Effect of Icosapent Ethyl on Gynoid Fat and Bone Mineral Health in the Metabolic Syndrome: A Preliminary Report.

PURPOSE: The metabolic syndrome (MetS) is a systemic disorder associated with reduced atheroprotective gynoid fat and bone mineral content (BMC). The goal of this pilot study was to assess whether administration of icosapent ethyl (IPE), a purified formulation of eicosapentaenoic acid, would maintain gynoid fat and BMC over a 9-month treatment period. METHODS: Patients with MetS aged ≥40 years were randomly assigned to receive 4 g daily of IPE (2 g BID with food) or placebo (paraffin oil 2 g BID with food) for 9 months. Data were collected at baseline and 9 months later. The data included anthropometric measures, biochemical analysis, and whole body fat mass, including gynoid fat. Bone mineral density and BMC were measured by using dual-energy X-ray absorptiometry. A two-tailed P value ≤ 0.05 was considered statistically significant. FINDINGS: The study sample consisted of 13 patients with MetS (mean age, 61.6 years; age range, 44-77 years; 77% female and 23% male). Compared with the IPE group, the placebo group experienced statistically significant mean reductions in percent gynoid fat (pre/post, 46.8%-43.5%; P = 0.02), BMC (pre/post, 2461 g-2423 g; P = 0.02), and bone mineral density (pre/post, 1.24 g/cm2 to 1.22 g/cm2; P = 0.05) over the 9-month study period. IMPLICATIONS: The results of this pilot study raise the possibility that IPE supplementation may preserve gynoid fat distribution and bone mineral health in patients with MetS. Larger, randomized longitudinal studies are necessary to determine the potential long-term metabolic benefits of IPE treatment.

Asymptomatic carotid stenosis is associated with mobility and cognitive dysfunction and heightens falls in older adults.

BACKGROUND: Atherosclerosis of the carotid bifurcation with plaque formation causes asymptomatic carotid artery stenosis (ACAS), which may also be associated with cerebral hypoperfusion. Cerebral hypoperfusion adversely affects multiple aspects of mobility and cognition. This study tests the hypothesis that community-dwelling older adults with a 50% or greater diameter-reducing ACAS will have mobility and cognitive impairments that heighten their risk for falls. METHODS: Eighty community-dwelling adults completed a mobility assessment (Short Physical Performance Battery, Berg Balance Scale, Four Square Step Test, Dynamic Gait Index, Timed Up and Go, and gait speed), self-reported physical function (Activities-Specific Balance Confidence, SF-12 Physical Function Component), and cognitive tests (Mini-Mental State Examination). Falls were recorded for the past 6 months. Standardized carotid ultrasound examination classified participants into no stenosis (<50% diameter reduction) (n = 54), moderate stenosis (50%-69%) (n = 17), and high-grade stenosis (70%-99%) (n = 9) groups. Linear and logistic regression analyses determined the associations between these measures and the degree of stenosis (three groups). RESULTS: Logistic regression analysis showed their degree of stenosis was associated with reductions in mobility (Short Physical Performance Battery [P = .008], Berg Balance Scale [P = .0008], Four Square Step Test [P = .005], DGI [P = .0001], TUG [P = .0004], gait speed [P = .02]), perceived physical function (ABC [P < .0001], SF-12 Physical Function Component [P < .0001]), and cognition (MMSE [P = .003]). Adults with moderate- and high-grade stenosis had a greater incidence of falls compared with those without stenosis (relative risk, 2.86; P = .01). Results remained unchanged after adjustment for age, sex and cardiovascular risk factors. CONCLUSIONS: ACAS is associated with impaired mobility and cognition that are accompanied with increased fall risk. These impairments increased with worsening severity.

A multimodal rehabilitation program for patients with ICU acquired weakness improves ventilator weaning and discharge home.

PURPOSE: To compare the effects of adding a progressive multimodal rehabilitation program to usual care (MRP + UC) versus UC alone on 1) functional mobility, strength, endurance and 2) ventilator weaning and discharge status of patients with ICU-acquired weakness (ICUAW) receiving prolonged mechanical ventilation (PMV). METHODS: Randomized pilot trial of an individualized MRP + UC versus UC in middle-aged and older ICU survivors with ICUAW receiving PMV. Outcomes compare changes in strength, mobility, weaning success and discharge home from a long-term acute care hospital (LTACH) between the groups. RESULTS: Eighteen males and 14 females (age 60.3 ±â€¯11.9 years) who received PMV for ≥14 days were enrolled. Despite no significant differences between groups in the changes in handgrip, gait speed, short physical performance battery or 6-min walk distance after treatment, the MRP + UC group had greater weaning success (87% vs. 41%, p < 0.01), and more patients discharged home than UC (53 vs. 12%, p = 0.05). Post hoc analyses, combining patients based on successful weaning or discharge home, demonstrated significant improvements in strength, ambulation and mobility. CONCLUSION: The addition of an MRP that improves strength, physical function and mobility to usual physical therapy in LTACH patients with ICUAW is associated with greater weaning success and discharge home than UC alone.

Resistance training reduces inflammation and fatigue and improves physical function in older breast cancer survivors.

OBJECTIVE: Resistance training (RT) reduces fatigue and improves physical function and quality of life (QOL) in breast cancer survivors (BCS). This may be related to reductions in systemic and tissue-specific inflammation. This pilot study examines the hypothesis that RT induces changes in systemic and tissue-specific inflammation that contribute to improvements in physical and behavioral function in postmenopausal BCS. METHODS: Eleven BCS (60 ±â€Š2 years old, body mass index 30 ±â€Š1 kg/m, mean ±â€ŠSEM) underwent assessments of fatigue (Piper Fatigue Scale), physical function, QOL (SF-36), glucose and lipid metabolism, and systemic, skeletal muscle, and adipose tissue inflammation (n = 9) before and after 16 weeks of moderate-intensity whole-body RT. RESULTS: Muscle strength improved by 25% to 30% (P < 0.01), QOL by 10% (P = 0.04), chair stand time by 15% (P = 0.01), 6-minute walk distance by 4% (P = 0.03), and fatigue decreased by 58% (P < 0.01), fasting insulin by 18% (P = 0.04), and diastolic and systolic blood pressure by approximately 5% (P = 0.04) after RT. BCS with the worst fatigue and QOL demonstrated the greatest improvements (absolute change vs baseline: fatigue: r = -0.95, P < 0.01; QOL: r = -0.82, P < 0.01). RT was associated with an approximately 25% to 35% relative reduction in plasma and adipose tissue protein levels of proinflammatory interleukin (IL)-6sR, serum amyloid A, and tumor necrosis factor-α, and 75% relative increase in muscle pro-proliferative, angiogenic IL-8 protein content by 75% (all P < 0.05). BCS with the highest baseline proinflammatory cytokine levels had the greatest absolute reductions, and the change in muscle IL-8 correlated directly with improvements in leg press strength (r = 0.53, P = 0.04). CONCLUSIONS: These preliminary results suggest that a progressive RT program effectively lowers plasma and tissue-specific inflammation, and that these changes are associated with reductions in fatigue and improved physical and behavioral function in postmenopausal BCS.

Clinical relevance of the modified physical performance test versus the short physical performance battery for detecting mobility impairments in older men with peripheral arterial disease.

PURPOSE: The study is to compare the Modified Physical Performance Test (MPPT) and Short Physical Performance Battery (SPPB) as metrics of mobility and function in older men with peripheral arterial disease (PAD). MATERIALS AND METHODS: A total of 51 men (55-87 years) with PAD underwent functional testing including the SPPB, MPPT, Walking Impairment Questionnaire (WIQ), stair ascent, and 6-min walk distance. Individuals were grouped according to SPPB and MPPT scores as not limited on either, limited only on the MPPT, or limited on both. RESULTS: The MPPT identified a higher proportion of patients as being functionally limited than the SPPB (p < 0.001). Men identified as limited only by the MPPT, and not the SPPB, were subsequently confirmed to have lower function on all measures compared to those not identified as limited by either the SPPB or the MPPT (p < 0.02). CONCLUSIONS: These findings suggest the MPPT is an appropriate measure to identify early declines in men with PAD and may identify global disability better than SPPB. Implications for rehabilitation Individuals with peripheral arterial disease have low activity levels and are at risk for a loss of independence and global disability. Early detection of decline in mobility and global function would allow for interventions before large changes in ambulatory ability or a loss of functional independence occur. This study shows the Modified Physical Performance Test may be an appropriate test to identify early decline in function in men with peripheral arterial disease.

Metabolic Benefits of Prior Weight Loss with and without Exercise on Subsequent 6-Month Weight Regain.

OBJECTIVE: To determine the 6-month follow-up effects after intentional 6-month weight loss alone (WL) and after weight loss with aerobic exercise (AEX + WL) on body composition, glucose metabolism, and cardiovascular disease risk factors in older postmenopausal women and to identify the mechanisms for weight regain. METHODS: Women (n = 65, BMI > 25 kg/m2 ) underwent maximal oxygen consumption testing, dual-energy x-ray absorptiometry, computed tomography scans, and oral glucose tolerance tests before and after 6 months of AEX + WL or WL and at 12 months ad libitum follow-up. Insulin sensitivity (M) (hyperinsulinemic-euglycemic clamp) was measured at baseline and 6 months. Thirty WL and thirty-five AEX + WL women completed a follow-up at 12 months. RESULTS: Similar weight loss was observed (-8%) in both groups from 0 to 6 months. Total fat mass, fat-free mass, visceral fat area, subcutaneous abdominal and midthigh fat areas, fasting glucose, insulin levels, homeostatic model assessment of insulin resistance (HOMA-IR), insulin areas under the curve, and triglyceride levels decreased similarly after WL and AEX + WL and remained lower at 12 months than at baseline, despite weight regain at 12 months. Initial M was associated with weight regain (r = -0.40, P < 0.01). Weight regain was related to independent changes in leptin and HOMA-IR from 6 to 12 months in a multiple regression model (r = 0.77, P < 0.0001). CONCLUSIONS: Reductions in body fat and improvements in insulin sensitivity after AEX + WL and WL were maintained at 12 months despite modest weight regain. Baseline insulin resistance partially predicted the magnitude of weight regain in postmenopausal women.

Effects of Weight Loss with and without Exercise on Regional Body Fat Distribution in Postmenopausal Women.

BACKGROUND/AIMS: The purpose was to determine whether lifestyle interventions have different effects on regional fat in women with normal glucose tolerance vs. impaired glucose tolerance (NGT vs. IGT). METHODS: Changes in glucose metabolism (2-h oral glucose-tolerance tests), android to gynoid fat mass ratio (dual energy X-ray absorptiometry [DXA]), visceral to subcutaneous abdominal fat area ratio (CT), and abdominal to gluteal subcutaneous fat cell weight (FCW; adipose tissue biopsies) were determined in 60 overweight postmenopausal women (45-80 years) following 6 months of weight loss alone (WL; n = 28) or with aerobic exercise (AEX + WL; n = 32). RESULTS: The interventions led to ∼8% decrease in weight, but only the AEX + WL group improved fitness (↑11% in VO2max) and reduced the android-to-gynoid fat mass ratio (↓5%; p < 0.05). Both NGT and IGT groups reduced visceral and subcutaneous abdominal fat areas and abdominal and gluteal FCWs, which related to improvements in homeostatic model assessment (r = 0.34-0.42) and 2-h glucose (r = 0.34-0.35), respectively (p < 0.05). The decline in FCW was 2× greater in women with IGT following WL (p < 0.05). The ratios of abdominal-to-gluteal FCW did not change following either intervention. CONCLUSIONS: The mechanisms by which WL with and without exercise impact regional fat loss should be explored as reductions in abdominal fat area and subcutaneous FCW appear to influence glucose metabolism. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.

Exercise with weight loss improves adipose tissue and skeletal muscle markers of fatty acid metabolism in postmenopausal women.

OBJECTIVE: The effects of 6-month weight loss (WL) versus aerobic exercise training (AEX)+WL on fat and skeletal muscle markers of fatty acid metabolism were determined in normal (NGT) and impaired (IGT) glucose tolerant African-American and Caucasian postmenopausal women with overweight/obesity. METHODS: Fat (gluteal and abdominal) lipoprotein lipase (LPL), skeletal muscle LPL, acyl-CoA synthase (ACS), ß-hydroxacyl-CoA dehydrogenase, carnitine palmitoyltransferase (CPT-1), and citrate synthase (CS) activities were measured at baseline (n = 104) and before and after WL (n = 34) and AEX+WL (n = 37). RESULTS: After controlling for age and race, muscle LPL and CPT-1 were lower in IGT, and the ratios of fat/muscle LPL activity were higher in IGT compared to NGT. Muscle LPL was related to insulin sensitivity (M value) and inversely related to G120 , fasting insulin, and homeostatic model assessment of insulin resistance. AEX+WL decreased abdominal fat LPL and increased muscle LPL, ACS, and CS. The ratios of fat/muscle LPL decreased after AEX+WL. The change in VO2 max was related to the changes in LPL, ACS, and CS and inversely related to the changes in fat/muscle LPL activity ratios. CONCLUSIONS: Six-month AEX+WL, and not WL alone, is capable of enhancing skeletal muscle fatty acid metabolism in postmenopausal African-American and Caucasian women with NGT, IGT, and overweight/obesity.

Poly is more effective than monounsaturated fat for dietary management in the metabolic syndrome: The muffin study.

BACKGROUND: The metabolic syndrome (MetS) is highly prevalent and associated with an increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle recommendations to treat MetS often include the replacement of saturated fats (SFAs) and monosaccharides with unsaturated fat. However, it is unclear whether metabolic parameters will improve more when the saturated fat in American Heart Association (AHA) diets is replaced with higher concentrations of monounsaturated or polyunsaturated fatty acids (MUFA or PUFA). OBJECTIVE: To test the hypothesis that an AHA diet enriched in MUFA improves lipoprotein lipids, insulin resistance, inflammation, and endothelial function to a greater extent than a diet enriched in PUFA in middle-aged men and women with MetS. METHODS: A prospective, open-label, parallel group design with randomization to a hypocaloric MUFA or PUFA-enriched diet after weight stabilization on an AHA step I diet. Participants consumed 3 MUFA-enriched or PUFA-enriched muffins daily with additional supplementation as required to ensure 25%-50% increases in dietary fat intake from these sources at the expense of SFA and the opposing unsaturated fat. Changes in MetS components were measured at baseline and after 6 months of dietary intervention. RESULTS: Thirty-nine participants (mean age, 60.8 years; 79% African-American, 60% women) with MetS completed the 6-month study. Compared to baseline, assignment to either MUFA (n = 23) or PUFA (n = 16) both were associated with weight loss (MUFA: -2.3 ± 1 kg, P = .06; PUFA: -4.6 ± 2 kg; P = .002), but PUFA was also associated with reductions in triglycerides (TG) (-30 ± 18 mg/dL, P = .02), systolic blood pressure (BP) (-7 ± 3 mm Hg, P = .01), diastolic BP (DBP) (-4 ± 2 mm Hg, P = .01) and improved flow mediated dilation (FMD) (7.1% ± 1.8% vs 13.6% ± 2%, absolute increase; P = .0001). When compared to MUFA treatment, PUFA intervention was associated with reduced TG (P = .04) and DBP (P = .07) as well as increased FMD (P = .04) even after adjustment for changes in weight. There was no effect on total cholesterol, low-density lipoprotein cholesterol, glucose, high-sensitivity C-reactive protein (hs-CRP), or other inflammatory proteins. Overall, 25% (4 of 16) assigned to PUFA and 13% (3 of 23) to MUFA converted to non-MetS status. CONCLUSION: Substitution of SFA with PUFA in patients with MetS is associated with greater reductions in TG and improvement in endothelial function than MUFA that is independent of weight loss. These preliminary findings raise the possibility that PUFA may be the unsaturated fat of choice to reduce cardiometabolic risk in patients with MetS.

Increased depression and metabolic risk in postmenopausal breast cancer survivors.

OBJECTIVE: Breast cancer survivors (BCS) are at high risk for the development of obesity, type 2 diabetes mellitus, and metabolic syndrome. There is increasing interest in the association between depression and metabolic dysfunction, which is relevant in this population as depression is often present in the chronic phase of cancer recovery. Thus, the aim of this study was to evaluate metabolic risk in BCS with and without depression compared to non-cancer controls. METHODS: African American (46 %) and Caucasian (54 %) postmenopausal BCS (N = 28; age: 60 ± 2 years; mean ± SEM) were matched for race, age (±2 years), and BMI (±2 kg/m(2)) to non-cancer controls (N = 28). Center for Epidemiologic Studies Depression Scale (CES-D) >16 or antidepressant medication usage was used to classify depression. Metabolic status was defined by 2-hr glucose during an OGTT and classification of metabolic syndrome. RESULTS: Compared to non-cancer controls, BCS had similar 2-hr glucose, but higher fasting glucose and total cholesterol, and were 2.5 times more likely to have metabolic syndrome (21 vs. 52 %)(P's < 0.05). Conversely, HDL-C was 16 % higher in BCS (P < 0.05). Forty three % of BCS were on antidepressants compared to 14 % in non-cancer controls, despite similar mean CES-D scores (6 ± 1). Depressed BCS (46 %) had a higher BMI, waist circumference, fasting glucose, and more metabolic syndrome components than non-depressed BCS (P's < 0.05). CONCLUSIONS: BCS have a heightened prevalence of depression that may be associated with an increased prevalence of metabolic syndrome. These results support the need to monitor weight gain, depression, and the progression of metabolic abnormalities after cancer diagnosis and treatment. Further studies into the mechanistic link between depression and metabolic disease are necessary to identify strategies that can offset their impact on obesity and associated cardiovascular risk following a breast cancer diagnosis.

Sarcopenia Is Associated With Lower Skeletal Muscle Capillarization and Exercise Capacity in Older Adults.

BACKGROUND: Skeletal muscle capillary rarefaction limits the transcapillary transport of nutrients and oxygen to muscle and may contribute to sarcopenia and functional impairment in older adults. We tested the hypothesis that skeletal muscle capillarization and exercise capacity (VO2max) are lower in sarcopenic than in nonsarcopenic older adults and that the degree of sarcopenia is related to lower skeletal muscle capillarization. METHODS: Body composition, VO2max, and vastus lateralis capillarization were determined in 76 middle-aged and older men and women (age = 61±1 years, body mass index [BMI] = 30.7±0.5kg/m(2) [mean ± SEM]). Participants were classified as sarcopenic if appendicular lean mass divided by BMI (ALMBMI) was less than 0.789 for men or less than 0.512 for women. RESULTS: Sarcopenic subjects (ALMBMI = 0.65±0.04, n = 16) had 20% lower capillary-to-fiber ratio, as well as 13% and 15% lower VO2max expressed as mL/kg/min or L/min, respectively, compared with sex-, race-, and age-matched participants without sarcopenia (ALMBMI = 0.81±0.05, n = 16; p < .05). In all 76 subjects, ALMBMI, thigh muscle cross-sectional area, and VO2max correlated directly with capillarization (r = .30-.37, p ≤ .05), after accounting for age, sex, and race. CONCLUSIONS: These findings suggest that low skeletal muscle capillarization is one factor that may contribute to sarcopenia and reduced exercise capacity in older adults by limiting diffusion of substrates, oxygen, hormones, and nutrients. Strategies to prevent the aging-related decline in skeletal muscle capillarization may help to prevent or slow the progression of sarcopenia and its associated functional declines in generally healthy older adults.

Aging, Fitness, and Marathon Times in a 91 Year-old Man Who Competed in 627 Marathons.

Aging is associated with a decline in maximal aerobic capacity (VO2max) that may be attenuated by chronic endurance exercise. This case study chronicles the changes in marathon times in a 91 year old man who completed 627 marathons and 117 ultramarathons over 42 years. He began running marathons at age 48. His yearly best times remained fairly constant at ~240 minutes from age 50 - 64 years and then gradually rose to about 260 minutes in his early seventies followed by a curvilinear deterioration as he approached his ninth decade. His times plateaued at ~ 600 minutes in his late eighties. Between ages 68 and 89 his VO2max declined from 43 to 20 ml/kg/min. His marathon times were highly correlated with his VO2max (r2=0.87). The decline in marathons times and VO2max may reflect the contributions of biological aging, changes in exercise training volume and intensity, injuries, and comorbid disease.

Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining.

Intramuscular signaling and glucose transport mechanisms contribute to improvements in insulin sensitivity after aerobic exercise training. This study tested the hypothesis that increases in skeletal muscle capillary density (CD) also contribute to exercise-induced improvements in whole-body insulin sensitivity (insulin-stimulated glucose uptake per unit plasma insulin [M/I]) independent of other mechanisms. The study design included a 6-month aerobic exercise training period followed by a 2-week detraining period to eliminate short-term effects of exercise on intramuscular signaling and glucose transport. Before and after exercise training and detraining, 12 previously sedentary older (65 ± 3 years) men and women underwent research tests, including hyperinsulinemic-euglycemic clamps and vastus lateralis biopsies. Exercise training increased Vo2max (2.2 ± 0.2 vs. 2.5 ± 0.2 L/min), CD (313 ± 13 vs. 349 ± 18 capillaries/mm(2)), and M/I (0.041 ± 0.005 vs. 0.051 ± 0.007 µmol/kg fat-free mass/min) (P < 0.05 for all). Exercise training also increased the insulin activation of glycogen synthase by 60%, GLUT4 expression by 16%, and 5' AMPK-α1 expression by 21%, but these reverted to baseline levels after detraining. Conversely, CD and M/I remained 15% and 18% higher after detraining, respectively (P < 0.05), and the changes in M/I (detraining minus baseline) correlated directly with changes in CD in regression analysis (partial r = 0.70; P = 0.02). These results suggest that an increase in CD is one mechanism contributing to sustained improvements in glucose metabolism after aerobic exercise training.

Association Between Vitamin D Status and Weaning From Prolonged Mechanical Ventilation in Survivors of Critical Illness.

BACKGROUND: In this study, we examined the association between 25-hydroxyvitamin D (25(OH)D) concentration and successful weaning from mechanical ventilation in a cohort of ICU survivors requiring prolonged mechanical ventilation. METHODS: This was a retrospective cohort study of ICU survivors admitted to a long-term acute care hospital. Demographic data were extracted from medical records, including 25(OH)D concentrations drawn on admission. Subjects were divided into 2 groups based on their 25(OH)D concentrations (deficient, < 20 ng/mL; not deficient, ≥ 20 ng/mL), and associations between 25(OH)D concentration and successful weaning were calculated. RESULTS: A total of 183 subjects were studied. A high prevalence of 25(OH)D deficiency was found (61%, 111/183). No association was found between 25(OH)D concentration and weaning from mechanical ventilation. Increased comorbidity burden (Charlson comorbidity index) was associated with decreased odds of weaning (odds ratio of 0.50, 95% CI 0.25-0.99, P = .05). CONCLUSIONS: Vitamin D deficiency is common in ICU survivors requiring prolonged mechanical ventilation. Surprisingly, there was no significant relationship between 25(OH)D concentration and successful weaning. This finding may be due to the low 25(OH)D concentrations seen in our subjects. Given what is known about vitamin D and lung function and given the low vitamin D concentrations seen in patients requiring long-term ventilatory support, interventional studies assessing the effects of 25(OH)D supplementation in these patients are needed.

High adipose LPL activity and adipocyte hypertrophy reduce visceral fat and metabolic risk in obese, older women.

OBJECTIVE: To determine whether higher subcutaneous adipose tissue lipoprotein lipase activity (AT-LPLA) is associated with greater triglyceride (TG) storage in subcutaneous adipose tissue (SAT), thereby reducing visceral adipose tissue (VAT) accumulation and metabolic dysfunction. METHODS: Obese postmenopausal women (60 ± 1 years, mean ± SEM; N = 101) had body composition measured by DXA and CT and had fat aspirations to measure fat cell weight (FCW) and AT-LPLA. Women were ranked by visceral to total abdominal fat ratio (VAT/TAF), and the lowest and highest groups (n = 24) matched for % fat and age. RESULTS: The prevalence of metabolic dysfunction was 7- to 10-fold higher in women with high VAT/TAF (Ps < 0.01). Women with low VAT/TAF had 11% and 6% lower abdominal and gluteal FCW but 28% and 54% higher AT-LPLA/10(6) cells in abdominal and gluteal fat, respectively. Abdominal FCW correlated with AT-LPLA in women with low (r = 0.63, P < 0.01) but not high (r = 0.14, P = 0.52) VAT/TAF, and these lines differed in slope (P < 0.05) and intercept (P < 0.01), suggesting greater capacity for TG storage with low VAT/TAF. There were no relationships between gluteal FCW and AT-LPLA. The relationship between SAT and abdominal AT-LPLA (r = 0.39, P < 0.01) suggests that higher AT-LPLA promotes TG storage. CONCLUSIONS: These results suggest that higher AT-LPLA is associated with SAT adipocyte hypertrophy, which reduces visceral adiposity and metabolic risk in obese, older women.

Evidence for threshold effects of 25-hydroxyvitamin D on glucose tolerance and insulin resistance in black and white obese postmenopausal women.

We identified normal vs. abnormal 25-hydroxyvitamin D [25(OH)D] concentrations by examining the relation of 25(OH)D to non-bone-related measures (plasma glucose, insulin resistance, lipids, blood pressure, fitness, obesity, and regional adiposity) and asking whether there is a 25(OH)D concentration above and below which the relation between 25(OH)D and outcome changes. We examined the relation between 25(OH)D and outcome by race to see whether race-specific normal ranges are needed, and we examined the role of insulin-like growth factor-1 (IGF-1) in modulating the relation between 25(OH)D and outcome. In a cross-sectional study of 239 overweight and obese, sedentary postmenopausal women without diabetes (83 black, 156 white), outcome measures included plasma lipids, glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), IGF-1, parathyroid hormone (PTH), aerobic fitness, body composition, subcutaneous abdominal and visceral fat, and blood pressure. We identified threshold effects in the association between 25(OH)D and these variables using piecewise linear regressions. We found that 25(OH)D was inversely related to fasting glucose, fasting and 2-h insulin, HOMA-IR, visceral abdominal fat, percentage fat, PTH, and triglycerides. Evidence for a threshold effect of 25(OH)D was found for 2-h glucose, 2-h insulin, fasting insulin, and HOMA-IR. There was no evidence suggesting the need for race-specific normal 25(OH)D concentrations. IGF-1 modulated the relation between 25(OH)D and outcome but only below, and not above, a threshold 25(OH)D concentration. Our findings suggest a threshold effect of 25(OH)D on glucose-insulin metabolism such that 25(OH)D ≥ ∼26 µg/L (65.0 pmol/L) supports normal glucose homeostasis and that the same cut point defining normal 25(OH)D concentration can be used in black and white women. This study was registered at clinicaltrials.gov as NCT01798030.

Increased skeletal muscle capillarization after aerobic exercise training and weight loss improves insulin sensitivity in adults with IGT.

OBJECTIVE: Transcapillary transport of insulin is one determinant of glucose uptake by skeletal muscle; thus, a reduction in capillary density (CD) may worsen insulin sensitivity. Skeletal muscle CD is lower in older adults with impaired glucose tolerance (IGT) compared with those with normal glucose tolerance and may be modifiable through aerobic exercise training and weight loss (AEX+WL). We tested the hypothesis that 6-month AEX+WL would increase CD to improve insulin sensitivity and glucose tolerance in older adults with IGT. RESEARCH DESIGN AND METHODS: Sixteen sedentary, overweight-obese (BMI 27-35 kg/m2), older (63 ± 2 years) men and women with IGT underwent hyperinsulinemic-euglycemic clamps to measure insulin sensitivity, oral glucose tolerance tests, exercise and body composition testing, and vastus lateralis muscle biopsies to determine CD before and after 6-month AEX+WL. RESULTS: Insulin sensitivity (M) and 120-min postprandial glucose (G120) correlated with CD at baseline (r = 0.58 and r = -0.60, respectively, P < 0.05). AEX+WL increased maximal oxygen consumption (VO2max) 18% (P = 0.02) and reduced weight and fat mass 8% (P < 0.02). CD increased 15% (264 ± 11 vs. 304 ± 14 capillaries/mm(2), P = 0.01), M increased 21% (42.4 ± 4.0 vs. 51.4 ± 4.3 µmol/kg FFM/min, P < 0.05), and G120 decreased 16% (9.35 ± 0.5 vs. 7.85 ± 0.5 mmol/L, P = 0.008) after AEX+WL. Regression analyses showed that the AEX+WL-induced increase in CD independently predicted the increase in M (r = 0.74, P < 0.01) as well as the decrease in G120 (r = -0.55, P < 0.05). CONCLUSIONS: Six-month AEX+WL increases skeletal muscle CD in older adults with IGT. This represents one mechanism by which AEX+WL improves insulin sensitivity in older adults with IGT.

Aerobic exercise and weight loss reduce vascular markers of inflammation and improve insulin sensitivity in obese women.

OBJECTIVES: To examine the relationships between plasma and tissue markers of systemic and vascular inflammation and obesity and insulin resistance and determine the effects of aerobic exercise training plus weight loss (AEX+WL) and weight loss (WL) alone on these biomarkers. DESIGN: Prospective controlled study. SETTING: Veterans Affairs Medical Center and University research setting. PARTICIPANTS: Overweight and obese sedentary postmenopausal women (N = 77). INTERVENTIONS: Six months, 3 d/wk AEX+WL (n = 37) or WL (n = 40). MEASUREMENTS: Total-body dual-energy X-ray absorptiometry, abdominal computed tomography, hyperinsulinemic-euglycemic clamps (a criterion standard method of assessing insulin sensitivity), adipose tissue biopsies (n = 28), and blood for homeostasis model assessment-insulin resistance, and soluble forms of intracellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). RESULTS: Body weight (P < .001), percentage of fat (P < .001), visceral fat (P < .005), triglyceride levels (P < .001), and systolic blood pressure decreased comparably after WL and AEX+WL (P = .04). Maximal oxygen consumption increased 16% after AEX+WL (P < .001). Insulin resistance decreased in both groups (P = .005). Glucose utilization according to the clamp increased 10% (P = .04) with AEX+WL and 8% with WL (P = .07). AEX+WL decreased CRP by 29% (P < .001) and WL by 21% (P = .02). SAA levels decreased twice as much after AEX+WL (-19%, P = .02) as after WL (-9%, P = .08). Plasma sICAM-1 and sVCAM-1 levels did not change, but women with the greatest reduction in plasma sICAM-1 levels had the greatest reductions in fasting glucose (P = .02), insulin (P = .02), and insulin resistance (P = .004). Gluteal ICAM messenger ribonucleic acid levels decreased 27% after AEX+WL (P = .02) and did not change after WL. CONCLUSION: Obesity and insulin resistance worsen markers of systemic and vascular inflammation. A reduction in plasma sICAM-1 is important to improve insulin sensitivity. CRP, SAA, and tissue ICAM decrease with exercise and weight loss, suggesting that exercise training is a necessary component of lifestyle modification in obese postmenopausal women.