bluuebunny/crossref_metadata_2025_split huggingface dataset:
118-LB: Preclinical Development of IDG-16177 as a Potent GPR40 Agonist for Treatment of Type 2 Diabetes
Authors: YOON JONG MIN , KIM DOHEE , LEE DON-GIL , AN KYUNG MI , LEE MYONG JAE , HONG CHANG-HEE , HONG DAHAE , KWAK HYUN-JUNG , JE IN-GYU , SONG HYO-JUNG 
Published: June 2020

GPR40/FFAR1 is a G-protein-coupled receptor predominantly expressed in pancreatic β-cells. GPR40 agonists are known to stimulate insulin secretion and reduce circulating glucose levels in a glucose-dependent manner. We investigated IDG-16177(ID11014A) as a GPR40 agonist and confirmed this drug has linear pharmacokinetic properties and is more potent than fasiglifam from in vitro and in vivo studies. In vitro metabolic stability of IDG-16177 was evaluated in mouse, rat, dog, monkey and human microsomes. IDG-16177 was metabolized mainly by CYPs in mouse, rat, monkey and human while it was metabolized mainly by UGTs in dog. Oral bioavailability of IDG-16177 was 88.1 ~ 109.9% in SD rats. The Cmax and AUC values of IDG-16177 increased in a dose-proportional manner in the dose range of 1 ~ 10 mg/kg. IDG-16177 was also well exposed in monkeys after 3 mg/kg administration. Glucose lowering effect was determined by oral glucose tolerance test (OGTT) in Sprague-Dawley (SD) rats and in various type 2 diabetes rats, respectively. IDG-16177 showed dose-dependently improvement of glucose tolerance in a single dosing study using SD and Goto-Kakizaki (GK) rats. IDG-16177 1mg/kg showed more effective in glucose tolerance than fasiglifam 10mg/kg in repeated dosing study of Zucker Diabetic Fatty (ZDF) rats. In this study, Cmax,ss and AUCss of IDG-16177 showed approximately 10 times lower than those of fasiglifam. These results show that IDG-16177 might be an effective drug candidate for treatment of type 2 diabetes.

Disclosure
J. Yoon: None. D. Kim: None. D. Lee: None. K. An: None. M. Lee: None. C. Hong: None. D. Hong: None. H. Kwak: None. I. Je: None. H. Song: None.
1183-P: Utilization of Low vs. High Dose of Newer Antihyperglycemic Agents
Authors: LAUTSCH DOMINIK , MCLEOD EUAN , WANG TONGTONG , GONZALEZ CLAUDIO D. , RAJPATHAK SWAPNIL , MALKANI SEEMA , JACKSON JAMES , MILLIGAN GARY , HIGGINS VICTORIA 
Published: June 2020

Evidence from clinical trials suggest that newer antihyperglycemic agents (AHAs) have a better clinical profile at a higher dose. However, the utilization of the different doses in the real world is not well known. This study aimed to assess the dose utilization of the 2 newer classes of AHAs using the 2018 Adelphi T2DM Disease Specific Programme, a survey involving 730 physicians and 8794 patients in the U.S. and Europe. The analysis included 1612 patients on sodium glucose cotransporter 2 inhibitors (SGLT2i) and 1073 patients on glucagon like peptide-1 receptor agonist (GLP-1RA), either monotherapy or combined therapy. Dose cut points for SGLT2i drugs were based on doses utilized in cardiovascular outcomes trials (at a compound level, Table 1). There is no standard cut point on dosing in GLP-1RA, therefore a conservative approach was applied (see Table for details). Analyses were performed at class level. SGLT2i drugs were more likely to be prescribed at a high dose (85.7%) to patients who were slightly younger than those receiving a lower dose (57.1 vs. 58.9 years). GLP-1RA were prescribed at high dose in 63.2% of the patients. Mean BMI was higher in patients receiving high dose of a GLP-1 receptor agonist.

Disclosure
D. Lautsch: Employee; Self; Merck & Co., Inc. E. McLeod: Employee; Self; Pfizer Inc. Stock/Shareholder; Self; Pfizer Inc. T. Wang: Employee; Spouse/Partner; Janssen Pharmaceuticals, Inc. Employee; Self; Merck & Co., Inc. C.D. Gonzalez: Employee; Self; Merck & Co., Inc. S. Rajpathak: Employee; Self; Menarini Group. S. Malkani: None. J. Jackson: None. G. Milligan: None. V. Higgins: None.

Funding
Merck Sharp & Dohme Corp; Pfizer Inc.
1192-P: Frequency of Care and Prevalence of Poor Glycemic Control in a Clinic Population with Type 1 Diabetes in Delhi, India
Authors: CRISTELLO ANGELICA , PRAVEEN PRADEEP A. , MAYER-DAVIS ELIZABETH J. , TANDON NIKHIL 
Published: June 2020

India faces one of the biggest diabetes burdens in the world. Type 1 diabetes (T1D) is mostly overlooked. Investigation of care models that improve T1D outcomes in India and other resource-constrained settings is critically needed. The All India Institute of Medical Sciences (AIIMS) in Delhi operates a free, weekly multidisciplinary T1D self-management clinic. As a preliminary investigation into the effectiveness of this model and the potential benefit of its dissemination, we examined whether frequency of engagement with T1D care among a 2016 sample of AIIMS patients (n=328) close to the frequency recommended by guidelines (3 visits/yr) was associated with a reduction in the prevalence of poor glycemic control (HbA1c&gt;9%) that is the norm among those with diabetes in India, and whether this differed by gender. With multivariate binomial generalized linear regression, we estimated the difference in prevalence of HbA1c&gt;9% comparing those who attended 0-1 clinic visits in 2016 to those who attended 2-3 visits (ref), and comparing those who attended &gt;3 visits to those who attended 2-3. The final adjustment set of T1D duration and gender was guided by directed acyclic graph and comparison of bias and precision of multiple models. T1D duration was 13.7± 9.0 yrs, mean age was 28.6±12.0 yrs, and HbA1c&gt;9% prevalence was 45.7% (n=150). Prevalence of HbA1c&gt;9% was high among those with 2-3 yearly visits (0.57; 95% CI: 0.43, 0.75). However, prevalence of HbA1c&gt;9% was an absolute 16% higher (95% CI: 0.04, 0.27; p=0.01) among those with 0-1 visits. Estimates of the benefit of &gt;3 visits remain unclear due to limitations including sparse data. We did not observe effect modification by gender (p=0.48). In sum, 2-3 vs. fewer yearly visits with a multidisciplinary outpatient team like the model delivered by AIIMS may help alleviate the high prevalence of HbA1c&gt;9% in India. Further research will identify which care features drive glycemic control improvements and may be feasibly adopted elsewhere.

Disclosure
A. Cristello: None. P.A. Praveen: None. E.J. Mayer-Davis: None. N. Tandon: None.
1199-P: Incentive-Based Behavior Goals in Pediatric Patients with Diabetes Mellitus
Authors: WU CRYSTAL K. , PATEL PRITI G. , LAI JANEE , BASHAR APAMEH , SIDEREWICZ KALLIE M. , TIWARI RISHITA , CUZMAN NANCY J. , PAYTON KATHLEEN , GORAL SHANNON , PATEL CHETANBABU M. 
Published: June 2020

Background: Children and adolescents with diabetes mellitus (DM) are faced with a unique set of challenges associated with the management of their disease. There is evidence that extrinsic rewards can help patients to meet health goals. Gift cards were used as incentives.
Objective: Assess the incentive program’s impact on patient hemoglobin A1c (HbA1c) during the program’s first year.
Methods: A retrospective chart review was conducted of all clinic patients with DM with clinic visits between February 24, 2018 and December 31, 2019. Any patient with DM seen in the TMCOne Pediatric Endocrinology clinic who set a behavioral modification and achieved that goal were included. Patients set two goals at each visit. In phase 1, if two goals were met patients received a $5 gift card or a small prize. In phase 2, if two subsequent goals were met, a $10 gift card or a larger prize was awarded. In phase 3, if four subsequent goals were met, a $20 gift card was rewarded. HbA1C values were recorded at baseline and after goals 2, 4, and 8.
Results: At baseline N=123 (45% F; ages 1-22), with a mean HbA1c of 8.3% (SD= 2.2). In phase 1, the change after the first two behavior modification goals were achieved was -0.19 (P = 0.43; SD=2.6). Only 37 were able to achieve goals 3 and 4. In phase 2, the mean HbA1c was 7.7% (SD= 1.9) and the change in HbA1c was -0.19 (P = 0.66y; SD=1.16). In phase 3, only 4 of the 123 patients were able to achieve goals 5, 6, 7 and 8. The mean HbA1c was 6.5% (SD=0.98). The change in HbA1c was +0.73 (P = 0.17; SD=0.66).
Conclusion: This study demonstrates the potential of extrinsic incentives to achieve the behavioral goals did not result in improvement of HbA1c values. The number of children who were able to achieve goals 3 and 4 dropped drastically compared to the those who are able to achieve goals 1 and 2. In addition, the mean HBA1c value dropped which with each phase. The SD of each phase also decreased. We surmise patients who maintained excellent control were more likely to start and complete the behavior change goals over an extended period of time.

Disclosure
C.K. Wu: None. P.G. Patel: None. J. Lai: None. A. Bashar: Other Relationship; Self; Medtronic. K.M. Siderewicz: None. R. Tiwari: None. N.J. Cuzman: None. K. Payton: None. S. Goral: None. C.M. Patel: None.

Funding
TMC Foundation
1247-P: Physical Activity and Cardiometabolic Health in Youth with Type 2 Diabetes
Authors: SLAGHT JANA L. , DART ALLISON , BLYDT-HANSEN TOM , SELLERS ELIZABETH , WICKLOW BRANDY , MCGAVOCK JONATHAN 
Published: June 2020

Background: Youth living with type 2 diabetes (T2D) are characterized by an increased cardiovascular disease (CVD) risk profile. It is unclear if regular vigorous intensity physical activity (PA) modifies this CVD risk.
Methods: Using a cross-sectional design, we compared cardiometabolic risk factors among 164 youth with T2D from the The Improving renal Complications in Adolescents with T2D through REsearch (iCARE) cohort, stratified according to participation in vigorous intensity organized sport. Outcomes of interest were HbA1c, ambulatory blood pressure (BP) parameters from 24 hr monitoring, hypertension according to 2017 American Academy of Pediatrics criteria and albuminuria determined from first morning urine samples. The main exposure, regular (≥ 3 days/week) participation in vigorous intensity organized sport was determined from a validated questionnaire (Adolescent Physical Activity Questionnaire).
Results: Youth were 15 ± 3 yrs, 78% lived in a rural town, 68% were girls, mean BMI Z score was 2.4 ± 1.1 and mean HbA1c was 9.6 ± 2.6%. Youth that participated in regular vigorous intensity organized sport (40%; n=67) achieved nearly twice the dose of PA than less active peers (176 vs. 108 MET-HR/week; p=0.001). After adjusting for duration of diabetes, BMI Z score, sex and current smoking status, youth with T2D who engaged in regular vigorous intensity organized sport displayed lower HbA1c (9.1%, vs. 9.9% p = 0.052), diastolic BP (70 vs. 73 mmHg, p = 0.002) and diastolic load (20 vs. 26%, p = 0.023). Compared to youth that did not participate in regular vigorous intensity organized sport, those who did displayed a lower odds of albuminuria (OR: 0.40 95% CI: 0.19-0.84) and hypertension (OR: 0.39 95% CI: 0.16-0.95).
Conclusions: Among youth living with T2D, self-reported frequent participation in vigorous organized sport is associated with lower CVD risk. These data need to be confirmed with prospective observational and experimental data.

Disclosure
J.L. Slaght: None. A. Dart: None. T. Blydt-Hansen: None. E. Sellers: None. B. Wicklow: None. J. Mcgavock: None.

Funding
Diabetes Canada (OG-3-11-3354-AD); Heart and Stroke Foundation of Canada; Canadian Institutes of Health Research (MOP-142309)
1252-P: Effects of a Pilot Sugar-Reduction Intervention on Diet and Continuous Blood Glucose in Teenagers on the Remote Pacific Island of Kiritimati
Authors: PLOWS JASMINE , RIOS CLAUDIA , BERGER PAIGE , JONES ROSHONDA B. , ALDERETE TANYA L. , STEINBERG SKYLAR , BANGAO TERAIRA , BEALE ELIZABETH , GORAN MICHAEL I. 
Published: June 2020

Introduction: Kiritimati is a remote Pacific Island with a high rate of type 2 diabetes (∼30%), potentially related to high sugar consumption starting early in life. This pilot study aimed to determine the effects of a short-term sugar-reduction intervention in Kiritimati teenagers.
Methods: The two high schools on the island were randomly assigned to a 7-day sugar-reduction intervention group (n=46) or control group (n=32). The intervention consisted of installation of a water filter at the school, distribution of individual water bottles, and a sugar-reduction presentation by a registered dietitian. 24-hour diet recalls were conducted at baseline and follow-up. Continuous blood glucose monitors (CGMs; FreeStyle Libre Pro) were used to assess 94 interstitial glucose measures over 14 days. A difference-in-differences analysis was used to address baseline differences between the schools. Data are presented as mean ± SD.
Results: At baseline, overweight/obesity prevalence was 50% (control group) vs. 43% (intervention group); age 17.2 ± 1.6 vs. 16.8 ± 1.8 years; mean blood glucose 88.3 ± 7.8 vs. 89.3 ± 31.5 mg/dL; added sugar consumption 122 ± 87 vs. 139 ± 77g/day; and %kcal from added sugars 18.3 ± 10.4 vs. 20.1 ± 9.5%. After the intervention, added sugar consumption decreased to 39 ± 47g (7.3 ± 8.3%kcal) in the intervention group without changing (133 ± 116g/19.2 ± 9.7%kcal) in the control group (time x group interaction p=0.003). However, there were no significant effects on any of the CGM measures.
Conclusion: Despite high rates of type 2 diabetes on the island as a whole, blood glucose was normal in high-school teenagers, and was unaffected by the intervention. However, added sugar consumption was high (∼20 %kcal), which was greatly improved after the intervention (∼7 %kcal). This study suggests that a simple sugar-reduction intervention could improve diet quality in teenagers on Pacific Islands with high rates of type 2 diabetes such as Kiritimati.

Disclosure
J. Plows: None. C. Rios: None. P. Berger: None. R.B. Jones: None. T.L. Alderete: None. S. Steinberg: None. T. Bangao: None. E. Beale: None. M.I. Goran: Advisory Panel; Self; Yumi. Other Relationship; Self; Penguin Random House.
1264-P: Distinguishing between Obese Patients with Type 1 Diabetes (T1DMob) and Type 2 Diabetes in Adolescence (T2DMad) at Presentation
Authors: BARBETTI FABRIZIO , BONFANTI RICCARDO , DELVECCHIO MAURIZIO , IAFUSCO DARIO ,   DIABETES STUDY GROUP OF ISPED
Published: June 2020

Obesity epidemic in childhood/adolescence may influence the mode of presentation of diabetes in conditions usually diagnosed in lean people like T1DM and MODY. The aim of our study was to identify clinical parameters useful for distinguishing betweeen obese patients with T1DM (T1DMob) and patients with T2DM with onset in adolescence (T2DMad). For this study, overweight/obesity was defined as BMI ≥ 95th centile for age and sex according to BMI calculator for child and teen of CDC. We compared 60 T1DMob patients (at least one T1DM autoab with high titer) with 36 patients with T2DMad (negative to T1DM autoabs). Patients with T2DMad and a parent with diabetes were considered as possibly being MODY, and excluded. We evaluated sex, ethnicity, birth weight, and age, plasma glucose, HbA1c, C-peptide, Cholesterol, HDL/Cholest., triglycerides (TG), and blood pressure (BP) at diabetes onset. Mean age at diagnosis was lower in T1DMob (9.7±3.0) than T2DMad (13.9±2.4) (p&lt;0.001), while fasting plasma glucose (20±10.5 vs. 16.2±8.6 mmol/L respectively) and HbA1c were not statistically different. C-peptide (1.0±0.9 vs. 4.0±3.5 ng/ml, p&lt;0.001), TG (104.9±77.9 vs. 284.5±297.6, p&lt;0.001), total Cholesterol (159.9±35.9 vs. 194.5±30.2, mg/dl, p=0.006), systolic BP (111.3±11.2 vs. 126.6±14.3 mm/Hg, p&lt;0.001) were lower, and HDL/Cholest. (48.7±23 vs. 32.3±10.1, p&lt;0.001) was higher in T1DMob. In 17 pubertal T1DMob patients (age at onset 13.2±2.2) C-peptide (1.5±1, p=0.001), TG (115.7±81.7, p=0.005), systolic BP (116.9±6.6, p=0.04) were still lower, and HDL/Cholest. (57.0±35.3, p=0.001) still higher than T2DMad. TG/HDL ratio, another index of insulin resistance (IR) was higher (11.2±15.2 vs. 2.6±2.2, p=0.001) in T2DMad. We conclude that parameters indicative of IR, a pathophyiologic component of T2DM, are profoundly altered in patients with T2DMad when compared to T1DMob, and that this does not appear to be linked to differences in age at diabetes presentation.

Disclosure
F. Barbetti: Consultant; Self; Amring. R. Bonfanti: Advisory Panel; Self; Abbott, Medtronic, Roche Diabetes Care. D. Iafusco: None.
1271-P: Plasma Calprotectin Is Associated with Obesity and Systemic Inflammation in Children
Authors: HASAN AMAL , KOCHUMON SHIHAB P. , ALKANDARI HESSA 
Published: June 2020

Purpose: Childhood obesity is a major risk factor for many chronic diseases including type 2 diabetes and cardiovascular disease. Plasma calprotectin is elevated in various inflammatory disorders, including obesity-associated low-grade inflammation. We measured the level of plasma calprotectin in obese children and assessed its association with key metabolic and inflammatory biomarkers.
Methods: The study included a total of 76 children (age 9.8±2.43 years), which were grouped according to the body mass index (BMI) into 3 groups: normal-weight (BMI &lt;85th percentile; n=12), over-weight (BMI 85-94th percentile; n=2) and obese (BMI ≥95th percentile, n=62). The plasma levels of metabolic and inflammatory biomarkers were quantified using commercially available ELISA kits.
Results: Calprotectin was directly correlated with the BMI (r=0.4, P=0.001, n=69), BMI percentile (r=0.5, P &lt;0.0001, n=69), and BMI Z-score (r=0.5, P&lt;0.0001, n=69). Calprotectin was directly correlated with body fat (%; r=0.3, P=0.02, n=63) and fat to muscle ratio (r=0.32, P=0.02, n=50) but inversely correlated with muscle (%) (r= ? 0.3, P=0.03, n=50). Calprotectin was inversely correlated with adiponectin (r= ? 0.3, P=0.04, n=57) but directly correlated with leptin (r=0.4, P=0.0005, n=75), and leptin to adiponectin ratio (r=0.45, P=0.0005, n=56). Calprotectin was directly correlated with CRP (r=0.4, P=0.003, n=54), IL-6 (r=0.44, P&lt;0.0001, n=76) and MCP-1 (r=0.3, P=0.02, n=76). Calprotectin was also directly correlated with resistin (r=0.3, P=0.02, n=76). Children with obesity (n=62) had significantly (P&lt;0.0001) higher levels of calprotectin compared to those with normal-weight (n=12). In the obese state, males (n=30) had significantly (P=0.03) higher levels of calprotectin compared to females (n=32).
Conclusion: Plasma calprotectin is elevated in children with obesity and is correlated with key metabolic and inflammatory biomarkers.

Disclosure
A. Hasan: None. S.P. Kochumon: None.

Funding
Kuwait Foundation for the Advancement of Science (RA-2011-018)
1277-P: Diabetes Camp Improves Diabetes Knowledge, Independence, and Mental Health in Youth with Type 1 Diabetes
Authors: WOOLLEY RYAN , AMANAT SHEILA , MUELLER KELLY 
Published: June 2020

American Diabetes Association Diabetes Camps are offered each summer to nearly 6,000 youth with diabetes across the United States. Camps are designed to facilitate a traditional summer camp experience in a medically-safe environment while fostering opportunities for children to develop basic diabetes self-care skills, overcome feelings of isolation, and gain self-confidence. In 2019, a study was conducted to assess the impact of camp on 1) knowledge of diabetes management, 2) ability to independently manage diabetes, and 3) emotional well-being of youth campers with type 1 diabetes.
A survey was administered via online questionnaires to caregivers of camp participants 1-week prior to camp (N=4,562) and 1-month post-camp (N=1,484). Key demographics were collected representing results from 55 summer camps across the country (55% female, mean age 12, 46% diagnosed ≤ 4 years, 10% diagnosed ≤ 1 year). Paired samples analysis using Wilcoxon signed-rank tests was performed to assess the level of change on each individual camper from pre-camp to one-month post-camp (N=1,343 pairs).
One month following camp, camper knowledge of diabetes management skills increased 31% after camp, and 38% of campers increased their confidence to try new methods to manage their diabetes. Campers’ ability to independently solve problems related to their diabetes management increased 17%, and 97% of campers were able to independently perform at least one diabetes management skill, such as draw up insulin, give own injections, or change pimp site. In addition, camper self-confidence increased 30%, and feelings of negative emotions decreased 31%. A statistically significant increase was seen in each measure (p≤0.001).
The evidence indicates that camp positively impacts a wide-range of camper outcomes, with more substantial improvement seen among younger campers and newly diagnosed campers. Future research will be conducted to better understand the longer-term impact of camp among return-campers.

Disclosure
R. Woolley: Employee; Self; American Diabetes Association. S. Amanat: None. K. Mueller: None.
1408-P: Gait Speed and Handgrip Strength in Middle-Aged Adults with Type 1 Diabetes: Comparison with Normative Values and Correlates
Authors: COSTACOU TINA , STROTMEYER ELSA S. , ORCHARD TREVOR J. 
Published: June 2020

Type 1 diabetes (T1D) is often described as a state of accelerated aging, although comparative data on physical performance measures between individuals with T1D and the general population are limited. We compared gait speed and handgrip strength of middle-aged adults with T1D with published normative data and further assessed correlates of physical function in T1D. Participants of the EDC study of childhood onset T1D who attended the 25-yr exam - when handgrip strength and gait speed were first assessed - were selected for study (n=204; 53.9% women; mean age, 51 (range, 30-69) years and duration, 43 (32-63) years). Within each decile of age, mean handgrip strength (kg) obtained from the dominant hand was lower in T1D compared with adults participating in the NIH Toolbox Study in both sexes (all p-values &lt;0.03). In contrast, both usual and maximum gait speed (m/s) were generally higher in T1D except in 60-69 year olds, where speeds were similar by diabetes status. Within individuals with T1D, diabetes duration, female sex, macroalbuminuria, and confirmed distal symmetric polyneuropathy were all inversely, and total lean mass and physical activity were positively related to handgrip strength and explained 62% of its variability. In addition, body mass index and smoking status, inversely, and physical activity positively related to gait speed and explained 23% of the variability in usual gait speed and 17% of the variability in maximum gait speed. No associations were seen with HbA1c.
In conclusion, although no differences were seen in gait speed, we observed reduced handgrip strength among middle-aged adults with long duration T1D compared with published normative values. Microvascular complications, body fatness and participation in physical activity explained and the vast majority of the variability in handgrip strength, pointing to the importance of healthy lifestyle choices in maintaining physical function in individuals with T1D in mid-life and early old age.

Disclosure
T. Costacou: None. E.S. Strotmeyer: None. T.J. Orchard: None.

Funding
National Institutes of Health (DK34818)