bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-Term Aerobic and Interval Training Improves Muscle Mitochondrial Function and Reveals a New Role for an Old Protein
Authors: PARSONS STEPHANIE , PINO MARIA F. , HODGES ANDREW P. , YI FANCHAO , CARNERO ELVIS A. , PRATLEY RICHARD E. , SMITH STEVEN R. , SPARKS LAUREN M. 
Published: June 2018

Exercise training has well-documented beneficial effects on skeletal muscle (muscle) mitochondrial function, which can be evaluated from clinical and molecular aspects within the same individual. We evaluated two cohorts at baseline: 1) lean/overweight sedentary (LOS) and 2) lean active (LA), and investigated the effects of three weeks of aerobic training in LOS subjects. All assessments were performed before (PRE) and following (POST) the intervention. In vivo muscle mitochondrial function was assessed by 31P-MRS (ATPmax). Muscle biopsies were performed in the vastus lateralis in the fasted state. Muscle tissue mitochondrial function was quantified via 14C-palmitate oxidation (14C-CO2) assays and high-resolution respirometry (Complex I, Complexes I+II, ETS). Transcriptomic profiles were examined by microarrays combined with in-depth bioinformatics analyses and validated via qRT-PCR. Fiber type and mitochondrial (mt)DNA copy number were quantified via immunohistochemistry and qPCR, respectively. LA subjects had significantly higher VO2peak and muscle mitochondrial function in vivo and in tissue vs. LOS PRE. Three weeks of aerobic training significantly improved muscle mitochondrial function in vivo and in tissue in LOS subjects [to the level of LA subjects] without affecting VO2peak, fiber type nor mitochondrial content. Global transcriptomic analyses revealed downregulation of Tribbles 1 in LOS PRE vs. LA that was confirmed by qRT-PCR in LOS PRE vs. LA. Tribbles 1 mRNA was significantly reduced with training (LOS PRE vs. POST) and inversely related with muscle tissue mitochondrial respiration. Our data identified a novel target related to exercise-induced improvements in muscle mitochondrial function and highlight a potential new role for Tribbles 1 in muscle oxidative capacity.

Disclosure
S. Parsons: None. M.F. Pino: None. A.P. Hodges: None. F. Yi: None. E.A. Carnero: 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.. S.R. Smith: None. L.M. Sparks: None.
Relationship of Physical Activity Behavior with Insulin Sensitivity over Five Years after Diagnosis of Type 2 Diabetes
Authors: PESTA DOMINIK , BOBROV PAVEL , ZAHARIA OANA P. , BÓDIS KÁLMÁN , KARUSHEVA YANISLAVA , MARKGRAF DANIEL F. , BURKART VOLKER , MÜSSIG KARSTEN , STRASSBURGER KLAUS , SZENDROEDI JULIA , RODEN MICHAEL 
Published: June 2018

Regular physical activity is a key element of lifestyle recommendations for patients with type 2 diabetes (T2D), yet adherence to physical activity (PA) and its association with insulin sensitivity in newly diagnosed T2D is less known.
This study assessed PA behavior during the first year after diagnosis and 5 years later by the validated Baecke questionnaire, which comprises sports-, leisure- and work-related activities, in recent-onset T2D (n=215) and healthy individuals (CON; n=84), adjusted for age, sex and body mass index. Insulin sensitivity was assessed from hyperinsulinemic-euglycemic clamps and maximal oxygen consumption (VO2max) from spiroergometry at baseline and after 5 years.
Patients with T2D had a lower total Baecke (8.1±1.4) and sports index (2.7±0.8) than CON (8.8±1.4; 3.2±0.8; all p&lt;0.05; mean±standard deviation). Compared to CON, VO2max was 28% lower in T2D (p&lt;0.05). Whole-body insulin sensitivity was 41% lower in T2D than in CON (p&lt;0.01). At baseline, sports index correlated positively with insulin sensitivity (T2D r=0.17; CON r=0.32, both p&lt;0.05) and VO2max (T2D r=0.38; CON r=0.32, both p&lt;0.01). Of note, higher PA participation at 5 years after diagnosis associated with decreased body weight (r=-0.30; p&lt;0.01) and improved physical performance (r=0.32; p&lt;0.05) in T2D. Although at 5 years changes in PA did not impact hemoglobin A1c as a parameter for glycemic control, higher PA participation associated positively with changes in whole-body insulin sensitivity in T2D (r=0.26; p&lt;0.05).
In conclusion, lower PA participation contributes to worsening of body weight, physical fitness and insulin resistance in T2D, even during the initial course of disease.

Disclosure
D. Pesta: None. P. Bobrov: None. O.P. Zaharia: None. K. Bódis: None. Y. Karusheva: None. D.F. Markgraf: None. V. Burkart: None. K. Müssig: None. K. Strassburger: None. J. Szendroedi: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi.
Oral Sodium Nitrite Improves Insulin Sensitivity, Blood Pressure, and Arterial Thickening in Adults with Uncontrolled Hypertension and Metabolic Syndrome
Authors: HUGHAN KARA S. , HELBLING NICOLE L. , ANTHONY STEVEN J. , DELANY JAMES , GOODPASTER BRET H. , GLADWIN MARK 
Published: June 2018

Introduction: Although nitrate and nitrite have traditionally been considered to be inert and potentially toxic metabolites of nitric oxide (NO) oxidation, it is now appreciated that both can be recycled to bioactive NO. Recent evidence suggests that the human nitrate-nitrite-NO pathway mediates signaling through NO to reduce blood pressure and endothelial function. The effects of oral nitrite on insulin sensitivity, however, are not known. Therefore, we developed the investigational drug, oral inorganic sodium nitrite, to assess its therapeutic effects.
Methods: Our goal was to examine the effect of 12 weeks of open-label oral sodium nitrite 40 mg three times daily in this pilot study. We employed hyperinsulinemic-euglycemic clamps to assess insulin sensitivity, flow mediated dilation (FMD) to measure endothelial function, and pulse wave velocity (PWV) and carotid intima media thickness (IMT) to measure arterial stiffening and thickening, respectively, in obese adults with metabolic syndrome and uncontrolled hypertension.
Results: Eighteen subjects were recruited with mean age 53 years, BMI 41 kg/m2 and BP 147/88 mmHg and 72% were female. Following 12 weeks of nitrite treatment, systolic (-10 mmHg), diastolic (-13 mmHg) and mean arterial pressures were reduced (-12 mmHg; all p&lt;0.001). Insulin stimulated glucose disposal tended to improve (14%; 7.4±0.7 at baseline to 8.4±0.8 mg/kg/min post, p=0.08) after oral nitrite treatment compared to baseline. Carotid IMT decreased from 0.762±0.02 at baseline to 0.727±0.03 mm post (p&lt;0.01), and FMD and PWV trended towards improvement with oral sodium nitrite treatment. There were no changes in body weight, BMI, fasting glucose, HbA1c or lipids.
Conclusion: Oral sodium nitrite treatment is a promising therapeutic to improve insulin sensitivity, blood pressure and arterial thickening in at-risk obese adults with metabolic syndrome and uncontrolled hypertension.

Disclosure
K.S. Hughan: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. N.L. Helbling: None. S.J. Anthony: None. J. DeLany: None. B.H. Goodpaster: None. M. Gladwin: Other Relationship; Self; National Institutes of Health, Globin Solutions, Bayer AG.
Improved Metabolic Flexibility Postbreakfast after Exercise Intervention in People with T2DM
Authors: CARNERO ELVIS A. , BOCK CHRISTOPHER P. , STEPHENS NATALIE , PRATLEY RICHARD E. , SMITH STEVEN R. , SPARKS LAUREN M. 
Published: June 2018

Exercise provides many metabolic benefits for people with type 2 diabetes; nevertheless, the ability to switch substrate oxidation from fat to carbohydrate and back, known as metabolic flexibility (MetFlex), in response to prolonged exercise training has not been thoroughly explored.
Purpose: The goal of this analyses was to investigate changes in MetFlex after an exercise intervention. We enrolled healthy sedentary participants with obesity (HSO) and participants with type 2 diabetes (T2DM) in a 10-week aerobic exercise intervention.
Methods: Seventeen participants with T2DM (8 females; 52.9 years; BMI= 36.9 kg/m2 and 9 males; 48.8 years; BMI= 33.3 kg/m2) and seven HSO (5 females; 44.8 years, BMI= 37.6 kg/m2 and 2 males; 46.5 years, BMI= 36.2 kg/m2) completed the intervention. MetFlex was assessed as the respiratory quotient (RQ) kinetic response after ingesting a standard high CHO breakfast during a 24-h energy expenditure measurement in a whole-room respiratory chamber. Briefly, the kinetics between the lowest RQ and highest RQ points were analyzed by a simple linear regression between time (1-minute resolution) and RQ units (RQUnits). Individual data were time-aligned and averaged for each group and moments (PRE and POST intervention), then slopes and intercepts for T2DM vs. HSO groups and PRE vs. POST were compared using a multiple regression model.
Results: At PRE-intervention, HSO group had a significantly lower intercept than T2DM (HSO=0.737 vs. T2DM=0.705; P&lt;0.001) and slower RQ kinetics as demonstrated by a greater slope (HSO=0.00448 RQUnits/min vs. T2DM=0.00332 RQUnits/min; F=18.1, P=0.001). After the exercise intervention only T2DM significantly increased their slope (POST= 0.003944 RQUnits/min; F=6.47, P=0.013).
Conclusions: Our results indicate that participants with diabetes significantly improve MetFlex following a prolonged aerobic exercise intervention.

Disclosure
E.A. Carnero: None. C.P. Bock: None. N. Stephens: 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.. S.R. Smith: None. L.M. Sparks: None.
Short-Term Interval and Continuous Training Improves Pancreatic ß-Cell Function Adjusted for Skeletal Muscle Insulin Resistance in Adults with Prediabetes
Authors: FRANCOIS MONIQUE E. , EICHNER NATALIE , GILBERTSON NICOLE M. , HEISTON EMILY M. , BARRETT EUGENE , MALIN STEVEN K. 
Published: June 2018

Exercise improves pancreatic function in an energy dose-dependent manner. We previously showed that when calories are matched, an acute exercise bout changes glucose-stimulated insulin secretion (GSIS) relative to multi-organ insulin resistance (IR) in an intensity-based manner during the immediate post-exercise period in people with prediabetes. However, the impact of short-term training intensity on ß-cell function is unknown. Thus, we examined the impact of high-intensity interval and moderate-continuous training on GSIS relative to multi-organ IR in adults with prediabetes. Thirty-one adults (Age: 61±8y; BMI: 33±6 kg/m2) with prediabetes according to ADA 75g OGTT and/or HbA1c criteria were randomized to energy-matched interval (INT: 60-min/d alternating 3-min at 90 and 50% HRpeak) or continuous training (CONT: 60-min/d 70% HRpeak) for 2 weeks. Fitness (VO2peak) and body mass were measured before and after, and a 120-min 75g OGTT with blood samples for glucose, insulin, C-peptide and FFA were determined every 30-min. GSIS (C-pep/Glc tAUC0-120min) and ß-cell function (Disposition Index [DI: GSIS/IR]) relative to skeletal muscle (InsulintAUC x GlctAUC), hepatic (HOMA-IR) and adipose (Adipose-IRfasting) IR were calculated. Training increased VO2peak (+1.1±2.1 mL/kg/min), and reduced body mass (-0.6±1.1 kg) and IR (-11±31%), independent of intensity (P&lt;0.05). INT and CONT also decreased GSIS to a similar extent (Interaction: P=0.88). Short-term training improved skeletal muscle DI by ∼24% (P&lt;0.05), but there was no effect on hepatic or adipose DI. Collectively, short-term INT and CONT training improves ß-cell function relative to skeletal muscle, but not hepatic or adipose, IR. These data suggest unique mechanisms regulate glucose metabolism following single vs. habitual physical activity in adults with prediabetes.

Disclosure
M.E. Francois: None. N. Eichner: None. N.M. Gilbertson: None. E.M. Heiston: None. E. Barrett: None. S.K. Malin: None.
Two Mechanisms Mediating Enhanced Glucose Tolerance with Regulator of GS Protein 14 Disruption; Increased Exercise Capacity and Increased Brown Adipose Tissue
Authors: OYDANICH MARKO , ZHANG JIE , VATNER DOROTHY E. , VATNER STEPHEN F. 
Published: June 2018

The goal of this investigation was to examine glucose tolerance and exercise capacity in the regulator of the G protein signaling 14 knock out (RGS14 KO) mouse. Exercise capacity, which affects glucose tolerance, was improved in the RGS14 KO compared to their wild type littermates (WTL), as reflected by a 64 ± 8%, p&lt;0.05, increase in total distance run on a treadmill. Glucose tolerance was also increased in the RGS14 KO, compared with their WTL, as reflected by a 40 ± 11%, p&lt;0.05, reduction in the area under the glucose curve after administration of 2g of glucose and monitoring blood glucose over the next 3 hours. The insulin tolerance test showed similar improvement in RGS14 KO. The RGS14 KO is also a model of obesity protection, as reflected by 44% less white adipose tissue in the inguinal fat pad, compared with WTL. However, brown adipose tissue (BAT) is increased in the RGS14 KO, as reflected by a 47% increase in the BAT index. To determine if BAT mediated the salutary effects of exercise and glucose tolerance in the RGS14 KO, we simulated a BAT KO, by removing it from the RGS14 KO and transplanting the BAT to their WTL. This resulted in a reversal of phenotype, where the WTL with transplanted BAT behaved like RGS14 KO and the RGS14 KO behaved like WTL; i.e., the WTL with transplanted BAT from RGS14 KO exhibited improved exercise capacity by 36 ± 5%, p&lt;0.05, compared with the RGS14 KO donors. Glucose tolerance showed the same pattern, where WTL with the RGS14 KO BAT transplants exhibited a 39 ± 6% reduction in area under the glucose curve, p&lt;0.05, compared with the RGS14 KO BAT donors. The insulin tolerance test showed similar improvement in the WTL mice with BAT transplant. Thus, there are two mechanisms by which glucose tolerance is enhanced in RGS14 KO: 1. Improved exercise capacity; and 2. Increased BAT, suggesting that either inhibiting RGS14 or increasing BAT would be novel therapeutic approaches to protect against diabetes and obesity.

Disclosure
M. Oydanich: None. J. Zhang: None. D.E. Vatner: None. S.F. Vatner: None.
T2D Users of a Digital Diabetes Management System Experience a Shift from Greater than 180 mg/dL to Normal Glucose Levels with Sustainable Results
Authors: HERSHCOVITZ YIFAT , FENIGER EITAN , DAR SHARON 
Published: June 2018

One of the goals of a digital diabetes management system is to improve the patient’s self-management and control of their condition. Blood glucose level reduction and sustainment of lower levels of blood glucose is one of the greatest challenges in managing diabetes. Digital engagement can play a pivotal role in the care of patients with diabetes and other chronical conditions, potentially improving patient’s compliance. The DarioTM Blood Glucose Monitoring System (BGMS) connects physically to a smart mobile device and automatically logs blood glucose measurements into a designated application (App). Data is transmitted to the Dario cloud.
Method: A retrospective data evaluation study was performed on the DarioTM cloud data base. A population of all active type 2 diabetic (T2D) users that took measurements with DarioTM BGMS on average of 20 measurements per month during 2017. The study assessed the ratio of all high blood glucose readings (180-400 mg/dL) and the ratio of all normal blood glucose readings (80-120 mg/dL) in their first month of use to their last month of use during 2017 as recorded in the database.
Results: For 17,156 T2D users activated during 2017 the average ratio of high events (180-400 mg/dL) was reduced by 19.3% (from 28.4% to 22.9% of the entire measurements). While at the same time, the ratio of normal range readings (80-120 mg/dL) was increased in 11.3% (from 25.6% to 28.5% of the entire measurements). The most significant shift occurred after one month of usage (14% decrease) and maintained stability over the following months throughout the full year.
Conclusion: The combination of a glucose meter and an App may promote behavioral modification and enhanced adherence to diabetes management, demonstrating improvement in glycemic outcomes and sustainment for a long period of time.

Disclosure
Y. Hershcovitz: Employee; Self; DarioHealth. E. Feniger: Employee; Self; DarioHealth. S. Dar: Employee; Self; DarioHealth.
Comparison of Effects of Low-Carbohydrate Diet and Calorie-Restricted Diet on Nonalcoholic Fatty Liver Disease in Japanese Patients with Type 2 Diabetes
Authors: NISHIMORI EITA , OGATA SATOSHI , NAKA MOTOJI 
Published: June 2018

Background: Nutrition therapies for type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD) are recommended for calorie-restricted diet (CRD) in Japan. Recently, the efficacy of low-carbohydrate diet (LCD) has been reported in these diseases. This study aimed to determine the effects of LCD on NAFLD in Japanese patients with T2DM compared with CRD.
Methods: We assigned 28 patients of NAFLD with T2DM in this 3-month prospective open-label randomized comparative trial. They were randomly allocated to either LCD (70-130 g/day of carbohydrate) group (n =14) or CRD (calories of 25 kcal/kg of ideal body weight per day) group (n =14). Abdominal computed tomography (CT) scan evaluated liver fat deposition by the liver-to-spleen attenuation ratio (L/S ratio) and visceral fat accumulation as the visceral fat area (VFA).
Results: The average age of patients at the start was 50 years old, BMI was 31 kg/m2, L/S ratio was 0.7, VFA was 163 cm2. The total intake energy of LCD after 3 months was 1,389 kcal (δ-386 kcal from the start, carbohydrate was 42% of the total energy), CRD was 1,513 kcal (δ-633 kcal, carbohydrate was 54%). Both diets achieved significantly improvement of L/S ratio, VFA, liver transaminase, body weight and HbA1c from baseline within groups after 3 months (P &lt; 0.05). Between the two diets, L/S ratio, liver transaminase, body weight and HbA1c showed a large tendency to improve in LCD, but no significant difference was noted. Significant improvement was observed in VFA of LCD. In the QoL score, "anxiety and dissatisfaction with treatment" was significantly improved in LCD.
Conclusions: Our findings suggest that LCD may be as effective as CRD in improving fatty liver in Japanese patients of NAFLD with T2DM, and that LCD may be less burdensome on patients than CRD.

Disclosure
E. Nishimori: None. S. Ogata: None. M. Naka: None.
Evaluation of Dietary Intakes of Macronutrients in Adults with Different A1c Levels
Authors: KELLY OWEN , KROK-SCHOEN JESSICA L. , LUO MENGHUA , TAYLOR CHRISTOPHER A. 
Published: June 2018

Nutritional modification is a key consideration for the management of diabetes. Characterization of dietary habits among adults with diabetes may help focus dietary behavior changes. Dietary intakes and hemoglobin A1c data from the 2005-2014 National Health and Nutrition Examination Survey (NHANES) were evaluated to assess differences in meal and snacking macronutrient patterns by A1c levels. Data from 20,2adults ≥ 30 years were categorized into the following groups using A1c values: &lt;5.7% (nondiabetes, n= 12,949); 5.7-6.4% (prediabetes, n=4,892); 6.5-6.9% (controlled diabetes, n=768); and ≥7%, (poorly controlled diabetes, n=1,597). Dietary intakes were assessed via a 24 hour dietary recall. Eating occasions were defined by the participant. Data analyses were weighted to create a nationally representative sample. Overall, the mean energy intakes were higher in the nondiabetes group by up to 264 kcal. Mean protein, carbohydrate and fat intakes were also higher in the nondiabetes group. Intakes for energy and macronutrients were similar across all groups at breakfast and dinner, however, at lunch and for all snacks combined, those without diabetes had higher intakes. Intakes of added sugars at eating occasions were also higher in the nondiabetes group and snacks contributed the most for all groups. The daily total number of carb choices for the nondiabetes, prediabetes and both diabetes groups were 17, 16, 15 and 15, respectively. For all groups, dinner was the largest meal and accounted for the highest carb choice values. Despite the overall reduction in energy and macronutrient intakes in those with elevated A1c, indicating they may be making perceived positive dietary behavior changes, all the groups diets are low in quality per Healthy Eating Index. There may need to be a greater focus on changing macronutrient quality, especially carbohydrates, when developing individualized medical nutrition therapy for people with diabetes or prediabetes.

Disclosure
O. Kelly: Employee; Self; Abbott. Employee; Spouse/Partner; Abbott. J.L. Krok-Schoen: None. M. Luo: Employee; Self; Abbott. C.A. Taylor: None.
Impact of the ENHANCED (diEtitiaNs Helping pAtieNts CarE for Diabetes) Trial on Optimal Care Outcomes in Adults with Type 2 Diabetes
Authors: BENSON GRETCHEN , SIDEBOTTOM ABBEY , HAYES JOY , BOUCHER JACKIE L. , VACQUIER MARC , MIEDEMA MICHAEL D. , SILLAH ARTHUR , VANWORMER JEFFREY 
Published: June 2018

Background: Clinical care for type 2 diabetes has improved, but remains suboptimal. Collaborative, team-based models that maximize the skills of different disciplines may improve care for type 2 diabetes, but few have been tested using rigorous research designs.
Objective: We investigated the effectiveness of a registered dietitian nutritionist-led (RDN) telemedicine program vs. usual care on type 2 diabetes optimal care goals, including A1C, blood pressure, tobacco use, and appropriate statin and aspirin use. For participants randomly assigned to the intervention group, RDNs utilized an approved treatment protocol to initiate/titrate therapies for blood glucose, hypertension and lipids, in addition to providing medical nutrition therapy. Outcomes were compared between the intervention vs. usual care group over one year.
Design: A randomized control trial design was used that included 118 adults with type 2 diabetes who were receiving care at two rural primary care clinics. Participants were randomized (March-December 2016) to usual (clinical) care or an intervention group that included usual care plus monthly RDN-led telemedicine visits for one year.
Results: Mixed model regression was used to examine outcomes between baseline and one year follow-up. Modest, but significantly greater improvement was observed for the intervention group in the number of optimal care measures met at follow-up, 3.7 compared to 3.2 among controls (p=.017) after adjusting for baseline. Among individual optimal care measures, the intervention group had a significantly greater increase in medication use, with 2.5 and 2.2 higher odds (compared to controls) of taking a statin and aspirin as appropriate, respectively.
Conclusions: The ENHANCED study care model, which utilized RDNs to initiate and titrate medications, modestly improved type 2 diabetes care outcomes for adults.

Disclosure
G. Benson: None. A. Sidebottom: None. J. Hayes: None. J.L. Boucher: None. M. Vacquier: None. M.D. Miedema: None. A. Sillah: None. J. VanWormer: None.