bluuebunny/crossref_metadata_2025 huggingface dataset:
1103-P: Balancing the Risk of DKA and Severe Hypoglycemia with Sotagliflozin in Adults with Type 1 Diabetes
Authors: PETTUS JEREMY , CARIOU BERTRAND , SAWHNEY SANGEETA , BANKS PHILLIP L. , DAVIES MICHAEL J. , LAPUERTA PABLO
Published: June 2020

Background: DKA and severe hypoglycemia (SH) are the 2 most important acute complications of type 1 diabetes (T1D). SGLT inhibitors are associated with an increased risk of ketosis and DKA. Sotagliflozin (SOTA), a dual SGLT 1 and 2 inhibitor, has been shown to reduce the incidence of documented hypoglycemia and SH as adjunct to insulin therapy in T1D. The objective was to determine if the increased risk of DKA with SOTA was offset by the reduction of SH.

Methods: Data were pooled from the inTandem 1 and 2, 52-week, placebo (PBO)-controlled studies in adults with T1D (N=1575). Events of DKA and SH were adjudicated by an IRC. Incidence and exposure-adjusted incidence rates (EAIR) were calculated along with numbers needed to treat or harm (NNT/NNH).

Results: A higher incidence of adjudicated DKA was seen with SOTA 200 and 400 mg (2.9 and 3.8%) compared to PBO (0.2%). However, SOTA was associated with a lower rate of hypoglycemia events with blood glucose levels ≤55 mg/dL and a lower incidence of adjudicated SH with SOTA 200 and 400 mg (5.7 and 4.4%) compared with PBO (7.4%). The absolute risk difference in EAIR between SOTA and PBO was 2.9 to 4.0 events per 100 patient-yr for DKA and -1.9 to -3.4 events per 100 patient-yr for SH (Figure). NNH for DKA (28) was similar to the NNT for SH (33) with SOTA 400 mg.

Conclusions: With SOTA added to insulin, the increase in DKA was similar in magnitude to the decrease in SH in adults with T1D.

Disclosure

J. Pettus: Consultant; Self; Diasome Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk Inc., Sanofi. B. Cariou: Advisory Panel; Self; Bristol-Myers Squibb, Gilead Sciences, Inc., Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; GENFIT. Research Support; Self; Amgen, Regeneron Pharmaceuticals. Speaker’s Bureau; Self; Abbott, AstraZeneca. S. Sawhney: None. P.L. Banks: Employee; Self; Lexicon Pharmaceuticals, Inc. M.J. Davies: Employee; Self; Lexicon Pharmaceuticals, Inc. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc.
1106-P: Effects of Long-Term Dapagliflozin Treatment on Hemorheology (D-PATH Study)
Authors: ONO SHOYA , NAKATANI YUKI , KAWABE ATSUHIKO , MIYASHITA YASUSHI , MATSUMURA MIHOKO , BANBA NOBUYUKI , ASO YOSHIMASA , YASU TAKANORI
Published: June 2020

Introduction: Hemorheology (blood viscosity) was reported to be a strong predictor of cardiovascular events in the Edinburgh Artery Study. However, deterioration in hemorheology through microvessels is a potential adverse effect of Sodium-glucose cotransporter-2 (SGLT2) inhibitors. This study aimed to clarify the effect of dapagliflozin on blood fluidity.

Method: This multi-center, open-label, randomized, comparative study included 90 patients with type 2 diabetes mellitu. Patients were randomly divided into treatment groups with and without dapagliflozin treatment, and each item was investigated. The primary endpoint was the whole blood transit time, based on the difference from the baseline to 16 weeks after enrollment, as measured by a microchannel array flow analyzer (MC-FAN). To assess this outcome, a 15% noninferiority margin (clinically significant cut-off value) was used. To test the noninferiority of the treatment, a t-distribution was used to calculate the 95% confidence interval to assess the difference from the baseline.

Results: The whole blood transit time in the dapagliflozin group was 41.8 ± 6.1 sec (mean ± SD) before administration, and 43.4 ± 6.8 sec at 16 weeks after dapagliflozin administration. In the control group, the whole blood transit time was 40.5 ± 3.0 sec before administration and 39.9 ± 3.8 sec after 16 weeks. The difference between groups from the baseline to 16 weeks after enrollment was 1.7 sec [0.2, 3.5] (95% C.I), confirming the noninferiority of dapagliflozin administration. Futher, the analysis Results of the differences between groups according to the some items (the baseline of hematocrit, HbA1c levels and the whole blood transit time) for baseline, demonstrating the noninferiority of dapagliflozin administration in these items.

Conclusion: Dapagliflozin was unlikely to have negative effects on blood fluidity after administration irrespective of the baseline Hematocrit, HbA1c levels and the whole blood transit time.

Disclosure

S. Ono: None. Y. Nakatani: None. A. Kawabe: None. Y. Miyashita: None. M. Matsumura: None. N. Banba: None. Y. Aso: None. T. Yasu: None.

Funding

AstraZeneca
1108-P: Resveratrol Inhibits Dapagliflozin-Induced Renal Gluconeogenesis through Modulating the PI3k/Akt/Foxo1 Pathway in HK-2 Cells
Authors: SUN XIAOYA
Published: June 2020

Aims: Dapagliflozin(Dapa) improves glycemia by increasing glucosuria, but it enhances renal gluconeogenesis, thus reducing its efficacy. Resveratrol (RSV) inhibits hepatic gluconeogenesis by increasing insulin sensitivity. Our study aims to determine if RSV can reduce dapa-induced renal gluconeogenesis via modulating the PI3K/Akt/FoxO1 pathway.

Methods: Glucose produced via gluconeogenesis was tested by glucose assay kit. Changes in insulin signaling and gluconeogenic key enzymes were detected by RT-PCR and western blot.

Results: Dapa induced glucose production and the expression of gluconeogenic enzymes (PEPCK, G6Pase) via increasing the expression of FoxO1 in HK-2 cells. RSV treatment reversed all these findings by up-regulating pFoxO1 expression. The PI3K inhibitor LY294002 restained the pFoxO1 expression and subsequently inhibited PEPCK and G6Pase expression via PI3K/Akt-mediated FoxO1 inactivation.

Conclusion: Our data show that RSV ameliorates gluconeogenesis via modulating the PI3K-Akt-FoxO1-PEPCK/G6Pase pathway in dapa-treated HK-2 cells. This mechanism provides a basis for pharmaceutial intervention in order to achieve better hypoglycemic effect in future animal and human research.

Disclosure

X. Sun: None.
112-OR: Integrative Analysis of Chromatin Accessibility and Genetic Risk in T1D Patients and Controls
Authors: ROBERTSON CATHERINE C. , CHEN WEI-MIN , ONENGUT-GUMUSCU SUNA , CONCANNON PATRICK J. , RICH STEPHEN S.
Published: June 2020

Motivation: Twin studies estimate 50% of type 1 diabetes (T1D) risk is genetic. Genetic association has implicated T cells as central to the disease process. Thus, we generated chromatin accessibility profiles from CD4+ T cells isolated from 135 T1D cases and 144 controls and investigated whether (1) there are patterns of chromatin accessibility that differ from T1D patients compared to healthy controls; (2) established T1D risk variants influence chromatin accessibility.

Methods: Frozen PBMCs were provided by the Type 1 Diabetes Genetics Consortium (T1DGC). CD4+ T cells were isolated using bead purification and Assay for Transposase Accessible Chromatin (ATAC-seq) was performed. ATAC-seq samples were processed using the PEPATAC pipeline and R packages edgeR and limm.

Results: We tested for differences in accessibility between individuals with and without T1D adjusting for sex, age, and experimental variability. We identified 516 chromatin regions peaks with differential accessibility by T1D status (2 with increased and 514 with decreased accessibility at FDR<0.05). Enrichment analysis with the software LOLA indicated these regions are enriched for ETS-1, AP1, and Maf transcription factor binding motifs. Next, we tested for association between T1D-associated variants and chromatin accessibility using available T1DGC genotypes. For each T1D variant with an observed chromatin accessibility quantitative trait locus effect (caQTL), we tested for colocalisation between the two signals and used publicly available expression QTLs (eQTL) to identify potential target genes. We identified six regions where data were consistent with a single variant driving association with T1D risk, chromatin accessibility in CD4+ T cells, and gene expression in whole blood, highlighting several candidate T1D genes: ANKRD55, IL6ST, BACH2, CENPW, SUOX, GDF11, GSDMB, ORMDL3, IKZF3, ERBB2, PNMT.

Conclusion: These results provide hypotheses about molecular mechanisms of T1D in CD4+ T cells.

Disclosure

C.C. Robertson: None. W. Chen: None. S. Onengut-Gumuscu: None. P.J. Concannon: Stock/Shareholder; Self; Amgen. Other Relationship; Self; 10x Genomics. S.S. Rich: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (DK111906)
113-LB: Home Diabetes Regimen and Admission HbA1c as Predictors of Hospital Glycemic Control: A Pooled Analysis of Inpatient Clinical Trials
Authors: URRUTIA MARIA A. , GUO YI , FAYFMAN MAYA , VELLANKI PRIYATHAMA , GALINDO RODOLFO J. , MIGDAL ALEXANDRA , DAVIS GEORGIA , ANZOLA ISABEL , ALBURY BONNIE S. , SCIOSCIA MARIA F. , ZAMUDIO KARLA W. , UMPIERREZ GUILLERMO E. , PASQUEL FRANCISCO J.
Published: June 2020

Glycated hemoglobin (HbA1c) on admission has been suggested as a predictor of glycemic control in the hospital. However, no studies have examined the interaction of pre-admission patient characteristics (i.e., complexity of home regimen or diabetes duration) and HbA1c on inpatient glycemic control. We pooled data from eight randomized controlled trials of patients assigned to a standardized basal-bolus insulin regimen in the hospital. Patients were categorized according to: A) increasing home regimen complexity [group 1: diet alone or ≤1 oral antihyperglycemic drugs (OADs) (n=338, 39%); group 2: two or more OADs (n=177, 20%); and group 3: insulin based regimens (n=356, 41%) and B) admission HbA1c categories (<7%, 7-9%, or >9%). Logistic regression models adjusting for age, gender, BMI, admission BG, and hospital service (medicine vs. surgery) were constructed to determine associations between home regimen complexity, diabetes duration, HbA1c and inpatient glycemic control. Compared to patients treated at home with OADs, patients using insulin had a longer duration of diabetes and higher admission HbA1c (both p<0.001). Compared to group 1 (reference), patients on insulin were less likely to achieve target glycemic control (mean BG 70-180 mg/dl without hypoglycemia) regardless of admission HbA1c [HbA1c <7% adjusted odd ratio (aOR) 0.36 (0.16, 0.81); HbA1c 7-9% aOR 0.5 (0.30, 0.91), or HbA1c >9% aOR 0.44 (0.24, 0.83), and had higher risk for hypoglycemia (all p<0.05). Patients with a longer duration of diabetes (>10 years) were less likely to achieve good glycemic control compared to patients with shorter duration of diabetes irrespective of home regimen complexity. Though admission HbA1c has been proposed as a predictor of inpatient glycemic control, our data show patients requiring complex therapy with insulin at home are less likely to achieve inpatient glucose targets independent of admission HbA1c.

Disclosure

M.A. Urrutia: None. Y. Guo: None. M. Fayfman: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. R.J. Galindo: Advisory Panel; Self; Lilly Diabetes. Consultant; Self; Valeritas, Inc. Research Support; Self; Novo Nordisk Inc. Other Relationship; Self; UpToDate. A. Migdal: None. G. Davis: None. I. Anzola: None. B.S. Albury: None. M.F. Scioscia: None. K.W. Zamudio: None. G.E. Umpierrez: None. F.J. Pasquel: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp. Research Support; Self; Dexcom, Inc., Merck Sharp & Dohme Corp., National Institutes of Health.
1133-P: Association of Higher Baseline BNP Levels with a Greater Reduction in Plasma Volume and Increase in Beta-Hydroxybutyrate via the SGLT2 Inhibitor Tofogliflozin in Type 2 Diabetes
Authors: YOSHIDA AKIHIRO , MATSUBAYASHI YASUHIRO , NOJIMA TOSHIAKI , SUGANAMI HIDEKI , OE MOMOKO , FUJIHARA KAZUYA , TANAKA SHIRO , KAKU KOHEI , SONE HIROHITO
Published: June 2020

Reduced plasma volume (PV) to decrease ventricular filling pressure and increased beta-hydroxybutyrate (BHB) as a substitute for the energy source by SGLT2 inhibitors (SGLT2is) might contribute to preserving the heart in type 2 diabetes mellitus (T2DM). However, the impact of SGLT2is on PV and BHB is little known according to cardiac workload. We investigated the effect of long-term treatment with the SGLT2i, tofogliflozin, on PV and BHB according to baseline brain natriuretic peptide (BNP) levels in T2DM. Analyzed were 774 T2DM patients who received tofogliflozin for 52 weeks as mono- and add-on-therapy in two phase-3 studies. Percent change in estimated PV (%ΔePV) was calculated by the Strauss formula: {100*(pre Hb/post Hb)*[(100 - post Ht)/(100 - pre Ht)] - 100}. We divided patients into two groups (Quartiles 1-3[Q1-3] and Quartile 4[Q4]) according to baseline BNP. Differences in characteristics were analyzed using unpaired t-test, wilcoxon rank sum test or Fisher’s exact test. Differences in changes between groups were analyzed using an analysis of covariance model. Multivariate analysis evaluated the association of baseline BNP with changed variables. Baseline characteristics were: male (71 vs. 52% *, * p<0.05, Q1-3 vs. Q4), age (mean: 57 vs. 64 y *), HbA1c (8.1 vs. 8.0%), BMI (26 vs. 25 kg/m2 *), BNP (median: 9 vs. 27 pg/mL *) and BHB (45 vs. 54 µmol/L). Reduction in Ln-transformed BNP (ln-BNP) was greater in Q4 (least square mean: -0.5 ln[pg/mL]) than in Q1-3 (-0.1) as was %ΔePV (Q4 [-6 %] vs. Q1-3 [-4]). Increase in Ln-transformed BHB (ln-BHB) was larger n Q4 (+0.7 ln[µmol/L]) than in Q1-3 (+0.5). Changes in HbA1c, body weight and blood pressure were similar. Q4 was independently correlated with the greater reduction in %ΔePV and increase in ln-BHB. Results suggested that reduced PV and increased BHB might be greater in T2DM patients with higher baseline BNP levels after long-term tofogliflozin therapy.

Disclosure

A. Yoshida: Employee; Self; Kowa Company, Ltd. Y. Matsubayashi: None. T. Nojima: Employee; Self; Kowa Company, Ltd. H. Suganami: Employee; Self; Kowa Company, Ltd. M. Oe: Employee; Self; Kowa Company, Ltd. K. Fujihara: None. S. Tanaka: None. K. Kaku: Advisory Panel; Self; Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc. Consultant; Self; Sanwa Kagaku Kenkyusho. Research Support; Self; Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. H. Sone: Research Support; Self; Kyowa Hakko Kirin Co., Ltd., Novartis AG, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.
1134-P: The Secretome of Visceral Adipose Cells Induces Apoptosis of Cardiac Progenitor Cells in Human Obesity: Protective Effects of the SGLT2 Inhibitor Dapagliflozin
Authors: PORRO STEFANIA , PERRINI SEBASTIO , CACCIOPPOLI CRISTINA , DORIA ROSSELLA , GENCHI VALENTINA ANNAMARIA , SCHIPANI ROSSELLA , CIGNARELLI ANGELO , NATALICCHIO ANNALISA , LAVIOLA LUIGI , GIORGINO FRANCESCO
Published: June 2020

This study aimed to assess whether the secretome from abdominal visceral (AV) and epicardial (E) adipose stem cells (ASC), ASC-derived mature adipocytes, and isolated AV mature adipocytes may affect the viability of cardiac progenitor cells (CPC) in human obesity, and whether dapagliflozin (DAPA) may reduce the proapoptotic effects in injured CPC. ASC were isolated from AV and E adipose tissue biopsies of nondiabetic subjects with varying levels of BMI and used before and after differentiation into adipocytes in vitro. CPC were isolated from right auricle biopsies of non-obese (Ob) subjects, preincubated in the presence or absence of 10 uM DAPA, and exposed or not to conditioned media (CM) of AV-ASC, E-ASC, AV-ASC-derived adipocytes and isolated AV mature adipocytes. The CM of AV-ASC and differentiated adipocytes from Ob subjects induced CPC apoptosis after 4-8-24 h (p<0.05). In addition, exposure of CPC to CM of Ob AV-ASC and mature adipocytes resulted in marked inhibition of insulin-stimulated Akt phosphorylation (Akt-Ph) (p<0.05). In contrast, the CM of AV-ASC and differentiated adipocytes from non-Ob subjects did not induce apoptosis nor impaired insulin signaling. Similarly, the CM of AV mature adipocytes isolated from Ob subjects induced a marked apoptosis of CPC (p<0.05) and inhibited insulin-stimulated Akt-Ph, whereas no effects were observed when CPC were exposed to CM of mature adipocytes isolated from non-Ob subjects. Of note, the CM of E-ASC isolated from Ob subjects also induced CPC apoptosis and impaired insulin-stimulated Akt-Ph (p<0.05), while these effects were not observed when CPC were exposed to CM of E-ASC from non-Ob subjects. The proapoptotic effects of the CM in the CPC were inhibited when these cells were pretreated with DAPA (p<0.05).

In conclusion, the secretome of adipose cells from Ob subjects impairs insulin action and viability of the CPC, and these effects can be counteracted by DAPA.

Disclosure

S. Porro: None. S. Perrini: None. C. Caccioppoli: None. R. Doria: None. V. Genchi: None. R. Schipani: None. A. Cignarelli: None. A. Natalicchio: Consultant; Self; AstraZeneca, Novo Nordisk Inc., Sanofi-Aventis. L. Laviola: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk Inc., Roche Diabetes Care, Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Medtronic. F. Giorgino: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Roche Diabetes Care, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., LifeScan, Inc., MedImmune, Merck Sharp & Dohme Corp., Roche Diabetes Care, Sanofi. Research Support; Self; Eli Lilly and Company, LifeScan, Inc., Takeda Development Centre Europe Ltd.
1136-P: Glucose Kinetics during Oral Glucose Challenge following Administration of Exenatide and Dapagliflozin Alone and in Combination in Type 2 Diabetes
Authors: ALATRACH MARIAM , AGYIN CHRISTINA , LAICHUTHAI NITCHAKARN , LAVRYNENKO OLGA , ADAMS JOHN M. , ABDUL-GHANI MUHAMMAD , TRIPLITT CURTIS L. , DEFRONZO RALPH A. , CERSOSIMO EUGENIO
Published: June 2020

Aim: To examine the effect of SGLT2i on endogenous glucose production (EGP), tissue glucose disappearance (Rd), and urinary glucose excretion (UGE) following glucose ingestion.

Study Design: 28 type 2 diabetes [T2D] patients (Age= 51±2 y; BMI=31.2±0.7; A1C=7.9±0.2%) received 8-hour 3-3H-glucose infusion after an overnight fast. Previously shown, EGP suppression by dapagliflozin (DAPA) compared to placebo (PCB) (Δ=-0.02±0.02 vs. -0.45±0.03, p<0.01 mg/kg.min) was impaired. On a separate day, subjects were randomized to receive 5-hour double-isotope (IV 3-[3H]-glucose and oral [14C]-glucose) OGTT (75-g) preceded by PCB, DAPA 10 mg, EXEN 5 µg, or DAPA+EXEN. Oral [RaO], EGP, Total and Tissue Rd, and UGE were calculated.

Results: During 0-300-min, RaO was 65 g in DAPA, 59 g in PCB, 46 g in EXEN, and 48 g in DAPA+EXEN. UGE was 31±4 g in DAPA and 30±4 g in DAPA+EXEN, but only 3±1 g in EXEN and 10±3 g in PCB (p<0.001 vs. DAPA and DAPA+EXEN).

Conclusion: The post-OGTT rise in PG was significantly reduced after DAPA+EXEN vs. each drug alone. This resulted from lower oral glucose appearance with greater UGE. During the OGTT, EGP suppression with DAPA (Δ = -0.8±0.1 mg/kg.min) was less than with PCB, EXEN, and DAPA/EXEN (p<0.05-0.01), while EGP suppression with DAPA/EXEN was similar to PCB but required a higher rise in insulin (p<0.05). Tissue glucose clearance was unchanged by any therapy.

Disclosure

M. Alatrach: None. C. Agyin: None. N. Laichuthai: None. O. Lavrynenko: None. J.M. Adams: None. M. Abdul-Ghani: None. C.L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Xeris Pharmaceuticals, Inc. R.A. DeFronzo: None. E. Cersosimo: None.
1140-P: Empagliflozin Attenuates Fasting and Postprandial Hyperglycemia in Totally Pancreatectomized Patients: A Randomized, Double-Blinded, Placebo-Controlled Crossover Trial
Authors: BAEKDAL MILLE , LUND ASGER , NIELSEN SOPHIE W. , STORKHOLM JAN H. , HANSEN CARSTEN , VILSBØLL TINA , KNOP FILIP K.
Published: June 2020

Insulin remains the only glucose-lowering treatment modality recommended in totally pancreatectomized (PX) patients. We investigated the effects of the sodium glucose transporter 2 (SGLT2) inhibitor empagliflozin on fasting and postprandial glucose concentrations in PX patients. In a randomized, double-blinded, placebo-controlled crossover study, 10 PX patients (age 65.7±6.4 [mean±SD] years; BMI 23.8±4.3 kg/m2) and 10 CTRLs (age 65±7.8 years; BMI 24.3±3.5 kg/m2) underwent a 3-hour liquid mixed meal test (MMT) preceded by two doses of 25 mg empagliflozin (administered the night before and on the morning of the MMT) and placebo, respectively. Basal insulin was administered as usual; no bolus insulin was administered during study days. Empagliflozin lowered fasting plasma glucose compared to placebo (5.0±0.5 vs. 7.9±0.9 mmol/l [mean±SEM], P=0.029) and postprandial plasma glucose excursions as assessed by baseline-subtracted area under curve (999±96 vs. 1,235±69 min×pmol/l, P=0.034) in the PX patients. In CTRLs, empagliflozin lowered fasting plasma glucose compared to placebo (5.2±0.1 vs. 5.5±0.1 mmol/l, P=0.021) without affecting postprandial glucose excursions significantly. Empagliflozin acutely and effectively decreases fasting plasma glucose and attenuates postprandial hyperglycemia in PX patients.

Disclosure

M. Baekdal: None. A. Lund: Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk A/S, Sanofi. S.W. Nielsen: None. J.H. Storkholm: None. C. Hansen: None. T. Vilsbøll: Advisory Panel; Self; AstraZeneca, Mundipharma International, Novo Nordisk A/S, Sun Pharmaceutical Industries Ltd. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medscape, Merck Sharp & Dohme Corp., Sanofi. F.K. Knop: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk A/S, Sanofi. Consultant; Self; Carmot Therapeutics, Inc., Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Gubra, Novo Nordisk A/S, Sanofi, Zealand Pharma A/S. Speaker’s Bureau; Self; AstraZeneca, Lupin Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Norgine B.V., Novo Nordisk A/S.
1146-P: The Effects of the SGLT2 Inhibitor Empagliflozin on Fatty Liver in Diet-Induced Obese Mice
Authors: WANG WEI , GUO WANRONG , JIAN YING , SHEN YUNFENG , XU FEN
Published: June 2020

SGLT2 inhibitors (SGLT2Is), which are known to reduce blood glucose by inhibiting the reabsorption of renal glucose and promoting the excretion of urine glucose, are a kind of novel antidiabetic drugs for the treatment of type 2 diabetes and were reported to have multiple beneficial effects on the complications of diabetes. However, whether and how SGLT2Is improve obesity-related fatty liver remains unclear. In our study, 8-week-old C57BL/6 mice were fed on a normal diet or a high-fat diet for 16 weeks. After the diet induction, they were divided randomly into four groups: the normal chow diet group (NC group), the normal diet + empagliflozin group (NCE group), the high-fat diet group (HFD group) and the high-fat diet + empagliflozin group (HFDE group). The NCE group and the HFDE group were administered empagliflozin by oral gavage for 4 weeks, while the NC group and the HFD group were administered the same amount of cosolvent. After four-week treatment, body weight and fasting blood glucose of HFDE group were significantly improved when compared to HFD group. In addition, improved glucose tolerance and insulin sensitivity were observed in HFDE group. Both the energy intake and water intake increased significantly after empagliflozin intervention. What’s more, daily urine volume was remarkably increased by empagliflozin. Although there was no difference in total body fat mass between HFD group and HFDE group, the weight of subcutaneous adipose tissue and brown adipose tissue were significantly reduced. Importantly, liver weight was also statistically reduced in HFDE group compared with the HFD group. Oil red O staining showed that the hepatic steatosis in the HFDE group was ameliorated compared to HFD group.

In conclusion, empagliflozin could significantly reduce the body weight and liver weight, and improve fasting blood glucose and hepatic steatosis. The underlying mechanism will be further explored.

Disclosure

W. Wang: None. W. Guo: None. Y. Jian: None. Y. Shen: None. F. Xu: None.
1148-P: Antioxidative Effects of Empagliflozin and Metformin in Type 1 Diabetes Mellitus Patients
Authors: JANIC MIODRAG , LUNDER MOJCA , SABOVIC MISO , JANEZ ANDREJ
Published: June 2020

Background: Favourable cardiovascular effects of SGLT2 inhibitors have been clearly revealed, whereas the underlying mechanism(s) still remain unknown. We explored the anti-oxidative action of empagliflozin (alone and in combination with metformin) in type 1 diabetes mellitus (T1DM) patients.

Methods: Forty T1DM male patients (age 44.7 ± 2.5 years, BMI 28.3 ± 0.6 kg/m2) were equally randomised into four groups: 1) control (placebo), 2) empagliflozin (25 mg daily), 3) metformin (2000 mg daily) and 4) combination (empagliflozin 25 mg daily and metformin 2000 mg daily). Oxidative stress parameters were assessed at inclusion and after 12 weeks of treatment, comprising of total antioxidative status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx), isoprostane, interleukin 6 (IL6) and advanced oxidation protein products (AOPP). One-way analysis of variance (ANOVA) with Bonferroni post-test was used for statistical analysis.

Results: Empagliflozin in combination with metformin significantly improved antioxidative status parameters by increasing TAS for up to 1.07-fold (P<0.01), SOD for up to 1.08-fold (P<0.001) and GPx for up to 1.15-fold (P<0.01), whereas empagliflozin or metformin alone were less effective. The prooxidants significantly decreased in groups treated with empagliflozin alone or empagliflozin in combination with metformin: isoprostane for up to 1.26-fold (P<0.001) and IL6 for up to 1.34-fold (P<0.01); whereas the level of AOPP significantly decreased only in the group treated with empagliflozin and metformin combination (for up to 1.22-fold; P<0.01). The levels of oxidative stress parameters in the control group remained unchanged.

Conclusion: We found that empagliflozin in combination with metformin provided powerful antioxidative defense in T1DM patients. The results could at least partially explain the beneficial effects of the two drugs beyond glucose control. Antioxidant activity should be focused on in further large clinical studies.

Disclosure

M. Janic: None. M. Lunder: None. M. Sabovic: None. A. Janez: None.
1154-P: Ending a Blanket Ban for Insulin-Treated Commercial Pilots: An Interdisciplinary Collaboration
Authors: LORBER DANIEL , FECH-BAUGHMAN SARAH
Published: June 2020

Background: In 1959, the Department of Transportation enacted safety regulations that included a blanket ban on insulin use by pilots. In 1996, in response to American Diabetes Association® (ADA) advocacy, the Federal Aviation Administration (FAA) began allowing insulin-treated (ITDM) pilots to fly privately. The success of this program led to approximately 500 pilots certified to fly privately with no adverse events related to diabetes. Nonetheless, the ban on insulin use remained intact for commercial pilots. Some ITDM pilots continued working but chose to avoid insulin and accept the resulting increased hyperglycemia and long term complications.

Interventions: The ADA began a strategy of multi-disciplinary interventions to reverse the blanket ban, including engaging “grassroots” and “grasstops” advocates, litigation, and legislative efforts. In 2014, an expert ADA medical panel reviewed relevant National Transportation and Safety Board data and recommended criteria to identify pilots capable of avoiding hypo and hyperglycemia in flight. When the FAA remained reluctant to overturn its longstanding policy, ADA continued its advocacy to encourage the FAA to adopt its recommendations by providing legal and medical support to ITDM pilots engaged in litigation against the FAA. Increasingly accurate continuous glucose monitoring (CGM) technology contributed to the FAA’s decision to overturn the blanket ban. Indeed, the new protocol requires pilots to use a CGM.

Results: In November 2019 the FAA published a new protocol for insulin-treated commercial pilots which eliminates the blanket ban.

Conclusions: The ADA’s unique structure and position enabled it to take the lead in dramatically improving the lives of pilots with diabetes. This achievement follows the ADA’s accomplishments for commercial drivers with diabetes and demonstrates that the ADA’s interdisciplinary collaboration model is successful in overcoming barriers to employment for people with diabetes.

Disclosure

D. Lorber: None. S. Fech-Baughman: None.
1162-P: Coverage, Formulary Restrictions, and Average Retail Prices of SGLT2 Inhibitors and GLP-1 Receptor Agonists across Medicare Part D Plans in 2019
Authors: LUO JING , FELDMAN ROBERT , ROTHENBERGER SCOTT D. , GELLAD WALID F.
Published: June 2020

Access to SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA) may be limited by high drug prices and insurance related barriers including prior authorization or step therapy requirements. These barriers are particularly challenging for seniors covered under Medicare’s prescription drug benefit (Part D). We used Q1 2019 national Part D Formulary files to examine: 1) the proportion of plans (weighted by enrollment) that cover a SGLT2i or GLP-1RA without prior authorization or step therapy and 2) the average retail price [IQR] for a 30-day supply of each medication. Among 3,992 plans (enrolling at least 37,980,936 beneficiaries), weighted coverage without prior authorization or step therapy for canagliflozin, dapagliflozin and empagliflozin was 53.2% (95% CI: 49.1 to 57.4), 63.7% (95% CI: 60.1 to 67.3) and 95.4% (95% CI: 94.3 to 96.4), respectively. Coverage without prior authorization or step therapy for GLP-1RA of ranged from 3.2% (95% CI: 1.8 to 4.6) for lixisenatide to a high of 87.4% (95% CI: 85.5 to 89.3) for dulaglutide. The mean retail price [IQR] for a 30-day supply of a SGLT2i or a GLP-1RA ranged from $295 [$285-$303] (ertugliflozin) to $512 [$501-$527] (canagliflozin) and $641.38 [$629-$657] (lixisenatide) to $946.17 [$930-$968] (liraglutide), respectively. In 2019, coverage without prior authorization and step therapy for SGLT2i and GLP-1RA were mixed across Part D plans. Most beneficiaries enrolled in plans that covered at least one SGLT2i and one GLP-1RA without restrictions. Cost sharing (i.e., high out-of-pocket payments) may be more problematic for patients than either prior authorization or step therapy.

Disclosure

J. Luo: Consultant; Self; Alosa Health. R. Feldman: None. S.D. Rothenberger: None. W.F. Gellad: None.

Funding

National Center for Advancing Translational Sciences (KL2TR001856)
1176-P: The Value of Quality Improvement Programs in Diabetes Care: Experience from the Prime Program
Authors: MITRI JOANNA , CHARLOT WANNA , ZANGER BRANDY L. , MILLAN-FERRO ANDREINA
Published: June 2020

The quality of diabetes care is suboptimal worldwide. The Joslin PRIME program assists healthcare professionals (HCPs) with improving diabetes outcomes using scalable quality improvement (QI) methodology. We present findings from a large-scale PRIME implementation focused on A1c reduction. An invitation was sent to 29 HCPs within a large multi-specialty medical group in Springfield, IL. Seventeen HCPs enrolled in the program. Each HCP identified a medical assistant or nurse within the practice to serve as the Diabetes Care Coordinator (DCC) and assist with leading QI activities. Following a live QI workshop, each team (HCP and DCC) learned how to create plan-do-study-act (PDSA) cycles, received a diabetes registry on patients with diabetes and established a plan to decrease the proportion of patients with A1c>9%. Teams were offered online CME, weekly support calls and guidance to implement QI activities using PDSA cycles. De-identified data including clinical metrics on all patients with diabetes, based on ICD-10 codes, cared for by 17 enrolled HCPs (EG) and 12 unenrolled HCPs (UG) were evaluated before and 5 months after institution of the program. Differences in proportion of patients with A1c>9% before the program (P1) and at 5 months (P2) were compared using Chi-square. Twelve participants completed at least one PDSA cycle and saw 39% of their patients with diabetes in 5 months, compared to 21% in the remaining participants. In the EG, P1 was 12% and P2 was 10% (p=0.037). In the UG, P1 was 11% and P2 was 10%, (p=0.136). The odds ratio of having A1c>9% was 0.79 (95% CI 0.63-0.99, p=0.037) in the EG and 0.86 (95% CI 0.71-1.05, p=0.136) in the UG. The proportion of patients with A1c>9% in the EG was significantly lower 5 months after institution of the program. Based on these preliminary data, the PRIME QI program, which is mostly delivered remotely, has the potential to assist HCPs to enhance the quality of diabetes care if applied at a larger scale.

Disclosure

J. Mitri: Consultant; Spouse/Partner; Janssen Pharmaceuticals, Inc., kymera. Consultant; Self; national dairy council/local dairy council. Research Support; Spouse/Partner; AbbVie Inc., beigene, Janssen Pharmaceuticals, Inc. Research Support; Self; Kowa Pharmaceuticals America, Inc., national dairy council. Research Support; Spouse/Partner; pharma cyclic, TG therapeutics. W. Charlot: None. B.L. Zanger: None. A. Millan-Ferro: None.
1178-P: Multicomponent Integrated Care Program Benefits on Cardiovascular Risk Factors for Adults with Diabetes and High Cardiovascular Risk: The DIABEMPIC Program
Authors: SILVA-TINOCO RUBÉN , CUATECONTZI ENEDINA TERESA C. , DELATORRE-SALDAÑA VIRIDIANA , GUZMAN EILEEN B. , CABRERA-GERARDO DOLORES , PRADA DIDDIER , VILLA-CORTÉS ANDREA , LEÓN-GARCÍA ENRIQUE , SEGOVIA-VELAZQUILLO ALMA , ZARATE CLAUDIA , ROMERO-IBARGUENGOITIA MARIA ELENA , GONZALEZ-CANTU ARNULFO
Published: June 2020

Cardiovascular disease (CVD) is a major cause of death/disability in people with diabetes, this impact could be even greater in low- middle-income countries, where large gaps exist in achieving diabetes care goals. We examined a quality initiative Multicomponent Integrated Care (MIC) program (DIABEMPIC, DIABetes EMPowerment and Improvement of Care) on diabetes care goals in persons with type 2 diabetes (PwT2D) implemented in a public primary care specialized diabetes clinic in Mexico City/Iztapalapa. DIABEMPIC is a 5-months empowerment-based program with the following components: interdisciplinary case management team, diabetes self-management education and support, individual/group sessions, shared medical appointments, patient-centered approach, audit and feedback, and guaranteed supply of medications. We evaluated the effect of the intervention on the improvement in diabetes care goals using a ’before and after’ design in participants with a high CV risk.

Results: total PwT2D were 610, of which 375 (61.1%) had high CV risk (10-year risk of cardiovascular disease ≥10% with Globorisk lab score). The mean (SD) age of this subgroup was 59.3 (9.4) years, 66% female, 56% had elementary or less education, 73% had medium-low or lower socioeconomic status. Mean diabetes duration was 13 (8) years, 21.8% with current smoking status, 61% with hypertension diagnosis. After the intervention systolic and diastolic blood pressure (-12, -4 mmHg respectively), A1c (-2.4%), triglycerides (-40 mg/dl), and non-HDL cholesterol (-36 mg/dl) decreased significantly (p<0.0001).

Conclusions: We found a high prevalence of high risk for CVD in primary care. This quality of care initiative had a valuable effect on CV-related diabetes care goals in a real-world setting. MIC strategies may play an important role to mitigate CVD burden in high-risk populations. We suggest further replications of this intervention.

Disclosure

R. Silva-Tinoco: Speaker’s Bureau; Self; Novo Nordisk Inc. E.C. Cuatecontzi: None. V. delaTorre-Saldaña: None. E.B. Guzman: None. D. Cabrera-Gerardo: None. D. Prada: None. A. Villa-Cortés: None. E. León-García: None. A. Segovia-Velazquillo: None. C. Zarate: None. M. Romero-Ibarguengoitia: None. A. Gonzalez-Cantu: None.
1179-P: Differences in Chronic Kidney Disease Management in Patients with and without Diabetes in a Large Care Delivery System
Authors: SPERL-HILLEN JOANN M. , CRAIN A. LAUREN , DESILVA MALINI B. , CHUMBA LILIAN
Published: June 2020

Background: Evidence-based chronic kidney disease (CKD) care can slow progression and avert complications. We evaluated evidence-based care gaps for stage 3 and 4 CKD in patients with and without diabetes (DM).

Methods: All patients age 18-75 with a primary care encounter between April and October 2019 in any of 32 clinics in a large Midwestern care system were evaluated for stage 3 or 4 CKD based on laboratory evidence of GFR 15-59 ml/min/1.73 m2 on 2 consecutive tests. Using programmed algorithms they were further assessed for CKD care gaps and classified as DM or no DM.

Results: Out of 5,336 patients with stage 3 or 4 CKD, 41% had DM. Patients with DM had a mean A1C of 7.5%, mean systolic BP 134, and 28.6% had A1C ≥8%. Compared to patients without DM, those with DM were slightly older (65.6, 66.2 years, p<.001), more likely to be male (41.9%, 47.9%, p<.001), African American (6.5%, 11.9%, p<.001) and have either stage 3b (19.9%, 30.6%, p<.001) or Stage 4 CKD (5.2%, 9.4%, p<.001).

Conclusion: CKD care for those with DM is better than for those without DM for most care elements, although large care caps remain for both groups. Of note, 28% of patients with DM had an A1C over 8%, and 15.3% of patients with DM had more advanced CKD with no evidence of seeing a nephrologist in the last year. Better care delivery strategies are needed for optimal CKD management including timely nephrology consultation.

Disclosure

J.M. Sperl-Hillen: None. A. Crain: None. M.B. DeSilva: None. L. Chumba: None.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (R18DK118463)
1190-P: Pharmacist-Led Clinical Interventions to Encourage Adherence to ADA Diabetes Guidelines and Improve Quality of Care
Authors: BANKS JENNIFER M. , TADDEI-ALLEN PATTY
Published: June 2020

Background: In addition to lifestyle modifications, pharmacotherapy is often required to achieve glycemic goals. In clinical practice, optimal treatment is not consistently implemented, often due to inadequate adherence to recommended guidelines.

Objective: To demonstrate the impact of a pharmacist-led diabetes clinical intervention program.

Methods: A retrospective analysis using collected diabetes program clinical interventions from July 1, 2019 through December 31, 2019 was performed. Members at least 18 years of age enrolled in a prescription plan administered by the pharmacy benefit manager with the pharmacist-led diabetes program who attempted to obtain diabetes medications were included in the analysis. A diabetes specialist reviewed members that did not meet previously established clinical algorithm programmed into the adjudication platform. Total number of clinical interventions and type of clinical intervention were described using descriptive statistics.

Results: The diabetes specialist pharmacist reviewed a total of 85 interventions. Out of these interventions, approximately 34% did not require additional clinical information from the provider and the medication adjudicated. Of the remaining interventions, providers accepted 75% of the recommendations: 30% “Medication changed to cost-effective therapeutic equivalent”, 27% “Medication discontinued”, 9% “New medication initiated”, and the remaining categories included “Medication dose decreased”, “Medication dose increased”, and “Medication dosing interval increased.”

Conclusion: The diabetes specialist pharmacist intervened to promote adherence to ADA guidelines and educate providers on patient specific factors such as medication adherence, polypharmacy, gaps-in-care, and financial considerations. Providers accepted recommendations 75% of the time, demonstrating willingness to collaborate with other clinicians to ensure optimal patient care.

Disclosure

J.M. Banks: None. P. Taddei-Allen: Advisory Panel; Self; Novo Nordisk A/S.
1193-P: “TechQuity” in Diabetes: Does Digital Health Technology Improve Equity?
Authors: CRAIG KELLY JEAN , RHEE KYU B.
Published: June 2020

Introduction: Higher diabetes mellitus (DM) burden and disparities in healthcare have been linked to factors including race/ethnicity, low socioeconomic status (SES), and geographic location.

Objective: To identify digital health interventions (DHIs) that improve health and healthcare delivery outcomes in populations disproportionately affected by DM.

Methods: A systematic scoping review evaluated DHIs to address global health disparities in cardiovascular (CV)-related diseases/disorders or cardiovascular disease (CVD). A subgroup analysis was performed to identify the impact of DHIs in DM populations. Pre-post DM-specific health (clinical/intermediate and patient-reported) and healthcare delivery outcomes (quality, utilization, and access to care including DHI technical evaluations) were abstracted.

Results: In the subgroup analysis, 21 of the 58 included studies (out of 4,298 relevant citations) examined DM populations. DM-specific health data were obtained from 13 of those studies examining primary (e.g., weight loss), secondary (e.g., diabetic retinopathy screening), tertiary (e.g., glucose control), or quaternary (e.g., overmedicalization) preventive DHIs. DHIs primarily targeted Black (29%), Hispanic (24%), low SES (62%), and/or rural (52%) populations in the United States (52%). DHIs commonly used electronic health records (28%) and decision support systems (19%). Eleven (85%) studies showed DHIs significantly improved outcomes, nine (70%) studies had no effect, and seven (54%) studies negatively impacted disparity populations. Eight (62%) studies were high-quality (e.g., RCTs). No trends could be identified to find associations of DHI type nor disparity group with preventive intervention success.

Conclusions: Preventive DHIs improved both health and healthcare delivery outcomes in DM-specific disparities identified in racial/ethnic groups and low SES populations in both rural and urban geographies globally.

Disclosure

K. Craig: Other Relationship; Self; Medtronic. K.B. Rhee: Employee; Self; IBM.
1195-P: Improving Diabetes Self-Management with a Mobile App: Results of a Pilot Program at a Safety Net Hospital System
Authors: MARCELLO ROOPA KALYANARAMAN , DOLLE JOHANNA , KAUR SHARANJIT , PATTERSON SAWKIA R. , DAVIS NICHOLA
Published: June 2020

For patients with type 2 diabetes, self-management remains a significant challenge. In recent years, the use of digital health technologies (DHTs) for chronic disease management has increased, with some facilitating improvements in diabetes outcomes. Historically, safety net systems have been slow to adopt DHTs, in part due to assumptions about literacy and the use of technology among low-income or non-English speaking patients. Additionally, the use of DHTs among diverse, low-income patient populations has not been well studied. NYC Health + Hospitals (H+H) is the largest safety net healthcare system in the nation. H+H launched a pilot program of BlueStar, an FDA-approved mobile app for diabetes self-management, among patients with poorly controlled type 2 diabetes at two of its acute care hospitals. The app was provided to patients in English and Spanish. Participants were able to record and receive feedback on their medications, blood glucose, blood pressure, and meals. Key aims of this pilot program were to: 1) increase patient education and support for diabetes self-management; 2) test the use of technology adaptation in a vulnerable patient population; and 3) improve diabetes outcomes as measured by reductions in A1c. Two hundred ninety-nine patients received the app, and 137 (46%) used the app at least once. Of these 137 patients, 52% used the app at least once per week; recording blood glucose and medication were the most frequently used features (82% and 62%, respectively). Among the first 196 patients enrolled, the mean reduction in A1c from baseline to six months post enrollment was 0.7 at hospital A (n=97) and 1.6 at hospital B (n=97). As compared to matched control patients at non-participating facilities, participants experienced a greater reduction in A1c of 0.1 (p=0.61) at hospital A and 0.7 (p=0.02) at hospital B. Results from the final analysis of all 299 participants as well as key themes from semi-structured interviews with patients 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)
1197-P: Low-Cost, High-Impact Interventions in Diabetes: Social Determinants of Health Screening in Routine Diabetes Care
Authors: MANAVALAN ANJALI , LEE DONNA , JANG ALYSSA , AGARWAL SHIVANI
Published: June 2020

Background: Social determinants of health (SDH) are known to negatively influence medical outcomes and are prevalent among people with diabetes, but systematic screening and use in routine diabetes care remains limited.

Methods: We used quality improvement methodology to pilot a SDH screening protocol in our diabetes center in an underserved community, and included new adult diabetes patients of 2 providers from October to December 2019. We used a standardized SDH screen offered by the EPIC electronic health record system, which included 10 questions on transportation issues, food security, affordability of medication, housing stability, personal safety, and financial strain, among others. We performed iterative tests of the algorithm to improve reliability. Completion of the screen and responses were tracked electronically. Feasibility and acceptability were assessed with brief interviews of clinic staff and patients after each screen cycle.

Results: Following implementation of the SDH screen protocol, 50 out of 53 (94%) eligible patients were screened (mean age 30, 53% female, 72% Medicaid). Patients who did not complete screens refused due to privacy concerns or were unable to respond due to developmental delay. One-third of patients (n= 17, 32%) reported at least 1 SDH. The most common SDH noted were lack of transportation to visits and food insecurity. Participants who reported SDH and desired assistance were referred to a care coordinator trained to address social needs. In brief post-screen interviews, staff and patients alike expressed high feasibility and acceptability of the SDH screen.

Conclusions: Screening for SDH is important, uncovering social needs that are relevant and impactful for diabetes outcomes, while still maintaining high staff and patient acceptability. Given potential for linkage to future payment, SDH screening should be incorporated into routine diabetes care.

Disclosure

A. Manavalan: None. D. Lee: None. A. Jang: None. S. Agarwal: None.