bluuebunny/crossref_metadata_2025 huggingface dataset:
932-P: Efficacy and Safety of Oral Semaglutide by Baseline Age in the PIONEER Clinical Trial Program
Authors: ARODA VANITA R. , BAUER ROBERT , HERTZ CHRISTIN L. , MONTANYA EDUARD , SØRRIG RASMUS , WARREN MARK L. , CARIOU BERTRAND
Published: June 2020

In an exploratory analysis of 7 global phase 3a trials (PIONEER 1-5, 7, and 8) we evaluated the effect of age at baseline on efficacy (<45, ≥45-<65, or ≥65 years) and safety (<65 or ≥65 years) for oral semaglutide (3, 7, 14 mg once daily) vs. comparators in patients with type 2 diabetes. Efficacy endpoints were change from baseline in HbA1c and body weight. Across all trials, there were 582, 3392, and 1683 patients aged <45, ≥45-<65, and ≥65 years, respectively. Baseline HbA1c was similar across age groups, whereas baseline body weight tended to be higher in younger patients. Overall, reductions in HbA1c were comparable across age groups for all trials and were generally larger with oral semaglutide than comparators, irrespective of age (Table). Body weight reductions were greater for oral semaglutide vs. comparators but without association between age and reductions in body weight. In general, proportions of patients with adverse advents (AEs) and AEs leading to treatment discontinuation were greater in the ≥65 vs. the <65 age group for oral semaglutide and comparators (Table). To conclude, the greater effects of oral semaglutide vs. comparators on HbA1c and body weight were seen for patients regardless of age group in the global PIONEER trials. For the <65 and ≥65 age groups, the safety profile of oral semaglutide was in line with other GLP-1RAs. Overall, there was a generally higher discontinuation rate in older patients.

Disclosure

V.R. Aroda: Consultant; Self; Duke, Novo Nordisk Inc., Sanofi. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Applied Therapeutics, Fractyl Laboratories, Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; IMNE, Medscape. R. Bauer: Employee; Self; Novo Nordisk A/S. C.L. Hertz: Employee; Self; Novo Nordisk A/S. E. Montanya: Advisory Panel; Self; Sanofi. Consultant; Self; Novartis Pharmaceuticals Corporation. Employee; Spouse/Partner; Almirall. Speaker’s Bureau; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S. R. Sørrig: Employee; Self; Novo Nordisk A/S. M.L. Warren: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi. Research Support; Self; Eli Lilly and Company, Gan & Lee Pharmaceuticals, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; AstraZeneca, Merck & Co., Inc., 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.

Funding

Novo Nordisk A/S
934-P: Association between CTRB1/2 RS7202877 (T>G) Polymorphism and Glycemic Response to Liraglutide in Greek People with Type 2 Diabetes
Authors: KYRIAKIDOU ARTEMIS , KYRIAZOU ANGELIKI V. , KOUFAKIS THEOCHARIS , VASILOPOULOS YIANNIS , AVRAMIDIS IAKOVOS , BALTAGIANNIS STEFANOS , MANTHOU ELENI , GOULIS DIMITRIOS G. , ZEBEKAKIS PANTELIS , KOTSA KALLIOPI
Published: June 2020

Previous research has demonstrated an association between genetic variation in the CTRB1/2 gene and response to incretin therapies. We aimed to evaluate the role of CTRB1/2 rs7202877 (T>G) polymorphism in glycemic response to liraglutide among Greek people with T2D. 116 adults with T2D (51% female, mean BMI 35.4±6.4 kg/m2, mean age 68.3±10.9 years), who had been on treatment with liraglutide for at least 6 months were genotyped for the rs7202877 polymorphism, using real-time PCR. Responders met at least one of the following criteria: i) achievement of good glycemic control defined as HbA1c level of <7%, either at 3 or 6 months after treatment initiation, ii) reduction of the baseline HbA1c levels by ≥1% after 3 or 6 months of liraglutide use, and iii) maintenance of the optimal glucose control (HbA1c <7%) that a patient had before switching to liraglutide, after 3 or 6 months of treatment. Patients who failed to fulfil any of those criteria, were characterized as non-responders. 81 (70%) patients were classified as responders and 35 (30%) as non-responders. 97 (84%) patients were homozygous for the wild type T allele (TT) and 19 (16%) patients carried one polymorphic G allele (TG). Heterozygotes tended to have better response to liraglutide treatment; still, the difference was not significant (OR: 1.25, 95% CI: 0.4, 3.8, P=0.69). The probability of being a responder was 45% greater, when the baseline HbA1c was increased by 1% (adjusted for gender and baseline weight OR: 1.45, 95% CI: 1.05, 2.1, P=0.048). Additionally, an increase in baseline weight by 10 kg was associated with 26% reduced probability of being a responder (adjusted for gender and baseline HbA1c OR: 0.97, 95% CI: 0.94, 0.99, P=0.011). Our findings do not suggest a role of CTRB1/2 rs7202877 in affecting glycemic response to liraglutide. Lower baseline body weight and higher baseline glycemia might be related to better glycemic control following treatment with liraglutide.

Disclosure

A. Kyriakidou: None. A.V. Kyriazou: Research Support; Self; Novo Nordisk A/S. T. Koufakis: None. Y. Vasilopoulos: None. I. Avramidis: None. S. Baltagiannis: None. E. Manthou: None. D.G. Goulis: None. P. Zebekakis: None. K. Kotsa: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Sanofi-Aventis, Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Menarini Group. Other Relationship; Self; Novo Nordisk Inc.

Funding

Novo Nordisk (91220)
936-P: Plasma Proteomic Profiling Delineates Treatment Efficacy of a GLP-1/GIP Coagonist in Female and Male Mice
Authors: HOFMANN SUSANNA M. , WEWER ALBRECHTSEN NICOLAI J. , TSCHÖP MATTHIAS H. , FEUCHTINGER ANNETTE , BRIELMEIER MARKUS , FINAN BRIAN , DIMARCHI RICHARD , KLEINERT MAXIMILIAN , SACHS STEPHAN , MÜLLER TIMO D. , STEMMER KERSTIN , MANN MATTHIAS
Published: June 2020

Objective: Polypharmacotherapy shows superior efficacy compared to monotherapy in correcting obesity and its co-morbidities in preclinical studies and clinical trials. Female organisms have been traditionally neglected in this research potentially contributing to an increased rate of adverse advents in women. To address this disparity we herein determined the efficacy of our monomeric peptide with a balanced agonism at the receptors for glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) to correct obesity, glucose metabolism, nonalcoholic fatty liver disease (NAFLD) and dyslipidemia in both sexes of a mouse model for diet-induced obesity (DIO) by combining physiological treatment endpoints with plasma proteomic profiling (PPP), a new unbiased diagnostic tool for the efficacy and optimization of pharmacological interventions.

Methods: We performed metabolic phenotyping along with PPP in body weight matched male and female DIO mice treated for 21 days with either PBS, the single GIP and GLP-1 monoagonists, or our GLP-1/GIP coagonist.

Results: GLP-1R/GIPR coagonism improved obesity, glucose intolerance, NAFLD and dyslipidemia with superior efficacy in both male and female mice compared to monoagonist treatments. PPP revealed in both sexes broader changes of plasma proteins after GLP-1/GIP coagonist compared to monoagonist treatments, including established and novel biomarkers for systemic inflammation, NAFLD and atherosclerosis. Subtle sex-specific differences have been observed in metabolic phenotyping and PPP.

Conclusions: We herein report enhanced efficacy of our GLP-1/GIP coagonist in both sexes relative to monoagonists for the treatment of metabolic disease. Wider sex-specific reductions of circulating proteins after GLP-1/GIP coagonist treatment may reflect additional metabolic benefits that are currently achieved exclusively after bariatric surgery.

Disclosure

S.M. Hofmann: Advisory Panel; Spouse/Partner; Novo Nordisk A/S. N.J. Wewer Albrechtsen: Research Support; Self; Mercodia, Novo Nordisk A/S, Novo Nordisk Foundation. Speaker’s Bureau; Self; Merck Sharp & Dohme Corp. M.H. Tschöp: Advisory Panel; Self; ERX Pharmaceuticals, Novo Nordisk Foundation. A. Feuchtinger: None. M. Brielmeier: None. B. Finan: Employee; Self; Novo Nordisk A/S. R. DiMarchi: Employee; Self; Novo Nordisk Inc. M. Kleinert: None. S. Sachs: None. T.D. Müller: Research Support; Self; Novo Nordisk Inc., Sanofi-Aventis. K. Stemmer: None. M. Mann: None.
938-P: The Relationship between Timing of Initiation on a Glucagon-Like Peptide-1 Receptor Agonist and HbA1c among Patients with Type 2 Diabetes
Authors: MALIK RALEIGH E. , MODY REEMA , LAGE MAUREEN J. , BOYE KRISTINA
Published: June 2020

Onjective: Examine the relationship between timing of initiation on a glucagon-like peptide-1 receptor agonist (GLP-1 RA) and HbA1c.

Methods: The IBM MarketScan databases from 1/1/13 through 12/31/17 were used to identify adults with type 2 diabetes (T2D) who initiated on a GLP-1 RA in 2015 (first such date = index date) and had ≥1 HbA1c result in the last 6 months of the 2 year pre-period and another HbA1c in the last 6 months of the 2 year post-period. Time to GLP-1 RA initiation was proxied by the number of classes of glucose-lowering agents (GLAs) prescribed in the pre-period, with fewer GLAs indicating earlier GLP-1 RA initiation. Paired t-tests were used to examine differences in HbA1c from pre-period to post-period. Multivariable analyses examined the relationship between time to GLP-1 RA initiation and post-period HbA1c.

Results: The cohort (N=1,122) was 54% female with mean age of 55 ± 8.5 [SD] years. Initiation on a GLP-1 RA was associated with a significant reduction in HbA1c (8.5% ± 1.9% pre-period v 7.9% ± 1.8% post-period; P<0.0001). Earlier initiation on a GLP-1 RA was associated with significantly lower post-period HbA1c and a significant increase in the likelihood of a patient achieving post-period HbA1c < 7% (Figure 1).

Conclusions: Earlier initiation on a GLP-1 RA was associated with significantly lower HbA1c and an increased likelihood of achieving HbA1c < 7%.

Disclosure

R.E. Malik: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. R. Mody: Employee; Self; Eli Lilly and Company. M.J. Lage: Consultant; Self; Eli Lilly and Company. Consultant; Spouse/Partner; Eli Lilly and Company. K. Boye: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Eli Lilly and Company.
939-P: HD-7671, a Nonpeptide Small Molecule for Orally Available GLP-1 Receptor Agonist, Improves Glucose Tolerance by Increasing Insulin Secretion
Authors: BAEK MYOUNGKI , KIM DAEHOON , KIM CHUN HWA , KIM DOO YOUNG , CHOI HYO SUN , KANG SEUNG JUN , LEE HANKYU , LEE KYUHWAN
Published: June 2020

Glucagon-like peptide-1 (GLP-1) mediates antidiabetogenic effects through the GLP-1 receptor (GLP-1R), which is targeted for the treatment of type 2 diabetes. Currently, GLP-1R agonists comprise a growing class of agents that deliver unprecedented efficacy in diabetes. We discovered a new small molecule GLP-1R agonist, HD-7671, and examined its efficacy in cynomolgus monkeys. The in vitro potency of HD-7671 was evaluated by measuring cAMP accumulation in cells with stable expression of human GLP-1R. HD-7671 stimulated cAMP accumulation and its EC50 value was 2.0 nM. In the cells transfected with human or cynomolgus monkey GLP-1R, HD-7671 promoted cAMP accumulation and its EC50 values for human and cynomolgus monkey GLP-1Rs were 4.5 nM and 7.1 nM, respectively. In contrast, HD-7671 showed no stimulatory activity on other animal species GLP-1Rs. In pharmacokinetic properties, the elimination half-life following oral administration(T1/2) was 0.99 hr in rats and 5.62 hr in cyno monkeys and Cmax was 10,183 ng/ml in rats and 1,423 ng/ml at 10mg/kg, respectively. To evaluate the in vivo insulinotropic effects of HD-7671, glucose stimulated insulin secretion was measured in compound treated in cyno monkeys undergoing an IVGTT. HD-7671 (dosed at 10mg/kg) decreased the blood glucose level and increased insulin secretion. These results demonstrate that HD-7671 has full agonistic activity on human and cynomolgus GLP-1R and improves glucose tolerance by stimulating insulin secretion.

In conclusion, HD-7671 has potential as an orally active, non-peptide GLP-1R agonist for the treatment of type 2 diabetes.

Disclosure

M. Baek: None. D. Kim: None. C. Kim: Employee; Self; Hyundai Pharmaceutical Co., Ltd. D. Kim: Employee; Self; Hyundai Pharm. H. Choi: Employee; Self; Hyundai Pharm. corp. S. Kang: Employee; Self; Hyundai pharm.corp. H. Lee: Employee; Self; Hyundai Pharm. K. Lee: Employee; Self; Hyundai Pharm.
94-LB: Long-Term Clinical Benefits of Early Combination Approach in Latin American Subpopulation of VERIFY Study
Authors: VENCIO SERGIO , MANOSALVA JUAN , MATHIEU CHANTAL , PROOT PIETER , PALDANIUS PAIVI M.
Published: June 2020

The VERIFY study showed long-term clinical benefits of the early combination therapy of vildagliptin with metformin (EC) vs. traditional stepwise approach initiating with metformin monotherapy (MET) in a multinational population of newly diagnosed adult patients with T2D (HbA1c 6.5-7.5%). This sub-analysis evaluated the outcomes in Latin American population. The primary endpoint was time to initial treatment failure (TF), defined as HbA1c ≥7.0% at two consecutive scheduled visits after randomization. The time to second TF was tested when patients in both groups were receiving and failing on the combination. A total of 537 eligible patients, 58.8% females, were randomly assigned to either receive the EC (n=266) or MET (n=271). EC significantly reduced the relative risk (RR) of time to initial TF by 47% vs. MET (HR [95% CI] 0.53 [0.4, 0.7]; p<0.0001). A total of 66.3% vs. 46.4% of patients achieved the primary endpoint in the MET and EC groups, with a median (interquartile range: IQR) time to TF of 33.4 (12.2, 60.1) and 59.8 (27.5, not estimable) months, respectively. The RR for time to secondary TF was reduced by 31% with EC (p<0.0092). With EC, HbA1c levels were consistently lower and higher proportion of patients maintained HbA1c <7.0%. Both treatment approaches were well tolerated, and only 3.2% participants discontinued the study due to adverse events. Seven patients in EC vs. three in MET, reported mostly one mild hypoglycemic episode, none leading to discontinuation. Similar to the global population, the long-term clinical benefits were achieved more frequently and without tolerability issues with the strategy of EC vs. standard-of-care MET in this Latin American population.

Disclosure

S. Vencio: None. J. Manosalva: None. C. Mathieu: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intrexon, MannKind Corporation, Medtronic, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk Inc., Pfizer Inc., Roche Diagnostic USA, Sanofi. Research Support; Self; Intrexon, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk Inc., Sanofi. P. Proot: None. P.M. Paldanius: Other Relationship; Self; Novartis AG.

Funding

Novartis AG
943-P: Role of Model-Informed Drug Development in Confirming Additional Clinical Benefits of Dulaglutide
Authors: THAM LAI-SAN , GEISER JEANNE , TANG CHENG CAI , SCHNECK KAREN , COX DAVID , MILICEVIC ZVONKO , BETHEL ANGELYN
Published: June 2020

Throughout the development cycle of dulaglutide, model-informed drug development (MIDD) was applied to facilitate and accelerate decision-making. Currently, dulaglutide 0.75 mg and 1.5 mg given subcutaneously once weekly (QW) is approved for the treatment of type 2 diabetes. Post-approval, pharmacokinetic/pharmacodynamic (PKPD) exposure-response and mechanistic quantitative system pharmacology (QSP) models which leveraged accrued phase 1 data led to the hypothesis that additional glycemic control was possible with higher dulaglutide doses of 3.0 mg and 4.5 mg. MIDD was utilized to design a phase 2 study which explored the safety and efficacy for 3.0 mg and 4.5 mg versus 1.5 mg QW doses and tested a dose escalation approach for mitigating gastrointestinal (GI) nausea/vomiting effects for the investigational doses. Phase 2 data enriched understanding of benefit-risk of the extended doses and refined the dose escalation scheme for the pivotal phase 3 trial (AWARD-11). Efficacy and GI tolerability from AWARD-11 closely resembled model-predictions. While MIDD has been most commonly applied in dose-selection, novel MIDD approaches were also adopted for the dulaglutide program to design a dose escalation scheme and evaluate drug-drug interactions (DDI). Acetaminophen PK from previous gastric emptying studies covering a wide range of dulaglutide doses was used to characterize the extent of gastric-emptying delay (GED) related to 4.5 mg of dulaglutide and this extent of GED was then applied to physiologically based pharmacokinetic (PBPK) models of individual commonly co-administered oral agents to simulate effect of delayed gastric emptying on their PK profiles. Overall, a range of quantitative models were successfully employed to predict effects of and inform clinical trial design for higher dulaglutide doses for patients needing additional glycemic control.

Disclosure

L. Tham: Employee; Self; Eli Lilly and Company. J. Geiser: Employee; Self; Eli Lilly and Company. C. Tang: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Novartis Pharmaceuticals Corporation. K. Schneck: Employee; Self; Eli Lilly and Company. D. Cox: Employee; Self; Eli Lilly and Company. Z. Milicevic: Employee; Self; Eli Lilly and Company. A. Bethel: Employee; Self; Eli Lilly and Company.
949-P: Dulaglutide Improves Kidney Fibrosis Biomarker Levels in Patients with Type 2 Diabetes and Moderate-to-Severe Chronic Kidney Disease
Authors: TUTTLE KATHERINE R. , WILSON JONATHAN M. , LIN YANZHU , QIAN HUI-RONG , KELLY-BORUFF KATHLEEN , GENOVESE FEDERICA , KARSDAL MORTEN A. , DUFFIN KEVIN L. , BOTROS FADY T.
Published: June 2020

The AWARD-7 clinical trial demonstrated that once-weekly dulaglutide slowed the decline in estimated glomerular filtration rate (eGFR) and decreased urine albumin/creatinine ratio compared to insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (CKD). Lower levels of urinary C3M, a marker for type III collagen degradation, and increased level of plasma PRO-C6, a marker for type VI collagen formation, have been reported to correlate with CKD progression and lower eGFR. This exploratory analysis evaluated changes in urinary C3M and plasma PRO-C6 in response to treatment with dulaglutide 1.5 mg compared to insulin glargine in AWARD-7. At baseline, urinary C3M and serum PRO-C6 levels were comparable between the dulaglutide 1.5 mg and insulin glargine groups. At week 26 and 52 of treatment, urinary C3M levels were significantly higher and serum PRO-C6 levels were significantly lower in the dulaglutide 1.5 mg group compared with insulin glargine group, respectively (Table).

In conclusion, dulaglutide was associated with decreased levels of biomarkers for type VI collagen formation and increased type III collagen degradation, suggesting a potential effect to reduce kidney fibrosis. These anti-fibrotic effects could be a potential mechanism for the beneficial effects observed with dulaglutide treatment on CKD in type 2 diabetes.

Disclosure

K.R. Tuttle: Consultant; Self; AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Goldfinch Bio, Novo Nordisk Inc. J.M. Wilson: Employee; Self; Lilly Diabetes. Y. Lin: None. H. Qian: Employee; Self; Eli Lilly and Company. K. Kelly-Boruff: Employee; Self; Eli Lilly and Company. F. Genovese: None. M.A. Karsdal: Stock/Shareholder; Self; Nordic Bioscience. K.L. Duffin: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Pfizer Inc. F.T. Botros: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
95-LB: Control-IQ Technology in the Real World: The First 30 Days
Authors: MUELLER LARS , CONSTANTIN ALEXANDRA , SINGH HARSIMRAN , HABIF STEPHANIE
Published: June 2020

The t:slim X2 insulin pump with Control-IQ technology from Tandem Diabetes Care, Inc. was cleared by the Food and Drug Administration in December 2019. This study examined the commercial introduction of Control-IQ technology in the U.S. We performed a retrospective analysis of users who uploaded at least 30 days of pre and 30 days of post Control-IQ software update usage data to Tandem’s t:connect® web application as of March 11, 2020 and had ≥75% CGM use during this time (n=1,659). Outcomes included total daily insulin and sensor glucose values during open and closed-loop use of Control-IQ technology. Changes in glycemic outcomes were analyzed using the Wilcoxon signed-rank test. The mean age of patients was 43 years, 52% female, and mean diabetes duration was 21 years. Ninety percent of patients reported type 1 diabetes, 4% type 2 diabetes, and 6% “other” or unknown. The Control-IQ software update led to a 10% increase (p<0.001) of median sensor time in range (70-180 mg/dL) to 78% (IQR =69%-85%) due to a 10% decrease in sensor time >180mg/dL to 21% (IQR= 13%-30%) and a 0.1% decrease of sensor time <70mg/dL to 1.1.% (IQR=0.5%-2.2%). Improvements in sensor time in range were consistent across age groups. Mean sensor glucose fell from 161 mg/dL to 148 mg/dL while the median total daily insulin increased from 48u to 49u. Median time in closed-loop was 96% (IQR = 93%-98%). These real-world data demonstrate improved sensor time in range without increasing hypoglycemia.

Disclosure

L. Mueller: Research Support; Self; Dexcom, Inc., Tandem Diabetes Care. A. Constantin: Employee; Self; Tandem Diabetes Care. Other Relationship; Self; Bigfoot Biomedical. H. Singh: Employee; Self; Tandem Diabetes Care. S. Habif: Employee; Self; Tandem Diabetes Care.
962-P: Impacts of Different Hypoglycemic Agents on Adipokines and Inflammatory Markers in Newly Diagnosed T2D Patients
Authors: DENG HONGRONG , YANG XUBIN , XU WEN , LV JING , ZENG LONGYI , YAO BIN , WENG JIANPING
Published: June 2020

Background: Adipokines and inflammatory markers contribute to the pathogenesis of T2D. This study investigated the impacts of T2D and different hypoglycemic agents on the important adipokines and inflammatory markers in newly diagnosed T2D patients.

Methods: The clinical parameters, leptin, adiponectin, resistin, fibroblast growth factor21, betatrophin, IL-1β and IFNγ were assessed in 41 normal-glucose controls and 416 newly diagnosed T2D patients. Then the patients were randomly assigned to receive exenatide, insulin or pioglitazone, with the above adipokines and inflammatory factors evaluated at 48 weeks.

Results: As shown in Table 1, compared with the controls, T2D patients had significantly higher IL-1β, lower leptin, adiponectin and IFNγ levels. Among the 416 patients, 342 patients completed the 48-week study. The HbA1c change (ΔHbA1c) were similar among groups. Exenatide significantly decreased the BMI and IL-1β, while increased IFNγ and adiponectin. Insulin markedly increased IL-1β and IFNγ. And pioglitazone only increased adiponectin. Multiple linear regression showed that Δleptin and Δadiponectin were associated with ΔBMI, but not with ΔHbA1c, fasting insulin or fasting C-peptide.

Conclusions: Exenatide has better impacts on improving IL-1β, IFNγ, and adiponectin levels than insulin and pioglitazone in T2D patients, which may probably due to decreasing BMI.

Disclosure

H. Deng: None. X. Yang: None. W. Xu: None. J. Lv: None. L. Zeng: None. B. Yao: None. J. Weng: None.

Funding

National Natural Science Foundation of China (81770821 to W.X.); National Key Research and Development Program of China (2016YFC1304801); Eli Lilly and Company
97-OR: Randomization to a Higher–Complex Carbohydrate vs. Conventional Diet in GDM Improves Glucose Tolerance and Results in Similar Cord Blood Insulin and Newborn Adiposity
Authors: HERNANDEZ TERI L. , FARABI SARAH S. , ARBET JARON , HIRSCH NICOLE , DUNN EMILY Z. , HEISS KRISTY P. , CARLI JAYNE MARTIN , KREBS NANCY F. , POWELL THERESA L. , REYNOLDS REGINA , VAN PELT RACHAEL E. , FRIEDMAN JACOB E. , BARBOUR LINDA (LYNN) A.
Published: June 2020

Robust evidence for specific nutrition therapy for gestational diabetes (GDM) is lacking. Preliminary data suggested our CHOICE diet, higher in complex carbohydrate (60%) and lower in fat (25%) reduced fasting glucose (FBG), free fatty acids (FFA), and newborn adiposity (NB%fat). We tested the hypothesis that 7-8 wks of CHOICE would improve insulin resistance, reduce FFA and NB%fat (2-wk PeaPod; 1° powered outcome) vs. a conventional low-carbohydrate (40%), higher fat (45%) diet (LC/CONV). After diagnosis (∼28-30 wks), 59 BMI-matched diet-controlled GDM women (mean±SD; BMI 32±5) were randomized to a eucaloric CHOICE or LC/CONV diet (7.2±1 wks; ALL MEALS PROVIDED). At baseline, a 2-hr 75g OGTT (with insulins) was performed and diet initiated. On day-4, a breakfast meal was given (30% of total calories) with fasting and hourly blood drawn x5 (gluc, insulin, FFA, triglycerides[TG]) for area-under-the curve (AUC). Measures were repeated at 36-37 wks. Of 59, 13 met exclusions (4 diet failures, 2/group). By ANCOVA (n=23/group), total and weight gain during diet were similar (CHOICE 1.9 vs. LC/CONV 1.8 kg) as was delivery wk (39.2 vs. 39.3 wks). At 37 wks, the meal gluc (p=0.001) and insulin AUCs (p=0.013) were lower for LC/CONV, though fasting gluc/insulin were similar. TG increased similarly. The FFA AUC decreased from 30-37 wks on CHOICE but rose on LC/CONV (p=0.016), and was lower for CHOICE at 37 wks (p=0.009). By the 37-wk OGTT, FBG decreased within both groups (CHOICE -7.2, LC/CONV -3.5 mg/dL, both p<0.01) but CHOICE led to improved (p=0.001) and lower gluc AUC (p<0.05)(similar insulin AUCs). Birthweight (3293 vs. 3303 g), anthropometrics, NB%fat (10.8±4 vs. 10.3±4%), and cord blood gluc, C-peptide, FFA and TG were similar. This RCT shows that complex carbohydrate can be liberalized by 20% above conventional recommendations and may improve gluc tolerance and similarly normalize fetal growth, expanding nutrition options in GDM.

Disclosure

T.L. Hernandez: None. S.S. Farabi: None. J. Arbet: None. N. Hirsch: None. E.Z. Dunn: None. K.P. Heiss: None. J. Martin Carli: None. N.F. Krebs: None. T.L. Powell: None. R. Reynolds: None. R.E. Van Pelt: None. J.E. Friedman: None. L.A. Barbour: None.

Funding

National Institutes of Health (R01DK101659, UL1TR002535); Janssen Research & Development, LLC
970-P: Comparative Assessment of the Effect of Vildagliptin and Metformin on Pancreatic Beta-Cell Function and Insulin Sensitivity in Newly Diagnosed Asian Indians with Type 2 Diabetes
Authors: SATHEESH KRISHNAMOORTHY , SNEHALATHA CHAMUKUTTAN , NANDITHA ARUN , RAGHAVAN ARUN , VINITHA RAMACHANDRAN , SUSAIRAJ PRISCILLA , RAMACHANDRAN AMBADY
Published: June 2020

Aim: To compare the effect of vildagliptin versus metformin on pancreatic beta-cell function among newly diagnosed, non-obese Asian Indians with type 2 diabetes (T2D) in 2 years.

Methods: Randomized, multicentric, controlled, parallel-group study of 2 years treatment with vildagliptin or metformin in drug-naïve T2D persons (baseline HbA1c - 7.0 - 8.5% and body mass index (BMI) < 25kg/m2). Plasma glucose, insulin, HbA1c and C-peptide were measured at intervals of 6 months for 2 years. We randomised 203 (104 men and 99 women) T2D persons in two groups. Group 1 was treated with metformin, 500mg - 2000mg (n = 100), and group 2, with vildagliptin 100mg (n = 103).

Results: In the metformin group 36% and in the vildagliptin group 27.2 % required only monotherapy for a median duration of 48 weeks (25 - 70 weeks). At the end of the study, changes in the area under the curve of insulin to glucose were non-significant in both groups. There were no changes in the postprandial C-peptide. Reduction in insulin resistance (HOMA-IR) was similar in both groups. Insulin sensitivity (Matsuda Index) increased significantly at 6 and 12 months with metformin but no change was seen in the vildagliptin group. The HbA1c level decreased significantly in both groups until 18 months. The fasting plasma glucose decreased significantly till 12 months in both groups. Postprandial plasma glucose decreased only with vildagliptin till 12 months. Occurrences of adverse events were similar in both groups. Higher C-peptide and lower HbA1c values at the baseline predicted better glycemic control with vildagliptin. Lower baseline HbA1c predicted good glycemic control with metformin.

Conclusion: Both metformin and vildagliptin had similar protective effects on the beta-cell function, reduced insulin resistance and glycemic levels. Improved insulin sensitivity was seen with metformin.

Disclosure

K. Satheesh: None. C. Snehalatha: None. A. Nanditha: None. A. Raghavan: None. R. Vinitha: None. P. Susairaj: None. A. Ramachandran: None.

Funding

India Diabetes Research Foundation
971-P: Renal Impairment Has No Impact on the Clinical Pharmacokinetics of Tirzepatide
Authors: URVA SHWETA , QUINLAN TONYA , LANDRY JOHN , MARTIN JENNIFER , LOGHIN CORINA
Published: June 2020

Novel dual GIP and GLP-1 receptor agonist, tirzepatide (TZP), is being developed as a potential weekly treatment for type 2 diabetes (T2DM), weight management and nonalcoholic steatohepatitis. This study evaluated the pharmacokinetics (PK) and tolerability of TZP in subjects with renal impairment (with or without T2DM) vs. healthy subjects with normal renal function. Subjects in this single-dose study were categorized by renal impairment defined by baseline estimated glomerular filtration rate (eGFR, MDRD equation): 14 with normal renal function (≥90 mL/min/1.73m2), 8 with mild impairment (60-89 mL/min/1.73m2), 8 with moderate impairment (30-59 mL/min/1.73m2), 7 with severe impairment (<30 mL/min/1.73m2) and 8 with end stage renal disease (ESRD) requiring dialysis. All subjects received a single subcutaneous dose of 5 mg TZP. Blood samples were collected to determine TZP plasma concentrations to estimate PK parameters. Adverse events were monitored to assess safety and tolerability. Log-transformed AUC0-∞, AUC0-tlast, and Cmax were evaluated by analysis of variance and 90% CI of the ratio between groups was estimated. Additionally, relationship between TZP PK parameters and eGFR (MDRD and CKD-EPI) and creatinine clearance (Cockcroft-Gault) was assessed by regression analysis. PK parameters were similar between subjects with severe renal impairment and healthy subjects (geometric LSM ratios [90% CI] of 1.03 [0.836, 1.27], 1.04 [0.841, 1.28] and 1.23 [0.966, 1.56] for AUC∞, AUC0-tlast, and Cmax, respectively). Similar results were observed when comparing the PK parameters of mild, moderate and ESRD groups vs. healthy subjects. There was no statistically significant relationship at the two-sided 10% significance level between exposure and eGFR. No notable differences in safety profiles were observed. There were no clinically relevant effects of renal impairment on TZP PK. Thus, patients with renal impairment treated with tirzepatide may not require dose adjustments.

Disclosure

S. Urva: None. T. Quinlan: None. J. Landry: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J. Martin: Employee; Self; Eli Lilly and Company. C. Loghin: Employee; Self; Eli Lilly and Company.

Funding

Eli Lilly and Company
98-LB: Individual Glycemic Response to Ultra-Rapid vs. Rapid Insulin Delivered Automatically with the Ilet Bionic Pancreas System
Authors: SHERWOOD JORDAN , ZHENG HUI , BALLIRO COURTNEY A. , EKHLASPOUR LAYA , BUCKINGHAM BRUCE A. , EL-KHATIB FIRAS , DAMIANO EDWARD , RUSSELL STEVEN J.
Published: June 2020

In a recent multicenter, random-order, home-use trial (NCT03565666), we examined automated glycemic control with the insulin-only configuration of the bionic pancreas (BP) using subjects’ typical insulin analogue, BP-T (aspart, n=7 or lispro, n=27), versus using the ultra-rapid faster aspart, BP-F. The dosing algorithm was identical in both arms and used the same setting for insulin absorption speed (tmax=65 minutes). The mean CGM glucose (CGMG) was similar between the BP-F and BP-T arms (154±11 vs. 155±13 mg/dl), as was the median percent time <54 mg/(0.6% [0.2-1.1%] vs. 0.6% [0-1.3%]). We used an autoregressive time series model to determine statistical significance for differences between the BP-F and BP-T arms in individual subjects. Nine subjects had a significantly lower mean CGMG during the BP-F arm (by 13±8 mg/dl), 10 subjects had a significantly higher mean CGMG during the BP-F arm (by 10±5 mg/dl), and 15 subjects had no significant difference between arms (nominal difference 2±2 mg/dl). One subject with a significantly lower mean CGMG in the BP-F arm also had a significant decrease of 1.4% in time <54 mg/dl (~20 minutes per day), one subject with no difference in mean CGMG between arms had a significant increase of 1.4% in time <54 mg/dl in the BP-F arm, and 32 subjects had no significant differences in time <54 mg/dl between arms. There was a statistically significant reduction in mean CGMG from the use of Fiasp without adjustment of the setting for insulin absorption speed for some subjects, but a similar number saw a significant increase in mean CGMG, while there was no difference for the remainder of subjects. Other studies are under way to test whether adjusting the BP insulin delivery algorithm tmax setting will allow more subjects to benefit from the use of faster aspart in the iLet.

Disclosure

J. Sherwood: None. H. Zheng: None. C.A. Balliro: None. L. Ekhlaspour: None. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Medtronic. Research Support; Self; Beta Bionics, Inc., Dexcom, Inc., Insulet Corporation, Medtronic, Tandem Diabetes Care. F. El-Khatib: Other Relationship; Self; Beta Bionics, Inc. E. Damiano: Board Member; Self; Beta Bionics, Inc. Employee; Self; Beta Bionics, Inc. Stock/Shareholder; Self; Beta Bionics, Inc. Stock/Shareholder; Spouse/Partner; Beta Bionics, Inc. S.J. Russell: Consultant; Self; Beta Bionics, Inc., ConvaTec Inc., Novo Nordisk A/S, Senseonics. Research Support; Self; Beta Bionics, Inc., Novo Nordisk A/S, Zealand Pharma A/S. Stock/Shareholder; Self; Companion Medical. Other Relationship; Self; Ascensia Diabetes Care, Roche Diabetes Care.

Funding

National Institutes of Health
98-OR: Placental DNA Methylation Changes Associated with Birthweight and Overlaps with Adult Type 2 Diabetes
Authors: TEKOLA-AYELE FASIL , WORKALEMAHU TSEGASELASSIE , ZENG XUEHUO
Published: June 2020

Background: There is cumulating evidence for associations between birthweight-lowering genetic factors and increased risk of type 2 diabetes (T2D). Given the crucial role of the placenta in supporting fetal growth, epigenetic mechanisms in placenta may lend insights into prevention of T2D in early life. We investigated epigenetic changes in placenta associated with birthweight and those that overlap with T2D risk.

Methods: DNA methylation was measured using Illumina’s Infinium Human Methylation450 Beadchip in placenta samples obtained from race/ethnic-diverse pregnant women who participated in the NICHD Fetal Growth Studies (n=301). Associations between DNA methylation and birthweight were tested using linear regression models. Next, we examined whether DNA methylation at loci previously implicated in adult T2D were associated with birthweight in placenta. The relationship between DNA methylation and gene expression was tested in 75 placenta samples profiled for both DNA methylation and gene expression. Statistical tests were considered significant at a false discovery rate < 0.05.

Results: Placenta methylation at 15 cytosine-phosphate-guanine (CpG) sites was significantly associated with birthweight, of which methylation at UBXN11, LBX2, CNIH2, and PDE9A was significantly associated with expression of nearby genes. At six CpG sites (MGRN1, AMIGO2, CHD3 and three intergenic regions) known in previous studies to be associated with adult T2D, we found significant associations between DNA methylation in placenta and birthweight. For all the six CpG sites, the methylation changes related to increased risk of T2D were associated with lower birthweight.

Conclusions: We found novel placental DNA methylation signatures associated with lower birthweight and higher risk of adult T2D. Our findings provide the first evidence to suggest that epigenetic changes in the placenta may be one potential mechanism that explains the link between early growth and later life T2D.

Disclosure

F. Tekola-Ayele: None. T. Workalemahu: None. X. Zeng: None.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development
980-P: Anticipating Regular Physical Activity with a New Artificial Pancreas System: A Pilot Study
Authors: GARCIA-TIRADO JOSE , BROWN SUE A. , LAICHUTHAI NITCHAKARN , MYERS HELEN E. , BRETON MARC D.
Published: June 2020

Glycemic control during and after exercise is challenging. APs reduce %<70 and TIR, but do not eliminate exercise-induced hypoglycemia. Recent work has shown that insulin reduction 90min prior to exercise may be optimal. We present the initial testing of an exercise-informed AP, able to anticipate regular exercise by up to 2h without user input. Eighteen adults with T1D were enrolled in a randomized crossover trial: 4-weeks data collection (DC: SAP+step counter) followed by two 32h supervised hotel stays (SH). During DC, participants were asked to exercise 4 times/week for >30min, between 4-7pm. During SH, participants used either a naïve AP (CTL) or exercise informed AP (EX) and participated in 45min of moderate exercise at 17:30 on day 1. Fifteen subjects completed the study, age 42.2±13.6, HbA1c 6.61±1.02, with no system related AEs. During exercise, EX and CTL had similar TIR 88.2 vs. 85.2%, with a tendency to less time <80mgdL, 14.8 vs. 8.2%, following a reduction of insulin from 2.4 to 1.8 U over the preceding 2h. Post exercise EX and CTL had similar TIR (87.2 vs. 85.5%) but EX had less %<70 1.1% vs. 8.9% p=0.04,overnight control was excellent in both case TIR: 98.1 vs. 99.4%; %<70: 0.1 vs. 0.6%. During the sedentary late afternoon (5-7pm day 2) there was no difference in TIR: 89.6 vs. 86.0%. APs can learn from prior exercise behaviors and anticipate them, potentially leading to reduced glycemic risk, and a more automated system.

Disclosure

J. Garcia-Tirado: None. S.A. Brown: Research Support; Self; Dexcom, Inc., Insulet Corporation, Roche Diabetes Care, Tandem Diabetes Care, Tolerion, Inc. N. Laichuthai: None. H.E. Myers: None. M.D. Breton: Research Support; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi, Tandem Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc., Tandem Diabetes Care.

Funding

National Institutes of Health (DP3DK106826)
987-P: Efficacy and Safety Comparison between U-100 Human Regular Insulin and Rapid-Acting Insulin When Delivered by V-Go Wearable Insulin Delivery in an Older Type 2 Diabetes Population
Authors: SUTTON DAVID R. , MORA PABLO F. , GORE ASHWINI , BALIGA BANTWAL , GOLDFADEN REBECCA F. , NIKKEL CARLA C. , SINK JOHN H. , ADAMS-HUET BEVERLEY A.
Published: June 2020

The price of insulin has risen substantially and been associated with higher out-of-pocket costs and quicker entry into the Medicare coverage gap, negatively impacting diabetes care in older adults. Evidence from a large health plan supports Human Regular Insulin (HRI), when used effectively, as a viable treatment option for many patients with T2D including older adults. In a recently completed multi-site, 14-week randomized, parallel, study (N=113), non-inferiority was demonstrated when switching from Rapid Acting Insulin (RAI) to HRI delivered by V-Go with a mean change ETD in A1C of -0.22% (95% CI -0.67, 0.22); p=0.007 favoring HRI and no statistical differences in insulin dose, weight or hypoglycemia. We explored these outcomes using mixed-effects models in a post-hoc analysis in pts ≥ 65 years of age. The intent to treat population consisted of 53 pts randomized to continue therapy with RAI (n=25) or switch to HRI (n=28). Non-inferiority for change in A1C between groups was demonstrated in this population. Insulin dose and hypoglycemia events were similar between groups. No severe hypoglycemia or moderate or severe adverse events were reported in either group. Similar to the overall study findings, use of HRI delivered by V-Go is an effective insulin therapy option in an older population and may decrease financial burdens.

Disclosure

D.R. Sutton: Employee; Spouse/Partner; Valeritas, Inc. Speaker’s Bureau; Self; Amarin Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Valeritas, Inc. P.F. Mora: Speaker’s Bureau; Self; Dexcom, Inc., Insulet Corporation, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi US, Valeritas, Inc. A. Gore: Advisory Panel; Spouse/Partner; Janssen Pharmaceuticals, Inc. Consultant; Spouse/Partner; Janssen Pharmaceuticals, Inc. Consultant; Self; Novo Nordisk Inc. Speaker’s Bureau; Spouse/Partner; Janssen Pharmaceuticals, Inc. Speaker’s Bureau; Self; Janssen Pharmaceuticals, Inc., Merck & Co., Inc. B. Baliga: Speaker’s Bureau; Self; Amarin Corporation, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Senseonics, Valeritas, Inc. R.F. Goldfaden: None. C.C. Nikkel: Employee; Self; Valeritas, Inc. Stock/Shareholder; Self; Valeritas, Inc. J.H. Sink: Employee; Self; Valeritas, Inc. B.A. Adams-Huet: Consultant; Self; Valeritas, Inc.

Funding

Valeritas, Inc.
995-P: Real-World Insulin Delivery Patterns for 1,202 Adults with Type 2 Diabetes Using the Omnipod Insulin Management System with Cloud-Based Data Management
Authors: HIRSCH IRL B. , WEINSTOCK RUTH S. , HUYETT LAUREN M. , JANTZ JAY , CHANG ALBERT , VIENNEAU TODD , LY TRANG T.
Published: June 2020

Insulin pump therapy is increasing in T2D but real-world use has not been well studied. This report describes insulin delivery and glucose data from adults with T2D using a tubeless insulin pump (Omnipod® Insulin Management System, Acton, MA) with an integrated blood glucose (BG) meter (Abbott Diabetes Care Inc., Alameda, CA) and data management system (DMS; Glooko, Mountain View, CA). Pump system usage data uploaded to the DMS from Feb.-Aug. 2019 were linked to a database of self-reported demographic data and de-identified. Insulin and BG data from ≥3 mo of system use per user were analyzed.

Adults (n=1,202) were aged (mean±SD) 58±11 yr: 47% female, 28% aged ≥65 yr. Total daily insulin was 61±29 units/d delivered as 60±16% basal. Percentage of total daily insulin from basal delivery was ≥50% for 73% of users, and ≥70% for 26%. Only 4.5% and 0.6% of users received ≥90% or <20% of daily insulin from basal delivery, respectively. Users bolused 3.5±1.9 x/d, with 7.8±4.5 units/bolus. Average bolus frequency was ≥1x/d for 95% of users, ≥2x/d for 81%, ≥3x/d for 55%, ≥4x/d for 29%, and ≥5x/d for 16%. About 1 in 5 regularly used the extended bolus or temporary basal rate features (EB/TBR, ≥3.33% of days with gaps <60 days, ≥3mo of use). BG test frequency was 2.1±1.5 x/d for those who used the integrated BG meter (n=853). Among these users, those who bolused <3 x/d (n=387) had a mean BG of 180±52 mg/dL, while those who bolused ≥3 x/d (n=466) had a mean BG of 167±36 mg/dL (p<0.001). Regular EB/TBR users (n=189) had a mean BG of 162±36 vs. 176±46 mg/dL for infrequent users (<3.33% of days, n=619, p<0.001).

These real-world data demonstrate positive self-management behaviors among a large cohort of adults with T2D using a tubeless insulin pump. Both basal and bolus insulin delivery were used by ≥95%, with 81% bolusing at least twice per day, and 22% using EB/TBR features. These results support the tubeless pump as a practicable option for those with T2D requiring insulin therapy.

Disclosure

I.B. Hirsch: Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care. Research Support; Self; Medtronic, Omnipod. R.S. Weinstock: Board Member; Self; JDRF. Consultant; Self; Insulogic LLC. Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Jaeb Center for Health Research, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. L.M. Huyett: Employee; Self; Insulet Corporation. J. Jantz: Employee; Self; Insulet Corporation. A. Chang: Employee; Self; Insulet Corporation. Stock/Shareholder; Self; Insulet Corporation. T. Vienneau: Employee; Self; Insulet Corporation. Stock/Shareholder; Self; Insulet Corporation. T.T. Ly: Employee; Self; Insulet Corporation.

Funding

Insulet Corporation
Glucose regulates microtubule disassembly and the dose of insulin secretion via tau phosphorylation
Authors: Admin Ada , Ho Kung-Hsien , Yang Xiaodun , Osipovich Anna B. , Cabrera Over , Hayashi Mansuo L. , Magnuson Mark A. , Gu Guoqiang , Kaverina Irina
Published: June 2020

The microtubule
cytoskeleton of pancreatic islet β-cells regulates glucose-stimulated insulin
secretion (GSIS). We have reported that the microtubule-mediated movement of
insulin vesicles away from the plasma membrane limits insulin secretion. High
glucose-induced remodeling of microtubule network facilitates robust GSIS. This
remodeling involves disassembly of old microtubules and nucleation of new
microtubules. Here, we examine the mechanisms whereby glucose stimulation
decreases microtubule lifetimes in β-cells. Using real-time imaging of
photoconverted microtubules, we demonstrate that high levels of glucose induce
rapid microtubule disassembly preferentially in the periphery of individual
β-cells, and this process is mediated by the phosphorylation of
microtubule-associated protein tau. Specifically, high glucose induces tau
hyper-phosphorylation via glucose-responsive kinases GSK3, PKA, PKC, and CDK5.
This causes dissociation of tau from and subsequent destabilization of
microtubules. Consequently, tau-knockdown in mouse islet β-cells facilitates
microtubule turnover, causing increased basal insulin secretion, depleting
insulin vesicles from the cytoplasm, and impairing GSIS. More importantly,
tau-knockdown uncouples microtubule destabilization from glucose stimulation.
These findings suggest that tau suppresses peripheral microtubules turning-over
to restrict insulin over-secretion at basal conditions and preserve the insulin
pool that can be released in following stimulation; high glucose promotes tau
phosphorylation to enhance microtubule disassembly to acutely enhance GSIS.
KUALITAS HIDUP PASIEN DENGAN PENYAKIT KARDIOVASKULAR DI YOGYAKARTA
Authors: Jumayanti Jumayanti , Wicaksana Anggi Lukman , Akhmad Budi Sunaryo Eri Yanuar
Published: June 2020

Kualitas hidup merupakan indikator utama bagi penyakit kardiovaskular. Penyakit kardiovaskular mendominasi dan menjadi penyakit utama penyebab kematian di Indonesia. Tujuan penelitian ini adalah untuk mengidentifikasi gambaran kualitas hidup pada pasien dengan penyakit kardiovaskular di Mlati, Yogyakarta. Penelitian ini adalah jenis penelitian deskriptif kuantitatif dengan desain cross-sectional. Penelitian dilakukan pada pasien dengan penyakit kardiovaskular yang berada di wilayah Puskesmas Mlati, Sleman, Yogyakarta. Pengambilan sampel menggunakan teknik multistage cluster sampling. Data diambil menggunakan kuesioner Medical Outcome Study 12-Item Short-Form Second-Version (MOS SF-12v2). Analisis data menggunakan tabel distribusi frekuensi terdiri dari rerata, standar deviasi dan frekuensi. Hasil penelitian menunjukkan bahwa terdapat 107 responden yang berpartisipasi. Jumlah responden per-penyakit, hipertensi (n = 97), stroke (n = 13), gagal jantung (n = 12) dan penyakit jantung koroner (n = 7). Gambaran demografi mayoritas usia ≥ 45 tahun; perempuan (63.6 %), pendidikan terakhir SMP (30.8%), tidak bekerja (66%), pendapatan rendah (78.5%) dan menikah (72.9%). Nilai kualitas hidup pada aspek fisik yaitu 42 ± 9.88 dan 56 ± 9.87 untuk aspek mental. Nilai kualitas hidup pada sub-domain vitality (61.67 ± 10.76) dan general health (35.19 ± 7.31) menduduki nilai tertinggi dan terendah. Skor kualitas hidup lebih tinggi pada domain mental daripada domain fisik.