bluuebunny/crossref_metadata_2025 huggingface dataset:
11-LB: A Phase 2 Study of Liquid Stable Glucagon to Treat Hypoglycemia-Associated Autonomic Failure
Authors: PETTUS JEREMY , NAKHLE SAMER , OVALLE FERNANDO , JUNAIDI MOHAMMED K. , CLOSE NICOLE C. , CONOSCENTI VALENTINA , NGUYEN ANH
Published: June 2020

Objective: To evaluate a novel, ready-to-use, liquid stable, continuous subcutaneous (SC) glucagon infusion (CSGI; Xeris Pharmaceuticals) for the treatment of Hypoglycemia Associated Autonomic Failure (HAAF) in adults with type 1 diabetes (T1D).

Method: This was a Phase 2 double-blind, randomized, placebo-controlled parallel trial in T1D adults with HAAF (Gold Score ≥4). Subjects were randomized to receive 1 month of high-rate CSGI (HCSGI, 80 μg/hour), low-rate CSGI (LCSGI, 20 μg/hour), or placebo. Epinephrine hormone response to hypoglycemia (assessed during stepwise hypoglycemia clamp procedure) and Gold Scores were measured at baseline, end of treatment, and both 3- and 6-months post-treatment.

Results: Forty-nine subjects were randomized to receive treatment (HCSGI n=15; LCSGI n=18; placebo n=16). No statistically significant differences in mean epinephrine hormone response or Gold Scores were observed across treatment arms at end of treatment. Long-term follow-up of the subjects was stopped early.

For completed follow-up clamps (31 subjects, 3 months; 22 subjects, 6 months), LCSGI did not exhibit differences to placebo. However, HCSGI 3 and 6 month mean epinephrine hormone responses were greater (p=NS) and Gold Scores improved [(-1.1±1.5 vs. 0.5±1.5; 3 months, p=NS) and (-1.2±1.5 vs. -0.6±0.9; 6 months, p=NS)].

The administration of CSGI was associated with mild to moderate nausea (5.9% for LCSGI and, 20% for HCSGI,) and vomiting (11.8% for LCSGI and 13.3% for HCSGI,). CSGI was not associated with pain, injection site reactions, or necrolytic migratory erythema. No related SAEs were reported.

Conclusion: Compared to placebo in a small group of T1D adults with HAAF, HCSGI may exhibit improvements in Gold Score at both 3 and 6 months. Mean serum epinephrine may be a suboptimal biomarker of HAAF. CSGI was safely used with concomitant insulin, and there were no related SAEs.

Disclosure

J. Pettus: Consultant; Self; Diasome Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk Inc., Sanofi. S. Nakhle: None. F. Ovalle: Research Support; Self; Gan & Lee Pharmaceuticals, Gilead Sciences, Inc., Lilly Diabetes, Novo Nordisk A/S, Sanofi, Xeris Pharmaceuticals, Inc. M.K. Junaidi: Employee; Self; Xeris Pharmaceuticals, Inc. N.C. Close: Employee; Self; EmpiriStat, Inc. V. Conoscenti: None. A. Nguyen: None.
1109-P: Blood Pressure (BP) Lowering Effect of Empagliflozin Is Related to Decreased L-Arginine Clearance in Diabetic Rats
Authors: KHEMAIS-BENKHIAT SONIA , VEYEL DANIEL , SCHINI-KERTH VALERIE , KRAWCZYK BARTLOMIEJ , PIEPER MICHAEL , MARK MICHAEL , MAYOUX ERIC
Published: June 2020

Introduction: The availability of L-arginine is the rate-limiting factor in Nitric Oxide (NO) synthesis, a potent vasodilatory factor. L-arginine plasma levels are blunted in diabetes, thus L-arginine supplementation decreases BP in animal diabetic models, and type 2 diabetic patients. Renal reabsorption of filtered L-arginine in the proximal tubule is mainly sodium dependent. Higher filtered glucose load in diabetes may alter sodium gradient via higher glucose reabsorption by sodium-glucose cotransporters (SGLTs).

Purpose: The mechanism by which SGLT2 inhibitors, such as Empagliflozin, decrease BP in type 2 diabetic patients, is still unknown. We hypothesize that SGLT2 inhibitors could decrease the urinary excretion of L-arginine, by restoring sodium gradient necessary for L-arginine reabsorption in the proximal tubule.

Methods: Male obese Zucker diabetic fatty/Spontaneously hypertensive heart failure hybrid (ZSF1) rats and their lean littermates (CTR) received either Empagliflozin or vehicle for 6 weeks. Levels of L-arginine in urine and plasma were quantified via Liquid Chromatography-Mass Spectrometry. Plasmatic cGMP level, a marker of NO production and urinary 8-hydroxydeoxyguanosine (8-OHdG) level, a marker of oxidative stress, were measured.

Results: The urinary level of L-arginine was higher in ZSF-1 rats compared to CTR ones, and plasmatic concentrations of L-arginine were lower in ZSF-1 rats compared to CTR ones. Both parameters were significantly reversed by Empagliflozin. Empagliflozin treatment increased plasmatic cGMP and decreased urinary 8-OHdG in diabetic rats.

Conclusion: Empagliflozin decreased urinary excretion of L-arginine, associated with an increased plasmatic concentration of L-arginine and cGMP, and decreased oxidative stress in diabetic rats. This suggests that Empagliflozin increased NO production and bioavailability. Such effects might contribute to the BP lowering effect of Empagliflozin in diabetics.

Disclosure

S. Khemais-Benkhiat: Employee; Self; Boehringer Ingelheim International GmbH. D. Veyel: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. V. Schini-Kerth: Research Support; Self; Boehringer Ingelheim International GmbH. B. Krawczyk: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Pieper: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Mark: Employee; Self; Boehringer Ingelheim International GmbH. E. Mayoux: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc.
115-LB: Oral Insulin–Induced Reduction in Liver Fat Content in T2DM Patients with Nonalcoholic Steatohepatitis
Authors: KIDRON MIRIAM , PERLES SHARON , KALOTI REEM , GHANTOUS RAMI , SANDOUKA SUHA F. , MALAABI YASMINE , SAFADI RIFAAT
Published: June 2020

Nonalcoholic fatty liver disease (NAFLD) and subsequent nonalcoholic steatohepatitis are leading causes of chronic liver disease, with disease progression directly associated with insulin resistance and T2DM. In light of the common risk factors, pathogenesis and complications with T2DM, direct insulin intervention has been suggested for T2DM patients with NAFLD. Recently, salient metabolic effects of oral insulin have been suggested, owing to first pass metabolism and local insulin availability and concentration in liver fat cells. This pilot study assessed the safety, tolerability and early effects on liver fat content of an oral insulin formulation (ORMD-0801), preprandially administered once-daily (2x8 mg capsules) for 12 consecutive weeks, to 8 T2DM patients with NASH. The 12-week ORMD-0801 treatment proved safe and tolerable in all patients, with no serious or severe adverse events recorded throughout the study period. The 12-week treatment induced a mean -6.9±6.8% reduction in liver fat content (sign test p value: 0.035), as measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). In parallel, concentrations of gamma-glutamyltransferase (GGTP), a key marker of chronic hepatitis, were significantly lower after 12 weeks of treatment as compared to baseline (-14.6±13.1 U/L; sign test p value: 0.008), as were fasting insulin levels (-96.5±206.0 pmol/L; sign test p value: 0.035). Taken together, these preliminary observations suggest a palliative effect of oral insulin on NASH in T2DM patients, as shown by reductions in liver fat content and chronic hepatitis. These encouraging findings will require further validation in large-scale, randomized clinical trials.

Disclosure

M. Kidron: Employee; Self; Oramed Pharmaceuticals. Stock/Shareholder; Self; Oramed Pharmaceuticals. S. Perles: Employee; Spouse/Partner; Haddassah Medical Center. Employee; Self; Oramed Pharmaceuticals. R. Kaloti: None. R. Ghantous: None. S.F. Sandouka: None. Y. Malaabi: None. R. Safadi: None.
115-OR: Early Insulin Pump Use in Pediatric Post–Total Pancreatectomy Islet Auto Transplantation Management
Authors: TELLEZ SIOBHAN E. , HORNUNG LINDSEY , COURTER JOSHUA D. , ABU-EL-HAIJA MAISAM , NATHAN JAIMIE D. , LAWSON SARAH , ELDER DEBORAH A.
Published: June 2020

Objective: Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical procedure for patients with chronic pancreatitis who experience debilitation and poor quality of life. Glucose targets are critical for islet survival. We hypothesized that early transition from intravenous insulin to insulin pump therapy would improve glucose control and impact hospital duration.

Research Design and Methods: We performed a retrospective analysis of 40 patients who underwent TPIAT. Prior to 2016, post-operative insulin was delivered intravenously and transitioned to multiple daily injections (MDI) followed by pump administration (n=14). After 2016, post-operative insulin was delivered intravenously followed by early transition to pump therapy (n=26). Outcomes analyzed between groups included: percentage of blood glucoses in target (80-120 mg/dL), hypoglycemia (<60 mg/dL) and hyperglycemia (>140 mg/dL), blood glucose variability, and length of stay after transition off intravenous insulin.

Results: Patients with early transition to pump therapy had a higher proportion of glucose values in target range (p=0.0003), a lower proportion of hyperglycemia (p=0.04), and a lower proportion of hypoglycemia, though not significant (p=0.33). In patients with early pump transition, variability in glucose values decreased over the first 10 days post-intravenous insulin (p=0.001) and post-transition median length of stay was shorter by 5 days (p=0.005).

Conclusions: Early pump therapy in this population achieved tighter glycemic control and reduced duration of stay.

Disclosure

S.E. Tellez: None. L. Hornung: None. J.D. Courter: None. M. Abu-El-Haija: None. J.D. Nathan: None. S. Lawson: None. D.A. Elder: None.
1163-P: Cost Effectiveness of Oral Semaglutide 14mg vs. Empagliflozin 25mg in Canada
Authors: LIU AIDEN R. , BECH PETER G. , FRIDHAMMAR ADAM , NILSSON ANDREAS , WILLIS MICHAEL , NUHOHO SOLOMON
Published: June 2020

Background: A1C lowering was significantly greater for oral semaglutide 14 mg than empagliflozin 25 mg for patients with type 2 diabetes mellitus (T2DM) uncontrolled on metformin in the 52-week, randomized, open-label PIONEER 2 trial (NCT02863328). We estimated the cost effectiveness of oral semaglutide vs. empagliflozin in Canada from the payer and societal perspectives.

Methods: Modeling methods were used to extrapolate benefits observed in PIONEER 2 to long-term costs and outcomes, including quality-adjusted life-years (QALYs), for patients treated with oral semaglutide or empagliflozin. As with analysis in other settings, the IHE-Diabetes Cohort Model (IHE-DCM) was used. The analysis was also run using the Economic and Health Outcomes microsimulation model (ECHO-T2DM). Patient baseline characteristics and treatment effects were sourced from PIONEER 2. In the model simulations, both agents were assumed discontinued and insulin initiated when A1C was >8.0%. Unit costs (CAD$) and utilities were sourced from the literature.

Results: Oral semaglutide was associated with more QALYs than empagliflozin over 40 years (0.39 with IHE-DCM and 0.34 with ECHO-T2DM). The gains came with increased costs (CAD$8,202 with IHE-DCM and CAD$9,255 with ECHO-T2DM), yielding incremental cost-effectiveness ratios (ICERs) of CAD$21,115 and CAD$27,496/QALY gained, respectively, below the often-cited willingness-to-pay threshold of CAD$50,000/QALY. When productivity costs and the full societal perspective are considered, the ICERs were CAD$18,239 and CAD$19,112, respectively. Sensitivity analyses that included cost, treatment effect, time horizon and biomarker rebound assumptions generally confirmed the results.

Conclusion: Two models independently found oral semaglutide to be cost-effective compared to empagliflozin over 40 years for the treatment of patients with T2DM uncontrolled on metformin in Canada. While uncommon, the use of two models can reduce decision-making uncertainty.

Disclosure

A.R. Liu: Employee; Self; Novo Nordisk Canada Inc. P.G. Bech: Employee; Self; Novo Nordisk Inc. Stock/Shareholder; Self; Novo Nordisk Inc. A. Fridhammar: None. A. Nilsson: None. M. Willis: Board Member; Self; The Swedish Institute for Health Economics. Consultant; Self; Janssen Global Services, LLC., Mundipharma International, Novo Nordisk A/S. Stock/Shareholder; Self; The Swedish Institute for Health Economics. S. Nuhoho: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Johnson & Johnson.

Funding

Novo Nordisk Canada Inc.
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>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>9% comparing those who attended 0-1 clinic visits in 2016 to those who attended 2-3 visits (ref), and comparing those who attended >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>9% prevalence was 45.7% (n=150). Prevalence of HbA1c>9% was high among those with 2-3 yearly visits (0.57; 95% CI: 0.43, 0.75). However, prevalence of HbA1c>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 >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>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<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<0.001), TG (104.9±77.9 vs. 284.5±297.6, p<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<0.001) were lower, and HDL/Cholest. (48.7±23 vs. 32.3±10.1, p<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 <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 <0.0001, n=69), and BMI Z-score (r=0.5, P<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<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<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 <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)
1437-P: A Newly Developed Diabetes Risk Index, Based on Lipoprotein Subfractions and Branched-Chain Amino Acids, Is Associated with Incident Type 2 Diabetes Mellitus in the PREVEND Cohort
Authors: FLORES-GUERRERO JOSE LUIS , CONNELLY MARGERY A. , SHALAUROVA IRINA Y. , GRUPPEN EKE G. , OTVOS JAMES D. , DULLAART ROBIN P.F. , BAKKER STEPHAN J.I.
Published: June 2020

Objective: Evaluate the ability of the Diabetes Risk Index (DRI) to predict incident type 2 diabetes mellitus (T2DM) in a large cohort.

Methods: The DRI was developed by combining the 6 lipoprotein subfractions in the Lipoprotein Insulin Resistance Index (LP-IR) and the branched chain amino acids valine and leucine, all of which have been shown previously to be associated with future T2DM. DRI scores were calculated in a total of 6134 nondiabetic men and women in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident T2DM.

Results: During a median follow-up of 8.5 years, 306 new T2DM cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI scores and incident T2DM with the hazard ratio (HR) for the highest versus lowest tertile being 7.49 (95% confidence interval: 5.01-11.19), P <0.001. After additional adjustment for BMI, family history of T2DM, alcohol consumption, diastolic blood pressure, total cholesterol, triglycerides, HDL cholesterol and HOMA-IR, the HR was attenuated but remained significant (HR 1.67 [1.01-2.76], P = 0.04). Similar results were obtained when DRI was analyzed as HR per 1 SD increase (HR 1.37 [1.14-1.65], P = 0.001). The Kaplan-Meier plot demonstrated that patients in the highest tertile of DRI scores presented at higher risk (p-value for log-rank test <0.001).

Conclusions: Higher DRI scores are associated with an increased risk of T2DM. The association is independent of clinical risk factors for T2DM including HOMA-IR, BMI and conventional lipids.

Disclosure

J. Flores-Guerrero: None. M.A. Connelly: Employee; Self; LabCorp. I.Y. Shalaurova: None. E.G. Gruppen: None. J.D. Otvos: Employee; Self; LabCorp. R.P.F. Dullaart: None. S.J.I. Bakker: None.
1439-P: One-Hour Postload Plasma Glucose Level Predicts Future Type 2 Diabetes in Hong Kong Chinese: A 12-Year Follow-Up Analysis
Authors: LUK ANDREA , LAU ERIC S. , KONG ALICE P. , CHOW ELAINE , MA RONALD C. , CHAN JULIANA C.
Published: June 2020

Background: There is a resurgence of interest in the role of 1-hour post-load plasma glucose (PG) in risk stratification for type 2 diabetes and a cut-off of 8.6 mmol/L has been proposed to define dysglycaemia in addition to other existing criteria of prediabetes. We examined the efficacy of 1-hour PG level in predicting future type 2 diabetes in a longitudinal community-based cohort of Hong Kong Chinese.

Methods: Between 2001-2003, 489 adults without diabetes underwent 75-gram oral glucose tolerance test (OGTT). Blood samples were collected at 0, 15, 30, 60 and 120 minutes for measurement of plasma glucose and insulin levels. Between 2012-2014, progression to diabetes was ascertained either by reviewing medical records or by repeating OGTT and HbA1c. Area under the receiver-operating characteristic (ROC) curve was calculated to assess the discrimination of each parameter (fasting PG, 1-hour PG, 2-hour PG, disposition index) for development of diabetes. High 1-hour PG was defined using threshold of 8.6 mmol/L.

Results: Over 12-year follow-up, 46 people (9.4%) developed diabetes. The area under ROC curve were 0.79 (95% CI 0.71, 0.86) for fasting PG, 0.84 (95% CI 0.78, 0.89) for 1-hour PG, 0.79 (95% CI 0.72, 0.86) for 2-hour PG, and 0.78 (95% CI 0.71, 0.85) for disposition index with no difference between each parameter. In multivariate logistic regression, high 1-hour PG was associated with new-onset diabetes with odds ratio (OR) 4.87 (95% CI 1.91, 14.1, p=0.002), independent of impaired fasting glucose (OR 2.19 [95% CI 0.87, 5.32, p=NA), impaired glucose tolerance (OR 3.69 [95% CI 1.67, 8.27, p=0.001]) and other clinical variables including age, sex, smoking, family history of diabetes, history of gestational diabetes, waist and blood pressure.

Conclusions: One-hour PG is similar to fasting and 2-hour PG in prediction of type 2 diabetes. High 1-hour PG identifies people with high risk of diabetes independent of other criteria of prediabetes and clinical risk factors.

Disclosure

A. Luk: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Roche Pharma. Other Relationship; Self; Merck Sharp & Dohme Corp. E.S. Lau: None. A.P. Kong: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Abbott, AstraZeneca, Sanofi. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. E. Chow: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck & Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. J.C. Chan: None.
1458-P: Association of Serum Creatinine Levels and Risk of Type 2 Diabetes Mellitus in Korea
Authors: SONG DO KYEONG , LEE HYE JIN , HONG YOUNG SUN , SUNG YEON-AH
Published: June 2020

Low skeletal muscle is known to be associated with insulin resistance and suggested as a potential risk factor for type 2 diabetes mellitus (T2DM). Serum creatinine is the primary metabolite of creatine in the skeletal muscle and used as a surrogate of muscle mass. Therefore, low serum creatinine levels may be associated with the risk of T2DM. However, there were few studies about the association between serum creatinine levels and the risk of T2DM in Korea. We aimed to evaluate the association between serum creatinine levels and the risk of T2DM in Korea. We analyzed a total of 264,832 nondiabetic adults older than 30 years of age who had undergone a national health examination from 2002 to 2012 in the Korean National Health Insurance Service Cohort. The serum creatinine was divided into four categories (<0.70, 0.70∼0.89, 0.90∼1.19, ≥1.20 mg/dl for men, <0.60, 0.60∼0.79, 0.80∼1.09, ≥1.10 mg/dl for women). Hazard ratios for T2DM were calculated using Cox proportional hazards models. In men, serum creatinine levels and the risk for T2DM showed an inverse J-shaped association, with the lowest risk among men with serum creatinine between 0.90 and 1.19 mg/dl. This inverse J-shaped association between serum creatinine level and the risk for T2DM was confirmed after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose. In women, subjects with highest serum creatinine level had the highest risk of T2DM. However, serum creatinine was not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. Lower serum creatinine was significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl even after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. Highest creatinine level was significantly associated with an increased risk of T2DM in women, however, this association disappeared after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose.

Disclosure

D. Song: None. H. Lee: None. Y. Hong: None. Y. Sung: None.
1466-P: Prevalence of Glucose Intolerance in the Roma Population from a Rural Area in the South Part of Romania: Călărași County
Authors: RUSU EMILIA , ENACHE GEORGIANA M. , RUSU FLORIN , COSOREANU ANDRADA , CIRSTEA CATALINA , BALEANU MARIA C. , RADULIAN GABRIELA
Published: June 2020

Background and Aim: The aim of this study was to evaluate the prevalence of glucose intolerance (diabetes, prediabetes) in Roma population living in rural settlements from Călărași County in the south part of Romania.

Methods: This cross-sectional, epidemiological, non-interventional study was conducted from March 2014 to May 2017 in several settlements from Călărași County, in Romania. We included 603 patients, 448 Roma (320 females/128 males) and 155 Romanian Caucasians (104 females/51 males), aged between 18 and 88 yr. Glucose intolerance was defined using American Diabetes Association criteria. Body mass index was classified using the definition of World Health Organization. Metabolic waist was defined as waist circumference over 80 cm in women and 94 cm in men.

Results: Prevalence of diabetes (newly diagnosed diabetes and known diabetes) was greater in Romanian Caucasians group, but in both groups larger than the published national data (34.8% vs. 23.6%, p=0.008). Obesity was present in 43.2% (n=67) of the Romanian Caucasians and 43.3% (n=194) of the Roma population (p=0.97). The average age was lower in Roma population (49.91±16.97 vs. 56.43±13.36 years, p<0.001). In Roma population group, the prevalence of prediabetes, newly diagnosed diabetes and known diabetes was 12.5% (n=56), 13.6% (n=61) and 10% (n=45) respectively. In Romanian Caucasians group, the prevalence of prediabetes, newly diagnosed diabetes and known diabetes was 12.9% (n=20), 14.8% (n=23), and 20% (n=31) respectively.

Conclusions: The study revealed a high prevalence of diabetes and obesity among the Romanian Caucasians and Roma population in the south part of Romania, Călărași County. Independent risk factors for diabetes in the Roma population were the metabolic waist (OR=2.539; 95% CI 1.309-4.925) and physical activity less than 30 minutes/day (OR=2.099; 95% CI 1.279-3.444).

Disclosure

E. Rusu: None. G.M. Enache: None. F. Rusu: None. M.C. Baleanu: None. G. Radulian: None.
1489-P: Racial/Ethnic Disparities in Deaths Due to Diabetes, Diabetes Ketoacidosis, and Diabetic Coma among Those Aged 1-44 Years: 1999-2017, United States
Authors: SHAYDAH SHARON , IMPERATORE GIUSEPPINA , MERCADO CARLA , BULLARD KAI M. , BENOIT STEPHEN R.
Published: June 2020

Although previous studies have reported disparities in diabetes mortality by race/ethnicity, little is known about deaths due to diabetes, diabetes ketoacidosis (DKA) or diabetic coma by race/ethnicity among the younger population in the U.S. We used National Vital Statistics System data for individuals aged 1-44 years from 1999 to 2017 filed in all 50 states and the District of Columbia obtained from CDC Wonder (wonder.cdc.gov). Diabetes-related deaths were based on any listed ICD-10 codes E10-E14. DKA or diabetic coma deaths were based on any listed ICD-10 codes E10-E14 with X.1 or X.0. Race/ethnicity was reported on death certificates and categorized as Hispanic, non-Hispanic (NH) Asian/Pacific Islander (API), NH black (B), or NH white (W). Results were age standardized to the 2000 U.S. population by 10 year age groups. In 2013-2017, DM-related deaths were lowest among NH APIs (1.4, 95% CI 1.3, 1.5) followed by Hispanics (2.8, 95% CI 2.5, 2.7) and NHWs (3.2, 95% CI 3.0, 3.2), and highest among NHBs (7.7, 95% CI 7.5, 7.8) (Figure). Diabetes-related death rates increased for all groups from 1999-2002 to 2013-2017 (p < 0.05); DKA or diabetic coma rates increased among NHWs and NHBs (p < 0.05). Exploring reasons for increased diabetes-related mortality among youth and young adults may help reduce disparities and prevent deaths.

Disclosure

S. Shaydah: None. G. Imperatore: None. C. Mercado: None. K.M. Bullard: None. S.R. Benoit: None.