Physical activity as a determinant of fasting and 2-h post-challenge glucose: a prospective cohort analysis of the NAVIGATOR trial.

AIM: To investigate whether previous physical activity levels are associated with blood glucose levels in individuals with impaired glucose tolerance in the context of an international pharmaceutical trial. METHODS: Data were analysed from the NAVIGATOR trial, which involved 9306 individuals with impaired glucose tolerance and high cardiovascular risk from 40 different countries, recruited in the period 2002-2004. Fasting glucose, 2-h post-challenge glucose and physical activity (pedometer) were assessed annually. A longitudinal regression analysis was used to determine whether physical activity levels 2 years (t-2 ) and 1 year (t-1 ) previously were associated with levels of glucose, after adjusting for previous glucose levels and other patient characteristics. Those participants with four consecutive annual measures of glucose and two consecutive measures of physical activity were included in the analysis. RESULTS: The analysis included 3964 individuals. Change in physical activity from t-2 to t-1 and activity levels at t-2 were both associated with 2-h glucose levels after adjustment for previous glucose levels and baseline characteristics; however, the associations were weak: a 100% increase in physical activity was associated with a 0.9% reduction in 2-h glucose levels. In addition, previous physical activity only explained an additional 0.05% of the variance in 2-h glucose over the variance explained by the history of 2-h glucose alone (R(2)  = 0.3473 vs. 0.3468). There was no association with fasting glucose. CONCLUSIONS: In the context of a large international clinical trial, previous physical activity levels did not meaningfully influence glucose levels in those with a high risk of chronic disease, after taking into account participants' previous trajectory of glucose control.

Feasibility of two levels of protein intake in patients with colorectal cancer: findings from the Protein Recommendation to Increase Muscle (PRIMe) randomized controlled pilot trial.

BACKGROUND: Low muscle mass (MM) predicts unfavorable outcomes in cancer. Protein intake supports muscle health, but oncologic recommendations are not well characterized. The objectives of this study were to evaluate the feasibility of dietary change to attain 1.0 or 2.0 g/kg/day protein diets, and the preliminary potential to halt MM loss and functional decline in patients starting chemotherapy for stage II-IV colorectal cancer. PATIENTS AND METHODS: Patients were randomized to the diets and provided individualized counseling. Assessments at baseline, 6 weeks, and 12 weeks included weighed 3-day food records, appendicular lean soft tissue index (ALSTI) by dual-energy X-ray absorptiometry to estimate MM, and physical function by the Short Physical Performance Battery (SPPB) test. RESULTS: Fifty patients (mean ± standard deviation: age, 57 ± 11 years; body mass index, 27.3 ± 5.6 kg/m2; and protein intake, 1.1 ± 0.4 g/kg/day) were included at baseline. At week 12, protein intake reached 1.6 g/kg/day in the 2.0 g/kg/day group and 1.2 g/kg/day in the 1.0 g/kg/day group (P = 0.012), resulting in a group difference of 0.4 g/kg/day rather than 1.0 g/kg/day. Over one-half (59%) of patients in the 2.0 g/kg/day group maintained or gained MM compared with 44% of patients in the 1.0 g/kg/day group (P = 0.523). Percent change in ALSTI did not differ between groups [2.0 g/kg/day group (mean ± standard deviation): 0.5% ± 4.6%; 1.0 g/kg/day group: -0.4% ± 6.1%; P = 0.619]. No differences in physical function were observed between groups. However, actual protein intake and SPPB were positively associated (ß = 0.37; 95% confidence interval 0.08-0.67; P = 0.014). CONCLUSION: Individualized nutrition counselling positively impacted protein intake. However, 2.0 g/kg/day was not attainable using our approach in this population, and group contamination occurred. Increased protein intake suggested positive effects on MM and physical function, highlighting the potential for nutrition to attenuate MM loss in patients with cancer. Nonetheless, muscle anabolism to any degree is clinically significant and beneficial to patients. Larger trials should explore the statistical significance and clinical relevance of protein interventions.

Quality of Life and Mental Health in Older Adults with Obesity and Frailty: Associations with a Weight Loss Intervention.

OBJECTIVE: To examine the bi-directional associations of a weight loss intervention with quality of life and mental health in obese older adults with functional limitations. DESIGN: Combined-group analyses of secondary variables from the MEASUR-UP randomized controlled trial. SETTING: Academic medical center. PARTICIPANTS: Obese community-dwelling men and women (N = 67; age ≥60; BMI ≥30) with functional limitations (Short Physical Performance Battery [SPPB] score of 4-10 out of 12). INTERVENTION: Six-month reduced calorie diet at two protein levels. MEASUREMENTS: Weight, height, body composition, physical function, medical history, and mental health and quality of life assessments (Center for Epidemiologic Studies Depression Scale [CES-D]; Profile of Mood States [POMS], Pittsburgh Sleep Quality Index [PSQI]; Perceived Stress Scale [PSS]; Satisfaction with Life Scale [SWLS]; and Short Form Health Survey [SF-36]) were acquired at 0, 3 and 6 months. RESULTS: Physical composite quality of life (SF-36) improved significantly at 3 months (ß = 6.29, t2,48 = 2.60, p = 0.012) and 6 months (ß = 10.03, t2,48 = 4.83, p < 0.001), as did several domains of physical quality of life. Baseline depression symptoms (CES-D and POMS) were found to predict lower amounts of weight loss; higher baseline sleep latency (PSQI) and anger (POMS) predicted less improvement in physical function (SPPB). CONCLUSION: The significant bi-directional associations found between a weight loss intervention and mental health/quality of life, including substantial improvements in physical quality of life with obesity treatment, indicate the importance of considering mental health and quality of life as part of any weight loss intervention for older adults.

Regulation of renal 25-hydroxyvitamin D-1-hydroxylase activity in the mouse after uninephrectomy.

Although renal hypertrophy occurs rapidly after uninephrectomy, restoring the majority of renal excretory function, it remains unknown whether similar compensatory mechanisms maintain 1,25-dihydroxyvitamin D production (and calcium homeostasis). To address this issue we compared plasma calcitriol levels and renal 25-hydroxyvitamin D (25OHD)-1-alpha-hydroxylase activity (in remnant kidneys) of mice at various times after uninephrectomy to similar observations obtained in sham-operated age- and sex-matched controls. At all times postoperatively, the uninephrectomized mice sustained plasma 1,25-dihydroxyvitamin D levels no different from those of shams. Maintenance of calcitriol production occurred secondary to a significant increment of renal 25OHD-1 alpha-hydroxylase activity (per mg DNA) 1-3 days after surgery when renal mass/function remained markedly depressed. In contrast, 10 and 21 days postoperatively, when hypertrophy was complete, enhanced enzyme function was no longer apparent. Throughout this period a significant inverse linear correlation existed between renal 25OHD-1 alpha-hydroxylase and the renal mass as well as glomerular filtration rate and renal blood flow. The variance in enzyme activity resulted in maintenance of a stable renal 25OHD-1 alpha-hydroxylase (per animal or total kidney mass) at all times investigated postuninephrectomy. Such compensatory regulation of vitamin D metabolism after unilateral kidney extirpation may be an important factor contributing to the low morbidity/mortality in the renal donor.

Cyclosporin-A increases synthesis of 1,25-dihydroxyvitamin D3 in the rat and mouse.

We have previously observed elevated serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D] levels in male rats treated with oral cyclosporin-A (CsA). This elevation was independent of changes in PTH, ionized calcium, or phosphate. This paper investigates the potential sources and mechanisms for this increase in both rats and mice. Kidney homogenates from rats treated for 14 days with (15 mg/kg) had a significant increase in 25-hydroxyvitamin D (25OHD)-24-hydroxylase (24-hydroxylase) activity (149 +/- 20 vs. 89 +/- 16 fmol/mg.min; P less than 0.05), but nonsignificant increases in 25OHD-1 alpha-hydroxylase (1 alpha-hydroxylase) activity compared to controls. Kidney homogenates from C57b16J mice after the administration of 30-50 mg/kg CsA for 3 days revealed a linear dose-related increase in renal 1 alpha-hydroxylase (r = 0.96; P less than 0.05), which became significant with doses of 30 mg/kg CsA or more (P less than 0.05). To investigate the source of this 1,25-(OH)2D production, serum 1,25-(OH)2D was measured before and 48 h after bilateral nephrectomy in rats receiving CsA for 16 days. The percent decrease in serum 1,25-(OH)2D values was not significantly different in CsA-treated and untreated rats (33.9 +/- 4.9% vs. 47.5 +/- 4.9%), indicating little or no contribution from nonrenal sources. Studies of MCRs and production rates (PRs) revealed that the elevated 1,25-(OH)2D values were due to enhanced production and not altered clearance (PR, 12.4 +/- 1.2 vs. 19.1 +/- 1.9 fmol/mg.min; P less than 0.01). CsA increases 1 alpha-hydroxylase activity and produces significant elevations in serum 1,25-(OH)2D levels in both rats and mice. This increase may have an impact on bone mineral metabolism and immune modulation in postorgan transplantation patients.

The effect of age on plasma zinc uptake and taste acuity.

Plasma uptake of a 25 mg oral dose of zinc was measured at 0, 1, 2, 3, and 4 h postdose in 16 elderly (mean age = 7.25 yr) and 12 young (mean age = 24.0 yr) subjects selected from a group of 62 healthy nonsmokers. Elderly and young subjects were divided into two groups based upon low or high detection thresholds for solutions of sodium chloride and sucrose. Mean fasting concentrations of plasma zinc were almost identical for the two age groups. Plasma response to a zinc dose was lower (p less than 0.05) in the elderly compared to that in the young, as indicated by plasma zinc levels at hours 2 and 3 postdose and by total area under the response curve. Moderate but significant age-associated increases in detection thresholds for both sodium chloride and sucrose were found; taste thresholds were not correlated to plasma uptake of the zinc dose in either age group.

Zinc, magnesium, copper, and protein concentrations in human saliva: age- and sex-related differences.

Normal concentrations of trace elements in parotid saliva, supernatant- and sediment-mixed saliva, plasma, and hair were determined in 278 healthy adults grouped as young (18-29 y), middle-aged (30-64 y), and elderly (65-93 y). Age-related increases (p less than 0.05) were observed in concentrations of zinc in the supernatant of mixed saliva and parotid saliva, copper in plasma, and protein in all fractions of saliva studied. Concentrations of zinc in salivary sediment and plasma did not vary with age. Age-related decreases (p less than 0.05) were found in concentrations of magnesium in mixed-saliva supernatant, copper in salivary sediment, and zinc and copper in hair. Males had higher concentrations of zinc in plasma (p less than 0.05) and of copper in sediment (p less than 0.01) than did females but lower amounts of copper in plasma and of protein in parotid saliva (p less than 0.05). Concentrations of zinc in saliva were not correlated with those in plasma or hair. Copper in mixed-saliva supernatant was positively associated with concentrations in plasma but negatively related to concentrations in hair.

Effects on blood lipids of a blood pressure-lowering diet: the Dietary Approaches to Stop Hypertension (DASH) Trial.

BACKGROUND: Effects of diet on blood lipids are best known in white men, and effects of type of carbohydrate on triacylglycerol concentrations are not well defined. OBJECTIVE: Our goal was to determine the effects of diet on plasma lipids, focusing on subgroups by sex, race, and baseline lipid concentrations. DESIGN: This was a randomized controlled outpatient feeding trial conducted in 4 field centers. The subjects were 436 participants of the Dietary Approaches to Stop Hypertension (DASH) Trial [mean age: 44.6 y; 60% African American; baseline total cholesterol: < or = 6.7 mmol/L (< or = 260 mg/dL)]. The intervention consisted of 8 wk of a control diet, a diet increased in fruit and vegetables, or a diet increased in fruit, vegetables, and low-fat dairy products and reduced in saturated fat, total fat, and cholesterol (DASH diet), during which time subjects remained weight stable. The main outcome measures were fasting total cholesterol, LDL cholesterol, HDL cholesterol, and triacylglycerol. RESULTS: Relative to the control diet, the DASH diet resulted in lower total (-0.35 mmol/L, or -13.7 mg/dL), LDL- (-0.28 mmol/L, or -10.7 mg/dL), and HDL- (-0.09 mmol/L, or -3.7 mg/dL) cholesterol concentrations (all P < 0.0001), without significant effects on triacylglycerol. The net reductions in total and LDL cholesterol in men were greater than those in women by 0.27 mmol/L, or 10.3 mg/dL (P = 0.052), and by 0.29 mmol/L, or 11.2 mg/dL (P < 0.02), respectively. Changes in lipids did not differ significantly by race or baseline lipid concentrations, except for HDL, which decreased more in participants with higher baseline HDL-cholesterol concentrations than in those with lower baseline HDL-cholesterol concentrations. The fruit and vegetable diet produced few significant lipid changes. CONCLUSIONS: The DASH diet is likely to reduce coronary heart disease risk. The possible opposing effect on coronary heart disease risk of HDL reduction needs further study.

Long-term protein and calorie restriction: alterations in nucleic acid levels of organs of male rats.

The effects of dietary restriction (calorie and/or protein) imposed at weaning on tissue concentrations of nucleic acids and protein were determined in young (one year) and old (two year) rats. In liver, calorie restriction increased protein concentration and decreased RNA/DNA and RNA/protein, while protein restriction elevated liver DNA and reduced protein and protein/DNA. These changes are consistent with decreased liver cell size in response to protein, but not calorie, restriction. Age also influenced these parameters, since DNA (elevated), RNA/protein (elevated), protein (reduced), and protein/DNA (reduced) differed in livers of old as compared to young rats. In kidney, DNA concentrations were unaffected by age or dietary restriction. Although protein and nucleic acid concentrations are commonly used as baselines for expressing other biochemical parameters, our results indicate that in liver, these factors vary both with age and nutritional status.

Differential effects of dietary caloric and protein restriction in the aging rat.

Numerous studies have shown caloric restriction retards the physiological decline and increases the life span of animals. However, in these studies protein consumption was also reduced; thus, whether the beneficial effects were due to caloric or to protein restriction is unclear. To examine independently the effects of caloric and protein restriction on growth, renal function, and survival, caloric restricted male rats were fed 18, 30 or 42 percent casein diets that provided two-thirds of the quantity of diet consumed by groups fed 12, 20, or 28 percent casein diets ad libitum, respectively. Hence, caloric restricted groups consumed the same amount of protein as their paired ad libitum fed groups but one-third fewer calories. The results showed that caloric restriction decreased mature body weight, increased the rate of attaining mature body weight, retarded the age-associated decline in renal function, and increased survival. Protein restriction had no effect on mature body weight, decreased maturation rate, improved renal function, and decreased survival. Thus, protein restriction did not contribute to the survival-promoting effects of caloric restriction in rats.

Treatment of osteoporosis. The psychological impact of a medical education program on older patients.

Participants in a therapeutic program for osteoporosis were studied to determine if program participation improved psychological outcomes. The 4-day program included intensive education about the disease and its prognosis, physical therapy education, nutritional counseling, and medical evaluation and treatment. All therapeutic patients enrolled in the program over a one-year period (N = 38) were interviewed individually pre- and post-participation. Knowledge of osteoporosis, level of social support, coping styles, and perceptions of the impact of pain and chronicity were assessed. Patients reported improved future outlook despite continued concern about pain and chronicity. Mention of depression was reduced, and knowledge of osteoporosis increased significantly. In addition, there were meaningful changes in patients' understanding of disease management. These included knowing when to make specific changes and avoid harmful actions. The findings suggest that an educational program can have a positive impact on patients' coping. Educational efforts may be an important component in the management of chronic disease.

Nutrition and function: is there a relationship between body mass index and the functional capabilities of community-dwelling elderly?

OBJECTIVE: To determine if there is a relationship between body mass index and the ability to perform the usual activities of living in a sample of community-dwelling elderly. DESIGN: Secondary data analysis of The National Health and Nutrition Examination Survey-I Epidemiologic Follow-up Study (1982-1984). Follow-up home interview of a population-based sample originally interviewed between 1971 and 1975 in the National Health and Nutrition Examination Survey-I (NHANES-I). PARTICIPANTS: Survivors of the original NHANES-I cohort who were 65 years of age or older and who were living at home at the time of the second interview (n = 3061). Excluded were those who could not be found, refused participation, or were institutionalized (n = 220), and those without complete height and weight data (n = 194). MAIN OUTCOME MEASURE: Functional status as measured by a 26-item battery. RESULTS: Bivariate analysis revealed a greater risk for functional impairment for subjects with a low body mass index or a high body mass index. The greater the extreme of body mass index (either higher or lower), the greater the risk for functional impairment. Logistic regression analysis indicated that both high and low body mass index continued to be significantly related to functional status when 22 other potential confounders were included in the model. CONCLUSION: The body mass index is related to the functional capabilities of community-dwelling elderly. The inclusion of this simple measurement in the comprehensive assessment of community-dwelling elderly is supported.

Osteoporosis in late life: does health locus of control affect psychosocial adaptation?

Osteoporosis, a metabolic bone disease most prevalent in older adults, is a major public health problem. Although management of osteoporosis through diet, exercise, and medication has improved, little is known about the psychosocial consequences of this disabling disease. In an attempt to identify patient characteristics that would provide physicians with insight into appropriate management styles for older osteoporotics, we assessed 103 patients with osteoporosis for their health locus of control (HLOC) orientation. We examined the relationship between HLOC and patient outcomes after participation in the Duke University Preventive and Therapeutic Program for Osteoporosis (DUPATPO) to determine whether HLOC was associated with functioning after program participation. More specifically, we asked whether internal or external HLOC was associated with decreases in depression, psychiatric symptoms, and stress symptoms, or with increases in self-esteem, exercise, and disease knowledge. We have shown in our earlier work (Gold et al, J Am Geriatr Soc 1989; 37:417) that program participation is associated with improved functioning in older adults. We now asked whether knowledge of a patient's HLOC would help predict these improvements. A comparison group (ie, older osteoporotics who did not participate in DUPATPO) was also assessed for HLOC to examine the possible association between HLOC and health behaviors regardless of the DUPATPO intervention. Our findings indicate that HLOC provided little useful information regarding patient outcomes. Although improvements were seen in the mental health of program participants, no association between these improvements and HLOC could be found.

Studies of a targeted risk reduction intervention through defined exercise (STRRIDE).

PURPOSE: The Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) trial is a randomized controlled clinical trial designed to study the effects of exercise training regimens differing in dose (kcal.wk-1) and/or intensity (relative to peak VO2) on established cardiovascular risk factors and to investigate the peripheral biologic mechanisms through which chronic physical activity alters carbohydrate and lipid metabolism to result in improvements in these parameters of cardiovascular risk in humans. METHODS: We will recruit 384 subjects and randomly assign them to one of three exercise training regimens or to a sedentary control group. The recruiting goal is to attain a subject population that is 50% female and 30% ethnic minority. The overall strategy is to use graded exercise training regimens in moderately overweight subjects with impairments in insulin action and mild to moderate lipid abnormalities to investigate whether there are dose or intensity effects and whether adaptations in skeletal muscle (fiber type, metabolic capacity, and/or capillary surface area) account for improvements in insulin action and parameters of lipoprotein metabolism. We will study these variables before and after exercise training, and over the course of a 2-wk detraining period. The study sample size is chosen to power the study to examine differences in responses between subjects of different gender and ethnicity to exercise training with respect to the least sensitive parameter-skeletal muscle capillary density. RESULTS: The driving hypothesis is that improvements in cardiovascular risk parameters derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle. CONCLUSION: Identification that amount and intensity of exercise matter for achieving general and specific health benefits and a better understanding of the peripheral mechanisms mediating the responses in carbohydrate and lipid metabolism to chronic physical activity will lead to better informed recommendations for those undertaking an exercise program to improve cardiovascular risk.

The effect of zinc deficiency and food restriction on prostaglandin E2 and thromboxane B2 in saliva and plasma of rats.

Zinc has been implicated in the regulation of prostaglandins and other arachidonic acid derivatives. Studies of zinc-deficient animals, however, are compromised by concomitant reduction in food intake that may also alter eicosanoid levels in body tissues and fluids. In this study, three groups of rats, designated as zinc-deficient, pair-fed and control, were fed diets containing 1 ppm, 15 ppm (in amounts paired to deficient rats) and 15 ppm Zn ad libitum, respectively, for 6 weeks. Saliva and blood were analyzed for PGE2 and TXB2 by radioimmunoassay. Saliva concentrations of both eicosanoids were lower (p less than 0.05) in the pair-fed animals, but not significantly altered by zinc deficiency. Plasma levels of PGE2 and TXB2 were unchanged by either zinc deficiency or food restriction. The results of this study support the contention that the effect of zinc on these prostaglandins is not mediated by altered rates of synthesis or degradation but rather by effects on eicosanoid function.

Community dwelling elderly are appropriate subjects for intensive dietary choice restriction studies.

There is a traditional belief that the elderly have difficulty coping with dietary change, and therefore have a diminished likelihood of successfully responding to nutritional interventions or restrictions. Using a controlled mild zinc-deficiency feeding study as a model for strict dietary intervention, we assessed psychological responses to severe dietary choice restriction in 15 Caucasian, elderly (66.12 +/- 4.43 years) males (n= 7) and females (n = 8). Participants completed the Medical Outcomes Study Short Form 36-Item Questionnaire (SF-36) as an index of QOL and the Multi-dimensional Health Locus of Control (MHLC) as a measure of health beliefs at pre-intervention baseline, post-intervention, and follow-up. No subjects dropped out nor were any meals missed during the entire 21-day feeding study period. No significant differences were detected across time on the MHLC (Internal F = 0.53, P = 0.6; Powerful Others F = 0.28, P = 0.8; Chance F = 1.1, P = 0.4.) by one-way ANOVA. Similarly, for the SF-36 no significant differences were found across time (F = 0.76, P = 0.5). Our results suggest that restricting dietary choices does not negatively impact older adult subjects and that they can cope well with dietary choice restriction and change. Older adults should not be overlooked for nutritional intervention solely due to age considerations.

Effect of age of initiation of feed restriction on growth, body composition, and longevity of rats.

Male Wistar rats were maintained on four dietary regimens: fed ad libitum throughout life (A); fed intermittently either during the first year of life and ad libitum thereafter (RA) or vice versa (AR); and fed intermittently throughout life (R). Low body weights, low amounts of body components (protein, fat, moisture, and ash), and long life spans were observed in R. AR and RA lost or gained body weight, respectively, after dietary transfer and lived longer than A. Maximum body weight and the age at which it was attained were correlated positively with life span in A. Predicted mature body weight was correlated negatively with life span in R. RA and AR differed in growth and body composition, but their life spans were similar and intermediate to those of A and R. Increases in life span were obtained by intermittent feeding during all or part of the life span, but growth and body composition data did not consistently explain the mechanism of this effect.