bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-World Health Outcomes of Insulin Glargine 300 U/mL (Gla-300) vs. Insulin Glargine 100 U/mL (Gla-100) in Patients with Type 1 (T1D) and Type 2 Diabetes (T2D) in the Canadian LMC Diabetes Patient Registry—The REALITY Study
Authors: ABITBOL ALEXANDER , BROWN RUTH E. , JIANDANI DISHAY , SAURIOL LUC , ARONSON RONNIE 
Published: June 2018

This retrospective cohort study evaluates real-world health outcomes in patients with T1D and T2D initiating Gla-300 or Gla-100 as part of their usual therapy in the largest specialist-led clinic group in Canada, between January 2015 and August 2017. The primary outcome was HbA1c change at 3-6 months. Four separate cohorts were evaluated. In the T1D cohort, 299 patients transferred from Gla-100 to Gla-300 had a significant HbA1c reduction of -0.2 ± 1.2%, with no change in weight, hypoglycemia or basal insulin dose (Table). Similarly, 488 patients with T2D transferred from Gla-100 to Gla-300 had a significant HbA1c reduction of -0.47 ± 1.37%, with no change in weight, hypoglycemia or basal insulin dose. In patients with T2D transferred from NPH or detemir (n=343), Gla-300 had a significantly greater reduction in HbA1c than Gla-100 (-0.30 ± 2.2%), with no change in weight, hypoglycemia or basal insulin dose in either group. For insulin-naïve T2D patients (n=1448), there were no significant differences between Gla-300 and Gla-100 in adjusted HbA1c or weight. Patients with T1D and T2D in a national specialist-led registry, who transferred from their usual basal insulin to Gla-300, significantly reduced their HbA1c, without increasing weight, basal insulin dose, nor hypoglycemia incidence.

Disclosure
A. Abitbol: Research Support; Self; JDRF, JA DeSeve Foundation, Lexicon Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; GlaxoSmithKline plc., Merck & Co., Inc.. Consultant; Self; Merck & Co., Inc.. Speaker's Bureau; Self; Merck & Co., Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Pfizer Inc., AstraZeneca. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Research Support; Self; Senseonics, Gilead Sciences, Inc.. Speaker's Bureau; Self; Amgen Inc., Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Employee; Self; LMC Diabetes & Endocrinology. Speaker's Bureau; Self; LMC Diabetes & Endocrinology, Valeant Pharmaceuticals International, Inc.. Consultant; Self; Valeant Pharmaceuticals International, Inc.. R.E. Brown: None. D. Jiandani: None. L. Sauriol: Employee; Self; Sanofi. R. Aronson: Other Relationship; Self; Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi, AstraZeneca. Research Support; Self; Eli Lilly and Company, Becton, Dickinson and Company, Merck & Co., Inc., Senseonics, Boehringer Ingelheim Pharmaceuticals, Inc..
Progression from Prediabetes to Type 2 Diabetes (T2DM) in 303 Hypogonadal Men With and Without Testosterone Treatment—Eight-Year Real-Life Data from a Registry
Authors: SAAD FARID , HAIDER AHMAD , HAIDER KARIM S. 
Published: June 2018

Background: Hypogonadism predicts T2DM and is highly prevalent in men with prediabetes.
Methods: Pooled data from 2 ongoing urological registries. 303 men had prediabetes by HbA1c according to ADA definition. 220 received treatment with 3-monthly injections of testosterone undecanoate (TU; T-group), 83 served as controls (CTRL). Anthropometric and metabolic parameters were measured over 8 years.
Results: Mean follow-up: 6.6 years (T-group), 5.6 years (CTRL). Mean age: 60.6±9.6 years. Under TU, HbA1c decreased from 5.9±0.2 to 5.5±0.3% at 8 years (p&lt;0.0001). In CTRL, HbA1c increased from 5.9±0.2 to 6.1±0.6% (p&lt;0.0005). At the last observation, all 220 patients (100%) in the T-group had an HbA1c &lt;6.5%. In CTRL, 35 men (42.2%) had progressed to T2DM with HbA1c &gt;6.5% The TyG index, a surrogate parameter for insulin resistance, decreased in the T-group from 9.3±0.4 to 9.0±0.4 at 8 years. In CTRL, the index increased from 8.9±0.6 to 9.3±0.4 at 8 years. At baseline, 158 men (52.1%) were obese, 126 men (41.6%) were overweight and 19 (6.3%) had normal weight. Weight decreased from 96.7±12.3 to 89.0±9.6 kg in the T-group and increased from 92.9±10.4 to 98.2±6.3 kg in CTRL. Waist circumference decreased from 104.2±7.1 to 98.2±6.5 cm in the T-group and increased from 102.5±9.7 to 106±3.2 cm in CTRL. Weight loss was 9.2±8.3% at 8 years in the T-group. In CTRL, weight increased by 9.2±3.9% at 8 years (p&lt;0.0001 for all). Adherence to TU was 100 per cent as all injections were performed and documented in the office.
Conclusion: Testosterone therapy prevented progression from prediabetes to T2DM in hypogonadal men while more than 40% of untreated hypogonadal men developed T2DM. This effect may have been supported by sustained weight loss and been mediated by the invariable increase in lean mass achieved by testosterone.

Disclosure
F. Saad: Employee; Self; Bayer AG. Stock/Shareholder; Self; Bayer AG, Novo Nordisk A/S. A. Haider: Research Support; Self; Bayer AG. K.S. Haider: Other Relationship; Self; Bayer AG.
Relationship of Ethnicity to Clinical Outcomes in iGlarLixi-Treated Patients with Type 2 Diabetes
Authors: MORA PABLO , CHAO JASON , SAREMI ARAMESH , DEX TERRY A , ROBERTS MICHELLE , UMPIERREZ GUILLERMO E 
Published: June 2018

Pharmacogenetic studies have shown significant differences among racial and ethnic groups. This post-hoc analysis of 2 30-week phase 3 trials of patients with type 2 diabetes uncontrolled on metformin ± oral antidiabetes drugs (OADs) (LixiLan-O: NCT02058147) or basal insulin ± OADs (LixiLan-L: NCT02058160) determined the safety of iGlarLixi vs. insulin glargine (iGlar) among Hispanic and non-Hispanic patients.
Analysis of variance/covariance was used for continuous variables and χ2/Cochran-Mantel-Haenszel for categorical variables. A generalized linear model using negative binomial distributions with factors of treatment arm and ethnicity, covariates of age and baseline weight or BMI, and log exposure as offset, was used for symptomatic hypoglycemia (plasma glucose ≤70mg/dL) rates. Adjusted hypoglycemia rates used the same model with mean values of age and baseline weight or BMI.
Across studies 20% (353/1730) of all patients were Hispanic. At baseline, Hispanic patients had significantly lower body weight, BMI, and fasting plasma glucose vs. non-Hispanic patients (all, P&lt;0.001). Overall, clinical outcomes were similar for Hispanic and Non-Hispanic patients, regardless of drug type (Figure). However, iGlarLixi demonstrates better glycemic control in both Hispanic and non-Hispanic patients, with similar safety outcomes to iGlar.

Disclosure
P. Mora: Advisory Panel; Self; Novo Nordisk Inc.. Consultant; Self; Sanofi US. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi US. J. Chao: None. A. Saremi: Employee; Self; Sanofi US. T.A. Dex: Employee; Self; Sanofi US. Stock/Shareholder; Self; Pfizer Inc., Merck Sharp & Dohme Corp., Teva Pharmaceutical Industries Ltd.. M. Roberts: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc..
Addition of GLP-1 Therapy to Insulin in C-Peptide-Positive Patients with Type 1 Diabetes
Authors: KUHADIYA NITESH D. , PROHASKA BENJAMIN , GHANIM HUSAM , DANDONA PARESH 
Published: June 2018

We have previously demonstrated that the addition of liraglutide to insulin significantly improves the glycemic control in patients with type 1 diabetes (T1D) with undetectable c-peptide. We have now investigated whether the addition of GLP-1 therapy to insulin in c-peptide positive patients with T1D will increase the c-peptide concentrations and improve the glycemia further with reduced insulin requirements. We conducted a retrospective analysis of 11 Caucasian patients with detectable c-peptide and positive GAD-65 antibodies treated with GLP-1 therapy for 12±1 weeks (baseline c-peptide: 0.43±0.09 ng/ml; baseline HbA1c: 10.63±0.87%; mean age: 43±5 years; mean age of diabetes diagnosis: 37±5 years; mean duration of diabetes: 6±2 years; mean BMI: 23± 1Kg/m2; mean body weight: 71±2 kg; 6 females, 5 males). At the end of 12± 1 weeks of GLP-1 therapy; c-peptide concentrations increased significantly from 0.43±0.09 to 1.42±0.42ng/ml(p=0.01); HbA1c fell from 10.63± 0.87% to 7.45± 0.52%(p&lt;0.01), body weight fell from 71±2.0 kg to 69±2 kg(p=0.06) and total insulin dose fell by 64% from 34.45±5.73 to 12.27±4.01 units(p&lt;0.01). 5 out of 11 patients did not require any insulin. 9 patients were initiated on liraglutide: 0.6 mg subcutaneous(sc) daily for one week, 1.2 mg daily for second week and then 1.8 mg daily thereafter. One out of these 9 patients did not tolerate 0.6 mg daily dose and stopped it due to nausea in the first week. 2 patients were initiated on dulaglutide(0.75 mg sc once a week for 2 weeks and then 1.5 mg once a week thereafter). We conclude that addition of GLP-1 therapy in GAD-positive and C-peptide positive patients with type 1 diabetes (T1D) results in 3.5 fold increase in c-peptide concentrations with improved glycemic control and more than 60% reduction in insulin requirements over a period of 12 weeks. Long term studies are needed to establish the durability of these benefits.

Disclosure
N.D. Kuhadiya: Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S, Janssen Scientific Affairs, LLC.. Advisory Panel; Self; AstraZeneca. Consultant; Self; Dexcom, Inc.. B. Prohaska: None. H. Ghanim: None. P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca.
Are We Misdiagnosing Diabetic Foot Osteomyelitis?
Authors: CRISOLOGO PETER A. , LA FONTAINE JAVIER , DAVIS KATHRYN , LAVERY LAWRENCE A. 
Published: June 2018

Rationale and Aim: To compare the incidence of osteomyelitis based on different operational definitions using the gold standard of bone biopsy.
Methods: We prospectively enrolled 35 consecutive patients who met the criteria of ?21 years of age, a moderately or severely infection based on the Infectious Diseases Society of America. Bone samples were obtained from all participating patients either by percutaneous bone biopsy or intraoperative if the patient required surgery in the operating room. Bone samples were analyzed for conventional culture, histology examination, and16S rRNA qPCR. We evaluated five definitions for osteomyelitis: 1. traditional culture 2. traditional histology 3. genetic sequencing 4. traditional culture and histology 5 genetic sequencing and histology.
Results: There was significant variability in the incidence of osteomyelitis based on the criteria for diagnosis. Traditional cultures identified significantly more cases of osteomyelitis than histology alone (68.6% vs. 45.7%, p=0.02). In every case that histology reported osteomyelitis; the bone culture was positive using traditional culture methods and genetic sequencing. 16S rRNA testing identified more cases of osteomyelitis compared to histology (82.9% vs. 45.7%, p=0.001) and compared to traditional cultures (82.9% vs. 68.6%, p=0.31). When both histology and traditional culture (68.6%) or histology and genetic sequencing based cultures (82.9%) were used to define osteomyelitis the incidence of osteomyelitis did not change.
Conclusions: There is considerable variability in the incidence of osteomyelitis based on how the gold standard of bone biopsy is defined in diabetic foot infections.

Disclosure
P.A. Crisologo: None. J. La Fontaine: None. K. Davis: None. L.A. Lavery: Speaker's Bureau; Self; Osiris Therapeutics, Inc., Integra LifeSciences. Research Support; Self; Cardinal. Speaker's Bureau; Self; Smith & Nephew. Research Support; Self; EO2. Consultant; Self; Aplion, Harbor MedTech, Boehringer Ingelheim GmbH, Medline Industries, Inc..
Heterologous Adipose–Derived Mesenchymal Stem Cells and Vitamin D Supplementation in Patients with Recent–Onset Type 1 Diabetes Mellitus–Six Months Follow-Up
Authors: DANTAS JOANA R. , CABRAL DEBORA A. , PEREIRA KARINA , PEREIRA MARIA F. , SOUTO DEBORA L. , NOLASCO MATHEUS , SOARES MARINA O. , GABBAY MONICA , COURI CARLOS E. , CLAUDIO-DA-SILVA CESAR S. , REBELATTO CARMEN K. , DIB SERGIO A. , OLIVEIRA JOSE EGIDIO P. , ZAJDENVERG LENITA , RODACKI MELANIE 
Published: June 2018

Objective: To evaluate the safety and efficacy of 6 months followup of infusion of heterologous adipose tissue derived mesenchymal stem cells (ADMSCs) of healthy donors + daily cholecalciferol (VD) in patients with recentonset T1D.
Methods: In this prospective open trial, patients with recentonset T1D between 1635 y/o received a single infusion of heterologous ADMSCs (kg x 106) + daily oral VD (2.000UI). Glycated hemoglobin (HbA1c), basal and stimulated Cpeptide (CP) after a mixed meal, insulin dose, adverse events, and glycemic variability (GV) through continuous glucose monitoring (CGM) were assessed at baseline (T0), after 3 (T3) and 6 (T6) months. Patients were compared to controls with recentonset T1D included in previous study that received 1) standard insulin treatment (INS); 2) insulin and VD. Chisquare and Wilcoxon tests were used for statistical analysis.
Results: Six patients (3 males) with mean age of 27 ± 7.1 y/o underwent ADMSC + VD intervention. There were no differences in insulin dose/kg (p=0.6), peak CP (p=0.75) and area under the curve of stimulated CP (p=0,25). All patients had increase in basal CP (p=0.03). HbA1c improved at T3 (0.03), with no difference at T6 (p=0.07). GV did not change after intervention. Increase in Basal CP and stimulated CP were similar between groups, ADMSCs+VD, VD and INS (Basal CP=100% vs. 58.8% vs. 45%, respectively, p=0.057, and stimulated CP=66.7% vs. 58.8% vs. 25% p= 0.058). One patient developed central retinal vein occlusion at T3, with resolution at T6 and another had recurrence of a benign ovarian tumor at T6.
Discussion: In patients with T1D, heterologous ADMSCs + VD supplementation is feasible and appears to be safe after 6 months of followup and resulted in improvement of basal CP. Although GV did not change after the infusion, all patients had an excellent glycemic control, preserved βcell function and low insulin requirements after the intervention with little complications.

Disclosure
J.R. Dantas: None. D.A. Cabral: None. K. Pereira: None. M.F. Pereira: None. D.L. Souto: None. M. Nolasco: None. M.O. Soares: None. M. Gabbay: None. C.E. Couri: None. C.S. ClaudiodaSilva: None. C.K. Rebelatto: None. S.A. Dib: None. J.P. Oliveira: None. L. Zajdenverg: None. M. Rodacki: Research Support; Self; Faperj. Speaker's Bureau; Self; Allergan, Novo Nordisk A/S. Speaker's Bureau; Spouse/Partner; Biogen.
IMG-1 Is Able to Normalize Blood Glucose Levels by Inhibiting Glucagon Levels in a Type 2 Diabetic Rat Model
Authors: POLLETT JONATHAN B. , THAI NGOC 
Published: June 2018

IMG-1 is a novel therapeutic compound for the treatment of diabetes. Ten-week-old diabetic ZDF rats were treated with IMG-1 either intravenously (IV) or per oral (PO) once a day and compared to no treatment over a thirty-five-day period. Weights and glucose levels were monitored twice a week. IMG-1 treated animals showed a marked decrease in BG levels within a week, (average BG levels of 179mg/dl for IMG-1 (IV) and 135mg/dl for PO). This finding was enduring for the entire 35-day period. Untreated controls had significantly elevated BG levels throughout the study, with average levels exceeding 400 mg/dl (481 mg/dl). Hemoglobin A1c (Hb1Ac) was measured at days 0 and 35. IMG-1 treated animals had significantly lower Hb1Ac (IV, 9.7%-&gt; 7.4%) and PO (10.8% -&gt;7.5%) while the untreated group maintained increased Hb1Ac levels (10.2%-&gt;12.3%). There was no significant difference in insulin levels between untreated and IMG-1 treated groups at any time point suggesting IMG-1 decreased insulin resistance. Glucagon levels were reduced in both IV and PO IMG-1 treated animals at days 15 (from 115pg/ml and 119pg/ml to 90pg/ml and 92pg/ml, respectively) and 35 (89pg/ml and 92pg/ml). Control animals had no significant difference in glucagon levels throughout the entire study. Based on these results, it appears that IMG-1 is able to normalize both blood sugar in ZDF animals and lower HbA1c and decrease glucagon levels without elevating insulin levels in these animals.

Disclosure
J.B. Pollett: Employee; Self; Imagine Pharma. N. Thai: Board Member; Self; Imagine Pharma.
Dapagliflozin Suppresses Plasma Hepcidin Concentrations
Authors: GHANIM HUSAM , HEJNA JEANNE M. , ABUAYSHEH SANAA , SHAH TANVI , KUMAR JAGDESH , BATRA MANAV , DANDONA PARESH 
Published: June 2018

Dapagliflozin and other SGLT2 inhibitors are known to increase hematocrit. One possible mechanism is glycosuria and polyuria and the loss of fluid from the vascular compartment. However, since type 2 diabetes is a pro-inflammatory state and since hepcidin, a known suppressor of erythropoiesis, is increased in pro-inflammatory states, we investigated the possibility that dapagliflozin suppresses hepcidin concentrations and thus increases erythropoiesis. Twenty-two patients with type 2 diabetes and normal renal function (mean age: 62.1±1.7 years) were randomly treated with placebo or dapagliflozin 10 mg daily for 12 weeks. In the dapagliflozin group, there was a fall in HbA1c from 7.1±0.2% to 6.7±0.2% (p&lt;0.05), increase in hemoglobin concentration from 13.2±0.8g/L to 13.8±0.4g/L (p&lt;0.05) and in Hct from 40.2±1.3% to 41.9±1.8% (p&lt;0.05). Plasma concentration of hepcidin fell from 265±26ng/mL to 215±24ng/mL (p&lt;0.05). There was no significant change in any of these indices in the placebo group. Since one of the mechanisms through which hepcidin inhibits erythropoiesis is the suppression of the expression of ferroportin, which transports iron from iron storage cells into plasma, we also measured ferroportin expression in peripheral blood mononuclear cells. The expression of this transporter was not altered. We conclude that dapagliflozin suppresses hepcidin concentrations significantly, consistent with an increase in erythropoiesis and hematocrit but by a mechanism not involving ferroportin expression.

Disclosure
H. Ghanim: None. J.M. Hejna: None. S. Abuaysheh: None. T. Shah: None. J. Kumar: None. M. Batra: Speaker's Bureau; Self; Eli Lilly and Company. P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca.
Bedside Blind Bone Biopsy (B4) for Suspected Diabetic Foot Osteitis–A Reliable Tool to Manage Medical Treatment?
Authors: FÉRON FLORINE , GAUTHIER DIANE-CÉCILE , GAUTIER JEAN-FRANÇOIS , KEVORKIAN JEAN-PHILIPPE 
Published: June 2018

Performed by a diabetologist, B4 has been recently shown as an easy and safe procedure. To assess Exclusive Medical Treatment (EMT: offloading, wound care ± antibiotherapy) determined by B4 in suspected Diabetic Foot Ulcer (DFU) osteitis, we compared DFU outcome between proved (B4+) and ruled out osteitis (B4-) with microbial culture.A prospective observational study was conducted in our Diabetology Unit during a 16-month period (12.17.2015-09.04.2017). Among 244 patients admitted with DFU, we included 31 (13%) consecutive patients with type 2 diabetes mellitus (T2DM) and clinical and/or radiological suspicion of osteitis. For each, B4 was decided by our DFU multidisciplinary board. B4 was performed ≥ 2 weeks after antibiotics discontinuation in case of prior exposure. A 6-weeks targeted antibiotherapy was indicated for proven osteitis by prolonged culture (B4+). In case of negative cultures (B4-), no antibiotherapy was prescribed. The primary outcome was the complete DFU healing with EMT at 6 months.Patients characteristics and results are summarized in Table 1. Around 50% of suspected osteitis was B4-, which prevented from unneeded antibiotics without poorer healing outcomes.B4 might be a reliable tool for managing EMT in suspected DFU osteitis.

Disclosure
F. Féron: None. D. Gauthier: None. J. Gautier: None. J. Kevorkian: None.
Pioglitazone Alters the Cargo Composition of Circulating Exosomes in Subjects with Type 2 Diabetes
Authors: NUNEZ LOPEZ YURY O. , PRATLEY RICHARD E. 
Published: June 2018

Pioglitazone (PIO) is an agonist of peroxisome proliferator-activated receptor-γ (PPARγ) which is predominantly expressed in adipose tissue and improves insulin sensitivity in patients with type 2 diabetes (T2D). We hypothesized that PIO effects are mediated, at least in part, by changes in the cargo composition (specifically, miRNAs) of circulating exosomes. We tested this hypothesis in a 3-month trial in which 24 patients with T2D who were well-controlled (HbA1c ≤ 7.0%) with diet/exercise or metformin were randomized to either PIO or placebo (PLA) treatment (NCT00656864). Levels of 42 miRNAs expressed in adipocyte exosomes were measured in exosomes isolated from fasting plasma samples obtained before and after treatment. Levels of exosomal miR-374b-5p, miR-20a-5p, miR-7-5p, and miR-195-5p changed significantly (fold change &gt; 1.5, P &lt; 0.05, FDR &lt; 0.17) in response to PIO treatment relative to PLA (Figure). Changes in exosomal miRNAs correlated with changes in fasting glucose and insulin levels (r &gt; 0.4, P &lt; 0.05, FDR &lt; 0.1). These data suggest that the change in the abundance of specific miRNAs in circulating exosomes may serve as a biomarker of response to PIO and that exosomal miR-374b-5p, miR-20a-5p, miR-7-5p, and miR-195-5p might play mechanistic roles in long-range inter-organ crosstalk.

Disclosure
Y.O. Nunez Lopez: None. R.E. Pratley: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Pfizer Inc., Sanofi-Aventis, Takeda Development Center Americas, Inc..