bluuebunny/crossref_metadata_2025 huggingface dataset:
1182-P: Strategies and Factors Associated with Top Performance in Primary Care for Diabetes: Insights from Mixed Methods
Authors: SOLBERG LEIF , PETERSON KEVIN A. , FU HELEN N. , EDER MILTON , JACOBSEN RACHEL
Published: June 2020

Background: Diabetes care quality has changed little over the past 12 years. To learn what strategies and factors seem most important for improvement, we conducted a mixed method analysis of clinic interviews and characteristics of clinics that are in the high, middle, and low quartiles on a composite measure for diabetes.

Method: We interviewed 31 leaders from 17 primary care clinics selected from the 416 that agreed to participate in a larger observational study of diabetes performance improvement. Semi-structured interviews on barriers and facilitators of diabetes care were recorded, transcribed, and analyzed for both comparison among clinics at different levels of performance on the outcome measure. We combined interview data with quantitative data about clinic performance on a standardized composite measure of diabetes outcomes and a survey of the presence of care management processes.

Results: Interview analysis identified 10 themes that provided unique insights into the factors and strategies that were associated with differences in performance level. The main difference among them was the degree to which top performing clinics used patient data to guide proactive and outreach methods to intensify treatment and monitor impact. Top clinics also reported fewer barriers and more facilitators than lower ranked ones, while all recognized key help from the larger organizations of which most were a part.

Conclusions: Top performing clinics’ approach to diabetes care differs from lower performing clinics focusing on proactive care occurring outside of the traditional practice setting. Although confirmatory studies are needed for these preliminary findings, clinical leaders might benefit by considering the value of replicating these differences.

Disclosure

L. Solberg: None. K.A. Peterson: None. H.N. Fu: None. M. Eder: None. R. Jacobsen: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R18DK110732)
119-OR: Total Pancreatectomy with Islet Autotransplantation in Diabetic and Prediabetic Patients with Intractable Chronic Pancreatitis
Authors: BACHUL PIOTR J. , BOREK PETER , ANTEBY ROI , BASTO LINDSAY , PEREA LAURENCIA , GOLAB KAROLINA , WANG LING-JIA , TIBUDAN MARTIN L. , PEREZ-GUTIERREZ ANGELICA , KOMORNICZAK MICHAL , NAGPAL SAJAN , LUCANDER AARON C. , DIMITROV MICHAEL , FUNG JOHN , MATTHEWS JEFFREY B. , WITKOWSKI PIOTR
Published: June 2020

Introduction: Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment option for nondiabetic patients with intractable chronic pancreatitis. The outcome and potential benefits for prediabetic and diabetic patients are less well established.

Method: Thirty-four patients underwent TPIAT were retrospectively divided into 3 groups according to pre-operative glycemic control: diabetes mellitus (DM) (n=5, 15%), Pre-DM (n=11, 32%) and Non-DM (n=18, 54%).

Results: Preoperative fasting c-peptide was detectable and similar in all 3 groups. Islet mass in the DM group was comparable to Pre-DM and Non-DM groups: (median 191,800), 111,800 and 232,000, respectively). Patients received islet mass of over the target level of 2,000 IEQ/kg in Pre-DM and DM at lower but clinically meaningful rates compared to the Non-DM group 45% (5/11) and 60% (3/5) for a combined 50% (8/16) rate, respectively, compared to 83% (15/18) for the non-DM group. At 1 year, fasting c-peptide and HbA1c did not differ between DM and Pre-DM groups but c-peptide was significantly higher in Non-DM. Islet transplantation failed (negative c-peptide) only in one patient. Preoperatively, all patients experienced pancreatic pain with daily opioid dependence in 60-70%. Pancreatic-type pain gradually subsided completely in all groups with no differences in other painful somatic symptoms.

Conclusions: Patients with diabetes and measurable preoperative c-peptide can achieve similar benefit from TPIAT, with comparable outcomes to prediabetic and nondiabetic patients including pain relief. Not surprisingly, endocrine outcomes for diabetic and prediabetic patients are substantially worse than in those with normal preoperative glucose control.

Disclosure

P.J. Bachul: None. P. Borek: None. R. Anteby: None. L. Basto: None. L. Perea: None. K. Golab: None. L. Wang: None. M.L. Tibudan: None. A. Perez-Gutierrez: None. M. Komorniczak: None. S. Nagpal: None. A.C. Lucander: None. M. Dimitrov: None. J. Fung: None. J.B. Matthews: None. P. Witkowski: None.
12-LB: Subcutaneous Administration of the Novel Somatostatin Receptor 2 Antagonist ZT-01 Restores the Glucagon Response to Hypoglycemia in STZ-Diabetic Rats to Normal Levels
Authors: FARHAT RAWAD , SIMONSON ERIC , RIDDELL MICHAEL , LIGGINS RICHARD , CHAN OWEN
Published: June 2020

Restoration of the lost glucagon response to hypoglycemia may be an effective means to prevent the onset of hypoglycemia in patients with type 1 diabetes (T1D). Elevation of the inhibitory hormone somatostatin in T1D may act on alpha cells, via the somatostatin receptor 2 (SSTR2), to suppress glucagon release during hypoglycemia. We previously demonstrated that a novel SSTR2 antagonist, ZT-01, exhibited superior efficacy at restoring the glucagon response to hypoglycemia compared to an established SSTR2 antagonist, PRL-2903, when given intraperitoneally at a dose of 10 mg/kg. In this study, we first evaluated the pharmacokinetics of ZT-01 in healthy Sprague-Dawley rats. Within one hour after intraperitoneal administration of a 10 mg/kg dose, ZT-01 achieved 10-fold higher plasma Cmax compared to PRL-2903; however, pancreas concentration at 6 h post-dose was almost 4-fold higher for PRL-2903 compared to ZT-01 and plasma concentrations were similar for both 24 h post-dose. We subsequently conducted a dose de-escalation study to identify the lowest dose of ZT-01 that could improve glucagon secretion in poorly controlled insulin-treated streptozotocin (STZ)-diabetic Sprague Dawley rats, under hypoglycemic clamp conditions. ZT-01 was administered subcutaneously one hour prior to the induction of hypoglycemia (blood glucose <60 mg/dL) at doses ranging from 0.1 µg/kg to 3 mg/kg. Administration of ZT-01 at 0.3 or 1 mg/kg improved the glucagon response by 5.3 or 6.3-fold, respectively (P<0.05), relative to the diabetic control group. The glucagon response in this dose range was comparable to that observed in nondiabetic rats administered vehicle. We therefore conclude that ZT-01 at doses ranging from 0.3 to 1 mg/kg normalized the glucagon response to hypoglycemia in STZ-diabetic rats and may be an effective compound for the prevention hypoglycemia in patients with T1D.

Disclosure

R. Farhat: None. E. Simonson: None. M. Riddell: Advisory Panel; Self; Zucara Therapeutics Inc. Consultant; Self; Lilly Diabetes. Research Support; Self; Dexcom, Inc., Insulet Corporation. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. R. Liggins: Advisory Panel; Self; Zucara Therapeutics Inc. Stock/Shareholder; Self; Zucara Therapeutics Inc. O. Chan: None.

Funding

JDRF; The Leona M. and Harry B. Helmsley Charitable Trust
1202-P: Association and Trends of Current Prevention Guidelines in Reducing Hospitalizations in People with Diabetes
Authors: ALBRIGHT RACHEL H. , FLEISCHER ADAM E.
Published: June 2020

Background: Specific outpatient services have been recommended to prevent diabetes complications. The purpose of this study is to assess the utilization and trends of preventative outpatient visits to providers in a population of people with diabetes, and evaluate which preventative services may offer the most protection against poor outcomes.

Methods: The National Health and Nutrition Examination Survey (NHANES) was used to examine the relationship between select outpatient services and risk of all-cause hospitalization in people with diabetes. We assessed five outpatient services commonly recommended: (1) examination from a physician (2) assessment of hemoglobin A1C (3) eye exam with pupil dilation (4) foot exam and (5) assessment from a diabetes specialist. Logistic regression models were performed to assess the independent association of outpatient services used in the past 1 year, and hospitalization within that same year.

Results: Ninety-nine percent of patients with diabetes engaged in at least one outpatient service every year between 2011 and 2016. Patients receiving a preventative foot exam within the last year experienced a protective effect against hospitalization within that year (OR 0.67, 95%CI 0.46, 0.96). Visiting a diabetes specialist produced a protective effect against hospitalization (OR 0.56, 95%CI 0.39, 0.82) if the visit occurred more than one year before the hospitalized event. No other outpatient services were associated with hospitalization. Findings of the final regression model were robust to sensitivity analysis.

Conclusion: Outpatient Services are consistently being used annually by the diabetic population, however, the services that show the most protection against all-cause hospitalization are utilized the least. Receiving a preventative foot exam and visiting a diabetes specialist were most effective at protecting patients from all-cause hospitalization, resulting in a 33% and 44% decreased risk, respectively.

Disclosure

R.H. Albright: None. A.E. Fleischer: None.
1208-P: Perspectives of Barriers and Enablers from Stakeholders of the Current Model of Care for Diabetes Management in an Australian Regional Area
Authors: KENNEDY ELIZABETH L. , NG ASHLEY , GORDON BRETT A. , SMITH GILLIAN , FORSYTH ADRIENNE
Published: June 2020

As the prevalence of type 2 diabetes (T2D) escalates, improved models of care (MoC) are necessary to provide the most appropriate care across different geographical locations. Current issues that influence diabetes health include physical, social and psychological factors. This study explores the perspectives of Stakeholders (staff members of community health services) relating to barriers and enablers towards the MoC for individuals with T2D. Semi-structured interviews were conducted with 21 stakeholders working in a semi-rural, low socio-demographic region of Victoria, Australia. Questions were designed to elicit participants’ views on factors that can facilitate or impede access to care, and how best to enhance adoption of an appropriate MoC. Interview transcripts were analysed thematically and categorised using the individual, relationship, community, and societal levels of the socio-ecological model. Stakeholders identified barriers such as living alone and socio-economic constraints, as important to individuals. In terms of relationship factors, many complex influences outside the control of the individual were identified as resulting in diabetes management becoming a non-priority. Transportation issues and lack of culturally sensitive/safe spaces were also identified as significant barriers for clinic attendance, as were lack of GP understanding of other health professionals’ roles, particularly in a multidisciplinary care setting. Improved diabetes management was identified as an enabler. Stakeholders also perceived implementing an holistic approach to diabetes management as an important enabler for attendance at community centres. This study concludes that stakeholders valued a focus on improving the accessibility of a MoC, by adopting a more integrated approach in a more culturally and physically approachable environment. This may enhance patients’ engagement and the sustainability of care.

Disclosure

E.L. Kennedy: None. A. Ng: Consultant; Self; Roche Diabetes Care, Ypsomed AG. B.A. Gordon: None. G. Smith: None. A. Forsyth: None.
1214-P: Assessing the Efficacy of Home-Based Kidney Care on Patient Activation Measure (PAM) among Patients with Diabetes
Authors: SHAH VALLABH , PANKRATZ VERNON S. , GHAHATE DONICA M. , BOBELU JEANETTE , NELSON ROBERT
Published: June 2020

Objective: Home-Based Kidney Care (HBKC) is a pragmatic treatment approach that addresses patient preferences and cultural barriers to healthcare. We previously reported the results of a clinical trial of HBKC vs. usual care in a cohort of Zuni Indians in New Mexico. This study investigated the potential for differential efficacy of HBKC vs. usual care according to type 2 diabetes status of the Zuni Indians who had participated in the trial.

Methods: Participants identified as having evidence of chronic kidney disease were enrolled into the original trial, and were randomized into either HBKC or usual care. Participants were subsequently categorized according to type 2 diabetes status. Linear regression models were used to test for the presence of a differential treatment effect by diabetes status and to estimate treatment effects within those with and without diabetes.

Results: The original study enrolled 63 participants into the HBKC group, and 62 into usual care. Twenty-four (38.1%) participants in the HBKC group and 32 (51.6%) in usual care had diabetes. The test for interaction between diabetes status and treatment arm suggested a significant differential treatment effect by diabetes status (p=0.022). The treatment effect among those with diabetes showed that PAM total scores increased by 16.0 points (95% Confidence Interval [CI]: 8.8 to 23.1) more in the HBKC group than in the usual care group, while changes in PAM total scores were similar in both treatment groups among those without diabetes (treatment effect [95% CI] = -1.4 [-12.4 to 9.6]).

Conclusions: We have previously shown that HBKC is effective in increasing the engagement of Zuni Indians with CKD in their healthcare. This secondary analysis suggests that the effectiveness of this intervention on increasing patient activation is most notable among those CKD patients who also have diabetes.

Disclosure

V. Shah: None. V.S. Pankratz: None. D.M. Ghahate: None. J. Bobelu: None. R. Nelson: None.

Funding

Patient-Centered Outcomes Research Institute
1218-P: Interactive Insulin Teaching by Pharmacists Prior to Hospital Discharge
Authors: ODOM JESSICA M. , GHIZZONI-BURNS ALYSON , PROBST MEGAN , SUTHERLAND MELANIE W. , FAIR MELISSA L. , WEBER SANDRA L.
Published: June 2020

The primary objective of this study was to evaluate the impact on patient health outcomes of incorporating iPad insulin education videos into standardized pharmacist insulin teaching prior to inpatient discharge. Inclusion criteria comprised of hospitalized patients >18 years old with either new insulin orders or, if taking insulin prior to admission, a HbA1c ≥ 8.5%. Patients were excluded if they did not speak English or were discharged to a facility. From July 2018 to January 2019, control patients (n=180) received standard, bedside insulin-administration education from a trained pharmacist. From February to June 2019, intervention patients (n=114) received pharmacist-deployed educational videos on iPads that included the same content as the standard education. The primary outcome was the change in an eight-item survey administered pre- and post-education, assessing confidence in insulin administration and storage, hypoglycemia management, and sharps disposal on a scale of 1 to 5, with 5 indicating highest confidence. Secondary outcomes included 30-day hospital readmission and change in HbA1c post-discharge. Pharmacist-provided education significantly improved confidence across all survey items in both the intervention and control groups (mean (SD) increase = 0.57 (0.74), p < 0.01). There were no statistically significant differences between groups after adjusting for age, sex, race/ethnicity, and prior insulin use. Baseline HbA1c was similar in both groups (10.7 vs. 10.9, p= 0.51) and decreased within 4 months post-discharge (9.4 vs. 8.7, p= 0.09). The decrease did not differ between groups. Diabetes-related readmissions were similar between the two groups (14 vs. 13%, p= 0.93). Inpatient education by pharmacists prior to discharge improved patient confidence in insulin administration for both traditional and technology-enhanced education groups. Technology-enhanced insulin education may reduce pharmacist burden without negatively impacting patient outcomes.

Disclosure

J.M. Odom: None. A. Ghizzoni-Burns: None. M. Probst: None. M.W. Sutherland: None. M.L. Fair: None. S.L. Weber: None.

Funding

Prisma Health
1222-P: Implementation of an Electronic Medical Record Tool to Improve Type 2 Diabetes Management in a Large Health System
Authors: MISRA-HEBERT ANITA D. , PANTALONE KEVIN M. , RAJPATHAK SWAPNIL , WEISS TRACEY , HAMATY MARWAN , ZIMMERMAN ROBERT S.
Published: June 2020

Guidelines recommend individualized treatment for patients with type 2 diabetes (T2D), avoidance of clinical inertia, and specific therapeutic choices for patients at risk for cardiovascular disease, congestive heart failure, or chronic kidney disease. However, a gap exists in translating these guidelines into practice.

We created an electronic medical record (EMR) tool to improve evidence-based treatment intensification for T2D and studied its implementation in endocrinology and primary care (PC). The tool included a best practice alert (BPA) informing providers at an office visit of an A1C ≥ 8% and prompted providers, within the tool, to make therapeutic choices based upon five priority care goals- cardiovascular risk reduction, A1c lowering, low hypoglycemia risk, cost, or weight loss.

After a 3-month pilot at one site, the tool was implemented using a stepped-wedge approach from March-November 2019 to all PC (N=52) and endocrinology (N=17) sites in our health system with 1903 eligible patient visits by November 2019. Within endocrinology, provider tool usage ranged from 94% of visits at the pilot site to 34% after full rollout; in PC, usage ranged from 52% during the pilot to just above 5%. Usage varied by practice site (range <1- 44%) and by provider (0 - 100%). Providers expressed interest in tool utility but reported the timing of the BPA, during a busy office visit, as a barrier to use. Of note, the BPA was deferred up to 20% of the time in PC citing patient nonadherence to current therapy.

Uptake of a point of care EMR tool to promote treatment intensification for T2D in endocrinology and PC demonstrated variation at the specialty, practice site, and provider levels. Our findings also suggest that, given time pressures, provider focused point of care EMR-based interventions to improve T2D care may need to be supplemented with tools asynchronous to the office visit and should address patient factors in adherence. Further analyses will focus on tool effects on A1c control.

Disclosure

A.D. Misra-Hebert: Research Support; Self; Agency for Healthcare Research and Quality, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. K.M. Pantalone: Consultant; Self; Bayer Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Merck & Co., Inc., Novo Nordisk Inc. Speaker’s Bureau; Self; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc. S. Rajpathak: Employee; Self; Menarini Group. T. Weiss: Employee; Self; Merck & Co., Inc. M. Hamaty: Research Support; Self; Merck & Co., Inc. R.S. Zimmerman: Research Support; Self; Bayer U.S., Merck & Co., Inc., Novo Nordisk A/S. Speaker’s Bureau; Self; LifeScan, Inc., Merck & Co., Inc. Stock/Shareholder; Self; Baxter, Bristol-Myers Squibb, Pfizer Inc., Procter & Gamble Company.
124-LB: Praliciguat, a Clinical-Stage Soluble Guanylate Cyclase (sGC) Stimulator, Improved Oral Glucose and Lipid Handling and Slowed Diabetic Weight Loss in TALLYHO Mice
Authors: SCHWARTZKOPF CHAD , CARVALHO ANDREW , HADCOCK JOHN , CURRIE MARK , JONES JULI E.
Published: June 2020

Background: Praliciguat (IW-1973) is an sGC stimulator in clinical development as a potential treatment for diabetic kidney disease. In animal models, praliciguat distributes broadly to tissues and elicits hemodynamic, anti-inflammatory, anti-fibrotic, and metabolic effects. Here, we assessed the metabolic effects of praliciguat in diabetic TALLYHO mice housed at thermoneutrality in order to minimize any confounding contribution of brown fat thermogenesis on metabolism, which is rare in humans but common in mice.

Methods: Six- to eight-week-old male TALLYHO/JngJ mice were maintained on low-fat diet (10% kcal from fat, LFD). Due to incomplete penetrance of the diabetic phenotype in this model, diabetic mice were identified prior to study initiation using HbA1c and urinary glucose/creatinine ratio as criteria. At 10-12 weeks of age, a diabetic control group (n=6) was maintained on LFD, while another group (n=6) was switched to LFD formulated with praliciguat to achieve a Cmax drug exposure similar to a 20 mg oral clinical dose. Plasma was collected at baseline and after 4 weeks of treatment. Oral glucose tolerance tests (OGTT) and oral lipid tolerance tests (LTT) were performed after 5 and 6 weeks of treatment, respectively.

Results: At week 4, praliciguat treatment attenuated the HbA1c increase in TALLYHO diabetic mice (+0.40 vs. +0.95%, in praliciguat and control groups, respectively P<0.05). At week 5, fasting glucose (561 ± 33 vs. 650 ± 46 mg/dl; -14%, P<0.01) and OGTT glucose AUC (-12%, P<0.01) were lower in praliciguat-treated mice than in untreated controls. At week 6, fasting plasma triglycerides (721 ± 97 vs. 1134 ± 190 mg/dl; -36%, P<0.05) and LTT triglyceride AUC (-23%, P<0.01) were lower in praliciguat-treated mice than in untreated controls. Body weight loss and food intake were lower in praliciguat-treated mice than in untreated mice.

Conclusion: Praliciguat improved nutrient handling in diabetic TALLYHO mice.

Disclosure

C. Schwartzkopf: None. A. Carvalho: Stock/Shareholder; Self; Cyclerion Therapeutics. J. Hadcock: None. M. Currie: Employee; Self; Cyclerion Therapeutics. Stock/Shareholder; Self; Cyclerion Therapeutics. J.E. Jones: None.
1253-P: Yields and Costs of Recruitment Methods with Participant Baseline Characteristics for a Diabetes Prevention Research Study in an Underserved Pediatric Population
Authors: VANDER WYST KILEY B. , OLSON MICAH , SOLTERO ERICA G. , KONOPKEN YOLANDA P. , KELLER COLLEEN , CASTRO FELIPE GONZÁLEZ , WILLIAMS ALLISON , FERNANDEZ ARLENE D.R. , HOOKER ELVA , PATRICK DONALD L. , AYERS STEPHANIE , HU HOUCHUN H. , PENA ARMANDO , KNOWLER WILLIAM C. , SHAIBI GABRIEL Q.
Published: June 2020

Background: Diabetes disproportionately impacts Latino youth, yet few diabetes prevention programs (DPP) have prioritized inclusion of this vulnerable population. Recruitment is often the most challenging aspect of clinical trials and the optimal strategy to meet enrollment goals is unknown. This report describes the recruitment yields, costs, and baseline characteristics for a DPP focused on Latino youth.

Methods: Recruitment methods included clinics, community efforts, media, and word-of-mouth with the goal of enrolling 120 Latino youth age 12-16 with obesity and prediabetes. Yields, costs, and baseline characteristics of youth were compared by recruitment method with final prediabetes eligibility determined by an Oral Glucose Tolerance Test (OGTT).

Results: Recruitment spanned 47 months and yielded 655 referrals from clinics (N=344), community efforts (N=143), media (N=137), and word-of-mouth (N=31). From this pool, 50% (N=325) declined participation and 14% (N=93) were ineligible by general inclusion criteria. A screening OGTT was performed on 237 youth with 52% (N=122) meeting prediabetes eligibility and 117 subsequently randomized. The clinical sites yielded the highest number of total referrals (53%, N=344/655) while word-of-mouth yielded the highest proportion (35%, N=11/31) of randomized participants per referral. There were no significant differences in anthropologic or diabetes risk biomarkers between recruitment sources. Community recruitment efforts were the most costly ($486/randomized participant) followed by media ($236/randomized participant) and clinic ($248/randomized participant).

Conclusions: These data suggest that yields and costs to recruit Latino youth into a DPP vary by method, and there were no differences in youth diabetes risk profiles. Recruiting hard-to-reach populations into clinical trials requires multiple strategies to meet target enrollment.

Disclosure

K.B. Vander Wyst: None. M. Olson: None. E.G. Soltero: None. Y.P. Konopken: None. C. Keller: None. F. González Castro: None. A. Williams: None. A.D.R. Fernandez: None. E. Hooker: None. D.L. Patrick: None. S. Ayers: None. H.H. Hu: None. A. Pena: None. W.C. Knowler: None. G.Q. Shaibi: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK10757901)
1258-P: Lack of Monitoring for Glucose Intolerance in Overweight and Obese Youth on Second-Generation Antipsychotics Despite Increased Risk
Authors: CRIMMINS NANCY A. , DELBELLO MELISSA P. , CORRELL CHRISTOPH , KLEIN CHRISTINA , BLOM THOMAS , WELGE JEFFREY
Published: June 2020

Second-generation antipsychotics (SGAs) increase risk for glucose intolerance in adults; less is known about risk in youth. MOBILITY is a large, multi-center, pragmatic study designed to assess the effect of metformin added to a lifestyle intervention compared to lifestyle alone on weight gain and metabolic parameters in overweight and obese pediatric (ages 8-19) patients with bipolar-spectrum disorders (BSD) receiving SGAs. Frank diabetes was an exclusion criterion. It was recommended to obtain baseline, +6 month, and +12 month fasting metabolic labs in this trial conducted in real-world psychiatry clinics. We estimated prevalence of glucose intolerance prior to intervention. We hypothesized that youth with elevated fasting plasma glucose (FPG) and hemoglobin A1C (HbA1C) would be more likely to have repeat metabolic assessment. Altogether, 684 youth (mean age=14.3 years, 53% male, 64% with baseline BMI ≥95th%ile) were included in these analyses. Baseline FPG was obtained in 73% (501/684); 12.1% of these had impaired fasting glucose (IFG). Baseline HbA1C was obtained in 53% (360/684); 11.1% had HbA1C ≥5.7%. Six patients (1.6%) had both measures elevated. Only 41% of patients with IFG and 40% of those with HbA1C ≥5.7% had repeat glucose measures within 1 year; neither were more likely to have repeat laboratory testing than patients with normal baseline laboratory results (OR=0.88, p=0.773; OR=0.85; p=1.00, respectively). Of six patients with both IFG and HbA1C elevated at baseline, only three had repeat laboratory testing; one of these developed diabetes on follow-up. Overweight and obese youth with BSD on SGA therapy have clinically relevant rates of glucose intolerance. However, assessment and, especially, reassessment of abnormal glucose status in this population is poor. Further studies are needed to identify and address barriers for evaluation for glucose intolerance in this at-risk population.

Disclosure

N.A. Crimmins: None. M.P. DelBello: None. C. Correll: Consultant; Self; Alkermes plc., Allergan plc., Janssen Pharmaceuticals, Inc., Lundbeck, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Sumitomo Dainippon Pharma Co., Ltd., Sunovion Pharmaceuticals Inc., Takeda Pharmaceutical Company Limited, Teva Pharmaceutical Industries Ltd. C. Klein: None. T. Blom: None. J. Welge: None.

Funding

Patient-Centered Outcomes Research Institute (to M.P.D.)
126-OR: Baseline Omega-3 Status Is Associated with Nerve Regeneration following 1 Year of Omega-3 Nutrition Therapy in Patients with Diabetic Neuropathy
Authors: LEWIS EVAN J.H. , PERKINS BRUCE A. , LOVBLOM LEIF ERIK , METHEREL ADAM , WOLEVER THOMAS , BRIL VERA
Published: June 2020

We have recently demonstrated that omega-3 nutrition therapy is associated with small nerve fiber regeneration in individuals with type 1 diabetes (T1D). It is unclear if baseline omega-3s relate to the presence of diabetic sensorimotor polyneuropathy (DSP) or nerve regeneration. Forty individuals with T1D participated in a 12-month single-arm open label study of seal oil omega-3 (10 mL/d; 750 mg EPA, 560 mg DPA acid, and 1,020 mg DHA). The primary outcome was the 1-year change in corneal nerve fiber length (CNFL) measured by in vivo corneal confocal microscopy, with sensory and nerve conduction measures as secondary outcomes. Plasma PUFAs were measured at 0, 4, 8 and 12-months. The 40 participants (53% female) had mean±SD age 48±14 years, body mass index 28.1±5.8 kg/m2, diabetes duration 27±18 years and 23(59%) had DSP. At baseline, participants with DSP had lower DHA concentration compared to those without (1.73±0.89% vs. 2.27±0.70, p=0.049). At 12-months, omega-3 nutrition therapy increased group mean plasma EPA by 185%, DPA by 29%, DHA by 79% (p<0.001) and decreased the omega-6 to omega-3 ratio by 45% (p<0.001). On average, CNFL increased 29±46% over the study, indicating small nerve fiber regeneration. This change was associated with the increase in total omega-3 (r=0.41, p=0.013), DPA (r=0.33, p=0.047) and DHA (r=0.42, p=0.012). There were 26(65%) participants that responded to therapy with a change in CNFL >0% and 9(22%) with a clinically significant loss of CNFL >-6%. At baseline, responders had higher total omega-3 (4.38±1.35% vs. 3.12±0.56%, p=0.010), EPA (0.91±0.47% vs. 0.59±0.23%, p=0.040) and DHA (2.16±0.90% vs. 1.34±0.40%, p=0.009).The change in these variables was not different between responders and non-responders (p>0.05). One year of seal oil omega-3 nutrition therapy increased blood omega-3s, while small nerve fiber regeneration appears to be related to baseline omega-3 status.

Disclosure

E.J.H. Lewis: Board Member; Spouse/Partner; Nutarniq Corp. Employee; Self; Nutarniq Corp. Stock/Shareholder; Self; Nutarniq Corp. B.A. Perkins: Consultant; Self; Abbott, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Other Relationship; Self; Medtronic. L. Lovblom: None. A. Metherel: None. T. Wolever: None. V. Bril: Advisory Panel; Self; Alexion Pharmaceuticals, Inc., Alnylam Pharmaceuticals, Takeda Canada. Consultant; Self; Akcea Therapeutics, CSL Behring, Sanofi. Research Support; Self; Biogen, Grifols, Momenta Pharmaceuticals.

Funding

Diabetes Canada (OG-2-13-4093-VB)
1263-P: Nutritional Reprogramming of Hepatic Metabolism by Feeding a Diet Containing Large, Phospholipid-Coated Lipid Droplets in Early Life Protects against Western Style Diet–Induced Insulin Resistance in Adult Mice
Authors: JELENIK TOMAS , KODDE ANDREA , PESTA DOMINIK , ROHBECK ELISABETH , DEWIDAR BEDAIR , PHIELIX ESTHER , OOSTING ANNEMARIE , VAN DER BEEK ELINE M. , RODEN MICHAEL
Published: June 2020

Early life nutrition possibly influences long-term metabolic outcomes. Previous studies in mice showed that adult obesity and energy metabolism can be improved by early life exposure to an infant milk formula (IMF) with large (3-5μm), (milk)-phospholipid coated lipid droplets (Concept diet, Nuturis®). This study examined the effects of the Concept diet on (adult) fasting insulin sensitivity and hepatic mitochondrial capacity. From postnatal day (PN) 16 to PN42, male C57BL/6j mice were exposed to a semisynthetic rodent diet containing Concept or Control (CTRL)-IMF. Subsequently, mice were fed either Western-style (WSD) or standard rodent diet (AIN) from PN42 to PN98 and sacrificed after 3 hours fasting, at PN98. Homeostasis model assessment insulin resistance index (HOMA-IR) was calculated from fasting insulin and glucose levels. Mitochondrial function was assessed by high-resolution respirometry in liver tissue at PN98 using substrates stimulating β-oxidation (β-OX) and tricarboxylic acid cycle (TCA) flux. Plasma thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, were measured fluorometrically. At PN98, WSD induced insulin resistance in CTRL, but not in Concept fed mice (p<0.05). Furthermore, Concept mice on WSD had a lower liver weight (p<0.05) and 69% higher maximal β-OX compared to CTRL (p<0.05). Liver fat content increased with WSD independent of initial diet (p<0.05) and was not different between CTRL and Concept groups. Yet, plasma TBARS were 23% lower in Concept compared to CTRL mice fed WSD (p<0.05).

In conclusion, early life feeding of the Concept diet improved hepatic oxidative capacity and protected adult mice against diet-induced insulin resistance. These results suggest that early postnatal metabolic priming may decrease systemic oxidative damage which can help to maintain liver health in an obesogenic environment.

Disclosure

T. Jelenik: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. A. Kodde: Employee; Self; Danone Nutricia Research. D. Pesta: None. E. Rohbeck: None. B. Dewidar: None. E. Phielix: None. A. Oosting: Employee; Self; Danone Nutricia Research. E.M. van der Beek: Employee; Self; Danone Nutricia Research. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S.

Funding

Danone Nutricia Research
1265-P: Understanding the Childhood Obesity Trend in Brazil: The Target for Diabetes Prevention
Authors: OLIVEIRA ANA LUISA , FREITAS FILIPE , CLEMENTINO MICHELE , MELO LARA G. , SILVA DYALLE C. , GARCIA PRISCILA , CORREIA MATHEUS , MENDES MARCUS VINICIUS , SANTOS MARIANA , OLIVEIRA ATILA A. , DECHICHI THEO , OLIVEIRA ANTONIO CESAR , OLIVEIRA ANA MAYRA
Published: June 2020

Diabetes mellitus (DM) in children is on the rise worldwide and it’s well established the relationship between it and obesity. The understanding of this risk factor for DM is critical to preventing the disease. The objective is to analyze epidemiological trends of weight in children, adding data from 2019. Temporal cross-sectional analysis of the years 2001, 2011 and 2019 was randomly done with children aged 5 to 9 years and proportionally selected from public and private schools in Feira de Santana, Bahia, Brazil. Overweight and obesity were defined using body mass index (BMI) ≥ the 85th and the 95th percentiles for age and gender, respectively. A total of 1.994 children were studied, being 699 (15.6±2.5 BMI; 366 [52%] girls; 7.1±1.3y), 714 (16.6±3.0 BMI; 348 [48.9%] girls; 7.6±1.4y), 581 (17.0±3.7 BMI; 303 [53.2%] girls; 6.9±2.2y) in 2001, 2011 and 2019 respectively. The excessive weight prevalence increased significantly from 2001, 2011 to 2019 (overweight [9.2%, 15.5% and 16.9%] and obesity [4.4%, 7.2%; 11.7%]) and normal weight decreased (86.4%, 68.6%, 61.9%) with p value <0.005 for all analyzes. Classifying by type of school, private (group 1) and public (group 2), in both groups comparing 2001, 2011 and 2019, the rate of normal weight decreased (84.2%, 68.6%, 59.4% for group 1 and 88.0%, 81.7% and 67.6% for group 2), also with significance. The prevalence of overweight significantly increased between 2001 and 2011 for both private (9.9%, 19.9%) and public (8.7%, 13.3%) sectors, but maintained itself stable for both between 2011 and 2019 (group 1[19.9%, 18.6%], group 2 [13.3%, 12.8%]). As for obesity, it did significantly increase in both groups through the entire period, at a rate of 6.0%, 11.5% and 13.2% in group 1 and 3.4%, 5.0% and 8.4% in group 2, respectively for 2001, 2011 and 2019. This trend towards increased prevalence of obesity in children from both the private and public sectors confirms the urgency in taking preventive measures to control not only obesity but its comorbidities such as DM.

Disclosure

A. Oliveira: None. F. Freitas: None. M. Clementino: None. L.G. Melo: None. D.C. Silva: None. P. Garcia: None. M. Correia: None. M. Mendes: None. M. Santos: None. A.A. Oliveira: None. T. Dechichi: None. A. Oliveira: None. A. Oliveira: None.
1267-P: Physical Fitness (PF), Weight Status, and Metabolic Risk in Japanese Adolescents
Authors: MORIKAWA SAKIKO Y. , FUJIHARA KAZUYA , NEDACHI RINA , IKEDA IZUMI , TAKEDA YASUNAGA , TAKEUCHI MIZUKI , HATTA MARIKO , ISHIGURO HAJIME , YAMADA TAKAHO , SONE HIROHITO
Published: June 2020

Although cardiorespiratory fitness (CRF) and muscular fitness (MF) are modifiable factors for metabolic risk, the role of weight status in these factors has not been clarified in the pediatric population. We examined associations between metabolic indices and CRF or MF according to weight categories and compared the prevalence of metabolic abnormalities among four groups stratified by combinations of PF and weight categories. Cross-sectionally analyzed were 1744 Japanese adolescents aged 13-14 years. The PF test included measurements of CRF (20-m shuttle run test), upper-limb strength (handgrip test), lower limb strength (standing long jump test), and muscular endurance (sit-ups). Participants were classified as non-overweight (non-OW) or overweight/obese (OW) according to BMI cutoffs by the International Obesity Task Force. Metabolic risk was defined as ≥1 SD of the clustered metabolic risk (estimated by summing standardized sex-specific Z scores of HbA1c, MAP, and non-HDL-C). After adjusting for BMI and other characteristics, linear regression analysis showed that non-HDL-C was inversely associated with CRF in the non-OW group (P <0.001) and with muscular endurance in the OW group (P = 0.002). In the OW group, coefficient of correlation showed that the clustered metabolic risk was slightly lower in those with higher sit-up scores even after adjusting for BMI and CRF (P = 0.06). As to the combination of weight status and PF, upper-limb strength or muscular endurance but not CRF were additively associated with metabolic risk; in comparison with the non-OW group in the second-lowest to highest quintiles, even the OW group in the second-lowest to highest quintiles of muscular endurance were 1.8 (1.1-2.8) times more likely to have metabolic risk while those in the lowest quintile had a 3.1 (1.7-5.7) greater likelihood.

In summary, relationships of metabolic risk with components of PF differed according to weight status. In OW adolescents, MF might be more useful for stratifying metabolic risk than CRF.

Disclosure

S.Y. Morikawa: None. K. Fujihara: None. R. Nedachi: None. I. Ikeda: None. Y. Takeda: None. M. Takeuchi: None. M. Hatta: None. H. Ishiguro: None. T. Yamada: None. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.
1269-P: A Prospective, Population-Based Study of Hypothalamic Gliosis, Obesity, and Weight Gain in Children
Authors: SEWAYBRICKER LETICIA E. , MELHORN SUSAN J. , SCHUR ELLEN
Published: June 2020

Hypothalamic gliosis is a cellular response that, in rodents, is necessary for weight gain and diet-induced obesity. Whether this inflammatory process in the mediobasal hypothalamus (MBH) plays a role in common obesity or change in weight status during growth and development in children is uncertain. Using T2-weighted MRI scans from a longitudinal population-based sample of young children, we measured signal ratios to evaluate evidence of MBH gliosis in relation to obesity and adiposity change over time. We included 169 children from 6 sites recruited as part of the NIH Adolescent Brain Cognitive Development (ABCD) study. Baseline T2-weighted MRI scans were analyzed for evidence of MBH gliosis based on the T2 intensity of the mean bilateral MBH/Amygdala signal ratio. Putamen/Amygdala was used as the control ratio. Models were adjusted for site, age, and sex. At baseline, mean age was 9.9 ± 0.6 y, 50% were female, and 64% were pre-pubertal. Mean BMI z-score was 0.77 ± 1.02 [23% with overweight (OV) and 21% with obesity (OB)]. At 1y assessments (10.8 mo. on average), mean ΔBMI z-score was 0.02 ± 0.36. MBH/Amygdala ratio was positively associated with BMI z-score (r=0.32, P<0.001) and waist/height ratio (r=0.26, P<0.001), a marker of metabolic risk, whereas the control ratio was not (r=-0.02, P=0.52 and r=-0.05, P=0.76). Overall, MBH/Amygdala ratio was not associated with ΔBMI z-score (r=-0.02, P=0.49), but a significant interaction [F(5,158)=5.16; P<0.001] indicated the relationship varied by group. Among children with OV, baseline MBH/Amygdala ratio positively correlated with ΔBMI z-score (r=0.43, P=0.01); this relationship was attenuated in children with OB (r=0.19, P=0.18) and absent among participants of normal weight (r=-0.07, P=0.36).

In conclusion, we found evidence that MBH gliosis is associated with excess adiposity in a large pediatric population. In children at risk for obesity, MBH gliosis may be an important predictor of increasing adiposity and metabolic risk.

Disclosure

L.E. Sewaybricker: None. S.J. Melhorn: None. E. Schur: None.

Funding

National Institutes of Health (R01DK117623, U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147, U01DA041093, U01DA041025)
1272-P: Diabetes Distress and Depressive Symptoms in Adolescents and Young Adults with Type 2 Diabetes
Authors: ROBERTS ALISSA J. , BAO HAO , QU PINGPING , KIM GRACE , YI-FRAZIER JOYCE , PIHOKER CATHERINE , MALIK FAISAL
Published: June 2020

Objectives: To assess rates of depression and diabetes distress (DD) in adolescents and young adults (AYAs) with type 2 diabetes (T2D) overall and by sociodemographic factors.

Methods: AYAs with T2D ages 13-21 years seen in a pediatric diabetes clinic between March 2018 and June 2019 completed the Patient Health Questionnaire-9 (PHQ-9) for depression screening and the Problem Areas in Diabetes - teen version (PAID-T) survey to assess for DD. Rates of depression and DD were calculated using standard PHQ-9 and PAID-T cut-offs. Chi-square tests were used to assess whether rates of depression and DD were associated with participant characteristics.

Results: The sample consisted of 64 AYAs with T2D (58% female, mean age 15.8 ± 2.0 years, mean HbA1c 8.3% ± 2.6%, mean BMI z-score 2.2 ± 0.6, 59% on insulin). Twenty-two percent of participants reported moderate to high depressive symptoms and 9% endorsed self-harm on the PHQ-9. There were no differences in rates of depression by sociodemographic factors. Twenty-three percent of participants reported elevated DD. Rates of DD were higher among those on insulin (p=0.01) and on public health insurance (p=0.01) (Table1).

Conclusions: Almost 1 in 4 AYAs with T2D endorse depression and DD. Our findings support the importance of mental health screening in AYAs with T2D, as well as the need for strategies to address psychological comorbidities in this population.

Disclosure

A.J. Roberts: None. H. Bao: None. P. Qu: None. G. Kim: None. J. Yi-Frazier: None. C. Pihoker: None. F. Malik: None.

Funding

Seattle Children’s Hospital
1273-P: Growth Differentiation Factor 15 (GDF15) Is Associated with Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Youth
Authors: GALUPPO BRITTANY , AGAZZI CRISTIANA , PIERPONT BRIDGET , SAMUELS STEPHANIE , TARABRA ELENA , CAPRIO SONIA , SANTORO NICOLA
Published: June 2020

Growth differentiation factor 15 (GDF15) has been associated with many important biological functions, such as food intake and weight regulation in response to metabolic stress. In animal models, it has also been noted that it may play a role in the progression of nonalcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in children. Nevertheless, the exact role of GDF15 in liver disease has yet to be elucidated. We aimed to explore the association of GDF15 with NAFLD in obese youth, and whether GDF15 changes similarly with changes in hepatic fat content (HFF%) over time. Fasting plasma GDF15 levels were measured by ELISA in obese youth with (89) and without (95) NAFLD. Additionally, fasting GDF15 levels were measured in 22 obese youth who progressed (11) or regressed (11) in HFF% by more than 30% over a two-year period. Abdominal MRI was performed on all subjects to quantify HFF%. For the first time, we describe a novel association between GDF15 and NAFLD in obese youth. Figure 1A shows a statistically significant difference in fasting GDF15 levels (p<0.0001) between three groups stratified by degree of HFF%. Figure 1B shows a statistically significant association between change in HFF% and change in GDF15 (p=0.01; r2=0.29). These data suggest that GDF15 levels change with change in intrahepatic fat content in obese youth and may serve as a biomarker for NAFLD in children.

Disclosure

B. Galuppo: None. C. Agazzi: None. B. Pierpont: None. S. Samuels: None. E. Tarabra: None. S. Caprio: None. N. Santoro: None.
128-OR: The Ipswich Neurodiab Study: A 5-Year Longitudinal Study Examining Natural History of Diabetes Polyneuropathy (DPN)
Authors: SHARMA SANJEEV , CROSS JEN , VAS PRASH R. , RAYMAN GERRY
Published: June 2020

This longitudinal, case-control study compares the progression of Small and Large Fibre Neuropathy (SFN and LFN respectively) in T1DM and T2DM and examines determinants of progression.

T1DM, T2DM and healthy controls (HC) groups each with 50 subjects were evaluated annually (2014-19). Functional SFN was assessed using the LDIFLARE test in the foot and structural SFN in the cornea [corneal nerve fibre density using confocal microscopy (CCMCNFD)]. LFN was assessed using vibration perception threshold (VPT) and sural nerve conduction velocity (SNCV) and amplitude (SNAP). At year 5 DPN was diagnosed if the Neurology Disability score (NDS) was ≥3 (DPN+).

Mean (±SD) age and sex distribution at baseline for T1DM was (41.4±15.0 yr; 27 males), T2DM (54.38±9.1; 25m) and HC (40.7±15.1; 24m).

T1DM with DPN+ had a significantly greater decline of LDIFLARE size compared to DPN- [0.15 v 0.08 cm2/yr; p=0.001] and of CCMCNFD (0.16v 0.10 fibres/mm2/yr; p=0.005).

In contrast in T2DM there was no difference between DPN+ and DPN- groups in LDIFLARE size (0.22v 0.15cm2/yr; p=0.09) and CCMCNFD (0.23v 0.16 fibres/mm2/yr; p=0.06).

Decline in small fibre function and structure in T1DM DPN- was no different from HCs. (LDIFLARE - 0.07cm2/yr; CCMCNFD - 0.05 fibres/mm2/yr) in contrast to all other groups.

In T1DM, the decline of LDIFLARE size and CCMCNFD correlated only with HbA1c change (p=<0.05). In T2DM they correlated with HbA1c, triglycerides and BP changes (p=<0.05).

There was no significant change of LFN indices (VPT, SNCV and SNAP; p=>0.05) over the 5yrs.

This - the first longitudinal comparative study of changes in small fibre nerve structure and function in T1DM and T2DM - demonstrates changes in SFN in both groups that are not paralleled by changes in LFN, supporting the concept that SFN precedes LFN in DPN, It further demonstrates important differences in determinants of progression between T1DM and T2DM; the former being related to glycaemic control and the latter to multiple metabolic factors.

Disclosure

S. Sharma: None. J. Cross: None. P.R. Vas: None. G. Rayman: None.