mg/dL, p=0.002), as well as VLDL and chylomicron triglyceride concentration (117.5±66.7 vs. 102.0±55.7 mg/dL, p=0.020) were observed following lifestyle intervention.

Conclusion: Lifestyle intervention significantly reduces LP-IR scores and lipoprotein particle parameters in obese adolescents with prediabetes and may decrease future risk of cardiometabolic disorders through improvements in insulin resistance and lipoprotein metabolism.

Disclosure

A.M. Renteria-Mexia: None. M. Olson: None. M.A. Connelly: Employee; Self; LabCorp. S. Vega-López: None. A. Williams: None. G.Q. Shaibi: None.

Funding

National Institute on Minority Health and Health Disparities (P20MD002316, U54MD002316); Programa para el Desarrollo Profesional Docente, para el Tipo Superior, México (to A.M.R-M.)
1345-P: Presymptomatic and Clinical T1D in The U.S., Sweden, and Finland: Joint Analysis of Four Birth Cohort Studies
Authors: ANAND VIBHA , LIU BIN , GHALWASH MOHAMED , KOSKI EILEEN , NG KENNEY , DUNNE JESSICA L. , HAGOPIAN WILLIAM , LUNDGREN MARKUS , LERNMARK ÅKE , ILONEN JORMA , VEIJOLA RIITTA , REWERS MARIAN ,   FOR T1DI STUDY GROUP
Published: June 2019

Four birth-cohort studies in the U.S. (DAISY, DEWIT), Sweden (DiPiS) and Finland (DIPP) were initiated in 1990s to early 2000. General population newborns and young first-degree relatives (FDR) of T1D patients, preselected on increased HLA risk, were followed for islet autoantibodies (AAb)and T1D. We harmonized their common variables, including AAb to insulin, IA-2, GAD, or ZnT8, HLA-DR-DQ risk genotypes, socio-demographics, diet, family history, glucose/HbA1c and anthropometric measures. The combined cohort included 22,312 subjects with AAb measured in 256,243 visits (mean 11±10 per subject) at 3-12 month intervals. During follow-up, 2279 (10%) subjects developed at least one AAb, 914 (4%) multiple AAb and 603 (3%) T1D. The cumulative risk of T1D differed by the number of AAb at seroconversion (Figure). T1D developed in 26% (95% CI 24-32%) of 1AAb, 62% (55-68%) of 2AAb and 84% (75-88%) of >=3AAb positive subjects in the 15y after seroconversion. T1D risk varied by HLA genotype: 40% (35-48%) in DR3/4-DQ2/8, 22% (18-31%) in DR4/x-DQ8/x and 21% (18-35%) in DR3/x-DQ2/x of 1AAb subjects and, respectively, in 82% (68-88%), 61%(50-65%)and 87% (32-98%)of 2AAb subjects. Once ≥2 AAb positive, HLA genotype was less predictive of progression to T1D. This harmonized dataset offers an unparalleled opportunity to validate and improve upon reported risk estimates for T1D development via novel analytical methods.

Disclosure

V. Anand: None. B. Liu: None. M. Ghalwash: None. E. Koski: None. K. Ng: None. J.L. Dunne: None. W. Hagopian: Research Support; Self; Novo Nordisk A/S. M. Lundgren: None. Å. Lernmark: None. J. Ilonen: None. R. Veijola: None. M. Rewers: None.

Funding

JDRF
1348-P: Celiac Disease in Children with T1D Varies among the World: An International, Cross-Sectional Study of 39,425 Patients from the SWEET Registry
Authors: TACZANOWSKA ANNA , SCHWANDT ANKE , AMED SHAZHAN , SVENSSON JANNET , SZYPOWSKA AGNIESZKA , KANAKA-GANTENBEIN CHRISTINA , TOTH-HEYN PETER , KREPEL VOLSKY SARIK
Published: June 2019

Comorbid celiac disease (CD) may affect the course of type 1 diabetes (T1D). We aimed to compare T1D children with and without CD. This study is based on the SWEET (Better control in Pediatric and Adolescent diabeteS:Working to crEate cEnTers of Reference) database. We included 39 425 patients aged ≤18 y. Regression models adjusted for demographics were applied to compare outcomes. CD was present in 1 804 subjects (4.6%). Prevalence of CD differed among regions: 1.9% Asia/Middle East, 4.3% Northern Europe, 5.1% Southern Europe, 5.3% North America/Canada and 6.1% Australia/New Zealand. Girls were diagnosed with CD significantly more often than boys (p< 0.01). Children with CD were younger at diabetes onset (p< 0.001), also when boys and girls were separately analyzed. CD subjects were significantly shorter (p= 0.002) and had lower BMI-SDS (p< 0.001) (Fig). HbA1c was lower in patients with CD (p< 0.001), even after adjustment for pump use (Fig). Across regions, gender differences in CD prevalence were not shown in Northern Europe and Asia/Middle East. HbA1c was lower in CD patients in Southern Europe and North America/Canada. In contrast, in Asia/Middle East, HbA1c was significantly higher among CD patients (p<0.001). No difference was found in Northern Europe. The frequency, anthropometric as well as metabolic consequences of CD in T1D children differs around the world.

Disclosure

A. Taczanowska: None. A. Schwandt: None. S. Amed: None. J. Svensson: Advisory Panel; Self; Janssen Pharmaceuticals, Inc., Medtronic. Speaker's Bureau; Self; Novo Nordisk A/S, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. A. Szypowska: None. C. Kanaka-Gantenbein: None. P. Toth-Heyn: None. S. Krepel Volsky: None.
1350-P: Safety and Pharmacokinetics of Technosphere Insulin in Pediatric Patients
Authors: GRANT MARSHALL L. , KRUEGER JOHN A. , FINEMAN MARK , SHARMA GAURAV , POMPILIO FRANK , KENDALL DAVID M.
Published: June 2019

Technosphere Insulin (TI) is an ultra-rapid, short-acting inhaled insulin that provides glycemic control in patients with diabetes. This ongoing, 2-part, open-label, interventional study aims to assess the efficacy and safety of TI in children aged 4 to 17 years with type 1 diabetes mellitus (T1DM) who are on a stable regimen of basal-bolus insulin therapy. Part 1 is a single-arm study that includes evaluation of insulin pharmacokinetics (PK) after a single prandial dose of TI (4, 8, or 12 units), followed by a 4-week titration period. Approximately 46 patients will be enrolled across 3 age cohorts: cohort 1 (13-17 years), cohort 2 (8-12 years), and cohort 3 (4-7 years). As of August 16, 2018, 15 patients had enrolled in cohort 1, 14 had received at least 1 dose, and 8 completed the titration period. Overall, 50% of the safety population (n=14) was female, mean duration of T1DM was 6.2 years, mean age was 15 years, and mean body mass index was 22.4 kg/m2. Initial PK results from cohort 1 demonstrated insulin metabolism similar to that in adult patients receiving TI. Insulin concentrations rapidly increased in the first 30 minutes after TI treatment and returned to baseline by 120 minutes for the 4-, 8-, and 12-unit doses. Mean postprandial glucose levels decreased within 1-hour postdose for the 8- and 12-unit dose groups. Seven patients developed treatment-related cough of mild (6 events) or moderate (1 event) severity. Seven patients experienced a total of 41 hypoglycemic events, but no patient required the assistance of another person to administer corrective carbohydrates. No clinically relevant declines in pulmonary function were reported. Two patients discontinued the study due to adverse events (cough, diabetic ketoacidosis). These data will help determine the appropriate age range for inclusion and recommended dosing for part 2, which will be a 1-year efficacy and safety study.

Disclosure

M.L. Grant: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation. J.A. Krueger: Employee; Self; Eli Lilly and Company, MannKind Corporation. Stock/Shareholder; Self; Eli Lilly and Company. M. Fineman: Consultant; Self; MannKind Corporation. Employee; Self; Elcelyx Therapeutics, Inc. Stock/Shareholder; Self; Elcelyx Therapeutics, Inc. G. Sharma: Employee; Self; MannKind Corporation. F. Pompilio: Employee; Self; MannKind Corporation. Stock/Shareholder; Self; Amgen Inc., MannKind Corporation. D.M. Kendall: Employee; Spouse/Partner; Amgen Inc. Employee; Self; MannKind Corporation. Stock/Shareholder; Self; MannKind Corporation.

Funding

MannKind Corporation
1359-P: Improving Transition Readiness in Teens with Type 1 Diabetes (T1D): Feasibility Results of a Pilot RCT
Authors: GARVEY KATHARINE , DEAN TAYLOR , CHRISTENSEN SINEAD , RICE KRISTEN , RICH VIRGINIA B. , TERRIO SHANNON , LAFFEL LORI M.
Published: June 2019

Suboptimal preparation for transition to adult care has been associated with adverse outcomes in youth with T1D. There is need for innovative curricular approaches acceptable to teens in order to optimize transition preparation and engagement. To create a feasible transition education model, we conducted 6 focus groups with teens and young adults with T1D (N=41) and 3 parent groups (N=23). Participants desired facilitated peer group education while maintaining 1:1 individualized T1D care. The Self-Management, Adherence and Readiness for Transition in T1D (SMART T1D) curriculum was derived from focus group themes and refined by a T1D Teen Advisory Committee (N=20) prior to packaging as 3 modules. Session topics included self-advocacy/adherence, T1D science education, and transition planning. Pediatric nurse specialists trained in motivational interviewing delivered SMART T1D in evening sessions over ∼9 months. Feasibility was assessed in a pilot RCT. Teens (N=40, 50% male, 85% white) with T1D were randomized to SMART T1D (N=20) or an attention control group (N=20) receiving 3 educational electronic newsletters, with both groups maintaining routine T1D care. Teens had mean±SD age 15.7±1.2 years, T1D duration 6.4±3.9 years, A1c 9.5±1.2%; 63% pump users. During the 1-year pilot RCT, we conducted 17 groups, with 1-6 teens in attendance/group (mean, median, mode=3/group); 15/20 teens attended 3 sessions, 2 attended 2 sessions, 3 attended 1 session. Review of 3 newsletters was confirmed by 19/20 controls. Only 3 teens withdrew (1 intervention, 2 control). Intervention feedback was very positive; 88% endorsed agree/strongly agree for recommending groups to other teens and 65% endorsed increased interest in transition information. Negative feedback related to scheduling/traveling to group sessions. SMART T1D was feasible and acceptable to most (95%) teens with T1D; future multi-center studies can assess portability, generalizability, and alternative virtual delivery models.

Disclosure

K. Garvey: None. T. Dean: None. S. Christensen: None. K. Rice: None. V.B. Rich: None. S. Terrio: None. L.M. Laffel: Advisory Panel; Self; Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Janssen Pharmaceuticals, Inc., UpToDate.

Funding

National Institutes of Health