Exercise increases TCA intermediate concentrations during low-calorie diet independent of insulin resistance among women with obesity.

Tricarboxylic acid cycle intermediates (TCAi) have been proposed to act as myokines that influence energy metabolism. We determined if 2-weeks of low-calorie diet with interval exercise (LCD + INT) would increase TCAi more than a low-calorie diet (LCD). Twenty-three women were randomized to 2-weeks of LCD (n = 12, 48.4 ± 2.5 years, 37.8 ± 1.5 kg/m2, ~1200 kcal/d) or LCD + INT (n = 11, 47.6 ± 4.3 years, 37.9 ± 2.3 kg/m2; 60 min/d supervised INT of 3 min 90% & 50% HRpeak). TCAi and amino acids (AA) were measured at 0 min of a 75 g OGTT, while glucose, insulin, and FFA were obtained at 0, 30, 60, 90, 120, and 180 min to assess total area under the curve (tAUC180min) and insulin resistance (IR; tAUC180min of Glucose × Insulin). Fuel use (indirect calorimetry) was also collected at 0, 60, 120, and 180 min as was fitness (VO2peak) and body composition (BodPod). Treatments reduced weight (p < 0.001), fasting RER (p = 0.01), and IR (p = 0.03), although LCD + INT increased VO2peak (p = 0.02) and maintained RER tAUC180min (p = 0.05) versus LCD. Treatments increased FFA tAUC180min (p = 0.005), cis-aconitate, isocitrate, and succinate (p ≤ 0.02), as well as reduced phenylalanine and tryptophan, cysteine (p ≤ 0.005). However, LCD + INT increased malate, citrate, α-ketoglutarate, and alanine more than LCD (p ≤ 0.04). Thus, INT enhanced LCD effects on some TCAi in women with obesity independent of IR.

Extracellular Vesicles in Metabolic and Vascular Insulin Resistance.

BACKGROUND: Insulin resistance is a major etiological factor in obesity, type 2 diabetes, and cardiovascular disease (CVD). Endothelial dysfunction may precede impairments in insulin-stimulated glucose uptake, thereby making it a key feature in development of CVD. However, the mechanism by which vascular tissue becomes dysfunctional is not clear. SUMMARY: Extracellular vesicles (EVs) have emerged as potential mediators of insulin resistance and vascular dysfunction. EVs are membrane-bound particles released by tissues following cellular stress or activation. They carry "cargo" (e.g., insulin signaling proteins, eNOS-nitric oxide, and miRNA) that are believed to promote inter-cellular and interorgan communications. Herein, we review the underlying physiology of EVs in relation to type 2 diabetes and CVD risk. Specifically, we discuss how EVs may modulate metabolic (e.g., skeletal muscle, liver, and adipose) insulin sensitivity, and propose that EVs may modulate vascular insulin action to influence both endothelial function and arterial stiffness. We lastly identify how EVs may play a unique role following exercise to promote metabolic and vascular insulin sensitivity changes. KEY MESSAGE: Gaining insight toward insulin-mediated EV mechanism has potential to identify novel pathways regulating cardiometabolic health and provide foundation for examining EVs as unique biomarkers and targets to prevent and/or treat chronic diseases.

Impact of Insulin-Induced Relative Hypoglycemia on Vascular Insulin Sensitivity and Central Hemodynamics in Prediabetes.

CONTEXT: Relative hypoglycemia (RH) is linked to sympathetic responses that can alter vascular function in individuals with type 2 diabetes. However, less is known about the role of RH on hemodynamics or metabolic insulin sensitivity in prediabetes. OBJECTIVE: Determine if RH alters peripheral endothelial function or central hemodynamics to a greater extent in those with prediabetes (PD) versus normoglycemia (NG). METHODS: Seventy adults with obesity were classified using ADA criteria as PD (n=34 (28F); HbA1c=6.02±0.1%) or NG (n=36 (30F); HbA1c=5.4±0.0%). Brachial artery endothelial function, skeletal muscle capillary perfusion, and aortic waveforms were assessed at 0 and 120min of a euglycemic clamp (40 mU/m2/min, 90 mg/dl). Plasma nitrate/nitrite and endothelin-1 (ET-1) were measured as surrogates of nitric oxide-mediated vasodilation and vasoconstriction, respectively. RH was defined as the drop in glucose (%) from fasting to clamp steady state. RESULTS: There were no differences in age, weight, or VO2max between groups. PD had higher HbA1c (P<0.01) and a greater drop in glucose in response to insulin (14 vs. 8%; P=0.03). Further, heart rate (HR) increased in NG compared to PD (P<0.01), while forward wave (Pf) decreased in PD (P=0.04). Insulin also tended to reduce arterial stiffness (cfPWV) in NG versus PD (P=0.07), despite similar increases in pre-occlusion diameter (P=0.02), blood flow (P=0.02), and lower augmentation index (AIx75) (P≤0.05). CONCLUSION: Compared with NG, insulin-induced RH corresponded with a blunted rise in HR and drop in Pf during insulin infusion in adults with PD, independent of changes in peripheral endothelial function.

Early chronotype favors appetite and reduced later day caloric intake among adults with obesity.

Late chronotype (LC) is related to obesity and altered food intake throughout the day. But whether appetite perception and gut hormones differ among chronotypes is unclear. Thus, we examined if early chronotype (EC) have different appetite responses in relation to food intake than LC. Adults with obesity were categorized using the Morningness-Eveningness Questionnaire (MEQ) as either EC (n = 21, 18F, MEQ = 63.9 ± 1.0, 53.7 ± 1.2 yr, 36.2 ± 1.1 kg/m2) and LC (n = 28, 24F, MEQ = 47.2 ± 1.5, 55.7 ± 1.4 yr, 37.1 ± 1.0 kg/m2). Visual analog scales were used during a 120 min 75 g oral glucose tolerance test (OGTT) at 30 min intervals to assess appetite perception, as well as glucose, insulin, GLP-1 (glucagon-like polypeptide-1), GIP (glucose-dependent insulinotrophic peptide), PYY (protein tyrosine tyrosine), and acylated ghrelin. Dietary intake (food logs), resting metabolic rate (RMR; indirect calorimetry), aerobic fitness (maximal oxygen consumption (VO2max)), and body composition dual-energy X-ray absorptiometry (DXA) were also assessed. Age, body composition, RMR, and fasting appetite were similar between groups. However, EC had higher satisfaction and fullness as well as reduced desires for sweet, salty, savory, and fatty foods during the OGTT (P <0.05). Only GIP tAUC0-120 min was elevated in EC versus LC (p = 0.01). Daily dietary intake was similar between groups, but EC ate fewer carbohydrates (p = 0.05) and more protein (p = 0.01) at lunch. Further, EC had lower caloric (p = 0.03), protein (p = 0.03) and fat (p = 0.04) intake during afternoon snacking compared to LC. Dietary fat was lower, and carbohydrates was higher, in EC than LC (p = 0.05) at dinner. Low glucose and high insulin as well as GLP-1 tAUC60-120 min related to desires for sweet foods (p < 0.05). Taken together, EC had more favorable appetite and lower caloric intake later in the day compared with LC.

Exercise Training Independent of Intensity Lowers Plasma Bile Acids in Prediabetes.

INTRODUCTION: People with obesity have high circulating bile acids (BA). Although aerobic fitness favors low circulating BAs, the effect of training intensity prior to clinically meaningful weight loss on BA is unclear. Test the hypothesis that 2-wks of interval (INT) versus continuous (CONT) exercise would lower plasma BAs in relation to insulin sensitivity. METHODS: Twenty-three older adults with prediabetes (ADA criteria) were randomized to 12 work-matched bouts of INT (n = 11; 60.3 ± 2.4y; 32.1 ± 1.2 kg/m 2 ) at 3 min at 50% HRpeak and 3 min at 90% HRpeak or CONT (n = 12; 60.8 ± 2.4y; 34.0 ± 1.7 kg/m 2 ) at 70% HRpeak cycling training for 60 min/d over 2 wks. A 180 min 75-g OGTT was performed to assess glucose tolerance (tAUC), insulin sensitivity (Siis) and metabolic flexibility (RER post-prandial - RER fast ; indirect calorimetry). BA (n = 8 conjugated and 7 unconjugated) were analyzed at 0, 30, and 60 min of the OGTT. Anthropometrics and fitness (VO 2 peak) were also assessed. RESULTS: INT and CONT comparably reduced BMI ( P < 0.001) and fasting RER ( P < 0.001), but raised insulin sensitivity ( P = 0.03). INT increased VO 2 peak as compared to CONT ( P = 0.01). Exercise decreased the unconjugated BAs CDCA iAUC 60min ( P < 0.001), DCA iAUC 60min ( P < 0.001), LCA iAUC 60min ( P < 0.001), and GCDCA iAUC 60min ( P < 0.001). Comparable reductions were also seen in the conjugated BAs HDCA iAUC 60min ( P = 0.01) and TLCA iAUC 60min ( P = 0.007). Increased VO 2 peak associated with lowered UDCA 0min (r = -0.56, P = 0.02) and CA iAUC 60min (r = -0.60, P = 0.005), while reduced BMI related to higher GDCA 0min (r = 0.60, P = 0.005) and GCDCA 0min (r = 0.53, P = 0.01). Improved insulin sensitivity correlated with lower GCDCA iAUC 60min (r = -0.45, P = 0.03) and GDCA iAUC 60min (r = -0.48, P = 0.02), while increased metabolic flexibility related to DCA iAUC 60min (r = 0.64, P = 0.004) and GCDCA iAUC 60min (r = 0.43, P = 0.05). CONCLUSIONS: Short-term training lowers some BA in relation to insulin sensitivity independent of intensity.

Intermediate versus morning chronotype has lower vascular insulin sensitivity in adults with obesity.

AIM: Chronotype reflects a circadian rhythmicity that regulates endothelial function. While the morning chronotype (MORN) usually has low cardiovascular disease risk, no study has examined insulin action on endothelial function between chronotypes. We hypothesized intermediate chronotypes (INT) would have lower vascular insulin sensitivity than morning chronotype (MORN). MATERIALS AND METHODS: Adults with obesity were classified per Morningness-Eveningness Questionnaire (MEQ) as either MORN (n = 27, 22 female, MEQ = 63.7 ± 4.7, 53.8 ± 6.7 years, 35.3 ± 4.9 kg/m2) or INT (n = 29, 23 female, MEQ = 48.8 ± 6.7, 56.6 ± 9.0 years, 35.7 ± 6.1 kg/m2). A 120 min euglycaemic-hyperinsulinaemic clamp (40 mU/m2/min, 90 mg/dl) was conducted to assess macrovascular insulin sensitivity via brachial artery flow-mediated dilation (%FMD; conduit artery), post-ischaemic flow velocity (resistance arteriole), as well as microvascular insulin sensitivity via contrast-enhanced ultrasound [e.g. microvascular blood volume (perfusion)]. Fasting plasma arginine and citrulline, as well as fasting and clamp-derived plasma endothelin-1 and nitrate/nitrite, were assessed as surrogates of vasoconstriction and nitric oxide-mediated vasodilation. Aerobic fitness (VO2max) and body composition (dual-energy X-ray absorptiometry) were also collected. RESULTS: MORN had a higher VO2max compared with INT (p < .01), although there was no difference in fat mass. While fasting FMD was similar between groups, insulin lowered FMD corrected to shear stress and microvascular blood volume in INT compared with MORN after co-varying for VO2max (both p ≤ .02). INT also had a lower fasting nitrate (p = .03) and arginine (p = .07). Higher MEQ correlated with elevated FMD (r = 0.33, p = .03) and lower post-ischaemic flow velocity (r = -0.33, p = .03) as well as shear rate (r = -0.36, p = .02) at 120 min. CONCLUSION: When measured during the morning, INT had a lower vascular insulin sensitivity than MORN. Additional work is needed to understand endothelial function differences among chronotypes to optimize cardiovascular disease risk reduction.

Cardiorespiratory fitness and submaximal exercise dynamics in normal-weight obesity and metabolically healthy obesity.

PURPOSE: Cardiorespiratory fitness (CRF) is critical for cardiovascular health. Normal-weight obesity (NWO) and metabolically healthy obesity (MHO) may be at increased risk for cardiovascular disease, but a comparison of CRF and submaximal exercise dynamics against rigorously defined low- and high-risk groups is lacking. METHODS: Four groups (N = 40; 10/group) based on body mass index (BMI), body fat %, and metabolic syndrome (MetS) risk factors were recruited: healthy controls (CON; BMI 18.5-24.9 kg/m2, body fat < 25% [M] or < 35% [F], 0-1 risk factors), NWO (BMI 18.5-24.9 kg/m2, body fat ≥ 25% [M] or ≥ 35% [F]), MHO (BMI > 30 kg/m2, body fat ≥ 25% [M] or ≥ 35% [F], 0-1 risk factors), or metabolically unhealthy obesity (MUO; BMI > 30 kg/m2, body fat ≥ 25% [M] or ≥ 35% [F], 2 + risk factors). All participants completed a V ˙ O2peak test on a cycle ergometer. RESULTS: V ˙ O2peak was similarly low in NWO (27.0 ± 4.8 mL/kg/min), MHO (25.4 ± 6.7 mL/kg/min) and MUO (24.6 ± 10.0 mL/kg/min) relative to CON (44.2 ± 11.0 mL/kg/min) when normalized to total body mass (p's < 0.01), and adjusting for fat mass or lean mass did not alter these results. This same differential V ˙ O2 pattern was apparent beginning at 25% of the exercise test (PGroup*Time < 0.01). CONCLUSIONS: NWO and MHO had similar peak and submaximal CRF to MUO, despite some favorable health traits. Our work adds clarity to the notion that excess adiposity hinders CRF across BMI categories. CLINICALTRIALS: gov registration: NCT05008952.

Examining the efficacy of a cardio-dance intervention on brain health and the moderating role of ABCA7 in older African Americans: a protocol for a randomized controlled trial.

Introduction: African Americans are two to three times more likely to be diagnosed with Alzheimer's disease (AD) compared to White Americans. Exercise is a lifestyle behavior associated with neuroprotection and decreased AD risk, although most African Americans, especially older adults, perform less than the recommended 150 min/week of moderate-to-vigorous intensity exercise. This article describes the protocol for a Phase III randomized controlled trial that will examine the effects of cardio-dance aerobic exercise on novel AD cognitive and neural markers of hippocampal-dependent function (Aims #1 and #2) and whether exercise-induced neuroprotective benefits may be modulated by an AD genetic risk factor, ABCA7 rs3764650 (Aim #3). We will also explore the effects of exercise on blood-based biomarkers for AD. Methods and analysis: This 6-month trial will include 280 African Americans (≥ 60 years), who will be randomly assigned to 3 days/week of either: (1) a moderate-to-vigorous cardio-dance fitness condition or (2) a low-intensity strength, flexibility, and balance condition for 60 min/session. Participants will complete health and behavioral surveys, neuropsychological testing, saliva and venipuncture, aerobic fitness, anthropometrics and resting-state structural and functional neuroimaging at study entry and 6 months. Discussion: Results from this investigation will inform future exercise trials and the development of prescribed interventions that aim to reduce the risk of AD in African Americans.

ß-Aminoisobutyric Acid Relates to Favorable Glucose Metabolism through Adiponectin in Adults with Obesity Independent of Prediabetes.

ß-Aminoisobutyric acid (BAIBA) is secreted by skeletal muscle and promotes insulin sensitivity, fat oxidation, and anti-inflammation. While BAIBA is purportedly lower in individuals with obesity, no work has examined if prediabetes (PD) differentially impacts BAIBA concentrations in people with obesity. Methods. Adults were classified as normal glucose tolerant (NGT; n = 22 (20F); 48.0 ± 2.4 yrs; 36.9 ± 1.2 kg/m2) or PD (n = 23 (18F); 54.2 ± 1.6 yrs; 38.4 ± 1.2 kg/m2) based on ADA criteria. A 180-minute 75 g OGTT was used to estimate fasting (HOMA-IR (liver)) and postprandial (Matsuda index (muscle)) insulin sensitivity as well as ß-cell function (disposition index (DI), glucose-stimulated insulin secretion adjusted for insulin sensitivity). Body composition and fasting measures of BAIBA, fat oxidation (indirect calorimetry), and adipokines were determined. Results. NGT and PD had similar BAIBA concentrations (1.4 ± 0.1 vs. 1.2 ± 0.1 µM, P = 0.23) and fat oxidation (P = 0.31), despite NGT having lower fasting (92.2 ± 1.2 vs. 104.1 ± 3.2 mg/dL, P = 0.002) and tAUC180min glucose (P < 0.001) compared to PD. Moreover, NGT had higher postprandial insulin sensitivity (P = 0.01) and higher total phase DIliver (P = 0.003) and DImuscle (P = 0.001). Increased BAIBA was associated with adiponectin (r = 0.37, P = 0.02), adiponectin/leptin ratio (r = 0.39, P = 0.01), and lower glucose and insulin at 180 minutes (r = -0.31, P = 0.03 and r = -0.39, P = 0.03, respectively). Adiponectin also correlated with lower glucose at 180 minutes (r = -0.45, P = 0.005), and mediation analysis showed that BAIBA was no longer a significant predictor of glucose at 180 minutes after controlling for adiponectin (P = 0.08). Conclusion. While BAIBA did not differ between NGT and PD, higher BAIBA is related to favorable glucose metabolism, possibly through an adiponectin-related mechanism. Additional work is required to understand how exercise and/or diet impact BAIBA in relation to type 2 diabetes risk.

Obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer's disease risk allele.

Introduction: Excess body weight and Alzheimer's disease (AD) disproportionately affect older African Americans. While mid-life obesity increases risk for AD, few data exist on the relationship between late-life obesity and AD, or how obesity-based and genetic risk for AD interact. Although the APOE-ε4 allele confers a strong genetic risk for AD, it is unclear if late-life obesity poses a greater risk for APOE-ε4 carriers compared to non-carriers. Here we assessed: (1) the influence of body mass index (BMI) (normal; overweight; class 1 obese; ≥ class 2 obese) on cognitive and structural MRI measures of AD risk; and (2) the interaction between BMI and APOE-ε4 in older African Americans. Methods: Seventy cognitively normal older African American participants (Mage = 69.50 years; MBMI = 31.01 kg/m2; 39% APOE-ε4 allele carriers; 86% female) completed anthropometric measurements, physical assessments, saliva collection for APOE-ε4 genotyping, cognitive testing, health and lifestyle questionnaires, and structural neuroimaging [volume/surface area (SA) for medial temporal lobe subregions and hippocampal subfields]. Covariates included age, sex, education, literacy, depressive symptomology, and estimated aerobic fitness. Results: Using ANCOVAs, we observed that individuals who were overweight demonstrated better hippocampal cognitive function (generalization of learning: a sensitive marker of preclinical AD) than individuals with normal BMI, p = 0.016, ηp2 = 0.18. However, individuals in the obese categories who were APOE-ε4 non-carriers had larger hippocampal subfield cornu Ammonis region 1 (CA1) volumes, while those who were APOE-ε4 carriers had smaller CA1 volumes, p = 0.003, ηp2 = 0.23. Discussion: Thus, being overweight by BMI standards may preserve hippocampal function, but obesity reduces hippocampal structure and function in older African Americans with the APOE-ε4 Alzheimer's disease risk allele.

Exercise blood pressure and heart rate responses to graded exercise testing in intermediate versus morning chronotypes with obesity.

Exaggerated exercise blood pressure (BP) is linked to cardiovascular disease (CVD). Although evening chronotypes have greater CVD risk than morning (Morn) types, it is unknown if exercise BP differs in intermediate (Int) types. Adults with obesity were classified as either Morn [n = 23 (18 females), Morning-Eveningness Questionnaire (MEQ) = 63.96 ± 1.0, 54.74 ± 1.4 yr, 33.7 ± 0.6 kg/m2] or Int [n = 23 (19 females), MEQ = 51.36 ± 1.1, 55.96 ± 1.8 yr, 37.2 ± 1.2 kg/m2] chronotype per MEQ. A graded, incremental treadmill test to maximal aerobic capacity (V̇o2max) was conducted. Systolic (SBP) and diastolic (DBP) blood pressure and mean arterial pressure (MAP), rate pressure product (RPP), heart rate (HR), and rate of perceived intensity (RPE) were determined at baseline, 4 min, 6 min, and maximal stages. HR recovery (HRR; maximum postexercise) was determined at 1 and 2 min postexercise. Preexercise fasted aortic waveforms (applanation tonometry), plasma leptin, nitrate/nitrite (nitric oxide bioavailability), and body composition (dual X-ray, DXA) were also collected. Int had lower V̇o2max and plasma nitrate (both P ≤ 0.02) than Morn. No difference in preexercise BP, aortic waveforms, or body composition were noted between groups, although higher plasma leptin was seen in Int compared with Morn (P = 0.04). Although Int had higher brachial DBP and MAP across exercise stages (both P ≤ 0.05) and higher HR, RPE, and RPP at 6 min of exercise (all P ≤ 0.05), covarying for V̇o2max nullified the BP, but not HR or RPE, difference. HRR was greater in Morn independent of V̇o2max (P = 0.046). Fasted leptin correlated with HR at exercise stage 4 (r = 0.421, P = 0.041) and 6 min (r = 0.593, P = 0.002). This observational study suggests that Int has exaggerated BP and HR responses to exercise compared with Morn, although fitness abolished BP differences.NEW & NOTEWORTHY This study compares blood pressure and heart rate responses with graded, incremental exercise between morning and intermediate chronotype adults with obesity. Herein, blood pressure responses to exercise were elevated in intermediate compared with morning chronotype, although V̇o2max abolished this observation. However, heart rate responses to exercise were higher in intermediate vs. morning chronotypes independent of fitness. Collectively, this exercise hemodynamic response among intermediate chronotype may be related to reduced aerobic fitness, altered nitric oxide metabolism, and/or elevated aortic waveforms.

Tracking Biomarker Responses to Exercise in Hypertension.

PURPOSE OF REVIEW: Strong evidence is evolving that physical exercise prevents hypertension and reduces blood pressure in patients with pre- and manifest HTN. Yet, identifying and confirming the effectiveness of exercise are challenging. Herein, we discuss conventional and novel biomarkers such as extracellular vesicles (EVs) which may track responses to HTN before and after exercise. RECENT FINDINGS: Evolving data shows that improved aerobic fitness and vascular function as well as lowered oxidative stress, inflammation, and gluco-lipid toxicity are leading biomarkers considered to promote HTN, but they explain only about a half of the pathophysiology. Novel biomarkers such as EVs or microRNA are providing additional input to understand the complex mechanisms involved in exercise therapy for HTN patients. Conventional and novel biomarkers are needed to fully understand the integrative "cross-talk" between tissues to regulate vasculature physiology for blood pressure control. These biomarker studies will lead to more specific disease markers and the development of even more personalized therapy in this field. However, more systematic approaches and randomized controlled trials in larger cohorts are needed to assess exercise effectiveness across the day and with different exercise types.

ß-Cell function during a high-fat meal in young versus old adults: role of exercise.

The acute effect of exercise on ß-cell function during a high-fat meal (HFM) in young adults (YA) versus old adults (OA) is unclear. In this randomized crossover trial, YA (n = 5 M/7 F, 23.3 ± 3.9 yr) and OA (n = 8 M/4 F, 67.7 ± 6.0 yr) underwent a 180-min HFM (12 kcal/kg body wt; 57% fat, 37% CHO) after a rest or exercise [∼65% heart rate peak (HRpeak)] condition ∼12 h earlier. After an overnight fast, plasma lipids, glucose, insulin, and free fatty acid (FFA) were determined to estimate peripheral, or skeletal muscle, insulin sensitivity (Matsuda index) as well as hepatic [homeostatic model assessment of insulin resistance (HOMA-IR)] and adipose insulin resistance (adipose-IR). ß-Cell function was derived from C-peptide and defined as early-phase (0-30 min) and total-phase (0-180 min) disposition index [DI, glucose-stimulated insulin secretion (GSIS) adjusted for insulin sensitivity/resistance]. Hepatic insulin extraction (HIE), body composition [dual-energy X-ray absorptiometry (DXA)], and peak oxygen consumption (V̇o2peak) were also assessed. OA had higher total cholesterol (TC), LDL, HIE, and DI across organs as well as lower adipose-IR (all, P < 0.05) and V̇o2peak (P = 0.056) despite similar body composition and glucose tolerance. Exercise lowered early-phase TC and LDL in OA versus YA (P < 0.05). However, C-peptide area under the curve (AUC), total phase GSIS, and adipose-IR were reduced postexercise in YA versus OA (P < 0.05). Skeletal muscle DI increased in YA and OA after exercise (P < 0.05), whereas adipose DI tended to decline in OA (P = 0.06 and P = 0.08). Exercise-induced skeletal muscle insulin sensitivity (r = -0.44, P = 0.02) and total-phase DI (r = -0.65, P = 0.005) correlated with reduced glucose AUC180min. Together, exercise improved skeletal muscle insulin sensitivity/DI in relation to glucose tolerance in YA and OA, but only raised adipose-IR and reduced adipose-DI in OA.NEW & NOTEWORTHY High-fat diets may induce ß-cell dysfunction. This study compared how young and older adults responded to a high-fat meal with regard to ß-cell function and whether exercise comparably impacted glucose regulation. Older adults secreted more insulin during the high-fat meal than younger adults. Although exercise increased ß-cell function adjusted for skeletal muscle insulin sensitivity in relation to glucose tolerance, it raised adipose insulin resistance and reduced pancreatic ß-cell function relative to adipose tissue in older adults. Additional work is needed to discern nutrient-exercise interactions across age to mitigate chronic disease risk.

A low-calorie diet raises ß-aminoisobutyric acid in relation to glucose regulation and leptin independent of exercise in women with obesity.

Introduction: ß-aminoisobutyric acid (BAIBA) is a suggested cytokine secreted from skeletal muscles that regulates insulin sensitivity, pancreatic function, and fat oxidation. However, no studies to date have examined if a low-calorie diet (LCD) or LCD + with interval exercise (LCD + INT) differentially raises BAIBA. The purpose was to examine if LCD or LCD + INT raises circulating BAIBA in relation to cardiometabolic health. Methods: For this, twenty-three women with obesity were randomized to either 2-weeks of LCD (n = 12, 48.4 ± 2.5 y, 37.84 ± 1.5 kg/m2; ∼1200 kcal/day) or LCD + INT (n = 11, 47.6 ± 4.3 y, 37.9 ± 2.3 kg/m2; ∼60 min/d of INT alternating 3 min of 90% and 50% HRpeak), with matched energy availability. Fasting BAIBA and adipokines along with glucose, insulin, C-peptide, and FFA after every 30 min up to 120 min were obtained during a 75 g OGTT to estimate total area under the curve (tAUC), insulin sensitivity (SIIS), pancreatic function [disposition index (DI)], and hepatic insulin clearance (HIC). Fuel use (indirect calorimetry) was tested at 0, 60, and 120 min of the OGTT along with fitness (VO2peak) and body composition (BodPod). Results: Both treatments lowered body weight (p < 0.001) and leptin (p < 0.001) but raised BAIBA (p = 0.007) and insulin sensitivity (p = 0.02). LCD + INT increased VO2peak (p = 0.02) and REE tAUC120min (p = 0.02) while LCD and LCD + INT decreased carbohydrate oxidation (CHOox) tAUC120min (p < 0.001). Increased BAIBA associated with reduced weight (r = -0.67, p < 0.001), leptin (r = -0.66, p = 0.001), CHOox tAUC120min (r = -0.44, p = 0.03) and DImuscle120min (r = -0.45, p = 0.03), but elevated HIC120min (r = 0.47, p = 0.02). Discussion: Concluding, LCD and LCD + INT increased BAIBA in relation to reduced body weight and pancreatic function in women with obesity. This suggests energy deficit is a key factor regulating circulating BAIBA.

Personalized versus generic digital weight loss interventions delivered on university campuses: a 6-month cost-benefit analysis.

Cost-effectiveness analyses of weight loss programs for university students can inform administrator decision-making. This study quantifies and compares the costs and cost-effectiveness of implementing two digitally-delivered weight loss interventions designed for university populations. Healthy Body Healthy U (HBHU) was a randomized controlled trial comparing TAILORED (personalized) versus TARGETED (generic) weight loss interventions adapted specifically for young adults to a CONTROL intervention. Participants (N = 459; 23.3 ± 4.4 years; mean BMI 31.2 ± 4.4 kg/m2) were recruited from two universities. Implementation costs were examined from a payer (i.e., university) perspective, comparing both the average cost effectiveness ratio (ACER) and the incremental cost effectiveness ratio (ICER) of the two interventions. Cost-effectiveness measures were calculated for changes in body weight, abdominal circumference, HDL cholesterol, systolic and diastolic blood pressure, and HbA1c. The overall 6-month implementation costs were $105.66 per person for the TAILORED intervention and $91.44 per person for the TARGETED intervention. The ACER for weight change was $107.82 for the TAILORED and $179.29 for the TARGETED interventions. The ICER comparing TAILORED with TARGETED for change in body weight was $5.05, and was even lower ($2.28) when including only those with overweight and not obesity. The ICERs for change in abdominal circumference, HDL cholesterol, systolic and diastolic blood pressure, and HbA1c were $3.49, $59.37, $1.57, $2.64, and $47.49, respectively. The TAILORED intervention was generally more cost-effective compared with the TARGETED intervention, particularly among those with overweight. Young adults with obesity may require more resource-intensive precision-based approaches.

Knowledge about the cost-effectiveness of weight loss programs for university students is needed to inform administrator decision-making regarding whether to provide such programming. This study examined the cost-effectiveness of two digitally-delivered weight loss interventions (i.e., TAILORED and TARGETED) designed for university students. The TAILORED intervention included information tailored to the individual, while the TARGETED intervention included only generic weight loss information. At 6 months, the average cost per kilogram of weight loss was $107.82 for TAILORED participants and $179.29 for TARGETED participants. The TAILORED intervention was generally more cost-effective compared with the TARGETED intervention.

Impact of Caloric Restriction and Exercise on Trimethylamine N-Oxide Metabolism in Women with Obesity.

Trimethylamine N-oxide (TMAO) is linked to cardiovascular disease (CVD) through partly altered central hemodynamics. We sought to examine if a low-calorie diet plus interval exercise (LCD+INT) intervention reduces TMAO more than a low-calorie diet (LCD) program alone in relation to hemodynamics, prior to clinically meaningful weight loss. Women with obesity were randomized to 2 weeks of LCD (n = 12, ~1200 kcal/d) or LCD+INT (n = 11; 60 min/d, 3 min at 90% and 50% HRpeak, respectively). A 180 min 75 g OGTT was performed to assess fasting TMAO and precursors (carnitine, choline, betaine, and trimethylamine (TMA)) as well as insulin sensitivity. Pulse wave analysis (applanation tonometry) including augmentation index (AIx75), pulse pressure amplification (PPA), forward (Pf) and backward pressure (Pb) waveforms, and reflection magnitude (RM) at 0, 60, 120, and 180 min was also analyzed. LCD and LCD+INT comparably reduced weight (p < 0.01), fasting glucose (p = 0.05), insulin tAUC180min (p < 0.01), choline (p < 0.01), and Pf (p = 0.04). Only LCD+INT increased VO2peak (p = 0.03). Despite no overall treatment effect, a high baseline TMAO was associated with decreased TMAO (r = -0.45, p = 0.03). Reduced TMAO was related to increased fasting PPA (r = -0.48, p = 0.03). Lowered TMA and carnitine correlated with higher fasting RM (r = -0.64 and r = -0.59, both p < 0.01) and reduced 120 min Pf (both, r = 0.68, p < 0.01). Overall, treatments did not lower TMAO. Yet, people with high TMAO pre-treatment reduced TMAO after LCD, with and without INT, in relation to aortic waveforms.

Getting Into Light Exercise (GENTLE-HF) for Patients With Heart Failure: the Design and Methodology of a Live-Video Group Exercise Study.

OBJECTIVE: Newer therapies have increased heart failure (HF) survival rates, but these therapies are rarely curative. The consequence of increased longevity is the likelihood that patients with HF will experience higher symptom burdens over time. Exercise such as cardiac rehabilitation programs can palliate symptom burdens, but numerous barriers prevent exercise participation and adherence. Small pilot studies indicate short-term beneficial effects of gentle forms of exercise such as yoga to address symptom burdens and accommodate comorbidities. Long-term symptom benefit and adherence to yoga are currently unknown. Therefore, a novel a home-based, gentle-stretching intervention that addresses issues of exercise access and adherence is described in this article. PURPOSE: The purpose of this article is to describe the background, design and study methodology of the Getting Into Light Exercise for HF (GENTLE-HF) randomized controlled trial. Gentle-HF will test a gentle stretching and education intervention compared to an education control group concerning symptom burden (dyspnea, exercise, activity adherence, depression, and anxiety) and quality of life. As an exploratory aim, we also will determine whether rurality moderates the relationships between exercise participation and symptom burden as a measure of health equity. METHODS: We designed a randomized controlled trial study (n = 234) with 2 arms: a gentle stretching intervention arm with HF education and an HF education-only control. Participants will be recruited from U.S. cardiology clinics in the mid-Atlantic and the San Francisco Bay areas. This recruitment strategy will include individuals from urban, suburban and rural areas and individuals that have diverse racial and ethnic backgrounds. All participants will be provided with an iPad set up to access HF educational topics, and the intervention arm will have both educational and gentle-stretching class links. Both arms will access the HF health education icons on their iPads weekly; they correspond to the 6 months (26 weeks) of study participation. Symptom burden (dyspnea, fatigue, exercise intolerance, depression, anxiety) and quality of life will be measured at the study's start and completion. Study adherence will be measured by using attendance rates and number of class minutes attended. RESULTS: The GENTLE-HF study is a randomized study that will test the effect of a home-based, video-conference-delivered gentle stretching and HF education intervention designed for patients with HF. The findings will inform whether gentle stretching can decrease symptom burden and potentially provide access to symptom palliation for a diverse population of patients with HF.

Relation of Aortic Waveforms with Gut Hormones following Continuous and Interval Exercise among Older Adults with Prediabetes.

Prediabetes raises cardiovascular disease risk, in part through elevated aortic waveforms. While insulin is a vasodilatory hormone, the gut hormone relation to aortic waveforms is less clear. We hypothesized that exercise, independent of intensity, would favor aortic waveforms in relation to gut hormones. Older adults (61.3 ± 1.5 yr; 33.2 ± 1.1 kg/m2) with prediabetes (ADA criteria) were randomized to undertake 60 min of work-matched continuous (CONT, n = 14) or interval (INT, n = 14) exercise for 2 wks. During a 180 min 75-g OGTT, a number of aortic waveforms (applanation tonometry) were assessed: the augmentation pressure (AP) and index (AIx75), brachial (bBP) and central blood pressure (cBP), pulse pressure (bPP and cPP), pulse pressure amplification (PPA), and forward (Pf) and backward pressure (Pb) waveforms. Acylated-ghrelin (AG), des-acylated ghrelin (dAG), GIP, and GLP-1active were measured, and correlations were co-varied for insulin. Independent of intensity, exercise increased VO2peak (p = 0.01) and PPA120min (p = 0.01) and reduced weight (p < 0.01), as well as AP120min (p = 0.02) and AIx75120min (p < 0.01). CONT lowered bSBP (p < 0.02) and bDBP (p < 0.02) tAUC180min more than INT. There were decreases dAG0min related to Pb120min (r = 0.47, p = 0.03), cPP120min (r = 0.48, p = 0.02), and AP120min (r = 0.46, p = 0.02). Declines in AG tAUC60min correlated with lower Pb120min (r = 0.47, p = 0.03) and cPP120min (r = 0.49, p = 0.02) were also found. GLP-1active 0min was reduced associated with lowered AP180min (r = 0.49, p = 0.02). Thus, while CONT exercise favored blood pressure, both intensities of exercise improved aortic waveforms in relation to gut hormones after controlling for insulin.