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© 2017 Warden et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Our objective is to identify genes that influence the development of any phenotypes of type 2 diabetes (T2D) or kidney disease in obese animals. We use the reproductively isolated UC Davis fatty Zucker strain rat model in which the defective chromosome 4 leptin receptor (LeprfaSte/faSte) results in fatty obesity. We previously produced a congenic strain with the distal half of chromosome 1 from the Brown Norway strain (BN) on a Zucker (ZUC) background (BN.ZUC-D1Rat183–D1Rat90). Previously published studies in males showed that the BN congenic donor region protects from some phenotypes of renal dysfunction and T2D. We now expand our studies to include females and expand phenotyping to gene expression. We performed diabetes and kidney disease phenotyping in chow-fed females of the BN.ZUC-D1Rat183-D1Rat90 congenic strain to determine the specific characteristics of the UC Davis model. Fatty LeprfaSte/faSteanimals of both BN and ZUC genotype in the congenic donor region had prediabetic levels of fasting blood glucose and blood glucose 2 hours after a glucose tolerance test. We observed significant congenic strain chromosome 1 genotype effects of the BN donor region in fatty females that resulted in decreased food intake, urine volume, glucose area under the curve during glucose tolerance test, plasma triglyceride levels, and urine glucose excretion per day. In fatty females, there were significant congenic strain BN genotype effects on non-fasted plasma urea nitrogen, triglyceride, and creatinine. Congenic region genotype effects were observed by quantitative PCR of mRNA from the kidney for six genes, all located in the chromosome 1 BN donor region, with potential effects on T2D or kidney function. The results are consistent with the hypothesis that the BN genotype chromosome 1 congenic region influences traits of both type 2 diabetes and kidney function in fatty UC Davis ZUC females and that there are many positional candidate genes.

The clinical effects and tolerability of a novel herbal formulation comprising the extracts of Sphaeranthus indicus and Garcinia mangostana were assessed in two similarly designed randomized, double-blind, placebo-controlled, clinical trials in 100 human subjects with a body mass index (BMI) between 30 and 40 kg/m2. Participants were randomized into two groups receiving either 400 mg of herbal blend twice daily or two identical placebo capsules. All subjects received three meals (2000 kcal/day) throughout the study and walked 5 days a week for 30 min. The primary outcome was reduction in body weight. Secondary outcomes were reduction in BMI and in waist and hip circumference. Serum glycemic, lipid, and adiponectin levels were also measured. Ninety-five subjects completed the trials, and data from these two studies were pooled and analyzed. At study conclusion (8 weeks), statistically significant reductions in body weight (5.2 kg; P

American Indians and Alaska Natives (ANs) report among the lowest levels of physical activity in the USA, but there is very little systematic research examining the determinants of physical activity patterns in these populations. This study investigated the relationships between enculturation (or cultural traditionality), psychosocial stress, and physical activity in a community-based sample of Yup'ik women and men living in rural AN communities. Associations between these variables and several metabolic risk factors were also examined.A sample of 488 Yup'ik participants (284 women and 204 men) from six villages in the Yukon-Kuskokwim Delta region completed a wellness survey and an array of physiological assessments [e.g., body mass index (BMI), blood pressure]. A subset of 179 participants also completed a 3-day pedometer assessment of physical activity.Multivariate linear regression models indicated that participants who were more enculturated (i.e., living more of a traditional lifestyle) and who experienced lower levels of psychosocial stress were significantly more physically active. In turn, both lower levels of psychosocial stress and higher levels of physical activity were associated with lower BMI, lower percent body fat, and lower waist circumference.Findings underscore the importance of gaining a culturally specific understanding of physical activity patterns in indigenous groups in order to inform effective health promotion strategies.

Linkage mapping in a backcross of {Brown Norway [BN/Crl (BN)] × ZUC- LeprfaSte(ZUC)} × ZUC identified a male-specific quantitative trait locus (QTL) for urinary albumin excretion (UAE) on rat chromosome 1. A homozygous ZUC.BN-( D1Rat42- D1Rat90)/Ste congenic was produced containing BN donor alleles from 135 to 276 Mb from chromosome 1 on the ZUC background. We observed threefold higher urinary albumin-to-creatinine ratios (ACR) in 15-wk-old Zucker background strain males than in same sex and age congenic animals when both strains are also homozygous for the ZUC leptin receptor fatty mutation ( LeprfaSte) ( P < 0.0001). We then linkage mapped within the donor region without confounded effects from other chromosomes. Phenotypes were collected in 248 F2 male rats in a population made by crossing parents heterozygous for both the BN donor region and ZUC LeprfaSte. Significant interactions were observed between the Lepr genotype and chromosome 1 QTL for six renal traits: urine volume, UAE at 10 and 15 wk, ACR, right kidney weight, and plasma urea nitrogen. A few traits, such as UAE and ACR, exhibit a second peak at the distal end of the chromosome. Hydronephrosis exhibited one or two QTLs contingent on adjustment for body weight. The results now demonstrate at least two sets of coincident traits with different correlations to kidney function.

Sodium chloride holds a unique position in the annals of human existence and science (1). For thousands of years, salt's high value has made it the foundation of a society, a currency of trade, and cause for wars. Over the past century, sodium chloride has been the subject of intense scientific research to understand its role in human physiology and its impact on health. The latter has focused primarily on salt's role in BP regulation, an issue fraught with controversy, as documented a decade ago (2) and still evident in the scientific literature (3,4). Since the first Surgeon General's Report Healthy People: Promotion and Disease Prevention published in 1979 (5), public health guidelines have recommended that adults consume less salt. This culminated in 2003 with the Institute of Medicine (IOM) Electrolyte DRI Committee targeting 2300 mg/d as the safe upper level of sodium in the diet (6). The 2005 Dietary Guidelines recommended this same level for healthy adults and 1500 mg/d for individuals at risk of hypertension (7). As increasingly more restrictive guidelines have been introduced over the past 30 yr, scientific research has continued to provide new insights regarding the effectiveness and safety of lowering sodium intake. Some, but certainly not all, of the newer data have supported the sodium guidelines (8,9), although the feasibility of their implementation remains in question. It has been assumed that if adults better understood how to reduce sodium in their diets and if more low-sodium foods were available, more individuals would be able to achieve these levels. Public health experts throughout the world have devised strategies targeting greater compliance with the lower sodium recommendations. In the United States (US), a special IOM committee has recently been charged to formulate such strategies (10). Great Britain initiated an intense …

Nutrition Reviews has had a continuing interest in the scientific basis of arguments for and against health claims on foods. Such claims were first authorized by the Food and Drug Administration (FDA) in 1993 under the terms of the Nutrition Labelling and Education Act of the U.S. Congress, passed in 1990. Since then there have been petitions that have resulted in a newly authorized claim for oats and other petitions directed toward modification or deletion of the originally approved claims. The Salt Institute, an industry-supported organization, has actively participated in the discussions regarding the sodium and hypertension health claim. The scientists signing this statement are familiar with the evolving understanding of the relationship between sodium and hypertension. The statement reviews more recent studies and critiques the arguments for a sodium health claim. We invite our readers to respond to the discussion in this controversial area of nutrition science and policy.

OBJECTIVE: To investigate the impact of a Westernizing diet on fat intake, red blood cell fatty acid composition, and health risks among Yup’ik Eskimos living in rural Alaskan Native communities. DESIGN: Diet data and blood specimens were collected from 530 Yup’ik Eskimos aged 14 to 94 years old. Height, weight, and waist circumference were measured. STATISTICAL ANALYSES: Comparisons of select fatty acid intake between participants in quintiles of traditional food intake (percent energy) were made using analyses of variance and post hoc Bonferroni tests. General linear models were used to determine the association between traditional food intake and health outcomes. RESULTS: Fatty acid composition of the diet differed according to the level of traditional food intake. Traditional food intake was positively associated with higher total fat, eicosapentaenoic acid, and docosahexaenoic acid intake. No association was observed between traditional food intake and saturated fatty acid intake; indeed, participants consuming more traditional foods derived a substantially smaller proportion of their dietary fatty acids from saturated fatty acids (P

Asthma is a serious health problem that is more prevalent among low-income persons. The risk of asthma and the severity of its symptoms may be increased by the low dietary intake of magnesium and other nutrients that protect against asthma, coupled with the high energy intakes that result in overweight and obesity. This study compared people with asthma to healthy controls, and showed that total body magnesium stores decreased with increasing weight, as measured by body mass index (BMI). Replacing low-magnesium foods with high-magnesium foods may be a practical, low-cost way to help reduce the risk of obesity and low magnesium status in people with asthma, especially in at-risk, low-income groups.

OBJECTIVES: To determine whether dietary westernization is associated with intake of select nutrients among Alaska Natives living in remote communities. To investigate participant characteristics associated with adherence to the traditional Alaska Native diet. STUDY DESIGN: Cross-sectional survey. METHODS: A 24-hour recall was collected from 241 men and 307 women aged 14-94 years living in seven remote communities of Western Alaska. Bivariate analyses and ANOVA were used to examine the relationship between energy from traditional foods (the primary variable of interest), participant characteristics and intake of select nutrients. RESULTS: Traditional foods accounted for 22% of energy intake.overall. This estimate varied by age, educational attainment, and geographic location. Participants in the highest quintile of traditional food intake consumed significantly more vitamin A, vitamin D, Vitamin E, Iron, and n-3 fatty acids than participants in the lowest quintile (p < 0.001). Intake of vitamin C, calcium, and total dietary fiber decreased with increased consumption of traditional foods (p < 0.001). CONCLUSIONS: The degree of dietary westernization contributes to nutrient intake, both positively and negatively, in a dose response manner. Participant characteristics, particularly age, must be addressed in the development of a nutrition education program since they are associated with distinct dietary intakes.Keywords: Alaska Natives; diet; dietary westernization; traditional foods(Int J Circumpolar Health 2007; 66(1):62-70)

Obesity is becoming a global epidemic in both children and adults, and it is associated with numerous co-morbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, is an independent risk factor for CVD and CVD risks have been also documented in obese children, and is associated with reduced life expectancy. A variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amount. As a whole, overweight/obesity predispose or is associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death through its impact on the cardiovascular system.

Magnesium (Mg) may be a significant factor in asthma management. There is debate about how to best assess Mg status. We evaluated multiple indices of Mg status and lung function in 52 people with mild to moderate asthma and 47 controls. Mg measures included serum total, ionized and erythrocyte Mg, intravenous Mg load retention and dietary recall. Methacholine challenge and pulmonary function tests were used to assess diagnosis and severity of asthma. Mg status was similar in asthma and controls, and was not correlated to lung function. Total serum Mg closely reflected ionized Mg and offers a useful clinical diagnostic monitor.

Obesity has been defined as a distinct disease by the World Health Organization, National Institutes of Health, Centers for Disease Control and Prevention, and the American Dietetic Association. In the United States, a major reimbursement challenge is to promote acceptance of obesity as a chronic disease and acceptance of its treatment by health management organizations, private insurers, and the government. The United States health care system is focused on treating individual obesity-related diseases, but does not treat obesity as the underlying cause. Reimbursement of obesity treatments using "condition coverage" based on the presence of other diseases does not allow obesity to be treated independently as a disease in itself. It is necessary to make major investments in research to determine the best methods and to match the treatment with the individual, to prevent obesity in vulnerable populations, and to develop more effective drugs and treatments for those already overweight or obese. There should be a more detailed analysis of the cost of obesity, costs associated with obesity and obesity-related disease treatment, and costs of inaction. The obesity epidemic is too large to be ignored. Health care professionals have a duty to be informed about the disease and to advocate for patients who need help. Registered dietitians can be key players in delivering obesity treatment.

Objective Chitosan is a primary ingredient in dietary weight-loss supplements. Its claimed activity is the binding and trapping of dietary fat, leading to fat excretion and weight loss without caloric restriction. We tested the fat-trapping capacity of a chitosan product in men and women. Design Participants (12 men, 12 women) were instructed to follow customized diet plans (five meals/day for 12 days). Oral charcoal markers defined two 4-day experimental periods. Two capsules were taken five times per day before each meal during the supplement period (2.5 g chitosan/day) and not during the control period. Feces were collected from day 2 to day 12. Feces from each period were pooled and analyzed for fat content. Results For men (mean±standard deviation=24.8±5.1 years, body mass index [BMI; calculated as kg/m 2 ] 26.6±4.5) the average daily was 137±31 g fat and 3,256±624 kcal. For women (23.3±5.0 years, BMI 24.1±3.5) average daily 89±16 g fat and 2,110±195 kcal. Each two-capsule dose was consumed with 28±11 g fat in males and 18±7 g in females (range =10-76 g/dose). Fecal fat excretion increased with chitosan by 1.8±2.4 g/day in males, P =.02, and did not increase with chitosan (0.0±1.4 g/day, P =.99) in females. Conclusions The fat trapped was clinically insignificant. For men, it would take more than 7 months to lose 1 pound of body fat. For women, no fat was trapped. This product, as with other similar products, fails to meet claims.

The prevalence of childhood and adolescent obesity has increased steadily over the past three decades such that obesity is now a major worldwide pediatric health risk factor. Pediatric obesity is associated with significant health problems, and is an important early risk factor for adult morbidity and mortality. This paper focuses on the role and components of optimal healing environments (OHEs) that may be useful in the management of childhood obesity: healing intention, healing relationships, health promotion and disease prevention, and healing spaces. Diet, physical activity, and behavior modification strategies used in the treatment of childhood obesity are also reviewed.

Objective: Effects of ectopic expression of the agouti signaling protein were studied on responses to diet restriction and exercise in C57BL/6J (B6) mice and obese B6 mice congenic for the yellow agouti mutation [B6.Cg-Ay (Ay)]. Research Methods and Procedures: Adult male Ay mice were either kept sedentary or exercised on a running wheel and fed ad libitum or diet restricted until weight matched to ad libitum-fed B6 control mice. Body composition, plasma lipids, leptin, and adiponectin were measured. mRNA levels for leptin, adiponectin, lipoprotein lipase, and pyruvate dehydrogenase kinase 4 were measured in a visceral (epididymal) and a subcutaneous (femoral) fat depot by real-time polymerase chain reaction. Results: Correlations among traits exhibited one of three patterns: similar lines for B6 and Ay mice, different slopes for B6 and Ay mice, and/or different intercepts for B6 and Ay mice. Correlations involving plasma leptin, mesenteric and epididymal adipose weights, or low-density lipoprotein-cholesterol were most likely to have different slopes and/or intercepts in B6 and Ay mice. mRNA levels for leptin, Acrp30, pyruvate dehydrogenase kinase 4, and lipoprotein lipase in epididymal adipose tissue were not correlated with corresponding levels in femoral adipose tissue. Discussion: The agouti protein interferes with leptin signaling at melanocortin receptors in the hypothalamus of Ay mice. Our results are consistent with the hypothesis that the melanocortin portion of the leptin-signaling pathway mediates effects primarily on certain fat depots and on some, but not all, components of cholesterol homeostasis.

Background: Obese premenopausal women are thought to be at low risk for osteoporosis due to increased body weight and effects of estrogen on weight-bearing bone. Objective: To examine the effect of restrained eating on obese women, we examined bone mineral density (BMD) and content (BMC) of the spine and femur in obese women who were restrained eaters, with emphasis on the relationship between BMC and determinants of bone mass, and current eating behaviors, dietary intake, physical activity, and indices of calcium regulation, bone metabolism, stress and inflammation. Design: A total of 78 obese, Caucasian, female, restrained eaters, ages 30–45 y, were enrolled in a weight lose program. Height, weight, bone turnover markers, serum parathyroid hormone (PTH), cortisol, c-reactive protein (CRP), dietary intake, eating behaviors, physical activity, and BMD and BMC were measured. Setting: This study was conducted at the University of California, in Davis, CA, USA. Results: In all, 31% of women had osteopenia or osteoporosis (OSTEO). In the OSTEO group, 87.5% of women had osteoporosis or osteopenia of the lumbar spine and 12.5% of the women had osteoporosis or osteopenia in femur. A significant positive correlation between BMC and energy expenditure (r=0.256), and a significant negative correlation between BMC and number of times on a weight loss diet (r=−0.250) and cognitive restraint (r=−0.239) were observed. No significant differences were observed between OSTEO women and nonosteoporotic women for current eating behaviors, dietary intake, physical activity habits, bone turnover, calcium regulation, stress, or inflammation. Conclusions: Obese restrained eaters are at risk for low bone mass. Prior dieting may be responsible. Chronic dieters should be encouraged to decrease their dietary restraint, develop healthy eating habits and increase physical activity.

In Brief The ideal model of obesity treatment is a comprehensive intervention including dietary, activity-related, behavioral, pharmacological, and/or surgical components that is geared toward individual needs, similar to the ideal treatment for diabetes. The main focus of any obesity intervention should be on health improvement instead of just body weight reduction. To resolve the controversies surrounding obesity, we must invest much more in research into the prevention of obesity and to ascertain those lifestyle or medical approaches that will make it easier for anyone to maintain a healthful energy balance.

This review explores whether fructose consumption might be a contributing factor to the development of obesity and the accompanying metabolic abnormalities observed in the insulin resistance syndrome. The per capita disappearance data for fructose from the combined consumption of sucrose and high-fructose corn syrup have increased by 26%, from 64 g/d in 1970 to 81 g/d in 1997. Both plasma insulin and leptin act in the central nervous system in the long-term regulation of energy homeostasis. Because fructose does not stimulate insulin secretion from pancreatic beta cells, the consumption of foods and beverages containing fructose produces smaller postprandial insulin excursions than does consumption of glucose-containing carbohydrate. Because leptin production is regulated by insulin responses to meals, fructose consumption also reduces circulating leptin concentrations. The combined effects of lowered circulating leptin and insulin in individuals who consume diets that are high in dietary fructose could therefore increase the likelihood of weight gain and its associated metabolic sequelae. In addition, fructose, compared with glucose, is preferentially metabolized to lipid in the liver. Fructose consumption induces insulin resistance, impaired glucose tolerance, hyperinsulinemia, hypertriacylglycerolemia, and hypertension in animal models. The data in humans are less clear. Although there are existing data on the metabolic and endocrine effects of dietary fructose that suggest that increased consumption of fructose may be detrimental in terms of body weight and adiposity and the metabolic indexes associated with the insulin resistance syndrome, much more research is needed to fully understand the metabolic effect of dietary fructose in humans.

BACKGROUND: The use of dietary supplements, especially those for weight control, is increasing. Advertising claims for some of these supplements may give consumers unrealistic expectations. For example, it is claimed that the supplement chitosan can block the absorption of up to 120 g of dietary fat per day. OBJECTIVE: To test the effect of a chitosan supplement used as directed, on the absorption of dietary fat. DESIGN: Seven healthy male volunteers with average age 28, range 23–30, average body mass index (BMI) 26, range 23–31, maintained a high fat intake (>120 g/day) for 12 days. On days 6–9, chitosan was taken as directed by the manufacturer prior to meals and snacks and totaled 15 capsules or 5.25 g of chitosan daily. A charcoal marker was consumed on days 2, 6 and 10 to mark the baseline and supplement periods. All feces were collected on days 2–12, and were divided based on the appearance of charcoal in the feces. Fecal fat content corresponding to the four baseline and four chitosan-supplemented days was measured. RESULTS: Average dietary fat intake did not differ between baseline (135±5 g), and chitosan (135±3 g) periods. Fecal fat excretion did not differ between the two periods (6.9±1.0 g/day baseline; 6.8±0.4 g/day chitosan). The fecal fat content as a percentage of fat consumed did not differ (5.1±0.7% baseline, 5.0±0.3% chitosan). Fecal mass did not differ (176±26 g/day baseline, 182±14 g/day chitosan). CONCLUSION: Consumption of this chitosan supplement did not increase fecal fat content and therefore did not block fat absorption.

We previously reported that a congenic rat with Brown Norway (BN) alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC). Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by1H nuclear magnetic resonance (NMR) spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9-24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF) level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age. © 2014 Warden et al.

Foods provide nutrients such as vitamins, minerals, protein, carbohydrate and fat and a host of other nonessential nutrients that may confer health benefits. Some “nutraceuticals” have been found to boost the immune system, enhance memory function and possibly slow the aging process. For example, flavonoids — which are found in red wine, purple grape juice, green tea and cocoa products — exhibit potent antioxidant activity in laboratory experiments and have been postulated to protect against coronary artery disease and reduce the risk of cancer. Recognizing potential health benefits from flavonoids and other plant extracts, some manufacturers are creating “functional” foods by fortifying, bioengineering and otherwise modifying foods so that they contain higher than normal concentrations of these components. With the exception of echinacea, St. John's wort and Ginkgo biloba, there is a paucity of scientific data for the majority of botanicals sold in health food stores and supermarkets. At the same time, adverse reactions to some botanicals have been documented in humans. Many would argue that government regulation of botanicals is inadequate. Further studies and comprehensive databases are needed to establish the safety and efficacy of popular and widely consumed dietary supplements.

Objective To assess the impact of increased consumption of milk, without other dietary advice, on older adults' energy and nutrient intakes, weight, cardiovascular risk factors (blood pressure, plasma lipid levels), and quality of life. Subjects/setting Two hundred four healthy men and women, aged 55 to 85 years, who consumed fewer than 1.5 dairy servings per day were chosen from six US academic health centers. Design Randomized, controlled open trial. Intervention Advice to increase skim or 1% milk intake by 3 cups per day (n=101) or to maintain usual diet (n=103) for 12 weeks after a 4-week baseline period. Main outcome measures Changes in energy and nutrient intake assessed from 3-day food records, body weight, blood pressure, and plasma lipid levels. Statistical analyses performed Group-by-time analysis of variance with repeated-measures, χ 2 test. Results Compliance with the intervention was good. Compared with controls, participants in the milk-supplemented group significantly increased energy, protein, cholesterol, vitamins A, D, and B-12, riboflavin, pantothen ate, calcium, phosphorus, magnesium, zinc, and potassium intakes. Prevalence of nutrient inadequacy, assessed for nutrients with Estimated Average Requirements, decreased among women in the milk group for magnesium (40% .at baseline vs 13% at 12 weeks, P P P P P =.002). Quality of life scores were high at baseline and remained high throughout. Applications/conclusions Older adults can successfully increase milk intake, thereby meaningfully improving their nutrient intakes. Dietitians can play a key role in disseminating this advice. J Am Diet Assoc. 2000; 100:810-817 .

Asthma is among the most common chronic diseases of the western world and has significant effects on patients' health and quality of life. Asthma is typically treated with pharmaceutical products, but there is interest in finding nonpharmaceutical therapies for this condition. Hypnosis has been used clinically to treat a variety of disorders that are refractive to pharmaceutical-based therapies, including asthma, but relatively little attention has been given recently to the use of clinical hypnosis as a standard treatment for asthma. Significant data suggest that hypnosis may be an effective treatment for asthma, but it is premature to conclude that hypnosis is unequivocally effective. Studies conducted to date have consistently demonstrated an effect of hypnosis with asthma. More and larger randomized, controlled studies are needed. Existing data suggest that hypnosis efficacy is enhanced in subjects who are susceptible to the treatment modality, with experienced investigators, when administered over several sessions, and when reinforced by patient autohypnosis. Children in particular appear to respond well to hypnosis as a tool for improving asthma symptoms.

Objective To compare a nutritionally complete prepared meal plan that meets national dietary guidelines to usual-care dietary therapy for hypertension, dyslipidemia, and glycemic control. Design Randomized, controlled trial. Subjects/setting Outpatients with hypertension, dyslipidemia, or diabetes mellitus (n=251) were recruited at 6 medical centers in the United States and Canada. Intervention The prepared meal plan, which was developed by university-based nutrition and cardiovascular scientists and food technologists at Campbell's Center for Nutrition & Wellness (CCNW), provided the optimal levels of macronutrients and micronutrients recommended for cardiovascular risk reduction in a variety of prepackaged meals and snacks. After a 4-week pretrial period to assess baseline state, participants were randomized to the CCNW plan or "usual-care" diet for 10 weeks. Main outcome measures Blood pressure, carbohydrate metabolism, lipoproteins, homocysteine, weight, nutrient intake, compliance. Statistical analyses performed Repeated measures analysis of variance. Results Lipoproteins, carbohydrate metabolism, blood pressure, and weight improved on both plans. Mean differences (±standard deviation) between baseline and follow-up for the CCNW plan and the usual-care plan, respectively, were total cholesterol, −0.41±0.64 and −0.20±.50mmol/L (between-group P P P =.67), diastolic blood pressure, −3.8±5.9 and −2.2±5.5mmHg ( P P P Applications/conclusion The nutritionally complete CCNW plan offers greater improvements in lipids, blood sugars, homocysteine, and weight loss than usual-care diet therapy. This prepackaged comprehensive nutrition program can augment both the prescription and practice of optimal dietary therapy. J Am Diet Assoc. 1999;99:1077–1083

OBJECTIVE: To evaluate the clinical effects of a comprehensive prepackaged meal plan, incorporating the overall dietary guidelines of the American Diabetes Association and other national health organizations, relative to those of a self-selected diet based on exchange lists in free-living individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 202 women and men (BMI < or = 42 kg/m2) whose diabetes was treated with diet alone or an oral hypoglycemic agent were enrolled at 10 medical centers. After a 4-week baseline period, participants were randomized to a nutrient-fortified prepared meal plan or a self-selected exchange-list diet for 10 weeks. On a caloric basis, both interventions were designed to provide 55-60% carbohydrate, 20-30% fat, and 15-20% protein. At intervals, 3-day food records were completed, and body weight, glycemic control, plasma lipids, and blood pressure were assessed. RESULTS: Food records showed that multiple nutritional improvements were achieved with both diet plans. There were significant overall reductions in body weight and BMI, fasting plasma glucose and serum insulin, fructosamine, HbA1c, total and LDL cholesterol, and blood pressure (P < 0.001 or better for all). In general, differences in major end points between the diet plans were not statistically significant. CONCLUSIONS: Glycemic control and cardiovascular risk factors improve in individuals with type 2 diabetes who consume diets in accordance with the American Diabetes Association guidelines. The prepared meal program was as clinically effective as the exchange-list diet. The prepared meal plan has the additional advantages of being easily prescribed and eliminating the complexities of meeting the multiple dietary recommendations for type 2 diabetes management.

Compared with the lean ( Fa/−) genotype, obese ( fa/fa) Zucker rats have a relative deficiency of muscle phospholipid arachidonate, and skeletal muscle arachidonate in humans is positively correlated with insulin sensitivity. To assess the hypothesis that the positive effects of exercise training on insulin sensitivity are mediated by increased muscle arachidonate, we randomized 20 lean and 20 obese weanling male Zucker rats to sedentary or treadmill exercise groups. After 9 wk, fasting serum, three skeletal muscles (white gastrocnemius, soleus, and extensor digitorum longus), and heart were obtained. Fasting insulin was halved by exercise training in the obese rat. In white gastrocnemius and extensor digitorum longus (fast-twitch muscles), but not in soleus (a slow-twitch muscle) or heart, phospholipid arachidonate was lower in obese than in lean rats ( P < 0.001). In all muscles, exercise in the obese rats reduced arachidonate ( P < 0.03, by ANOVA contrast). We conclude that improved insulin sensitivity with exercise in the obese genotype is not mediated by increased muscle arachidonate and that reduced muscle arachidonate in obese Zucker rats is unique to fast-twitch muscles.

Increased arterial pressure is known to be influenced by a variety of nutrients. Compliance with dietary recommendations for risk reduction is often limited by the complexity of their implementation. In addition, how improvements in total diet, rather than single nutrients, influence concomitant cardiovascular risk factors has not been thoroughly explored. We assessed the effects of a nutritionally complete prepared meal program, the Campbell's Center for Nutrition and Wellness plan (CCNW), compared with dietary therapy in which participants received a structured nutritional assessment and prescription and selected their own foods, in 101 women and men with mild-to-moderate hypertension. Outcome measures included blood pressure (BP), lipids and lipoproteins, glucose, glycosylated hemoglobin (HbA1c), insulin, homocysteine, nutrient intake, compliance, and quality of life. Both dietary interventions significantly lowered BP (P < .0001), while simultaneously improving the overall cardiovascular risk profile. Significantly greater benefits were observed with the CCNW plan as compared with the participant selected diet in cholesterol and LDL levels (both P < .0001), LDL:HDL (P < .001), HbA1c (P < .05), homocysteine (P < .001), total nutrient intake (P < .0001), compliance (P < .0001), and quality of life (P < .001). This study demonstrates that improving the total diet to include the full array of recommended dietary guidelines, rather than focusing on single nutrients, has significant benefits for the cardiovascular risk profile of hypertensive persons beyond BP control. Compared with typical dietary therapy, the comprehensive CCNW meal plan has significantly greater effects on multiple cardiovascular risk factors while yielding greater compliance and improved quality of life.

Popular demand for and scientific interest in complementary or alternative medicine, particularly medicinal botanicals, has increased considerably in recent years. The medicinal botanicals with the longest tradition, and for which extensive data are available, are Chinese herbal medicines and their Japanese counterparts--Kampo medicines. This review focuses on some representative examples of studies examining the effects of some traditional Chinese medicines on various aspects of the immune response. In vitro as well as in vivo studies are cited, the latter including not only animal experiments but also clinical trials. Although by no means exhaustive, this review attempts to show that much research has focused on the specific beneficial effects of Chinese herbal medicines. Studies examining the mechanisms by which they exert their immunomodulatory actions, however, are found much less frequently. Nonetheless, even the limited number of mechanistic experiments presented here reveal that numerous mechanisms are likely involved in the various actions of even a single medicine. It will be the elucidation of such mechanisms that will provide the scientific basis for establishing the efficacy and safety of not only Chinese herbal medicines but all forms of medicinal botanicals.

Background: Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet. Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction. Objective: To assess the clinical effects of this plan, which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins, minerals, and macronutrients, compared with a patient-selected American Heart Association Step I and Step II diet plan. Methods: This multicenter, randomized, parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension, dyslipidemia, or diabetes. Following calculation of prescriptions to meet individual nutritional requirements based on the HarrisBenedict equation, participants were randomized to the Campbell's Center for Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast, lunch, and dinner meals provided to participants, or a nutritionist-guided American Heart Association Step I and Step II diet, in which participants self-selected foods to meet their nutrition prescription for 10 weeks. Main Outcome Measures: Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c), and insulin levels; body weight; dietary intake; and quality of life. Results: Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life (P≤.001 for all findings except low-density lipoprotein-high-density lipoprotein ratio,P=.25) all improved on both nutrition plans. Mean differences (±SD) between baseline and treatment clinical values for the CCNW and the self-selected diet groups (between-groupPvalues), respectively, were as follows: systolic BP, -6.4±9.2 mm Hg and -4.6±9.0 mm Hg (P=.02);ic BP, -4.2±5.7-4.2±5.7 -3.0±5.1 m-3.0±5.1 mm Hg (P=.006)rol, -0.32±0.58-0.32±0.58 mmol/L and -0.27±0.56 mmol/L(-12.4±22.5 mg/dL and -10.4±21.9 mg/dL) (P=.30); glucose, -0.65±1.88 mmol/L andm-0.75±2.03 mmol/L (-11.7±34.0 mg/dL and -13.5±36.6 mg/dL) (P=.10); and HbA1c, -0.4%±0.8% and -0.3%±0.7% (P=.66). Weight loss with the CCNW and self-selected plans, respectively, was as follows: men, -4.5±3.6 kg and -3.5±3.3 kg; and women, -4.8±3.0 kg and -2.8±2.8 kg. Quality of life was significantly improved for daily and work activities (P Conclusions: Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease. The CCNW plan resulted in greater clinical benefits, nutritional completeness, and compliance than the self-selected diet. The CCNW is a comprehensive nutrition plan, convenient for both prescription and practice, and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease. disease. Arch Intern Med. 1997;157:169-177

Background The recommendation to restrict dietary sodium for management of hypertensive cardiovascular disease assumes that sodium intake exceeds physiologic need, that it can be significantly reduced, and that the reduction can be maintained over time. In contrast, neuroscientists have identified neural circuits in vertebrate animals that regulate sodium appetite within a narrow physiologic range. This study further validates our previous report that sodium intake, consistent with the neuroscience, tracks within a narrow range, consistent over time and across cultures. Methods Peer-reviewed publications reporting 24-hour urinary sodium excretion (UNaV) in a defined population that were not included in our 2009 publication were identified from the medical literature. These datasets were combined with those in our previous report of worldwide dietary sodium consumption. Results The new data included 129 surveys, representing 50,060 participants. The mean value and range of 24-hour UNaV in each of these datasets were within 1 SD of our previous estimate. The combined mean and normal range of sodium intake of the 129 datasets were nearly identical to that we previously reported (mean = 158.3±22.5 vs. 162.4±22.4 mmol/d). Merging the previous and new datasets (n = 190) yielded sodium consumption of 159.4±22.3 mmol/d (range = 114-210 mmol/d; 2,622-4,830mg/d). Conclusions Human sodium intake, as defined by 24-hour UNaV, is characterized by a narrow range that is remarkably reproducible over at least 5 decades and across 45 countries. As documented here, this range is determined by physiologic needs rather than environmental factors. Future guidelines should be based on this biologically determined range.

The clinical effects and tolerability of a novel herbal formulation comprising the extracts of Sphaeranthus indicus and Garcinia mangostana were assessed in two similarly designed randomized, double-blind, placebo-controlled, clinical trials in 100 human subjects with a body mass index (BMI) between 30 and 40 kg/m2. Participants were randomized into two groups receiving either 400 mg of herbal blend twice daily or two identical placebo capsules. All subjects received three meals (2000 kcal/day) throughout the study and walked 5 days a week for 30 min. The primary outcome was reduction in body weight. Secondary outcomes were reduction in BMI and in waist and hip circumference. Serum glycemic, lipid, and adiponectin levels were also measured. Ninety-five subjects completed the trials, and data from these two studies were pooled and analyzed. At study conclusion (8 weeks), statistically significant reductions in body weight (5.2 kg; P

The sections in this article are: 1 Consequences of Overnutrition 1.1 Thrifty Gene: Altered Lipid Metabolism 1.2 Animal Models 1.3 Physiological Consequences 2 Factors Influencing the Response to Overnutrition 2.1 Gender 2.2 Age 2.3 Genetics 2.4 Exercise 2.5 Stress 2.6 Diet Composition 2.7 Season/Food Availability 3 Physiological Mechanisms Underlying Responses to Overnutrition 3.1 Cellular 3.2 Endocrine Mechanisms 3.3 Neural Mechanisms Mediating the Response to Overnutrition 4 Summary

To develop recommendations for the design of special foods for young children, we measured total daily energy consumption from semisolid food mixtures with energy densities of 1.67, 2.93, 4. 18, or 6.28 kJ/g (0.4, 0.7, 1.0, or 1.5 kcal/g) and that were fed ad libitum three, four, or five times per day to 18 fully weaned children from 6 to 18 mo of age who were recovering in the hospital from malnutrition. The diets were generally indis- tinguishable by sensory qualities, and were fed in a randomized sequence. The mean amounts consumed (g . kg body wt ' � d 1) were significantly less with successively greater energy density of the diet (P < 0.001). The total daily consumption was = 16% more when the number of meals was increased from three to four per day, with energy density controlled for (P < 0.001), and 7% more when the feeding frequency rose from four to five meals per day (P = 0.005). The total daily energy intakes (kJ . kg body wt ' � d i) increased significantly with the more concentrated diets (P < 0.001) and varied positively in relation to feeding frequency (P < 0.001). Approximately 15-20 mm were required per meal for the children to reach satiety. The total amount of time required to feed the children each day was related to the number of meals served (P < 0.001) and not to energy density. Implications for child feeding are discussed. Am J Clin Nutr 1995;62:13-8.

A number of investigators have reported on the clinically significant relationship between diabetes mellitus and impaired wound healing. Diabetic patients have an increased frequency of infection, delayed scar formation, and poor bony union. Investigations completed in our laboratory have demonstrated that insulin-like growth factor type 1 (IGF-1), a somatomedin C, has shown promise for accelerating bony repair. The purpose of this study was to examine the effects of recombinant IGF-1 on standardized, critical-size calvarial defects in 25 adult, male streptozocin-induced diabetic rats. From our study, it appears that IGF-1 exerts a potentiating effect on the repair of bony defects in diabetes-induced rats.

The Wistar Diabetic Fatty rat (WDF fafa) is a congenic strain of the Wistar Kyoto rat. Studies using blood glucose reveal that only fatty male (not female) WDF rats spontaneously develop hyperglycemia when fed a stock diet. Blood glucose values have not provided consistent results for evaluation of glycemic status in fatty male WDF rats. Zucker fatty (fafa) rats, while sharing the fa gene and the development of hyperinsulinemia and hyperlipemia, do not spontaneously become hyperglycemic. In order to examine strain differences and the effects of age on long-term average glycemic status in WDF and Zucker rats, glycated hemoglobin (GHb) was analyzed. Glycated hemoglobin was measured in male lean and obese WDF and Zucker rats at 2, 3, 6, and 12 months of age. Nonfasted plasma glucose was measured in male lean and obese WDF rats at 2, 3, 6, and 12 months of age and in lean and obese Zucker rats at 3, 6, and 12 months of age. Plasma insulin was measured in lean and obese WDF and Zucker rats at 3, 6, and 12 months of age. Obese WDF rats had significantly elevated GHb compared to lean controls at 3, 6, and 12 months of age. Glycated hemoglobin was substantially above the normal range (3.8-6.5%) at 3 months of age (14.1%). Glycated hemoglobin significantly declined in the obese WDF rats between 6 and 12 months of age. Nonfasted plasma glucose was significantly elevated in the obese WDF rats at 3 months (14.1 +/- 2.1 mM/L) and 6 months of age (16.2 +/- 2.3 mM/L) compared to lean controls. At 12 months of age there was no difference in plasma glucose between obese and lean WDF rats. Obese and lean Zucker rats had similar levels of GHb and plasma glucose at all ages. In conclusion, GHb provides more integrated data for classifying disease status of WDF rats and evaluation of potential long-term complications associated with hyperglycemia.

Adipose tissue was obtained from six women undergoing liposuction twice at 6-mo intervals. Samples obtained bilaterally from abdomen, inner thigh, and outer thigh had fatty acids quantified by gas chromatography. There were no important differences between sides or over time. The saturates 14:0, 16:0, 18:0, and 20:0 were higher in abdominal adipose than in outer thigh (P < 0.002 for all); 16:1 and 18:1 omega 9 were lower in abdomen vs outer thigh (P < 0.01), whereas 18:1 omega 7 and 20:1 omega 9 were unchanged. Polyunsaturates 18:2 omega 6, 20:3 omega 6, and 20:4 omega 6 were higher in outer thigh than in abdomen (P < 0.06), and inner thigh values were intermediate. These changes in fatty acid composition resulted in lower mean triglyceride melting points from abdomen to inner thigh to outer thigh, and suggest that temperature may influence the selection process determining the variation in adipose fatty acid composition with anatomical location. Because the site-specific differences included essential fatty acids, selective uptake as well as potential differences in in situ fatty acid modification are indicated.

The purpose of the present investigation was to study the role of two potential contributory factors, hyperphagia and alterations in fuel metabolism, on the development of tissue trace element accumulation in the experimentally induced diabetic rat. The role of increased mineral intake associated with diabetic hyperphagia on tissue trace element accumulation was evaluated by feeding control and diabetic rats high-carbohydrate (HC) diets which varied in Zn, Cu, Mn, and Mg concentrations. Diabetic rats were hyperphagic and had lower plasma Mg, and higher liver Zn, Cu, and Mn concentrations than control rats, regardless of dietary mineral intake. In a second study, diabetic hyperphagia was reduced by feeding control and diabetic rats a HC, high-fat (HF), or high-protein (HP) diet; the effects of altering diabetic metabolism on trace element status was studied. Liver Mn and Zn concentrations of diabetic rats fed the HF diet were lower than diabetic rats fed the HC diet and HP diet, and were similar to control rats. Liver Cu concentrations of diabetic rats fed the HF and HP diets were lower than diabetic rats fed the HC diet and were similar to control rats. While diabetic rats, in general, had higher plasma glucagon concentrations and lower percent body fat than control rats, diabetic rats fed the HF diet had similar plasma glucagon and percent body fat to control rats. These data suggest that tissue-specific biochemical needs, such as the need for metals as cofactors for enzymes, rather than hyperphagia per se, may drive the accumulation of trace elements in the diabetic animal.

The male obese Wistar Diabetic Fatty (WDF) rat is a genetic model of obesity and non-insulin dependent diabetes (NIDDM). The obese Zucker rat shares the same gene for obesity on a different genetic background but is not diabetic. This study evaluated the degree of insulin resistance in both obese strains by examining the binding and post binding effects of muscle insulin receptors in obese rats exhibiting hyperinsulinemia and/or hyperglycemia. Insulin receptor binding and affinity and tyrosine kinase activity were measured in skeletal muscle from male WDF fa/fa (obese) and Fa/? (lean) and Zucker fa/fa (obese) and Fa/Fa (homozygous lean) rats. Rats were fed a high sucrose (68% of total Kcal) or Purina stock diet for 14 weeks. At 27 weeks of age, adipose depots were removed for adipose cellularity analysis and the biceps femoris muscle was removed for measurement of insulin binding and insulin-stimulated receptor kinase activity. Plasma glucose (13.9 vs. 8.4 mM) and insulin levels (14,754 vs. 7440 pmol/L) were significantly higher in WDF obese than in Zucker obese rats. Insulin receptor number and affinity and TK activity were unaffected by diet. Insulin receptor number was significantly reduced in obese WDF rats ( 2.778 +/- 0.617 pmol/mg protein), compared to obese Zucker rats (4.441 +/- 0.913 pmol/mg potein). Both obese strains exhibited down regulation of the insulin receptor compared to their lean controls. Maximal tyrosine kinase (TK) activity was significantly reduced in obese WDF rats (505 +/- 82 fmol/min/mg protein) compared to obese Zucker rats (1907 +/- 610 fmol/min/mg protein). Only obese WDF rats displayed a decrease in TK activity per receptor. These observations establish the obese WDF rat as an excellent model for exploring mechanisms of extreme insulin resistance, particularly post-receptor tyrosine kinase-associated defects, in non-insulin dependent diabetes.

We previously reported that serotonergic activity was reduced in the ventromedial hypothalamic nucleus (VMN) of obese vs. lean male Zucker rats. To verify that this reduction was associated with genotype rather than gender, we measured monoamines and their major metabolites in hypothalamic nuclei of 11-week-old female lean (Fa/Fa) and obese (fa/fa) Zucker rats. In addition, since the thermic response to cold is reported to differ between lean and obese rats, some rats were also exposed to 9 degrees or 22 degrees C for 2h to determine if cold exposure altered hypothalamic monoaminergic activity. As in males, levels of 5-hydroxyindoleacetic acid [5-HIAA; major metabolite of serotonin (5-HT)] and the ratio of 5-HIAA/5-HT were lower in the VMN of obese vs. lean females (P = 0.008, 0.001, respectively). 5-HIAA/5-HT was also reduced in the paraventricular (PVN) and suprachiasmatic nuclei (SCN) of the obese compared to the lean females. Cold exposure significantly stimulated brown fat mitochondrial GDP binding in lean but not obese rats. Similarly, levels of norepinephrine, dopamine (DA), 5-HIAA, and 5-HT in the PVN, and 5-HIAA in the SCN increased in cold-exposed lean but not obese rats. In contrast, VMN and preoptic 3,4-dihydroxyphenylacetic acid (DOPAC; major metabolite of DA) increased in the cold-exposed obese but not lean animals. We conclude that: (1) the blunted peripheral response to cold in obese vs. lean Zucker rats is accompanied by altered hypothalamic monoaminergic activity, the physiological role of which needs further evaluation; and 2) depressed VMN serotonergic activity is associated with the obese genotype (fa/fa) rather than gender and as such may contribute to the reduced sympathetic and enhanced parasympathetic outflow from the VMN.

The purpose of this investigation was to evaluate insulin-stimulated skeletal muscle glucose uptake in male Fischer 344 rats, age 6, 12, and 27 mo, fed either a sucrose (S: 66.6% sucrose, 17.6% protein, 6.4% fat) or sucrose-free (SF: 66.6% starch, 17.6% protein, 6.4% fat) diet for 3 mo. Skeletal muscle glucose uptake (Rg) in perfused hindlimbs was estimated from the uptake and subsequent phosphorylation of radiolabeled 2-deoxyglucose (2DG) in the gastrocnemius (GN), extensor digitorum longus (EDL), and soleus (SOL) muscles. Rat hindlimbs were perfused at a rate of 10 ml.min-1 with a modified Krebs Henseleit buffer containing bovine red blood cells (hematocrit: 40%) and 5.85 mmole.L-1 glucose along with 358 pmoles.L-1 followed by 3580 pmoles.L-1 insulin. There was no effect of diet on plasma glucose levels measured at weeks 1, 7, and 11 of the dietary period. A significant effect of age on estimated glucose uptake in the GN was demonstrated due primarily to greater uptake in the 27-mo compared to the 6-mo-old animals. This significant effect of age was not evident in the EDL or SOL, nor were there significant effects of diet in any muscle. These data suggest that insulin-stimulated glucose uptake in perfused hindlimbs is not attenuated with senescence or with the feeding of a sucrose diet for 3 months.