bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short Sprints during Exercise Reduce Exercise-Mediated Hypoglycaemia in Type 1 Diabetes in a Real-Life Setting
Authors: CHETTY TARINI , ROBY HEATHER , PARAMALINGAM NIRUBASINI , DART JULIE , SOON WAYNE , SMITH GRANT J. , SHETTY VINUTHA B. , FOURNIER PAUL A. , JONES TIM , DAVIS ELIZABETH A. 
Published: June 2018

Background: Short sprints have been shown to prevent exercise induced hypoglycaemia in controlled laboratory settings. Using a randomised controlled study design, we tested the hypothesis that incorporating sprinting into moderate intensity exercise can reduce the incidence of exercise mediated hypoglycaemia in individuals with T1D in a real-life setting.
Methods: Individuals with T1D, diagnosed for &gt;1 year, aged 14-35 years, with an HbA1c of ≤9% were recruited into a prospective randomised controlled cross over study. Participants completed three 14-day periods in random order. In one period participants adhered to their usual exercise management (control period), in the other 2 periods, participants additionally incorporated 10s (every 20 mins) or 4s sprints (every 2 mins) into moderate intensity exercise. Outcome measures included the incidence of hypoglycaemia (defined as sensor glucose readings &lt;3.1mmol/L for ≥ to 20 minutes) over the 14-day period; and percent time spent &lt;3.1mmol/L and &lt;3.5mmol/L. CGM data were analysed using a mixed model approach.
Results: 24 participants completed the study, performing a total of 420 exercise episodes. The 10s period was associated with fewer hypoglycaemia events (&lt;3.1mmol/L) than the control period (adjusted incidence rate ratio of 0.67, 95% CI 0.46-0.98: p=0.04), with a hypoglycaemia incidence rate of 0.40 (95% CI 0.26-0.55), 0.33 (95% CI 0.21-0.45) and 0.28 (95% CI 0.17-0.38) events per day in the control, 4s and 10s periods respectively. The 10s period was associated with a reduction in time spent &lt;3.5mmol/L (control vs. 10s period, 3.1% vs. 2.1%, p=0.03) and time spent &lt;3.1mmol/L (control vs.10s period, 1.9% vs. 1.2%, p= 0.03) compared to the control period. There was no increase in nocturnal hypoglycaemia during the sprinting periods.
Conclusion: In a real-life setting the inclusion of 10s sprints into moderate intensity exercise reduces the incidence of hypoglycaemia, without increasing the risk of nocturnal hypoglycaemia.

Disclosure
T. Chetty: None. H. Roby: None. N. Paramalingam: None. J. Dart: None. W. Soon: None. G.J. Smith: None. V.B. Shetty: None. P.A. Fournier: None. T. Jones: None. E.A. Davis: None.
Real-World Flash Glucose Monitoring in a Developing Country
Authors: CALLIARI LUIS EDUARDO P. , XU YONGJIN , JANGAM SUJIT , HAYTER GARY , DUNN TIMOTHY 
Published: June 2018

Previous studies showed results of flash glucose monitoring (FreeStyle LibreTM) in European countries. This study evaluated real-world impact of device use and glucose metrics using a cross-sectional observational design in a developing country - Brazil. A server collected de-identified data from readers, and completed sensors (&gt;120 hours of operation) were analysed. Comparison of 1,569,588 sensors (237,747 readers) worldwide were made with 57,713 sensors (8,979 readers) from Brazil. Readers were divided into 10 rank-ordered groups by daily scan rate. Users worldwide performed a mean (±SD) of 13.2±8.9 daily glucose scans and a rate of 13.5±9.1/day in Brazil (p=0.002). Time in range (70-180 mg/dL) increased from 13.5 to 16.2 h/day (20% increase, p&lt;0.001) comparing the lowest and highest scan groups in Brazil, with a similar association worldwide (12.0 to 16.3 h/day; 35% increase; p&lt;0.001). Time in hyperglycemia decreased from 10.6 to 6.4 h/day (40% decrease, p&lt;0.001) comparing low with high frequency users worldwide. Brazil users had a similar decrease, though the lowest scan group was 90-minutes lower (9.2 and 6.4 h/day; 30% decrease; p&lt;0.001). Similar daily scan rates were observed in Brazil and worldwide, and those users having the highest daily scans also had the most time in range and least time in hyperglycemia. This is the first study showing that a developing country in Latin America can also benefit from flash glucose monitoring.

Disclosure
L.P. Calliari: Board Member; Self; Abbott. Speaker's Bureau; Self; Novo Nordisk Inc.. Board Member; Self; Sanofi. Speaker's Bureau; Self; Medtronic, Roche Diagnostics Corporation. Board Member; Self; Eli Lilly and Company. Y. Xu: Employee; Self; Abbott. S. Jangam: Employee; Self; Abbott. G. Hayter: Employee; Self; Abbott. T. Dunn: Employee; Self; Abbott.
Predicting Exercise-Related Changes in Glucose in People with Type 1 Diabetes Using Linear Models and Incorporating Knowledge of Prior Exercise
Authors: TYLER NICHOLE S. , REDDY RAVI , EL YOUSSEF JOSEPH , CASTLE JESSICA R. , JACOBS PETER G. 
Published: June 2018

Exercise-related hypoglycemia in T1D is frequent and can be life-threatening. The ability to predict glucose changes at the start of exercise could significantly improve exercise outcomes for people with T1D. We developed multivariate adaptive regression splines (MARS) to predict changes to blood glucose dynamics and to assess whether including past glucose changes during exercise improves prediction accuracy. Data was collected from 20 adults during a 4-arm, 4-day, outpatient artificial pancreas (AP) study (14 F, weight: 76.3 ±14.6 kg, age: 35.2 ± 4.6 years, height: 172.0 ± 10.6 cm). Days 1 and 4 of the study consisted of identical controlled meals and aerobic exercise events at an academic medical center. Insulin delivery data, heart rate, continuous glucose measurement (CGM) data, and carbohydrate intake were recorded. Subjects exercised at 60% of their maximal VO2 for 45 minutes. Using the 160 aerobic exercise sessions, 2 linear predictive models were developed to estimate glucose drop during exercise: (1) a model excluding past exercise history (naïve), and (2) a model including past exercise (historical). A greedy approach was used to eliminate non-predictive features and build sparse models consisting of CGM at the start of exercise, the rate of change of CGM within 5 minutes of exercise, the metabolic expenditure 5 minutes into exercise, and participant height. Leave-one-out cross validation was done to fit the model and estimate root-mean squared error (RMSE). R2 was calculated between empirical and predicted glucose drops. The naïve model was able to predict glucose drop to within 18.7 mg/dL. Including historical exercise data improved accuracy and increased R2 only nominally (naïve R2=0.78, RMSE=18.7, historical R2= 0.81, RMSE=17.54). Results demonstrate prediction accuracy of linear models in estimating exercise-related glucose changes with moderate improvement by including prior exercise data.

Disclosure
N.S. Tyler: None. R. Reddy: None. J. El Youssef: None. J.R. Castle: Consultant; Self; Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk Inc. P.G. Jacobs: Stock/Shareholder; Self; Pacific Diabetes Technologies.
Sexual-Dimorphism in Exercise-Induced Beiging and Altered Mitochondrial Function in Inguinal White Adipose Tissue (iWAT) from the Mouse
Authors: NIGRO PASQUALE , MIDDELBEEK ROELAND , ALVES CHRISTIANO R. , ALBERTSON BRENT G. , ROWLAND LESLIE A. , WAGNER ANA B. , PRINCE NOAH B. , HIRSHMAN MICHAEL F. , GOODYEAR LAURIE J. 
Published: June 2018

Regular physical exercise has numerous benefits on metabolic health, likely involving adaptations to many tissues, including adipose tissue. There are conflicting reports on the effects of exercise training on adaptations to iWAT and we hypothesized that these discrepancies may stem in part from sex-specific differences. Male and female 10 week old C57BL6/J mice were housed in cages with (trained) or without (sedentary) running wheels for 11 days (n=6-9/sex/experiment). Males performed less voluntary exercise vs. females (56±7 vs. 78±5 km; p&lt;0.05). In males, training decreased iWAT fat pad weight (19.6%) and adipocyte size (19%) (both p&lt;0.05), whereas training did not have these effects on iWAT in females, most likely due to increased food intake. Training did not alter perigonadal WAT weight or adipocyte size in either sex. In iWAT, training in males increased mRNA of the beiging genes Ucp1 (304%; p&lt;0.01); Pgc1α (228%; p&lt;0.05); Cidea (206%; p&lt;0.05); and Dio2 (197%; p&lt;0.01), as well as Ucp1 protein (124%; p&lt;0.01), but none of these markers were increased in females. Exercise training also increased mitochondrial parameters in iWAT only from males, including basal respiration (170%; p&lt;0.01), glycolytic capacity (227%; p&lt;0.001) and the mitochondrial fission genes Opa1 (235%; p&lt;0.05), Mfn1 (231%; p&lt;0.001), and Mfn2 (229%; p&lt;0.01). Since exercise may increase testosterone in male mice, we tested the effects of testosterone on iWAT beiging and mitochondria. iWAT of male and female mice were treated with testosterone (10μM) for 24 hours. Interestingly, testosterone increased Ucp1 protein (175%; p&lt;0.05) and mRNA (386%; p&lt;0.05) in iWAT from male, but not in females. We conclude that voluntary wheel running in mice results in beiging and mitochondrial adaptations to iWAT exclusively in males. Sex-specific differences in WAT function will be important to consider in all research investigating adipose tissue beiging and mitochondrial function.

Disclosure
P. Nigro: None. R. Middelbeek: None. C.R. Alves: None. B.G. Albertson: None. L.A. Rowland: None. A.B. Wagner: None. N.B. Prince: None. M.F. Hirshman: None. L.J. Goodyear: None.
Dietary Protein Intake Is Not Associated with Progression of Diabetic Nephropathy in Patients without Macroalbuminuria
Authors: KAJI AYUMI , HASHIMOTO YOSHITAKA , SAKAI RYOSUKE , OKAMURA TAKURO , YAMAZAKI MASAHIRO , FUKUI MICHIAKI 
Published: June 2018

Background/Aims: Diabetic nephropathy is an important problem in patients with diabetes. However, little is known about the effect of dietary protein intake on albuminuria in patients with diabetes. Thus, the aim of this study was to clarify the association between dietary protein intake and change in urinary albumin excretion (UAE) or estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.
Methods: In this retrospective cohort study, we included 143 patients (71 men, average 64.0 (10.5) years, and median 14.5 (6.7-38.5) mg/gCr) without macroalbuminuria (UAE over 300 mg/gCr). Change in UAE or eGFR was defined as increase of UAE or GFR/follow-up duration (year). Habitual protein intake was estimated by a self-administered diet history questionnaire.
Results: Median follow-up duration was 5 years. Logistic regression analyses showed that baseline UAE was associated with change in UAE (β = 0.217, p = 0.012), but the protein intake was not (β = -0.064, p = 0.454) (Table). In addition, baseline Cr was associated with change in eGFR (β = 0.344, p = 0.001), but the protein intake was not (β = 0.001, p = 0.988).
Conclusions: Dietary protein intake was not associated with change in UAE or eGFR. This result suggests that protein restriction is not necessary in patients without macroalbuminuria.
Multiple regression analysis on δUAE or δeGFRδUAEstandardized regression coefficientp valueδeGFRstandardized regression coefficientp valueLog (UAE+1)0.2170.012Log (UAE+1)0.0490.560Protein intake (g/kg/day)-0.0640.454Protein intake (g/kg/day)-0.0330.698Usage of RAS inhibitor0.1140.193Usage of RAS inhibitor-0.2020.021Creatinine0.0470.646Creatinine0.398&lt;0.001Age-0.0030.977Age0.0610.490BMI0.1190.184BMI-0.0420.634Men-0.1430.163Men0.1210.237

Disclosure
A. Kaji: None. Y. Hashimoto: Research Support; Self; Asahi Kasei Corporation, Fuji Foundation for Protein Research, Japan Society for the Promotion of Science, MSD K.K.. R. Sakai: None. T. Okamura: None. M. Yamazaki: None. M. Fukui: Research Support; Self; Grant-in-Aid for Scientific Research (C), Ono Pharmaceutical Co., Ltd., AstraZeneca, Astellas Pharma US, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Kissei Pharmaceutical Co., Ltd., MSD K.K., Novo Nordisk Foundation.
Clinical Study of Astaxanthin on Glucose Tolerance in Nondiabetic Subjects
Authors: URAKAZE MASAHARU , KOBASHI CHIKAAKI , SATOU YUKIHIRO , TAKAGI MASATOSHI , SHIGETA KOUICHI , TOSHIMA MASAHIRO , TAKAHASHI JIRO , NISHIDA MITSUNORI 
Published: June 2018

Astaxanthin (ASTX) is a xanthophyll carotenoid produced by Haemococcus pluvialis, and is found in microalgae, plankton, krill and other seafood. ASTX has strong antioxidant activity, which is an attractive nutraceutical for further investigation in diabetes, lipid profile, and atherosclerotic cardiovascular disease where antioxidant cellular protection may be of clinical benefit. We already reported the effects of astaxanthin (randomized, double-blind, placebo-controlled study) on glucose metabolism and lipid profile in 44 healthy volunteers in the 10th Asia Pacific Conference on Clinical Nutrition 2017. Here we report the effects of ASTX on glucose metabolism in 29 subjects whose HbA1c was from 5.6 % to 6.4 % at baseline. Data of 75g OGTT and HbA1c in 29 subjects (16 in ASTX group and 13 in Placebo group) were analyzed. After ASTX (12mg/day) supplementation for 12 weeks, the glucose level at 30 min by 75g OGTT was significantly decreased compared to before. The level of HbA1c was also significantly decreased compared to before. Furthermore, we assessed indices of insulin resistance derived from OGTT. Both Matsuda index and hepatic insulin resistance were improved after ASTX (12mg/day) supplementation, although muscle insulin sensitivity index was unchanged. Our results suggest that ASTX might have beneficial effects on the prevention of diabetes in subjects whose HbA1c was from 5.6 % to 6.4 %, including subjects with prediabetes.

Disclosure
M. Urakaze: Research Support; Self; Fuji Chemical Industry Co., Ltd.. C. Kobashi: None. Y. Satou: None. M. Takagi: None. K. Shigeta: None. M. Toshima: Research Support; Self; Fuji Chemical Industry Co., Ltd. J. Takahashi: Employee; Self; Fuji Chemical Industry Co., Ltd. M. Nishida: Other Relationship; Self; Fuji Chemical Industry Co., Ltd..
Saccharin Does Not Affect Insulin Resistance in 14 Overweight Adults without Diabetes
Authors: RADHOLM KARIN , KALIN KENNY , WENNBERG MARIA , WOODWARD MARK , ESQ.  , BÄCKHED FREDRIK , ROLANDSSON OLOV 
Published: June 2018

Background: Most non-caloric artificial sweeteners (NAS) are not digested, but come in contact with the gut microbiota, an interaction that has been associated with impaired glucose control. We aimed to further investigate whether NAS affect insulin sensitivity.
Methods: The study was an open label study where participants acted as their own controls before and after exposure of 240 mg saccharin/day for three months. Participants were 55-65 years old, with a body mass index of 26-29 kg/m2 without diabetes. Insulin sensitivity was assessed by use of hyperinsulinemic-euglycemic clamps and ’M value’ was calculated by dividing the glucose infusion rate during the last 60 minutes of the clamp by body weight (mg/kg/min).
Results: Of the 14 included participants, one did not complete the study. There was no change in insulin resistance after exposure to saccharin. The mean M value difference (∆M) for all participants was 0.0 (SD 1.6). ∆M was not related to age (p value 0.162) or sex (p value 0.578). Individual M values from the first and second insulin clamp are shown in the Figure and indicate some individual responses.
Conclusions: In contrast to the larger epidemiologic studies, we did not observe a strong effect of NAS on insulin sensitivity. Some individuals exhibited impaired insulin sensitivity and we are currently investigating whether individualized responses are dependent on shifts in the gut microbiota.

Disclosure
K. Radholm: None. K. Kalin: None. M. Wennberg: None. M. Woodward: None. F. Bäckhed: Board Member; Self; Metabogen AB. Stock/Shareholder; Self; Metabogen AB. Advisory Panel; Self; Ferring Pharmaceuticals. O. Rolandsson: None.
Effect of High ß-Glucan Barley on Postprandial Plasma Glucose Levels in Subjects with Normal Glucose Tolerance and Patients with Type 2 Diabetes
Authors: HIGA MARIKO , HASHIMOTO AYANA , HAYASAKA MOE , HIJIKATA MAI , UEDA AYAMI , ODA KENZABURO , KATO DAISUKE , YAMASHITA KAORU , ICHIJO TAKAMASA 
Published: June 2018

Increasing evidence supports a more prominent role for postprandial glucose (PPG) regulation in the management of type 2 diabetes. Viscous dietary fibers including oat and barley β-glucan are one of the most effective classes of functional food ingredients for reducing PPG. We investigated the effect of high β-glucan barley on postprandial plasma glucose and C-peptide levels using a meal tolerance test and continuous glucose monitoring (CGM) in 15 subjects with normal glucose tolerance (NGT) and 29 type 2 diabetic patients. A 500-kcal meal tolerance test, using white rice alone (white rice) or white rice mixed with 50% of barley (Kirari-mochi®) containing 1.5-times β-glucan higher than usual barley (barley), was performed, and plasma glucose and C-peptide levels were measured every 30 minutes for 180 minutes. Daily glucose variability was measured using CGM over two days, while subjects consumed 1600-kcal or 1800-kcal test meals consisting of white rice or barley. Subsequently, a meal tolerance test with identical carbohydrate quantity (52g carbohydrate) with or without 1.8g of β-glucan, was performed in 7 diabetic patients. In NGT subjects and diabetic patients, the incremental area under the curve (AUC) of plasma glucose and C-peptide levels for 180 minutes after the meal tolerance test were significantly decreased following the consumption of barley compared to the consumption of white rice alone. The studies using CGM have demonstrated that the consumption of barley lead to a significant decrease in the 24-h standard deviation of blood glucose (24-h SDBG) and mean amplitude of glycemic excursion (MAGE) in diabetic patients. Similar results were obtained in subsequent tests with identical carbohydrate quantity but with β-glucan.
In conclusion, these results suggest that high-β-glucan barley may contribute to decreased PPG levels and endogenous insulin secretion in both patients with type 2 diabetes and the subjects with NGT.

Disclosure
M. Higa: None. A. Hashimoto: None. M. Hayasaka: None. M. Hijikata: None. A. Ueda: None. K. Oda: None. D. Kato: None. K. Yamashita: None. T. Ichijo: None.
Carnosine Supplementation Reduces Plasma Soluble Transferrin Receptor in Healthy Overweight or Obese Individuals—A Pilot Randomised Trial
Authors: DE COURTEN BARBORA , UKROPEC JOZEF , ALDINI GIANCARLO , UKROPCOVA BARBARA , BAYE ESTIFANOS 
Published: June 2018

Abnormalities of iron homeostasis has been shown to cause insulin resistance, type 2 diabetes and cardiovascular disease. Treatment with iron chelators has shown to reverse several chronic diseases including type 2 diabetes. Carnosine, an over-the-counter food supplement with chelating properties, has been shown to lower serum iron and glucose concentrations in diabetic rodents. We have previously shown that carnosine supplementation prevented worsening of glucose metabolism in healthy overweight and obese adults. Yet, the role of carnosine on markers of iron metabolism in humans has not been investigated. We aimed to determine whether carnosine supplementation has an effect on iron parameters in overweight and obese, otherwise healthy adults. We included twenty-six participants, which were randomly allocated to receive 1g carnosine (n=14) or identical placebo (n=12) twice daily for 12 weeks. Iron parameters including iron, ferritin, transferrin, soluble transferrin receptor, total iron binding capacity and iron saturation were measured in serum or plasma by standard commercial assays (Beckman Coulter Diagnostics, New South Wales, Australia). Carnosine supplementation decreased plasma soluble transferrin receptor compared to placebo (mean change difference: -0.07 ± 0.0mg/l, p = 0.04). None of the other iron parameters were different between carnosine and placebo groups. Soluble transferrin receptor was inversely associated with urinary carnosine concentrations after adjusting for age, sex and body mass index (β coefficient: -0.01; 95% confidence interval: -0.02 to -0.003). Neither carnosinase-1 activity nor content correlated with soluble transferrin receptor. Our findings suggest that carnosine may regulate iron metabolism in high risk groups that may contribute to the prevention of insulin resistance and type 2 diabetes. Larger human clinical trials are required to confirm our results.

Disclosure
B. de Courten: None. J. Ukropec: None. G. Aldini: None. B. Ukropcova: None. E. Baye: None.
Increase in Galectin-3 Contributes to Glucose Intolerance and Insulin Resistance following Exposure to the Common Food Additive Carrageenan
Authors: TOBACMAN JOANNE K. , BHATTACHARYYA SUMIT , FEFERMAN LEONID 
Published: June 2018

Exposure to low concentration of the common food additive carrageenan (CGN) leads to impaired glucose tolerance and insulin resistance in C57BL/6J mice, due to CGN’s pro-inflammatory effects and changes in phospho-IRS1 phosphorylation. CGN is a sulfated polysaccharide with α-1,3 and β-1,4 galactosidic bonds. Other studies showed: 1) CGN reduced activity of arylsulfatase B, which removes sulfate groups from N-acetylgalactosamine 4-sulfate residues of chondroitin 4-sulfate (C4S) and dermatan sulfate; and 2) galectin-3 binds less with C4S when ARSB is reduced. Increase in galectin-3, which binds to β-galactosides, was reported to inhibit insulin signaling (Li P et al) by effects on the insulin receptor. This background led to the current assessment of effects of the no-CGN diet on galectin-3 levels in serum and galectin-3 mRNA in circulating mononuclear cells. Blood samples were obtained from adults with prediabetes before and after dietary intervention. Baseline serum galectin-3 values averaged 8.94 ng/ml (range 4.06-12.64). In 7 patients on a no-CGN diet for 12 weeks, the mean level declined to 7.25 ng/ml (p=0.006, paired t-test). In contrast, serum galectin-3 was unchanged in participants on the CGN-containing control diet and increased by over 2 ng/ml in subjects on their regular diet. mRNA expression of galectin-3 (NGALS3) in circulating mononuclear cells of patients on the no-CGN diet declined by 69%, and increased by 36% in the CGN-containing diet group and by 98% in the regular diet group (p=0.0002, 1-way ANOVA). Also, serum galectin-3 levels increased to 1.72 times baseline in C57BL/6J mice given CGN in their water supply for 12 weeks. In HepG2 cells, exogenous galectin-3 (25 µg/ml) inhibited insulin-induced glucose uptake by 39%, and was highly correlated with decline in tyrosine phosphorylation of IRS-1. These findings suggest that CGN contributes to glucose intolerance and insulin resistance, in part, by effects on galectin-3.

Disclosure
J.K. Tobacman: None. S. Bhattacharyya: None. L. Feferman: None.