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Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is to review the current literature and key clinical trials

Peripheral arterial disease (PAD) is a common atherosclerotic disease affecting the quality of life of > 8 million Americans. PAD is characterized by atherosclerotic stenoses of arteries that supply the lower extremities and is associated with a marked increase in the short-term risk of heart attack, stroke, amputation, and death. Adherence to pharmacological therapies and modification of lifestyle factors, including increasing moderate physical activity along with supervised exercise, smoking cessation, and a healthy dietary intake, are central to the successful management of PAD. The improvement of an adverse cardiovascular risk profile is a proven and crucial strategy to lower the risk of major morbid and mortal events for individuals with PAD. [ABSTRACT FROM AUTHOR]

In a previous study, large variability in iodine content was found among samples of store brand retail milk at a single time point in a sampling taken from 24 nationwide U.S. locations for the USDA FoodData Central database, but the sampling plan was not designed to detect differences among locations. This follow-up study was carried out to evaluate iodine levels in retail milk across the U.S. over time. Milk samples (2% fat) were collected bimonthly in fourteen locations for one year and analyzed in duplicate. Control materials were used to support accuracy of results and ensure precision across analytical batches. The overall mean and standard error (SE) for iodine concentration were 82.5 (7.0) µg/240 mL serving, which was comparable to the previous national mean [85.0 (5.5) µg/240 mL]. A similar wide range among individual samples was detected (27.9-282 µg/240 mL). For some locations, the mean iodine concentration differed significantly from others, and differed from the national average by amounts ranging from -47 µg to +37 µg per serving. The between-sample range within location was large for some (up to 229 µg/serving) and minimal for others (as little as 13.2 µg/serving). These findings suggest iodine intake from some retail milk supplies could be over- or underestimated relative to the national average, even if the national average is suitable for population-wide intake estimates.

Data on the iodine content of foods and dietary supplements are needed to develop general population intake estimates and identify major contributors to intake. Samples of seafood, dairy products, eggs, baked products, salts, tap water, other foods and beverages, and dietary supplements were collected according to established sampling plans of the U.S. Department of Agriculture (USDA) and the U.S. Food and Drug Administration (FDA). Samples were assayed for iodine content using inductively coupled plasma mass spectrometry with rigorous quality control measures. The food data were released through a collaboration of USDA, FDA, and the Office of Dietary Supplements-National Institutes of Health (ODS-NIH) as the USDA, FDA, and ODS-NIH Database for the Iodine Content of Common Foods at www.ars.usda.gov/mafcl. Iodine data for dietary supplements are available in the ODS-USDA Dietary Supplement Ingredient Database and the ODS Dietary Supplement Label Database. Data from the iodine databases linked to national dietary survey data can provide needed information to monitor iodine status and develop dietary guidance for the general U.S. population and vulnerable subgroups. This iodine information is critical for dietary guidance development, especially for those at risk for iodine deficiency (i.e., women of reproductive age and young children)., Competing Interests: Conflicts of interest The authors, shown above, have no conflicts of interest.

Background: Factor VIIc, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) are cardiovascular disease (CVD) risk factors and are modulated, in part, by fat type and amount., Objective: We evaluated fat type and amount on the primary outcomes: factor VIIc, fibrinogen, and PAI-1., Methods: In the Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA) Trial, 2 controlled crossover feeding studies evaluated substituting carbohydrate or MUFAs for SFAs. Study 1: healthy participants (n = 103) were provided with (8 wk) an average American diet [AAD; designed to provide 37% of energy (%E) as fat, 16% SFA], a Step 1 diet (30%E fat, 9% SFA), and a diet low in SFA (Low-Sat; 26%E fat, 5% SFA). Study 2: participants (n = 85) at risk for CVD and metabolic syndrome (MetSyn) were provided with (7 wk) an AAD, a step 1 diet, and a high-MUFA diet (designed to provide 37%E fat, 8% SFA, 22% MUFA)., Results: Study 1: compared with AAD, the Step 1 and Low-Sat diets decreased mean factor VIIc by 1.8% and 2.6% (overall P = 0.0001), increased mean fibrinogen by 1.2% and 2.8% (P = 0.0141), and increased mean square root PAI-1 by 0.0% and 6.0% (P = 0.0037), respectively. Study 2: compared with AAD, the Step 1 and high-MUFA diets decreased mean factor VIIc by 4.1% and 3.2% (overall P < 0.0001), increased mean fibrinogen by 3.9% and 1.5% (P = 0.0083), and increased mean square-root PAI-1 by 2.0% and 5.8% (P = 0.1319), respectively., Conclusions: Replacing SFA with carbohydrate decreased factor VIIc and increased fibrinogen in healthy and metabolically unhealthy individuals and also increased PAI-1 in healthy subjects. Replacing SFA with MUFA decreased factor VIIc and increased fibrinogen but less than carbohydrate. Our results indicate an uncertain effect of replacing SFA with carbohydrate or MUFA on cardiometabolic risk because of small changes in hemostatic factors and directionally different responses to decreasing SFA. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT00000538?term=NCT00000538&rank=1 as NCT00000538., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Iodine intake is of contemporary public health interest. The recommended daily iodine intake is 150 µg for most adults, and milk is an important source of iodine in the U.S. diet. Iodine concentration in cow's milk is affected by diet and iodine supplementation levels, milking sanitation practices, and other factors. Current analytical iodine data in U.S. retail milk are crucial for evaluating population-wide health outcomes related to diet. Samples of whole (3.25% fat), 2%, 1%, and skim (0-0.5% fat) milk were procured from 24 supermarkets across the U.S. using a census-based statistical plan. Iodine was analyzed by inductively coupled plasma mass spectrometry, including certified reference materials and control samples to validate results. No difference in iodine content was found between milkfat levels (F 3,69 1.033, p = 0.4). Overall mean (SEM) was 85(5.5) µg/serving (240 mL). However, the 95% prediction interval of 39-185 µg/serving for individual samples indicated high variability among individual samples. Given the recommended 150 µg iodine per day for most adults along with the study mean, one milk serving can provide approximately 57% of daily intake. Researchers, health care professionals, and consumers should be aware of iodine variability in milk, while additional research is needed to investigate the impact of iodine variability factors., Competing Interests: The authors declare no conflicts of interest.

Objective: This review summarizes the current and previous data on dietary supplement (DS) use collected from participants in the National Health and Nutrition Examination Survey (NHANES), describes the NHANES dietary supplement database used to compute nutrient intakes from DSs, discussed recent developments and future direction, and describes many examples to demonstrate the utility of these data in informing nutrition research and policy., Background and History: Since 1971, NHANES, has been collecting information on the use of DSs from participants. These data are critical to national nutrition surveillance and have been used to characterize usage patterns, examine trends over time, assess the percentage of the population meeting or exceeding nutrient recommendations, and to help elucidate the sources contributing nutrients to the diet of the US population., Rationale: Over half of adults and about one-third of children in the United States use at least one dietary supplement in the past 30 days. Dietary supplements contribute to the dietary intake of nutrients and bioactive compounds in the US and therefore need to be assessed when monitoring nutritional status of the population and when studying diet-health associations., Recent Developments: With the recent development and availability of the Dietary Supplement Label Database (DSLD), a comprehensive DS database that will eventually contain labels for all products marketed in the US, NHANES DS data will be more easily linked to product information to estimate nutrient intake from DS., Future Directions: Over time, NHANES has both expanded and improved collection methods. The continued understanding of sources of error in collection methods will continue to be explored and is critical to improved accuracy., Conclusions: NHANES provides a rich source of nationally representative data on the usage of dietary supplements in the US., Competing Interests: Conflicts of interest and funding disclosure: J. J. Gahche, R.L. Bailey, N. Potischman, A.G. Ershow, K.A. Herrick, N. Ahluwalia have no conflicts of interest. J.T. Dwyer has stock in several drug companies, some of which may sell dietary supplements. There is no funding to disclose.

Objective: To describe the history, key features, recent enhancements, and common applications of the Dietary Supplement Label Database (DSLD)., Background and History: Although many Americans use dietary supplements, databases of dietary supplements sold in the United States have not been widely available. The DSLD, an easily accessible public-use database was created in 2008 to provide information on dietary supplement composition for use by researchers and consumers., Rationale: Accessing current information easily and quickly is crucial for documenting exposures to dietary supplements because they contain nutrients and other bioactive ingredients that may have beneficial or adverse effects on human health. This manuscript details recent developments with the DSLD to achieve this goal and provides examples of how the DSLD has been used., Recent Developments: With periodic updates to track changes in product composition and capture new products entering the market, the DSLD currently contains more than 71,000 dietary supplement labels. Following usability testing with consumer and researcher user groups completed in 2016, improvements to the DSLD interface were made. As of 2017, both a desktop and mobile device version are now available. Since its inception in 2008, the use of the DSLD has included research, exposure monitoring, and other purposes by users in the public and private sectors., Future Directions: Further refinement of the user interface and search features to facilitate ease of use for stakeholders is planned., Conclusions: The DSLD can be used to track changes in product composition and capture new products entering the market. With over 71,000 DS labels it is a unique resource that policymakers, researchers, clinicians, and consumers may find valuable for multiple applications., Competing Interests: Conflicts of interest: JT Dwyer, RA Bailen, L Saldanha, J Gahche, R Costello, JM Betz, Cindy Davis, RL Bailey, N Potischman, A Ershow, B Sorkin, A Kuszak,L Rios-Avila, F Chang, J Goshorn, K Andrews, P Pehrsson, P Gusev, J Harnly, CJ Hardy, N Emenaker, KA Herrick, no conflicts of interest.

Launched in 2008, the Dietary Supplement Label Database (DSLD) permits the search of any term that appears anywhere on product labels. Since then, the database's search and download features have been periodically improved to enhance use for researchers and consumers. In this review, we describe how to customize searches and identify products and ingredients of interest to users in the DSLD, and provide the limitations of working with information derived from dietary supplement product labels. This article describes how data derived from information printed on product labels are entered and organized in the DSLD. Among the challenges are determining the chemical forms, types of extract, and amounts of dietary ingredients, especially when these are components of proprietary blends. The FDA announced new dietary supplement labeling regulations in May 2016. The 2017 DSLD has been updated to reflect them. These new regulations and examples cited in this article refer to this redesigned version of the DSLD. Search selection characteristics such as for product type and intended user group are as described in FDA guidance and regulations for dietary supplements. For this reason, some age groups (such as teens and seniors) and marketing recommendations for use (e.g., weight loss, performance, and other disease- or condition-specific claims) are not included in the search selections. The DSLD user interface features will be revised periodically to reflect regulatory and technologic developments to enhance user experience. A comprehensive database derived from analytically verified data on composition would be preferable to label data, but is not feasible for technical, logistic, and financial reasons. Therefore, a database derived from information printed on product labels is the only practical option at present for researchers, clinicians, and consumers interested in the composition of these products., (© Crown copyright 2018.)

In the United States, the American Thyroid Association recommends that women take a dietary supplement containing 150 &micro;g of iodine 3 months prior to conception and while pregnant and lactating to support fetal growth and neurological development. We used data from the National Health and Nutrition Examination Survey 2011&ndash;2014 to describe the use of dietary supplements with and without iodine in the past 30 days among 2155 non-pregnant, non-lactating (NPNL) women; 122 pregnant women; and 61 lactating women. Among NPNL women, 45.3% (95% Confidence Interval [CI]: 42.0, 48.6) used any dietary supplement and 14.8% (95% CI: 12.7, 16.8) used a dietary supplement with iodine in the past 30 days. Non-Hispanic black and Hispanic women were less likely to use any dietary supplement as well as one with iodine, than non-Hispanic white or non-Hispanic Asian women ( p < 0.05). Among pregnant women, 72.2% (95% CI: 65.8, 78.6) used any dietary supplement; however, only 17.8% (95% CI: 11.4, 24.3) used a dietary supplement with iodine. Among lactating women, 75.0% (95% CI: 63.0, 87.0) used a dietary supplement; however, only 19.0% (95% CI: 8.8, 29.2) used a dietary supplement with iodine. Among NPNL women using a supplement with iodine, median daily iodine intake was 75.0 &micro;g. Self-reported data suggests that the use of iodine containing dietary supplements among pregnant and lactating women remains low in contrast with current recommendations.

Iodine is an essential micronutrient required for normal growth and neurodevelopment; thus, an adequate intake of iodine is particularly important for pregnant and lactating women, and throughout childhood. Low levels of iodine in the soil and groundwater are common in many parts of the world, often leading to diets that are low in iodine. Widespread salt iodization has eradicated severe iodine deficiency, but mild-to-moderate deficiency is still prevalent even in many developed countries. To understand patterns of iodine intake and to develop strategies for improving intake, it is important to characterize all sources of dietary iodine, and national databases on the iodine content of major dietary contributors (including foods, beverages, water, salts, and supplements) provide a key information resource. This paper discusses the importance of well-constructed databases on the iodine content of foods, beverages, and dietary supplements; the availability of iodine databases worldwide; and factors related to variability in iodine content that should be considered when developing such databases. We also describe current efforts in iodine database development in the United States, the use of iodine composition data to develop food fortification policies in New Zealand, and how iodine content databases might be used when considering the iodine intake and status of individuals and populations., Competing Interests: The authors declare no conflicts of interest.

Background: Prenatal supplements are often recommended to pregnant women to help meet their nutrient needs. Many products are available, making it difficult to choose a suitable supplement because little is known about their labeling and contents to evaluate their appropriateness., Objective: To determine differences between prescription and nonprescription prenatal supplements available in the United States regarding declared nutrient and nonnutrient ingredients and the presence of dosing and safety-related information., Design: Using two publicly available databases with information about prenatal supplement products, information from prescription and nonprescription product labels were extracted and evaluated. For the 82 prescription and 132 nonprescription products, declared label amounts of seven vitamins and minerals, docosahexaenoic acid (DHA), the presence of other nonnutrient components, and the presence of key safety and informational elements as identified in two Department of Health and Human Services Office of Inspector General (OIG)'s 2003 reports were compiled and compared., Results: Compared with nonprescription products, prescription products contained significantly fewer vitamins (9±0.2 vs 11±0.3; P≤0.05) and minerals (4±0.1 vs 8±0.3; P≤0.05). Declared amounts of folic acid were higher in prescription products, whereas vitamin A, vitamin D, iodine, and calcium were higher in the nonprescription products. Amounts of iron, zinc, and DHA were similar. Virtually all products contained levels of one or more nutrients that exceeded the Recommended Dietary Allowances for pregnant and/or lactating women. Product type also influenced ingredients added. Fewer prescription products contained botanical ingredients (6% prescription vs 33% nonprescription) and probiotics (2% prescription vs 8% nonprescription). Only prescription products contained the stool softener docusate sodium., Conclusions: Our analysis of prenatal supplements indicates that prescription and nonprescription supplements differ in terms of declared composition and nutrient strength, but have labels that are similarly sparse regarding aspects of use such as dosing information., (Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

One in five Americans experiences disability that affects their daily function because of impairments in mobility, cognitive function, sensory impairment, or communication impairment. The need for rehabilitation strategies to optimize function and reduce disability is a clear priority for research to address this public health challenge. The National Institutes of Health (NIH) recently published a Research Plan on Rehabilitation that provides a set of priorities to guide the field over the next 5 years. The plan was developed with input from multiple Institutes and Centers within the NIH, the National Advisory Board for Medical Rehabilitation Research, and the public. This article provides an overview of the need for this research plan, an outline of its development, and a listing of six priority areas for research. The NIH is committed to working with all stakeholder communities engaged in rehabilitation research to track progress made on these priorities and to work to advance the science of medical rehabilitation.This article is being published almost simultaneously in the following six journals: American Journal of Occupational Therapy, American Journal of Physical Medicine and Rehabilitation, Archives of Physical Medicine and Rehabilitation, Neurorehabilitation and Neural Repair, Physical Therapy, and Rehabilitation Psychology. Citation information is as follows: NIH Medical Rehabilitation Coordinating Committee. Am J Phys Med Rehabil. 2017;97(4):404-407., (Copyright © Wolters Kluwer Health, Inc. 2017.)

The Office of Dietary Supplements of the NIH convened 3 workshops on iodine nutrition in Rockville, Maryland, in 2014. The purpose of the current article is to summarize and briefly discuss a list of research and resource needs developed with the input of workshop participants. This list is composed of the basic, clinical, translational, and population studies required for characterizing the benefits and risks of iodine supplementation, along with related data, analyses, evaluations, methods development, and supporting activities. Ancillary studies designed to use the participant, biological sample, and data resources of ongoing and completed studies (including those not originally concerned with iodine) may provide an efficient, cost-effective means to address some of these research and resource needs. In the United States, the foremost question is whether neurobehavioral development in the offspring of mildly to moderately iodine-deficient women is improved by maternal iodine supplementation during pregnancy. It is important to identify the benefits and risks of iodine supplementation in all population subgroups so that supplementation can be targeted, if necessary, to avoid increasing the risk of thyroid dysfunction and related adverse health effects in those with high iodine intakes. Ultimately, there will be a need for well-designed trials and other studies to assess the impact of maternal supplementation on neurodevelopmental outcomes in the offspring. However, 2 basic information gaps loom ahead of such a study: the development of robust, valid, and convenient biomarkers of individual iodine status and the identification of infant and toddler neurobehavioral development endpoints that are sensitive to mild maternal iodine deficiency during pregnancy and its reversal by supplementation., (© 2016 American Society for Nutrition.)

The NIH Office of Dietary Supplements (ODS) convened 3 workshops on iodine nutrition in 2014, each held in Rockville, Maryland. These workshops were part of the ongoing ODS Iodine Initiative, begun in 2011 in response to concerns that US pregnant women may be at risk of iodine deficiency and that a high fraction of prenatal dietary supplements do not contain the recommended amounts of iodine. The primary purpose of the workshops was to consider the data and resources necessary to evaluate the clinical and public health benefits and risks of maternal iodine supplementation in the United States. The first workshop focused on the assessment of iodine intake, the second focused on the assessment of iodine status, and the third focused on the design and interpretation of clinical trials of maternal iodine supplementation. Here we provide the background of the ODS Iodine Initiative, summarize the 3 workshops held in 2014, and introduce the articles that arose from the workshops and are published in this supplement issue., (© 2016 American Society for Nutrition.)

Objective: To explore the relationship between gender, native artery diameters, and outcomes of stent revascularization (ST) in the "Claudication: Exercise versus Endoluminal Revascularization" trial., Methods: A comparative analysis was performed of the impact of gender, age, weight, height, body mass index, and body surface area on revascularization outcomes at baseline and 6months in 55 arterial segments of aorta, common iliac artery, and external iliac artery (EIA)., Results: Women demonstrated smaller diameter of the EIA. However, the clinical outcomes of revascularization were not negatively affected by the gender-based differences., Conclusion: Gender-based differences are unlikely to significantly impact outcome of ST., (Published by Elsevier Inc.)

Cardiovascular disease risk factor control as primary prevention in patients with type 2 diabetes mellitus has changed substantially in the past few years. The purpose of this scientific statement is to review the current literature and key clinical trials pertaining to blood pressure and blood glucose control, cholesterol management, aspirin therapy, and lifestyle modification. We present a synthesis of the recent literature, new guidelines, and clinical targets, including screening for kidney and subclinical cardiovascular disease for the contemporary management of patients with type 2 diabetes mellitus., (© 2015 by the American Diabetes Association and the American Heart Association, Inc.)

Background: Hormonal status influences haemostatic factors including fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), and concentrations differ among men, premenopausal and postmenopausal women. This study examines how phases of the menstrual cycle influence variability of fibrinogen, factor VII and PAI-1., Design: We studied 103 subjects (39 premenopausal women, 18 postmenopausal women and 46 men) during three, randomized, 8-week energy- and nutrient-controlled experimental diets in the Dietary Effects on Lipids and Thrombogenic Activity (DELTA) Study. Fasting blood samples were collected weekly during the last 4 weeks of each diet period, and haemostatic factors were quantified. Two linear mixed-effects models were used for fibrinogen, factor VII and PAI-1: one to estimate and compare group-specific components of variance, and the other to estimate additional fixed effects representing cyclical functions of day of menstrual cycle in premenopausal women., Results: Systematic cyclical variation with day of menstrual cycle was observed for fibrinogen (P < 0.0001), factor VII (P = 0.0012) and PAI-1 (P = 0.0024) in premenopausal women. However, the amplitude of cycling was small relative to the total magnitude of intra-individual variability. In addition, the intra-individual variance and corresponding coefficient of variation observed in premenopausal women did not differ from postmenopausal women and men., Conclusions: The variability in haemostatic factors in premenopausal women is no greater than for postmenopausal women or men. Consequently, premenopausal women can be included in studies investigating haemostatic factor responses without controlling for stage of menstrual cycle., (© 2014 Stichting European Society for Clinical Investigation Journal Foundation.)

A trans-National Institutes of Health initiative, Nutrition and Dietary Supplement Interventions for Inborn Errors of Metabolism (NDSI-IEM), was launched in 2010 to identify gaps in knowledge regarding the safety and utility of nutritional interventions for the management of inborn errors of metabolism (IEM) that need to be filled with evidence-based research. IEM include inherited biochemical disorders in which specific enzyme defects interfere with the normal metabolism of exogenous (dietary) or endogenous protein, carbohydrate, or fat. For some of these IEM, effective management depends primarily on nutritional interventions. Further research is needed to demonstrate the impact of nutritional interventions on individual health outcomes and on the psychosocial issues identified by patients and their families. A series of meetings and discussions were convened to explore the current United States' funding and regulatory infrastructure and the challenges to the conduct of research for nutritional interventions for the management of IEM. Although the research and regulatory infrastructure are well-established, a collaborative pathway that includes the professional and advocacy rare disease community and federal regulatory and research agencies will be needed to overcome current barriers., (Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

The association between renal cell cancer (RCC) and intake of fruit, vegetables and nutrients was examined in a population-based case-control study of 323 cases and 1827 controls; dietary intake was obtained using a mailed questionnaire. Cancer risks were estimated by OR and 95 % CI, adjusting for age, sex, smoking, obesity, hypertension, proxy status, alcohol consumption and dietary fat intake and energy. Intake of vegetables was associated with a decreased risk of RCC (OR 0·5; 95 % CI 0·3, 0·7; P trend = 0·002), (top compared to the bottom quartile of intake). When intake of individual nutrients was investigated, vegetable fibre intake was associated with decreased risks (OR 0·4; 95 % CI 0·2, 0·6; P < 0·001), but this was not the case with fruit fibre (OR 0·7; 95 % CI 0·4, 1·1) or grain fibre (OR 1·0; 95 % CI 0·6, 1·5). β-Cryptoxanthin and lycopene were also associated with decreased risks, but when both were included in a mutually adjusted backwards stepwise regression model, only β-cryptoxanthin remained significant (OR 0·5; 95 % CI 0·3, 0·8). When other micronutrients and types of fibre were investigated together, only vegetable fibre and β-cryptoxanthin had significant trends (P < 0·01) (OR 0·6; 95 % CI 0·3, 0·9) (OR 0·5; 95 % CI 0·3, 0·9), respectively. These findings were stronger in those aged over 65 years (P interaction = 0·001). Among non-smokers, low intake of cruciferous vegetables and fruit fibre was also associated with increased risk of RCC (P interaction = 0·03); similar inverse associations were found for β-cryptoxanthin, lycopene and vitamin C. When nutrients were mutually adjusted by backwards regression in these subgroups, only β-cryptoxanthin remained associated with lower RCC risk. These findings deserve further investigation in ongoing prospective studies when sample size becomes sufficient.

The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

Recent epidemic increases in the U.S. prevalence of obesity and diabetes are a consequence of widespread environmental changes affecting energy balance and its regulation. These environmental changes range from exposure to endocrine disrupting pollutants to shortened sleep duration to physical inactivity to excess caloric intake. Overall, we need a better understanding of the factors affecting individual susceptibility and resistance to adverse exposures and behaviors and of determinants of individual response to treatment. Obesity and diabetes prevention will require responding to two primary behavioral risk factors: excess energy intake and insufficient energy expenditure. Adverse food environments (external, nonphysiological influences on eating behaviors) contribute to excess caloric intake but can be countered through behavioral and economic approaches. Adverse built environments, which can be modified to foster more physical activity, are promising venues for community-level intervention. Techniques to help people to modulate energy intake and increase energy expenditure must address their personal situations: health literacy, psychological factors, and social relationships. Behaviorally oriented translational research can help in developing useful interventions and environmental modifications that are tailored to individual needs., (Copyright 2009 Diabetes Technology Society.)

Summary: Renal cell carcinoma (RCC) rates in the US have risen, along with those of obesity and hypertension. We investigated the interactive relationship with obesity and hypertension (HT) through a population-based case-control study of RCC in Iowa consisting of 406 cases and 2434 controls. Data on height and weight at various ages and history of HT were collected and interaction tested by log-likelihood ratio tests. After adjustment, both obesity and HT were independently and interactively associated with increased RCC risk. Hypertensive subjects, obese (BMI ≥ 30) at age 40 were 4.2 (CI: 2.38-6.53) times more likely to develop RCC as normotensive individuals of normal weight (BMI < 25). A similar interactive pattern was observed for obesity at age 60 (p = 0.02). Interaction with obesity was more evident in women (pinteraction = 0.04 age 40, pinteraction = 0.01 age 60). Our findings suggest that maintaining body weight and/or controlling HT are strategies for preventing RCC.:, (© 2007 Asian Oceanian Association for the Study of Obesity . Published by Elsevier Ltd. All rights reserved.)

Energy balance disorders account for a large public health burden. The obesity epidemic in particular is one of the most rapidly evolving public health problems of our day. At present, two-thirds of American adults and one-sixth of American children and adolescents are considered either overweight or obese. Public health concern about obesity is high because of the increased risk and increased mortality of cardiovascular disease, Type 2 diabetes, many forms of cancer, gallbladder disease, and osteoarthritis. These risks increase with the severity of the obesity. Excess adipose tissue, representing fat storage, ultimately derives from an imbalance between energy intake and energy expenditure. Conversely, undesirable and inadvertent loss of body weight and muscle mass, as seen in aging and cachectic states of chronic diseases such as heart failure and cancer, have serious clinical and functional consequences without satisfactory clinical or behavioral solutions. Innovative engineering technologies could help to address unresolved problems in energy balance, intake, and expenditure. Novel sensors, devices, imaging technologies, nanotechnologies, biomaterials, technologies to detect biochemical markers of energy balance, mathematical modeling, systems biology, and other approaches could be developed, evaluated, and leveraged through multidisciplinary collaborations. Engineers, physical scientists, and mathematicians can work with scientists from other relevant disciplines who possess expertise in obesity and nutrition. Furthermore, the possibility of re-engineering the "built environment" to encourage higher levels of physical activity has been suggested as another promising and important approach to which engineers can contribute (see http://www.obesityresearch.nih.gov). Ultimately, systematic application of the "Engineering Approach" can help in developing the needed technologies and tools to facilitate research and eventually support therapeutic advances and behavioral change. This article summarizes important public health concerns related to disordered energy balance and describes research priorities identified at a recent National Science Foundation-National Institutes of Health workshop. Research funding opportunities are described as posted on the NIH Guide to Grants and Contracts (see http://www.nih.gov/grants/guide).

The role that dietary factors play in preventing heart failure (HF) and in improving prognosis is increasingly recognized, indicating a need for well-grounded guidelines that can provide recommendations for daily nutrient intakes. At present, however, the state of dietary guidance is more satisfactory for persons at risk of HF (Stages A and B) than for those with a diagnosis of HF (Stages C and D). For individuals at risk of HF, a good starting point is provided by governmental and professional society guidance directed at dietary management of cardiovascular risk factors such as hypertension, hyperlipidemia, and obesity. These dietary recommendations are consonant with epidemiologic research suggesting that improving risk factor profiles likely will lower the risk of developing HF. For patients with diagnosed HF, however, little information is available to define optimal nutrient intakes and optimal food patterns. Dietary services have been shown useful in improving clinical outcomes, but nutritional management must be individualized to the patient's needs and must accommodate pharmacologic therapy, multiple co-morbidities, the possible need for nutritional supplements, repeated hospitalizations, salt and fluid retention, voluntary vs. involuntary weight loss, and other nutritional issues relevant to the aged population who comprise the majority of HF patients. Progress in the field will require well-designed clinical investigations addressing nutrient intake, nutrient metabolism, and nutritional status while mindful of the complex pathophysiology of HF.

The obesity epidemic is one of the most rapidly evolving public health problems of our day. At present, 2/3 of American adults and 1/6 of American children and adolescents are considered either overweight or obese. Public health concern about obesity is high and reflects documented increased risk of cardiovascular disease, type 2 diabetes, many forms of cancer, gallbladder disease, and osteoarthritis, and increased mortality from these ailments, especially among the most obese. Innovative engineering technologies are needed to address a large range of problems in energy balance, intake, and expenditure that are associated with the obesity epidemic. Excess adipose tissue, representing fat storage, ultimately derives from an imbalance between energy intake and energy expenditure. Novel sensors, devices, imaging technologies, nanotechnology, biomaterials, and other approaches need to be developed and evaluated through multidisciplinary collaborations between engineers, physical scientists, and scientists with expertise in obesity and nutrition. The goal is to encourage research to develop useful technologies and tools to facilitate research and eventually to support therapeutic advances and behavioral change. Furthermore, the possibility of re-engineering the "built environment" to encourage higher levels of physical activity has been suggested as another promising and important approach to which engineers can contribute (see http://www.obesityresearch.nih.gov).

Dietary intervention studies of human beings produce valuable information regarding dietary effects on biological processes and risk factors for chronic diseases. Using the well-controlled feeding approach, participants consume only foods that have been precisely prepared in a research kitchen, whereas in behavioral counseling studies, participants self-select their foods within guidelines. Because controlled feeding studies meticulously control experimental diets, they are intellectually and logistically challenging to conduct. They afford exciting opportunities for dietetic professionals in designing protocols, developing budgets, and collaborating in multidisciplinary research teams. Research dietitians use food composition data and chemical analysis of menus to prepare research diets with precision. They determine the energy requirements of subjects and adjust diets as required, most often for weight maintenance, throughout the study. All people involved in research must be attentive to the ethical treatment of the study participants while motivating them to adhere to the protocol requirements. Dietitians possess many of these skills, but may require training specific to well-controlled feeding studies. Information related to the conduct of controlled feeding studies has recently become more accessible. We provide an overview of well-controlled feeding study methodologies, proficiencies for planning and implementing these studies, and training resources.

The nature of the association between alcohol consumption and renal cell carcinoma (RCC) is not well understood, but there are indications of effect modification by gender. The authors report data from a population-based case-control study conducted in Iowa from 1986 to 1989. RCC cases (261 men and 145 women) were identified through the Iowa Cancer Registry, while controls (1,598 men and 831 women) were randomly selected from the general population, frequency matched on age and gender. Subjects provided detailed information on a mailed questionnaire regarding demographic, anthropometric, lifestyle, dietary, and medical history risk factors. In age-adjusted analysis, there was a decrease in risk for women who reported consuming more than three servings (median among drinkers) of alcohol per week (odds ratio = 0.5, 95% confidence interval: 0.2, 0.9) compared with never drinkers. No evidence of an association among men was noted (odds ratio = 1.1, 95% confidence interval: 0.8, 1.5). Multivariate adjustment for anthropometric, lifestyle, smoking, and dietary factors did not alter the findings. Analysis by type of alcohol suggested that the inverse association was strongest for beer consumption, but estimates were imprecise. These findings suggest an inverse association of alcohol consumption and RCC development among women but not among men.

Two nutrition intervention trials were conducted in Linxian, China, where the esophageal/gastric cardia cancer mortality rates are among the highest in the world and there is suspicion that the population's chronic deficiencies of multiple nutrients are etiologically involved. Both trials were randomized, double-blind, and placebo-controlled, and tested the effect of multiple-vitamin and multiple-mineral supplements in lowering the rates of cancer. In the first trial, the Dysplasia Trial, 3318 individuals with a cytologic diagnosis of esophageal dysplasia received daily vitamin and mineral supplements or placebos for 6 years. The second trial, the General Population Trial, involved 29,584 individuals and used a one-half replicate of a 2(4) fractional factorial design, which enabled the testing of daily supplementation of four different vitamin and mineral combinations and placebo for a period 5 1/4 years. This article describes the design and methods of these studies as well as the baseline characteristics and compliance behavior of the participants in these two trials, the largest cancer chemoprevention studies reported to date.

Background: A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals. In humans, epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian, China, have persistently low intake of multiple nutrients and exhibit one of the world's highest rates of esophageal/gastric cardia cancer, with an exceptionally high risk of esophageal dysplasia., Purpose: To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia, we conducted a 6-year prospective intervention trial in Linxian., Methods: Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were randomly assigned to receive, throughout that period, daily supplementation with 14 vitamins and 12 minerals or placebo. Doses were typically two to three times U.S. Recommended Daily Allowances. Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from samples of individuals randomly selected without replacement every 3 months throughout the trial. Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years., Results: A total of 324 deaths occurred during the 6-year intervention period; 167 occurred in the control (placebo) group and 157 occurred in the supplement group. Cancer was the leading cause of death (54% of all deaths); 18% were due to cerebrovascular diseases and 29% to other causes. Cumulative esophageal/gastric cardia death rates were 8% lower (relative risk [RR] = 0.92; 95% confidence interval [CI] = 0.67-1.28) among individuals receiving supplements rather than placebo, a nonsignificant (P > .10) difference. Risk of total mortality was 7% lower (RR = 0.93; 95% CI = 0.75-1.16; P > .10), total cancer 4% lower (RR = 0.96; 95% CI = 0.71-1.29; P > .10), cerebrovascular disease 38% lower (RR = 0.62; 95% CI = 0.37-1.06; P = .08), and other diseases 12% higher (RR = 1.12; 95% CI = 0.74-1.69; P > .10) among the treated group. Cumulative cancer incidence rates were nearly the same in the two groups., Conclusions: No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus., Implications: Although no statistically significant short-term benefits were observed, longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia.

Background: Despite theoretically higher requirements for water due to physiologic demands of pregnancy and lactation, little is known of actual ranges of intake in pregnant and lactating women., Methods: Population-based estimates of total water and tapwater intake in women of reproductive age were derived using data from the 1977-78 USDA Nationwide Food Consumption Survey. Three-day average intakes were calculated for 188 pregnant women, 77 lactating women, and 6,201 non-pregnant, non-lactating control women., Results: Total water intake (mean +/- SD) was 1,940 +/- 686 g/day (median 1,835) for control women, 2,076 +/- 743 g/day (median 1,928) for pregnant women and 2,242 +/- 658 g/day (median 2,164) for lactating women. Tapwater intake was 1,157 +/- 635 g/day (median 1,065) for control women, 1,189 +/- 699 g/day (median 1,063) for pregnant women, and 1,310 +/- 591 g/day (median 1,330) for lactating women. Total water intake was equal to or greater than 3,000 g/day among 7 percent of control women, 11 percent of pregnant women, and 13 percent of lactating women. Tapwater intake was equal to or greater than 2,000 g/day among 10 percent of control women, 15 percent of pregnant women, and 8 percent of lactating women., Conclusions: These results should be useful in estimating amounts of nutrients and toxic substances that women of reproductive age obtain through the water supply.

A case-control study involving interviews with 1,244 patients (758 males and 486 females) with cancer of the esophagus or gastric cardia and 1,314 population-based controls (789 males, 525 females) was carried out in Linxian, a rural county in North Central China with one of the world's highest mortality rates for these tumors. Cancer risks tended to rise with increasing intake of wheat and corn, but no association was found with adult intake of pickled vegetables, the leading a priori suspect, and risks were not elevated among those consuming low quantities of fresh vegetables or fruits. Few differences in preparation or storage of food or water were detected, although cancer patients reported less fluid intake than controls. Few persons reported drinking alcoholic beverages. Smoking was reported by 61% of the male cases and was a mild risk factor, related more to cancer of the cardia than of the esophagus. The risk was increased by 70% among those whose parents had esophageal or stomach cancer, but only slightly among those whose spouses had such cancers, suggesting that exposure early in life and/or genetic effects may be involved.

A case-control study involving interviews with 672 female lung cancer patients and 735 population-based controls was conducted to investigate the high rates of lung cancer, notably adenocarcinoma, among women in Shanghai. Cigarette smoking was a strong risk factor, but accounted for only about one-fourth of all newly diagnosed cases of lung cancer. Most patients, particularly with adenocarcinoma, were life-long non-smokers. The risks of lung cancer were higher among women reporting tuberculosis and other pre-existing lung diseases. Hormonal factors were suggested by an increased risk associated with late menopause and by a gradient in the risk of adenocarcinoma with decreasing menstrual cycle length, with a 3-fold excess among women who had shorter cycles. Perhaps most intriguing were associations found between lung cancer and measures of exposure to cooking oil vapors. Risks increased with the numbers of meals cooked by either stir frying, deep frying or boiling; with the frequency of smokiness during cooking; and with the frequency of eye irritation during cooking. Use of rapeseed oil, whose volatiles following high-temperature cooking may be mutagenic, was also reported more often by the cancer patients. The findings thus confirm that factors other than smoking are responsible for the high risk of lung cancer among Chinese women and provide clues for further research, including the assessment of cooking practices.

The ability of a supplement to counteract seasonal alterations in nutritional status for certain vitamins was studied in Linxian, an area in northern China with high rates of esophageal cancer. 150 subjects took one daily pill from April to August (16 weeks), whereas 50 subjects did not take any supplement. Deficiencies of ascorbic acid, riboflavin, folic acid, retinol and tocopherol were prevalent at the outset of the study. The changes in diet occurring between the end of the winter (April) and the start of the autumn vegetable harvest (August) were reflected in greatly improved ascorbic acid status and slightly improved riboflavin status. Plasma retinol, tocopherol, alpha-carotene and beta-carotene were little affected by season, whereas erythrocyte folate levels declined. The ascorbic acid, riboflavin, folate, retinol and tocopherol status of the supplemented subjects was significantly improved. After 16 weeks of supplementation, erythrocyte folate levels of subjects with esophageal dysplasia were improved but remained significantly lower than those of normal supplemented subjects, targeting folic acid as a nutrient of particular interest in this precancerous condition.

The present study suggests a correlation between concanavalin A-driven blastogenesis and the clinical course of head and neck cancer. Blastogenesis assays were conducted on peripheral blood lymphocytes from controls and from patients with squamous cell carcinoma (SCC) of the head and neck. Our results indicated that 3H-thymidine incorporation in response to concanavalin A and phytohemagglutinin stimulation were significantly lower for patients' than for controls' lymphocytes, whereas PWM stimulation was not statistically different in these two groups. Differences between patients and controls were most notable with concanavalin A stimulation. Five of seventeen patients had a response to concanavalin A stimulation that was in the normal range when expressed as relative to control values. The clinical course of these five patients seems to point to a better prognosis than that of the remaining patients who had below-normal mitogenic responses.

In order to isolate the effects of the type of dietary fat from those of dietary cholesterol on the circulating pool of cholesterol, plasma lipoproteins were characterized in juvenile rhesus monkeys fed semipurified diets containing 31% of calories as corn oil or coconut oil. Half the diets contained 300 mg of cholesterol per 1000 kcal. The fatty acids of cholesteryl esters and phospholipids varied significantly with dietary fat such that saturated and monounsaturated fatty acids replaced polyunsaturated fatty acids in low-density lipoproteins (LDL) and high density-lipoproteins of rhesus monkeys fed coconut oil. Dietary cholesterol alone induced small but significant increases in the cholesteryl ester: triglyceride ratio in both very low-density lipoproteins and LDL. Whereas neither saturated fat (coconut oil) nor cholesterol alone substantially altered the plasma cholesterol concentration or lipoprotein profile, together these dietary components interacted synergistically to produce a significant elevation in plasma cholesterol. This was due primarily to a significant rise in the cholesteryl ester fraction of LDL, disproportionate to any change in LDL protein concentration. The data are consistent with current hypotheses that relate parameters of LDL turnover and clearance to their macromolecular structure and physicochemical characteristics.

A 24-week pilot study of daily or weekly multiple vitamin supplementation among 852 adults in Linxian, where the rate of esophageal cancer is exceptionally high, demonstrated the feasibility of an intervention trial in this population. Compliance, when judged by pill count, was high for both frequencies of pill use. Only 2% of the subjects refused to take any pills, and, among pill takers, over 95% were reported to be taking most of their pills at the end of the study. Biochemical confirmation of high compliance was demonstrated in urine and blood tests, which showed markedly improved vitamin levels after supplementation. Results of the pilot study indicated that a system in which barefoot doctors were used in pill distribution was effective and that established field operating procedures for a full-scale intervention trial in this area were acceptable.

In estimating the sample size for a case-control study, epidemiologic texts present formulae that require a binary exposure of interest. Frequently, however, important exposures are continuous and dichotomization may result in a 'not exposed' category that has little practical meaning. In addition, if risks vary monotonically with exposure, then dichotomization will obscure risk effects and require a greater number of subjects to detect differences in the exposure distributions among cases and controls. Starting from the usual score statistic to detect differences in exposure, this paper develops sample size formulae for case-control studies with arbitrary exposure distributions; this includes both continuous and dichotomous exposure measurements as special cases. The score statistic is appropriate for general differentiable models for the relative odds, and, in particular, for the two forms commonly used in prospective disease occurrence models: (1) the odds of disease increase linearly with exposure; or (2) the odds increase exponentially with exposure. Under these two models we illustrate calculation of sample sizes for a hypothetical case-control study of lung cancer among non-smokers who are exposed to radon decay products at home.

A case-control study involving interviews with 1,200 patients with esophageal cancer and 1,200 population-based controls has been initiated in Linxian, a county in North Central China with perhaps the world's highest mortality rates for this tumor. Here we describe the rationale, study methods, and results of a pilot study that established the feasibility of the investigation.

A case-control study is currently under way in Beijing, People's Republic of China, involving approximately 165 patients with invasive moles or choriocarcinoma, 165 with hydatidiform moles, and 330 population controls, who were matched to the patients with invasive moles or choriocarcinoma on age and interval since last pregnancy. The interviews are focused on a number of suspected risk factors, including previous pregnancy outcomes, history of hydatidiform mole, medical factors, drug usage, family history, and diet. A brief background of the study and methods as established through a previous pilot study are given.

Plasma levels of nutrients in 196 individuals were assayed as part of a study of the feasibility of a nutrition intervention trial in Linxian, a county in North Central China with exceptionally high rates of esophageal cancer. High-performance liquid chromatography analyses of samples collected in April 1983 showed low (relative to United States standards) base-line levels for retinol, alpha-tocopherol, and beta- and alpha-carotene. Repeat sampling in August 1983 revealed significantly increased plasma levels of retinol and alpha-tocopherol among those who had in the interim received daily supplementation with multivitamin pills containing the Recommended Dietary Allowance levels of those nutrients but not among those without supplementation. Levels of carotenes, which were not included in the pills, tended to increase regardless of supplementation, consistent with seasonal variations in availability of carotenoid-containing foods. Atomic absorption spectrophotometry analyses showed essentially normal levels of copper and zinc in plasma. Neither was affected by vitamin supplementation (the pills did not contain minerals) nor seasonal variation. The data are generally consistent with prior biochemical surveys in indicating marginal or low status of several nutrients in Linxian and in showing that supplementation with vitamins can effectively raise blood nutrient levels.