bluuebunny/crossref_metadata_2025 huggingface dataset:
196-OR: A Meal Detection Algorithm for the Artificial Pancreas: A Randomized Controlled Clinical Trial in Adolescents with Type 1 Diabetes
Authors: PALISAITIS EMILIE , FATHI ANAS EL , HAIDAR AHMAD , VON OETTINGEN JULIA E. , LEGAULT LAURENT
Published: June 2020

Background: People with type 1 diabetes occasionally forget to announce meals to their insulin pump, which degrades glycemic control. We have developed a meal detection algorithm for the artificial pancreas (AP) that detects unannounced meals and delivers boluses.

Methods: We conducted a randomized crossover trial in adolescents aged 12-18 years with type 1 diabetes. We compared (i) CSII, (ii) AP, and (iii) AP with a meal detection algorithm (AP+MDA) in controlling post-prandial glucose levels after a meal without a bolus. Participants underwent three 9-hour interventions which included breakfast with a CHO-matched bolus and lunch without a bolus. The primary outcome was the iAUC of the glucose excursions from the start of lunch to 4 hours post-lunch.

Results: 11 participants (mean age 14.9±1.3, HbA1c 8.3±0.6%) were included. Compared to CSII, AP+MDA decreased iAUC from the start of lunch to 4 hours post-lunch from 24±9.5 h.mmol/L to 15±8 h.mmol/L (p=0.03). The AP+MDA reduced time > 10 mmol/L after the missed bolus by -21.6% (IQR: [-39.4- -3.8]) compared to CSII (p=0.02). The mean meal detection time was 41.8±16 minutes after meal consumption.

Conclusions: The AP+MDA successfully decreased iAUC after an unannounced meal in adolescents with type 1 diabetes. Longer and larger studies are needed to evaluate the efficacy of this meal detection algorithm in real-world settings.

Disclosure

E. Palisaitis: None. A. El Fathi: None. A. Haidar: Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc., Eli Lilly and Company. J.E. von Oettingen: None. L. Legault: Advisory Panel; Self; Dexcom, Inc., Lilly Diabetes. Research Support; Self; AstraZeneca K.K., Merck & Co., Inc., Sanofi-Aventis. Other Relationship; Self; Lilly Diabetes.
1967-P: Retinoic Acid Signaling Suppresses Adipogenic Differentiation of Fibro/Adipogenic Progenitors and Benefits Skeletal Muscle Regeneration Impaired Due to Obesity
Authors: ZHAO LIANG , ZHU MEI-JUN , DU MIN
Published: June 2020

Impaired regeneration of skeletal muscle in obese individuals is accompanied with fatty degeneration. Retinoic acid (RA) supplementation promotes myogenesis but inhibits white adipogenesis. The objective of this study was to examine the effects of RA on the restoration of skeletal muscle after injury under obese condition and its effects on the physiological functions of fibro/adipogenic progenitors (FAPs) which coordinate regeneration process. ROSA26-RARαDN mice were crossed with Pdgfra-cre/ER mice; in these cross-bred mice (RARαDN), tamoxifen induces RA signaling blockage specific in PDGFRα+ FAPs. Following injury, RA enhanced muscle regeneration, which was abolished due to the blockage of RA signaling in FAPs, accompanied with ectopic adipocyte accumulation, showing the mediatory roles of RA receptor signaling. Consistently, in diet-induced obese mice, muscle regeneration was inhibited but adipogenesis was enhanced; RA effectively reduced adipogenesis in the regenerated skeletal muscle of obese mice, but such beneficial effect disappeared in HFD mice with RA signaling blockage in FAPs.

In summary, our studies showed that RA signaling controls the adipogenic differentiation of FAPs and RA treatment effectively inhibits adipogenesis during skeletal muscle regeneration and promotes muscle repair of obese mice.

Disclosure

L. Zhao: None. M. Zhu: None. M. Du: None.

Funding

National Institutes of Health (R01HD067449)
197-OR: Six Months Experience on Hybrid Closed-Loop System in Children and Adolescents Previously Treated with Multiple Daily Injections
Authors: PETROVSKI GORAN , CAMPBELL JUDITH , ALKHALAF FAWZIYA , UMER FAREEDA , HUSSAIN KHALID
Published: June 2020

Aim: Evaluation of six months experience on MiniMed 670G Hybrid Closed Loop (HCL) system in patients with type 1 diabetes (T1D), previously treated with Multiple Daily Injections (MDI).

Methods: This is a 6-months prospective observational study of patients (7 to 18 years) with T1D on MDI, starting the MiniMed 670G system, using a 10-day initiation protocol: 2-days, HCL system assessment; 5-days, HCL system training (2-hours sessions in 5 consecutive days); 3-days, Manual Mode use of HCL system and 6 months, Auto Mode use of the HCL system.

Results: MiniMed 670G was initiated in 47 patients (age 12.2±3.2 years). All patients used the system for six months period. Auto Mode usage was 87.2% at the first month and 89.6% at the 6-months of Auto Mode initiation. The mean HbA1c decreased from 8.4±1.5% (68±16.4 mmol/mol) at baseline, 6.7±0.8% (50±8.7 mmol/mol) at 3-months (p=0.021), to 6.9±0.7% (52±7.7 mmol/mol) at 6-months of MiniMed 670G initiation (p=0.024). Time in Range (70-180mg/dL) significantly increased over the time (Figure 1). No severe hypoglycemia nor DKA were found.

Conclusion: Children and adolescents with T1D can successfully initiate the HCL system, achieve and maintain better glycemic control than previous MDI regimen. Low attrition rate and the sustainability of the results are likely due to patients’ selection, structured educational program and HCL system by itself.

Disclosure

G. Petrovski: None. J. Campbell: None. F. AlKhalaf: None. F. Umer: None. K. Hussain: None.
1975-P: Effects of Bariatric Surgery on the Incidence of Heart Failure and Atrial Fibrillation in Patients with Type 2 Diabetes and Obesity: A Nationwide, Matched, Observational Cohort Study
Authors: HÖSKULDSDOTTIR GUDRUN , SATTAR NAVEED , MIFTARAJ MERVETE , NASLUND INGMAR , OTTOSSON JOHAN R. , FRANZÉN STEFAN , SVENSSON ANN-MARIE , ELIASSON BJORN
Published: June 2020

Aims: Obesity and diabetes are both risk factors for atrial fibrillation (AF) and heart failure (HF). Our aim was to study the effects of bariatric surgery on incidence of HF and AF in patients with type 2 diabetes (T2D) and obesity.

Methods: In this register-based nationwide cohort study we compared individuals with T2D and obesity that underwent Roux-en-Y gastric bypass surgery (GBP) between 2007 and 2013 with individuals with T2D that did not undergo surgery. Propensity score matching was performed on the basis of sex, age, BMI and calendar time. Data were gathered from the Swedish National Diabetes Register and Scandinavian Obesity Surgery Registry as well as other national databases for our main outcomes of hospitalization for HF and/or AF.

Results: We identified 5321 individuals with T2D that had undergone GBP and 5321 matched controls. Follow up was up to 9 years. Our results show a 44% lower risk for AF (HF 0.56, 0.42-0.75, p < 0.001), 71% for HF (HR 0.29, 0.21-041, p <0.001) and 75% lower risk for simultaneous diagnosis of AF and HF (HR 0.25, 0.13-0.29, p < 0.001) in the surgical group.

Conclusion: Our study suggests that bariatric surgery may substantially lower risk for HF and AF in patients with T2DM that undergo GBP as compared to patients who do not. These data reiterate importance of excess weight on such outcomes.

Disclosure

G. Höskuldsdottir: None. N. Sattar: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. M. Miftaraj: None. I. Naslund: Consultant; Self; Baricol Bariatrics AB, Sweden, Ethicon,Johnson&Johnson A/S, Denmark. Other Relationship; Self; AstraZeneca. J.R. Ottosson: Advisory Panel; Self; Johnson & Johnson Medical Devices Companies. S. Franzén: None. A. Svensson: None. B. Eliasson: Consultant; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi.
198-OR: Individual Response of Automated Glycemic Control with the iLet Bionic Pancreas in the Insulin-Only vs. Bihormonal Configuration with the Stable Glucagon Analog Dasiglucagon
Authors: SHERWOOD JORDAN , BALLIRO COURTNEY A. , JAFRI RABAB Z. , CASTELLANOS LUZ E. , HILLARD MALLORY , SELAGAMSETTY RAJENDRANATH , GREAUX EVELYN , ZHENG HUI , EL-KHATIB FIRAS , DAMIANO EDWARD , RUSSELL STEVEN J.
Published: June 2020

In an outpatient, home-use, random-order, controlled trial we compared automated glycemic control with the iLet bionic pancreas in the insulin-only (IOBP) vs. the bihormonal (BHBP) configurations for one week each in adult subjects (n=10) with type 1 diabetes. Subjects used their typical insulin analog (lispro or aspart) during both arms of the study. During the BHBP period the iLet delivered micro-doses of dasiglucagon, a glucagon analog stable in aqueous solution (Zealand Pharma). The insulin control algorithm was identical in both configurations, was initiated solely based on each subjects’ body mass without any information regarding patients’ baseline insulin needs, and used a glucose target of 110 mg/dl. The mean CGM glucose was lower in the BHBP arm vs. the IOBP arm (139±11 vs. 149±13 mg/dl, p=0.004) while the % of time with CGMG <54 mg/dl was nominally reduced (0.2%, IQR 0-0.4 vs. 0.6%, IQR 0.2-1.1%, p=0.11). We used an autoregressive time series model to determine statistical significance for differences between arms for each individual subject. Eight subjects had a significantly lower mean CGMG during the BHBP arm (p<0.05, mean improvement 12±7 mg/dl), while in the remaining two subjects there was no significant difference (nominal absolute difference 2±1 mg/dl). Eight of the ten subjects had a nominal reduction of the % of time <54 mg/dL in the BHBP arm (mean nominal difference -0.5%, range -0.1 to -1.0%), none of which were statistically significant. Here we demonstrated significant benefit of adding dasiglucagon in eight of ten subjects, allowing them to achieve a lower mean glucose without increased rates of hypoglycemia, in a trial comparing the BHBP and IOBP configurations of the iLet.

Disclosure

J. Sherwood: None. C.A. Balliro: None. R.Z. Jafri: None. L.E. Castellanos: None. M. Hillard: None. R. Selagamsetty: Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. E. Greaux: None. H. Zheng: None. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care.

Funding

Beta Bionics, Inc.
1982-P: Laparoscopic Sleeve Gastrectomy as Bridge to Kidney Transplantation: Pilot Study in Subjects with Renal Failure and Obesity
Authors: HRÁDKOVÁ VIKTORIE , KASALICKY MOJMIR , RAJNOCHOVA-BLOUDICKOVA SILVIE , LANKOVA IVANA , KRATOCHVILOVA HELENA , MRAZ MILOS , DVORAKOVA KATERINA , SLABA SARKA , MENDL JIRI , VIKLICKY ONDREJ , FRONEK JIRI , HALUZIK MARTIN
Published: June 2020

Obesity and associated metabolic complications are established risk factors for the development and progression of chronic kidney disease; however, BMI (body mass index)>35 kg/m2 is a contraindication for kidney transplantation. The aim of our study was to reduce excess body weight via laparoscopic sleeve gastrectomy (LSG) in obese patients with end-stage renal disease (ESRD) in order for them to become eligible for the transplantation program.

Subjects with ESRD undergoing hemodialysis or peritoneal dialysis and BMI>35kg/m2 without serious comorbidities were included into the study. Anthropometric and biochemical parameters were measured before and 1, 3 and 6 months after LSG.

In the thus far enrolled 7 subjects (6 females, aged 47.6 ± 9.6 years) LSG resulted in improved body weight (118.0 ± 17.6 vs. 107.5 ± 14.5 vs. 105.5 ± 14.4 vs. 99.5 ± 10.7 kg for baseline vs. 1 vs. 3 vs. 6 months, p<0.001) and BMI (42.5 ± 3.8 vs. 38.6 ± 3.2 vs. 37.4 ± 2.8 vs. 37.0 ± 3.1 kg/m2 for baseline vs. 1 vs. 3 vs. 6 months, p<0.001) with 3 subjects achieving target BMI<35 kg/m2 1-6 months after LSG enabling their inclusion in the kidney transplantation waiting list. Weight loss was accompanied by significant decrease of systolic (160.0 ± 25.0 vs. 128.7 ± 31.2 mmHg, p=0.042) and diastolic (99.0 ± 13.6 vs. 75.5 ± 12.0 mmHg, p=0.022) blood pressure with antihypertensive medication being reduced in 2 subjects. The only subjects with diabetes mellitus (type 1) showed improvement in fasting glucose (15.8 vs. 9.3 mmol/l) and HbA1c (84 vs. 68 mmol/mol) and a 25% reduction of prandial insulin dose 1 month after LSG. No peri- or postoperative complications have been observed to date.

To conclude, our pilot data suggest LSG to be an efficient and safe method to achieve the necessary weight reduction enabling renal transplantation in subjects with renal failure and higher degrees of obesity.

Disclosure

V. Hrádková: None. M. Kasalicky: None. S. Rajnochova-Bloudickova: None. I. Lankova: None. H. Kratochvilova: None. M. Mraz: None. K. Dvorakova: None. S. Slaba: None. J. Mendl: None. O. Viklicky: None. J. Fronek: None. M. Haluzik: Advisory Panel; Self; Lilly Diabetes, Sanofi. Consultant; Self; Ethicon US, LLC. Speaker’s Bureau; Self; AstraZeneca, Mundipharma International, Novartis AG, Novo Nordisk A/S.

Funding

Institute for Clinical and Experimental Medicine (00023001)
1983-P: Dihomo-Gamma-Linolenic Acid and Estimated Delta-5-Desaturase Activity Are Associated with Obesity and Metabolic Components in Type 2 Diabetic Patients
Authors: SAITO MANABU , HIGA MARIKO , SUZUKI TAKAYUKI , MICHISHITA MOE , HIJIKATA MAI , YAMASHITA KAORU , IKEHARA KAYOKO , ICHIJO TAKAMASA
Published: June 2020

Polyunsaturated fatty acid (PUFA) is an essential class of dietary fatty acids, because of the lack of endogenous enzymes for desaturation in humans. Previous research on n-3 PUFA has demonstrated several health benefits and antiatherogenic actions, but n-6 PUFA have not received much research attention. We investigated whether serum fatty acid composition, especially n-6 PUFAs and desaturase activity, is associated with obesity in type 2 diabetic patients. Subjects were 80 type 2 diabetic patients (age: 60.3±13.9 years) who had no EPA agent intake. They were divided into two groups: obese group (n=52) with a BMI more than 25 kg/m2 and non-obese group (n=28) with a BMI less than 25 kg/m2. Fatty acid levels in serum were measured using gas chromatography. The desaturase activity for n-6 PUFAs was calculated as the arachidonic acid/dihomo-gamma-linolenic acid (DGLA) ratio for Δ5 desaturase (D5D). The obese group revealed a higher saturated fatty acid (SFA) and DGLA levels than those in the non-obese group. No significant difference was observed in the serum n-3 PUFA levels between the two groups. The D5D index of the obese group was significantly lower than that of the non-obese group. Serum DGLA levels showed significant positive correlations with waist circumference, BMI, triglyceride, and hepatic AST and ALT levels. Moreover, SFA showed a significant positive correlation with BMI. The levels of D5D index showed a significant negative correlation with BMI. Increase in serum DGLA levels was related to the number of metabolic factors. These results suggest that type 2 diabetic patients with obesity had changes in their blood fatty acid profile, especially increased DGLA levels. The high levels of blood DGLA indicate downregulation of n-6 metabolism, probably caused by the decreased activity of D5D. The fat quality in the diet and changes in desaturase activity might contribute to the development of obesity.

Disclosure

M. Saito: None. M. Higa: None. T. Suzuki: None. M. Michishita: None. M. Hijikata: None. K. Yamashita: None. K. Ikehara: None. T. Ichijo: None.
199-LB: Diabetes, Macrophage Dysfunction, and Mesh Complications
Authors: LIANG RUI , LOPA SAMIA
Published: June 2020

Objective: Diabetic women who receive polypropylene meshes in the surgical repair of stress urinary incontinence and/or pelvic organ prolapse have a ~5-fold increased risk in developing mesh complications, mainly mesh exposure and pain. Macrophage plays important roles in inflammation and mesh-tissue integration. This study aims to establish an association between diabetes and macrophage dysfunction at the mesh implantation site.

Methods: Diabetic (n=20) vs. nondiabetic (n=28) mesh-tissue complexes excised from women with mesh complications were assessed for macrophage phenotype transition, efferocytosis and immune mediator production with TUNEL apoptotic cell labeling, immunofluorescence, NanoString and Luminex multiplex assays. Significance of all statistical tests was set at 0.05 level.

Results: Demographic parameters were not different except that BMI was higher in diabetic women (p=0.04). In diabetic vs. nondiabetic specimens, the ratio of pro-healing M2 to pro-inflammatory M1 was 50% lower; the ratio of apoptotic cells/CD68+ macrophages was 50% higher; normal correlations of molecules involved in cell apoptosis (BCL10 and TRAF3) and CD68 were disrupted (Figure); and levels of chemokines CCL11, CCL13, CXCL10 were significantly increased (all p<0.05).

Conclusion: Diabetes was associated with macrophage dysfunction at the mesh implantation site, which may contribute to short-term and long-term mesh complications.

Disclosure

R. Liang: None. S. Lopa: None.

Funding

Pennsylvania Department of Health
1990-P: The Improvement of Liver Function Correlates Positively with Decreasing FABP1 Level in Chinese Patients with Obesity after Laparoscopic Sleeve Gastrectomy: A 12-Month Follow-Up Study
Authors: MA HUIHUI , HUI YOU , QU SHEN
Published: June 2020

Objective: Various studies have documented the liver fatty acid-binding protein (FABP1) were closely related to liver function. However, the interrelation between the liver function and FABP1 in Chinese patients with obesity after laparoscopic sleeve gastrectomy (LSG) is unclear. Therefore, we aimed to interpret the correlation between FABP1 level and progression of liver function in obese patients, during a 12-month follow-up.

Methods: This study included 131 individuals: 54 had normal weight (BMI:21.63±1.52kg/m2),77 had obesity (BMI:39.67±6.14kg/m2). The subjects were divided into three tertiles (Q1, Q2, and Q3) according to FABP1 levels: Q1, <16.35ng/ml; Q2, 16.35∼34.30ng/ml; Q3, >=34.30ng/ml. FABP1 levels were measured using ELISA.

Results: Serum FABP1 levels were significantly higher in patients with obesity (29.71±22.35 ng/ml, P< 0.001) than normal weight individuals (13.70±9.48 ng/ml). FABP1 level was decreased at 6 and 12 months after LSG (15.00±10.27ng/mL, P<0.001, and 12.74±7.64 ng/mL, P<0.001).At baseline, compared to the bottom tertile (Q1), middle (Q2) and upper (Q3) tertile of FABP1 were related to higher liver enzyme level. Besides, after LSG, liver enzymes declined rapidly in Q2 and Q3 than Q1. Correlation analysis found that the decrease in FABP1 level was positively correlated with the decrease in ALT, AST, and γ-GT at 6 and 12 months after LSG. After adjusting for age, sex, ΔTC, ΔTG, ΔHDL, ΔLDL, ΔFBG, ΔFINS, ΔFCP, ΔFFA, and ΔUA, linear regression analysis revealed the decreased FABP1 levels was only positively correlated with the alterations of ALT (R2=0.769, P=0.001) and AST (R2=0.836, P<0.001) at 12 months after LSG.

Conclusion: Our results suggested obesity was strongly associated with up-regulated serum FABP1 level. In addition, the improvement of liver function was positively correlated with changes in FABP1 at 12 months in Chinese patients with obesity after LSG.

Disclosure

H. Ma: None. Y. Hui: None. S. Qu: None.

Funding

National Natural Science Foundation of China (81700752, 81970677)
1994-P: Task-Oriented Connectivity Analysis of Disease-Dependent Effects of Diet
Authors: WATT CHARLES , STANLEY THEODORA K. , LACADIE CHERYL , LAM KATHERINE W.Y. , SAVOYE MARY , SINHA RAJITA , CONSTABLE TODD , SEO DONGJU , HWANG JANICE J. , BELFORT-DEAGUIAR RENATA
Published: June 2020

Previous results have demonstrated that short-term dieting attenuates neuronal inhibitory control on appetite measured with blood-oxygen-level-dependent (BOLD) responses to a food cue task. Because recent studies have suggested that functional connectivity measured during the task is strongly predictive of disease states, we sought to investigate the effect of weight loss on brain functional connectivity during the picture viewing task. Sixteen healthy obese (10F/6M, age 44.4±8 years, BMI 32.7±2) and 9 type 2 diabetes (T2DM) obese subjects (5F/4M, age 48±9, BMI 33.9±2) underwent functional MRI (fMRI) before and after an 8-week low-calorie diet. Brain connectivity (BOLD) was recorded while subjects viewed preselected images (high-calorie food, low-calorie food, and non-food). Participants lost 2.9±2.8 kg (p<0.05) weight after the diet. Using intrinsic connectivity distribution (ICD) analysis, there was a significant diet effect (p< 0.01) in the inferior pons, hypothalamus, and inferior medial hippocampus across all subjects. Diet by group interaction in ICD (p <0.001) was observed in the inferior anterior amygdala, inferior medial hippocampus, and hypothalamus, brain regions involved in the modulation of emotion and glucose metabolism. These results highlight the adaptive nature of neuronal control on diet and provide novel evidence for a variable nature of inhibitory neuronal adaptions in metabolic diseases.

Disclosure

C. Watt: None. T.K. Stanley: None. C. Lacadie: None. K.W.Y. Lam: None. M. Savoye: None. R. Sinha: None. T. Constable: None. D. Seo: None. J.J. Hwang: Research Support; Self; General Electric. R. Belfort-DeAguiar: Research Support; Self; Silver Palate Kitches.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (P30DK045735, K23 DK098286-02, R01DK020495); National Institutes of Health (UL1TR001863)
20-OR: Psychological Impact and Need for Psychological Care and Support: What Do People with Diabetes and Caregivers Say? Results of a Scientific Survey of 9,869 People with Diabetes and Caregivers in Denmark
Authors: SKOVLUND SOREN E. , NIELSEN KASPER A. , EJSKJAER NIELS
Published: June 2020

Aim: To characterize the need for and access to psychological care and self-care support for People With Diabetes (PWD) and Caregivers (CG) in Denmark.

Methods: The national diabetes survey (Life with Diabetes 2019) was designed by the Danish Diabetes Association, Steno Diabetes Center North, and Aalborg University with PWD and CG to benchmark Impact/daily life, Access to care, technology and services and understand key wishes and priorities. The study used pre-validated, national PRO diabetes and purpose-built Likert items/scales, as well as open-ended items for mixed-methods research. E-mail invites were sent to 38.820 members of the Danish Diabetes Association. Statistics were done with (STATA/SPSS 26) and coding and thematic analysis with (NVIVO12).

Results: 9.108 PWD and 761 CG completed the survey: 71% had T2 and 26% T1 diabetes. 51% were women. All Danish regions were represented: Capital (n=2.753), South (n=2365), Central (n=2.126), Zealand (n=1.490) and North (n=1.082). Age/gender was similar to the general population. Impact: 19% of PWD felt distress (diabetes taking up “too much of daily life”). Access: 18% of PWD (24% women vs. 12% men) needed a referral for a psychologist, but had not been offered one. 36% of PWD/21% of CG did not get the support they needed to deal with diabetes related emotions. Wishes: 19% reported a major need for system wide improvement in psychosocial support and analyses of 1.100 free text responses identified detailed problem/improvement areas, notably within: 1) access to new technology, 2) quality of care in primary practice 3) Whole-person care beyond medicine (exercise, diet, mental health).

Conclusions: This is the largest nationwide Danish survey to date to quantify as well as qualitatively characterize a major need for better access to psychological and other non-medical diabetes care in Denmark.

Disclosure

S.E. Skovlund: None. K.A. Nielsen: None. N. Ejskjaer: None.

Funding

Danish Diabetes Association
2007-P: Weight Change and Intentionality of Weight Loss Relate to Mortality Risk in the Postintervention (Years 8-16) Phase of Look AHEAD
Authors: WING RENA R. , CLARK JEANNE , ESPELAND MARK , HILL JAMES O. , JEFFERY ROBERT W. , JOHNSON KAREN C. , KNOWLER WILLIAM C. , NEIBERG REBECCA H. , OLSON KAYLONI , PI-SUNYER XAVIER , STEINBERG HELMUT O. , WYATT HOLLY
Published: June 2020

The health effects of weight loss in older individuals with diabetes is unclear, perhaps related to intentionality of the weight loss. Look AHEAD (LA) is a randomized trial comparing intensive lifestyle intervention for intentional weight loss with diabetes support and education (control) in 5145 individuals (age 45-76 at baseline) with overweight/obesity and type 2 diabetes. We examined the association of weight change trajectories post-intervention (i.e., yrs 8 to 16; M± SD percent weight change= -3.10% ±10.1), and concurrent risk of mortality by comparing weight gainers (N=226), maintainers (N=1459), modest losers (N=2206), and steep losers (N=415). Both weight loss groups were older, more likely to be in DSE, and lost less weight in yrs 1-8. In Cox proportional hazards regression models, adjusted for sex, race, baseline obesity, age, and treatment, mortality risk among the 4 weight change categories differed significantly (p<0.0001). Relative to maintainers, the hazard ratio for death was non-significantly lower in gainers (HR= .58, 95%CI 0.30,1.11) but significantly higher in modest losers (HR=1.49, 95%CI 1.20,1.36) and steep losers (HR=1.87, 95%CI 1.39,2.53). Adjusting for weight change baseline to year 8 did not alter the associations. Subsequent analyses examined the difference in the hazard ratios for death in those who reported having lost >10 lb over 2 most recent 6-month assessments intentionally, unintentionally, or through the combination (intentional + unintentional), relative to maintainers (no weight loss>10 lb). Adjusted analyses showed that the HR for mortality was significantly greater in both the unintentional (HR=3.26, 95%CI 2.35,5.01) and the combination (HR=2.63, 95%CI 1.28,5.39), but not different in the intentional weight loss group (HR=1.05, 95%CI 0.61,1.81) relative to maintainers. These data suggest that unintentional weight loss is associated with increased risk of mortality in older individuals with diabetes.

Disclosure

R.R. Wing: None. J. Clark: None. M. Espeland: Other Relationship; Self; Boehringer Ingelheim International GmbH, Ironwood Pharmaceuticals. J.O. Hill: Stock/Shareholder; Self; Gelesis, Shakabuku LLC. R.W. Jeffery: None. K.C. Johnson: None. W.C. Knowler: None. R.H. Neiberg: None. K. Olson: None. H.O. Steinberg: None. H. Wyatt: Research Support; Self; National Cattleman’s Association, Novo Nordisk Inc. Stock/Shareholder; Self; Shakabuku LLC. Other Relationship; Self; FoodMinds.

Funding

National Institutes of Health
201-LB: NKG2D Signaling within Pancreatic Islets Reduces NOD Diabetes and Is Associated with CD8+ Central Memory T-Cell Generation
Authors: TREMBATH ANDREW , SHARMA NEEKUN , GERLING IVAN C. , MATHEWS CLAYTON E. , MARKIEWICZ MARY A.
Published: June 2020

Type 1 diabetes is an autoimmune disease in which the pancreatic β islet cells are destroyed. The main drivers of type 1 diabetes are islet-specific T cells. These cells must escape a myriad of tolerance mechanisms that control their activation in healthy individuals. Understanding these mechanisms is critical to developing better strategies to inhibit the disease. One pathway implicated in this process is NKG2D signaling. However, the importance of NKG2D to diabetes pathogenesis is unclear owing to conflicting results from studies in which NKG2D signaling was inhibited globally. Our previous studies indicate that these inconsistent findings are due to differential effects of NKG2D signaling in response to islet antigen and the microbiota. Therefore, new experimental approaches are required to determine the roles of NKG2D during diabetes development. To this end, we generated two novel mouse models. These are transgenic NOD mice that have enhanced NKG2D ligand expression in β cells (RIP-RAE1ε mice), and NOD mice lacking expression of the NKG2D ligand endogenously expressed in islets, H60a. We found that the RIP-RAE1ε mice and H60a-deficient mice had decreased and increased diabetes, respectively. These data demonstrate that increasing NKG2D signaling within the pancreas protects, whereas eliminating NKG2D signaling enhances, NOD diabetes. Further, we show that the NKG2D-mediated protection is associated with an increase in CD8+ central memory T cells (Tcm) in vivo, which correlates with NKG2D signaling-induced generation of both mouse and human CD8+ central memory T cells in vitro, and that CD8+ Tcm protect against diabetes in the NOD.SCID adoptive transfer model. Taken together, these data indicate that NKG2D signaling protects against diabetes by enhancing the generation of a protective CD8+ Tcm population.

Disclosure

A. Trembath: None. N. Sharma: None. I.C. Gerling: None. C.E. Mathews: None. M.A. Markiewicz: Consultant; Self; Johnson & Johnson.

Funding

American Diabetes Association (1-12-JF-41 to M.A.M.); National Institutes of Health (P30GM103326, P30CA168524, UC4DK104167, UC4DK104155, U54HD090216, P30DK020579, P30GM122731); JDRF (5-SRA-2018-557-Q-R, 17-2012-595); The Leona M. and Harry B. Helmsley Charitable Trust (2018PG-T1D053); American Association of Immunologists
201-OR: Automated Insulin Delivery (AID) System Performance with and without Meal Announcement: Effect of Meal Macronutrient Content
Authors: BARTEE AMY , BRAZG RONALD L. , KATZ MICHELLE , LALONDE AMY , WOLPERT HOWARD , JONES RICHARD
Published: June 2020

Missed meal boluses contribute to suboptimal glucose control. There has been limited evaluation of missed boluses for complex or high glycemic index meals while on hybrid closed loop AID systems. Ten subjects with type 1 diabetes (50% male), age 52±10 y, A1C 7.1±0.9%, insulin requirement 0.5±0.2 U/kg/day, used the Lilly investigational AID system (model predictive control algorithm) during a 48 h inpatient observation with 6 meals. For each subject, the 2 breakfast (pancake; [60 g carbohydrate (CHO), 15±4 g fat]) and 2 dinner (pizza; [53±3 g CHO, 20±1 g fat]) meals were identical, and were consumed with or without a pre-meal insulin bolus. Lunch meals were subject-selected (44±16 g CHO, 7±5 g fat), and appropriate pre-meal boluses were administered. Time-in-range (TIR, 70-180 mg/dL) overnight was 99.2±9.5% and following the lunches was 82.1±26.4%. In contrast, TIR following pancake and pizza challenges with bolus were 56.0±34.4% and 65.8±29.6%, and without bolus were 17.8±5.1% and 36.5±25.2%, respectively. Incremental area under the curve (0-2 h) following the pancake meal was larger than the pizza meal within both the bolused and non-bolused scenarios (Table). This study highlights the importance of structured, but varied meal challenge tests in the evaluation of AID system performance. Meal macronutrient content affects AID performance in bolused and non-bolused scenarios.

Disclosure

A. Bartee: None. R.L. Brazg: None. M. Katz: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. A. LaLonde: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. H. Wolpert: Employee; Self; Eli Lilly and Company. R. Jones: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.
202-LB: Diabetes-Induced Modulation of a Specialized Macrophage Implicated in Bone and Nerve Repair
Authors: SALISBURY ELIZABETH A. , MEJIA JULIO A. , GUGALA ZBIGNIEW , DAVIS ALAN R. , OLMSTED-DAVIS ELIZABETH
Published: June 2020

Altered inflammatory responses are associated with impaired bone and nerve healing in diabetes. However, the detailed mechanisms of these responses and their contribution to neuropathy and poor fracture healing remain unclear. We previously identified a cell population expressing factors associated with brown adipocytes (uncoupling proteins and the β3-adrenergic receptor (ADRβ3)), which is activated by neuroinflammation and contributes to de novo bone formation. Single cell RNA-sequencing revealed these cells are macrophages. In this study, we investigated the role of this newly identified macrophage population during bone formation in wild type and diabetic mice. De novo bone formation was induced by intramuscular delivery of cells producing bone morphogenetic protein 2. After four days, ADRβ3+ cells were isolated by FACS to evaluate expression of different macrophage markers and macrophage polarization by qPCR. These cells expressed a unique set of markers similar to CNS macrophages, including TMEM119. Polarization assays to induce either a pro-inflammatory (M1) or reparative (M2) macrophage phenotype revealed these cells possess plasticity but are distinct from bone marrow-derived macrophages and microglia. In vivo addition of LPS to promote M1 polarization during de novo bone formation led to a reduction in bone volume. When a unicortical fracture was introduced to the femur, ADRβ3+ macrophages were observed within the fracture callus after seven days, indicating a role for these cells in the reparative process. Analysis of de novo bone formation and fracture in C57BL/6- ob/ob mice showed reduced numbers of ADRβ3+ macrophages. Initial histological analysis of human nerves indicates expansion of these ADRβ3+ cells in type 2 diabetes. These data suggest alterations to a novel macrophage population with reparative potential in diabetes. Further characterization of these cells may provide new approaches to direct their action for desired bone and nerve repair.

Disclosure

E.A. Salisbury: None. J.A. Mejia: None. Z. Gugala: None. A.R. Davis: None. E. Olmsted-Davis: None.

Funding

National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01R066556); U.S. Department of Defense (W81XWH-16-1-0649, W81XWH-17-1-0628)
202-OR: Basal Insulin Digital Titration App vs. Enhanced Paper Titration Tool: A Randomized Control Study
Authors: PHILIS-TSIMIKAS ATHENA , FORTMANN ADDIE L. , BASTIAN ALESSANDRA , KANCHI ARATI , ABAD RICARDO , SHENG TONG , PARKS LINDA , GREENFIELD MICHAEL , CLEMENTS MARK A.
Published: June 2020

Self-adjusting insulin is challenging for people with type 2 diabetes (PWT2D). Mobile health technologies (mHealth) can help PWT2D track blood glucose more easily, but it remains unclear whether an mHealth-enabled digital therapeutic tool can effectively support basal insulin (BI) titration in a large multispecialty health care setting. We randomized 242 PWT2D on BI (baseline HbA1c 7.5% - 12.5%) to use either an app-based self-titration tool [Mobile Insulin Dosing System (MIDS)] or an enhanced paper titration tool based on a stepped algorithm with diabetes educator support (control) for 16 weeks. Cohort characteristics for the intent to treat sample (MIDS n = 117; control n = 120) were: median age 61 years [IQR: 53 - 69], 41.7% female, 75.9% non-Hispanic White, 11.4% new to insulin, median duration of diabetes 11 years [IQR: 7 - 18], and median baseline HbA1c of 8.7% [IQR: 8.0 - 9.6]. Improvements in HbA1c (-1.3% [IQR: -2.2 - -.5] and -1.2% [IQR: -1.9 - -.5]; both Ps < .05) with increased median insulin dose (+8 IU [IQR: 2 - 22] and +10 IU [IQR: 2 - 25.5]; both Ps < .05) and no change in hypoglycemia were observed at 16 weeks in both the MIDS and control groups, respectively. No differences in HbA1c (P = .48) or insulin dose change (P = .34) were observed between the groups. Among SMBG readings recorded during the study, the mean proportion of readings between 70-180 mg/dL (76.8% ± 22.0; 70.0% ± 26.7; p<0.05) and >250 mg/dL (4.9% ± 9.2; 9.2% ± 18.4; p<0.05) both favored the MIDS group. The use of MIDS and the enhanced paper-based tool for BI self-titration both resulted in higher insulin dose and significantly improved glycemic control among PWT2D who were relatively uncontrolled despite most already being treated with insulin. An mHealth-enabled digital therapeutic tool such as MIDS may offer an effective alternative option for PWT2D and their HCPs for titrating BI to non-mHealth approaches; future RCTs will more clearly elucidate the efficacy of MIDS compared to usual care.

Disclosure

A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. A.L. Fortmann: None. A. Bastian: None. A. Kanchi: Employee; Self; Glooko, Inc. Stock/Shareholder; Self; Glooko, Inc. R. Abad: Employee; Self; Glooko, Inc. T. Sheng: Employee; Self; Glooko, Inc. L. Parks: Employee; Self; Glooko, Inc. M. Greenfield: Consultant; Self; Glooko, Inc. M.A. Clements: Consultant; Self; Glooko, Inc. Other Relationship; Self; Glooko, Inc.
2027-P: A Retrospective Study of Weight and Metabolic Changes in Patients with Obesity (BMI≥30 Kg/m2) after Endoscopic Sleeve Gastroplasty (ESG) or Laparoscopic Sleeve Gastrectomy (LSG)
Authors: BENIAS PETROS , VEGESNA ANIL K. , LEUNG TUNG MING , ZISKOVICH KARINA , INLALL DAMIAN , PORETSKY LEONID , MILLER LARRY S.
Published: June 2020

Weight reduction in obese individuals lowers comorbidities. LSG is the most common bariatric procedure in use today, but there is a need for less invasive approach. ESG, a novel incisionless, minimally invasive procedure, involves endoscopic plication of the greater curvature of the stomach reducing its length and width. We compared weight and metabolic changes associated with these procedures. A single center retrospective study was performed of consecutive patients that underwent LSG or ESG. SAS and multivariate mixed model were used to determine percentage change of total body weight (TBW), BMI, BSA (body surface area), HbA1c and total cholesterol level (TC). 25 patients were recruited (11[44%] had LSG and 14[56%] had ESG). The average age of LSG group was 47±3.9 and ESG group was 39±4.2 years. There was no statistical difference in the age, gender, or race between the groups. 29% of LSG patients and 10% of ESG patients had diabetes. Results are in the Table; * indicates significant differences between the groups.

Conclusions: In this limited retrospective study, patients who underwent LSG had a higher % reduction in TBW, BMI and BSA than those who underwent ESG. There was no statistical difference between the groups in the HbA1c or TC change. These preliminary data should be confirmed in larger prospective randomized trials.

Disclosure

P. Benias: Consultant; Self; Apollo EndoSurgery. A.K. Vegesna: None. T. Leung: None. K. Ziskovich: None. D. Inlall: None. L. Poretsky: None. L.S. Miller: None.

Funding

New York State Department of Health
2029-P: Role of Adipose Tissue Macrophage–Derived F13A1 in Regulating Preadipocyte Hyperplasia during Obesity
Authors: ELIZONDO DIANA M. , GELETKA LYNN M. , FLESHER CARMEN G. , LUMENG CAREY N.
Published: June 2020

The epidemic of DM has increased in the last decades and is the leading cause of decreased life expectancy. AT adapts to nutrient excess by balancing hypertrophy and hyperplasia that contribute to AT expansion. Unhealthy AT expansion seen in a person with diabetes is characterized by decreased preadipocyte (PA) content, and increased adipocyte size. AT macrophages (ATM) contribute to unhealthy AT expansion by blocking adipogenesis, promoting adipocyte hypertrophy, fibrosis and insulin resistance (IR). Many of the cellular and molecular mechanisms by which adipocyte numbers and size is regulated by ATMs in vivo are still unknown, especially in human obesity. This study focused on the hypotheses that ATM expression of F13A1, a tissue transglutaminase enzyme shown to regulate fibrin networks during tissue growth: 1) modulates abundance of preadipocyte (PA) populations during obesity and DM states, and 2) contributes to adipocyte hypertrophic states and potential metabolic dysfunction. The premise for these studies was based on evidence that F13A1 is increased in Visceral AT (VAT) of DM individuals compared to non-DM and that it is produced by a tissue remodeling ATM subset increased in DM. We utilized nondiabetic (NDM) and DM human secondary PA treated with F13A1 and assessed the following: 1) F13A1 expression requirement for the inhibition of healthy PA expansion in obesity, and 2) the mechanisms by which its function leads to arrested proliferation. Results showed that F13A1 impairs PA proliferation through its exerted effects on PA ECM fibronectin crosslink leading to: 1) downregulation of downstream gene proliferative signaling pathways and 2) defaulted adipocyte differentiation with hypertrophic profiles as an antagonistic response to decreased proliferation. These studies have advanced our understanding of ATM-derived F13A1 as a potential immunotherapeutic target to improve AT function.

Disclosure

D.M. Elizondo: None. L.M. Geletka: None. C.G. Flesher: None. C.N. Lumeng: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (T32DK101357)
204-LB: The In Vitro Characteristics of Human Islet Cells from Diverse Donors, Coaggregated with Human Mesenchymal Stromal Cells to form “Neo-islets”, Are Consistently Identical: Relevance to Clinical Trials in Diabetic Subjects
Authors: GOOCH ANNA , CHOWDHURY SABIHA S. , ZHANG PING , HU ZHUMA , WESTENFELDER CHRISTOF
Published: June 2020

We reported that allogeneic “Neo-Islets” (NIs), organoids composed of ~ equal numbers of Mesenchymal Stromal Cells and culture expanded Islet Cells (ICs) do, when given i.p., omentally engraft and permanently restore euglycemia in auto-immune diabetic NOD mice, i.e., without the use of either encapsulation devices or antirejection drugs. Similarly, spontaneously diabetic pet dogs treated with allogeneic canine NIs (cNIs) significantly improve glycemia with ~ 50% reduction in insulin needs (> 2 years), and this without immune response. In preparation for a Phase I Clinical Trial we tested whether human ICs in NIs (hNIs) are biologically comparable to canine Islet Cells (cICs) and cNIs, i.e., cells from a larger diabetes model. In our preclinical mouse and dog studies, insulin and other islet hormone gene expression levels were used as indicators of ICs in NIs to adequately re-differentiate into insulin and islet-specific endocrine cells when implanted i.p., thereby resulting in physiological control of T1DM.Human islet cells from 6 donors of different demographics were cultured, passaged to P4, and their growth rates, insulin and other islet-associated endocrine genes’ expression levels, secretion of insulin in response to glucose stimulation (GSIS), and NI formation abilities were compared.

Results: (1) hICs and hNIs show comparable gene expression profiles to those of cICs and cNIs, and hNIs show identical GSIS responses to those of cNIs. (2) Insulin gene expression profiles of hICs are stable as a function of population doublings and independent of donor diversity.

In conclusion, these data indicate that donor variability does not appear to be a significant factor in this NI technology, facilitating our IND work and further demonstrating hNIs’ translational potential in a planned Clinical Trial in subjects with T1DM.

Disclosure

A. Gooch: Employee; Self; SymbioCellTech. S.S. Chowdhury: Employee; Self; SymbioCellTech. P. Zhang: Employee; Self; SymbioCellTech. Z. Hu: Employee; Self; SymbioCellTech. C. Westenfelder: Consultant; Self; SymbioCellTech.
2044-P: Loss of CB1R Protects against Streptozotocin-Induced ß-Cell Dysfunction in Mice
Authors: ASEER KANIKKAI RAJA , O’CONNELL JENNIFER F. , EGAN JOSEPHINE M.
Published: June 2020

Approximately 1.25 million Americans have type 1 diabetes mellitus (T1DM), resulting from autoimmune β-cell destruction: there is no known way to prevent such destruction of β-cells. We have already reported that activation of cannabinoid 1 receptor (CB1R) contributes to the pathogenesis of pancreatic β-cell dysfunction during high fat feeding. To uncover if CB1R signaling might influence toxin-induced β-cell injury, we induced β-cell destruction in wild type mice (WT: n=8) and in mice in which CB1R was genetically nullified in β-cells only (β-CB1R-/-: n=8) in adulthood by five daily injections of streptozotocin (STZ; 50 mg/kg intraperitoneally [IP]), a toxin selective for β-cells. We found that β-CB1R-/- mice had random blood glucose (BG) levels in the range of 137-220 mg/dL throughout the study period (28 days following STZ) as well as preserved insulin secretion with superior glucose tolerance after a glucose challenge (2g/kg) at day 8, 15 or 27, relative to their WT littermates (random BG 500-600 mg/dL). CB1R-deficient β-cells exhibited significant increases in autophagy flux following STZ. We determined that mice or β-cells lacking CB1R had reduced mTOR activation and increased nuclear translocation of TFEB, a key prerequisite for lysosome biogenesis and autophagy. Importantly, we found that CB1R deletion protected against oxidative stress, endoplasmic reticulum stress, and prevented the induction of apoptosis by STZ. These anti-stress functions were accompanied by increased phosphorylation of AKT (ser) 473 and ERK1/2 in β-cells, which reveals a previously unrecognized route for mTOR/AKT axis to regulate autophagy that coordinately is permissive to β-cell survival. We conclude that CB1R nullification confers resistance to pancreatic β-cell dysfunction by upregulating autophagy and subsequently antagonizing the decline in lysosomal activity. Altogether, we propose that CB1R is a potential therapeutic target during the honeymoon phase of T1DM.

Disclosure

K. Aseer: None. J.F. O’Connell: None. J.M. Egan: None.
2056-P: In Vivo Human Islet Compensation and Dysfunction to Diet-Induced Obesity: A Phase 0 Preclinical Model
Authors: KERR-CONTE JULIE A. , THEVENET JULIEN , PASQUETTI GIANNI , PETIT PAULINE , CLABAUT CLARA , GMYR VALERY , BONNER CAROLINE , GARGANI SOFIA , PATTOU FRANCOIS
Published: June 2020

A translational discrepancy exists between animal models used for diabetes research and diabetes in man, thus human relevant models must become a priority. We showed that collectively human islet grafts from 26 donors statistically significantly adapted their function and endocrine and β-cell mass to HFD (high fat diet) in vivo in 233 RAG2KO mice. Human islet compensation occurs at 6 weeks and metabolic dysfunction upon chronic ≥10 weeks HFD. Herein, gene expression studies (GeneChip® Human Gene 2.0 ST Arrays) identified molecular pathways involved. Indeed, human islets compensate to HFD by upregulating hormones, transcription factors, antioxidants, and unfolded protein response genes, and then become dysfunctional at 10 wks -by downregulating these genes. Herein we show Krebs cycle and Mitochondrial electron transport chain was targeted with a transient increase at 6wk and then a drop-in expression at 10 wks; whereas uncouplinggene expression UCP2 and 3 increased. Glycolysis remained upregulated. Explanations for expanded islet and beta mass in HFD (vs. CTL) may be found in cell cycle heatmap. Lastly, a marker of activated stellate cells TAGLN, and matrix genes rose during islet dysfunction (fibrosis?).

Conclusion: This human-based model system progressively depicts defects identified in human pre and T2DM that could serve as a “phase 0” in vivo model to test new targets and develop effective therapies in man.

Disclosure

J.A. Kerr-Conte: None. J. Thevenet: None. G. Pasquetti: None. P. Petit: None. C. Clabaut: None. V. Gmyr: None. C. Bonner: None. S. Gargani: None. F. Pattou: None.

Funding

JDRF; Programme d’investissements d’avenir; LabEx; European Genomic Institute for Diabetes (ANR-10-LABX-46)