bluuebunny/crossref_metadata_2025_split huggingface dataset:
579-P: Exercise Upregulates Extracellular Vesicles (EVs) Proteins Involved in Immunomodulatory and Mitochondrial Pathways in Human Subjects
Authors: VAMVINI MARIA , NIGRO PASQUALE , GOODYEAR LAURIE , MIDDELBEEK ROELAND J.W. 
Published: June 2023

Emerging data suggest that single bouts of exercise increase circulating hormones, cytokines, and EVs, and that these circulating factors may play a fundamental role in the beneficial effects of exercise on health. Here, we identify circulating factors in response to both acute exercise and exercise training and determine the effects of nutritional status on these responses. Blood samples were first collected before and immediately after an acute bout of maximal exercise in healthy, lean subjects (N=8, 3M/5F; age=27±2, V̇O2peak=28.4±1.2ml/kg/min). Subjects then completed a 10 wk moderate-intensity aerobic exercise training program (up to 65-70% VO2peak, 4x/week) with the same post-training sample collection. Proteomics (SOMAscan) quantified 1,310 circulating factors. In the untrained state, acute exercise upregulated 196 proteins and after training exercise upregulated only 65 proteins, with 47 proteins simultaneously upregulated in both the untrained and trained state. Interestingly, cellular component analysis showed that 1/3 of these shared proteins are localized in EVs. Next, we determined the baseline effects of exercise training in the fed and fasted state in the absence of acute exercise. Training upregulated 220 and 178 proteins in fed and fasted state, respectively. Exercise training commonly upregulated 120 proteins in the fed and fasted state with 1/3 localized in EVs. Integration using Vesiclepedia of the upregulated proteins in all 4 comparison groups showed 3 upregulated proteins in both acute exercise and training regardless of nutritional status: PPIF, PTPN6, and CLEC1B. These proteins are found in macrophages and neutrophils, and mediate immunomodulatory effects, promote tissue remodeling, and mitochondrial function. As EVs deliver molecules to cells altering their metabolism, they may play an important role in mediating the beneficial effects of exercise and warrant further mechanistic studies.

Disclosure
M.Vamvini: None. P.Nigro: None. L.Goodyear: None. R.J.W.Middelbeek: Research Support; Novo Nordisk.

Funding
Daiichi Sankyo; National Institutes of Health (R01DK099511 to L.G.), (5P30DK36836), (F32DK126432), (K23DK114550 to R.J.W.M.); Joslin Diabetes Center (to M.V.); Boston Area Diabetes Endocrinology Research Center (to R.J.W.M.)
583-P: Prediction of Hypoglycaemia in the 24 Hours after Exercise in Adults with Type 1 Diabetes
Authors: RILSTONE SIAN K. , OLIVER NICK , GODSLAND IAN F. , HILL NEIL E. 
Published: June 2023

Background and Aims: Exercise uptake is low in people with type 1 diabetes (T1D), with hypoglycaemia fear cited as the main barrier. We establish factors that predict hypoglycaemia after exercise.
Materials and Methods: People with T1D exercising regularly (minimum 150min/week) recorded the type, timing and duration of exercise, and heart rate, for 80 days using a smartwatch. Participants used Dexcom G6 Continuous Glucose Monitoring throughout. Predictors of hypoglycaemia were analysed.
Results: 24 (8 men), mean (SD) age 35 (11) years, duration of diabetes 14 (7) years, BMI 26 (4.7) kg/m2 and HbA1c of 58 (12) mmol/mol recorded 1454 activities with complete CGM. During the 24 hours after exercise, increasing age and baseline HbA1c increased the risk of experiencing hypoglycaemia &lt;70mg/dL (Age OR 1.028 (95% CI 1.019 - 1.038); HbA1c OR 1.027 (95% CI 1.016 - 1.037)), with similar results at other thresholds. Every additional minute of activity increased exposure to hypoglycaemia &lt;70mg/dL (OR 1.007 (95% CI 1.004-1.010)), 54mg/dL (OR 1.011 (95% CI 1.008-1.014)) and 50mg/dL (OR 1.010 (1.007-1.014)). Exercising in the afternoon reduced the risk of hypoglycaemia at all thresholds (70mg/dL OR 0.766 (95% CI 0.602-0.975), 54mg/dL OR 0.575 (95% CI 0.403-0.820) 50mg/dL OR 0.503 (95% CI 0.330-0.766)) compared to the morning. Females had a reduced risk of hypoglycaemia &lt;70mg/dL compared to males (OR 0.696 (95% CI 0.556-0.871)). Running (OR 2.898 (95% CI 1.958-4.290) and cycling (OR 2.989 (95%CI 2.154 - 4.148)) increased exposure to hypoglycaemia &lt;70mg/dL compared to walking. In multivariate analysis, age (p=0.002), baseline HbA1c (p=0.004), sex (p&lt;0.001), activity type (p&lt;0.001), duration (p=0.009) and timing of exercise (p=0.004) were significant predictors of hypoglycaemia in the 24 hours after exercise.
Conclusion: To empower adults with T1D to avoid hypoglycaemia after exercise, education and support should focus on the timing, duration, and activity type, alongside support to optimise HbA1c.

Disclosure
S.K.Rilstone: None. N.Oliver: Advisory Panel; Dexcom, Inc., Medtronic, Roche Diabetes Care, Research Support; Dexcom, Inc., Medtronic. I.F.Godsland: None. N.E.Hill: Research Support; Dexcom, Inc.
584-P: Similar Variability in Pre- and Post-exercise Glucose Levels between Morning-Fasted and Afternoon-Fed Resistance Exercise in Adults with Type 1 Diabetes
Authors: MCCLURE REID , NITZ CORBIN J. , YARDLEY JANE E. 
Published: June 2023

Background: Exercise increases longevity and decreases the incidence/progression of diabetes-related complications for those with type 1 diabetes (T1D), but it complicates blood glucose management. Understanding variability in blood glucose response to exercise may help guide choices of exercise strategies for people with T1D. Our primary objective was to compare the variability in capillary glucose (CG) response to morning, fasted resistance exercise (AMre), to afternoon post-prandial exercise (PMre). We hypothesized that CG responses would be less variable during morning fasted RE.
Methods: Seven participants [4F/3M; mean (SD): age = 29.1 (11.3) yrs; diabetes duration = 19.4 (6.7) yrs; HbA1c = 7.5 (0.7)%] completed a standardized resistance exercise protocol (3 sets of 8 repetitions of seven exercises involving all major muscle groups with 90 seconds between sets) three times in the morning (~7am) while in a fasted state and three times in the afternoon (~5pm) in a fed state. Sessions were performed in a random order with at least 48 hrs between sessions. Participants aimed for close consistency in the timing of the sessions, any associated meals (PMre only) and related insulin adjustments. To determine the intra-individual variability in CG response during AMre and PMre, as well as subsequent 30-minute recovery periods, we performed paired t-tests of the within-participant SD of the change in CG.
Results: From the beginning to the end of RE, mean within-participant SD of CG change was 1.2 (0.5) and 1.9 (1.2) mmol/L during AMre and PMre respectively (p=0.08), and 1.2 (0.4) and 1.2 (1.2) mmol/L during subsequent 30-minute recovery periods (p=0.98).
Conclusion: For adults with T1D the variability in CG response may be similar between AMre and PMre. More data are needed to clarify these effects.

Disclosure
R.Mcclure: None. C.J.Nitz: None. J.E.Yardley: Speaker's Bureau; Dexcom, Inc., Abbott.

Funding
LifeScan
585-P: Lactate Kinetics in Type 1 Diabetes—A 1-13C Lactate Study
Authors: ROMERES DAVIDE , RUCHI FNU , YADAV YOGESH , COBELLI CLAUDIO , BASU ANANDA , BASU RITA 
Published: June 2023

Lactate kinetics in individuals with type 1 diabetes (T1D) has not been assessed quantitatively. Defining lactate kinetics in T1D under steady state condition is vital for estimating non-steady state lactate turnover. We studied 5 T1D and 7 nondiabetic (ND) anthropometrically matched participants during [1-13C]-sodium-lactate bolus injection in the resting, overnight fasted state. A two-compartment model with loss only from the peripheral compartment reliably described [1-13C]-lactate kinetics. Volume of distribution of the accessible compartment, V1, was similar between T1D and ND groups (40.32±21.08 vs. 47.64±33.32 mL/kg, p=0.76) thus concordant to plasma volume (~40 ml/kg). The irreversible loss from the peripheral compartment was impaired in T1D vs ND (0.08±0.03 vs. 0.13±0.03 min−1, p=0.03); rate of lactate appearance (12.4±5.2 vs. 18.5±9.6 µmol/kg/min, p=0.34), disappearance (12.7±5.2 vs. 18.8±9.7 µmol/kg/min, p=0.34) and lactate clearance (15.9±4.7 vs. 21.9±7.8 mL/kg/min, p=0.20) were numerically but not statistically lower in T1D vs. ND individuals. To conclude, we have defined lactate kinetics under resting, overnight fasted state in T1D and ND subjects. While the volume of distribution was similar in both groups, irreversible loss from the peripheral compartment was lower in T1D subjects. Further studies are needed to better define lactate kinetics during exercise in individuals with and without T1D.

Disclosure
D.Romeres: None. F.Ruchi: None. Y.Yadav: None. C.Cobelli: None. A.Basu: None. R.Basu: Consultant; Sparrow Pharmaceuticals Inc, Research Support; Abbott Diabetes, AstraZeneca.

Funding
National Institutes of Health (DK29953 to R.B.), (DK85516 to A.B.)
587-P: AS160 Expression, but Not AS160 Serine-588, Threonine-642, and Serine-704 Phosphorylation, Is Essential for Elevated Insulin-Stimulated Glucose Uptake by Skeletal Muscle from Female Rats after Acute Exercise
Authors: WANG HAIYAN , ZHENG AMY , ARIAS EDWARD B. , KWAK SEONGEUN , PAN XIUFANG , YUE YONGPING , DUAN DONGSHENG , CARTEE GREGORY D. 
Published: June 2023

One exercise bout can substantially enhance subsequent insulin-stimulated glucose uptake (ISGU) in skeletal muscle. Evidence suggests that the insulin signaling protein Akt Substrate of 160 kDa (AS160; also known as TBC1D4) may be involved in this outcome. Supporting this idea, we recently reported that in male rats, AS160 expression was essential for increased postexercise-ISGU (PEX-ISGU). Furthermore, AS160 phosphorylation on Ser588, Thr642, and Ser704 was required for a portion (~45%) of the elevated PEX-ISGU. We now use the same approach to test AS160’s role in elevated PEX-ISGU in female rats. The initial experiment tested if AS160 is essential for exercise effects on ISGU by studying wildtype (WT) and AS160-kockout (AS160-KO) rats. The next experiment used AS160-KO rats together with an adeno-associated virus (AAV) approach to determine if AAV-delivery of WT-AS160 could restore the exercise benefit on ISGU. The final experiment employed AS160-KO rats and AAV-delivery of either WT-AS160 or AS160 mutated to prevent phosphorylation of key sites (Ser588, Thr642, and Ser704) to evaluate the requirement of phosphorylation on these sites for improved PEX-ISGU. The results from the first two experiments using female rats were very similar to our earlier findings with male rats: 1) AS160 expression was essential for increase PEX-ISGU; and 2) restoring muscle AS160 expression of AS160-KO rats rescued exercise’s ability to improve ISGU. However, in contrast to the results in male rats, preventing AS160 phosphorylation on Ser588, Thr642, and Ser704 did not diminish the magnitude of elevated PEX-ISGU in female rats. Future research will be required to elucidate the mechanisms underlying the sexual dimorphism with regard to the role of AS160 phosphorylation in elevated PEX-ISGU.

Disclosure
H.Wang: None. A.Zheng: None. E.B.Arias: None. S.Kwak: None. X.Pan: None. Y.Yue: None. D.Duan: None. G.D.Cartee: None.

Funding
National Institutes of Health (R01DK071771)
59-LB: Patient-to-Peer Education—An Unconventional Prescription for Teens with Type 1 Diabetes
Authors: PACK RICHARD , ARONSON LAUREN N. , VYAS NEHA V. , PIERCE JESSICA 
Published: June 2023

Introduction: Type 1 diabetes (T1D) is a chronic condition affecting nearly 200,000 youths in the US with increasing incidence. There is often decreased adherence to therapy in adolescents because of challenges in managing T1D combined with social and metabolic changes. Therefore, addressing the individual and social factors affecting treatment is essential in teens with T1D. To date, scant research exists on how to improve patient’s self-care in the context of their relationships to peers without T1D.
Objectives: We aimed to test feasibility of a brief socio-educational intervention designed to improve patient perceived social support, diabetes self-care behaviors, and glycemic levels among teens with T1D.
Methods: A medical student encouraged participants to 1) develop a SMART goal for improving self-care of T1D, 2) recruit peers without T1D to help achieve the goal, and 3) educate peers on the goal’s importance to their health. Participants were surveyed prior to goalsetting and 3-4 months post-intervention to assess social support, self-care, self-efficacy, and intervention acceptability; measures of glycemia were also gathered from the EMR. Thematic analysis of participant goals and plans with peers was performed.
Results: All 13 participants who attended an info meeting consented to join the study; 8 completed study surveys. On average, there was a 0.9% decrease in HbA1c among the small cohort. Survey results reflect participants were satisfied with the intervention and were more interested in working with others to care for their T1D. Thematic analysis revealed teens primarily wanted assistance, reminders, and encouragement from peers for completing their T1D self-care goals.
Conclusions: This intervention is a potentially low cost and feasible tool that may improve teens with T1Ds’ perceived social support, diabetes knowledge, treatment adherence, and overall health. More research into the effects of encouraging positive patient-peer interactions is warranted.

Disclosure
R. Pack: None. L. N. Aronson: None. N. V. Vyas: None. J. Pierce: None.
598-P: No Relationship between Sedentary Behavior Patterns and Peak Oxygen Consumption (VO2peak) among Overweight Individuals With and Without Type 2 Diabetes
Authors: WHIPPLE MARY O. , PINTO ANA J. , RAFFERTY DEIRDRE , SCALZO REBECCA L. , ABUSHAMAT LAYLA , SCHAUER IRENE E. , HUEBSCHMANN AMY G. , CLARK ETHAN , REGENSTEINER JUDITH G. , REUSCH JANE E.B. 
Published: June 2023

Background: Sedentary behavior (SB) has negative effects on health, even in the context of achieving physical activity (PA) guidelines. It is unclear how total volume and patterns of accumulation of SB may vary among overweight/obese adults with and without uncomplicated type 2 diabetes (T2D) and whether SB is related to aerobic capacity.
Purpose: To examine SB patterns and their relationship to estimated peak oxygen consumption (VO2peak) among adults with uncomplicated T2D and overweight controls.
Methods: This was a secondary analysis of baseline data from VA-MIXED (NCT03419195), a trial in physically inactive, overweight/obese adults aged 30-55 with and without T2D. Daily pattern of PA/SB was assessed via activPAL for 7 days. Participants completed a cycle ergometer graded exercise test to measure maximal workload. VO2peak was estimated using the American College of Sports Medicine metabolic equation. Pearson correlation, two-sample t-tests, and multiple linear regression analyses were used to examine relationships between variables overall and by T2D status.
Results: Baseline data were available for 21 participants (8 T2D, 13 overweight controls), mean (SD) age 43.3 (7.6) yrs, BMI 34.6 (5.6) kg/m2. Participants were sedentary (11.7 [2.2] h/day). There were no differences in step count; stepping, standing, or sedentary time; sit-to-stand transitions, and time in SB bouts ≥1 hour by T2D status (all p&gt;0.11). Correlations between SB variables and VO2peak were not significant (all p&gt;0.20). The relationship between total SB and VO2peak did not change when T2D status was included in the model (β −2.22, p=0.39).
Discussion: Objectively measured SB patterns were similar between overweight controls and adults with uncomplicated T2D and did not correlate with VO2peak. Future studies should examine these variables in larger cohorts and evaluate if SB patterns are associated with variability in response to exercise.

Disclosure
M.O.Whipple: None. J.E.B.Reusch: Advisory Panel; Medtronic. A.J.Pinto: None. D.Rafferty: None. R.L.Scalzo: None. L.Abushamat: None. I.E.Schauer: None. A.G.Huebschmann: None. E.Clark: None. J.G.Regensteiner: None.

Funding
American Diabetes Association (1-21-CMF-003 to L.A.); National Institutes of Health (P50CA244688, P30DK116073, UL1TR001082, R01AG066562, R01DK124344, K12HD057022); Ludeman Family Center for Women’s Health Research; U.S. Department of Veterans Affairs (BX004533, BX002046, CX001532)
599-P: The Effects of Cardiac Rehabilitation and Exercise Training in Hospital among Patients of Diabetic Cardiovascular Disease with Sarcopenic Obesity
Authors: KAYAMA YOSUKE 
Published: June 2023

Background: The patients of type 2 diabetes have known to have a higher chance of having Sarcopenic obesity, in which the increase of body fat and the decrease of extremity muscles is observed. A high level of lower-limb muscle has been known to associated with a lower risk of cardiovascular mortality in patients with cardiovascular diseases. The effects of cardiac rehabilitation (CR) on the patients of diabetic cardiovascular disease with sarcopenic obesity has not been well known. The aim of this study was to examined the change of body compositions and of lower-limb muscle strength between diabetic (DM) and nondiabetic (Non-DM) cardiovascular disease patients during CR.
Methods: A total of 82 male patients were assigned to the study who discharged from the acute-phase treatments for ischemic heart disease (IHD) or heart failure (HF) (DM group; n=33, Non-DM group; n=49). The body compositions and the lower-limb muscle strength were evaluated before and after CR twice a week for 5 months and analyzed retrospectively.
Results and Conclusions: The DM group before performing the CR showed significant increase in body fat and decrease in lower-limb muscle strength, compared with the non-DM group (p&lt;0.05). The effects of increasing lower-limb muscle strength after CR were observed in both DM and non-DM groups (n,c). Moreover, HF patients had weaker lower-limb muscle strength before CR than IHD patients (p&lt;0.05) and it was even weaker among the DM. However, after CR, the increasing effects of lower-limb muscle tended to be stronger in the DM group. These data showed that the patients with diabetic cardiovascular disease with sarcopenic obesity have a chance to have increase of the lower-limb muscle strength after CR as well as that of nondiabetic cardiovascular disease. A lower-limb muscle might be a new scale and a therapeutic target in patients with cardiovascular disease.

Disclosure
Y. Kayama: None.
6-LB: GPR119 Agonist PRM A Increases Glucagon Response to Hypoglycemia in Rats
Authors: KWOK DAVID W.K. , ALEXANDER DIANE , BEELEY NIGEL R.A. , KELLEY DAVID 
Published: June 2023

Glucagon (Gcg) is crucial in the counter-regulatory response (CRR) to hypoglycemia yet this is severely impaired in T1D. This pathophysiology was recognized 50 years ago, but only recently have drug targets emerged to amplify Gcg CRR in T1D. One promising target is the receptor GPR119, expressed in gut endocrine cells and pancreatic islets with highest expression on α-cells, 10-fold greater than on β-cells. In the current study, a GPR119 agonist (PRM A) was given by oral gavage at doses of 3, 10 and 30 mg per kg (mpk), to rats (Sprague-Dawley, groups of 8) two hours prior to induction of hypoglycemia by an insulin tolerance test (ITT), using a dose of 1.25 Units per kg, given by intra-peritoneal injection at t=0 min. A vehicle-treated (V) control and a positive comparator group, given the GPR119 agonist MBX-2982 (10 mpk) were also studied. MBX-2982 is currently being used in a clinical trial to assess its effect on Gcg CRR in volunteers with T1D challenged with a hypoglycemic clamp. In rats in the current study, severe hypoglycemia was induced during the ITT; blood glucose nadir was achieved by 60 min in association with peak insulin ≥ 100 µU/ml. Glucose and insulin were similar across groups. The healthy V rats mounted a normal Gcg CRR, with a peak value of 26±10 pM, 5-fold above baseline. Pre-treatment with PRM A significantly amplified Gcg CRR relative to V (to 86±17, 79±18, and 85±12 pM; at 3, 10, and 30 mpk; p&lt;0.0001 vs V). The Gcg AUC during the ITT was nearly 50% greater with all doses of PRM A (p&lt;0.05 vs V) and the peak Gcg CRR was shifted earlier (p&lt;0.01 vs V). MBX-2982 pre-treated rats, relative to V, trended to a higher peak (49±14 vs 26±10 pM) and AUC Gcg (7292±2039 vs 6855±1306 pM*h), but neither difference was significant, whereas the differences for PRM A were strongly significant for time and treatment.
In summary, PRM A, a potent GPR119 agonist, tripled peak Gcg CRR during an ITT in healthy rats, affirming that the target of GPR119 holds promise as a novel means to mitigate the dangerous risk of hypoglycemia for individuals with T1D.

Disclosure
D. W. K. Kwok: None. D. Alexander: None. N. R. A. Beeley: None. D. Kelley: Consultant; Pramana Pharmaceuticals, Inc, Kallyope.

Funding
Pramana Pharmaceuticals Inc.
60-OR: A Pilot Study Evaluating an Insulin and Pramlintide Fully Closed-Loop Delivery System
Authors: ODABASSIAN MADISON , TSOUKAS MICHAEL , COHEN ELISA , PASQUA MELISSA-ROSINA , RUTKOWSKI JOANNA , HAIDAR AHMAD 
Published: June 2023

We conducted a randomized, controlled, pilot study to eliminate carbohydrate counting (CC) in adults with type 1 diabetes using an automated insulin (insulin aspart and faster aspart) and pramlintide dual-pump fully closed-loop delivery system. The interventions included 5 arms (n = 11, 8 F, A1C 7.4%) and participants underwent 14 hours of outpatient, free-living, supervised interventions of (i) faster aspart with CC, (ii) faster aspart and pramlintide at a 1u:8µg ratio without CC, and (iii) faster aspart and pramlintide (1:10) without CC (iv) insulin aspart and pramlintide (1:8) without CC, and (v) insulin aspart and pramlintide (1:10) without CC. One participant opted out of the two insulin aspart and pramlintide arms. Prior to each dual-hormone intervention, participants had a 2-4-day drug dose-escalation period. P-values are not reported as this is an underpowered pilot study. During the faster aspart and pramlintide interventions, the mean time in target range (70-180 mg/dL) was 69% (24%) and 77% (13%) with the 1:8 and 1:10 ratios, respectively. During the aspart and pramlintide interventions, the time in range was 71% (15%) and 77% (11%) with the 1:8 and 1:10 ratios, respectively. Compared to the control arm where time in range was 72% (26%), both the insulin aspart and faster aspart arms with the 1:10 ratio provided numerical improvements to time in range. The median time spent below 54mg/dL with each respective ratio was 1.3% (0, 4.5), 0.6% (0, 2.4) on the aspart arms and 0.0% in the faster aspart and control arms. The mean total insulin used throughout the interventions was 38.2 (23.5) units on the control arm, 31.8 (18.4) and 32.5 (17.5) on the faster aspart 1:8 and 1:10 respectively, and 36.6 (26.9) and 32.2 (23.5) on the insulin aspart 1:8 and 1:10 arms respectively. This pilot study suggests that our fully automated dual-hormone delivery system has the potential to alleviate carbohydrate counting without degrading time in the target range; and it will be investigated in a larger subsequent study.

Disclosure
M.Odabassian: None. M.Tsoukas: Speaker's Bureau; Novo Nordisk Canada Inc., Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Janssen Scientific Affairs, LLC, AstraZeneca, Sanofi. E.Cohen: None. M.Pasqua: None. J.Rutkowski: None. A.Haidar: Consultant; Eli Lilly and Company, Other Relationship; Bigfoot Biomedical, Inc., Research Support; Adocia, Dexcom, Inc., Tandem Diabetes Care, Inc.