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Biomedical subjects

John D Sorkin

Publications and source records attributed to John D Sorkin.

At least 19 recordsLinked to original sources
PubMed2007

Determinants of walking function after stroke: differences by deficit severity.

OBJECTIVES: To investigate the relationship of cardiovascular fitness (Vo(2)peak), neurologic deficits in balance and leg strength, and body composition to ambulatory function after stroke and to determine whether these relationships differ between those with milder versus more severe gait deficits. DESIGN: Cross-sectional correlation study. SETTING: Outpatient clinic of an academic medical center. PARTICIPANTS: Seventy-four people (43 men, 31 women; mean age +/- standard deviation, 64+/-10y) with chronic hemiparetic stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Thirty-foot (9.1-m) walk velocity, 6-minute walk distance, Vo(2)peak, Berg Balance Scale score, bilateral quadriceps eccentric torque, total and regional lean mass, and percentage of fat mass. RESULTS: Short-distance walking correlated significantly with cardiovascular fitness, balance, paretic leg strength, nonparetic leg strength, percentage of body fat, and paretic lean mass but not with nonparetic lean mass. Long-distance walking correlated significantly with cardiovascular fitness, balance, paretic leg strength, nonparetic leg strength, and paretic lean mass but not with percentage of body fat or nonparetic lean mass. Stepwise regression showed that cardiovascular fitness, balance, and paretic leg strength were independently associated with long-distance walking (r(2)=.60, P<.001). Variance in long-distance walking was largely explained by balance for those who walked more slowly (<.48m/s) for short distances (r(2)=.42, P<.001) and by cardiovascular fitness for those who walked more quickly (>.48m/s) for short distances (r(2)=.26, P=.003). CONCLUSIONS: Short-distance walking after stroke is related to balance, cardiovascular fitness, and paretic leg strength. Long-distance walking ability differs by gait deficit severity, with balance more important in those who walk more slowly and cardiovascular fitness playing a greater role in those who walk more quickly. Improved understanding of the factors that predict ambulatory function may assist the design of individualized rehabilitation strategies across the spectrum of gait deficit severity in those with hemiparetic stroke.

Adult↗
PubMed2006

Dehydroepiandrosterone secretion in healthy older men and women: effects of testosterone and growth hormone administration in older men.

CONTEXT: Aging is associated with diminished gonadal steroid and GH/IGF-I axis activity; whether these changes contribute to the parallel declines of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) production is unknown, as are the effects of sex steroid and/or GH administration on DHEA and DHEAS production. OBJECTIVE: Our objective was to evaluate morning DHEAS concentrations and nocturnal DHEA secretory dynamics in healthy older men and women, before and after chronic administration of sex steroid(s) alone, GH alone, sex steroid(s) combined with GH, or placebo alone. DESIGN: We compared nocturnal DHEA secretory dynamics (2000 h to 0800 h, sampling every 20 min, analyzed by multiparameter deconvolution and approximate entropy algorithms) in healthy older (65-88 yr) men (n = 68) and women (n = 36), both before and after 26 wk of administration of sex steroid(s) alone [testosterone (T) in men or estrogen/progesterone in women], GH alone, sex steroid(s) combined with GH, or placebo alone. RESULTS: Morning concentrations of DHEAS were lower; nocturnal DHEA pulsatile production rate, burst frequency, and amplitude were higher; and half-life was shorter in women (P < 0.05). Nocturnal integrated DHEA concentrations, total production rate, and approximate entropy did not differ significantly by sex. Because of small treatment group sizes in women, only hormone intervention results in men are presented. In men, T and T plus GH administration significantly decreased nocturnal integrated DHEA but not morning DHEAS concentrations. GH alone exerted no significant effects on nocturnal DHEA secretion or morning DHEAS. CONCLUSIONS: Spontaneous nocturnal DHEA secretion is sexually dimorphic in healthy older individuals, and T administration decreases nocturnal DHEA secretion in older men. The clinical significance of sex steroid modulation of DHEA secretion in older persons remains to be elucidated.

Aged↗
PubMed2006

High prevalence of abnormal glucose metabolism and poor sensitivity of fasting plasma glucose in the chronic phase of stroke.

BACKGROUND: Cardiovascular disease is the leading cause of death in long-term stroke survivors, and whole-body glucose metabolism is strongly linked to cardiovascular disease risk. This study provides important preliminary information on the prevalence of abnormal glucose metabolism in chronic stroke patients (mean 3 years after stroke) and reports on the utility of screening for abnormalities using fasting plasma glucose (FPG) in this population. METHODS: Two hundred and sixteen chronic hemiparetic stroke patients were screened for diabetes status by medical history and FPG. A subset (n = 80) was evaluated by oral glucose tolerance test to assess the utility of screening for abnormalities using FPG alone. RESULTS: Seventy-five of the 216 (35%) had type 2 diabetes by medical history. Another 70 were either diabetic (n = 11) or had impaired fasting glucose (n = 59) based on a single blood draw at the time of screening. FPG among non-diabetic stroke patients had a sensitivity of 49% for predicting abnormalities in the 2-hour glucose level during oral glucose tolerance test. Cumulative results identify 77% as abnormal (impaired or diabetic) on the basis of medical history, fasting plasma glucose, and/or 2-hour glucose level. CONCLUSIONS: The prevalence of abnormal glucose metabolism is extremely high in chronic stroke and is underestimated on the basis of FPG.

Aged↗
PubMed2006

Phosphodiesterase 4D polymorphisms and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study.

An association between polymorphisms within the phosphodiesterase 4D gene (PDE4D) and ischemic stroke was initially reported in older adults from Iceland and has been supported by studies in several other primarily elderly populations. In the present study, we examined the association between PDE4D polymorphisms and early-onset ischemic stroke in a biracial female population. A systematic search for polymorphisms in the highly evolutionary conserved regions of PDE4D was performed on 48 African-American and 48 Caucasian participants. Novel and known polymorphisms were then prioritized and genotyped in the entire study population of 224 cases of first ischemic stroke among women aged 15-49 and 211 age- and ethnicity-balanced control subjects. Forty novel and previously reported polymorphisms with a minor allele frequency greater than 0.05 were determined, with 23 polymorphisms selected for analysis in the full case-control sample. Single nucleotide polymorphism (SNP), linkage disequilibrium and haplotype analyses were performed. SNP rs918592, found in an intron near the 5' end of the gene, was significantly associated with stroke (age- and race-adjusted odds ratio (OR=1.5, P=0.007), with four other SNPs showing significant, albeit less strong, associations. The magnitude of association was similar across African-Americans and Caucasians and across multiple stroke subtypes (e.g. atherosclerotic, lacunar and non-lacunar of undetermined etiology). The association of rs918592 with stroke was confined exclusively to current smokers (OR=3.2, P=0.00014), with no association observed among never-smokers (OR=0.9, P=0.75) or former smokers (OR=1.2, P=0.66), demonstrating a gene-environment interaction (P=0.03). A strong dose-response relationship was also seen among current smokers. No specific risk haplotypes were identified.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Effects of GH and/or sex steroids on circulating IGF-I and IGFBPs in healthy, aged women and men.

Circulating GH, IGF-I, IGFBP-3, and sex steroid concentrations decrease with age. GH or sex steroid treatment increases IGFBP-3, but little is known regarding the effects of these hormones on other IGFBPs. We assessed the effects of 26 wk of administration of GH, sex steroids, or GH + sex steroids on AM levels of IGF-I, IGFBPs 1-5, insulin, glucose, and osteocalcin and 2-h urinary excretion of deoxypyridinolline (DPD) cross-links in 53 women and 71 men aged 65-88 yr. Before treatment, in women and men, IGF-I was directly related to IGFBP-3 (P < 0.001 and P < 0.0001) and IGFBP-1 to IGFBP-2 (P = 0.0001). In women, IGFBP-1 was inversely related to insulin (P < 0.0005) and glucose (P < 0.005) and IGFBP-4 to osteocalcin (P < 0.01). IGFBP-4 and IGFBP-5 were not significantly related to DPD cross-links. GH and/or sex steroid increased IGF-I levels in both sexes, with higher concentrations in men (P < 0.001). In women, the IGF-I increment after GH was attenuated by hormone replacement therapy (HRT) coadministration (P < 0.05). Hormone administration also increased IGFBP-3. IGFBP-1 was unaffected by GH + sex steroids, whereas GH decreased IGFBP-2 by 15% in men (P < 0.05). Hormone administration did not change IGFBP-4, whereas in men IGFBP-5 increased by 20% after GH (P < 0.05) and 56% after GH + testosterone (P = 0.0003). These data demonstrate sexually dimorphic IGFBP responses to GH. Additionally, HRT attenuated or prevented GH-mediated increases in IGF-I and IGFBP-3. Whether GH and/or sex steroid administration alters local tissue production of IGFBPs and whether the latter influence autocrine or paracrine actions of IGF-I remain to be determined.

Aged↗
PubMed2006

Does having children extend life span? A genealogical study of parity and longevity in the Amish.

BACKGROUND: The relationship between parity and life span is uncertain, with evidence of both positive and negative relationships being reported previously. We evaluated this issue by using genealogical data from an Old Order Amish community in Lancaster, Pennsylvania, a population characterized by large nuclear families, homogeneous lifestyle, and extensive genealogical records. METHODS: The analysis was restricted to the set of 2,015 individuals who had children, were born between 1749 and 1912, and survived until at least age 50 years. Pedigree structures and birth and death dates were extracted from Amish genealogies, and the relationship between parity and longevity was examined using a variance component framework. RESULTS: Life span of fathers increased in linear fashion with increasing number of children (0.23 years per additional child; p =.01), while life span of mothers increased linearly up to 14 children (0.32 years per additional child; p =.004) but decreased with each additional child beyond 14 (p =.0004). Among women, but not men, a later age at last birth was associated with longer life span (p =.001). Adjusting for age at last birth obliterated the correlation between maternal life span and number of children, except among mothers with ultrahigh (>14 children) parity. CONCLUSIONS: We conclude that high parity among men and later menopause among women may be markers for increased life span. Understanding the biological and/or social factors mediating these relationships may provide insights into mechanisms underlying successful aging.

Aged↗
PubMed2005

Treadmill exercise rehabilitation improves ambulatory function and cardiovascular fitness in patients with chronic stroke: a randomized, controlled trial.

BACKGROUND AND PURPOSE: Physical inactivity propagates disability after stroke through physical deconditioning and learned nonuse. We investigated whether treadmill aerobic training (T-AEX) is more effective than conventional rehabilitation to improve ambulatory function and cardiovascular fitness in patients with chronic stroke. METHODS: Sixty-one adults with chronic hemiparetic gait after ischemic stroke (>6 months) were randomized to 6 months (3x/week) progressive T-AEX or a reference rehabilitation program of stretching plus low-intensity walking (R-CONTROL). Peak exercise capacity (Vo2 peak), o2 consumption during submaximal effort walking (economy of gait), timed walks, Walking Impairment Questionnaire (WIQ), and Rivermead Mobility Index (RMI) were measured before and after 3 and 6 months of training. RESULTS: Twenty-five patients completed T-AEX and 20 completed R-CONTROL. Only T-AEX increased cardiovascular fitness (17% versus 3%, delta% T-AEX versus R-CONTROL, P<0.005). Group-by-time analyses revealed T-AEX improved ambulatory performance on 6-minute walks (30% versus 11%, P<0.02) and mobility function indexed by WIQ distance scores (56% versus 12%, P<0.05). In the T-AEX group, increasing training velocity predicted improved Vo2 peak (r=0.43, P<0.05), but not walking function. In contrast, increasing training session duration predicted improved 6-minute walk (r=0.41, P<0.05), but not fitness gains. CONCLUSIONS: T-AEX improves both functional mobility and cardiovascular fitness in patients with chronic stroke and is more effective than reference rehabilitation common to conventional care. Specific characteristics of training may determine the nature of exercise-mediated adaptations.

Aged↗
PubMed2005

Steps after stroke: capturing ambulatory recovery.

BACKGROUND AND PURPOSE: Nearly two thirds of stroke survivors have deficits impairing ambulatory recovery. Conventional mobility outcome measures such as timed walks and functional independence measure (FIM) do not quantify free-living ambulatory behavior. This study compared step activity monitoring (SAM) with established instruments to assess ambulatory recovery across the outpatient subacute stroke rehabilitation phase. METHODS: We measured FIM mobility subscale, SAM-derived daily steps, Stroke Impact Scale (SIS) mobility scores, and timed walks in 11 subjects after discharge from inpatient rehabilitation and again 3 months later. RESULTS: Significant improvement was measured in free-living step activity (mean gain 80%; P=0.001) but not with timed walks (P=0.4), FIM (P=0.08), or SIS mobility scales (P=0.3). CONCLUSIONS: Microprocessor-linked SAM is a sensitive indicator of ambulatory recovery that measures improvements not captured by other conventional outcome instruments.

Activities of Daily Living↗
PubMed2005

Relationship between objective measures of peripheral arterial disease severity to self-reported quality of life in older adults with intermittent claudication.

OBJECTIVES: The aim of this study was to determine the relation between functional measures of peripheral arterial disease (PAD) severity with both disease-specific and generic self-reported health-related quality-of-life (HR-QOL) measures, as well as the relation between the two types of HR-QOL measures. METHODS: This was a cross-sectional observation of participants from the community and primary care or vascular surgery clinics in an academic Veterans Administration medical center. Eighty patients with symptomatic Fontaine stage II PAD provided physiologic measures and self-response questionnaires. Objective measures included the ankle-brachial index (ABI), time to maximum claudication pain on a graded exercise test, and a 6-minute floor-walking distance. Self-reports included the Walking Impairment Questionnaire (WIQ), a disease-specific HR-QOL measure and the Medical Outcomes Study (MOS) Short-Form 36 (SF-36), a generic HR-QOL measure. RESULTS: Patients (mean age 70 +/- 8 [+/- SD] and 85% men) exhibited moderate-to-severe PAD by objective measures of ABI (0.65 +/- 0.19) and time in minutes to maximal claudication on a graded exercise test (7:54 +/- 4:58). Significant correlations were found between these measures and the WIQ distance, MOS-Physical Function, and MOS-Role Limitations due to physical dysfunction. The SF-36 and the WIQ subscales were significantly correlated. CONCLUSION: In older PAD patients with intermittent claudication, objective measures of disease severity are correlated with a self-reported, disease-specific and generic HR-QOL.

Aged↗
PubMed2005

The relation of fasting and 2-h postchallenge plasma glucose concentrations to mortality: data from the Baltimore Longitudinal Study of Aging with a critical review of the literature.

OBJECTIVE: Under the auspices of the National Institutes of Health, American Diabetes Association, and World Health Organization, expert committees lowered the fasting plasma glucose (FPG) concentration diagnostic for diabetes from 7.8 to 7.0 mmol/l and defined 6.1-6.9 mmol/l as impaired fasting glucose (IFG) and <6.1 mmol/l as normal fasting glucose. In 2003, IFG was lowered to 5.6-6.9 mmol/l and normal fasting glucose to <5.6 mmol/l. Reports of the relationship between glucose concentration and all-cause mortality have been inconsistent. It is not known if the 2-h plasma glucose (2hPG) concentration from an oral glucose tolerance test (OGTT) adds to the predictive power of FPG. RESEARCH DESIGN AND METHODS: We followed 1,236 men for an average of 13.4 years to determine the relationship between both FPG and 2hPG and all-cause mortality. RESULTS: Risk for mortality did not increase until the FPG exceeded 6.1 mmol/l. Risk increased by approximately 40% in the 6.1-6.9 mmol/l range and doubled when FPG ranged from 7.0 to 7.7 mmol/l. A combination of the 2hPG and FPG allowed better estimation of risk than the FPG alone. Within any category of FPG, risk generally increased as the 2hPG increased, and within any category of 2hPG, risk generally increased as the FPG increased. CONCLUSIONS: These data support the decision to lower the FPG diagnostic for diabetes from 7.8 to 7.0 mmol/l, show that both IFG and impaired glucose tolerance have risks between the normal and diabetic ranges, and show that the OGTT adds predictive power to that of FPG alone and should not be abandoned. The lowering of IFG to 5.6 mmol/l from 6.1 mmol/l, at least for mortality, is, however, not supported by our results.

Adolescent↗
PubMed2004

Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial.

CONTEXT: Reorganization in central motor networks occurs during early recovery from hemiparetic stroke. In chronic stroke survivors, specific rehabilitation therapy can improve upper extremity function. OBJECTIVE: To test the hypothesis that in patients who have chronic motor impairment following stroke, specific rehabilitation therapy that improves arm function is associated with reorganization of cortical networks. DESIGN, SETTING, AND PATIENTS: A randomized controlled clinical trial conducted in a US ambulatory rehabilitation program with 21 patients (median [IQR], 50.3 [34.8-77.3] months after unilateral stroke). Data were collected between 2001 and 2004. INTERVENTIONS: Patients were randomly assigned to bilateral arm training with rhythmic auditory cueing (BATRAC) (n = 9) or standardized dose-matched therapeutic exercises (DMTE) (n = 12). Both were conducted for 1 hour, 3 times a week, for 6 weeks. MAIN OUTCOME MEASURES: Within 2 weeks before and after the intervention, brain activation during elbow movement assessed by functional magnetic resonance imaging (fMRI) and functional outcome assessed using arm function scores. RESULTS: Patients in the BATRAC group but not in the DMTE group increased hemispheric activation during paretic arm movement (P = .03). Changes in activation were observed in the contralesional cerebrum and ipsilesional cerebellum (P = .009). BATRAC was associated with significant increases in activation in precentral (P<.001) and postcentral gyri (P = .03) and the cerebellum (P<.001), although 3 BATRAC patients showed no fMRI changes. Considering all patients, there were no differences in functional outcome between groups. When only BATRAC patients with fMRI response were included (n = 6), BATRAC improved arm function more than DMTE did (P = .02). CONCLUSIONS: These preliminary findings suggest that BATRAC induces reorganization in contralesional motor networks and provide biological plausibility for repetitive bilateral training as a potential therapy for upper extremity rehabilitation in hemiparetic stroke.

Aged↗
PubMed2004

Hostility and distraction have differential influences on cardiovascular recovery from anger recall in women.

This study investigated the relation of dispositional hostility to cardiovascular reactivity during an anger-recall task and of hostility and distraction to posttask recovery in 80 healthy women (ages 18-30). Half were randomly assigned to distraction during recovery. Hostility predicted slower systolic blood pressure and preejection period during recovery. Distraction was related to faster cardiac recovery, higher high-frequency (HF) power, lower low-frequency (LF) power and LF:HF ratios, and lower state anger and rumination during recovery. These results indicate deleterious influences of hostility on cardiovascular recovery but not during anger recall. The findings also show beneficial effects of distraction in expediting cardiovascular recovery, possibly through reducing rumination and anger.

Adolescent↗
PubMed2004

Regional bone mineral density after resistive training in young and older men and women.

PURPOSE: The purpose of this study was to determine the effects of 6 months of whole-body resistive training (RT) on total and regional bone mineral density (BMD) and bone mineral content (BMC) by age and gender in young and older men and women. METHODS: Younger men (n=10) and women (n=7) aged 20-29 years (25+/-1 years) and older men (n=10) and women (n=10) aged 65-74 years (69+/-1 years) participated in 6 months of progressive whole-body RT. Upper- and lower-body strength was assessed by the one repetition maximum (1RM) test, and total body fat, lean tissue mass, femoral neck BMD, Ward's triangle BMD, greater trochanter BMD, total-body BMD, and L2-L4 spine BMD were determined by dual-energy X-ray absorptiometry before and after 6 months of RT. RESULTS: Percent body fat decreased only in the young men (P<0.05). Lean tissue mass increased after training in young men and women and older men (P<0.05) but did not change significantly in older women. Upper- and lower-body 1RM strength increased in all groups (P<0.01). Overall, there was a significant increase in BMD at the femoral neck, ward's triangle and greater trochanter BMD, as well as total body BMC and leg BMC (P<0.05). Total-body BMD and L2-L4 spine BMD did not change with RT. There were no gender differences in the training response between men and women for any of the BMD regions and no age differences in the training response, except for a trend between young and older subjects for femoral neck (P<0.08). CONCLUSION: A 6-month RT program increases muscle mass and improves BMD of the femoral region in young and healthy older men and women as a group, with a trend for this to be greater in young subjects.

Adaptation, Physiological↗
PubMed2003

Reliability of treadmill exercise testing in older patients with chronic hemiparetic stroke.

OBJECTIVE: To assess the test-retest reliability of cardiopulmonary measurements during peak effort and submaximal treadmill walking tests in older patients with gait-impaired chronic hemiparetic stroke. DESIGN: Nonrandomized test-retest. SETTING: Hospital geriatric research stress testing laboratory. PARTICIPANTS: Fifty-three subjects (44 men, 9 women; mean age, 65+/-8y) with chronic hemiparetic gait after remote (>6mo) ischemic stroke. Patients had mild to moderate chronic hemiparetic gait deficits, making handrail support necessary during treadmill walking. INTERVENTIONS: Peak effort and submaximal effort treadmill walking tests were conducted and then repeated on a separate day at least a week later. Main outcome measures Reliability coefficients (r) were calculated for heart rate, systolic blood pressure (SBP), oxygen consumption (Vo(2) [L/min]), Vo(2) (mL.kg(-1).min(-1)), respiratory exchange ratio (RER), rate-pressure product (RPP), and oxygen pulse during peak effort testing. The reliability coefficients for all but SBP and RPP data were calculated from the submaximal tests. RESULTS: Heart rate (r=.87), Vo(2)peak (L/min) (r=.92), Vo(2)peak (mL.kg(-1).min(-1)) (r=.92), and oxygen pulse (r=93) were highly reliable parameters during maximal testing in this population. Submaximal testing produced highly reliable results for V.o(2) (L/min) (r=.89) and oxygen pulse (r=.85). All cardiopulmonary measures except RER had a reliability coefficient greater than.80 during submaximal testing in this population. CONCLUSION: Our study provides the first evidence that peak effort treadmill testing provides highly reliable oxygen consumption measures in chronic hemiparetic stroke patients using minimal handrail support. The submaximal tests were at or near the threshold level of reliability for the 2 most important measures of V.o(2) (L/min) and V.o(2) (mL.kg(-1).min(-1)) (r=.89, r=.84, respectively), with the remaining measures falling above.70.

Adult↗
PubMed2003

Predictors of body fat gain in nonobese girls with a familial predisposition to obesity.

BACKGROUND: Conflicting evidence exists on the causal factors underlying the development of excess adiposity in children. OBJECTIVE: We determined the effect of energy expenditure (EE), muscle energetics, and physical fitness on weight and fat gain in prepubertal girls with or without a predisposition to obesity. DESIGN: Normal-weight girls (n = 101) were recruited at 8 y of age according to parental body mass index. Eighty-eight girls completed the 2-y study, and the groups were as follows: LN, girls with 2 lean parents; LNOB, girls with 1 obese and 1 lean parent; and OB, girls with 2 obese parents. Measurements of weight, height, and body composition were taken 1 and 2 y after baseline. Girls underwent baseline measurements of EE by 24-h calorimetry and doubly labeled water, of muscle metabolism by (31)P nuclear magnetic resonance, and of fitness. RESULTS: Fat mass (FM) and percentage body fat (%BF) differed significantly between the groups at years 1 and 2; the OB group had higher FM (P = 0.03) and %BF (P = 0.046) at year 1 and higher FM (P = 0.047) at year 2 than did the LN group. After adjustment for baseline weight, group, time, ethnicity, and Tanner stage, sleep EE, basal EE, 24-h EE, and peak oxygen uptake were negatively associated with FM and %BF (P < 0.04). After adjustment for the same variables, muscle oxidative capacity and free-living total EE were negatively and positively predictive, respectively, of changes in %BF between 8 and 10 y of age (both P = 0.04). CONCLUSIONS: Nonobese girls with 2 obese parents have a significant risk of developing obesity. High free-living total EE and low muscle oxidative capacity predict high rates of fat gain.

Adipose Tissue↗
PubMed2002

Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.

CONTEXT: Hormone administration to elderly individuals can increase lean body mass (LBM) and decrease fat, but interactive effects of growth hormone (GH) and sex steroids and their influence on strength and endurance are unknown. OBJECTIVE: To evaluate the effects of recombinant human GH and/or sex steroids on body composition, strength, endurance, and adverse outcomes in aged persons. DESIGN, SETTING, AND PARTICIPANTS: A 26-week randomized, double-blind, placebo-controlled parallel-group trial in healthy, ambulatory, community-dwelling US women (n = 57) and men (n = 74) aged 65 to 88 years recruited between June 1992 and July 1998. INTERVENTIONS: Participants were randomized to receive GH (starting dose, 30 micro g/kg, reduced to 20 micro g/kg, subcutaneously 3 times/wk) + sex steroids (women: transdermal estradiol, 100 micro g/d, plus oral medroxyprogesterone acetate, 10 mg/d, during the last 10 days of each 28-day cycle [HRT]; men: testosterone enanthate, biweekly intramuscular injections of 100 mg) (n = 35); GH + placebo sex steroid (n = 30); sex steroid + placebo GH (n = 35); or placebo GH + placebo sex steroid (n = 31) in a 2 x 2 factorial design. MAIN OUTCOME MEASURES: Lean body mass, fat mass, muscle strength, maximum oxygen uptake (VO(2)max) during treadmill test, and adverse effects. RESULTS: In women, LBM increased by 0.4 kg with placebo, 1.2 kg with HRT (P =.09), 1.0 kg with GH (P =.001), and 2.1 kg with GH + HRT (P<.001). Fat mass decreased significantly in the GH and GH + HRT groups. In men, LBM increased by 0.1 kg with placebo, 1.4 kg with testosterone (P =.06), 3.1 kg with GH (P<.001), and 4.3 kg with GH + testosterone (P<.001). Fat mass decreased significantly with GH and GH + testosterone. Women's strength decreased in the placebo group and increased nonsignificantly with HRT (P =.09), GH (P =.29), and GH + HRT (P =.14). Men's strength also did not increase significantly except for a marginally significant increase of 13.5 kg with GH + testosterone (P =.05). Women's VO(2)max declined by 0.4 mL/min/kg in the placebo and HRT groups but increased with GH (P =.07) and GH + HRT (P =.06). Men's VO(2)max declined by 1.2 mL/min/kg with placebo and by 0.4 mL/min/kg with testosterone (P =.49) but increased with GH (P =.11) and with GH + testosterone (P<.001). Changes in strength (r = 0.355; P<.001) and in VO(2)max (r = 0.320; P =.002) were directly related to changes in LBM. Edema was significantly more common in women taking GH (39% vs 0%) and GH + HRT (38% vs 0%). Carpal tunnel symptoms were more common in men taking GH + testosterone (32% vs 0%) and arthralgias were more common in men taking GH (41% vs 0%). Diabetes or glucose intolerance occurred in 18 GH-treated men vs 7 not receiving GH (P =.006). CONCLUSIONS: In this study, GH with or without sex steroids in healthy, aged women and men increased LBM and decreased fat mass. Sex steroid + GH increased muscle strength marginally and VO( 2)max in men, but women had no significant change in strength or cardiovascular endurance. Because adverse effects were frequent (importantly, diabetes and glucose intolerance), GH interventions in the elderly should be confined to controlled studies.

Aged↗
PubMed2002

Sleep-disordered breathing and insulin resistance in middle-aged and overweight men.

Sleep-disordered breathing is a prevalent condition associated with impairment of daytime function and may predispose individuals to metabolic abnormalities independent of obesity. The primary objective of this study was to determine the metabolic consequences and community prevalence of sleep-disordered breathing in mildly obese, but otherwise healthy, individuals. One hundred and fifty healthy men, without diabetes or cardiopulmonary disease, were recruited from the community. Measurements included polysomnography, a multiple sleep latency test, an oral glucose tolerance test, determination of body fat by hydrodensitometry, and fasting insulin and lipids. The prevalence of sleep-disordered breathing, depending on the apnea-hypopnea index (AHI) cutoff, ranged from 40 to 60%. After adjusting for body mass index (BMI) and percent body fat, an AHI gt-or-equal, slanted 5 events/h was associated with an increased risk of having impaired or diabetic glucose tolerance (odds ratio, 2.15; 95% CI, 1.05-4.38). The impairment in glucose tolerance was related to the severity of oxygen desaturation (DeltaSa(O(2))) associated with sleep-disordered breathing. For a 4% decrease in oxygen saturation, the associated odds ratio for worsening glucose tolerance was 1.99 (95% CI, 1.11 to 3.56) after adjusting for percent body fat, BMI, and AHI. Multivariable linear regression analyses revealed that increasing AHI was associated with worsening insulin resistance independent of obesity. Thus, sleep-disordered breathing is a prevalent condition in mildly obese men and is independently associated with glucose intolerance and insulin resistance.

Adult↗