bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the Real-World Use of Combination Insulin Glargine-Lixisenatide in Patients with Type 2 Diabetes Mellitus—A Retrospective Review from an Ambulatory Care Endocrinology Practice
Authors: STRYKER MATTHEW D. , BLOW CURTIS A. , FRIEDMAN ERICA B. , BUSCH ROBERT S. , KANE MICHAEL P. 
Published: June 2018

Purpose: This is a pre-post observational study from an endocrinology ambulatory care practice assessing the effectiveness and safety of a single injectable combination antidiabetic agent, the basal insulin, insulin glargine, and the glucagon-like peptide-1 (GLP-1) receptor agonist, lixisenatide, to background therapy for patients with type 2 diabetes mellitus (T2DM).
Methods: The study population will consist of subjects with T2DM who have failed to achieve adequate glycemic control and require the addition of once-daily insulin glargine-lixisenatide (iGlarLixi). Five groups will be assessed: patients initiating iGlarLixi, patients on a basal insulin at baseline, patients on a GLP-1 receptor agonist at baseline, patients on basal insulin and GLP-1 receptor agonist (single-entity products) at baseline and patients only on oral antidiabetic agents at baseline. Potential subjects will be identified via a computerized text search of medication lists from patients’ electronic medical records, which will be reviewed to ascertain if study criteria are met.
Outcome: The primary study outcome is change in HbA1c. Secondary outcomes include percentage of patients achieving an HbA1c of &lt; 7% or ≤ 6.5%, change in weight, change in systolic and diastolic blood pressures and change in lipid parameters. Safety will be assessed via collection of reported adverse effects.
Results: Thirty subjects initiated therapy with iGlarLixi and 23 had follow-up data. The mean duration of T2DM was 11.3 years and baseline HbA1c was 8.27%. The median starting dose of iGlarLixi was 30 units and the mean dose at follow-up was 41 units. After an average of about 4 months on therapy, HbA1c decreased by 0.94% in the entire cohort (p = 0.02). Fifty-seven percent of subjects achieved an HbA1c &lt; 7% and 26% achieved an HbA1c ≤ 6.5%. iGlarLixi was well tolerated and discontinuation was low (3 subjects) and mainly due to medication cost.

Disclosure
M.D. Stryker: Other Relationship; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Other Relationship; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Regeneron Pharmaceuticals, Inc.. C.A. Blow: None. E.B. Friedman: None. R.S. Busch: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca. Research Support; Self; Bayer AG, Intarcia Therapeutics, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Sanofi US. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Amarin Corporation. M.P. Kane: None.
Novel Risk Panel for CAD and All-Cause Mortality in Type 1 Diabetes
Authors: KESHAWARZ AMENA , SIPPL RACHEL M. , REBUCK HEATHER , DONALD SARAH , HUANG SHARON Y. , CHRISTENSON ROBERT H. , SNELL-BERGEON JANET K. 
Published: June 2018

Coronary artery disease (CAD) prevalence is increased and life expectancy is reduced by more than a decade in people with type 1 diabetes (T1D) compared to nondiabetics (non-DM), but traditional risk factors do not explain all of the increased risk. We examined whether three novel risk markers, high-sensitive cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and growth differentiation factor 15 (GDF-15), are elevated in T1D and predict CAD and mortality.
1,416 adults age 19-56 (652 T1D, 754 non-DM) were enrolled in the Coronary Artery Calcification in type 1 diabetes (CACTI) study from 2000-2002. We assessed CAD events (fatal or non-fatal myocardial infarction, coronary artery bypass graft, or angioplasty) with annual follow-up questionnaires. In-person visits occurred at 3, 6, and 12 years after baseline. Serum samples from the visit prior to a CAD event or death or from the last in-person visit were available for 1,389 participants and were assayed for hs-cTnT, NT-proBNP, and GDF-15 at the University of Maryland. Elevated marker levels were defined as those above the 95th percentile among non-DM participants. Biomarker levels were compared by T1D status in linear regression, and logistic regression was used to examine associations with CAD and all-cause mortality.
Age- and sex-adjusted LSmeans ± SE for log hs-cTnT (2.0±0.02 vs. 1.6±0.02, p&lt;0.0001), log NT-proBNP (3.8±0.04 vs. 3.5±0.03, p#x003C;0.0001), and log GDF-15 (6.5±0.02 vs. 6.2±0.02, p#x003C;0.0001) were significantly higher in T1D than non-DM participants. Over the follow-up period, there were 72 CAD events (53 T1D, 19 non-DM) and 76 deaths (58 T1D, 18 non-DM). Having elevated levels of all 3 vs. none of the markers was a significant predictor of both CAD (OR [95% CI] 6.4 [2.0-20.7]) and all-cause mortality (OR [95% CI] 10.7 [3.3-35.4]), independent of age, sex, renal function and T1D status.
A panel of novel markers, hs-cTnT, NT-proBNP, and GDF-15, are elevated in T1D and may help identify those at risk for CAD events and mortality.

Disclosure
A. Keshawarz: None. R.M. Sippl: None. H. Rebuck: None. S. Donald: None. S.Y. Huang: None. R.H. Christenson: Consultant; Self; Roche Diagnostics Corporation, Siemens, Becton, Dickinson and Company. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation.
Altered Gonadal Fat Stromal Cell Populations in Adipocyte-Specific Oncostatin M Receptor Knockout Mice—A Possible Role for Local SDF1
Authors: ELKS CARRIE M. 
Published: June 2018

The IL-6 family cytokine, oncostatin M (OSM), has several physiological roles, but its exact role in adipose tissue homeostasis is still unclear. We recently reported that high-fat diet-fed male mice with an adipocyte-specific deletion of the OSM-specific receptor (OSMR FKO mice) were insulin-resistant and had increased markers of inflammation in epididymal adipose tissue (eWAT). In the current study, we more closely examined eWAT stromal cell populations in high-fat fed OSMR FKO mice using flow cytometry. Results from flow cytometry studies revealed that, despite no differences in eWAT weights between genotypes, OSMR FKO mice had significantly fewer stromal cells per gram eWAT. Although there were fewer stromal cells overall, a significantly higher percentage of these cells were CD45+ leukocytes. Significant decreases in the numbers of adipose tissue macrophages (CD64+; CD11c+/-) and preadipocytes (CD45-; CD31-; Sca1+) were also observed in OSMR FKO eWAT. A cytokine array was performed on eWAT to assess differences in tissue cytokine profiles that may contribute to the alterations observed in stromal cell populations. Array results indicated a significant decrease in stromal cell-derived factor 1 (SDF1) protein expression in eWAT of OSMR FKO mice. Future studies will focus on the role of adipocyte OSM signaling as a regulator of adipose tissue SDF1 production and stromal cell homeostasis. Overall, our results suggest a homeostatic role for adipocyte OSM signaling in the maintenance of stromal cell populations in gonadal fat.

Disclosure
C.M. Elks: None.
Meta-analysis of HbA1c-Lowering Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Combination with Insulin in T2DM Patients
Authors: YANG JIN , TIAN QING , TANG YUEXIN , SHAH ARVIND K. , ZHANG RUYA , CHEN GUOJUAN , ZHANG YE , RAJPATHAK SWAPNIL , HONG TIANPEI 
Published: June 2018

Randomized controlled trials (RCTs) have evaluated the efficacy of dipeptidyl peptidase-4 inhibitors (DPP-4i) as add-on therapy to insulin compared to insulin alone in T2DM patients, while there have been differences in the magnitude of the outcome effect across studies. This updated systematic review and meta-analysis aimed to evaluate the effect of DPP-4i in combination with insulin on HbA1c in T2DM patients.
MEDLINE, EMBASE, and Cochrane databases were searched for RCTs that compared DPP-4i plus insulin to insulin alone for T2DM patients, with or without background therapy with other oral agents. The primary endpoint was the absolute change of HbA1c from baseline. Weighted mean difference (WMD) with 95% confidence intervals (CI) was calculated using a random effect model. The methodological quality of included RCTs was evaluated using the Cochrane risk of bias tool.
Eighteen RCTs involving 6,493 patients with average follow-up of 32 weeks were identified and analyzed. DPP-4i plus insulin showed greater reduction in HbA1c than insulin alone (WMD -0.52%, 95% CI -0.61 to -0.43; P&lt;0.0001) (Figure 1).
In conclusion, compared with use of insulin alone, DPP-4i in combination with insulin can significantly lower HbA1c levels in T2DM patients. Further analysis is needed to better understand effects of this combination therapy on other outcomes, such as hypoglycemia and insulin.

Disclosure
J. Yang: None. Q. Tian: None. Y. Tang: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc.. Employee; Spouse/Partner; GlaxoSmithKline plc.. Stock/Shareholder; Spouse/Partner; GlaxoSmithKline plc. A.K. Shah: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. R. Zhang: Employee; Self; Merck Sharp & Dohme Corp. G. Chen: Employee; Self; Merck Sharp & Dohme Corp.. Y. Zhang: None. S. Rajpathak: Employee; Self; Merck & Co., Inc. T. Hong: Advisory Panel; Self; Novo Nordisk A/S, AstraZeneca.
Effectiveness and Tolerability of Vildagliptin plus Metformin Compared with Other Oral Dual Antidiabetes Agents in Different Baseline BMI Patients with Type 2 Diabetes—A Real-World Study (China PDS)
Authors: JIN HUI , HAN YING , CHEN LIXIAN , HU DAQING , YANG NAILONG , SHI XIAOYUN , LI QUANMIN , LIANG LINLANG , ZANG LI , LIU MINGMING , HE JAMES , MU YIMING 
Published: June 2018

Background and Aim: The real-world study of China PDS with 2083 type 2 diabetes mellitus (T2DM) patients showed that vildagliptin plus metformin (VM) therapy could effectively control the HbA1c with good tolerability. Here, we present the results of baseline BMI subgroups.
Materials and Methods: In China PDS, T2DM patients with poor glycemic control on monotherapy were assigned to either VM dual therapy or other oral dual agents(OD) therapy according to local physician’s decision. For this analysis, patients were divided into three subgroups according to baseline BMI(&lt;24kg/m2, 24-28kg/m2, &gt;28kg/m2). The primary outcome was the proportion of patients with HbA1c&lt;7% and without tolerability events(hypoglycemia, weight gain, or discontinuation due to gastrointestinal event) at 12th month. Secondary outcomes included mean changes in HbA1c from baseline to study endpoint and tolerability.
Results: In total, 389(149 in VM vs. 240 in OD) patients in BMI&lt;24kg/m2 group, 625(304 in VM vs. 321 in OD) patients in BMI 24-28kg/m2 group, and 260(151 in VM vs. 109 in OD) patients in BMI&gt;28kg/m2 group were enrolled. Compared with OD, significantly higher proportion patients reached primary outcome in VM in BMI&lt;24kg/m2 group (47.0% vs. 35.0%; P=0.019), in BMI 24-28kg/m2 group (52.6% vs. 33.3%; P&lt;0.001), and in BMI&gt;28kg/m2 group (51.0% vs. 33.9%; P=0.006). Mean HbA1c changes were significantly greater in VM than in OD(BMI&lt;24kg/m2: -1.23% vs. -0.76%; BMI 24-28kg/m2: -1.32% vs. -0.79%; BMI&gt;28kg/m2: -1.29% vs. -0.84%; P&lt;0.for all). VM resulted in less tolerability findings than OD in BMI&lt;24kg/m2 (11.4% vs. 19.2) and BMI 24-28kg/m2 (3.6% vs. 14.6%) groups (P&lt;0.for both), but not in BMI &gt;28kg/m2 group (4.6% vs. 5.5%, P&gt;0.05).
Conclusion: In different baseline BMI groups, vildagliptin plus metformin dual therapy was associated with better glycemic control and was well tolerated compared with OD.

Disclosure
H. Jin: None. Y. Han: None. L. Chen: None. D. Hu: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.
Effect of an Add-On SGLT2 Inhibitor on the Efficacy of DPP-4 Inhibitor Therapy in Improving Postprandial Hyperglycemia
Authors: ONISHI TETSUROU , TANIGUCHI YUKIKO , MORI YUTAKA 
Published: June 2018

Objective: This study was conducted to investigate the effect of an add-on SGLT2 inhibitor on the efficacy of DPP-4 inhibitor therapy improving postprandial hyperglycemia in terms of its effect on diurnal glycemic variability (GV) to provide insight into the effect of the SGLT2 inhibitor on incretin-responsive insulin secretion.
Patients and Methods: This study enrolled 12 type 2 diabetic patients with inadequate glycemic control despite treatment with the DPP-4 inhibitor teneligliptin (T) (20 mg/day) (Age, 69.5±7.4 years; BMI, 27.2±3.7 kg/m2; HbA1c, 7.7±0.7%). All patients were treated with add-on canagliflozin (Cana) 100 mg/day for 8 weeks and compared for diurnal GV before and after treatment with add-on Cana using CGM.
Results: With the initiation of add-on Cana, a significant decrease was noted in body weight and BMI (P &lt; 0.05). The HbA1c and GA values were significantly decreased (P &lt; 0.05) and the adiponectin values significantly increased (P &lt; 0.05). The diurnal GV indices, such as the SD of glucose values, total area between the 24-h mean glucose levels and glucose curve, and mean amplitude of glucose excursions (MAGE) significantly decreased (P &lt; 0.05), as the pre-breakfast glucose values and the 24-hour mean glucose values significantly decreased with add-on Cana. Additionally, treatment with add-on Cana led to a significant decrease in the % of time in hyperglycemia but no significant change in the % of time in hypoglycemia.
Conclusions: The mechanisms through which add-on Cana reduced diurnal GV in type 2 diabetic patients receiving T may be accounted for as follows: add-on Cana improved incretin-responsive insulin secretion through resolution of glucotoxicity resulting in enhancement of the efficacy of T in improving postprandial hyperglycemia, as well as weight loss through calorie loss via glycosuria, which, coupled with attendant improvements in insulin resistance, led to improvements in postprandial hyperglycemia and reductions in diurnal GV.

Disclosure
T. Onishi: None. Y. Taniguchi: None. Y. Mori: None.
AAV-Mediated Overexpression of BMP7 in White Adipose Tissue Induces Adipogenesis and Ameliorates Insulin Resistance
Authors: LORENTE ESTEFANIA CASANA , JIMENEZ VERONICA , FRAILE VICTOR SACRISTÁN , MUÑOZ SERGIO A. , PALLARÉS CLAUDIA JAMBRINA , RODÓ JORDI , DARRIBA SARA , MALLOL CRISTINA , GARCIA MIQUEL , LEON XAVIER , GRASS IGNASI , FRANCKHAUSER SYLVIE , BOSCH FATIMA 
Published: June 2018

Obesity and type 2 diabetes are strongly associated and a major health problem because of their alarmingly growing prevalence worldwide. The hypertrophic expansion of white adipose tissue (WAT) promotes ectopic fat accumulation and development of insulin resistance whereas WAT hyperplasia is associated with preservation of insulin sensitivity. Several members of the Bone Morphogenetic Protein (BMP) family have been shown to play a role in white and/or brown adipogenesis and energy homeostasis. Although BMP7 has extensively been reported to induce brown adipogenesis in vitro, its role on WAT expandability and its potential contribution to insulin sensitivity remains to be elucidated. Here, we showed that local administration of adeno-associated viral vectors (AAV) encoding BMP7 in WAT resulted in hyperplasic expansion of WAT together with reduced liver steatosis and amelioration of insulin sensitivity in both HFD-fed and ob/ob obese mice. In contrast, the AAV-mediated overexpression of BMP7 specifically in the liver did not promote WAT hyperplasia although the circulating levels of BMP7 achieved were similar to those obtained after intra-WAT administration of AAV vectors. Nevertheless, when liver-derived BMP7 circulating levels were further increased, body weight and insulin sensitivity were normalised in HFD-fed as well as in ob/ob mice. Altogether, these results unravel a new role of BMP7 on white adipogenesis. In addition, this study suggests the potential of BMP7 gene therapy to ameliorate obesity and insulin resistance.

Disclosure
E. Casana Lorente: None. V. Jimenez: None. V. Sacristán Fraile: None. S.A. Muñoz: None. C. Jambrina Pallarés: None. J. Rodó: None. S. Darriba: None. C. Mallol: None. M. Garcia: None. X. Leon: None. I. Grass: None. S. Franckhauser: None. F. Bosch: None.
The Impact of Endocrinology Consultation in the United States on Global Diabetes Care
Authors: ALI KHAWLA F. , MIKHAEL ALEXANDRA , ZAYOUNA CHRISTINE , CECILIA LANSANG M. 
Published: June 2018

Introduction: Medical travel, a form of patient mobility across borders, has gained significant momentum in the last years. Nevertheless, limited evidence exists regarding the clinical outcomes for these patient-sought treatments at U.S. institutions. We aimed to examine the characteristics of global patients referred to our institution for short-term diabetes management and the impact of our consultation on the cohort’s glycemic control.
Methods: We identified adult patients with established diabetes mellitus, who sought medical care at the Cleveland Clinic Foundation between the years 2010 and 2016 from the following countries: Bahrain, Qatar, UAE, Kuwait, Saudi Arabia and Oman, and were seen at least once by an endocrinology provider. Our control group included an internationally identical cohort with diabetes mellitus, but without an office visit to endocrinology. Continuous, normally distributed data were described using means and standard deviations (SD), while non-normally distributed data were described using medians and quartiles. To assess the impact of our endocrine consultations, changes in HbA1C were assessed after single and multiple endocrine visits using paired t-tests.
Results: Our study included 1,1subjects (771 in study group, 337 in control group), with a mean age (±SD) of 61.3±12.7 years, 62% male, and a median follow-up duration of 136 days [IQR: 57, 660]. Compared to controls, study subjects had higher baseline mean HbA1C level (8.0±1.8% vs. 7.1±1.4%, p&lt;0.001) and higher prevalence of cardiovascular disease (64.6% vs. 56.0%, p=0.006). After only one visit with endocrinology, there was a significant decrease in mean HbA1C of -1.00% (95% CI:-1.23, -0.78) (p&lt;0.001). The greatest degrees of change in mean HbA1C were -1.47% (95% CI: -2.21, -0.74) and -1.27% (95% CI: -1.89, -0.66) after 3 and 4 visits, respectively (p&lt;0.001).
Conclusion: Global patients seen for diabetes management had a significant drop of nearly 1 point in HbA1c even after one endocrinology consultation.

Disclosure
K.F. Ali: None. A. Mikhael: None. C. Zayouna: None. M. Lansang: None.
Persistence to Treatment with DPP-4 Inhibitors, SGLT2 Inhibitors, and GLP-1-RAs Compared with Insulin after Failure with First Antidiabetic Drug in T2DM Patients
Authors: JERMENDY GYORGY , ROKSZIN GYÖRGY , ABONYI-TÓTH ZSOLT , WITTMANN ISTVAN , KEMPLER PETER 
Published: June 2018

Adequate persistence to antidiabetic treatment is highly important to achieve proper glycemic control. Data on persistence with new antidiabetic drugs are limited. The aim of the study was to evaluate the persistence to treatment with DPP-4-inhibitors, SGLT2-inhibitors and GLP-1-RAs in comparison to insulin (INS) in a nationwide cohort of T2DM patients. Using the database of the Hungarian National Health Insurance Fund, the persistence to the treatment with DPP-4-inhibitors (n=59,900), SGLT2-inhibitors (n=26,052), GLP-1-RAs (n=17,332) and INS (n=51,781) was analyzed between 2014 and 2016. We captured the antihyperglycemic agents either in monotherapy or in add-on combinations after failure with first antidiabetic drug. Persistence was defined as the duration of time from initiation to discontinuation of the particular therapy. A permissible gap of 180 days (grace period) was allowed. The results are reported as the rate of persistent patients at year 1 and year 2. The persistence of DPP-4-inhibitors and SGLT2-inhibitors was similar at year 1 (68%, 67%), both of which decreased by year 2 (55% and 56%, respectively). The persistence of GLP-1-RAs was 66% at year 1, which decreased remarkably to year 2 (51%). DPP-4-inhibitors + metformin in fix combination had higher persistence (64% and 50%) than that of free add-on combinations (43% and 29%, at year 1 and year 2, respectively). Similar trend was observed regarding SGLT2-inhibitors + metformin fix vs. free add-on combinations at year 1 (75% vs. 55%). Treatment with INS had a relatively high persistence (71% and 61% at year 1 and year 2, respectively). Persistence to treatment with innovative drugs was the highest in patients with age of 40-60 years. Persistence data of different antihyperglycemic agents provide useful information and should be considered as one of components that help to guide the proper decision at initiation of antidiabetic treatment.

Disclosure
G. Jermendy: None. G. Rokszin: None. Z. Abonyi-Tóth: None. I. Wittmann: None. P. Kempler: None.
Physician Visits and Antidiabetic Medication Use among Adolescents with Type 2 Diabetes with Commercial Insurance or Medicaid
Authors: CURTIS SARAH , JOHNSTON JOSEPH A. , ANDERSON PAMELA W. , SCHROEDER KRISTA M. , WU JIANMIN , ZEITLER PHIL 
Published: June 2018

Background: Type 2 diabetes (T2D) is becoming more prevalent in adolescents. Multi-disciplinary care with periodic follow-up is required to ensure optimal management with lifestyle modification and medications. The purpose of this study was to estimate physician visitation rates and antidiabetic medication use (including off-label use) among adolescents with T2D and examine the impact of insurance type (Commercial vs. Medicaid).
Methods: We used data from the Truven MarketScan Commercial and Medicaid administrative claims databases to identify a cohort of adolescents aged 10-17 years with T2D (≥2 T2D diagnoses or ≥1 T2D diagnosis and ≥1 antidiabetic medication) with continuous medical and prescription enrollment in 2015. Patients with gestational diabetes, diabetes complicating pregnancy, and secondary diabetes were excluded. Visits to specified providers (pediatric endocrinologist, pediatrician, and family practitioner) and use of medications overall and by class were assessed.
Results: Substantially more commercially insured than Medicaid patients had ≥1 visit to any specified provider (88% vs. 45%) and to pediatric endocrinologists (33% vs. 14%). The use of any antidiabetic medication was similar in both insurance types (92% vs. 90%); however, off-label use was higher in commercially insured patients (9% vs. 6%), specifically those visiting only family practitioners (12%). The most commonly used off-label drug class was sulfonylureas.
Conclusions: A higher proportion of commercially insured adolescents received multi-disciplinary care. While use of any antidiabetic medication was similar, off-label use was greater among commercially insured. Concerted efforts are needed to enhance patient access, generate evidence regarding non-approved medications, and educate providers about optimal care of youth with T2D, particularly on the use of sulfonylureas, which are not recommended by current guidelines.

Disclosure
S. Curtis: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. J.A. Johnston: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. P.W. Anderson: Other Relationship; Self; Eli Lilly and Company. K.M. Schroeder: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. J. Wu: None. P. Zeitler: Consultant; Self; Daiichi Sankyo Company, Limited, Merck & Co., Inc., Eli Lilly and Company, Takeda Development Center Americas, Inc., Boehringer Ingelheim GmbH.