[show abstract][hide abstract] ABSTRACT: Advancing age is accompanied by changes in metabolic characteristics, such as reduced insulin sensitivity and low levels of vitamin D, which may exacerbate age-related declines in physical function.
The aim of the present study was to determine the associations between insulin-glucose dynamics, vitamin D metabolites, and performance on a battery of motor tasks in healthy, non-diabetic older adults.
Sixty-nine community-dwelling men and women (65-90 years) were recruited. Insulin-glucose dynamics were determined by an intravenous glucose tolerance test, and vitamin D metabolites were measured. Motor function was characterized by the time to walk 500 m, chair-rise time, lower body strength, dorsiflexor steadiness and endurance time, and muscle coactivation.
Significant unadjusted correlations were found between insulin-glucose dynamics and 1,25-dihydroxyvitamin D [1,25(OH)2D] with walk time, strength, steadiness, endurance time, and muscle activation (p < 0.05). A significant amount of the variance in walking endurance was explained by the sex of the individual, 1,25(OH)2D, and fasting blood insulin (R (2) = 0.36, p < 0.001). Strength could be partially explained by age, body fatness, and fasting glucose (R (2) = 0.55, p < 0.001).
Poor motor function in non-diabetic older men and women was associated with indices of insulin-glucose dynamics and the bio-active vitamin D metabolite 1,25(OH)2D. Walking endurance and strength were explained by 1,25(OH)2D and fasting blood glucose and insulin, even after adjusting for age, sex, and body fat.
Motor function in a relatively small sample of non-diabetic older men and women was associated with metabolic factors that increase in prevalence with aging.
Aging - Clinical and Experimental Research 10/2013; · 1.01 Impact Factor
[show abstract][hide abstract] ABSTRACT: A novel microfluidic chromatography device coupled with tandem mass spectrometry (LC-MS/MS) was utilized for the multiplex analysis of 5 steroids (testosterone, dihydrotestosterone, progesterone, cortisol, cortisone) in human serum. The use of microfluidics allowed for reduction of the chromatographic flow rate to 3μl/min with overall method run times comparable to standard flow LC-MS/MS methods reported in the literature, corresponding to a 150 fold decrease in solvent consumption. Furthermore, a simple sample preparation protocol was employed requiring injection of only 0.5μl of sample, corresponding to a 100-400 fold increase in on-column sensitivity as compared to published standard flow assays. The measured LOQ for both testosterone and progesterone was 0.4ng/mL, representing an improvement over reported literature values obtained by standard flow methods employing comparable sample preparation and large injection volumes. The LOQs for cortisol (1.9ng/mL), cortisone (0.3ng/mL), and dihydrotestosterone (1.4ng/mL) were all within a biologically relevant range. A comparison of clinical serum samples was performed for the analysis of testosterone using this microfluidic LC-MS/MS assay and the Beckman Access II automated antibody-based measurement system. The immunoassay results were systematically higher due to matrix interference which was easily resolved with the increased chromatographic resolution obtained in the microflow LC-MS/MS assay.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 07/2013; 934C:16-21. · 2.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: The purpose of this study is to compare the impact of older age and nursing home residence on the incidence and morbidity of severe sepsis. MATERIALS AND METHODS: This was a retrospective analysis of 19460 emergency department visits from the 2005 to 2009 National Ambulatory Medical Care Surveys with diagnosis of infection with or without severe sepsis (acute organ dysfunction). Clinical outcomes included intensive care unit (ICU) admission, hospital length of stay (LOS), and in-hospital mortality. RESULTS: Older adults (age ≥65 years) were 5-fold more likely to have infections classified as severe sepsis than younger adults (6.5% vs 1.3%), and nursing home residents were 7-fold more likely to have a severe sepsis diagnosis compared with nonnursing home residents (14% vs 1.9%). Among visits for severe sepsis, older adults, compared with younger adults, had modestly higher rates of ICU admission (27% vs 21%), hospital LOS (median, 6 vs 5 days), and in-hospital mortality (24% vs 16%). Nursing home residents with severe sepsis, compared with nonnursing home residents, had significantly higher rates of ICU admission (40% vs 21%), hospital LOS (median, 7 vs 5 days), and in-hospital mortality (37% vs 15%). CONCLUSIONS: Older adults and particularly nursing home residents have a disproportionately high incidence of and morbidity from severe sepsis.
Journal of critical care 05/2013; · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: Context:Aging in men is associated with reduced testosterone (T) levels and physiological changes leading to frailty, but the benefits of T supplementation are inconclusive.Objective:We studied the effects of T supplementation with and without progressive resistance training (PRT) on functional performance, strength, and body composition.Design, Setting, and Participants:We recruited 167 generally healthy community-dwelling older men (66 ± 5 years) with low-normal baseline total T levels (200-350 ng/dL).Intervention:Subjects were randomized to placebo or transdermal T gel [2 doses targeting either a lower (400-550 ng/dL) or higher (600-1000 ng/dL) T range] and to either PRT or no exercise for 12 months.Main Outcome Measure:The primary outcome was functional performance, whereas secondary outcomes were strength and body composition.Results:A total of 143 men completed the study. At 12 months, total T was 528 ± 287 ng/dL in subjects receiving any T and 287 ± 65 ng/dL in the placebo group. In the PRT group, function and strength were not different between T- and placebo-treated subjects, despite greater improvements in fat mass (P = .04) and fat-free mass (P = .01) with T. In the non-PRT group, T did not improve function but improved fat mass (P = .005), fat-free mass (P = .03), and upper body strength (P = .03) compared with placebo. There were fewer cardiovascular events in the T-treated groups compared with placebo.Conclusions:T supplementation was well tolerated and improved body composition but had no effect on functional performance. T supplementation improved upper body strength only in nonexercisers compared with placebo.
The Journal of clinical endocrinology and metabolism 03/2013; · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: N-acetyl-4-aminophenol (ACET) may impair musculoskeletal adaptations to progressive resistance exercise training (PRT) by inhibiting exercise-induced muscle protein synthesis and bone formation. To test the hypothesis that ACET would diminish training-induced increases in fat-free mass (FFM) and osteogenesis, untrained men (n = 26) aged ≥50 years participated in 16 weeks of high-intensity PRT and bone-loading exercises and were randomly assigned to take ACET (1,000 mg/day) or placebo (PLAC) 2 h before each exercise session. Total body FFM was measured by DXA at baseline and week 16. Serum bone-specific alkaline phosphatase (BAP) and C-terminal crosslinks of type-I collagen (CTX) were measured at baseline and week 16. Vastus lateralis muscle biopsies were performed at baseline and weeks 3 and 16 for prostanoid, anabolic, and catabolic gene expression by RT-PCR. In exercise-compliant men (ACET, n = 10; PLAC, n = 7), the increase in FFM was not different between groups (p = 0.91). The changes in serum BAP and CTX were not different between groups (p > 0.7). There were no significant changes in any of the target genes at week 3. After 16 weeks of PRT, the mRNA expressions of the anabolic marker p70S6K (p = 0.003) and catabolic marker muscle-atrophy F-box (MAFbx) (p = 0.03) were significantly reduced as compared to baseline in ACET. The mRNA expression of the prostanoids were unchanged (all p ≥ 0.40) in both groups. The administration of ACET (1,000 mg) prior to each exercise session did not impair PRT-induced increases in FFM or significantly alter bone formation markers in middle aged and older men.
[show abstract][hide abstract] ABSTRACT: Neuromuscular electrical stimulation (NMES) can facilitate the recovery of quadriceps muscle strength after total knee arthroplasty (TKA), yet the optimal intensity (dosage) of NMES and its effect on strength after TKA have yet to be determined.
The primary objective of this study was to determine whether the intensity of NMES application was related to the recovery of quadriceps muscle strength early after TKA. A secondary objective was to quantify quadriceps muscle fatigue and activation immediately after NMES to guide decisions about the timing of NMES during rehabilitation sessions.
This study was an observational experimental investigation.
Data were collected from 30 people who were 50 to 85 years of age and who received NMES after TKA. These people participated in a randomized controlled trial in which they received either standard rehabilitation or standard rehabilitation plus NMES to the quadriceps muscle to mitigate strength loss. For the NMES intervention group, NMES was applied 2 times per day at the maximal tolerable intensity for 15 contractions beginning 48 hours after surgery over the first 6 weeks after TKA. Neuromuscular electrical stimulation training intensity and quadriceps muscle strength and activation were assessed before surgery and 3.5 and 6.5 weeks after TKA.
At 3.5 weeks, there was a significant association between NMES training intensity and a change in quadriceps muscle strength (R(2)=.68) and activation (R(2)=.22). At 6.5 weeks, NMES training intensity was related to a change in strength (R(2)=.25) but not to a change in activation (R(2)=.00). Furthermore, quadriceps muscle fatigue occurred during NMES sessions at 3.5 and 6.5 weeks, whereas quadriceps muscle activation did not change.
Some participants reached the maximal stimulator output during at least 1 treatment session and might have tolerated more stimulation.
Higher NMES training intensities were associated with greater quadriceps muscle strength and activation after TKA.
[show abstract][hide abstract] ABSTRACT: Testosterone levels decrease with age. This decline is steeper during "critical illnesses". Cardiac surgery is a particular representative model of major clinical condition producing stress responses similar to those observed during severe nonsurgical illness. Cardiac revascularization with extracorporeal circulation is characterized by marked postoperative complications such as insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction. These phenomena are more evident in older subjects, who are particularly vulnerable in the post-operative state, a condition that has been recently termed as "acute postoperative frailty". We recently showed that in older men with low ejection fraction undergoing cardiac revascularization with extracorporeal circulation, there is a profound decline in anabolic hormones, including testosterone. After surgery testosterone concentration frequently declines to less than 200 ng/dl, a situation suggestive of overt hypogonadism. Since men with low testosterone levels have a high probability of developing mobility limitations, we considered this a rationale for the perioperative use of testosterone treatment in older men undergoing cardiac revasularization surgery. We hypothesized that testosterone supplementation at this time might attenuate the impressive post-surgical catabolic hormonal milieu. The aim of this manuscript is to elucidate an ongoing randomized clinical trial in older men (70+ years old) undergoing elective cardiovascular revascularization with extracorporeal circulation. This randomized clinical trial will evaluate the effects of intramuscular testosterone administration on clinical and functional outcomes in this population. The study will also address potential mechanisms underlying the expected beneficial effects of testosterone supplementation including improvement of insulin sensitivity, markers of inflammatory status and improved hemoglobin levels.
[show abstract][hide abstract] ABSTRACT: Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1-year follow-up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6-month exercise-based weight loss program and returned for follow-up at 18 months. Dual-energy X-ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m(2). They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow-up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (-1.7 ± 3.5%; P = 0.002) and hip (-0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C-terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (-0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: -3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone-deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss.
[show abstract][hide abstract] ABSTRACT: Vitamin D is associated with a variety of health outcomes, but the exact definition of vitamin D sufficiency remains controversial.
We sought to define skeletal-related vitamin D sufficiency by estimating maximum PTH suppression in the U.S. population.
We performed a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES), 2003-2006. We examined the association between serum 25-hydroxyvitamin D (25OHD) level and serum PTH level in 14,681 participants aged ≥6 yr. We also evaluated the 25OHD-PTH association using 2 thresholds of hyperparathyroidism: PTH≥45 pg/ml and ≥75 pg/ml.
The mean 25OHD level was 24 ng/ml and mean PTH was 42 pg/ml. PTH≥45 pg/ml was present in 35% of the population, while PTH≥75 pg/ml was present in 7%. The prevalence of 25OHD levels <40 ng/ml and <30 ng/ml was 95% and 77%, respectively. In both unadjusted and adjusted models, there was a strong inverse relationship between 25OHD and PTH. Compared to 25OHD≥40 ng/ml, the 25OHD-PTH association was 2.36 [95% confidence interval (CI), 2.08-2.67] times greater for 25OHD<5 ng/ml and 1.12 (95%CI, 1.07-1.17) times greater for 25OHD 30-39.9 ng/ml. Compared to 25OHD≥40 ng/ml, 25OHD levels of 20- 29.9 ng/ml [odds ratio (OR) 2.0 (95%CI, 1.4-2.8)] but not 30- 39.9 ng/ml [OR 1.1 (95%CI, 0.8-1.6)] were independently associated with PTH≥45 pg/ml.
Optimal vitamin D status, defined by estimated maximum PTH suppression, does not occur until at least 25OHD levels ≥40 ng/ml. Using these thresholds, most of the U.S. population needs more vitamin D. Large, prospective studies are needed to determine optimal vitamin D supplementation.
Journal of endocrinological investigation 05/2011; 35(1):42-8. · 1.65 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the effects of dehydroepiandrosterone (DHEA) therapy on changes in central adiposity, insulin action and blood lipids. Many of the actions of DHEA in humans are thought to be mediated through its conversion to sex hormones, which are modulators of adiposity, muscularity and insulin sensitivity. The effects of DHEA replacement on regional tissue composition, glucose metabolism and blood lipid profile in older adults have been inconsistent.
A randomized, double-blinded, placebo-controlled trial. The intervention was oral DHEA 50 mg/day or placebo for 12 months.
Fifty-eighty women and 61 men, aged 60-88 years, with low serum DHEA sulphate (DHEAS) levels at study entry.
Computed tomography measures of abdominal fat areas, thigh muscle and fat areas, DXA-derived trunk fat mass, serum glucose and insulin responses to an oral glucose challenge, and fasted serum total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were assessed before and after the intervention.
There were no significant (P > 0·05) differences between the DHEA and placebo groups in the changes in regional tissue composition or glucose metabolism. HDL-cholesterol (P = 0·01) and fasted triglycerides (P = 0·02) decreased in women and men taking DHEA.
Restoring serum DHEAS levels in older adults to young adult levels for 1 year does not appear to reduce central adiposity or improve insulin action. The benefit of DHEA on decreasing serum triglycerides must be weighed against the HDL-lowering effect.
[show abstract][hide abstract] ABSTRACT: Age-related differences in force steadiness have been extensively examined and used as an index of motor function. However, the functional relevance of steadiness remains unclear.
The aim here was to evaluate the relations among hand strength, steadiness, and function across the adult life span.
Seventy-five adults (45 women; 18-89 yr) performed three strength, two steadiness, and four functional tests with both hands. Strength was measured during index finger abduction, precision pinch, and handgrip, and steadiness was measured during index finger abduction and precision pinch. Functional tests included the Grooved Pegboard test, the game Operation™, a scissor task, and a tracing task.
Moderate correlations were observed between both steadiness tasks and performance on the Grooved Pegboard test (R(2) = 0.57 and R(2) = 0.46, respectively) and Operation™ (R(2) = -0.47 and R(2) = -0.57, respectively).
The relation between measures of steadiness and hand function suggests that the physiological mechanisms responsible for differences in steadiness also contribute to differences in the performance of fine motor tasks with the hand.
Medicine and science in sports and exercise 04/2011; 43(4):560-7. · 3.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: We have previously shown a favorable association of subcutaneous leg fat with markers of insulin resistance and dyslipidemia in postmenopausal women. It is not known whether there is a sex dimorphism in the association of lower-body adiposity with reduced metabolic risk. Thus, our primary aim was to determine whether the favorable association of thigh subcutaneous fat, independent of abdominal fat, is also observed in older men. Mid-thigh and abdominal fat areas were measured by computed tomography (CT) in 108 older men and postmenopausal women (mean ± s.d.; 69 ± 7 years). Additionally, trunk and leg fat mass (FM) were measured by dual-energy X-ray absorptiometry (DXA). Markers of insulin resistance and dyslipidemia were determined from oral glucose tolerance tests and lipid and lipoprotein measurements, respectively. Outcomes were fasted and postchallenge (area under the curve, AUC) insulin (INS(AUC)) and glucose (GLU(AUC)), product of the insulin and glucose AUC (INS(AUC) × GLU(AUC)), triglycerides (TG), and high-density lipoprotein (HDL)-cholesterol. Consistent with our previous findings in postmenopausal women, adjusting for DXA trunk FM revealed a favorable association of DXA leg FM with the metabolic risk outcomes in both older men and postmenopausal women. Likewise, adjusting for CT abdominal visceral fat generally revealed a favorable association of CT thigh fat with metabolic risk outcomes in women, but not men. The discordance between the DXA and CT results in men is unclear but may be due to sex differences in visceral fat accrual. The mechanisms underlying the protective effect of thigh fat on metabolic risk factors need to be elucidated.
[show abstract][hide abstract] ABSTRACT: Prostaglandins (PGs) are essential signaling factors in bone mechanotransduction. In animals, inhibition of the enzyme responsible for PG synthesis (cyclooxygenase) by nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the bone-formation response to loading when administered before, but not immediately after, loading. The aim of this proof-of-concept study was to determine whether the timing of NSAID use influences bone mineral density (BMD) adaptations to exercise in humans. Healthy premenopausal women (n = 73) aged 21 to 40 years completed a supervised 9-month weight-bearing exercise training program. They were randomized to take (1) ibuprofen (400 mg) before exercise, placebo after (IBUP/PLAC), (2) placebo before, ibuprofen after (PLAC/IBUP), or (3) placebo before and after (PLAC/PLAC) exercise. Relative changes in hip and lumbar spine BMD from before to after exercise training were assessed using a Hologic Delphi-W dual-energy X-ray absorptiometry (DXA) instrument. Because this was the first study to evaluate whether ibuprofen use affects skeletal adaptations to exercise, only women who were compliant with exercise were included in the primary analyses (IBUP/PLAC, n = 17; PLAC/PLAC, n = 23; and PLAC/IBUP, n = 14). There was a significant effect of drug treatment, adjusted for baseline BMD, on the BMD response to exercise for regions of the hip (total, p < .001; neck, p = .026; trochanter, p = .040; shaft, p = .019) but not the spine (p = .242). The largest increases in BMD occurred in the group that took ibuprofen after exercise. Total-hip BMD changes averaged -0.2% +/- 1.3%, 0.4% +/- 1.8%, and 2.1% +/- 1.7% in the IBUP/PLAC, PLAC/PLAC, and PLAC/IBUP groups, respectively. This preliminary study suggests that taking NSAIDs after exercise enhances the adaptive response of BMD to exercise, whereas taking NSAIDs before may impair the adaptive response.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2010; 25(6):1415-22. · 6.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: Most mechanical forces acting on the skeleton are generated either through impact with the ground (i.e., gravitational loading) or through muscle contractions (i.e., muscle loading). If one of these conduits for activating mechanotransduction in bone is more effective than the other with respect to developing or maintaining bone strength, this would have important clinical implications for prescribing physical activity for the prevention or treatment of osteoporosis. This section of the symposium considered whether there is evidence from studies of humans that the effectiveness of physical activity to preserve bone health is dependent on whether the activities stimulate the skeleton primarily through gravitational or muscle loading. Conclusive evidence is lacking, but several lines of research suggest that physical activities that involve impact forces, and therefore generate both gravitation and muscle loading, are most likely to have beneficial effects on bone metabolism and reduce fracture risk.
Medicine and science in sports and exercise 10/2009; 41(11):2050-5. · 3.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVES: To evaluate the association between serum 25-hydroxyvitamin D (25(OH)D) levels and mortality in a representative U.S. sample of older adults.DESIGN: Prospective cohort from the Third National Health and Nutrition Examination Survey (NHANES III) and linked mortality files.SETTING: Noninstitutionalized U.S. civilian population.PARTICIPANTS: Three thousand four hundred eight NHANES III participants aged 65 and older enrolled from 1988 to 1994 and followed for mortality through 2000.MEASUREMENTS: Primary exposure was serum 25(OH)D level at enrollment. Primary and secondary outcomes were all-cause and cardiovascular disease (CVD) mortality, respectively.RESULTS: During the median 7.3 years of follow-up, there were 1,493 (44%) deaths, including 767 CVD-related deaths. Median 25(OH)D level was 66 nmol/L. Adjusting for demographics, season, and cardiovascular risk factors, baseline 25(OH)D levels were inversely associated with all-cause mortality risk (adjusted hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92–0.98, per 10 nmol/L 25[OH]D). Compared with subjects with 25(OH)D levels of 100 nmol/L or higher, the adjusted HR for subjects with levels less than 25.0 nmol/L was 1.83 (95% CI=1.14–2.94) and for levels of 25.0 to 49.9 nmol/L was 1.47 (95% CI=1.09–1.97). The association appeared stronger for CVD mortality (adjusted HR=2.36, 95% CI=1.17–4.75, for subjects with 25[OH]D levels<25.0 nmol/L vs those ≥100.0 nmol/L) than for non-CVD mortality (adjusted HR=1.42, 95% CI=0.73–2.79, for subjects with 25[OH]D levels<25.0 nmol/L vs those ≥100.0 nmol/L).CONCLUSION: In noninstitutionalized older adults, a group at high risk for all-cause mortality, serum 25(OH)D levels had an independent, inverse association with CVD and all-cause mortality. Randomized controlled trials of vitamin D supplementation in older adults are warranted to determine whether this association is causal and reversible.
Journal of the American Geriatrics Society 08/2009; 57(9):1595 - 1603. · 3.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: The mechanisms by which dehydroepiandrosterone (DHEA) replacement increases bone mineral density (BMD) in older adults are not known. Objective: The aims were to determine the effects of DHEA therapy on changes in sex hormones and IGF-I and their associations with changes in BMD.
A randomized, double-blinded, placebo-controlled trial was conducted at an academic research institution. Participants were 58 women and 61 men, aged 60-88 yr, with low serum DHEA sulfate (DHEAS) levels.
The intervention was oral DHEA 50 mg/d or placebo for 12 months.
BMD and serum DHEAS, testosterone, estradiol (E(2)), estrone (E(1)), SHBG, IGF-I, and IGF binding protein 3 were measured before and after intervention. Free testosterone and estrogen (FEI) indices were calculated.
The average changes in hip and spine BMD (DHEA vs. placebo) ranged from 1.1 to 1.6%. Compared with placebo, DHEA replacement increased serum DHEAS, testosterone, free testosterone index, E(1), E(2), FEI, and IGF-I (all P < 0.001) and decreased SHBG (P = 0.02) in women and, in men, increased DHEAS, E(1), FEI (all P < 0.001), and E(2) (P = 0.02) and decreased SHBG (P = 0.037). The changes in total and regional hip BMD were associated with 12-month E(2) (all P <or= 0.001) and FEI (all P <or= 0.013). The effects of DHEA treatment were eliminated by adjustment for 12-month E(2).
The significant increases in hip BMD in older adults undergoing DHEA replacement were mediated primarily by increases in serum E(2) rather than direct effects of DHEAS.
[show abstract][hide abstract] ABSTRACT: To determine the relative contributions of adiposity and muscularity to multi-dimensional performance-based and perceived physical function in older adults living independently.
Data from 109 women and men, aged 60 or older, with low serum dehydroepiandrosterone (DHEA) sulfate levels were included in this cross-sectional analysis of baseline measures from a single-site, randomized, controlled trial of DHEA replacement therapy. Physical function was determined by means of performance on the 100-point Continuous Scale-Physical Functional Performance (CS-PFP) test and by self-reporting using the physical function subscale of the Medical Outcomes Short Form-36 (SF36PF). Body composition was measured by dual-energy X-ray absorptiometry (DXA). Linear regression analyses were used to determine the contributions of body mass index (BMI; kg body mass/m2), fat index (FI; kg fat/m2), and appendicular skeletal muscle index (ASMI; kg muscle/m2) to the CS-PFP and SF36PF scores, adjusted for age and sex.
Age-adjusted regression analyses indicated that FI, but not ASMI, was a significant (P<0.001) determinant of CS-PFP (R2=0.54) and SF36PF (R2=0.37). When adjusted for age and sex, BMI was nearly as good a predictor of CS-PFP (R2=0.50) and SF36PF (R2=0.34) as FI.
Adiposity was a stronger predictor of measured and self-reported physical function than was muscularity in older adults living independently. BMI, adjusted for sex, is a reasonable substitute for adiposity in the prediction of physical function.
[show abstract][hide abstract] ABSTRACT: Data from large clinical trials of postmenopausal women suggest that the incidence of diabetes is reduced in women randomized to estrogen-based hormone therapy when compared with placebo. Whether this is due to an effect of estrogen on insulin or glucose metabolism remains unclear.
Our objective was to test the hypothesis that estradiol (E(2)) increases insulin secretion and clearance.
Serum insulin and C-peptide (CPEP) responses to hyperglycemia (250 mg/dl) plus iv L-arginine were measured on 2 separate days, with (EST) and without [control (CON)] subacute (24 h) transdermal E(2) administration.
There were 11 postmenopausal women (mean +/- sd; 55 +/- 4 yr) included in this study.
Insulin secretion and clearance were estimated from the CPEP area under the curve and the molar ratio of CPEP to insulin area under the curve, respectively. Mean glucose disposal rate (GDR) was estimated from the rate of glucose infusion during the final 30 min of the hyperglycemic clamp.
There were no differences in insulin secretion or clearance between the EST and CON days. Fasting glucose was lower on the EST compared with the CON (93 +/- 6 vs. 98 +/- 8 mg/dl), but mean GDR was not different. However, when one outlier was excluded from analysis, GDR was increased after EST compared with CON. Furthermore, a strong inverse association was observed between years since menopause and E(2)-mediated changes in GDR (r = -0.794; P = 0.004).
Contrary to our hypothesis, 24-h transdermal E(2) administration did not alter insulin secretion or clearance in postmenopausal women. However, a longer time since menopause was associated with a reduced effect of E(2) to increase glucose uptake.