Loretta DiPietro

Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study

Summary Recent muscle biopsy studies have shown a relation between intramuscular lipid content and insulin resistance. The aim of this study was to test this relation in humans by using a novel proton nuclear magnetic resonance (1H NMR) spectroscopy technique, which enables non-invasive and rapid ( ∼ 45 min) determination of intramyocellular lipid (IMCL) content. Normal weight non-diabetic adults (n = 23, age 29 ± 2 years, BMI = 24.1 ± 0.5 kg/m2) were studied using cross-sectional analysis. Insulin sensitivity was assessed by a 2-h hyperinsulinaemic ( ∼ 450 pmol/l)-euglycaemic ( ∼ 5 mmol/l) clamp test. Intramyocellular lipid concentrations were determined by using localized 1H NMR spectroscopy of soleus muscle. Simple linear regression analysis showed an inverse correlation (r = –0.692, p = 0.0017) between intramyocellular lipid content and M-value (100–120 min of clamp) as well as between fasting plasma non-esterified fatty acid concentration and M-value (r = –0.54, p= 0.0267). Intramyocellular lipid content was not related to BMI, age and fasting plasma concentrations of triglycerides, non-esterified fatty acids, glucose or insulin. These results show that intramyocellular lipid concentration, as assessed non invasively by localized 1H NMR spectroscopy, is a good indicator of whole body insulin sensitivity in non-diabetic, non-obese humans. [Diabetologia (1999) 42: 113–116]

A survey for assessing physical activity among older adults.

In 1988, the Yale Physical Activity Survey (YPAS) was designed and then administered to healthy older populations of volunteers (aged 60-86) to establish its 2-wk repeatability and relative validity. Among the 76 volunteers in the repeatability substudy, correlation coefficients between the two administrations of the survey for the eight YPAS summary indices ranged from 0.42 (P = 0.0002) to 0.65 (P = 0.0001). Among the 25 subjects in the validation substudy, weekly energy expenditure (r = -0.47; P = 0.01) and daily hours spent sitting (r = 0.53; P = 0.01) correlated with resting diastolic blood pressure, while the YPAS activity dimensions summary index (composed of questions on vigorous activity, leisurely walking, moving, sitting, and standing) correlated positively with estimated VO2max (r = 0.58; P = 0.004) and inversely with percent body fat (r = -0.43; P = 0.03). The YPAS index of vigorous activity also correlated positively with estimated VO2max (r = 0.60; P = 0.003) and the moving index correlated marginally with body mass index (r = -0.37; P = 0.06). We conclude that the YPAS demonstrates adequate repeatability, and some validity by correlating with several physiologic variables reflecting habitual physical activity. The value of the YPAS, however, in accurately assessing low intensity activity remains to be established.

Randomized Controlled Trial of Aerobic Exercise on Insulin and Insulin-like Growth Factors in Breast Cancer Survivors: The Yale Exercise and Survivorship Study

Background: High insulin and insulin-like growth factor-I (IGF-I) levels may be associated with an increased breast cancer risk and/or death. Given the need to identify modifiable factors that decrease insulin, IGF-I, and breast cancer risk and death, we investigated the effects of a 6-month randomized controlled aerobic exercise intervention versus usual care on fasting insulin, IGF-I, and its binding protein (IGFBP-3) in postmenopausal breast cancer survivors. Methods: Seventy-five postmenopausal breast cancer survivors were identified from the Yale-New Haven Hospital Tumor Registry and randomly assigned to an exercise (n = 37) or usual care (n = 38) group. The exercise group participated in 150 minutes per week of moderate-intensity aerobic exercise. The usual care group was instructed to maintain their current physical activity level. A fasting blood sample was collected on each study participant at baseline and 6 months. Blood levels of insulin and IGF were measured with ELISA. Results: On average, exercisers increased aerobic exercise by 129 minutes per week compared with 45 minutes per week among usual care participants (P < 0.001). Women randomized to exercise experienced decreases in insulin, IGF-I, and IGFBP-3, whereas women randomized to usual care had increases in these hormones. Between-group differences in insulin, IGF-I, and IGFBP-3 were 20.7% (P = 0.089), 8.9% (P = 0.026), and 7.9% (P = 0.006), respectively. Conclusions: Moderate-intensity aerobic exercise, such as brisk walking, decreases IGF-I and IGFBP-3. The exercise-induced decreases in IGF may mediate the observed association between higher levels of physical activity and improved survival in women diagnosed with breast cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(1):306–13)

Physical Activity, Body Weight, and Adiposity: An Epidemiologic Perspective

Overweight is a common problem in the United States, especially among minority women and persons of lower socioeconomic status and lower educational attainment. Moreover, the prevalence of reported inactivity may be highest in these same population subgroups. Both overweight and sedentary behavior are important risk factors for chronic disease morbidity and mortality; however, there is encouraging evidence that moderate to higher levels of physical activity may provide protection from certain chronic diseases, even among persons with established risk factors. Several methodological issues preclude the ability to determine accurately the impact of physical activity on body weight and adiposity. These issues include (a) a low prevalence of higher-intensity physical activity in the general population, (b) measurement error with regard to self-reported activity, especially that of lower-intensity, (c) inappropriate time frame of the physical activity assessment, (d) effect modification by age and gender, and (e) failure to adjust for important statistical confounders. Despite these methodological issues, the inverse association between physical activity and weight has been reported in several cross-sectional epidemiologic studies, which consistently report lower body weight, or more favorable distribution of body fat, with higher categorical levels of self-reported physical activity. Directionality of the physical activity and weight relation cannot be determined from these studies, however, and the few longitudinal epidemiologic studies that have assessed the influence of physical activity on the risk of weight gain report inconclusive results. This is possibly because a one-time assessment of physical activity if not adequate in describing the contribution of habitual physical activity on long-term weight maintenance. Therefore, longitudinal population-based studies with multiple assessments of physical activity over long follow-up periods are necessary to determine this relationship. In any case, the evidence suggests that persons concerned with overweight, or especially the prevention of overweight and obesity, should increase their physical activity. Sociodemographic characteristics such as age, gender, educational level, and weight are associated with physical activity patterns and choices. Therefore, these characteristics should be considered by professionals when implementing physical activity interventions for weight control. Walking is accessible to all segments of the U.S. population. Because walking is convenient, low cost, and safe, and can result in weight loss if done regularly for durations of at least 20-30 min, its relative merits should be stressed in weight reduction and maintenance programs. Furthermore, to reduce the morbidity and mortality associated with overweight, obesity, and sedentary behavior, priority for intervention programs should be directed at persons in the most vulnerable sectors of the population.

Physical activity patterns associated with cardiorespiratory fitness and reduced mortality : The aerobics center longitudinal study

OBJECTIVES This study examined cross sectionally the physical activity patterns associated with low, moderate, and high levels of cardiorespiratory fitness. METHODS Physical activity was assessed by questionnaire in a clinic population of 13,444 men and 3972 women 20 to 87 years of age. Estimated energy expenditure (kcal.wk-1) and volume (min.wk-1) of reported activities were calculated among individuals at low, moderate, and high fitness levels (assessed by maximal exercise tests). RESULTS Average leisure time energy expenditures of 525 to 1650 kcal.wk-1 for men and 420 to 1260 kcal.wk-1 for women were associated with moderate to high levels of fitness. These levels of energy expenditure can be achieved with a brisk walk of approximately 30 minutes on most days of the week. In fact, men in the moderate and high fitness categories walked between 130 and 138 min.wk-1, and women in these categories walked between 148 and 167 min.wk-1. CONCLUSIONS Most individuals should be able to achieve these physical activity goals and thus attain a cardiorespiratory fitness level sufficient to result in substantial health benefits.

Physical activity in the prevention of obesity: current evidence and research issues.

PURPOSE The relation between habitual physical activity and the prevention of overweight and obesity in adults based on the evidence from the epidemiologic literature is described. METHODS Literature was reviewed of current findings from large population-based studies of forward directionality in which physical activity was considered as a primary study factor. RESULTS The longitudinal evidence suggests that habitual physical activity plays more of a role in attenuating age-related weight gain, rather than in promoting weight loss. Moreover, recent data suggest that increasing amounts of physical activity may be necessary to effectively maintain a constant body weight with increasing age. CONCLUSION Over decades, small savings in excess weight gain accumulate into net savings that may be quite meaningful with regard to minimizing the risk associated with obesity-related disorders. The question remains as to how important maintaining a constant body weight through middle age and into older age is to healthy, already-active people of normal body weight.

Exercise improves body fat, lean mass, and bone mass in breast cancer survivors.

Given the negative effects of a breast cancer diagnosis and its treatments on body weight and bone mass, we investigated the effects of a 6‐month randomized controlled aerobic exercise intervention vs. usual care on body composition in breast cancer survivors. Secondary aims were to examine the effects stratified by important prognostic and physiologic variables. Seventy‐five physically inactive postmenopausal breast cancer survivors were recruited through the Yale–New Haven Hospital Tumor Registry and randomly assigned to an exercise (n = 37) or usual care (n = 38) group. The exercise group participated in 150 min/week of supervised gym‐ and home‐based moderate‐intensity aerobic exercise. The usual care group was instructed to maintain their current physical activity level. Body composition was assessed at baseline and 6‐months through dual‐energy X‐ray absorptiometry (DXA) by one radiologist blinded to the intervention group of the participants. On an average, exercisers increased moderate‐intensity aerobic exercise by 129 min/week over and above baseline levels compared with 45 min/week among usual care participants (P < 0.001). Exercisers experienced decreases in percent body fat (P = 0.0022) and increases in lean mass (P = 0.047) compared with increases in body fat and decreases in lean mass in usual care participants. Bone mineral density (BMD) was also maintained among exercisers compared with a loss among usual care participants (P = 0.043). In summary, moderate‐intensity aerobic exercise, such as brisk walking, produces favorable changes in body composition that may improve breast cancer prognosis.

The epidemiology of physical activity and physical function in older people

A primary goal of studies of successful aging is to identify the modifiable factors related to the plasticity of higher physical function; however, little is known about the relationship between habitual physical activity (especially that of lower- to moderate-intensity) and the maintenance of day-to-day functioning in older people. The purpose of this paper is to address the question of how patterns of physical activity translate into altered physical function among healthy older populations. In this paper, physical activity is classified as a behavior, whereas physical function is classified as performance, comprised of a series of increasingly integrated steps. Recent data from several epidemiologic studies suggest that physical activity is associated with the maintenance of more basic components of physical function, as well as with higher-order task or goal-oriented functions in healthy older people. Moreover, higher levels of physical activity appear to be associated with better functioning, even in those with already-existing chronic disease. Recent CDC/ACSM health recommendations call for incorporating at least 30 min of any activity into the daily schedule. Therefore, regular participation in activities of moderate intensity (such as walking, gardening, house/yard work) should be encouraged among the general older community.

Estrogen influences osmotic secretion of AVP and body water balance in postmenopausal women

To determine if estrogen upregulates osmotic secretion of arginine vasopressin (AVP) and alters body water balance, we infused hypertonic (3% NaCl) saline in 6 women (68 ± 3 yr) after 14 days of 17β-estradiol (transdermal patch, ∼0.1 mg/day, E2) and placebo (control) administration. Hypertonic saline was infused at 0.1 ml ⋅ kg-1 ⋅ min-1for 120 min, and after a 30-min equilibration period, the subjects drank water ad libitum for 180 min. E2 increased basal plasma estradiol concentration from ≤12 to 80 ± 12 pg/ml and plasma AVP concentration (P[AVP]) from 2.1 ± 0.7 to 3.1 ± 0.8 pg/ml ( P< 0.05), but not plasma osmolality (Posm, 288 ± 1 and 287 ± 1, for control and E2, respectively). Hypertonic saline infusion increased Posm by 18 ± 1 and 17 ± 1 mosmol/kgH2O and P[AVP] by 5.2 ± 0.5 and 4.9 ± 0.4 pg/ml for control and E2 treatments, respectively. The P[AVP]-Posmrelationship shifted upward after E2, with no change in sensitivity (slope, 0.36 ± 0.02 and 0.33 ± 0.03 pg ⋅ ml-1 ⋅ mosmol-1for control and E2, respectively). Water intake was similar between control and E2 (24 vs. 22 ml/kg), but by 180 min of drinking, urine output and free water clearance ([Formula: see text]) were reduced by 5.6 ± 2.3 ml/kg and 2.6 ± 2.0 ml/min, respectively ( P < 0.05) after E2. Plasma aldosterone concentration was unaffected by E2, but fractional sodium excretion was reduced from 2.7 ± 0.5 to 1.7 ± 0.4% ( P < 0.05) at 180 min of drinking. Our data suggest that E2augments osmotic AVP secretion, thereby implicating elevated AVP as a contributor to water retention in high E2 states; however, an increase in renal sodium reabsorption was a major component of the enhanced fluid retention.

Improvements in Cardiorespiratory Fitness Attenuate Age-related Weight Gain in Healthy Men and Women: The Aerobics Center Longitudinal Study

OBJECTIVE: To determine the longitudinal relation of change in cardiopulmonary fitness to subsequent change in body weight in a cohort of healthy middle-aged adults.DESIGN: Prospective cohort study.SUBJECTS: Participants were 4599 men and 724 women (43±9 y) receiving at least three medical examinations between 1970 and 1994. Examinations included assessment of cardiorespiratory fitness by maximal exercise tests and measurement of body weight.MEASUREMENTS: Change in fitness was calculated as the difference in maximal treadmill time between the first and second examination (mean interval, 1.8 y). Weight change was calculated as the difference in body weight between the first and last examination (mean follow-up, 7.5 y).RESULTS: There was a small, yet statistically significant weight gain over the follow-up (0.61±5.29 kg for men and 1.51±4.67 kg for women; P<0.001). Estimates from the multiple linear regression modeling show that each 1 min improvement in treadmill time, significantly attenuated weight gain in both men (b=−0.60; P<0.001) and women (b=−0.60; P<0.001), respectively. Moreover, each 1 min improvement in treadmill time, reduced the odds of a ≥5 kg gain by 14% in men (odds ratios (OR))=0.86; 95% confidence interval (CI): 0.83-0.89) and by 9% in women (OR=0.91; 95%CI:0.83-1.00) and the odds of a ≥10 kg gain by 21% in both men (OR=0.79;95% CI:0.75-0.84) and women (OR=0.79;95%CI:0.67-0.93)CONCLUSIONS: Improvements in fitness, appear important in attenuating age-related weight gain in healthy middle-aged adults. Thus, an active life-style should be promoted early and maintained through adulthood to prevent substantial weight gain and obesity with age.