bluuebunny/crossref_metadata_2025 huggingface dataset:
723-P: Efficacy and Safety of Once-Daily Fixed-Ratio Coformulation of Degludec-Aspart plus Empa-Lina 25/5 FDC in Post-Discharge COVID-19 Pneumonitis T2DM Patients Treated with Dexamethasone during Inpatient Stay
Authors: BHATTACHARYYA SUPRATIK
Published: June 2021

Background: Poor compliance is reported in hospitalised patients with T2D and COVID-19 who are discharged on Basal Bolus therapy (BBT). Hence, it is mandatory to explore novel therapeutic approaches.

Methods: A single-centred retrospective study aimed to evaluate the safety and efficacy of once daily IDegAsp plus Empagliflozin-Linagliptin FDC ± Metformin in T2DM patients who were non-compliant to BBT after being discharged from hospital post dexamethasone therapy.

Results: A retrospective chart analysis performed between 01 June 2020 and 31st December 2020 yielded a record of 67 patients (33 Female and 34 Male) meeting the eligibility criterion. Mean age of patients is 59.63 ± 9.89 years. Of the 67 patients, 59 (88.05%) were non-compliant with 3 bolus doses, 43 (64.18%) with 2 bolus doses and 21 (31.34%) with one bolus dose. The compliance was highest with once daily basal insulin in 64 (94.02%) of patients. It was further observed that the basal dose was sub-optimally up titrated to achieve fasting plasma glucose target and hence 100% failed to achieve their glycemic goals 14 days post discharge. The patients non-compliant with BBT regime and failing to achieve glycemic target post discharge, were switched to once daily IDegAsp along with Empa-Lina 25/5 FDC ± 1 gram of metformin. At the end of 13 weeks, the HbA1c reduced from 10.67±2.1% to 6.85±0.54% (p<0.001) with FPG and PPG both declining from 212.72±52.01 to 118.68±15.54 mg/dL (p<0.001) and 318.22±108.47 to 154.72±27.05 mg/dL (p<0.001) respectively. The initial co-formulation dose requirement was 37.81±7.42 units which subsequently reduced to 17 ± 7.29 units, (p<0.001).

Conclusion: Switching to once daily IDegAsp and Empa-Lina 25/5 FDC ± Metformin was an efficacious and safe alternative to Basal Bolus regimen post discharge for COVID-19 pneumonitis in T2DM patients treated with Dexamethasone during in-patient stay.

Disclosure

S. Bhattacharyya: None.
734-P: Cellular Internalization and Localization of Once-Weekly Basal Insulin Fc (BIF)
Authors: VOLK CATHERINE , ZHANG CHEN , MOYERS JULIE S.
Published: June 2021

Basal Insulin Fc (BIF, LY3209590) is an insulin Fc-fusion protein in clinical testing as a once weekly treatment for diabetes mellitus. BIF is comprised of a human single-chain insulin fused to a human IgG2 Fc domain through a peptide linker. The cellular internalization characteristics of BIF compared to native insulin using U2OS cells expressing human insulin receptor (hIR) are reported in this work. Internalization and sub-cellular localization were visualized by immuno-fluorescent confocal microscopy in U2OS cells expressing human insulin receptor. Internalization of BIF was observed, and the insulin and Fc moieties remained co-localized. Co-localization studies using an antibody to the early endosomal marker Early Endosome Antigen 1 (EEA1) showed that human insulin and BIF (insulin and Fc moieties) were rapidly internalized and co-localized with EEA1. During ligand washout, the remaining insulin and Fc moieties of BIF remained largely co-localized with EEA1 and a concomitant loss of immunostaining was observed, similar to human insulin. Studies using an antibody to the lysosomal marker Lysosomal Associated Membrane Protein-1 (LAMP-1) revealed a low level of lysosomal localization for human insulin and BIF (insulin and Fc moieties), indicating a similar intracellular trafficking pattern of human insulin and BIF to the lysosomal degradative pathway. The co-localization of remaining ligand decreased over time. IR internalization and transport to early endosomes was measured using an enzyme complementation assay. The EC50 for BIF was 4.7 ± 2.1 nM (n = 3), and the EC50 for human insulin was 0.06 ± 0.01 nM (n = 3).

In summary, BIF stimulated IR internalization to a similar maximum level; however, with decreased potency versus human insulin. The subcellular trafficking pattern of BIF is similar to human insulin. BIF undergoes rapid internalization and transport to early endosomes with limited transport to the lysosomes and undergoes loss of cellular immunostaining during ligand washout.

Disclosure

C. Volk: None. C. Zhang: Employee; Self; Eli Lilly and Company. J. S. Moyers: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
771-P: The Effect of Adding Acarbose to Insulin Therapy in Type 1 Diabetes Mellitus: A Systematic Review and Meta-analysis
Authors: LIU ZHIGU , YANG DAIZHI , XU WEN , LV JING , LIN HUIMIN , LIU ZIYU , DENG HONGRONG , YAN JINHUA , YAO BIN
Published: June 2021

Objective: Acarbose is proved to improve glucose control and glucose variability in T2DM. However, few studies focused on the effect of acarbose in T1DM. We hereby evaluated the efficacy and safety of adding acarbose to insulin in T1DM.

Methods: A literature search on PubMed/Medline, Web of Science, Cochrane Library, Embase, Clinicaltrails.gov, CNKI, Wanfang Database and VIP Database for articles published before November 30, 2020 was performed to identify randomized controlled trials (RCTs) that investigated the efficacy of acarbose adding to insulin therapy among T1DM patients. Statistical analyses were performed by using Revman 5.3.

Results: A total of 7 RCTs with 517 patients were included. The age of participants was 18 to 65 years, and the intervention duration ranged from 7 to 24 weeks. Compared with placebo, the addition of acarbose resulted in decreased HbA1c (SMD= -0.27%, 95% CI: -1.17%~ -0.63%), mean blood glucose (SMD= -1.88 mmol/L, 95% CI: -2.75~ -1.01 mmol/L), fasting plasma blood glucose (FBG, SMD= -0.98 mmol/L, 95% CI: -3.32~ -0.63 mmol/L), 2h postprandial blood glucose (PPG, SMD= -2.65 mmol/L, 95% CI: -3.58~ -1.71 mmol/L), total daily insulin dose (SMD= -0.34 U, 95% CI: -0.52~ -0.15 U), and improved glucose variability parameters including MAGE (SMD= -1.42 mmol/L, 95% CI: -2.27~ -0.57 mmol/L) and the LAGE (SMD= -1.36 mmol/L, 95% CI: -2.41~ -0.30 mmol/L). The change of body weight and lipid profiles were similar between the two groups. In terms of adverse events, acarbose increased the risk of gastrointestinal complaints (OR= 1.80, 95% CI: 1.52~ 2.13), while the occurrence of hypoglycemia was similar (SMD= -0.93, 95% CI: -2.60~0.74).

Conclusion: The addition of acarbose to insulin could improve overall glucose control in T1DM patients, including HbA1c, mean blood glucose, FBG, PPG, and glucose variability as well. However, gastrointestinal adverse effects should be considered although acarbose did not increase the risk of hypoglycemia in this population.

Disclosure

Z. Liu: None. D. Yang: None. W. Xu: None. J. Lv: None. H. Lin: None. Z. Liu: None. H. Deng: None. J. Yan: None. B. Yao: None.

Funding

National Key Research and Development Project of China (2017YFC1309602)
777-P: Efficacy of SGLT2 Inhibitors and GLP1-Receptor Agonists in Asians with Type 2 Diabetes: A Systemic Review and Meta-analysis
Authors: JOHNSON RYAN , FRANCO MELISSA , STAAB ERIN M. , KNITTER ALEXANDRA C. , WAN WEN , ALEXANDER JASON , LAITEERAPONG NEDA
Published: June 2021

Background: Clinical trials of SGLT2Is and GLP1RAs have shown improved outcomes in patients with type 2 diabetes, but comprehensive data of their effectiveness in the Asian subpopulation are lacking. A systematic review and meta-analysis of clinical trials evaluating SGLT2Is and GLP1RAs was conducted to assess their efficacy in Asians with type 2 diabetes.

Methods: PubMed, Scopus, and clinicaltrials.gov were searched from inception to July 2019 for randomized controlled trials (≥52 weeks) that enrolled Asians with type 2 diabetes and reported outcome data for SGLT2Is or GLP1RAs compared to placebo or other diabetic medications. Using random effect models, binary outcomes were evaluated with relative risks (RR) and continuous outcomes were evaluated with standardized mean differences (MD).

Results: The analysis included 9 trials for SGLT2Is and 11 trials for GLP1RAs. Compared to placebo, SGLT2Is reduced HbA1c (MD: -0.70%, 95% CI: -1.29% to -0.10%) and weight (MD: -1.52 kg, -2.08 to -0.96 kg); compared to other diabetic medications, SGLT2Is reduced systolic blood pressure (MD: -6.42 mmHg, -9.43 to -3.41 mmHg). Compared to placebo, SGLT2Is increased the risk of genital infection (RR: 2.51, 1.01 to 6.21) but reduced the risk for renal events (RR: 0.69, 0.57 to 0.84). GLP1RAs were associated with lower HbA1c (MD: -0.65%, -1.07% to -0.22%) and weight (MD: -2.06 kg, -3.20 to -0.93 kg) when compared to other diabetic medications. GLP1RAs also reduced major cardiovascular events compared to placebo (RR: 0.72, 0.59 to 0.89). Data were not available for comparisons between GLP1RAs and placebo for other outcomes. Neither SGLT2Is or GLP1RAs had sufficient evidence to suggest their use was associated with a change in all-cause mortality.

Conclusion: In the Asian subpopulation, clinical trials provide evidence for a reduction in cardiovascular risk factors and some diabetes-related adverse events by SGLT2Is and GLP1RAs.

Disclosure

R. Johnson: None. M. Franco: None. E. M. Staab: None. A. C. Knitter: None. W. Wan: None. J. Alexander: None. N. Laiteerapong: Other Relationship; Self; American Diabetes Association.

Funding

American Diabetes Association (1-18-JDF-037 to N.L.)
781-P: Beyond Glucosuria: Urine Metabolome Signature Associated with Dapagliflozin in Wild-Type Mice
Authors: ILAIWY AMRO , MINCEY ADAM , BAIN JAMES R. , MUEHLBAUER MICHAEL , CAMPBELL JONATHAN , D’ALESSIO DAVID A.
Published: June 2021

Background: Glucosuria is a hallmark feature of diabetes. When blood glucose exceeds 200 mg/dl, the amounts reaching the renal tubule overwhelm the capacity of glucose transport and cause glucosuria. SGLT2 inhibitors (SGLT2i) prevent reclamation of glucose from the renal filtrate, leading to glucosuria as well. While SGLT2i promote weight loss and provide cardiovascular protection, those effects are not explained by their glycosuric effect.

Hypothesis:Factors initiated by SGLT-2 blockade lead to excretion of substrates other than glucose, thus creating a unique signature of urine metabolome in SGLT2i-treated mice that may help identify renal responses to SGLT2 inhibition and correspond with system-wide beneficial effects.

Methods: To study SGLT2i effects on the urine metabolome, we used C57BL/6 age-matched male mice. Mice were fasted for three hours and then given either Dapagliflozin (Dapa) or PBS via oral gavage. Capillary glucose was checked prior to gavage. Five hours later, capillary glucose levels were checked again and urine samples were collected for untargeted metabolomics.

Results: Dapa reduced post-gavage glucose by an average Δ of 62.5 mg/dl (p=0.0001). No significant reduction was noted in glucose in the PBS group (Δ=9.2 mg/dl, p=0.52). Glucose was present in the urine of all mice treated with Dapa. Dapa treatment was associated with a unique signature of urine metabolome, with 17 metabolites significantly altered compared to control (P<0.05). While hyperoxaluria has been linked to progression of CKD, mice treated with Dapa had lower level of Oxaluria. Enrichment analysis identified metabolism of Phenylalanine and unsaturated fatty acids to be most affected.

Conclusion: Dapa is associated with excretion of metabolites other than glucose that generates a unique signature of urinary metabolome. Identification of renal response to SGLT2i may help further understand mechanisms of cardiovascular protection and weight loss mediated by SGLT2i.

Disclosure

A. Ilaiwy: None. A. Mincey: None. J. R. Bain: None. M. Muehlbauer: None. J. Campbell: None. D. A. D'alessio: Advisory Panel; Self; Eli Lilly and Company, Sun Pharmaceutical Industries Ltd., Research Support; Self; Eli Lilly and Company, Merck & Co., Inc.

Funding

Endocrine Fellows Foundation (5T32DK007012); National Institute of Diabetes and Digestive and Kidney Diseases
784-P: Does Sacubitril/Valsartan Combination Therapy Provide Additional Renal Benefits in Type 2 Diabetes Mellitus Receiving Canagliflozin?
Authors: GUPTA VISHAL , TELI VAISHALI
Published: June 2021

Aim: Study the effect of Sacubitril/valsartan (SV) combination therapy on renal functions in T2DM receiving canagliflozin (C).

Methodology: Between July and Sept 2018, T2DM patients aged 18-75 yrs, irrespective of baseline A1c, receiving SVC or C were retrospectively identified. The use of angiotensin receptor blockers (ARB) was 28.6% in SVC gr and 57% in C gr. Propensity score 1:1 matching was done for gr receiving SVC (49 patients) with C (49 patients) for variables to minimise confounding. Patients were evaluated 3 mthly for cardio-renal biomarkers (BMI, A1c, SBP, DBP, Lipid profile (TC, LDL, TG, HDL), Hs-CRP, Nt-ProBNP, creatinine (Cr), eGFR and microalbumin/creatinine ratio {UACR}) for 1 yr. T2DM with H/O IHD, revasularisation, major surgery, K+>5.5Meq/L and eGFR<45 were excluded. Baseline characteristics were analysed using descriptive statistics. Continuous variables were analysed using paired and unpaired t-test expressed as mean ± standard error. For interaction between drug class, ANOVA was used and p value <0.05 was considered significant (S).

Results: Baseline (B) characters: well matched except for age-yrs (SVC 61.27+9.43 and C 56+9.68, p-0.024) and NT-proBNP-pg/ml (SVC 438.68+758.13 vs. C 58.43+53.475, p-0.001). SVC, B-12mnths - S change in SBP, Hba1c, TC, LDL, TG, UACR and hs-CRP. C, B-12mnths - S change in BMI, SBP, DBP, HbA1c, TC, LDL, TG. SVC Versus C at 12mnths - No S difference seen for BMI-kg/m2 (SVC 0.381+0.297 vs. C 0.934+0.215, P-0.136), S-BP-mm (SVC 8.51+2.62 vs. C 6.429+2.349, p-0.556), D-BP-mm (SVC 2.143+1.582 vs. C 2.959+1.457, p-0.705), A1c-% (SVC 0.644+0.143 vs. C 0.677+0.190, p-0.88), Cr-mg% (SVC -0.009+0.025 vs. C 0.0067+0.0225, p-0.638), eGFR (SVC 1.307+2.388 vs. C 1.554+3.177, p-0.953), UACR mg/gm (SVC 52.876+22.684 vs. C 49.517+39.943, p-0.920), hs-CRP mg/L and Lipid Profile. There was no interaction with use of ARB for eGFR (p-0.074) and UACR (p-0.056).

Conclusion: SV does not provide additional renal benefits in T2DM receiving C.

Disclosure

V. Gupta: None. V. Teli: None.
787-P: Individualized Estimated GFR Slope Analysis Is Needed to Preserve Renal Function by SGLT2 Inhibitors in Patients with DKD
Authors: KASHIMA KOJI , SHIMIZU HIROYUKI , YAMADA MASANOBU
Published: June 2021

Objective: SGLT2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) with CKD. Since eGFR declining speed is different in each patient, we assessed renal protective effects by individual eGFR slope analysis.

Methods: A total of 75 patients with T2D with advanced CKD stage 3-4, treated by SGLT2i (empagliflozin 65% and others) were analyzed. The duration of diabetes at the time of recruitment were as follows: stage 3a (n=29); 11.9±5.4 yrs, stage 3b (n=28); 19.9±12.1 yrs, and stage 4 (n=18); 13.8±8.5 yrs. The mean of age was 70.3±12.2 yrs old. GLP-1RA (Liraglutide; n=36, Duraglutide; n=1) was used in 41%, 64% and 44% respectively. Most rapid baseline slopes were calculated from 46±20 months before using SGLT2i, and slopes after adding SGLT2i were calculated from 31±9 months.

Results: 1) In total, the initiation of SGLT2i decreased eGFR from 46.1±14.1 to 43.6±13.5ml/min/1.73m2 (P<0.001) on first month. 2) Individualized most rapid slopes were improved from -6.4±9.1 to -1.6±3.3ml/min/1.73m2/year (P<0.001). 3) Slopes were improved in all stages, stage 3a: -4.1±3.7 to -1.1±3.4 (P<0.001) and stage 3b; -4.9±3.7 to -1.6±2.9 (P<0.001), and stage 4; -12.4±16.3 to -2.2±3.7ml/min/1.73m2/year (P<0.03). 3) The proportion of responders (defined as their ratios of slopes are reduced < 1.0 after addition of SGLT2i) in each stage were as follows: stage 3a; (22/29), stage 3b; (22/28), stage 4; (16/18). Slopes in responders (61/75) were improved as follows, -7.4±9.8 to -1.0±2.9ml/min/1.73m2/year (P<0.0001). Slopes in non-responders (14/75) were worsened as follows, -2.0±2.0 to -4.1±3.5ml/min/1.73m2/year (P<0.001). 4) Slopes in rapid decliners (13/75) were remarkably improved from -18.9±16.4 to -1.5±3.6ml/min/1.73m2/year (P<0.01) with combined use of GLP-1RA (11/13), who had macro-albuminuria (9/13) and nephrosis (7/13).

Conclusion: To pursuit the renal benefits of SGLT2i, individualized slope analysis is needed for patient-centered care.

Disclosure

K. Kashima: None. H. Shimizu: None. M. Yamada: None.
794-P: Predictors of Hemoglobin (Hb) and Its Changes Focusing on Anemia and Polycythemia after Administration of the SGLT2 Inhibitor Tofogliflozin
Authors: MATSUBAYASHI YASUHIRO , YOSHIDA AKIHIRO , SUGANAMI HIDEKI , KAKU KOHEI , SONE HIROHITO
Published: June 2021

SGLT2 inhibitors (SGLT2is) increase hematocrit (Ht) and Hb, which may contribute to correcting anemia but also might cause secondary polycythemia. We investigated predictors of Hb after short- and long-term therapy with tofogliflozin (TOFO), a SGLT2i, and explored its impact on Hb in relation to anemia and polycythemia in type 2 diabetes mellitus (T2DM). Analyzed were 774 T2DM patients (66% male) who received TOFO for 52 weeks in two phase 3 studies. Mean baseline characteristics were age 59 y, HbA1c 8%, BMI 26 kg/m2, hemoglobin 15 g/dL and eGFR 84 mL/min/1.73m2. Participants were divided into the Anemia group (baseline Hb <13 g/dL in men and <12 g/dL in women, mean baseline Hb 11.8 g/dL) and Polycythemia group (>16.5 g/dL in men and >16 g/dL in women, mean baseline Hb 17.2 g/dL). Paired t-tests analyzed differences from baseline to weeks 4 and 52. Generalized linear model explored predictors of Hb at weeks 4 and 52. Correlation analysis was performed by Spearman’s product-moment correlation coefficients. Hb was significantly increased at week 4 [mean, +0.14g/dL*; *p<0.05 vs. baseline] and week 52 (+0.34g/dL*). Higher baseline brain natriuretic peptide and lower Ht and triglycerides (TG) were independently correlated with greater increases in Hb at week 4. Lower baseline Hb and TG were significantly correlated with greater increases in Hb at week 52. Higher baseline TG levels and proportion of fatty liver as a comorbidity were observed with higher baseline Hb values. Hb had significantly changed at week 52 in Anemia (+0.94*) and Polythycemia groups (-0.29*). Change in Hb was significantly correlated with change in TG at week 52 (Rho=0.42, p<0.05) in Polycythemia but not Anemia. Increased Hb after short-term TOFO therapy may be due to hemoconcentration while Hb may be corrected according to baseline Hb levels after long-term TOFO therapy. Lower TG in relation to improved fatty liver may be related to correction of higher Hb levels.

Disclosure

Y. Matsubayashi: None. A. Yoshida: Employee; Self; Kowa Company, Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd. K. Kaku: Advisory Panel; Self; Novo Nordisk Pharma Ltd., Consultant; Self; Sanwa Kagaku Kenkyusho, Research Support; Self; Taisho Pharmaceutical Co., Ltd., Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Eli Lilly Japan K. K., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co. 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.
8-OR: Depression and Diabetes Distress in African American and Latino Parents of Children with Type 1 Diabetes (T1D)
Authors: CARREON SAMANTHA A. , JONES JASMINE N. , GARCIA ARIADNE REYES , PETERS KEYISHI S. , CHRISTOPHER KRYSTAL K. , HILLIARD MARISA E. , BUTLER ASHLEY
Published: June 2021

Introduction: Parents of young children experience high levels of depression and diabetes distress immediately post-diagnosis. However, there is a limited understanding of these factors later in the disease course, especially among parents from racial/ethnic minority groups who face management difficulties and persistent T1D health disparities (i.e., higher HA1c). This study described parental depressive symptoms, diabetes distress and adherence among African American and Latino parents of children with T1D duration > 1 year.

Methods: African American (n = 39) and Latino (n = 26) parents of children age 5-10 years (M 9.0 ± 1.7 yrs; M HA1c = 9.0 ± 1.9; M T1D duration = 3.7±2.2 yrs) were enrolled in a behavioral intervention trial. At baseline they reported on demographics, treatment adherence (Diabetes Self-Management Questionnaire, DSMQ), diabetes distress (Problem Areas in Diabetes Revised for parents, PAID-PR), and depressive symptoms (Center for Epidemiological Studies-Depression, CES-D). HA1c was extracted from the medical record.

Results: Over one-quarter (27%) of African American (M CES-D = 13.6 ± 9.5) and 42% of Latino (M CES-D = 14.1 ± 8.8) parents reported moderate/severe depressive symptoms. Nearly half (49%) of African American (M PAID-PR = 56.7 ± 19.7) and 38% of Latino (M PAID-PR = 50.2 ± 17.8) parents reported diabetes distress above a clinical cutoff. Both African American and Latino parents reported high levels of adherence (M DSMQ = 25.9 ± 4.7 and 26.7 ± 4.3, respectively, out of 35).

Conclusions: Substantial proportions of African American and Latino parents of school-aged children who have been managing T1D for at least 1 year experience serious mood concerns, both diabetes-specific and general. High levels of T1D adherence indicate resilience in the face of such challenges. Supporting parental psychosocial functioning should be a high priority for diabetes care providers, especially among minority families who may be experiencing elevated challenges.

Disclosure

S. A. Carreon: None. J. N. Jones: None. A. Reyes garcia: None. K. S. Peters: None. K. K. Christopher: None. M. E. Hilliard: None. A. Butler: None.

Funding

National Institutes of Health (1DP3DK113236)
801-P: SGLT2 Inhibitor, Luseogliflozin, Prevent Sarcopenia by Improving Extracellular Lipidome
Authors: BAMBA RYO , OKAMURA TAKURO , HASHIMOTO YOSHITAKA , SENMARU TAKAFUMI , HAMAGUCHI MASAHIDE , FUKUI MICHIAKI
Published: June 2021

Aims: It has been reported that there is a close relationship between sarcopenia obesity and metabolic disorder such as lipid metabolism. Here we investigated the effect on lipid metabolism of the sodium glucose cotransporter-2 inhibitor (SGLT-2i) luseogliflozin in skeletal muscle. We preformed microarray analysis of mRNA in skeletal muscle and investigated the lipid profile in skeletal muscle and serum.

Methods: Eight-week-old mice were fed a standard diet or a standard diet supplemented with luseogliflozin (0.01% w/w chow) for 8 weeks. Mice were divided into the following three genotype/diet groups: Db/m mice without (w/o) SGLT-2i, Db/Db w/o SGLT-2i, and Db/Db with SGLT-2i. After 8 weeks of diet, in each group, body weight, glucose tolerance, muscle weight and cross-sectional area, free fatty acid concentration, muscle and gene expression in serum were investigated.

Results: The ratio of soleus muscle to body weight and the cross-sectional area of soleus muscle were significantly higher in Db/Db mice with SGLT-2i than in Db/Db mice w/o SGLT-2i. In addition, the concentration of saturated fatty acids in skeletal muscle and serum of Db/Db mice with SGLT-2i was significantly lower than that w/o SGLT2i, and the expression of Fasn, Elovl6, and Scd1, which are involved in fatty acid synthesis, in skeletal muscle was significantly increased in Db/Db w/o SGLT-2i compared to Db/m mice with SGLT-2i, and significantly decreased in Db/Db with SGLT-2i compared to mice w/o SGLT-2i. Furthermore, in cell experiments using C2C12 myotube cells, the administration of saturated fatty acid increased the expression of muscle atrophy-related genes.

Conclusion: The administration of luseogliflozin suppressed skeletal muscle atrophy and reduced the concentration of saturated fatty acids in skeletal muscle. Based on these findings, we hypothesized that secondary effects, other than the hypoglycemic effects of SGLT2i, might lead to the alleviation of obesity-dependent sarcopenia.

Disclosure

R. Bamba: None. T. Okamura: None. Y. Hashimoto: None. T. Senmaru: None. M. Hamaguchi: Research Support; Spouse/Partner; AstraZeneca K. K. M. Fukui: None.
804-P: Empagliflozin Reduces Inflammation and Bioenergetics in Proinflammatory Human Macrophages: Clues to Mechanisms of Blood Vessel Protection?
Authors: SPIGONI VALENTINA , CINQUEGRANI GLORIA , FANTUZZI FEDERICA , LORUSSO SIMONA , CAS ALESSANDRA DEI , BONADONNA RICCARDO C.
Published: June 2021

SGLT-2 inhibitors (SGLT2i) reduce cardiovascular (CV) risk in people with type 2 diabetes and atherosclerotic CV diseases. The inflammatory function of macrophages (Mφ) - which play a pivotal role in atherosclerosis - is strictly dependent on their metabolism.

Aim: To determine whether empagliflozin (EMPA) reduces inflammation and modifies bioenergetic metabolism in proinflammatory human Mφ (M1).

Methods: M1 were differentiated from healthy donors’ monocytes and incubated with/without EMPA 100 µM for 16h. Biomarkers of inflammation and oxidative stress were quantified by qPCR. Steady-state energetic metabolism (fluxes: pmol/min for 5x104 cells) was measured by indirect microcalorimetry [oxidations of lipids (LipOX,) glucose and amino acids; anaerobic glycolysis (AnaerGlyc); tricarboxylic acid cycle (TCA); energy expenditure (EPR); maximum estimate of ATP production (ATPflux)] which is based on the integration of measured O2 and H+ (Agilent Seahorse), lactate and NH4 (enzymatic method) fluxes with the stoichiometric equations of metabolic pathways.

Results: In M1, EMPA reduces (≈50%) inflammation (IL1β, IL8, TNFα and MCP1; p<0.05-0.001) and oxidative stress (GPX and HO-1; p <0.05). EMPA lowers OCR (133±9.7 vs. 153±10.3, p<0.001), LipOX (1.15±0.1 vs. 1.33±0.1; p<0.005), TCA (45±3 vs. 52±4; p<0.001), AnaerGlyc (210±23 vs. 268±24; p<0.01), ATPflux (1097±94 vs. 1313±94; p<0.005) and EPR (83±7 vs. 98±7 µJ/min; p<0.001). After dissipating mitochondrial membrane potential and forcing maximal OCR with FCCP, TCA (77±11 vs. 97±12, p=0.001), LipOX (1.7±0.3 vs. 2.2±0.4, p<0.005) and EPR (125±17 vs. 153±17; p<0.005), but not AnaerGlyc, remain inhibited by EMPA.

Conclusions: EMPA alters M1 inflammation along with cytosolic (AnaerGlyc) and - to a greater extent - mitochondrial (TCA) bioenergetics. EMPA-induced metabolic dysfunction of M1 in vivo might result into reduced metaflammation and contribute to SGLT2i-dependent CV protection.

Disclosure

V. Spigoni: None. G. Cinquegrani: None. F. Fantuzzi: None. S. Lorusso: None. A. Dei cas: Other Relationship; Self; Novo Nordisk. R. C. Bonadonna: Advisory Panel; Self; Sanofi, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company.

Funding

Italian Diabete Ricerca Foundation; Eli Lilly Italy
813-P: Demonstrating the Economic Health Benefit of Using the PromarkerD In Vitro Diagnostic Test in the Prediction of Diabetic Kidney Disease
Authors: BURCHENAL WILL , DATAR MANASI , PETERS KIRSTEN E. , FERNANDEZ GARETH C. , MORRISON JOHN C. , LIPSCOMBE RICHARD J.
Published: June 2021

Diabetic kidney disease (DKD) develops in 1 in 3 people with type 2 diabetes (T2D) and is the leading cause of end-stage renal disease (ESRD). DKD currently costs the US healthcare system USD 50 billion annually. PromarkerD is a simple biomarker-based blood test that can predict future renal function decline in T2D patients who have no or mild existing DKD (eGFR >30).

This study estimated the net savings to US payers from covering the PromarkerD test versus current standard of care (SOC). Model inputs included costs and frequency of testing, costs associated with changes to patient medication strategies, and cost-savings from slowed DKD progression and averted ESRD interventions (dialysis and kidney transplants). All estimates and inputs for the model were collected from recent peer-reviewed literature, established insurance payment rates, and PromarkerD clinical studies.

Results showed that over ten years the net savings for US payers by adopting PromarkerD testing for T2D patients (KDIGO DKD category G1-3b) would exceed USD 14 billion and the equilibrium point (costs equal savings) can be achieved after two years. Primarily, savings arise from slower DKD stage progression, with contributions from delayed dialysis and transplants, and also from fewer unplanned dialyses.

This economic study demonstrates that improved management of T2D patients through the use of early, accurate and cost-effective prognosis with the PromarkerD test could result in substantial savings to US payers in the treatment of DKD. Employing this alternative PromarkerD testing regime over the current SOC would enable early interventions for at-risk patients, thereby decreasing the need for expensive interventions such as dialysis and transplants, or unnecessary adoption of new therapeutic treatments.

Disclosure

W. Burchenal: Research Support; Self; Proteomics International. M. Datar: Research Support; Self; Proteomics International. K. E. Peters: Employee; Self; Proteomics International, Stock/Shareholder; Self; Proteomics International. G. C. Fernandez: Employee; Self; Proteomics International, Stock/Shareholder; Self; Proteomics International. J. C. Morrison: Consultant; Self; Proteomics International. R. J. Lipscombe: Employee; Self; Proteomics International.
816-P: Diabetes Education and Cost Savings with Telemedicine Delivery in Rural Communities
Authors: GAMMOH EMILY , JOHNSON PATRICIA A. , KRALL JODI S. , NG JASON , SIMINERIO LINDA M. , BANDI ARCHANA
Published: June 2021

The high prevalence of diabetes mellitus (DM) and shortage of Diabetes Care and Education Specialists (DCES) in rural communities requires providers and patients to travel long distances to access care. This burden impedes optimal DM management and increases cost. Telemedicine for Reach, Education, Access, Treatment, and Ongoing Support (TREAT-ON) is a Diabetes Education and Support (DSMES) model, where a DCES provides DSMES to patients identified as high risk (A1c >9% or unplanned care). TREAT-ON was initiated in February 2020, where DSMES was provided via telemedicine (TM) visits, previously delivered face-to-face (F2F) to high-risk patients. In this retrospective study, the DCES overall costs (fuel, tolls, and postage), travel time for care delivery, and number of patients seen over a 6-month period (March-August 2019) was compared to (March-August 2020) after TM practices were adopted.

From March to August 2019, 59 of 91 patient referrals were completed, compared to 110 of 167 referrals from March to August 2020. The percentage of successful referrals were similar in both groups (64.8% vs. 65.9%). However, the percent of referrals declined by patients were higher in 2019 (18.7%) vs. 2020 (9.0%). Of 59 referrals completed in 2019, 54 were F2F and five TM whereas in 2020 twelve were F2F and 98 TM. Lower average cost per patient was noted in 2020 ($38.85 vs. $6.20). A similar reduction in average travel time per patient was seen, 99 min vs. 16 min in 2020. TREAT-ON model translated to a direct cost savings of $1,606 and reduction of DCES travel time of 67.6 hours equating to a gain of 8.4 workdays opening care opportunities for an additional 67 new referrals.

DSMES is a pillar of DM care and alternative methods to expand DSMES services remain imperative. Our early TREAT-ON data shows that telemedicine offers a time and cost-effective approach to DSMES with potential to reach a larger population when compared to traditional F2F visits, and helps to address a current DSCES shortage.

Disclosure

E. Gammoh: None. P. A. Johnson: None. J. S. Krall: Research Support; Self; Becton, Dickinson and Company, Sanofi. J. Ng: Research Support; Self; Sanofi-Aventis. L. M. Siminerio: Advisory Panel; Self; Abbott Diabetes, Bayer U. S., Research Support; Self; Becton, Dickinson and Company. A. Bandi: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (1R34DK123370-01)
821-P: A Retrospective Chart Review and Comparison of HbA1c Goals to Proposed Calculator Models
Authors: ZUZEK ALEONA C. , KELLY CLARE , KASSEM LAURE SAYYED , RAJPAL AMAN
Published: June 2021

Setting individualized goals for glycemic control is widely accepted as standard of care in the management of diabetes mellitus. This requires integration of numerous factors into the goal HbA1c, many of which can be subjective. Few tools are available to assist in goal-setting, including an online calculator based on work by Cahn et al (1). We aimed to evaluate the current practice of setting personalized HbA1c targets at an academic medical center and compare the targets to those derived from the calculator model and the VA/DoD (Department of Defense) DM guidelines (2). A chart review of outpatient diabetes visits in both primary care and diabetes specialty clinics was performed from 11/2019-12/2020. Documentation of HbA1c goals was assessed. All patient factors that contribute to goal-setting were gathered and a proposed HbA1c goal via calculator model and VA/DoD guidelines was set for each patient. A comparison between these HbA1c goals was conducted. Of the 100 patient charts reviewed, only 25% (25/100) included a specified goal HbA1c. Of those, 88% (22/25) of the clinicians’ goals matched the calculated HbA1c goal, whereas only 32% (8/25) matched the estimated HbA1c based on VA/DoD guidelines. Documentation of individualized glycemic targets in the management of DM is not routinely practiced. When HbA1c goals are specified, they tend to correlate well with suggested goals obtained via a comprehensive calculator and less so with guidelines that rely heavily on a clinician’s subjective assessment. These findings suggest an opportunity to provide further education on setting individualized goals of care in the management of DM, as well as the utility of calculator models in assisting clinicians in daily practice.

Cahn A, et al. Clinical Assessment of Individualized Glycemic Goals⋯ Diabetes Care. 2015;38(12):2293-2300.VA/DoD Clinical Practice Guideline for the Management of Type 2 DM in Primary Care. https://www.healthquality.va.gov/guidelines/CD/diabetes/VADoDDMCPGFinal508.pdf.

Disclosure

A. C. Zuzek: None. C. Kelly: None. L. Sayyed kassem: None. A. Rajpal: None.
829-P: Improving Diabetes Self-Management with a Peer-to-Peer Mentoring Program: Final Results of a Pilot Program at a Safety Net Health Care System
Authors: MARCELLO ROOPA KALYANARAMAN , DOLLE JOHANNA , KAUR SHARANJIT , PATTERSON SAWKIA R. , DAVIS NICHOLA
Published: June 2021

New York City Health + Hospitals (NYC H+H) is the largest safety net healthcare system in the nation, serving more than one million patients each year. Most of NYC H+H’s patients are low-income and people of color, who, in NYC as in the rest of the nation, bear a disproportionate burden of chronic diseases. At NYC H+H, 18% of patients have diagnosed diabetes, and nearly 23,000 (39%) of the 59,000 patients monitored in NYC H+H’s diabetes registry have poorly controlled diabetes (A1c ≥ 8). In an effort to support these patients’ diabetes management between their regular visits, NYC H+H launched a pilot program of InquisitHealth, a one-on-one peer mentoring service that matches patients with mentors who have controlled their own diabetes and received training to become peer coaches. Several small, randomized, controlled trials have demonstrated the program’s effectiveness in reducing A1c, but there is limited evidence of its effectiveness in a real-word setting. The key aims of this pilot program were to: 1) bridge the gap between patients and providers outside of clinic visits, 2) increase patient education on and support for diabetes self-management, and 3) improve patients’ diabetes outcomes as evidenced by reductions in A1c. The pilot program enrolled 336 patients at two NYC H+H facilities for a twelve-month intervention. Among the first 180 patients enrolled at one large acute care hospital, the mean reduction in A1c from baseline to six months following enrollment was 1.08. As compared to propensity score-matched control patients at a similar non-participating hospital in the NYC H+H network, participants experienced a greater reduction in A1c of 0.61 (-1.08 vs. -0.47, p<0.01). Results from the 12-month final analysis of all participants will be presented.

Disclosure

R. Kalyanaraman marcello: None. J. Dolle: None. S. Kaur: None. S. R. Patterson: None. N. Davis: None.

Funding

National Institutes of Health (UL1TR001445)
835-P: Characteristics, Comorbidities, and Tobacco Cessation Outcomes in an Underserved Community with and without Diabetes and Health Disparities
Authors: WANG FEI , ALLOTEY PRINCE A. , VESTERGAARD MAI , VERGARA CUNEGUNDO M.D. , WILKEN JOEL L. , HAREL OFER
Published: June 2021

Background: Current smoking in the U.S. disproportionately affects low-income populations with healthcare disparities. Diabetes independently confers substantial atherosclerotic cardiovascular disease risk, and those who smoke have worse health outcomes.

Purpose: To increase screening and cessation services in a priority population through a systems level change.

Methods: A cross-cultural cohort of staff in large safety net health system were trained as tobacco treatment specialists. A bi-lingual (Spanish-English) program coordinator provided outreach to increase awareness and referrals to the tobacco treatment program. Optimization of an electronic medical record enabled an ambulatory smoking cessation framework. Baseline characteristics and abstinence rates at 7-months were compared between the intervention and usual care cohorts. Dichotomous or categorical variables are presented as percentages and compared between groups using Chi-square. Continuous variables are presented as means with standard deviations and compared using independent t-tests using R software version 3.6.1.

Results: From 2018 through 2020, there were 400 referrals. Two-hundred opted into the tobacco cessation program (intervention cohort) and 200 opted out to usual care (control cohort). The average age was 54 years with a mean use of 17 cigarettes per day. Most participants were female (53%), predominantly Hispanic (61%), and received public insurance (88%). In subgroup analyses, 34% and 27% of patients had diabetes in the intervention and usual care cohorts, respectively. The 7-month abstinence rate was 30% versus 5% (p value 0.000) in the intervention versus usual care cohorts, respectively.

Conclusion: Creating a sustainable tobacco cessation pathway within a large health-system improves population health access and quit rates in underserved communities with health disparities.

Disclosure

F. Wang: None. P. A. Allotey: None. M. Vestergaard: None. C. M. D. Vergara: None. J. L. Wilken: None. O. Harel: None.

Funding

Connecticut Department of Public Health Tobacco and Health Trust Fund (DPH2017-0097)
852-P: Improving the Quality of Health Care Transitions for Young Adults at an Adult Endocrinology Clinic
Authors: GILBERT MATTHEW P. , DEVOE STEPHEN G. , KENNEDY AMANDA G. , OGELBY MONICA , CONSIGLI ALYSSA , ZIMAKAS PAUL JAMES , REPP ALLEN B. , ROBINSON KEITH J.
Published: June 2021

Background: Young adults, transitioning from pediatric to adult endocrinology clinics, are at risk for adverse events. As these patients assume responsibility for their care, ensuring an effective process for health care transition (HCT) and integration into an adult clinic is imperative. Yet, there is a scarcity of data on implementing HCT best practice guidelines into adult endocrinology care using QI methodology.

Objective: To improve the quality of HCTs for young adult patients (18-26 years of age) diagnosed with a variety of endocrinologic conditions by implementing Got Transition’s Six Core Elements of Health Care Transition 2.0 and utilizing the Integrating Young Adults into Adult Health Care toolkit.

Methods: A team of pediatric and adult endocrinology clinicians, QI experts, and patient and family advisors (PFAs) was established to guide implementation of the Six Core Elements. Got Transition measurement tools (Current Assessment of Health Care Transition Activities-CAHCTA; Health Care Transition Process Measurement Tool-HCTPMT) were used to establish baseline scores and track progress on a quarterly basis. The team developed a “Welcome Packet” to orient and integrate young adults into adult endocrinology care. QI tools were used to identify current clinical processes and opportunities for system changes through Plan-Do-Study-Act (PDSA) cycles.

Results: From October 2019 to July 2020, baseline scores improved on both the CAHCTA by 84.6% (Baseline: 13; Q1: 15; Q2: 23; Q3: 24) and the HCTPMT by 1,250.0% (Baseline: 2; Q1: 16; Q2: 25; Q3: 27). PFAs provided feedback about the Welcome Packet. PDSA Cycle 1 included a “pre-visit” during new patient visits to orient patients to adult endocrinology care using the Welcome Packet. PDSA Cycle 2 focused on piloting the Endocrine Society Patient Self-assessment.

Conclusion: The implementation of HCT best practice guidelines using rigorous QI methodology can significantly improve young adults’ integration into adult health care.

Disclosure

M. P. Gilbert: Consultant; Self; Novo Nordisk. S. G. DeVoe: None. A. G. Kennedy: None. M. Ogelby: None. A. Consigli: None. P. Zimakas: None. A. B. Repp: None. K. J. Robinson: None.
863-P: Diagnostic and Care Gaps for Nonalcoholic Fatty Liver Disease in Poorly Controlled Type 2 Diabetes: A Role for Endocrinology?
Authors: ALEXOPOULOS ANASTASIA-STEFANIA , DUFFY RYAN , KOBE ELIZABETH A. , MOYLAN CYNTHIA A. , JEFFREYS AMY S. , COFFMAN CYNTHIA , SOLIMAN DIANA , GERMAN JASHALYNN , CROWLEY MATTHEW
Published: June 2021

Nonalcoholic fatty liver disease (NAFLD) and its complications disproportionately impact individuals with T2DM. NAFLD prevalence is thought to be 60-70% in T2DM. In response to this, guidelines now recommend additional liver testing and risk stratification of NAFLD in patients with T2DM who have elevated liver enzymes or steatosis seen on ultrasound. In this secondary analysis of data from a randomized trial of a telehealth intervention, we investigated NAFLD testing and care patterns in a cohort of Veterans with poor T2DM control across two VA sites (n=244) over a 2-year period (2018-2020). Mean HbA1c and BMI were 9.8% (SD 1.5%) and 35.0 kg/m2 (SD 6.3), respectively. Only 6.6% (n=16) had a documented diagnosis of NAFLD. Excluding those with known NAFLD or other liver diseases (i.e., hepatitis B/C [n=14], alcohol overuse [n=6]), the majority of patients had documented liver enzyme (87%, n=184) and platelet (89%, n=187) testing. Based on established lab criteria for NAFLD diagnosis (i.e., at least two ALT ≥ 40 IU/mL in men, ≥ 31 IU/mL in women, ≥ 6 months apart), 17% (n=36) had undiagnosed NAFLD. Despite available lab data, no patients had a lab-based risk stratification score (such as the fibrosis-4 index or NAFLD fibrosis score) documented in clinical notes or electronic problem lists. Only 7% of patients had undergone liver ultrasound (n=15) and 2.4% Fibroscan (n=5), which are the usual first-line imaging modalities for diagnosis and risk stratification of NAFLD, respectively. Of patients with persistently elevated liver enzymes (n=36), only 14% (n=5) were referred to Hepatology.

In summary, this study highlights the underrecognition of NAFLD in T2DM, even in patients with poor glycemic control and obesity who are exceedingly high risk of NAFLD complications. Since Endocrinologists commonly see patients with high metabolic risk, this study also highlights an important role for Endocrinologists in the proactive detection and risk stratification of NAFLD in T2DM.

Disclosure

A. Alexopoulos: None. R. Duffy: None. E. A. Kobe: None. C. A. Moylan: None. A. S. Jeffreys: None. C. Coffman: None. D. Soliman: None. J. German: None. M. Crowley: None.
868-P: The Efficacy of Personalized Diabetes Management Using an Electronic Medical Record-Integrated Mobile Application
Authors: YUN JAE-SEUNG , LIM SUN-YOUNG , CHA SEON-AH , YOON KUN-HO , AHN YU-BAE , LEE EUN YOUNG , KO SEUNG-HYUN
Published: June 2021

Background: We aim to evaluate the efficacy of personalized intervention based on a mobile phone application in patients with type 2 diabetes (T2DM).

Methods/Design: This is a 26-week randomized controlled, open-label, and parallel group trial. A total of 275 patients with T2DM having HbA1c ≥7.5% were recruited from two medical centers. Participants were randomized 1:1:1 and assigned to three groups: 1) usual care, 2) mobile diabetes management, or 3) mobile diabetes management with personalized feedback from health care professionals every two weeks. In groups 2 and 3, a mobile application integrated with the hospital electronic medical record (EMR) system is used to support diabetes management in addition to usual care. The primary outcome is change in HbA1c from baseline to 26 weeks; there are ten additional secondary outcomes, including insulin resistance, and lifestyle changes.

Results: Of the 275 initial participants, 20 (7.3%) dropped out. Mean participant age is 52.2±12.4 years, females comprise 56.4%, and the mean duration of diabetes is 11.5±8.6 years. Baseline characteristics including HbA1c are not significantly different between the groups. During the first 12 weeks, significant reduction in % change of HbA1c was observed in both mobile app-based intervention groups relative to the control group (group 1, -6.0±11.1% vs. group 2, -9.2±13.3% vs. group 3, -10.7±12.0%; P value=0.041). Participants in the intervention group measured their blood glucose more frequently, but occurrence of hypoglycemia was not different among the three groups. The majority (87.4%) of app-using participants were satisfied with the app, indicating that it was easy to use and made them adherent to their diabetes care.

Discussion: This trial is currently ongoing and will evaluate the clinical efficacy, features promoting clinical efficacy and patient engagement, and cost effectiveness of diabetes management using an EMR-integrated mobile application in patients with T2DM.

Disclosure

J. Yun: None. S. Lim: None. S. Cha: None. K. Yoon: None. Y. Ahn: None. E. Lee: None. S. Ko: None.

Funding

Korea Health Industry Development Institute (HI19C0784)