bluuebunny/crossref_metadata_2025 huggingface dataset:
451-P: Palmitic Acid–Induced lncRNA PARAIL Regulates Inflammation via Restricting HuR Localization to Cytoplasm in Human Monocytes and Macrophages
Authors: TANWAR VINAY S. , REDDY MARPADGA A. , DAS SADHAN , SAMARA VISHNU AMARAM , ABDOLLAHI MARYAM , DEY SUCHISMITA , GANGULY RITUPARNA , LANTING LINDA L. , STAPLETON KENNETH , NATARAJAN RAMA
Published: May 2022

Obesity and diabetes are associated with chronic inflammation induced by the elevated circulating levels of Palmitic acid (PA) and also result from impaired resolution of inflammation in macrophages. Here, we examined the role of PA-induced long non-coding RNAs (lncRNAs) in the resolution of inflammation. Our RNA-seq analysis showed that PA induced several lncRNAs including a novel PA-regulatedanti-nflammatoryIncRNA (PARAIL) in CD14+ human monocytes. We found PARAIL was also upregulated by lipopolysaccharide and bacterial infection in human monocytes and macrophages, suggesting its role in adaptive immunity. PARAIL knockdown in human macrophages enhanced PA-induced key inflammatory cytokine genes and delayed resolution of inflammation. RNA-pulldown coupled with mass spectrometry showed that PARAIL interacts with Hu Antigen R (HuR) an RNA-binding and AU-rich element (ARE) binding protein that regulates inflammation. We also identified AREs in PARAIL that interact with HuR. Further, knockdown of HuR and PARAIL additively increased the expression of inflammatory genes compared to knockdown of HuR or PARAIL alone suggesting PARAIL mediated resolution of inflammation relies on HuR function. Moreover, PARAIL knockdown decreased HuR protein levels, suggesting PARAIL increases HuR stability to decrease inflammatory genes and promote resolution of inflammation. In addition, Parail was also downregulated in macrophages from mouse models of diabetes and accelerated atherosclerosis. Together, these data suggest that upregulation of PARAIL under inflammatory conditions can contribute to unique feedback pro-resolution mechanisms via PARAIL-HuR interaction to restrain fatty acid-induced inflammation. However, PARAIL downregulation during obesity/ diabetes can further augment inflammation. LncRNAs like PARAIL therefore represent novel tools to combat inflammation associated with these metabolic disorders.

Disclosure

V.S.Tanwar: None. R.Natarajan: None. M.A.Reddy: None. S.Das: None. V.Samara: None. M.Abdollahi: None. S.Dey: None. R.Ganguly: None. L.L.Lanting: None. K.Stapleton: None.

Funding

National Institutes of Health (NIH RDK 065073)
452-P: Liraglutide Decreases Neointimal Growth in Control and Western Diet–Fed Mice, and Its Effect Is Insulin Dependent
Authors: GONZALEZ MAREL , LIU ZHIWEI , GIACCA ADRIA
Published: May 2022

Restenosis following percutaneous transluminal angioplasty and stenting is increased in subjects with insulin resistance and diabetes. Our preclinical models of restenosis show that insulin treatment is vasculoprotective in insulin sensitive conditions but insulin's effect is diminished or lost in Western diet induced insulin resistant conditions. Accordingly, early insulin treatment has not proven to provide cardiovascular disease (CVD) protection in subjects with dysglycemia, while the effect of intensive insulin treatment of type 2 diabetes (T2D) is debated. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are a new class of antidiabetic drugs that reduce the CVD risk of T2D. Several animal studies have shown that GLP-1RA decrease neointimal growth in models of restenosis; however, the mechanisms of the CVD actions of these drugs remain elusive. GLP-1RA are insulin secretagogues, therefore their effect may be partly mediated by the insulin receptor (IR) . The objective of this study was to determine if insulin receptor (IR) deficiency in endothelial cells (EC) attenuates the effect of GLP-1RA to decrease neointimal growth after arterial injury. Endothelial deficient IR mice were generated by crossing IR floxed mice with mice expressing tamoxifen-inducible Cre recombinase under the control of Tie2 promoter. Mice were fed a low-fat (LFD) or a high-fat-high-sucrose (HFSD) Western diet and implanted with an osmotic pump delivering liraglutide, a GLP-1RA prototype (1mol/kg/day) , or vehicle prior to femoral artery wire injury. In LFD- as well as in HFSD-fed IR-floxed controls, liraglutide decreased neointimal area (NA) and intima-to-media ratio (I/M) . In LFD-fed endothelial IR deficient mice liraglutide had no effect. These data suggest that IR in ECs is important for the anti-restenotic effect of GLP1-RA, which is preserved in Western diet induced insulin resistant conditions unlike the effect of insulin. *First and second authors contributed equally

Disclosure

M.Gonzalez: None. Z.Liu: None. A.Giacca: None.
463-P: Effects of Imeglimin, a New Oral Hyperglycemic Agent, on High Glucose and Low Glucose–Induced Cell Death and Mitochondrial Dysfunction in Schwann Cells
Authors: KATO AYAKO , TATSUMI YASUAKI , NIHEI WATARU , YAKO HIDEJI , HIMENO TATSUHITO , KONDO MASAKI , KATO YOSHIRO , NAKAMURA JIRO , KAMIYA HIDEKI , SANGO KAZUNORI , KATO KOICHI
Published: May 2022

It is known that hyperglycemia-induced oxidative stress is a major cause of the pathogenesis of diabetic neuropathy, and hyperglycemia-induced mitochondrial ROS production is considered as one pivotal mechanism of increased oxidative stress. On the other hand, imeglimin is a new class of oral hypoglycemic agents called “glymines” containing tetrahydrotriazines, which targets mitochondrial dysfunction. We investigated the effects of imeglimin on cell death and mitochondrial dysfunction induced by high glucose and low glucose in Schwann cells. Immortalized adult mouse Schwann (IMS32) cells were cultured for 1 hour in the medium with normal glucose concentration of 5.5 mM, low glucose of 2.5 mM, and high glucose of 25 mM. Compared to normal glucose, not only high glucose but also low glucose decreased cell viability of IMS32 cells and increased mitochondrial oxidative stress. Mitochondrial membrane potential was also decreased either by high glucose or low glucose. In addition, mitochondrial oxygen consumption rate (OCR) was increased by low glucose as well as high glucose. Mitochondria isolated from IMS32 cells exposed to high glucose and low glucose for 1 hour exhibited increased activity of complex I. The expression of complex I protein was unchanged by high glucose for 1 hour. Imeglimin ameliorated the decrease in cell viability and improved the mitochondrial dysfunctions via inhibiting the increase of mitochondrial oxidative stress, OCR and the activity of complex I caused by high glucose and low glucose. These results indicate that hyperglycemia and hypoglycemia induce mitochondrial dysfunction in nerves, and that imeglimin may prevent against diabetic neuropathy by attenuation mitochondrial dysfunction and cell death in Schwann cells.

Disclosure

T. Himeno: None. J. Nakamura: None. H. Kamiya: Research Support; Abbott Japan Co., Ltd., Eli Lilly and Company, Japan Tobacco Inc., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Company Limited, Terumo Corporation. Speaker's Bureau; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharma K.K., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd. K. Sango: None. K. Kato: None.
467-P: The Relationship between Diabetic Peripheral Neuropathy and Metformin Treatment in Type 2 Diabetes Mellitus
Authors: PAN QI , LUO JINGYI , GUO LIXIN
Published: May 2022

Background: Metformin is the first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM) . However, the use of metformin may lead to neuropathy by affecting the absorption of vitamin B12. Our objective was to explore the association between the application of metformin and diabetic peripheral neuropathy (DPN) .

Methods: The multicenter randomized cross-sectional study was conducted in 13 hospitals in Beijing from October 2015 to April 2016. T2DM Patients were divided into confirmed DPN group, suspected DPN group and non-DPN group by the five physical examinations (Ankle reflex, acupuncture pain, temperature, vibration, and pressure) . Non-parametric Mann-Whitney test was used for the comparison between non-normally distributed variables between two groups. Chi-square test was used for the comparison of categorical variables. The risk factors of DPN in T2DM Patients were assessed using logistic regression.

Results: Compared with patients without metformin, patients taking metformin were more likely to suffer from DPN and suspected DPN (P < 0.0for both) . Similar results were obtained after stratifying the data based on age, BMI, and HbA1c. It was shown that the application of metformin was a risk factor for DPN (OR = 5.06, 95%Cl: 3.90-6.56; P < 0.001) and suspected DPN (OR = 3.58, 95%Cl: 2.78-4.62; P < 0.001) in T2DM patients after the adjustment for age, BMI and HbA1c. In addition, prolonged application of metformin, increased cumulative and single doses would also be associated with the risk of DPN (P < 0.0for all) .

Conclusion: The application of metformin was observed relate to DPN in T2DM patients. The vitamin B12 concentration and peripheral nerve function of T2DM patients with the application of metformin should be monitored.

Disclosure

Q.Pan: None. J.Luo: None. L.Guo: None.

Funding

National Key R&D Program of China (2020YFC2009006)
469-P: Sodium–Glucose Cotransporter 2 Inhibitors Decrease the Frequency of Antivascular Endothelial Growth Factor Agent Injection in Patients with Type 2 Diabetes Complicated by Diabetic Macular Edema
Authors: ISHIBASHI RYOICHI , KOSHIZAKA MASAYA , MAEZAWA YOSHIRO , YOKOTE KOUTARO , TAKATSUNA YOKO , TATSUMI TOMOAKI , YAMAMOTO SHUICHI , INABA YOSUKE , SHIKO YUKI , KAWAKAMI EIRYO
Published: May 2022

Aims: Diabetic macular edema (DME) leads to impaired vision. The first line of treatment is intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent. However, there are patients who are refractory to this. We reported patients whose DME were refractory to anti-VEGF agents and showed improvement by using sodium glucose cotransporter 2 inhibitors (SGLT2is) . The effectiveness of SGLT2is for DME was assessed using a health insurance claim database.

Methods: The JMDC inc. database covering million Japanese patients between 2005-20was used for analysis. Patients with type 2 diabetes (T2D) with DME were included, and those who were undergo dialysis, had other ocular diseases that may be treated by anti-VEGF agents, or were not on treatment with any antidiabetic drug introduced after 2014 were excluded. Propensity score matching was performed between SGLT2i users and non-users. The frequency and the duration of intravitreal injection of anti-VEGF agent after the period from the start of SGLT2is or other antidiabetic drugs were analyzed.

Results: In this study, 340 matched patients with T2D were analyzed. Initiation of SGLT2is revealed a decrease in the frequency of anti-VEGF agent injection (2.7 ± 4.1 vs. 3.8 ± 4.6 times, p < 0.001; the Wilcoxon signed rank test, p < 0.001, 95%CI -0.25 to -0.085; the Poisson regression, p < 0.001, HR 0.80, 95% CI 0.73 to 0.87; the recurrent event analysis) and an extension in the duration for the requirement of the first injection of anti-VEGF agent (the number of patients who received no anti-VEGF agents, 96 vs. 32, p < 0.001; the log-rank test) .

Conclusion: Using SGLT2is for patients with T2D complicated by DME extended the duration for the requirement of the first anti-VEGF agent injection and decreased the frequency of anti-VEGF agent injection. SGLT2is may be an option for DME treatment.

Disclosure

R.Ishibashi: Research Support; Astellas Pharma Inc., Boehringer Ingelheim International GmbH, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., YL Biologics, ZERIA Pharmaceutical Co.,Ltd. E.Kawakami: None. M.Koshizaka: None. Y.Maezawa: None. K.Yokote: None. Y.Takatsuna: None. T.Tatsumi: None. S.Yamamoto: None. Y.Inaba: None. Y.Shiko: None.
472-P: Sex Differences in the Effect of High Serum Uric Acid on the Incidence of Vision-Threatening Retinopathy in Those with Type 2 Diabetes
Authors: YAMAMOTO MASAHIKO , FUJIHARA KAZUYA , ISHIGURO HAJIME , YAGUCHI YUTA , ISHIZAWA MASAHIRO , YAMADA MAYUKO H. , OSAWA TAEKO , KITAZAWA MASARU , KANEKO MASANORI , MATSUBAYASHI YASUHIRO , IWANAGA MIDORI , YAMADA TAKAHO , KODAMA SATORU , SONE HIROHITO
Published: May 2022

Elevated serum uric acid reportedly increases the risk of development and progression of diabetic retinopathy with conflicting results. However, whether it also increases the incidence of severe vision-threatening diabetic eye diseases has been scarcely investigated. Also unknown is whether there are sex differences in the incidence of advanced retinopathies. To clarify this, we utilized ICD-and medical treatment codes from a nationwide claims database that finally included 13,721 type 2 diabetes patients (mean age 50 y, HbA1c 7.0%, mean follow-up period 5.8 y, 10,962 men) . During the study period, 388 patients developed vision-threatening treatment-required diabetic eye diseases (4.9/1000 person-years) . Multivariate Cox analysis demonstrated that a serum uric acid ≥7.1 mg/dl was significantly positively associated in men with future occurrence of treatment-required diabetic eye diseases, but not in women. Hazard ratios for those with serum uric acid ≥7.1 mg/dl for incident treatment-required diabetic eye diseases were 1.36 (95% confidence interval, 1.01-1.85) in men and 2. (0.71-6.08) in women, compared with the reference group (<7.1 mg/dl) after adjusting for covariates. This finding suggested that the effect of high serum uric acid on the development of vision-threatening retinopathy in individuals with type 2 diabetes differed between men and women. Although estrogen-induced effects, decreased antioxidant activity, and increased oxidative stress may partially explain the differences in results between men and women, further investigation is needed.

Disclosure

M. Yamamoto: None. K. Fujihara: None. H. Ishiguro: None. M. Ishizawa: None. M.H. Yamada: None. T. Osawa: None. M. Kitazawa: None. M. Kaneko: None. M. Iwanaga: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited.

Funding

The Japan Society for the Promotion of Science and the Ministry of Health, Labor and Welfare, Japan. (18K17897)
474-P: Efficacy of Saroglitazar on Diabetes Dyslipidemia with Higher Triglyceride
Authors: SINHA AJAY
Published: May 2022

Objectives: Diabetes and diabetic dyslipidemia with high triglycerides (TGs) are commonly associated. Saroglitazar is the first dual PPAR α/γ agonist which has been approved in India for diabetes dyslipidemia management. This study aimed at evaluation of the efficacy and long-term safety of Saroglitazar on diabetic dyslipidemia with very high triglyceride (>500 mg/dl) in real-world clinical practice.

Methods: This investigation took up the form of a real-world retrospective observational study. In this retrospective study, we identified 150 patients with diabetic dyslipidemia with triglycerides >500 mg/dL at baseline) . They were treated with Saroglitazar once daily.

Results: Significant reduction of TG and LDL-cholesterol was observed from baseline to 12th weeks 669.93±81.22 to 268.72±82.32 mg/dl and from 167.68±10. to 118.88±12 mg/dl. This study showed that in addition to statins, Saroglitazar paved the way for significant improvement in all the lipid parameters. At 52 weeks, a reduction in values of TG of 66.9%, LDL-C of 38.47%, total cholesterol of 44.84 %, and non- HDL-C of 52.62 % was evident. Adding Saroglitazar in patients on existing antidiabetic medications had highlighted a crucial 0.8% absolute reduction in HbA1c. Significant amounts of improvements in postprandial plasma glucose and fasting have also been seen.

Conclusion: This study concludes that there are no adverse alterations in serum creatinine and edema. Saroglitazar can be considered as an effective therapeutic option in diabetic dyslipidemia with very high triglycerides levels. It is very safe for long-term use.

Disclosure

A.Sinha: None.
477-P: Vagal GLP-1–Mediated Reductions in Postprandial Lipids Are Sensitive to Fructose Feeding
Authors: HOFFMAN SIMON S. , ALVARES DANIELLE C. , ADELI KHOSROW
Published: May 2022

Dyslipidemia is a common co-morbidity of insulin resistance, where chronic elevations in hepatic and intestinal lipoproteins are linked to cardiovascular disease. Postprandial production is regulated in-part by gut-derived hormones such as glucagon-like peptide (GLP) -1. Although degradation-resistant analogs of GLP-1 continue to work in diabetic individuals, none have examined whether GLP-1s endogenous neuroendocrine signalling pathways are affected by diet-induced dyslipidemia. Thus, we sought to test whether native GLP-1 could modulate postprandial lipids in a fructose-fed hamster model.Hamsters were fed either a chow or fructose-enriched (FF) diet for 14 days, then received a portal vein injection of either GLP-1 (7-36) or vehicle control to examine if they remained responsive to portal GLP-1. Separately, in hamsters fed either chow or a fat/fructose/cholesterol enriched (FFC) diet we performed nodose ganglia (NG) injections with GLP-1 (7-36) or vehicle. To recapitulate the loss of vagal GLP-1R signalling in the absence of dietary intervention we selectively deafferented GLP-1R containing NG neurons via injection of the cytotoxin saporin conjugated to exendin-4. After treatment, animals received a gavage of olive oil and an intraperitoneal injection of poloxamer to prevent lipoprotein clearance. Postprandial triglyceride-rich lipoproteins isolated via density ultracentrifugation were assessed via blood draws over a 6-hour period.Chow-fed hamsters saw significant reductions in post-prandial lipids after portal GLP-1 injection, whereas FF-fed hamsters were unaffected. Chow-fed hamsters were similarly responsive to GLP-1 (7-36) injection into the NG, displaying reduced postprandial lipids; however, FFC-fed hamsters showed no reduction in plasma lipids. Finally, selective deafferentation of NG GLP-1R-containing neurons caused significant rises in postprandial TG and TRL, underscoring the importance of GLP-1R insensitivity in states of metabolic disease.

Disclosure

S.S.Hoffman: None. D.C.Alvares: None. K.Adeli: None.

Funding

CIHR Foundation Grant
489-P: Flap Reconstructions for Gangrenous COVID Toes
Authors: SWERDLOW MARK , KRESS GAVIN T. , SHIN LAURA
Published: May 2022

Objective: Describe the clinical courses of and reconstructive methods utilized for two patients with diabetes who presented with gangrenous feet following Covid-and required partial foot amputations.

Background: Covid-produces mainly respiratory symptoms but has a variety of atypical presentations and sequelae. Serious complications are increased in patients with underlying medical conditions such as diabetes mellitus. By generating a prothrombotic milieu, SARS-CoV-2 increases the risk for arterial and venous thromboses. Inflammatory damage and micro-thromboses are thought to contribute to acro-ischemia, colloquially known as “Covid Toes,” which presents cutaneously as chilblain-like lesions.

Case Report: (1) A 57 year old female presented to vascular clinic with pedal gangrene one month after developing painful discoloration in her right toes. After angioplasty restored pedal blood flow, she received a TMA with a local fillet flap. (2) A 41 year old female presented to vascular clinic with extensive pedal gangrene three months after hospitalization for Covid-19. After arteriotomy improved pedal blood flow, she underwent a Lisfranc amputation followed by SCIP flap reconstruction.

Conclusion: Sufficient evidence suggests that Covid-impairs microcirculatory function and can be especially detrimental in diabetic patients. Reconstructive techniques in patients with severe Covid Toes help patients regain functionality.

Disclosure

M.Swerdlow: None. G.T.Kress: None. L.Shin: None.
49-LB: Use of Financial Incentives to Promote Adolescent Type 1 Diabetes Self-Management—A Pilot Randomized Controlled Trial
Authors: MALIK FAISAL , CHEN TOM , MANZUETA MARIA , YI-FRAZIER JOYCE , PIHOKER CATHERINE , LEBLANC JESSICA L. , SHAH SEEMA K. , WRIGHT DAVENE
Published: May 2022

Background: Providing individuals with immediate, consistent inducements for health behaviors that do not provide proximal tangible benefits may promote adherence to diabetes self-management behaviors.

Objective: To evaluate whether financial incentives lead to improvement in glycemic control and self-management behaviors in adolescents with type 1 diabetes.

Methods: We conducted a randomized controlled crossover study with 12-18 year olds with type 1 diabetes. Adolescents self-selected target self-management behaviors (e.g., increase continuous glucose monitor [CGM] sensor wear time) and outcome goals (e.g., improve time in range [TIR]) and could earn up to $180 in each 3-month intervention cycle. Adolescents cycled through 3 study arms every 3 months: gain-framed payment where adolescents earned money for meeting behavioral goals, loss-framed payment where adolescents lost a portion of a weekly payment for not meeting behavioral goals, and usual care. Adolescents earned or lost $1.75 per day in the financial incentives arms, and a $2.75 weekly bonus for meeting their outcome-based goal. Goals were modeled against study arms with generalized linear mixed models to account for the longitudinal nature of the crossover design.

Results: Out of 39 participants (mean age 16.1 years, 54% male, mean baseline HbA1c 9.42%, 38% insulin pump use, 95% CGM use) , 34 completed the trial. Mean HbA1c aggregated over all interventions was lower compared to baseline at 9.07% (p=0.13) and there was no difference in HbA1c among the 3 arms. Compared to the mean TIR for those under usual care of 39%, mean TIR under gain- and loss-frames were 45% (p<0.01) and 43% (p<0.01) , respectively. Compared to a mean 41% behavioral goal attainment within usual care, mean behavioral goal attainment under gain- and loss-frames were 50% (p<0.01) and 45% (p<0.01) , respectively.

Conclusions: Financial incentives can improve adolescent self-management behaviors and time in range in the short term and merits further longitudinal study to evaluate the effects on glycemic control and health care utilization.

Disclosure

F. Malik: n/a. T. Chen: None. M. Manzueta: None. J. Yi-frazier: None. C. Pihoker: None. J. L. Leblanc: None. S. K. Shah: None. D. Wright: None.

Funding

American Diabetes Association (1-18-ICTS-100)
493-P: Medical Assistant Health Coaching for Type 2 Diabetes in Primary Care: A Pragmatic, Cluster-Randomized Controlled Trial
Authors: FORTMANN ADDIE L. , PHILIS-TSIMIKAS ATHENA , CLARK TAYLOR , BAGSIC SAMANTHA R. SPIERLING , SANDOVAL HALEY , SAVIN KIMBERLY L. , ROESCH SCOTT , GALLO LINDA
Published: May 2022

While good cardiometabolic control can reduce complications in type 2 diabetes (T2D) , many individuals do not achieve clinical targets. This real-world trial compared medical assistant health coaching (MAC) to usual care (UC) in improving outcomes among adults with T2D and ≥ 1 of the following in the past 90 days: HbA1c ≥ 8%, LDL ≥ 100 mg/dL, SBP ≥ 140 mm/Hg. This N=600 study was conducted from 2016-2021 at four cluster-randomized clinics within two diverse health systems in Southern CA: a large, private insurance-based system [n = 298, majority non-Hispanic White, English-speaking, mid/upper socioeconomic status (SES) ]; M age = 70.2 ± 12.6] and a Federally-Qualified Health Center (n = 302, majority Hispanic, Spanish-speaking, lower SES; M age = 56.9 ± 12.0) . MAC and UC received diabetes care as usual in primary care, with referral to diabetes education and/or specialists as indicated. MAC also received in-clinic and telephone-based health coaching for up to one year (1-14 sessions; M = 5.2 ± 2.8) . Baseline mean HbA1c = 8.8 ± 2.2%, LDL = 101.8 ± 44.8 mg/dL, and SBP = 137.9 ± 19.4 mm/Hg. From baseline to 12-months, the percentage of individuals meeting quality metrics increased in both groups: HbA1c < 8% (MAC: 74.8 to 79.9%; UC: 64.0 to 80.4%) , LDL < 100 mg/dL (MAC: 75.7 to 84.9%; UC: 72.6 to 82.4%) , SBP < 140 mm/Hg (MAC: 75.0 to 86.9%; UC: 80.2 to 86.4%) . When outcomes were analyzed continuously using multi-level modeling, both MAC and UC demonstrated statistically significant improvements on all clinical outcomes; however, the rate of improvement was largely equivalent across groups (time-by-group ps > .05) . Due to the pragmatic nature of this trial, there was marked variation (by design) in intervention duration and intensity across participants, and in clinical and sociodemographic characteristics of participants across health systems. Additional analyses examining under what conditions and/or for whom the MAC intervention may prove more/less effective will be presented.

Disclosure

A.L.Fortmann: Consultant; Ascensia Diabetes Care, Employee; Dexcom, Inc. A.Philis-tsimikas: Advisory Panel; Bayer AG, Novo Nordisk, Research Support; Lilly Diabetes, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk, Viking Therapeutics. T.Clark: None. S.R.Spierling bagsic: None. H.Sandoval: None. K.L.Savin: None. S.Roesch: None. L.Gallo: None.

Funding

NIH/NIDDK 1R18DK104250
5-LB: Dulaglutide in Youth with Type 2 Diabetes (T2D) —Results of the AWARD-PEDS Randomized, Placebo-Controlled Trial
Authors: ARSLANIAN SILVA A. , CHO JANG IK , HANNON TAMARA S. , ZEITLER PHILIP , CHAO LILY , BARRIENTOS MARGARITA , BOUCHER-BERRY CLAUDIA C. , BISMUTH ELISE , DIB SERGIO A. , COX DAVID
Published: May 2022

AWARD-PEDS was a Phase 3 trial to assess the efficacy and safety of dulaglutide (DU) , a once-weekly GLP-1 receptor agonist, in youth (10 to <18 years old) with T2D treated with lifestyle alone or on stable metformin with or without basal insulin. Participants (mean age, 14.5 yrs; mean BMI, 34.1 kg/m2) were randomized to placebo (N=51) , DU 0.75 mg (N=51) , or DU 1.5 mg (N=52) . The primary aim was to demonstrate superiority of DU (pooled doses) vs. placebo for change in HbA1c at 26 weeks. Analyses included all patients with ≥1 dose of study drug, excluding data after initiation of rescue therapy. DU was superior to placebo (figure) in improving glycemic control measured by change in HbA1c, percent of patients with HbA1c <7%, and change in fasting glucose at Week 26. No effect of DU was observed on BMI change (p=0.776) . Fewer patients assigned to DU compared to placebo required rescue therapy (2.9% vs. 17.6% respectively, p=0.003) . Incidence of common GI adverse events was higher in DU group vs. placebo [nausea (14.6% vs. 7.8%) , vomiting (15.5% vs. 3.9%) , diarrhea (18.4% vs. 13.7%) ] but comparable to that observed in adults.

In conclusion, in youth with inadequately controlled T2D treated with or without metformin and/or basal insulin, once weekly DU 0.75 mg or 1.5 mg was superior to placebo in improving glycemic control without an effect on BMI through 26 weeks, with a safety profile consistent with that established in adults.

Disclosure

S. A. Arslanian: Advisory Panel; Eli Lilly and Company, Novo Nordisk. Research Support; Eli Lilly and Company, Novo Nordisk. Other Relationship; AstraZeneca. J. Cho: None. T. S. Hannon: Advisory Panel; Eli Lilly and Company. P. Zeitler: Consultant; Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Takeda Pharmaceutical Company Limited. L. Chao: None. M. Barrientos: Research Support; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Research & Development, LLC, Novo Nordisk. C. C. Boucher-Berry: None. E. Bismuth: None. S. A. Dib: None. D. Cox: Employee; Eli Lilly and Company.

Funding

Eli Lilly and Company
5-OR: Tcf21 Functions as a Rate-Limiting Factor during Visceral Adipose Tissue Development
Authors: LIU QIANGLIN , LI CHAOYANG , GAO PEIDONG , WANG LESHAN , LI YUXIA , SHIRI MOHAMMAD , ALKAIFI FOZI N. , SUN JIANGWEN , FU XING
Published: May 2022

Using an inducible lineage-tracing mouse line, we identified that Tcf21, a bHLH transcription factor gene, is expressed in visceral adipose tissue (VAT) but not in subcutaneous adipose tissue. In VAT, Tcf21 is expressed in mesenchymal progenitor cells but not in adipocytes. Tcf21 lineage progenitor cells actively proliferate followed by differentiation into adipocytes during neonatal development but have limited adipogenic capacity in adult mice even when fed with a high-fat diet (HFD) . Bulk RNAseq and ATACseq analyses of Tcf21 lineage progenitor cells isolated from mice of different ages or adiposities revealed the dynamic gene expression and chromatin accessibility in Tcf21 lineage progenitor cells. In particular, higher expression of pro-mitotic genes was observed in neonatal mice followed by an elevation of pro-adipogenic gene expression. Increased expression of inflammatory genes and fibrotic genes was observed in Tcf21 lineage progenitor cells from obese mice. Using transcriptomic and motif enrichment data, we constructed a gene regulatory network mediating the gene expression changes in Tcf21 lineage progenitor cells. Single-cell RNAseq and immunostaining identified multiple subpopulations of Tcf21 lineage cells including 2 major subpopulations including a mesothelial subpopulation and an interstitial subpopulation. Using an inducible cell-type-specific Tcf21 KO mouse line, we identified that neonatal deletion of Tcf21 in Tcf21 lineage progenitor cells led to their increased adipogenic differentiation during postnatal development and improved metabolism after HFD treatment. In vitro loss-of-function and gain-of-function studies showed that Tcf21 inhibits the adipogenic differentiation of VAT progenitor cells. Mechanistic studies identified that Tcf21 inhibits adipogenesis and developmental progress of VAT progenitor cells through promoting the expression of Dlk1, a negative regulator of adipogenesis, mainly in the interstitial subpopulation.

Disclosure

Q.Liu: None. C.Li: None. P.Gao: None. L.Wang: None. Y.Li: None. M.Shiri: None. F.N.Alkaifi: None. J.Sun: None. X.Fu: None.

Funding

Louisiana Board of Regents (BOR.Fu.LEQSF (2019-22) -RD-A-01) ; NIH/NIDDK (1R15DK122383) ; NIH/NIGMS (P20GM130555) ; NIH/NHLBI (1R01HL157519) .
511-P: Perspective on Technology Training in Individuals with Type 1 Diabetes
Authors: ANDRE CAMILLE C. , LIAO XIYUE
Published: May 2022

The importance of training on diabetes technology has significantly changed with rapidly increasing use of technology in diabetes care, including use of insulin pumps, continuous glucose monitors, and automated insulin delivery (AID) systems. This study aimed to assess patient perspectives on technology training, and how nutrition, exercise and other aspects of health are discussed during healthcare appointments.

We conducted an IRB approved 42 question online survey for people living with type 1 diabetes (T1D) . Participants were recruited from the T1D Exchange Online Community by email over a 3 week period. Survey questions covered education on diabetes technology, nutrition, mental health and other medical conditions.

Of the 666 adult respondents, 581 reported receiving care from an endocrinologist and 533 used an insulin pump. With regard to advanced pump features, 55% reported their provider educated them on use of temporary basal rates for exercise, while 38% learned about temporary rates from a T1D online community, and 6.2% learned from a friend. Less than 50% of participants using an AID system talked with their provider about settings adjustments around exercise. Provider education around nutrition focused mainly on carb counting vs. other topics (low carb diet, food choices, effect on blood sugar; p=0.03) . Only 30% reported receiving education from their provider on use of advanced pump features around meals, and only 13% reported their provider discussed healthy eating often or always at clinic visits. Participants expressed a strong desire to receive education on low carb diets and different food choices as their primary need.

People with T1D continue to seek and receive advice for important topics related to diabetes management from online communities. They also seek information regarding nutrition and technology that is not discussed frequently at visits with their provider. Further development of educational materials for providers and people with T1D should address these needs.

Disclosure

C.C.Andre: None. X.Liao: None.
513-P: Diabetes Mobile Apps: A Resource for Inpatient Education and Support?
Authors: KRALL JODI S. , NG JASON , SIMINERIO LINDA M.
Published: May 2022

Diabetes mellitus (DM) -related hospitalizations are recognized as important opportunities for self-management intervention. Yet, there remains a need for practical delivery strategies.

Objective: To assess provider perspectives on DM mobile apps as a tool for self-management education and support in the inpatient setting.

Methods: Healthcare professionals (n=33) who oversee or provide DM care and education to hospitalized patients completed a validated survey about DM mobile apps.

Results: Only 21% of respondents had previously used an app for DM education. Of those who had never used a DM app, 100% indicated that they would consider recommending one to their patients. For 82% of respondents, patient access to and interest in app use were rated as the most important factors in their decision to recommend apps. Patient acuity and time were also noted as key considerations. In fact, 54% of respondents were only willing to spend 5 minutes to download and teach app use. Hospitalized patients considered best candidates for apps are those newly diagnosed with DM, new to insulin, admitted with a DM-related complication, or requiring additional education/support (change in treatment plan) . Perceived benefits of apps in relation to self-management were to reinforce education (71%) , support education with trustworthy information (62%) , and serve as a resource after discharge (56%) . Some respondents also foresaw a role for apps in teaching patients during hospitalization, especially younger patients generally viewed as more interested in apps. Most respondents agreed the following features are important for apps in education and support: Content is developed by DM experts (91%) , provide answer to basic DM self-management questions (96%) , user experience can be customized (91%) , and include features for logging/tracking glucose results (91%) .

Conclusions: Hospital-based providers offer valuable insights into DM app use. Exposing them to apps to support patient self-management warrants strong consideration.

Disclosure

J.S.Krall: Research Support; Becton, Dickinson and Company, Sanofi. J.Ng: Research Support; Sanofi. L.M.Siminerio: Advisory Panel; Abbott, Bayer AG, Research Support; Becton, Dickinson and Company, Sanofi.

Funding

Becton, Dickinson and Company
523-P: The Results of Virtual Diabetic “Boot Camp”
Authors: CHEN YI-JU , UDEH UBA C. , RAJAK KRIPA , AMIRIAN ASLAN , ATRASH ANAS , YARI KOLSOUM , JOSHI RENU
Published: May 2022

Introduction: The use of telemedicine exponentially increased during the COVID-pandemic as it provided easier access as well as the provision of safety via social distancing. A 12-week intense telemedicine diabetic Bootcamp was therefore launched for patients with uncontrolled DM intended for high-quality outpatient diabetic care.

Methods: Patients with DM seen at ambulatory clinics with HbA1c > 8.0%, were voluntarily enrolled from September 2020 to November 2021. The dietitians and diabetic educators conducted biweekly visits via telehealth. Patient demographics, HbA1c, BMI, BP were compared before and after the intervention.

Results: A total of 134 patients were included for analysis and 94 patients (70.2%) completed the visits. Mean HbA1c change was -2.09% ± 2.4%, and HbA1c reduction was similarly observed across different age groups, gender, ethnicity, BMI, referred clinic types [Table 1]. A greater HbA1c reduction in patients who completed the visits was noted although it was not statistically significant. We found a negative correlation between the initial HbA1c and the change of HbA1c (coefficient -0.7709, p<0.0001, r2= 0.3899) . No significant BMI or MAP change was observed.

Conclusions: This quality improvement project demonstrated an improvement in HbA1c for all poorly controlled diabetic patients, regardless of patient characteristics. Moreover, higher initial HbA1c was associated with a greater HbA1c reduction.

Disclosure

Y.Chen: None. U.C.Udeh: None. K.Rajak: None. A.Amirian: None. A.Atrash: None. K.Yari: None. R.Joshi: n/a.
525-P: The Influence of Age of on the Weight Loss Outcome of Women in the National Diabetes Prevention Program
Authors: OTTUR MEGHANA , COOKE GREGG , RAJAN SINDHU
Published: May 2022

In the National Diabetes Prevention Program (DPP) developed by the CDC, participants receive health-coach facilitated education on lifestyle modification to develop better eating and exercise habits with the goal of losing 5-7% weight over the course of a year. Incorrect assumptions about weight loss can lead to reduced participation and low outcomes in DPP. This study aims to determine the truth of common assumptions about weight loss and the impact that such assumptions have on the effectiveness of DPP. A common assumption observed is that women of menopausal age (45-60) find it more difficult to lose weight and we hypothesized that women at the menopausal age will achieve the weight loss goal at a slower rate compared to younger women of pre-menopausal age (18-44) .

Weight loss is defined as the difference between initial and final weight as a percentage of initial weight; a positive value indicates weight loss. Effectiveness is defined as the percentage of participants who achieve a specific weight loss threshold. The data used was the number of days until each participant achieved the weight loss goal of 5%. This was divided into two groups: 641 women aged 45-60) , and 278 women aged 18-44. A Students t-test was then performed on the data sets to measure the effect of assumptions about menopause and weight loss.

Contrary to the hypothesis, we found that menopausal women to be just as likely to achieve the 5% weight loss goal as pre-menopausal women in the same amount of time. This indicates that the assumption is untrue, however it is a useful assumption in the sense that it can encourage menopausal women to lose weight.

Disclosure

M.Ottur: None. G.Cooke: None. S.Rajan: None.
534-P: Sustained Improvement of Whole-Body Oxidative Capacity but Not Insulin Sensitivity after Detraining of People with Type 2 Diabetes
Authors: MASTROTOTARO LUCIA , APOSTOLOPOULOU MARIA , SAATMANN NINA , GRANATA CESARE , HARTWIG SONJA , KARUSHEVA YANISLAVA , GANCHEVA SOFIYA , LEHR STEFAN , AL-HASANI HADI , SZENDROEDI JULIA , RODEN MICHAEL
Published: May 2022

High-intensity interval training (HIIT) improves skeletal muscle mitochondrial oxidative capacity in humans with different degrees of insulin sensitivity, whereas it increases insulin sensitivity along with number of circulating small extracellular vesicle (SEV) mainly in insulin resistant individuals with or without T2D (T2D, IR) . In order to examine the sustainability of metabolic effects induced by HIIT, this study tested whether the observed effects on insulin sensitivity, oxidative capacity and SEV number remain and/or differ between insulin sensitive (IS) , IR and T2D humans.

Twenty T2D and age- and BMI-matched IR and 12 IS individuals (HbA1c in %: 7.2±0.2, 5.4±0.1, 5.4±0.1; M-value in mg*kg-1*min-1: 3.0±0.4, 4.2±0.4, 7.4±0.4) performed a 12-week HIIT cycling protocol for 3 d/week. Whole-body insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamps, physical fitness (VO2max) by spiroergometry and myocellular pathways of insulin sensitivity by immunoblotting of muscle biopsies at baseline, 72 h after the last HIIT bout and 4 weeks (detraining) later. SEV were isolated from serum by size exclusion chromatography.

Compared to HIIT, insulin sensitivity decreased in T2D after detraining (p<0.01) , instead VO2max decreased in T2D and IR (p<0. and p<0.05) , although it remained higher than baseline (p<0.0 and p=0.05) . Of note, HIIT-induced reduction of the nuclear factor-κB protein (p<0.vs. baseline) disappeared in IR after detraining, whereas decreased protein kinase Cε activity was sustained in T2D (p<0.vs. HIIT and p<0.vs. baseline) , who also showed higher circulating SEV number (p<0.vs. baseline) .

In conclusion, HIIT-induced increases in physical fitness and SEV number, but not insulin sensitivity are maintained at least after short-term detraining in T2D. Characterization of SEV cargo might help to better understand the differences in metabolic responses to detraining in individuals with and without T2D

Disclosure

L.Mastrototaro: None. J.Szendroedi: Advisory Panel; Boehringer Ingelheim International GmbH. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. M.Apostolopoulou: n/a. N.Saatmann: None. C.Granata: None. S.Hartwig: None. Y.Karusheva: None. S.Gancheva: None. S.Lehr: None. H.Al-hasani: Consultant; Bayer AG.
535-P: The Effect of Starting Blood Glucose Levels on Electrolyte Balance During and After Exercise in Type 1 Diabetes
Authors: MOMENI ZEINAB , BOULÉ NORMAND G. , PRADO CARLA , YARDLEY JANE E.
Published: May 2022

ADA guidelines recommend that people with type 1 diabetes (PWT1D) start exercise with blood glucose (BG) levels of 7-mmol/L. Those fearing hypoglycemia often start higher, which may affect kidney function and electrolyte balance. We examined serum and urine electrolyte concentration during aerobic exercise (cycling 45 min at 60%VO2peak) in PWT1D (10F/2M, mean±SD: age 29±7 years, VO2peak 37.8±7.6 mL/kg/min, A1C 7.6±0.8%) and age, sex, and fitness-matched controls. Control participants (CON) completed a single exercise session with BG in normal physiological range, while PWT1D completed two sessions with different starting BG levels: 8-mmol/l (MOD) , and 12-14 mmol/l (HI) .

Urine specific gravity, glucose and potassium were higher during exercise and recovery in MOD when compared to CON (effect of treatment p<0.05) , with only urine glucose being higher in HI when compared to MOD (effect of treatment p<0.05) . Serum sodium, potassium, magnesium, and calcium increased from pre to post exercise in all sessions, with sodium being higher, and magnesium and calcium being lower in MOD versus CON (effect of treatment p<0.05) . There was no difference in these electrolytes between MOD and HI sessions (effect of treatment p>0.05) in PWT1D. Serum glucose decreased during exercise in MOD and HI sessions (effect of time p<0.05) , with serum glucose being higher during the HI session (effect of treatment p<0.05) . The lack of significant differences in electrolytes between MOD and HI sessions suggests that exercise with higher BG levels does not pose immediate risk during exercise of moderate intensity and duration. Further studies should examine the impact of hyperglycemia on electrolyte balance during longer or more intense exercise sessions.

Disclosure

Z.Momeni: None. N.G.Boulé: None. C.Prado: Consultant; Pfizer Inc., Other Relationship; Abbott, Fresenius Kabi, Nestle Health Science, Nutricia. J.E.Yardley: Research Support; Abbott, Dexcom, Inc., LifeScan, Speaker's Bureau; Abbott Diabetes.

Funding

Alberta Diabetes Institute
537-P: Timing of Moderate-to-Vigorous Physical Activity Is Associated with Improvements in Glycemic Control in Type 2 Diabetes in the Look AHEAD Study
Authors: QIAN JINGYI , XIAO QIAN , WALKUP MICHAEL P. , CODAY MACE , ERICKSON MELISSA , UNICK JESSICA L. , JAKICIC JOHN M. , HU KUN , SCHEER FRANK A. , MIDDELBEEK ROELAND
Published: May 2022

Background: We examined the association of time-of-day bout-related moderate-to-vigorous physical activity (bMVPA) with changes in glycemic measures and use of antidiabetic medications in adults with type 2 diabetes.

Methods: Look AHEAD participants were randomly assigned to a lifestyle intervention or a control group, in which the most intensive intervention occurred in Year 1. Among 1755 participants (age, mean ± SD 60 ± 7 years; 57% women) with 7-day waist-worn accelerometry data at Year 1, we grouped them by the timing of bMVPA (≥3 METs in ≥min bouts) : ≥50% of bMVPA during the same time period (Morning, Midday, Afternoon, or Evening; N=191-258) , <50% of bMVPA in any time period (Mixed; N=379) , and ≤1 day with bMVPA per week (Inactive; N=485) . Analyses were adjusted for covariates including socio-demographic factors, randomization arm, and clinics; then further adjusted for weekly bMVPA volume and intensity.

Findings: Timing of bMVPA was associated with changes in HbA1c across Year 1 (P=0.01) , independent of weekly bMVPA volume and intensity. Participants in the afternoon group as compared to the inactive group had a greater HbA1c reduction (mean: -0.16%; 95%CI: -0.33% to 0%) . Among non-insulin users the odds of discontinuation vs. maintaining or initiating antidiabetic medications across Year 1 trended to differ between the bMVPA timing groups (P=0.09) , with the afternoon group having the highest odds of discontinuation (OR vs. inactive group: 1.86; 1.14 to 3.02) .

Interpretation: Timing of bMVPA may be linked with improvements in glycemic control in adults with type 2 diabetes. While regular physical activity remains to be the cornerstone for blood glucose management in diabetes, our findings suggested that exercise interventions aimed to increase glycemic control in patients with diabetes can be enhanced by engaging in physical activity at specific times of the day. Experimental protocols are needed to test the causality.

Disclosure

J.Qian: None. R.Middelbeek: Research Support; Novo Nordisk. Q.Xiao: None. M.P.Walkup: None. M.Coday: None. M.Erickson: None. J.L.Unick: None. J.M.Jakicic: Advisory Panel; Spark360, Wondr Health, WW International, Inc. K.Hu: None. F.A.Scheer: None.

Funding

National Institutes of Health (K99HL148500, DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, DK56992, R01HL140574, RF1AG059867, RF1AG064312)