Exercise Prescription for Postprandial Glycemic Management.

The detrimental impacts of postprandial hyperglycemia on health are a critical concern, and exercise is recognized a pivotal tool in enhancing glycemic control after a meal. However, current exercise recommendations for managing postprandial glucose levels remain fairly broad and require deeper clarification. This review examines the existing literature aiming to offer a comprehensive guide for exercise prescription to optimize postprandial glycemic management. Specifically, it considers various exercise parameters (i.e., exercise timing, type, intensity, volume, pattern) for crafting exercise prescriptions. Findings predominantly indicate that moderate-intensity exercise initiated shortly after meals may substantially improve glucose response to a meal in healthy individuals and those with type 2 diabetes. Moreover, incorporating short activity breaks throughout the exercise session may provide additional benefits for reducing glucose response.

Cardiac Magnetic Resonance for Prophylactic Implantable-Cardioverter Defibrillator Therapy in Ischemic Cardiomyopathy: The DERIVATE-ICM International Registry.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is the most effective prophylactic strategy against sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM) and left ventricle ejection fraction (LVEF) ≤35% as detected by transthoracic echocardiograpgy (TTE). This approach has been recently questioned because of the low rate of ICD interventions in patients who received implantation and the not-negligible percentage of patients who experienced SCD despite not fulfilling criteria for implantation. OBJECTIVES: The DERIVATE-ICM registry (CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy; NCT03352648) is an international, multicenter, and multivendor study to assess the net reclassification improvement (NRI) for the indication of ICD implantation by the use of cardiac magnetic resonance (CMR) as compared to TTE in patients with ICM. METHODS: A total of 861 patients with ICM (mean age 65 ± 11 years, 86% male) with chronic heart failure and TTE-LVEF <50% participated. Major adverse arrhythmic cardiac events (MAACE) were the primary endpoints. RESULTS: During a median follow-up of 1,054 days, MAACE occurred in 88 (10.2%). Left ventricular end-diastolic volume index (HR: 1.007 [95% CI: 1.000-1.011]; P = 0.05), CMR-LVEF (HR: 0.972 [95% CI: 0.945-0.999]; P = 0.045) and late gadolinium enhancement (LGE) mass (HR: 1.010 [95% CI: 1.002-1.018]; P = 0.015) were independent predictors of MAACE. A multiparametric CMR weighted predictive derived score identifies subjects at high risk for MAACE compared with TTE-LVEF cutoff of 35% with a NRI of 31.7% (P = 0.007). CONCLUSIONS: The DERIVATE-ICM registry is a large multicenter registry showing the additional value of CMR to stratify the risk for MAACE in a large cohort of patients with ICM compared with standard of care.

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study: prognostic value of cardiac magnetic resonance-derived right ventricular parameters substudy.

AIMS: Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan-Meier curves and cox regression were used to investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8 ± 14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0 ± 10.8. Median follow-up was 959 days (interquartile range: 560-1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio = 1.44; 95% CI [1.09-1.91]; P = 0.01). On subgroup analyses, the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHA III/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function. CONCLUSION: RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression.

Effects of a Long Chain n-3 Polyunsaturated Fatty Acid-rich Multi-ingredient Nutrition Supplement on Body Composition and Physical Function in Older Adults with Low Skeletal Muscle Mass.

Six months of supplementation with a multi-ingredient nutrition supplement was investigated in older adults with low skeletal muscle mass given the recently purported benefits of such approaches. Community-dwelling older adults (age, 74.9 ± 3.6 y; M/F, 18/19) participated in a double-blind, placebo-controlled, randomized trial involving daily consumption of either fruit juice placebo (PLA) or supplement (SUPP) in the form of a 200-mL carton of a juice-based emulsion of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) (3000 mg as 1500 mg docosahexaenoic acid and 1500 mg eicosapentaenoic acid), whey protein isolate (8 g), vitamin D3 (400 IU), and resveratrol (150 mg). Body composition, physical function, and circulating markers of metabolic health were assessed at baseline (PRE), and after 3 (MID) and 6 (POST) months of supplementation. Lean body mass (LBM) was unchanged in either group, but fat mass increased in SUPP by 1.41 (0.75, 2.07) kg at POST (+6.4%; p < .001; d = 0.20). Hand-grip strength was maintained in SUPP, but declined in PLA by 2.50 (0.81, 4.19) kg at POST (-6.8%; p = .002; d = 0.38). Short physical performance battery score was unchanged in PLA, but increased in SUPP by 1.13 (0.41, 1.84) above PRE at POST (p = .001; d = 0.47). Circulating markers of metabolic health were unchanged in response to the intervention in either PLA or SUPP. Long-term supplementation with an LC n-3 PUFA-rich multi-ingredient nutrition supplement demonstrates potential efficacy for improving physical function in older adults in the absence of exercise training and independent of a change in LBM.

Atrial Fibrillation and Peri-Atrial Inflammation Measured through Adipose Tissue Attenuation on Cardiac Computed Tomography.

BACKGROUND: Inflammation plays a key role in atrial fibrillation (AF). Epicardial adipose tissue around the atrial wall can influence atrial morpho-functional properties. The aim of this study was to assess whether an increased quantity and/or density of adipose tissue located around the left atrium (Fat-LA) are related to AF, independently from atrial size. METHODS: eighty patients who underwent AF ablation and 80 patients without history of AF were selected. The Fat-LA mass was quantified as tissue within -190 to -30 Hounsfield Units (HU) on cardiac computed tomography angiograms (CCTA), and the mean adipose tissue attenuation was assessed. RESULTS: Adipose tissue mass was higher in patients with AF (5.42 ± 2.94 mL) versus non-AF (4.16 ± 2.55 mL, p = 0.007), but relative fat quantity did not differ after adjusting for atrial size. Mean fat density was significantly higher in AF (-69.15 HU) versus non-AF (-76.82 HU, p < 0.0001) participants. In the logistic regression models, only the addition of mean Fat-LA attenuation led to a significant improvement of the model's chi-square (from 22.89 of the clinical model to 31.69 of the clinical and adipose tissue attenuation model, p < 0.01) and discrimination (AUC from 0.775 to 0.829). CONCLUSIONS: Fat-LA volume is significantly greater only in absolute terms in patients with AF, but this difference does not hold after adjusting for the larger LA of AF subjects. On the contrary, a higher Fat-LA density was associated with AF, independently from LA size, providing incremental value over other variables that are associated with AF.

CarDiac magnEtic Resonance for prophylactic Implantable-cardioVerter defibrillAtor ThErapy in Non-Ischaemic dilated CardioMyopathy: an international Registry.

AIMS: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients. METHODS AND RESULTS: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort. CONCLUSION: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation.

Effects of exercise before and/or after a mixed lunch on postprandial metabolic responses in healthy male individuals.

PURPOSE: Exercise plays an important role in preventing and treating postprandial dysmetabolism. We investigated the postprandial metabolic responses to a standard lunch when a session of aerobic exercise is performed in the early postprandial phase or divided between the pre- and postprandial period. METHODS: Nine healthy volunteers consumed a standardised mixed lunch and rested for the following 3 h (Con) or performed 40 min of cycling at 65% V̇O2max after lunch (CPPEx), or two 20-min sessions, one before (SplitEx1) and the other after lunch (SplitEx2), at the same intensity. RESULTS: At 1-h post-lunch, a significant reduction (P < 0.001) in glycaemia was observed for CPPEx (- 25 ± 10%) and SplitEx (- 34 ± 7%) compared to Con. Yet, a post-exercise rebound lessened the exercise effect on the glycaemic area under the curve (AUC) at 2 and 3 h. At 1 h, a significant reduction (P < 0.009) in plasma insulin (SplitEx - 53 ± 31%; CCPEx - 48 ± 20%) and C-peptide (SplitEx - 57 ± 20%; CCPEx - 47 ± 24%) was observed compared to Con. Glucose-dependent insulinotropic polypeptide (GIP) increased after the meal, without differences between conditions. Compared with SplitEx1, cortisol response was attenuated during SplitEx2 and CPPEx. At 3 hours, triglyceride AUC was significantly higher (P = 0.039) in SplitEx compared to Con (+ 19 ± 8%). CONCLUSION: Forty minutes of postprandial exercise or 20 min of pre- and postprandial exercise are both effective at attenuating the glycaemic and insulinaemic response to a mixed lunch, while a higher lipaemia was found in the pre- and postprandrial exercise condition.

Manifestations of Skull Base IgG4-Related Disease: A Multi-Institutional Study.

OBJECTIVE: IgG4-related disease (IgG4-RD) is a recently recognized disease characterized by fibroinflammatory infiltrates rich in IgG4+ plasma cells that can present as isolated tumor-like lesions of the head and neck. The objective of the current study was to describe the cranial base manifestations of IgG4-RD. METHODS: Review of all cases at three tertiary-referral centers since disease description in 2003. RESULTS: Eleven patients were identified at a median age at presentation of 58 years (IQR, 38-65; 55% male). Ten (91%) patients had isolated skull base masses without systemic disease. Cranial neuropathies were commonly observed in the abducens (45%), trigeminal (18%), and facial nerves (18%). Lesions frequently involved the cavernous sinus (55%; 6/11) with extension to the petroclival junction in 50% (3/6). Infiltration of the internal auditory canal was present in 27% (3/11) with one case demonstrating erosion of the bony labyrinth. Preliminary clinical diagnoses commonly included nasopharyngeal cancer, pituitary macroadenoma, cholesteatoma, and meningioma / multiple meningioma syndrome. Local biopsy demonstrated >30 IgG4-positive plasma cells per high-powered field or an IgG4:IgG ratio greater than 40% in all cases. Rapid and durable clinical improvement was seen in 91% following corticosteroid and rituximab therapy. CONCLUSIONS: IgG4-RD nonspecifically presents as a rare cause of the skull base mass. Often presenting without concomitant systemic disease, local diagnostic biopsies are required. Obtaining adequate tissue specimen is complicated by densely fibrotic cranial base lesions that are frequently in close proximity to critical neurovascular structures. Primary medical therapy with corticosteroids and rituximab is effective in most patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2574-2580, 2020.

Clinical and Prognostic Significance of Serum IgG4 in Chronic Periaortitis. An Analysis of 113 Patients.

Objective: Chronic periaortitis (CP) is a rare fibro-inflammatory disorder that incorporates idiopathic retroperitoneal fibrosis, inflammatory abdominal aortic aneurysms, and perianeurysmal retroperitoneal fibrosis. CP is included in the spectrum of IgG4-related disease. Since CP patients rarely undergo diagnostic biopsies, serum IgG4 levels are often used to classify CP as IgG4-related. However, the clinical and prognostic significance of serum IgG4 in CP is unknown. Methods: We measured serum IgG4 in active CP patients and compared the clinical characteristics, response to therapy and outcome of patients with high and normal levels. We also tested the diagnostic significance of IgG4 by comparing its levels in CP patients, healthy and disease controls (malignancies, Erdheim-Chester disease, large-, and small-vessel vasculitis). Results: We studied 113 consecutive patients with active CP. Twenty-four (21.2%) had high serum IgG4 (>135 mg/dL). The demographic, laboratory, and clinical characteristics of patients with high and normal IgG4 were similar, and so were the rates of ureteral obstruction and the disease characteristics on CT, MRI, and 18F-FDG-PET. Patients with high IgG4 only had a higher frequency of extra-retroperitoneal fibro-inflammatory lesions (p = 0.005). There were no significant differences in response to therapy and relapses between the two groups. Serum IgG4 levels did not discriminate CP from controls. Conclusions: Serum IgG4 levels are high in a minority of CP patients and do not identify specific clinical or prognostic subgroups; only a higher frequency of extra-retroperitoneal lesions is found in high-IgG4 patients. Serum IgG4 levels do not help in the differential diagnosis between CP and its mimics.

Carbohydrate Supplementation Does Not Improve 10 km Swimming Intermittent Training.

The aim of the present study was to test the effectiveness of carbohydrate (CHO) feeding supplemented every 2.5-km, as in official races, on the performance, rating of perceived exertion (RPE), and glycaemia during a 10-km intermittent training workout in elite open-water swimmers. A randomized crossover design was used. Participants completed two 10-km intermittent training sessions (20 × 500-m). The relative velocity was expressed in percentage of a single 500-m. Glycaemia was monitored by continuous glucose monitoring. Participants had to ingest either 1 L of tap water (WAT; 0.50 L·h-1) or 120 g of CHO in the form of 8% solution (60 g·h-1). The 15-point RPE scale was used during the trials. A two-way ANOVA for repeated measures was performed (p < 0.05). The relative velocity of each 500-m was not significantly different between the two trials. No significant differences emerged in the relative velocity of the last 500-m between trials. Average RPE was not statistically different between the two trials (11 ± 3 in WAT and 12 ± 3 in CHO). In the last 500-m, glycaemia was significantly higher in the CHO trial (5.92 ± 0.47 mmol·L-1 in CHO; 5.61 ± 0.61 mmol·L-1 in WAT). CHO ingestion did not improve performance or affect RPE during a 10-km intermittent training in elite open-water swimmers.

Targeting the extradomain A of fibronectin allows identification of vascular resistance to antiangiogenic therapy in experimental glioma.

INTRODUCTION: Clinical application of antiangiogenic therapy lacks direct visualization of therapy efficacy and vascular resistance. We aimed to establish molecular imaging during treatment with sunitinib using the fibronectin extradomain A specific small immunoprotein(SIP)-F8 in glioma. METHODS: Biodistribution analysis of F8-SIP-Alexa-555 was performed in SF126-glioma bearing or control mice (n = 23 and 7, respectively). Intravital microscopy(IVM) was performed on a microvascular level after 7 days (n = 5 per group) and subsequently after 6 days of sunitinib treatment (n = 4) or without (n = 2).Additionally, near infrared fluorescence(NIRF) imaging was established with F8-SIP-Alexa-750 allowing non-invasive imaging with and without antiangiogenic treatment in orthotopic tumors (n = 38 divided in 4 groups). MRI was used to determine tumor size and served as a reference for NIRF imaging. RESULTS: F8-SIP demonstrated a time and hemodynamic dependent tumor specific accumulation. A significantly higher vascular accumulation occurred with antiangiogenic treatment compared to untreated tumors enabling visualization of resistant tumor vessels by F8-SIP-mediated NIRF imaging. In orthotopic tumors, sunitinib reduced F8-SIP-Alexa-750 enrichment volume but not fluorescence intensity indicative of F8-SIP accumulation in fewer vessels. CONCLUSION: F8-SIP is highly tumor specific with time and hemodynamic dependent biodistribution. The higher vascular accumulation to remaining vessels enables molecular imaging and targeting of therapy resistant tumor vessels.

Effect of combined resistance and endurance exercise training on regional fat loss.

BACKGROUND: The present study tested the possibility of a localized fat mass (FM) reduction by means of training programmes focusing on specific bodily regions. METHODS: Sixteen physically inactive women (age: 31±4; BMI: 27.5±2.1), randomly allocated to two groups, completed an 8 week training programme. In one group (UpBdResist) training sessions consisted of upper body resistance exercises followed by 30-minute cycling at 50%VO2max, while the other group (LwBdResist) performed lower body resistance exercises followed by 30 minutes on an arm-ergometer. Regional body composition was assessed by DEXA and skin fold measures. RESULTS: Regardless of a similar reduction in both groups, UpBdResist training elicited a greater reduction of the upper limbs (UL) FM as compared to the lower limbs (LL) (Δ% UL vs. LL: -12.1±3.4 vs. -4.0±4.7; P=0.02). Conversely, in the LwBdResist group, FM loss was more pronounced in the LL as compared to the UL (Δ% UL vs. LL: -2.3±7.0 vs. -11.5±8.2, P=0.02). Likewise, LwBdResist elicited a larger effect on lean mass (LM) of the LL as compared to UL (Δ% LL vs. UL: +8.4±5.8 vs. -2.7±5.0, P<0.01), yet no differences between upper and lower limb LM changes were detected in UpBdResist group. CONCLUSIONS: The present data suggest that a training programme entailing localized explosive resistance exercise, prior to an endurance exercise bout, may target specific adipose tissue sites eliciting localised fat mass loss in the upper and lower limbs.

Plasma Creatine Kinetics After Ingestion of Microencapsulated Creatine Monohydrate with Enhanced Stability in Aqueous Solutions.

Creatine monohydrate represents one of the largest sports supplement markets. Enhancing creatine (CRE) stability in aqueous solutions, such as with microencapsulation, represents innovation potential. Ten physically active male volunteers were randomly assigned in a double-blind design to either placebo (PLA) (3-g maltodextrin; n = 5) or microencapsulated CRE (3-g creatine monohydrate; n = 5) conditions. Experimental conditions involved ingestion of the samples in a 70-mL ready-to-drink format. CRE was delivered in a novel microencapsulation matrix material consisting entirely of hydrolyzed milk protein. Three hours after ingestion, plasma creatine concentrations were unchanged during PLA, and averaged ∼45 µM. During CRE, plasma creatine concentration peaked after 30 min at 101.6 ± 14.9 µM (p < 0.05), representing a 2.3-fold increase over PLA. Thereafter, plasma creatine concentration gradually trended downwards but remained significantly elevated (∼50% above resting levels) 3 hr after ingestion. These results demonstrate that the microencapsulated form of creatine monohydrate reported herein remains bioavailable when delivered in aqueous conditions, and has potential utility in ready-to-drink formulations for creatine supplementation.

Exercise at lunchtime: effect on glycemic control and oxidative stress in middle-aged men with type 2 diabetes.

PURPOSE: Postprandial hyperglycemia and glycemic oscillations have been associated with increased oxidative stress. We sought to investigate the effect of two walking exercise protocols performed during lunchtime on glycemic control and oxidative stress in type 2 diabetic (T2D) patients. METHODS: Nine T2D patients participated in three randomized crossover trials; a control trial (Con), with participants having a standard lunch followed by their normal daily activities and two exercise trials (ContEx and Splitex). In ContEx, subjects performed 40 min of brisk walking 40 min after lunch, whereas in SplitEx the walking exercise was divided in two 20-min isoenergetic bouts, before and 40 min after meal. 24-h glycemic control was monitored by continuous glucose monitoring. 24-h urinary levels of 8-iso PGF2ɑ were measured as a marker of oxidative stress. RESULTS: SplitEx resulted in less time spent in moderate hyperglycemia after lunch vs ContEx (42.4 ± 38.7% vs 68.2 ± 32.7%, P = 0.04). ContEx reduced hyperglycemic time after breakfast consumed the morning after the exercise session (58.3 ± 29.6 Con vs 40.2 ± 33.4% ContEx, P = 0.02). Compared with Con, 24-h urinary isoprostanes were decreased both in ContEx (-68%, P = 0.02) and SplitEx (-63%, P = 0.04). CONCLUSIONS: Splitting an exercise session into two bouts, pre- and post-lunch, affects mainly the glycemic response to lunch, while a single-continuous isoenergetic session exerts its effect later in the 24-h period. Both exercise modalities effectively attenuate systemic oxidative stress with similar overall benefits.