bluuebunny/crossref_metadata_2025_split huggingface dataset:
No Drug–Drug Interaction between Dorzagliatin and Metformin in Type 2 Diabetes Patients
Authors: CHEN LI , ZHAO GUIYU , REN SHUANG , ZHANG YI , DU DANIEL 
Published: June 2018

Dorzagliatin (HMS5552) is a new glucokinase activator and showed excellent antidiabetic effects in type 2 diabetes (T2D) patients with good tolerability. It is in Phase 3 clinical development for a new oral antidiabetic drug. Drug-drug interaction (DDI) potential between dorzagliatin and Metformin was investigated in an open-label clinical study in Chinese T2D patients. T2D subjects (n=15) in general good health between 18 and 70 years old, BMI of 22 to 38 kg/m2, fasting C-peptide &gt;0.3 nmol/L, and HbA1c 7% to 12% were randomized in the study. They had been diagnosed of T2D for at least 3 months and were taking a stable daily dose of ≥1000 mg of Metformin for at least 4 weeks. All subjects were standardized to Metformin 500 mg BID for at least two weeks prior to study day 1. In the study, subjects were treated with Metformin (500 mg BID) on days 1-2 and a morning dose only on day 3 before PK samples were collected for 24 hours. On days 4-7, subjects were treated with Metformin (500 mg BID) and dorzagliatin (50 mg BID), and day 8 morning a single dose of each drug was given before PK samplings. Subjects were then treated with dorzagliatin (50 mg BID) on days 9-12, a single dose only on day 13 morning, and followed by PK samplings. Pharmacodynamic (PD) parameters (glucose, insulin and C-peptide levels) were evaluated on days 3, 8 and 13. Study results demonstrated that Metformin had no effect on the exposure of dorzagliatin (Cmax and AUC0-t). The AUC0-t of Metformin remained unchange when co-administered with dorzagliatin while the Cmax was slightly lower than Metformin alone. It is concluded that there was no significant DDI between dorzagliatin and Metformin. Dose adjustment is not warranted when they are co-administered. PK/PD analysis suggested that co-administration of dorzagliatin and Metformin compared to each drug alone can further improve glycemic control in T2D patients. Both drugs were well tolerated in the study.

Disclosure
L. Chen: None. G. Zhao: None. S. Ren: None. Y. Zhang: None. D. Du: None.
Pleiotropic Effects of Totum-63—Simultaneous Targeting of Multiple Diabetes Mediators
Authors: CHAVANELLE VIVIEN , OTERO YOLANDA F. , SIRVENT PASCAL , CANI PATRICE D. , PELTIER SEBASTIEN 
Published: June 2018

In 2015, 30.3 million Americans had diabetes, and 84.1 million Americans had prediabetes. Up to 70% of individuals with prediabetes will eventually develop type 2 diabetes (T2D). Additional intervention strategies are needed to manage prediabetes. The pathophysiology of T2D is complex and characterized by alterations in many tissues. We have previously shown that Totum-63 is effective to prevent glucose homeostasis impairments in rodent models of T2D. In an open phase I/II clinical study, Totum-63 also improved glucose and insulin responses to a standardized breakfast in healthy subjects. In order to better understand the mechanisms involved in the beneficial effects of Totum-63, we have conducted early interventions with oral administration of Totum-63 in high fat-fed mice and in db/db mice. Body weight gain and fat mass accumulation, known as early mediators of insulin-sensitivity defectiveness, were markedly lowered. Liver and skeletal muscle insulin signaling pathways were activated in a similar fashion despite lower circulating insulin levels, suggesting an improvement in insulin sensitivity. Hepatic triglyceride content, known as a powerful inductor of liver insulin resistance, was reduced. Totum-63 administration increased liver gene expression of FGF-21, which has been involved in the regulation of many metabolic pathways. In db/db mice, Totum-63 administration delayed the defect of insulin secretion, suggesting a protective role on pancreatic beta-cells. Finally, Totum-63 also showed preventive effects on high fat diet-induced gut microbiota dysbiosis, that has been postulated as a key driver of many metabolic disturbances.
In conclusion, Totum-63 displays pleiotropic beneficial effects on tissues known as major contributors to T2D development. Totum-63 is a promising intervention strategy to prevent T2D development, and is currently under investigation in phase II clinical trial.

Disclosure
V. Chavanelle: Employee; Self; Valbiotis. Y.F. Otero: Employee; Self; Valbiotis. P. Sirvent: Employee; Self; Valbiotis. P.D. Cani: Research Support; Self; Tate&Lyle. Consultant; Self; Biocodex. Stock/Shareholder; Self; A-Mansia Biotech SA. Research Support; Self; Pilèje, Valbiotis. S. Peltier: Board Member; Self; Valbiotis.
Implementation of a Perioperative Insulin Protocol in an Advanced Practice Provider (APP)–Led Limb Salvage Hospitalist Team
Authors: ODEDOSU KEHINDE , OCONNELL KATHLEEN K. , JORDAN MICHELLE C. , GUNASEKARAN UMA , FOX PAMELA E. , MCNULTY JACQUELINE N. , HARDER STEPHEN , MENEGHINI LUIGI 
Published: June 2018

We implemented a standardized perioperative insulin management protocol (PIP) for patients with hyperglycemia and acute diabetic foot problems. Our multidisciplinary quality improvement (QI) project retrospectively compared outcomes in the APP-led hospitalist team (TU) using the PIP vs. other hospitalist teams (OT) managing similar patients. We chose glargine U100 as the basal insulin to simplify preoperative dose adjustments. There were no statistical differences in either arm with respect to mean age (53-57 years), female distribution (26-27%), mean weight (85-94 kg) and race/ethnicity (Hispanic 52-62%, Black 34-21% and non-Hispanic white 11-17%). Patients in TU (n=44) and OT (n=42) were started on basal/bolus insulin 80 v 74% of the time, respectively. Initial basal insulin doses (units) were similar (24 ± 12 v 26 ± 24), while initial prandial insulin amounts were higher in TU than OT (21 ± 10 v 13 ± 12; p&lt;0.01), respectively. Use of insulin types were consistent with PIP protocol and hospital formulary guidelines, with TU using glargine and aspart in 89% and 82% of patients, while OT used NPH and Regular in 69% and 76% of patients, respectively. Mean admission A1C (9.1±2.3 v 9.2±2.2 %) and capillary blood glucose (CBG in mg/dl) (239±117 v 257±123) were similar for TU and OT. Mean CBG during hospitalization was lower for TU (163 ± 31 v 187 ± 44; p&lt;0.01). Pre-op (145 ± 49 v 153 ± 50; p=0.48) and immediately post-op (153 ± 74 v 162 ± 81; p=0.59) CBGs were similar for TU and OT, respectively. Hypoglycemia (CBG&lt;70) occurred in 32% of TU and 19% of OT (p=0.18) with only one CBG&lt;50 recorded in each arm. There were no differences in ER visits or readmissions within 30 days of discharge; there was a trend for shorter hospital LOS in TU (14±8 v 18±9 days; p=0.08). A standardized PIP improved perioperative glycemic control without increasing hypoglycemia risk. Wider implementation of this protocol through incorporation into electronic order sets will be the next step in our QI initiative.

Disclosure
K. Odedosu: None. K.K. OConnell: None. M.C. Jordan: Employee; Spouse/Partner; Accenture. U. Gunasekaran: None. P.E. Fox: None. J.N. McNulty: None. S. Harder: None. L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Sanofi US, Novo Nordisk Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Other Relationship; Self; American Diabetes Association.
Implementation of the DP-Transfers Project in Catalonia—A Translational Method to Improve Diabetes Screening and Prevention in Primary Care
Authors: COSTA BERNARDO , MESTRE SANTIAGO , BARRIO FRANCISCO , CABRE JOAN-JOSEP , COS FRANCESC XAVIER , AGUILAR SOFIA , SOLE CLAUSTRE , CASTELL CONXA , ARIJA VICTORIA , LINDSTROM JAANA ,   THE CATALAN DIABETES PREVENTION RESEARCH GROUP
Published: June 2018

Background: DP-TRANSFERS(Diabetes Prevention-Transferring findings from European research to society) is a large scale national program aimed at translating a lifestyle diabetes prevention intervention (DE-PLAN-CAT) in primary care centers in Catalonia.
Methods: Multidisciplinary committee evaluated the programme. Participants without diabetes aged 45-75 years (FINDRISC&gt;11 and/or prediabetes) were posible candidates. Implementation was a 4-channel transfer approach (institutional relationships, facilitator WS, collaborative groupware, programme website) and built upon a 3-step (screening, intervention, follow-up) real-life strategy. The 2-year lifestyle intervention program included an initial 9-hour and 15-hour continuity module, 6 and 10 sessions respectively. A 3-level (centre, professionals and participants) descriptive analysis was conducted using cluster sampling by contributing centres to assess results and barriers identified one year after implementation.
Results: Between June2016 and July2017, 103 PHCC 1.4 million inhabitants (27.9% of all centres), 5professionals agreed to participate. After 1 year,83 centres (80.6%) remained active and 3professionals (60.3%) were involved. Implementation was not feasible in 20 centres (19.4%) 5 main barriers: lack of staff support; discontinuity of the initial effort; increase of workload; shift in professional status and lack of acceptance. Overall, 1819 people were screened and 1458 (80.1%) followed the lifestyle intervention, with 1190 (81.6% or 65.4% of those screened) participating in the basic module and 912 in the continuity (62.5% or 50.1%, respectively).
Conclusions: Large-scale lifestyle intervention in primary care can be properly implemented using existing public health resources. Regrettably, one fifth of the centres and more than one third of the professionals showed substantial resistance to performing these additional activities.

Disclosure
B. Costa: None. S. Mestre: None. F. Barrio: None. J. Cabre: None. F. Cos: Speaker's Bureau; Self; Novartis Pharmaceuticals Corporation. Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Sanofi Pasteur. Speaker's Bureau; Self; Sanofi Pasteur. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Research Support; Self; Eli Lilly and Company. S. Aguilar: None. C. Sole: None. C. Castell: None. V. Arija: None. J. Lindstrom: None.
Out-of-Pocket Costs for Patients with Type 2 Diabetes Mellitus
Authors: DAVIS CHRISTIAN , BURGEN EMILY , CHEN GUOQING J. 
Published: June 2018

Objective: Type 2 diabetes mellitus is a growing epidemic in the United States. In 2015 alone, it affected 30.2 million people. Additionally, the cost of managing type 2 diabetes continues to rise. This condition requires long-term management, and the out-of-pocket costs for type 2 diabetes are not well-characterized. The objective of this study was to understand the magnitude of out-of-pocket costs for type 2 diabetes.
Methods: We identified studies in the PubMed databank that were published between 2000 and 2017. From these studies, we examined the amount spent on out-of-pocket costs by type 2 diabetes patients.
Results: Across the ten studies examined, we found a cost range of $143 per year to $2210 per year, a mean cost of $2063 per year, and a median cost of $435 per year. There is a wide range in cost of out-of-pocket costs for people with diabetes.
Conclusion: Clearly, there is not a consistent cost measurement through all of the studies. Some of the variation is accounted for by different definitions of out-of-pocket cost across the studies. To help better inform patients and healthcare policy decision-makers accurately assessing out-of-pocket cost per year in patients with diabetes, there needs to be a consistent definition of out-of-pocket costs, as well as a consistent way to measure out-of-pocket costs.

Disclosure
C. Davis: None. E. Burgen: None. G.J. Chen: None.
Patient Experience after Being Discharged with Newly Prescribed Insulin or Oral Hypoglycemic Agents
Authors: MADHUN NABIL Z. , CALOGERAS ELLEN , NIWATTISAIWONG SOAMSIRI , CECILIA LANSANG M. 
Published: June 2018

Objective: To identify issues surrounding discharge from hospitalization in patients newly prescribed insulin or oral hypoglycemic agents.
Methods: We conducted telephone surveys and retrospective chart reviews on adult patients satisfying the aforementioned conditions one week after they were discharged from an academic medical center. Data gathered included glucose levels, logistical issues in obtaining medications or testing supplies, and barriers for testing and treating DM. We compared A1c during and after admission, and identified factors associated with change in A1c.
Results: We attempted to contact 141 eligible patients phone, and reached 98. Of 98 patients, 85 were scheduled with a follow-up with PCP or endocrinology within 60 days of discharge, 13 patients were discharged without follow-up scheduled; 76 were discharged with enough supplies and medication to last until next follow-up. Regarding overall glucose control after discharge, 69 patients were completely to very satisfied, 18 were somewhat satisfied, 11 were slightly to not at all satisfied.
Fifty patients had repeat A1c available after admission (median 116 days, IQR 92, 196). There was a significant decrease in A1c (admission mean 9.5% ± SD 2.7 vs. follow-up 7.0% ± 1.5, p &lt;0.0001). There was no statistically significant change in percentage A1c reduction whether patient received bedside delivery (-22.3% ± 18.8) or not (-23.5% ± 22.0; p = 0.825), or between medical (-25.4% ± 20.4) and surgical services (-16.2% ± 18.7, p = 0.134). Patients utilizing bedside delivery program (pharmacy bringing discharge medications to patient’s room) were more likely to receive the correct diabetes testing supplies and medications (95.2%) than those who did not use the service (71.1%) (p=0.003).
Conclusion: Most patients were satisfied with DM education and readiness upon discharge. Bedside delivery may help improve percentage of discharge with correct supplies and medications.

Disclosure
N.Z. Madhun: None. E. Calogeras: None. S. Niwattisaiwong: None. M. Lansang: None.
Care of the Transgender Adolescent with Type 1 Diabetes
Authors: AVILA JONATHAN , AYE TANDY 
Published: June 2018

Approximately 1% of high school aged youth identify as transgender and recent increased societal acceptance of gender dysphoria (GD) has resulted in higher utilization of gender affirming medical interventions. Given that type 1 diabetes (T1D) is one of the most common chronic disease in childhood, it is expected that pediatric diabetes providers will encounter adolescents with both T1D and GD. Pioneering studies from the Netherlands in 1998 described the first use of pubertal suppression with a gonadotropin releasing hormone agonist (GnRHa) in adolescents and the addition of gender affirming sex hormone, testosterone or estrogen, to transition the person to the true gender identity. The Pediatric Endocrine Society, Endocrine Society, and World Professional Association for Transgender Health have published guidelines and standards of care for gender affirming providers. However, very little has been published about the specific considerations in the treatment of these adolescents who have T1D and GD. We report on our experience (n=5) of the unique challenges of managing the T1D during gender transition. There is risk for infection, diabetic ketoacidosis, poor adherence, diabulimia, anxiety and depression in these adolescents. Close monitoring and open conversations between the pediatric diabetes provider and the adolescent with T1D and GD are essential.

Disclosure
J. Avila: None. T. Aye: None.
Long-Term Reduction in Hyperglycemia in Advanced Type 1 Diabetes—The Value of Induced Aerobic Glycolysis by BCG Vaccinations
Authors: KUHTREIBER WILLEM , TRAN LISA , NGUYEN BRIAN , JANES SOPHIE E. , DEFUSCO AUDREY A. , FAUSTMAN DENISE L. 
Published: June 2018

Mycobacteria are among the oldest co-evolutionary partners of humans. Attenuated Mycobacterium bovis, known as the Bacillus Calmette Guérin (BCG) vaccine, has been administered globally for 100 years for TB prevention. BCG vaccination shows clinical promise in numerous autoimmune diseases, including multiple sclerosis (MS) and type 1 diabetes (T1D). In published Phase II clinical trials in MS, BCG shows benefit starting 2 years after administration with continuing effectiveness at year 5. Here we report on the long-term stabilizing effect of BCG vaccination on blood sugar control in advanced T1D with 8 years of follow-up data. The data examines T1D subjects with long-term disease (&gt;10 years duration) who received 2 doses of BCG 4 weeks apart. Starting after year 3, only BCG vaccinated T1D subjects had lowered HbA1c near normal (BCG treated 6.18+/-.34, placebo 7.07+/-.41, reference diabetic 7.22+/-.17, p=0.02; year 5 data with n=46 total subjects). Continued follow-up of 6 subjects for 8 years total confirmed the ability of BCG vaccinations to maintain lowered HbA1c levels without hypoglycemia (BCG treated 6.65+/-.26 vs. 7.22+/-.38, p=0.0002). Glucagon challenge tests were performed once HbA1cs were lowered but did not confirm a therapeutic return of C-peptide levels for improved blood sugar control. Pre-clinical NOD mouse data had shown in mice that BCG induces massive islet regeneration for restore murine blood sugars. In humans, BCG’s impact on blood sugars appears to be driven by a novel mechanism—a systemic shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis, a state of high glucose utilization as measured by metabolomics, RNAseq and cellular glucose uptake, in subjects receiving a long-term benefit with BCG vaccinations. These clinical and novel mechanistic findings, buttressed with further murine testing, set the stage for a safe and cost effective way to possibly improve blood sugars in humans with diabetes.

Disclosure
W. Kuhtreiber: None. L. Tran: None. B. Nguyen: None. S.E. Janes: None. A.A. DeFusco: None. D.L. Faustman: None.
Metformin Improves Insulin Resistance (IR) and Vascular Health in Youth with Type 1 Diabetes (T1D)
Authors: NADEAU KRISTEN J. , BJORNSTAD PETTER , SCHÄFER MICHAL , BROWNE LORNA , BAUMGARTNER AMY , REYES YESENIA GARCIA , MANIATIS ARISTIDES , WADWA R. PAUL , NAYAK SUNIL , PYLE LAURA , CREE-GREEN MELANIE , REUSCH JANE E. 
Published: June 2018

Cardiovascular disease is the leading cause of mortality in T1D and relates to IR. We demonstrated that lean and obese T1D youth have IR and that metformin improves surrogate markers of IR in obese T1D youth. Yet, little is known about vascular health in T1D youth or about the effect of metformin on directly-measured IR or vascular health. In The Effects of MEtformin on cardiovasculaR function in AdoLescents with type 1 Diabetes (EMERALD) study, we hypothesized that T1D youth have impaired vascular function and that metformin decreases IR and improves vascular health. 49 T1D youth ages 12-21 years (40% with BMI ≥ 90%ile; 44% male) and 24 controls of similar age, BMI and sex underwent phase contrast MRI of the ascending (AA) and descending aorta (DA) to determine aortic pulse wave velocity (PWV) and wall shear stress (WSS). T1D youth also had carotid intima-media thickness (cIMT) by ultrasound, DXA scan, fasting labs following overnight IV glycemic control, and a hyperinsulinemic-euglycemic clamp (80 mU/m2/min insulin) to assess IR (glucose infusion rate [mg/kg/min)]/insulin or M/I). T1D youth were then randomized 1:1 to 2g of metformin or placebo daily, and all measures repeated at 3 months. At baseline, T1D youth vs. controls had elevated aortic PWV (AA: 3.7±0.2 vs. 2.5±0.4 m/s, p&lt;0.05; DA: 4.2±0.2 vs. 3.1±0.3 m/s, p=0.02) and WSS (AA: 1.1±0.04 vs. 0.9±0.N/m2, p=0.003; DA: 1.6±0.vs. 1.1±0.07 N/m2, p&lt;0.0001). Compared to the placebo group, T1D youth in the metformin group had no baseline differences but had improvement at 3 months in M/I (12.2±3.2 vs. -2.4±3.6 uIU/uL, p&lt;0.01), AA PWV (-1.1±1.1 vs. 4.1±1.6 m/s, p&lt;0.04), AA WSS (-0.03±0.04 vs. 0.2±0.N/m2, p&lt;0.03) and far wall diastolic cIMT (-0.04±0.01 vs. 0.00±0.01 mm, p=0.04) in baseline-adjusted models. T1D youth have IR and vascular dysfunction compared to controls of similar age, sex and BMI. Metformin mitigated IR and improved aortic and carotid health in T1D youth, and thus may hold promise as a cardiovascular protective intervention.

Disclosure
K.J. Nadeau: None. P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. M. Sch fer: None. L. Browne: None. A. Baumgartner: None. Y. Garcia Reyes: None. A. Maniatis: None. R. Wadwa: Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; MannKind Corporation, Dexcom, Inc., Xeris Pharmaceuticals, Inc., Bigfoot Biomedical. S. Nayak: None. L. Pyle: None. M. Cree-Green: None. J.E. Reusch: Research Support; Self; Merck & Co., Inc.. Board Member; Self; American Diabetes Association. Research Support; Self; AstraZeneca. Other Relationship; Self; Sanofi-Aventis.
Pediatric Case Series of Cystic Fibrosis and Type 1 Diabetes Autoimmunity
Authors: KIM GRACE , MERJANEH LINA 
Published: June 2018

Background: Diabetes is the most common comorbidity in individuals with cystic fibrosis (CF) Autoimmunity was reported to be no greater in CF related diabetes (CFRD) than in the general population and routine screening for type 1 diabetes (T1D) antibodies is not recommended. We report 3 patients with CF, diabetes and T1D autoimmunity.
Clinical cases: Patient 1 and 2 are Caucasian siblings with CF, genotype ∆F5homozygous and pancreatic insufficiency. Patient 1 is a male who presented at age 16 with polyuria, polydipsia and weight loss. Fasting glucose was 350 mg/dL. C peptide was 1.1 ng/ml and Hba1c was &gt;14%. T1D antibodies showed (Anti GAD 147, negative Islet cell antigen antibody 512 (IA2), ZNT8 and insulin antibodies). Current insulin requirement at age 22 is 0.8 units/kg/day with Hba1C ranging from 6.7-12.0%. Patient 2 is a female diagnosed with CFRD at age 9 with an oral glucose tolerance test. Fasting glucose was 92 mg/dL and 2-hour glucose 209 mg/dL. C peptide 7.1 ng/ml. Hba1c 6.7%. T1D antibodies were negative at presentation. At age 14, because of increase in insulin requirement, T1D antibodies were retested and positive (Anti GAD 31, IA2 52, znt8 0.955). Her current insulin dose at age16 is 0.7units/kg/day with Hba1c ranging 6.7-12.7%. Patient 3 is a prepubertal biracial (African American, Caucasian) female with CF, genotype 1 copy of ∆F5and 1 copy of ∆I507, pancreatic insufficiency and Hashimoto’s hypothyroidism. She presented at age 9 with polyuria, polydipsia and weight loss. She was in DKA with glucose 686 mg/dL, bicarbonate 5 mEq/L, BOHB 5.4 mmol/L, C-Peptide 0.1 ng/ml, HbA1C &gt;14%. T1D antibodies were positive (Anti GAD 192, IA2 183, ZnT8 0.177, Insulin 0.017). Current insulin dose at age 11 is 0.55 unit/kg/day with Hba1c ranging 7.7-10.2%.
Conclusion: T1D needs to be considered in a CF patient with hyperglycemia when patient is prepubertal, symptomatic, in DKA, or requiring high insulin doses. Correct diagnosis allows for proper treatment and help prevent short and long-term diabetes complications.

Disclosure
G. Kim: None. L. Merjaneh: None.