bluuebunny/crossref_metadata_2025_split huggingface dataset:
SH2B3 (lnk) Regulates Type 1 Diabetes Immune Phenotypes
Authors: CAMARGO ANA , PERRY DANIEL J. , BRUSKO TODD M. , WALLET MARK A. 
Published: June 2018

Background: The type 1 diabetes (T1D)-associated risk gene SH2B Adaptor Protein 3 (SH2B3) encodes a phosphatase with specificity for Janus Kinase 2 (JAK2). We hypothesized that variations in SH2B3 would affect immune signaling pathways relevant to T1D autoimmunity. Here we report: 1) Occurrence of the SH2B3 risk variant among T1D patients, unaffected first-degree relatives and controls; 2) Prevalence of SH2B3 risk genotype in African Americans in the Southeastern U.S.; and 3) Alterations to immune composition associated with the SH2B3 risk variant.
Approach and Results: 1) The University of Florida Diabetes Institute (UFDI) cohort (n=1946) was analyzed for genetic risk of T1D using a Taqman single nucleotide polymorphism (SNP) genotyping array with coverage of 32 SNPs. Two SNPs (rs3184504 and rs653178) corresponding to SH2B3 were in perfect linkage disequilibrium and will be described here as minor (T1D risk) or common variant. Among Caucasian subjects, the odds ratio (OR) for the minor variant among T1D subjects was 1.30 (1.06-1.59, p=1.42x10-2), similar to previous reports. Among African American subjects, the minor variant OR was elevated (2.93, 1.22-7.03, p=1.30x10-2), representing the most highly-associated non-HLA gene. Complete blood count (CBC, n=954) and flow cytometric human immunophenotyping (HIP, n=252) were performed on a subset of subjects. Individuals carrying the risk variant of SH2B3 had significantly more blood monocytes and neutrophils but similar numbers of lymphocytes compared to non-carriers. HIP revealed a significantly higher frequency of type 1 (CXCR3+) CD8+ T cells in subjects with the risk variant of SH2B3.
Conclusions: The risk variant of SH2B3 is associated with both increased risk for T1D and seroconversion in Caucasian and African American subjects. Phenotypically, this element of T1D genetic risk presents as increased frequency of some myeloid cell populations and either expansion or polarization of CD8+ T cells bearing the canonical Th1 chemokine receptor CXCR3.

Disclosure
A. Camargo: None. D.J. Perry: None. T.M. Brusko: Stock/Shareholder; Self; OneVax, LLC. Advisory Panel; Self; Caladrius Biosciences, Inc.. Consultant; Self; Merck & Co., Inc., Sanofi-Aventis. M.A. Wallet: None.
Do Statins Adversely Affect Skeletal Muscle Function?
Authors: CORTES TIFFANY M. , DASARI SURENDRA , ROBINSON MATTHEW M. , NAIR K. SREEKUMARAN 
Published: June 2018

Objective: Statins are well known to cause myalgia and in very rare cases rhabdomyolysis. It remains to be determined whether statin treatment causes any adverse effects on muscle precluding benefits of exercise. We investigated the impact of statin therapy on exercise capacity, muscle strength, mitochondrial respiration, and gene expression in older adults before and after a 12 week exercise program consisting of either aerobic interval (HIIT), resistance (RT), or combined aerobic and resistance (CT) training.
Design: Participants aged 65 and older reported in a prior exercise study were analyzed to determine the impact of statin use. Anthropometric measurements, muscle strength, exercise tolerance and a muscle biopsy for determination of mitochondrial respiration and gene transcripts (RNA sequence) were obtained at baseline and then repeated after 12 weeks of exercise training.
Results: Among participants, 7 were in CT (2 on statins, 5 not on statins), 8 were in HIIT (4 on statins, 4 not on statins), and 8 were in RT (2 on statins, 6 not on statins) groups. Statin and non-statin users at baseline had no observed significant difference in BMI (p=0.936), VO2 (p=0.812), leg press strength (p=0.916), state 2 respiration (p=0.266), state 3 respiration complex I and II (p=0.345), stage 4 respiration (p=0.231) or gene transcripts of 15232 genes examined. Following 12 week exercise program, no significant differences were noted between statin and non-statin users in their BMI (9=0.149), VO2 (p=0.681), leg press strength (p=0.925), state 2 respiration (p=0.078), state 3 respiration complex 1 and II (p=0.142), or state 4 respiration (p=0.945). Significant differences were noted in gene transcripts in statin and non-statin users in CT+RT group (6 genes) and HIIT group (33 genes).
Conclusion: Although there is a slight difference in gene expression in statin and non-statin users, this difference does not have a significant effect on exercise tolerance, muscle strength or mitochondrial respiration after a 12 week exercise program.

Disclosure
T.M. Cortes: None. S. Dasari: None. M.M. Robinson: None. K. Nair: None.
Are Physical Activity Associations with Bone Mineral Density Modified by Metabolic Traits?
Authors: BUTTAN ANSHU , GUO XIUQING , IDA CHEN YII-DER , HSUEH WILLA , ROTTER JEROME I. , GOODARZI MARK O. 
Published: June 2018

We assessed the relationship of physical activity with BMD at various sites (by DEXA), and examined potential modifying factors, including insulin sensitivity by euglycemic clamp in 765 healthy subjects. Responses from physical activity questionnaires were used to determine total physical activity (PA), moderate physical activity (mod-PA), and sedentary time. Neither activity nor sedentary time correlated with rib, L-spine, or T-spine BMD in univariate analysis (Table). Significant univariate variables were included in multivariate analyses. In multivariate analyses of arm BMD, only female sex (β=-0.74, P&lt;0.0001) and adiponectin (β=-0.08, P=0.016) were significant. Multivariate analyses of pelvis BMD found independent associations with BMI (β=0.35, P&lt;0.0001), female sex (β=-0.18, P=0.0003), PA (β=0.10, P=0.04), and mod-PA (β=0.12, P=0.024). Age (β=-0.11, P=0.003), female sex (β=-0.67, P&lt;0.0001), BMI (β=0.25, P&lt;0.0001), and mod-PA (β=0.11, P=0.005) were independently associated with leg BMD. These results suggest that BMD increases with the physical activity in the arms, legs, and pelvis and is inversely related to sedentary time in the pelvis and legs, and these associations may be modified by age, sex, BMI, and adiponectin, depending on the site, with physical activity being more important to pelvis and leg BMD than arm BMD. Sedentary time, CRP, PAI-1 and insulin sensitivity play a minor role in BMD.Table: Association of Activity and Metabolic Traits with Arm, Pelvis, and Leg BMDArm average BMDPelvis BMDLeg average BMDTotal physical activity (PA)r=0.20 (P&lt;0.0001)r=0.11 (P=0.0033)r=0.20 (P&lt;0.0001)Moderate PAr=0.36 (P&lt;0.0001)r=0.11 (P=0.0036)r=0.33 (P&lt;0.0001)Sedentary timeNot significantr=-0.09 (P=0.015)r=-0.09 (P=0.015)AgeNot significantNot significantr=-0.10 (P=0.0051)BMINot significantr=0.36 (P&lt;0.0001)r=0.20 (P&lt;0.0001)Sex (M-F mean difference)0.13 (P&lt;0.0001)0.(P&lt;0.0001)0.17 (P&lt;0.0001)Adiponectinr=-0.22 (P&lt;0.0001)r=-0.20 (P&lt;0.0001)r=-0.18 (P=0.0002)C-reactive protein (CRP)r=-0.22 (P&lt;0.0001)r=0.12 (P=0.012)r=-0.13 (P=0.0045)Plasminogen activator inhibitor-1 (PAI-1)Not significantr=0.13 (P=0.0045)r=0.12 (P=0.015)Insulin sensitivityr=0.13 (P=0.0005)r=-0.20 (P&lt;0.0001)Not significant

Disclosure
A. Buttan: None. X. Guo: None. Y. Chen: None. W. Hsueh: Advisory Panel; Self; Merck & Co., Inc., AstraZeneca, Novo Nordisk Inc.. J.I. Rotter: None. M.O. Goodarzi: None.
Decreased Bioelectrical Impedance Phase Angle in Children and Adolescents with Newly Diagnosed Type 1 Diabetes—A Case-Control Study
Authors: WIECH PAWEł , BAZALINSKI DARIUSZ , BINKOWSKA-BURY MONIKA , KORCZOWSKI BARTOSZ , DąBROWSKI MARIUSZ 
Published: June 2018

Bioelectrical impedance phase angle (PA) is considered to be the most sensitive indicator of the nutritional and functional status. The aim of this study was to assess the body composition and nutritional status of children and adolescents with newly diagnosed type 1 diabetes (T1DM) by using bioelectrical impedance analysis (BIA) with PA calculation. PA has not been evaluated in such population yet.Study group consisted of 63 children and adolescents (28 girls) aged 4 to 18 years, with newly diagnosed T1DM. The same number of healthy girls and boys, without diabetes or other chronic disease having impact on the nutritional status, strictly matched by gender and age in a 1:1 case-control manner consisted control group. In both groups a BIA was performed and PA was calculated to assess the body composition and nutritional status. In T1DM patients BIA was performed after acid-base and water-electrolyte balance were normalized.Results are summarized in the table. Mean HbA1c at the time of T1DM diagnosis was 11.37 ± 2.26%. No correlation between PA and HbA1c was found.
In conclusion, the lower PA score together with lower MM%, BCM% and BCMI in children and adolescents with T1DM indicate their worse nutritional and functional status compared to healthy subjects. To assess the predictive and prognostic value of these findings further prospective studies in this population are required.

Disclosure
P. Wiech: None. D. Bazalinski: None. M. Binkowska-Bury: None. B. Korczowski: None. M. Dąbrowski: Other Relationship; Self; Ascensia Diabetes Care, AstraZeneca, Berlin-Chemie AG, Eli Lilly and Company, MSD K.K., Sanofi-Aventis, Servier.
Changing Food Patterns in Indian Children
Authors: JHINGAN ASHOK KUMAR 
Published: June 2018

Introduction: Change in food patterns has played an important role in making children overweight and obese as seen in the recent years. It has become a matter of concern since one in five children studying in schools of Delhi, have been reported obese or overweight. These overweight and obese children have 70% risk of becoming over-weight/obese adults.
Methods: We conducted a study to observe the effect of food habits on children in 8 schools in Delhi. In this study 1155 children studying in class 3rd, 4th and 5th were included and a regular follow-up was done. A questionnaire was prepared to know about food habits, choice and change in food habits.
Results: The analysis of data revealed some disturbing facts about eating patterns and preferences for fast foods. It was observed, 39% of children preferred fast foods like burgers, pizzas, french-fries as compared to 11% who liked eating fruits. 44% of the children drink 1 soft drink per day. Class 3rd children, only 11% preferred fast food Class 4th children -the percentage remarkable increased to 39% preference for fast food. Class 5th children, alarming observation was that in Class 5th the percentage rose to 66% in these children for preference to fast food.
Discussion: The present study indicated that a lot of preventable factors like family members, television and media ads plays and important in increasing this preference for fast food in children. Children started developing preference for fast food from class 3rd and by the time they reached class 5th majority of them had developed a preference for the fast food.
Conclusions: Recommendations since the above category children have the highest incidence to become overweight / obese and this can lead to diabetes and it’s complications in adult years Intervention should be initiated from class 3rd onwards by family, schools authorities and media to create an environment so that children get inclined towards healthy food habits.

Disclosure
A. Jhingan: None.
Effectiveness and Tolerability of Vildagliptin plus Metformin Dual Therapy Compared with Insulin Secretagogue plus Metformin Dual Therapy in Patients with Type 2 Diabetes—A Real-World Study (China PDS)
Authors: CHEN LIXIAN , HAN YING , HU DAQING , JIN HUI , YANG NAILONG , SHI XIAOYUN , LI QUANMIN , LIANG LINLANG , ZANG LI , LIU MINGMING , HE JAMES , MU YIMING 
Published: June 2018

Background and Aim: The China PDS aims to investigate the effectiveness and safety of vildagliptin dual therapy in type 2 diabetes mellitus (T2DM) patients. Here, we compared the vildagliptin plus metformin (VM) and insulin secretagogue plus metformin (ISM).
Materials and Methods: China PDS was a prospective, 1-year, real-world study conducted in 52 sites in patients with T2DM and inadequately controlled on monotherapy. Eligible patients were assigned either vildagliptin dual therapy or other dual therapy according to local physician’s decision. The proportions of patients with HbA1c&lt;7%, without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event), and tolerability were compared in VM and ISM in this study.
Results: In total, 933 patients received vildagliptin dual therapy with 64.7% for VM, while 670 patients received other dual therapy with 48.7% for ISM (Table 1). Compared with ISM (31.6%), VM (50.8%) had higher proportion of patients reaching the primary outcome (P&lt;0.001; adjusted OR, 2.14; 95% CI, 1.59-2.87). VM (5.8%) had less tolerability events than ISM (16.4%) (RR, 0.386; 95% CI, 0.26-0.58).
Conclusion: China PDS demonstrates that in a real-life setting, VM was effective in glycemic control and was well tolerated when compared with ISM.

Disclosure
L. Chen: None. Y. Han: None. D. Hu: None. H. Jin: 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.
Effectiveness and Tolerability of Vildagliptin plus Metformin Compared with Other Oral Dual Agents in Different Regional Patients with Type 2 Diabetes—A Real-World Study (China PDS)
Authors: ZANG LI , HAN YING , CHEN LIXIAN , HU DAQING , JIN HUI , YANG NAILONG , SHI XIAOYUN , LI QUANMIN , LIANG LINLANG , LIU MINGMING , HE JAMES , MU YIMING 
Published: June 2018

Background and Aim: China PDS aims to investigate the real-world effectiveness and tolerability of vildagliptin plus metformin (VM) in patients with type 2 diabetes mellitus (T2DM), compared with other oral dual agents (OD). In this study, we present the results of different regional subgroup analysis.
Materials and Methods: In China PDS, T2DM patients with inadequate glycemic control on monotherapy were assigned to either VM dual therapy or OD therapy according to local physician’s decision. In this prespecified subgroup study, patients were divided into three groups according to their geographic regions (East China, North China, and South China). 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 the HbA1c change from baseline to study endpoint, and tolerability.
Results: In total, 357 (126 in VM vs. 231 in OD) patients in East China, 499 (292 in VM vs. 207 in OD) patients in North China, and 65 (27 in VM vs. 38 in OD) patients in South Chinawere enrolled. Compared with OD, significantly higher proportion of VM treated patients achieved primary outcome in East China (49.2% vs. 28.1%, P &lt;0.001), North China (52.1% vs. 39.1%, P=0.004), and in South China (66.7% vs. 36.8%, P=0.018). Mean HbA1c changes were significantly greater in VM than in OD in East China (-1.24% vs. -0.55%, P&lt;0.001) and North China groups (-1.35% vs. -0.93%, P=0.011), but not in South China group (-2.12% vs. -1.31%, P=0.147). VM resulted in less tolerability findings than OD in East China (6.3% vs. 18.2) and North China (6.5% vs. 15.0%) groups (P&lt;0.for both), but not in South China group (3.7% vs. 26.3%, P&gt;0.05).
Conclusion: In all regional subgroups, vildagliptin plus metformin dual therapy was generally associated with good glycemic control and was well tolerated.

Disclosure
L. Zang: None. Y. Han: None. L. Chen: None. D. Hu: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. M. Liu: None. J. He: None. Y. Mu: None.
“Alarming" T-Regulatory Cells (Tregs) to Protect from Type 1 Diabetes (T1D)
Authors: SHARMA RAHUL , SABAPATHY VIKRAM 
Published: June 2018

Defects in IL-2 signaling and Tregs correlate with susceptibility to T1D. Helminth burden also negatively correlates with the incidence of T1D. The alarmin IL-33 and its receptor ST2 are elicited in anti-helminth immunity, which also increase Tregs, M2 macrophages and Th2 response. We hypothesized that IL-33 may cooperate with IL-2 in promoting Tregs to protect from T1D. Indeed, a major subset of Tregs express ST2, thus enabling a role for IL-33 in Treg biology. Non-obese diabetic (NOD) mice, which have less Tregs than the nondiabetic NOD.Idd3 congenic mice, also exhibit less ST2+ Tregs (13±3%) than NOD.Idd3 (38±11%). For better cooperativity and preferential targeting of Tregs, we generated a hybrid cytokine (IL233) bearing IL-2 and IL-33 activities in a single molecule. Recent-hyperglycemia onset NOD mice (n≥6/group) were treated with daily injections (3.3pmol/g) of IL-2 and/or IL-33 or IL233 for 5 days. IL-33 alone offered a similar, if not better reversal of T1D with a 70% cumulative incidence (CI) compared to IL-2 alone (80% CI), whereas IL233 offered the best protection with 50% of mice remaining in remission 10-weeks post-treatment. There was a robust increase in the proportion of Tregs in pancreatic lymph node in IL233 group (25±3.7%) compared to 10±3.9%, 16±4.1%, 14±4.3% and 19±4.3% in Saline, IL-2 only, IL-33 only and IL-2 and IL-33 groups respectively. IL233 treatment also increased the levels of Tregs and group-2 innate lymphoid cells in an alternate species (rats) and blocked high-dose streptozotocin (STZ)-induced beta-cell death. Interestingly, the average islet size was bigger in the rats treated with IL233 in the STZ model, indicating a role of IL233 in islet growth and repair. Thus, IL233 utilizes the synergy of IL-2 and IL-33 to promote Tregs and bears strong therapeutic potential for T1D.

Disclosure
R. Sharma: None. V. Sabapathy: None.
Diabetes Management in Hospitalized Patients with Type 2 Diabetes (T2D) during Fasting Periods
Authors: RAINER RAPHAEL , ELSAYED HESHAM , ABERER FELIX , BECK PETER , PIEBER THOMAS R. , DONSA KLAUS , PLANK JOHANNES , MADER JULIA K. 
Published: June 2018

To date little data exists on diabetes management during fasting periods on the general ward. The aim of the analysis was to assess standardized diabetes management using GlucoTab® - a digital algorithm driven basal-bolus insulin therapy - in hospitalized patients with T2D in the fasting period. Data from two clinical trials were pooled. Patients were included in the analysis if they had at least one fasting period during hospital stay at the general ward. Periods of fasting were compared with periods of regular food intake. Out of 191 T2D patients 91 (48%, 5 on surgical and 86 patients on internal medicine wards, 32 female, age 68 ± 12 years, HbA1c 67 ± 19 mmol/mol, BMI 30 ± 15 kg/m2, diabetes duration 15 ± 11 years, creatinine 1.8 ± 1.4 mg/dl, length of hospital stay 10 ± 6 days) were included comprising overall 131 fasting periods. Mean blood glucose was lower during fasting periods as compared to periods with regular food intake (153 ± 38 vs. 158 ± 24 mg/dl, p = 0.033). Hypoglycemia (&lt;70 mg/dl) was documented in 1.35% (fasting) vs. 1.91% (non-fasting) of all measurements, respectively. In neither period BG &lt;40 mg/dl occurred. Insulin doses during fasting vs. non-fasting were as follows: bolus insulin 18.0 ± 12.7 vs. 26.0 ± 17.1 U; basal insulin 20.7 ± 13.2 vs. 22.3 ± 15.2 U. Fasting is common among patients on a general ward. Our data demonstrate that standardized diabetes management by GlucoTab® using a basal-bolus insulin algorithm is safe and effective in fasting state.

Disclosure
R. Rainer: None. H. Elsayed: None. F. Aberer: None. P. Beck: Employee; Self; decide Clinical Software GmbH. T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. K. Donsa: Stock/Shareholder; Self; decide Clinical Software GmbH. J. Plank: None. J.K. Mader: Speaker's Bureau; Self; Roche Diabetes Care Health and Digital Solutions, Novo Nordisk A/S. Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Becton, Dickinson and Company. Speaker's Bureau; Self; Sanofi. Research Support; Self; ConvaTec Inc., Menarini Group. Speaker's Bureau; Self; Medtronic. Research Support; Self; Novo Nordisk A/S, Sanofi.
A Reusable Cap for Disposable Insulin Pens Protects Insulin against Temperature-Induced Degradation
Authors: PFÜTZNER ANDREAS , NAGAR RON , REEH WOLFGANG 
Published: June 2018

Insulin has to be kept at 4-8° C (∼ 39°F to 47°F) until use and once opened, is supposed to be stable for 28 to 30 days at room temperature. Exposure to extreme cold or heat leads to insulin degradation in a very short time with loss of glucose-lowering efficacy. ViVi-Cap (TempraMed Inc.) is a reusable storage device, which is available for all existing disposable pen devices in the U.S. and EU. It works without external power supply requirements based on an ultra-high vacuum insulation and an additional heat consumption by a calorimetry-based phase-change technology.
Five disposable insulin pens (FlexPen, Insulin aspart) were kept for one week under extreme temperature conditions for 5 days (each day: 8 h at 50 °C and 16 h at 22 °C) either without protection, in a frio device (freshly prepared each day) and in the ViViCap. Samples were taken every day and insulin degradation was determined in accordance with U.S. pharmacopoia by appropriate HPLC methods for insulin aspart, and high and low molecular weight degradation molecules. Each experiment was performed in triplicate.
Insulin aspart without protection was shown to have more than 2% impurities already after one day (Frio: 2 days, ViViCap: &gt;5 days). High molecular weight products appeared in measurable quantities after two days without protection (Frio: 3 days, ViViCap &gt; 5 days, p&lt;0.01 against the other 2 storage conditions).
ViVi-Cap was superior to the other tested conditions with respect to stabilizing insulin aspart during storage under extreme temperature conditions. The device provides an easy to use solution for maintaining insulin efficacy under daily life conditions.

Disclosure
A. Pfützner: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Consultant; Self; Lifecare. Speaker's Bureau; Self; Berlin-Chemie AG. Research Support; Self; Boehringer Ingelheim GmbH. R. Nagar: Stock/Shareholder; Self; TempraMed Ltd.. W. Reeh: None.