bluuebunny/crossref_metadata_2025 huggingface dataset:
1147-P: Pseudo Insulin Resistance: Palmitate Inactivates Insulin Signaling but Stimulates Basal Glucose Uptake in 3T3-L1 Adipocytes
Authors: PODKUYCHENKO NIKITA , MICHURINA SVETLANA , STAFEEV IURII , KHAPCHAEV ASKER Y. , SHIRINSKY VLADIMIR P. , VOROTNIKOV ALEXANDER V.
Published: June 2021

Increased levels of circulating free fatty acids (FFA) is the major risk factor for type 2 diabetes in obesity. While the long-term effects of increased FFA on adipose tissue likely involve latent inflammation, the short-term effects on insulin-sensitive adipocytes are less clear. We treated fully differentiated 3T3-L1 adipocytes with increased concentrations (0.3-1 mM) of a typical FFA, palmitate, for 2 days, and measured insulin stimulation of 2-deoxyglucose (2-DG) uptake. The insulin cascade and AMPK activities, Glut-1 and Glut-4 levels were measured by western blots (WB). Glut-4 translocation was measured either by WB after cell membrane fractionation, or by fluorescence analysis after lentiviral transduction of adipocytes with Glut-4 construct containing C-terminal mCherry and outer Myc epitope insertion in the Glut-4 extracellular loop. While fluorescence of mCherry reported the total Glut-4, that of anti-Myc antibody revealed Glut-4 exposed on the plasma membrane. Palmitate dose dependently increased basal 2-DG uptake, whereas insulin-stimulated uptake and Glut-4 translocation to the plasma membrane were significantly reduced only by high (1 mM) palmitate. High palmitate did not alter Glut-1 and Glut-4 expression, but reduced IRS phosphorylation (Tyr612) and completely ceased that of Akt (Thr308/Ser473) and AS160 (Ser318) in the absence or presence of insulin, as well as phosphorylation of ACC (Ser-79) by AMPK. These results suggest that the short-term effects of palmitate on adipocytes are associated with “pseudo” insulin resistance, i.e., an increased basal glucose uptake likely due to the “pull” mechanism for increased triglyceride turnover, and the loss of insulin stimulation possibly due to fill-up of fat depots.

Disclosure

N. Podkuychenko: None. S. Michurina: None. I. Stafeev: None. A. Y. Khapchaev: None. V. P. Shirinsky: None. A. V. Vorotnikov: None.

Funding

Russian Foundation for Basic Research (20-015-00471)
187-LB: Leveraging Information across Multiple Related Glycaemic Traits Improves Fine-Mapping Resolution
Authors: SOENKSEN JANA , CHEN JI , ASIMIT JENNIFER L. ,   MAGIC, BARROSO INÊS
Published: June 2021

Glycaemic traits fasting insulin (FI), fasting glucose (FG), 2-hour glucose (2hGlu) and glycated haemoglobin (HbA1c) are used to diagnose and monitor type 2 diabetes (T2D). MAGIC (Meta-Analysis of Glucose and Insulin-related traits Consortium) identified 242 loci associated with these traits in 281,416 individuals, from 6 ancestries. European (EUR) ancestry fine-mapping resulted in credible sets accounting for 99% of the posterior probability of association (99CS) with a median of 55 SNPs. Trans-ancestry (TA) fine-mapping led to 99CS with a median of 45 SNPs. Here, we investigated whether fine-mapping resolution could be improved by leveraging data across multiple related traits. We used the novel method FLexible And SHared information Fine-Mapping (flashfm), which takes advantage of sharing of information between traits. We compared its performance with single-trait FINEMAP results. We conducted EUR fine-mapping for 53 loci associated with ≥2 glycaemic traits (p<10-6, N=119 loci-trait associations). EUR ancestry FINEMAP results were used as input for flashfm. Default parameters were used, except a prior odds of 80% (TOdds=0.25) of a shared causal variant across traits was used. 99CS were used to compare single-trait and flashfm results. Flashfm successfully fine-mapped 48 loci (106 locus-trait associations, 5 loci could not be run). At 40/106 locus-trait associations flashfm led to 99CS with ≤10 SNPs, of which 4 had a single SNP, prioritising SNPs for functional follow-up. Fine-mapping across ≥2 traits reduced the number of SNPs in the 99CS in 80.1% (85/106) of locus-trait associations. The median number of SNPs in the 99CS were significantly reduced from 50 to 19 (p=1.1 x10-13). In 47.3% (44/93) of locus-trait associations flashfm reduced the 99CS size compared to TA fine-mapping. Our results show that leveraging data across multiple related traits is a useful approach to improve single-ancestry fine-mapping resolution, and that it may also improve TA fine-mapping.

Disclosure

J. Soenksen: None. J. Chen: None. J. L. Asimit: None. Magic: n/a. I. Barroso: Stock/Shareholder; Self; Incyte Corporation, Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc.

Funding

Research England; Medical Research Council (MR/R021368/1)
195-LB: Lower Nonresponse Rates to 3-Antigen HBV Vaccine among Adults with Diabetes, Age 45 and Over, or Obesity Compared with a Single-Antigen HBV Vaccine: PROTECT Study
Authors: DIAZ-MITOMA FRANCISCO , VESIKARI TIMO , LANGLEY JOANNE M. , HOSSAIN ALOMGIR , MACHLUF NATHALIE , SPAANS JOHANNA , YASSIN-RAJKUMAR BEBI , ANDERSON DAVID E. , POPOVIC VLAD ,   PROTECT STUDY GROUP
Published: June 2021

Diabetes mellitus (DM), older age (≥45 years) and obesity (BMI >30 kg/m2) are associated with lower response to immunizations and worse outcomes of chronic hepatitis B infection. Therefore, there is a need to enhance immunogenicity of HBV vaccine for adults, especially those with DM, older age, and obesity. PROTECT study compared the immunogenicity and safety of 3-doses of 3-antigen / 3A-HBV (Sci-B-Vac) and 1-antigen / 1A-HBV (Engerix-B) HBV vaccines administered at months 0, 1 and 6. The study enrolled 1607 adults age ≥18 years in the US (42.3%), Europe (41.6%) and Canada (16.1%). Immunogenicity, measured as rate of non-response (% not achieving anti-HBs levels ≥10 mIU/mL), anti-HBs geometric mean concentration (GMC), and safety were evaluated in all adults and key subgroups of interest. Of 1607 study participants, 7.5% (3A-HBV arm) and 8.0% (1A-HBV arm) had a stable and well controlled DM (HbA1c <8.5%), 81.4% were age ≥45 years and 36.7% had BMI >30 kg/m2. Overall non-response rates were 23.5% (1A-HBV) and 8.6% (3A-HBV). For diabetics, non-response rates were 41.7% (1A-HBV) and 16.7% (3A-HBV), for those age ≥45 years, 34.3% (1A-HBV) and 16.4% (3A-HBV) and for BMI >30 kg/m2, 31.9% (1A-HBV) and 10.8% (3A-HBV). Mean GMC of anti-HBs was higher for 3A-HBV compared to 1A-HBV (1424.5 vs. 235.4 mIU/mL) and consistently higher across key subgroups, including those with DM, age ≥45 years and BMI >30 kg/m2. Safety of 3A-HBV was comparable to 1A-HBV except for higher rates of injection site pain, tenderness and myalgia of mild to moderate severity and mean duration of 1-2 days. Completion rate of all 3 vaccine doses was high at 96.8% (1A-HBV) and 95.2% (3A-HBV). Immunization with 3A-HBV achieved lower rates of non-response compared to 1A-HBV in all adults, including those with diabetes, older age, and obesity.

Disclosure

F. Diaz-mitoma: Consultant; Self; VBI Vaccines. Protect study group: n/a. T. Vesikari: Research Support; Self; VBI Vaccines. J. M. Langley: Research Support; Self; GlaxoSmithKline plc., Medicago, VIDO, Entos, Merck & Co., Inc., Pfizer Inc., Sanofi. A. Hossain: None. N. Machluf: Employee; Self; VBI Vaccines. J. Spaans: Employee; Self; VBI Vaccines Inc. B. Yassin-rajkumar: None. D. E. Anderson: Employee; Self; VBI Vaccines, Inc., Stock/Shareholder; Self; VBI Vaccines, Inc. V. Popovic: Employee; Self; VBI Vaccines.
208-OR: Fat Mass and Insulin Resistance Are Independent Risk Factors for Polyneuropathy in Non-DM Subjects Who Underwent Bariatric/Metabolic Surgery
Authors: KIM KYUHO , OH TAE JUNG , CHOI SUNGHEE , JANG HAK CHUL
Published: June 2021

Background: Obesity is an important risk factor for polyneuropathy (PN) in subjects with DM. However, PN can be detected in subjects without overt DM but with risk factors for DM such as metabolic syndrome. Therefore, it is worthy to investigate the prevalence of PN in obese subjects and to discover the underlying mechanisms of the association between obesity and PN.

Methods: We analyzed the data of 184 subjects who underwent bariatric/metabolic surgery. PN was diagnosed when a Michigan Neuropathy Screening Instrument score was ≥ 2.5. Total body fat mass and percentage were measured by bioimpedance analysis, and visceral fat area (VFA) was quantified by computed tomography. According to DM status, obesity-related parameters were compared between subjects with PN and those without PN. The association between obesity-related parameters and PN was analyzed using logistic regression models.

Results: Of 184 subjects (mean age, 39.1 years; mean BMI, 38.6 kg/m2), 39.7% were diagnosed with DM. The prevalence of PN was 9.0% in non-DM group and 21.9% in DM group. In non-DM group, subjects with PN showed higher HOMA-IR, fat mass, and VFA compared with those without PN. HOMA-IR (OR, 1.492; 95% CI, 1.110-2.005), fat mass (OR, 1.087; 95% CI, 1.008-1.171), and VFA (OR 1.013; 95% 1.001-1.024) were significantly associated with PN even after adjustment of known risk factors of PN. In DM group, subjects with PN showed higher body weight, BMI, waist circumference, and VFA compared with those without PN. However, after adjustment of known risk factors of PN, these obesity related parameters were not significantly associated with PN.

Conclusion: Fat mass and insulin resistance might be independent risk factors in development of PN for obese subjects without DM. PN evaluation might be necessary in subjects with morbid obesity even before development of overt DM, and we need to investigate whether weight loss intervention can prevent or delay PN in obese subjects.

Disclosure

K. Kim: None. T. Oh: None. S. Choi: None. H. Jang: None.
226-OR: ADA Presidents’ Select Abstract: Exercise Training Promotes Mitochondrial Remodeling in Skeletal Muscle of Type 2 Diabetes Humans
Authors: MASTROTOTARO LUCIA , APOSTOLOPOULOU MARIA , PESTA DOMINIK , STRASSBURGER KLAUS , KARUSHEVA YANISLAVA , GANCHEVA SOFIYA , SZENDROEDI JULIA , RODEN MICHAEL
Published: June 2021

Altered mitochondrial dynamics may contribute to impaired mitochondrial function and insulin sensitivity in type 2 diabetes (T2D). High intensity interval training (HIIT) can induce mitochondrial biogenesis in healthy humans, but its impact on mitochondrial remodeling in insulin resistant states is still unclear. To this end, this study examined the effect of HIIT on mitochondrial function and dynamics in T2D as well as in insulin resistant (IR) and sensitive (IS) glucose tolerant humans to elucidate the interplay between mitochondrial turnover and muscle insulin sensitivity. Twenty T2D, 11 IR and 12 IS humans age- and BMI-matched (HbA1c in %: 7.2 ± 0.2, 5.4 ± 0.1, 5.5 ± 0.1; M-value in mg*kg-1*min-1: 3.0 ± 0.4, 4.1 ± 0.3, 7.4 ± 0.4) performed a 12-week HIIT cycling protocol for 3 days/week. Before the intervention (baseline) and 72 h after the last exercise bout, whole-body insulin sensitivity was measured by hyperinsulinemic-euglycemic clamps, whereas mitochondrial respiration and dynamics were assessed by high resolution respirometry and immunoblotting of skeletal muscle biopsies. After HIIT, all participants showed improved cardiorespiratory fitness and increased muscle maximal oxygen uptake (p<0.001 vs. baseline), whereas insulin sensitivity increased only in T2D and IR (M-value; 4.3 ± 0.5 and 5.7 ± 0.6; p<0.01 vs. baseline). Moreover, HIIT doubled muscle citrate synthase activity in all groups, while biomarkers of mitochondrial fission (p<0.01), fusion (p<0.001) and mitophagy (p<0.001 for phospho-Parkin(Ser65) and p<0.05 for phospho-Pink(Thr257)) increased only in T2D.

In conclusion, this study suggests that mitochondrial fusion and fission synergically respond to chronic exercise training and likely contribute to the exercise training response of insulin sensitivity at least in overt T2D. Targeting these mechanisms might help to better understand muscle insulin resistance and to identify novel therapeutic strategies for tailored prevention and treatment of T2D.

Disclosure

L. Mastrototaro: None. M. Apostolopoulou: None. D. Pesta: None. K. Strassburger: None. Y. Karusheva: None. S. Gancheva: None. J. Szendroedi: None. M. Roden: Advisory Panel; Self; Allergan plc, Bristol-Myers Squibb Company, Novo Nordisk A/S, Research Support; Self; Boehringer Ingelheim International GmbH, Danone Nutricia, Sanofi-Aventis Deutschland GmbH.
308-OR: Effectiveness of Telemedicine Intervention on Improving Glycemia and Reducing Pharmacologic Therapy in Older Adults with Type 2 Diabetes
Authors: ADAMS REBECCA N. , ATHINARAYANAN SHAMINIE J. , ROBERTS CAROLINE G.P. , VOLK BRITTANIE M. , FELL BRANDON , MCKENZIE AMY L.
Published: June 2021

Background: We previously demonstrated that carbohydrate restricted nutrition therapy delivered virtually resulted in safe and sustained reduced blood glucose (BG), resulting in deprescription of antihyperglycemic medications in patients with T2D ≤65 years. Given concerns regarding polypharmacy and risk of hypoglycemia (HYPO) in older adults with T2D, this treatment approach may confer benefit.

Methods: At the time of analysis, 279 adults aged ≥65 years at enrollment (27% female, 69±1.6 years, HbA1c: 7.5±1.5%) enrolled in our clinic at least 1 year prior. Data were obtained from medical records to assess changes in BG and medication use among patients retained 1 year and incidence of HYPO in all patients enrolled. Patients provided >1 BG per day on average. Glucose values and patient-reported events were used to identify level 1 (54-69 mg/dL), level 2 (<54 mg/dL), and level 3 (severe requiring third-party assistance) HYPO events.

Results: Among 201 (72%) patients treated 1 year, mean glucose declined (-18.8±3.7 from 147.3±3.8 mg/dL, p<0.001). Among 144 patients taking 231 medications other than metformin at enrollment, 141/231 (61%) of medications were deprescribed, including 45% of insulins and 85% of sulfonylureas. Among the 38 patients still prescribed insulin at 1 year, the average dosage decreased from 98.5±66.0 to 36.2±29.2 IU/day (p<0.001). The average number of diabetes prescriptions per patient declined from 1.2±0.9 to 0.5±0.7 (p<0.001). There were 149 level 1 HYPO events per 100 person-years (p-y), 28 level 2 events per 100 p-y, and no level 3 events reported.

Discussion: The majority of older adults continued treatment for at least 1 year. Improved glycemia concurrent with discontinuation of many high-risk medications and no known severe HYPO events in older adults with T2D suggests this treatment approach may reduce risk and cost associated with polypharmacy and HYPO in older adults with T2D.

Disclosure

R. N. Adams: Employee; Self; Virta Health Corp., Stock/Shareholder; Self; Virta Health Corp. S. J. Athinarayanan: Employee; Self; Virta Health Corp. C. G. P. Roberts: Employee; Self; Virta Health Corp., Stock/Shareholder; Self; Virta Health Corp. B. M. Volk: Employee; Self; Virta Health Corp., Virta Health Corp. B. Fell: None. A. L. Mckenzie: Employee; Self; Virta Health Corp., Stock/Shareholder; Self; Virta Health Corp.
371-P: Impact of Sodium Intake on the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: Analysis of Data from the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial
Authors: HORIKAWA CHIKA , AIDA REI , TANAKA SHIRO , KAMADA CHIEMI , YOSHIMURA YUKIO , KODERA REMI , FUJIHARA KAZUYA , MORIYA TATSUMI , ARAKI ATSUSHI , SONE HIROHITO
Published: June 2021

Excessive sodium intake is regarded as a crucial factor related to developing and worsening of cardiovascular disease (CVD). However, epidemiological studies on this topic in patients with type 2 diabetes are sparse. We investigated the associations between sodium intake and CVD risk in Japanese patients with type 2 diabetes from the analysis of pooled data from two nation-wide prospective longitudinal studies. Data were analyzed on 2428 individuals whose dietary intake at baseline was assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 6-year risk of a CVD event. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. Mean sodium intake in quartiles ranged from 2494 mg to 6166 mg/day and more than three-quarters of participants had sodium intake more than the recommended dietary allowance by American Diabetes Association (< 2300 mg/day). After adjustment for confounders, HRs for CVD in patients with sodium intake in the 2nd, 3rd, and 4th quartiles compared with sodium intake in the 1st quartile were analyzed, and no significant differences were shown between sodium intake and CVD [Q2: 0.77 (95%CI, 0.48-1.23); Q3: 1.03 (0.65-1.63); and Q4: 1.31 (0.80-2.14), trend p = 0.131]. Results of subgroup analysis according to age showed that patients aged 39 through 59 years in the higher quartiles of sodium intake compared with the 1st quartile had a significantly higher incidence of CVD [Q2: 1.37 (0.57-3.33); Q3: 1.68 (0.70-4.03); and Q4: 4.16 (1.63-10.58), trend p = 0.004]. However, no significant association between sodium intake and CVD in participants aged over 60 years. Findings indicated that high sodium intake is associated with elevated incidence of CVD in younger patients with type 2 diabetes.

Disclosure

C. Horikawa: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. R. Aida: None. S. Tanaka: None. C. Kamada: None. Y. Yoshimura: None. R. Kodera: None. K. Fujihara: None. T. Moriya: None. A. Araki: None.

Funding

Japan Society for the Promotion of Science (19H04028)
378-P: Upregulation of Regenerating Gene IV and Hepatocyte Growth Factor in Cardiomyocytes by Intermittent Hypoxia and Its MicroRNA-Mediated Mechanism
Authors: TAKASAWA SHIN , ITAYA-HIRONAKA ASAKO , YAMAUCHI AKIYO , MAKINO MAI , SAKURAMOTO-TSUCHIDA SUMIYO , UCHIYAMA TOMOKO , TAKEDA YOSHINORI , KYOTANI YOJI , OTA HIROYO
Published: June 2021

Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]) and is a risk factor for cardiovascular disease (CVD) and insulin resistance. However, the mechanisms linking IH stress and CVD remain elusive. We exposed rat H9c2 and mouse P19.CL6 cardiomyocytes either to sustained hypoxia (1% O2 [SH]), 70 cycles/24 h of IH (5 min SH/10 min normoxia [21% O2]), mimicking SAS patients, or normoxia for 24 h, analyzed mRNA expression and found that IH significantly increased the mRNA levels of regenerating gene (Reg) IV and hepatocyte growth factor (Hgf). Reg IV and Hgf in IH-treated cell medium were also increased. In order to analyze the IH-induced expression mechanisms of Reg IV and Hgf genes, we prepared reporter plasmids containing Reg IV and Hgf upstream of luciferase reporter gene, and transfected them into P19.CL6 cardiomyocytes. The promoter activities of the genes were not increased by IH. Target mRNA search of microRNA (miR)s revealed that both the mRNAs have a potential target sequence for miR-499. The miR-499 level of IH-treated cells was significantly decreased than that of normoxia-treated cells. To clarify the role of miR-499, miR-499 mimic and non-specific control RNA (miR-499 mimic NC) were introduced into P19.CL6 cells, and the IH-induced up-regulation of Reg IV and Hgf was abolished by introduction of miR-499 mimic. We also measured apoptosis of IH/SH-stimulated P19.CL6 cells by TUNEL method and found that SH but not IH increased apoptosis and that Reg IV and Hgf in cultured medium significantly reduced. The addition of Reg IV and/or Hgf in the culture medium attenuated the SH-induced apoptosis. These results indicate that IH stress increased levels of Reg IV and Hgf mRNA via the inhibition of the miR-499-mediated mRNA degradation, leading to protect cardiomyocytes against hypoxia -induced apoptosis.

Disclosure

S. Takasawa: None. A. Itaya-hironaka: None. A. Yamauchi: None. M. Makino: None. S. Sakuramoto-tsuchida: None. T. Uchiyama: None. Y. Takeda: None. Y. Kyotani: None. H. Ota: None.
379-P: Aldose Reductase Inhibition by AT-001 Prevents Diabetic Cardiomyopathy via Reducing Myocardial Fatty Acid Oxidation Rates
Authors: GOPAL KESHAV , KARWI QUTUBA G. , DAKHILI SEYED AMIRHOSSEIN TABATABAEI , WAGG CORY S. , PERFETTI RICCARDO , RAMASAMY RAVICHANDRAN , USSHER JOHN R. , LOPASCHUK GARY
Published: June 2021

Cardiovascular diseases, including diabetic cardiomyopathy (DbCM), are major causes of death in people with type 2 diabetes (T2D). Several studies have suggested that aldose reductase (AR), an enzyme activated under hyperglycemic conditions, can alter cardiac energy metabolism and deteriorate cardiac function. We investigated whether inhibition of AR, using a next-generation inhibitor AT-001, can mitigate DbCM by modulating cardiac energy metabolism. Human AR overexpressing transgenic (hAR-Tg) and control C57BL/6J mice were subjected to experimental T2D (high-fat diet [60% kcal from lard] for 10-wks with a single intraperitoneal streptozotocin injection of 75 mg/kg at 4-wks). AR inhibition by AT-001 treatment (40 mg/kg/daily) for 3-wks significantly improved cardiac energetics in hAR-Tg mice with T2D. AT-001 treated mice exhibited significantly decreased cardiac fatty acid oxidation rates compared to the vehicle-treated mice (608 ± 66 vs. 1200 ± 176 nmol.min-1.g dry wt-1, respectively), which was accompanied by a decrease in cardiac oxygen consumption in AT-001 treated mice (44 ± 8 vs. 61 ± 11 µmol.min-1.g dry wt-1). Furthermore, treatment with AT-001 prevented cardiac structural and functional abnormalities present in DbCM, including diastolic dysfunction as reflected by an increase in the tissue Doppler E’/A’ ratio (1.6 ± 0.12 vs. 1.38 ± 0.1) and decrease in E/E’ ratio (26.6 ± 1 vs. 33 ± 4.9). AT-001 treatment also prevented cardiac hypertrophy as reflected by a decrease in LV mass (90.5 ± 2.2 vs. 125 ± 14 mg). We conclude that AT-001 prevents cardiac structural and functional abnormalities in DbCM, and normalizes cardiac energetics by shifting cardiac metabolism towards a nondiabetic metabolic state.

Disclosure

K. Gopal: None. Q. G. Karwi: None. S. Tabatabaei dakhili: None. C. S. Wagg: None. R. Perfetti: Stock/Shareholder; Self; Applied Therapeutics. R. Ramasamy: Consultant; Self; Applied Therapeutics, Research Support; Self; Applied Therapeutics. J. R. Ussher: None. G. Lopaschuk: None.
523-P: Psychosocial Impact of COVID-19 on Pediatric Diabetes
Authors: DIMENTSTEIN KAREN , YEE SHANIQUE , VALENZUELA JESSICA M. , PAN BERNARD , SNYDER MEG , WOLF RISA
Published: June 2021

Background: Individuals with diabetes have been disproportionately affected by the COVID-19 pandemic. Data on the impact of COVID-19 on youth with T1D is scarce. We sought to determine the impact on youth with T1D and their families including the extent to which they experienced COVID-related disruptions and distress.

Methods: The COVID-19 Exposure and Family Impact Survey (CEFIS) was administered to caregivers of youth with T1D at two comprehensive diabetes clinics in the northeast and southern U.S. Items were scored and analyzed using SPSS. Themes were coded for open-ended questions. Health data were extracted from EMR.

Results: Mothers (85%) of 47 youth (72%NHW, 24%NHB, 4%H) with T1D (HbA1c M=8.3%) ranging from 6 to 17 years participated. Insulin pumps were used by 66% and CGMs by 17%. The most frequent COVID-related challenges endorsed were school/childcare closure (95.1%), education disruption (87.2%) and inability to visit/care for family (74.5%). Fewer caregivers reported difficulty accessing food (11.3%), necessary health care (9.4%), or medicine (5.7%). Areas of negative impact included child’s access to medical supplies (2.6), physical activity level and diet (M=2.7), as well as caregiver anxiety (M =3.2), mood (M =2.8), sleeping, eating, and exercise (M=2.7). Caregivers reported COVID-related distress for themselves (M=5.8) and their child (M=5.0; scale 1-10). Common themes regarding the impact of COVID-19 were increased health anxiety, limited social interaction, and routine disruption. Caregivers noted benefits in family cohesion. Both positive and negative impact on diabetes management were described by caregivers. Quotes from caregivers will be presented.

Conclusions: This ongoing study highlights early findings on the impact of COVID-19 on youth and families with T1D. Clinicians and researchers should consider the psychosocial impact of COVID-19 on youth with T1D and tailor diabetes care accordingly.

Disclosure

K. Dimentstein: None. S. Yee: None. J. M. Valenzuela: None. B. Pan: None. M. Snyder: None. R. Wolf: Consultant; Self; NEMA Research.
542-P: Club: A Novel Approach to Improve Self-Management in Youth with Type 2 Diabetes
Authors: CHANG NANCY T. , MUÑOZ CYNTHIA E. , YASUDA PATRICE M. , CHAO LILY
Published: June 2021

Background: Adherence with treatment recommendations is challenging for many youths with type 2diabetes (T2D). Interventions to address their specific barriers are needed.

Objective: CLUB (Control your diabetes by Learning life skills and Understanding your Barriers) is a group intervention that targets the unique psychosocial needs of youth with T2D. The objectives are to foster peer support, enhance diabetes-related skill acquisition, and facilitate emotional adjustment to T2D and its management.

Methods: Youth with HbA1c > 8% are referred to CLUB. CLUB includes four sessions over a 6-monthperiod. Youth meet as a group and parents convene separately. A pediatric psychologist facilitates the youth group. A bilingual nurse practitioner facilitates parent groups in English and Spanish. CLUB participants were matched with controls by gender, age, and duration of diagnosis.

Results: Of the 105 referred patients, 64 patients attended at least one session and 42 patients completed at least three sessions. Mean age of youth in the latter cohort was 15.3 years (SD 2.0yrs) and 70% were female. Ethnic background of the participants was predominantly Latinx. Median duration of diabetes diagnosis was 2.0 years (IQR 2.2 yrs). Mean HbA1cbaseline was 11.0%(SD 2.2%). Baseline HbA1c did not differ between cohorts. CLUB participation did not improveHbA1c (mean change in HbA1cControl =-0.14% and HbA1cCLUB=-0.32%, P=0.7283), but there was a positive correlation between HbA1c change (HbA1cfinal-HbA1cbaseline) and the time to completion of CLUB (P=0.0087).

Conclusion: CLUB is an innovative program that targets psychosocial barriers for youth with T2D. Though participants’ HbA1c did not improve, youth and their parents reported enjoyment of their experience. Preliminary data suggests that consistent participation in CLUB yielded a greater reduction in HbA1c compared to program completion over longer periods of time. This model and its potential to improve T2D health behaviors for diverse youth will be further examined.

Disclosure

N. T. Chang: None. C. E. Muñoz: None. P. M. Yasuda: None. L. Chao: None.
681-P: Effect of 3-Month Therapy with SGLT2 Inhibitors and GLP-1 Agonists on Ambulatory Blood Pressure in Patients with Type 2 Diabetes Mellitus
Authors: PAPAZAFIROPOULOU ATHANASIA , PAPANTONIOU STYLIANI S. , RALLATOU MARIA , MELIDONIS ANDREAS J. , ANTONOPOULOS STAVROS
Published: June 2021

Background and Aims: It is known that SGLT-2 inhibitors and GLP-1 agonists show a favorable profile in the reduction of body weight as well as blood pressure (BP). Therefore, the purpose of this study is to evaluate the effect of SGLT-2 inhibitors and GLP-1 agonists on ambulatory BP in patients with poorly controlled type 2 diabetes (T2D).

Materials and Methods: A total of 74 patients with T2D: 42 on GLP-1 agonists (group Α) [20 men, mean age (±standard deviation) 60.6±9.4 years, HbA1c 8.5±1,1%, body mass index (BMI) 37.1±5.3 Kg/m2, T2D duration 10.1±4.3] and 32 on SGLT-2 inhibitors (group Β) [16 men, mean age 64.8±7.1 years, HbA1c 8.2±1.3%, BMI 32,1±9,2 Kg/m2]. All patients underwent a complete clinical and laboratory examination. Ambulatory BP recording at baseline and three months after initiation of treatment with the oscillometric Mobil-O-Graph NGW 24-hour ambulatory BP and PWA monitor (IEM; Stolberg, Germany).

Results: At baseline, mean daytime systolic and diastolic BP in group A were: 128.0±11.2 and 77.2±11.0 mmHg and in group B: 129.6±14.8 and 78.1±9.9 mmHg, respectively (P=0.78 and P=0.81, respectively, for the comparison between the study groups). Regarding the nighttime recordings of BP in group A, mean systolic and diastolic BP were: 127.5±12.6 and 73.7±14.2 mmHg. In group B, mean systolic and diastolic BP were: 126.3±12.5 and 74.1±8.7 mmHg (P=0.57 and P=0.67, respectively, for the comparison between the study groups). After 3-month therapy, mean systolic BP (group A versus B) was 124.0±7.8 versus 128.2±10.4 mmHg (P=0.04) and mean diastolic BP, 73.5±7.8 versus 78.3±7.8 mmHg (P=0.05). Regarding nighttime systolic BP was 118.6±11.1 (group Α) versus 117.4±9.3 mmHg (group Β) (P=0.54) and for mean diastolic BP 68.1±9.8 (group Α) versus 69.6±7.1 mmHg (group Β) (P=0.69).

Conclusion: Three-month therapy with GLP-1 agonists had a favorable effect of ambulatory systolic and diastolic BP compared to SGLT-2 inhibitors.

Disclosure

A. Papazafiropoulou: None. S. S. Papantoniou: None. M. Rallatou: None. A. J. Melidonis: None. S. Antonopoulos: None.
718-P: Long-Term Safety of Intranasal Insulin (INI) in Insulin-Dependent Type 2 Diabetes (T2DM-IDDM): A Safety Substudy of Memory Advancement by Intranasal Insulin in Type 2 Diabetes (MemAID) Trial
Authors: BECERRA LAURA APONTE , MENDEZ BRAHYAN GALINDO , KHAN FAIZAN , MANTZOROS CHRISTOS , NOVAK PETER , LIOUTAS VASILEIOS , NGO LONG H. , NOVAK VERA ,   MEMAID INVESTIGATORS, TREVINO J.
Published: June 2021

INI has emerged as a potential treatment for T2DM-related functional decline and is safe in adults without T2DM. However, INI safety in T2DM-IDDM is unknown. We aimed to demonstrate safety of long-term INI use in T2DM-IDDM MemAID participants. We screened 86 participants with T2DM-IDDM, 14 were randomized (9 INI/5 Placebo), 9 started treatment (5 INI [60±14 years, 2 Female]; 4 Placebo [68±2 years, 1 Female]). Of those, 2-INI and 3-Placebo participants completed 24 weeks of treatment and 24 weeks of follow-up. Participants underwent one week of continuous glucose monitoring (CGM)(Medtronic IPro2) at baseline and after INI (Novolin® R ) or placebo initiation. HbA1c, fasting plasma and capillary glucose, and insulin were measured throughout the study. Insulin levels were unchanged across the study. In 2 INI-treated participants, HbA1c, fasting plasma and capillary glucose declined from baseline, but the average values were similar during treatment and follow up, and comparable to 3 placebo-treated participants. Both INI-treated participants had adjustments of IDDM regimens. Capillary glucose did not decline 2 hours after INI administration, and there were no interactions between INI and subcutaneous insulin. There were no INI-related serious adverse events. Of 13 hypoglycemia (HG) episodes across the study, 2 asymptomatic level-1 HG (15.4%) occurred in INI group and 7 (53.8%) in placebo group. There were 2 asymptomatic level-2 HG (15.4%) in both INI and placebo groups. INI therapy was not associated with serious adverse events or HG in older participants with T2DM-IDDM. This study may pave the way towards future larger studies evaluating the safety of concomitant administration of INI and subcutaneous insulin (NCT02415556).

Disclosure

L. Aponte becerra: None. B. Galindo mendez: None. F. Khan: None. C. Mantzoros: Advisory Panel; Self; Amgen Inc., GENFIT, Intercept Pharmaceuticals, Inc., Novo Nordisk, Regeneron Pharmaceuticals Inc. P. Novak: Other Relationship; Self; Dysimmune Foundation, Endonovo Therapeutics, Oxford Press. V. Lioutas: Consultant; Self; QMetis. L. H. Ngo: Consultant; Self; Five Islands Consulting, Other Relationship; Self; Radiological Society of America. Memaid investigators (j. trevino): n/a. V. Novak: Advisory Panel; Spouse/Partner; Endonovo Therapeutics, Inc., Consultant; Spouse/Partner; Dysimmune Foundtation, Other Relationship; Spouse/Partner; Oxford University Press.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK103902); U.S. Food and Drug Administration (IND107690); Novo Nordisk (ISS-001063), Medtronic (NERP15-0310); World Health Organization (UTN-U111-1175-1588)
Diabetes With Multiple Autoimmune and Inflammatory Conditions Linked to an Activating SKAP2 Mutation
Authors: Rutsch Niklas , Chamberlain Chester E. , Dixon Wesley , Spector Lauren , Letourneau-Freiberg Lisa R. , Lwin Wint W. , Philipson Louis H. , Zarbock Alexander , Saintus Karline , Wang Juehu , German Michael S. , Anderson Mark S. , Lowell Clifford A.
Published: June 2021

OBJECTIVE

Multiple genome-wide association studies have identified a strong genetic linkage between the SKAP2 locus and type 1 diabetes (T1D), but how this leads to disease remains obscure. Here, we characterized the functional consequence of a novel SKAP2 coding mutation in a patient with T1D to gain further insight into how this impacts immune tolerance.

RESEARCH DESIGN AND METHODS

We identified a 24-year-old individual with T1D and other autoimmune and inflammatory conditions. The proband and first-degree relatives were recruited for whole-exome sequencing. Functional studies of the protein variant were performed using a cell line and primary myeloid immune cells collected from family members.

RESULTS

Sequencing identified a de novo SKAP2 variant (c.457G>A, p.Gly153Arg) in the proband. Assays using monocyte-derived macrophages from the individual revealed enhanced activity of integrin pathways and a migratory phenotype in the absence of chemokine stimulation, consistent with SKAP2 p.Gly153Arg being constitutively active. The p.Gly153Arg variant, located in the well-conserved lipid-binding loop, induced similar phenotypes when expressed in a human macrophage cell line. SKAP2 p.Gly153Arg is a gain-of-function, pathogenic mutation that disrupts myeloid immune cell function, likely resulting in a break in immune tolerance and T1D.

CONCLUSIONS

SKAP2 plays a key role in myeloid cell activation and migration. This particular mutation in a patient with T1D and multiple autoimmune conditions implicates a role for activating SKAP2 variants in autoimmune T1D.
Рhysical and chemical analyses of the adsorption capacity of transcarpathian clinoptilolite
Authors:   Lviv Polytechnic National University, Kochubei V. V. , Yaholnyk S. G. ,   Lviv Polytechnic National University, Yaremchuk Y. V. ,   Іnstitute of Geology and Geochemistry of Combustible Minerals of NAS of Ukraine, Manchak A. I. ,   Lviv Polytechnic National University
Published: June 2021

The IR spectroscopy and complex thermal analysis were used to analyze the adsorption capacity of Transcarpathian clinoptilolite, both naturally occurring and activated, relative to water vapor. It was found that activation of clinoptilolite with an H2SO4 25 %-solution causes dealumination and the appearance of additional adsorption centers, allowing maximum adsorption of water vapor. Activation with a 5 % solution of HCl at the 1:10 solid-liquid ratio ensures the significant dealumination of the mineral with no breakdown of its structure and the occurrence of transient pores and macropores in this mineral. Due to such activation clinoptilolite is far more able to absorb molecules of the green dye.
Theoretical analysis and experimental study of H2S dissociation processes in ultrahigh-frequency plasmotron
Authors:   Lviv Polytechnic National University, Znak Z. О.
Published: June 2021

Theoretical analysis of aerodynamic conditions in a plasma chemical reactor with tangential gas supply is carried out. It is shown that due to the creation of a swirling flow in the reactor there is a pressure gradient, due to this along the vertical axis there is a vacuum zone, which contributes to the occurrence of plasma discharge. On the basis of the carried-out experimental researches of plasmolysis of hydrogen sulphide in a swirling stream and the analysis of images of the plasma discharge with use of monochromatic light filters the general structure of the plasma discharge is established. The influence of the temperature gradient in the reactor on the possibility of the formation of sulphur clusters as a prerequisite for the formation of a high molecular weight product – polymeric sulphur – was established.
New mixed manganites-chromites RMn1–xCrxO3 and manganites-gallates RMn 1–xCrxO3
Authors:   Lviv Polytechnic National University, Hreb V. M. , Lutsyuk I. V. ,   Lviv Polytechnic National University, Kochubei V. V. ,   Lviv Polytechnic National University, Vasylechko L. O. ,   Lviv Polytechnic National University
Published: June 2021

Nanocrystalline powders of new mixed manganites-chromites RMn0.5Cr0.5O3 (R = Pr, Sm, Er) and manganites-gallates RMn1-xGaxO3 (R = Pr, Sm, Eu; x = 0.25, 0.5) with orthorhombic perovskite structure were obtained by sol-gel citrate route. Crytal structure parameters and microstructural parameters of the materials were established depending on the synthesis conditions. Based on the resuts obtained formation of conntinuos solid solutions RMn1-xCrxO3 in the RMnO3-RCrO3 systems and limited solid solitions in the RMnO3-RGaO3 systems were predicted.
Marketing analysis of the market segment of drugs – derivatives of 9,10-anthraquinone in Ukraine
Authors:   Lviv Polytechnic National University, Stasevych M. V. , Zvarych V. I. ,   Lviv Polytechnic National University
Published: June 2021

A marketing analysis of the pharmaceutical market for drugs - derivatives of 9,10-anthraquinone was carried out. It is shown that in the Ukrainian market, the vast majority of the assortment of these drugs is formed by foreign-made drugs, the leaders of which are the manufacturing countries Austria, Italy, Germany and India. It has been determi ned that the majority of anthraquinone drugs are represented by agents for the treatment of diseases of various types of cancer and strengthening of the intestinal reticulum. It has been established that “Sinbias Pharma” LLC is engaged in the production of four anticancer substances in Ukraine. For preparations based on anthraquinone-containing medicinal herbal raw materials, domestic manufacturers are PJSC “Liktravy” and PJSC Pharmaceutical Factory “Viola”, and the producers of senna glycosides are JSC “Lubnypharm”, “Ternopharm” LLC and Pharmaceutical company “Zdorovye”. Injection solutions, lyophilisates, tablets and hard capsules are the main dosage forms of drugs – derivatives of 9,10-anthraquinone.
Biotechnological aspects of obtaining biologically active substances of Adonis vernalis
Authors:   Lviv Polytechnic National University, Hamada V. R.
Published: June 2021

This article shows the possibility of using a biotechnological method to obtain biologically active compounds based on in vitro cultivation of callus cultures. The callus biomass of Adonis vernalis was obtained in vitro by using the biotechnological method. The extracts based on callus biomass of Adonis vernalis were obtained. The content of flavonoids and phenolic compounds was determined. The antioxidant activity of callus biomass of Adonis vernalis has also been studied. The research results show that the content of biologically active substances and biological activity in callus biomass does not differ from plant raw materials.
Obtaining of nanocomposites based on montmorillonite and polyamide in solution
Authors:   Lviv Polytechnic National University, Krasinskyi V. V. , Suberlyak O. V. ,   Lviv Polytechnic National University, Zemke V. M. ,   Lviv Polytechnic National University, Chekailo M. V. ,   Lviv Polytechnic National University, Pankiv M. O. ,   Lviv Polytechnic National University
Published: June 2021

The method of obtaining nanocomposites based on polyamide-6 and montmorillonite intercalated by polyvinylpyrrolidone by precipitation from a solution in formic acid was developed in the work. The structure and physical interaction between the components of nanocomposites were studied by the methods of XRD, IR spectroscopic, and microscopic analyzes. The presence of polyvinylpyrrolidone in the structure of nanocomposites obtained from the solution was confirmed by IR spectroscopic analysis. Using SEM images, it was established that exfoliated montmorillonite particles with sizes from 100 to 200 nm are present in the structure of nanocomposites.
Microscopic and ultramicroscopic structure of typical chordae tendineae of the human’s left ventricle bicuspid valve
Authors: Malyk Yu. , Semeniuk T. , Penteleichuk N.
Published: June 2021

Objective – to determine the features of the micro- and submicroscopic structure of typical chordae tendineae of the mitral valve of the human heart.Materials and methods. This study was made on preparations of 35 human hearts, in particular the chordae tendineae of the bicuspid valves of the left ventricles of children and people of early and middle adulthood using the methods of light and electron microscopy.Results. The study of typical chordae tendineae of the mitral valve leaflets was made using the microscopic method and the method of electron microscopy. The areas where the chordae tendineae diverge from the papillary muscles, the middle third of the chordae tendineae, and the place of attachment of the chordae tendineae to the mitral valve leaflets were studied. Chordae tendineae are covered with endothelium from all sides. A peripheral collagen-elastic layer of loose fibrous connective tissue is localized under the endothelium, along the entire perimeter of the chordae tendineae and it differs in structure in different parts of the chordae at the submicroscopic level. Bundles of densely packed collagen fibers, which are oriented rectilinearly along the chordae, form the core of the chordae tendineae. Bundles of striated cardiac typical muscle cells are localized in areas where the chordae tendineae origin from the papillary muscles. It was found that in the composition of the chordae tendineae of children the cellular component in the fibrous connective tissue predominates during comparing the typical chordae tendineae of different aged people.Conclusions. This morphological study made it possible to obtain new information and to clarify the data that are already known to morphologists on the micro- and submicroscopic structure of typical chordae tendineae of the mitral valve of the human heart. We found that differences in the histological structure are more typical for the areas of origin of typical chordae tendineae from the papillary muscles and areas of their attachment to the leaflets of the mitral valve. The diameter of the core of the chordae tendineae increases and the thickness of the loose peripheral collagen-elastic layer decreases with age. The received data can serve as a theoretical basis for the further comparative morphological and clinical studies of the mitral valve of the human heart. That, in turn, will facilitate to an increasing the level of diagnostic, to improve methods of prevention and treatment of minor heart anomalies, congenital and acquired defects of the valvular apparatus of the heart.
Activity of inflammation in patients with chronic obstructive pulmonary disease and anemia
Authors: Radchenko O. , Fedyk O.
Published: June 2021

Patients with chronic obstructive pulmonary disease (COPD) in combination with anemia of chronic disease (ACD), are of particular interest to both scientific and practical health care. The purpose of the work - to study the activity of systemic inflammation.Material and methods. The results of the examination of 475 patients with exacerbation of COPD were analyzed, which were divided into two groups: group I - 155 people (61,3% men and 38,7% women) with ACD; group II - 320 patients (46,9% of men and 53,1% of women) without the anemic syndrome. Determination of the activity of the inflammatory process was performed by hemocytogram, serum markers of inflammation and integrated hematological indices. The results of the study. It was found that COPD in combination with ACD was accompanied by activation of the inflammatory process (erythrocyte sedimentation rate, segmented neutrophils content) and suppression of lymphocyte-monocyte inflammation, significantly higher integral hematological indices (leukocyte shift index; ratio of leukocytes, non-segmented neutrophils and all neutrophils to the erythrocyte sedimentation rate; the ratio of neutrophils to lymphocytes and the integrated index of inflammation), which increased with the deepening of the anemic syndrome, increasing patients age and was more pronounced in women. Activation of inflammation was associated with deterioration of bronchial patency according velocity parameters (Tiffno index, mean and peak volumetric velocities, maximal volumetric velocities by 25% and 75% of the forced ungs vital capacity). Anemic syndrome was also associated with higher levels of C-reactive protein (p>0,05), general fibrinogen (p<0,05) and seromucoids (p>0,05), the content of which varied in parallel with the leukocyte shift index. Conclusion. Anemic syndrome, as a manifestation of persistent systemic inflammation, worsens the course of a chronic obstructive pulmonary disease through affecting the respiratory function and the inflammatory process activation.
Characteristic of malabsorption syndrome at the modern stage
Authors: Zub L. , Shkarutyak A.
Published: June 2021

Today, the term "malabsorption syndrome" is widely used in medical practice as a general term to describe the symptoms of indigestion, absorption, and transport by the intestinal mucosa of adequately digested foods, including vitamins and trace elements, resulting in a variety of metabolic disorders.The purpose of this review is to analyze scientific data that highlight information on modern views on the etiology, mechanisms of development and clinical manifestations of malabsorption syndrome.Conclusion. Today, data on the mechanisms of development and progression of the malabsorption syndrome have been significantly expanded. This makes it possible to develop methods of prevention of the trigger factors, timely correct treatment and prevention of complications of this syndrome.