Treatment Choices in a National Cohort of Canadian Women With Symptomatic Uterine Fibroids.

OBJECTIVES: To describe treatment choices made at the time of enrollment in CAPTURE, a Canadian patient registry for women with symptomatic uterine fibroids (UFs), and to define demographic and clinical characteristics that independently predict these choices. METHODS: Women arranging appointments for UF care were eligible to enrol. At the time of the enrollment visit, women's self-reported treatment histories were noted, along with their clinical characteristics. Tretment options were discussed and chosen during that visit. Patients could choose medical and/or surgical treatment, or they could opt for no active treatment (i.e., "watchful waiting"); treatment decisions were not binding. RESULTS: The most common medication proposed and chosen was ulipristal acetate (UPA), and the most common procedure was myomectomy. These treatments were also the most commonly identified in patients' histories. Medication alone and medication in combination with surgery were the most common treatment approaches chosen (46% and 26%, respectively). Surgery alone and watchful waiting were chosen by 14% and 13% of patients, respectively. Significant predictors of active treatment included patient pregnancy plans, overall symptom severity, and prior treatment history (medical and surgical). Other parameters, including patient age and history of specific UF symptoms, appear to influence the choice of medical therapies (UPA, gonadotropin-releasing hormone agonists, or other options) and procedures (myomectomy or hysterectomy). CONCLUSIONS: This real-world study documents the patient factors associated with the treatment decisions of women seeking care for symptomatic UFs in contemporary Canadian gynaecology practice. Subsequent analyses will follow the outcomes of these treatments over two years in this population.

A Patient Registry for the Management of Uterine Fibroids in Canada: Protocol for a Multicenter, Prospective, Noninterventional Study.

BACKGROUND: Uterine fibroids are the most common benign tumor in women. Among those with fibroids, approximately 30% become symptomatic, with abnormal uterine bleeding, pelvic pain, and bulk symptoms. Despite the high prevalence of fibroids, little information is available regarding symptoms, treatment choices, and outcomes for patients. OBJECTIVE: A Canada-wide patient registry was established to understand the real-world practice. This registry included patient presentation and treatment preferences, health care provider attitudes, and clinical outcomes in the management of symptomatic uterine fibroids. METHODS: This study is a prospective, noninterventional, observational patient registry. It will include women diagnosed with uterine fibroids and being managed for symptoms. Participant inclusion criteria were (1) at least 18 years of age, (2) premenopausal with a confirmed diagnosis of uterine fibroids, and associated symptoms, and (3) initiating treatment (drug intervention, procedure intervention, or a combination of both) or watchful waiting. Patients (or legal representative) must understand the nature of the project and provide written informed consent before enrollment. Participant exclusion criteria were (1) they have known or suspected clinically significant pelvic pathology not associated with uterine fibroids, and (2) they are undergoing an emergency hysterectomy at the initial visit. Outcomes will be evaluated in the context of routine clinical practice. RESULTS: Participant recruitment of this registry began in July 2015. This study currently has a total sample of 1500 patients. CONCLUSIONS: This registry, a first in Canada, will accumulate evidence on the risks and benefits of watchful waiting, and medical and procedural interventions. It will contribute to enhancing access to treatment options for patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02580578; https://clinicaltrials.gov/ct2/show/NCT02580578 (Archived by WebCite at http://www.webcitation.org/6yax4Hpvr). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/10926.

Burden of symptomatic uterine fibroids in Canadian women: a cohort study.

OBJECTIVE: Due to variability in size, number, and location of uterine fibroids (UFs), symptoms can range widely among women. We sought to characterize burden of illness and quality of life (QoL) among women with symptomatic UFs. RESEARCH DESIGN AND METHODS: An online survey queried the gynecologic health and menstrual cycle of Canadian women aged 20 to 49. Respondents reporting current UFs were assigned an Overall Severity Score based on a validated health-related QoL questionnaire (the UFS-QOL) and were dichotomized as having mild or moderate/severe UF. Subjects with moderate/severe UFs were matched 1:3 to non-UF subjects on age, race, and parity. RESULTS: Of 9413 women with complete data, 384 (4.1%) reported physician-diagnosed UFs; of these, 50.6% met criteria for moderate/severe symptoms. Compared with matched non-UF respondents, moderate/severe UF respondents reported significantly greater mean menstrual duration (6.2 vs 5.0 days), more healthcare visits (emergency department, walk-in, family doctor, and specialist; total 10.5 vs 4.9 visits/6 months), and greater use of prescription analgesics (47.7% vs 26.7%) and iron supplements (29.7% vs 12.2%) (P < 0.05 for all). They spent more on feminine hygiene products ($32.0 vs $21.6/month) and reported losing nearly a full day of work/month (mean 7.6 hours) due to UFs. Women with moderate/severe UFs also scored lower on all QoL domains, compared to those with mild UF symptoms. Survey responses consistent with moderate/severe UFs were also identified in women who made no report of physician-diagnosed UFs, some of whom may be experiencing substantial burden due to undiagnosed UFs or other gynecologic conditions with related symptoms. LIMITATIONS: All outcomes recorded in this online survey were based on self-report. Therefore, respondents' claims of medical diagnoses, including medical history, UF status and the presence or absence of potentially confounding comorbidities, could not be confirmed clinically. CONCLUSIONS: Women experienced significant healthcare utilization, medication use, and financial and QoL burdens as a result of moderate/severe UF symptoms. Prevalence of moderate/severe UFs may be conservatively estimated at 2%, based on this cohort of reproductive-age Canadian women. The extent of UF underdiagnosis in the general population remains to be elucidated.

Non-melanoma Skin Cancer in Canada Chapter 1: Introduction to the Guidelines.

BACKGROUND: Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma, represents the most common malignancy. OBJECTIVE: The aim of this document is to provide guidance to Canadian health care practitioners on NMSC management. METHODS: After conducting a literature review, the group developed recommendations for prevention, management, and treatment of basal cell carcinomas, squamous cell carcinomas, and actinic keratoses. These tumour types are considered separately in the accompanying articles. The Grading of Recommendations Assessment, Development and Evaluation system was used to assign strength to each recommendation. RESULTS: This introduction describes the scope and structure of the guidelines and the methods used to develop them. The epidemiology of NMSC is reviewed, as are the pathophysiologic changes occurring with damage to the skin, which lead to the formation of actinic keratoses and invasive squamous or basal cell carcinomas. CONCLUSIONS: This introduction describes the need for primary prevention and offers an overview of treatment options that are discussed in later chapters of the guidelines.

Non-melanoma Skin Cancer in Canada Chapter 5: Management of Squamous Cell Carcinoma.

BACKGROUND: Squamous cell carcinoma (SCC) is the second-most common form of non-melanoma skin cancer (NMSC). OBJECTIVE: To provide guidance to Canadian health care practitioners regarding management of SCCs. METHODS: Literature searches and development of graded recommendations were carried out as discussed in the accompanying introduction (chapter 1 of the NMSC guidelines). RESULTS: SCCs are sometimes confined to the epidermis, but they can also invade nearby tissues and, in some cases, metastasize to neighbouring lymph nodes or other organs. This chapter discusses the natural history, staging, prognosis, and management of SCC--a tumour type that is less common but typically more aggressive than BCC. For this reason, margin control is strongly preferred in treating SCCs. CONCLUSIONS: Although approaches such as cryosurgery and radiation therapy may be considered for some patients, surgical excision--sometimes coupled with radiation--remains the cornerstone of SCC management. Patients with high-risk SCC may also be considered for referral to an appropriate multidisciplinary clinic.

Delayed access to treatments for rare diseases: who's to blame?

The development and commercialization of drugs for rare diseases, termed 'orphan drugs', has historically been economically unattractive. However, because of the introduction of legislation that provides financial and regulatory incentives for the development of orphan drugs, new developments are making their way through the regulatory approval processes. Unfortunately, delays in availability of new drugs for treating rare disease continue to persist. This paper reviews the approach of several regulatory jurisdictions to orphan drugs in an effort to determine their relative effectiveness in providing patient access. Generally speaking, regulatory authorities across jurisdictions have recognized the need to enhance timely access to safe, effective treatment for patients with rare diseases and have been able to shift the approval timelines for access to new care. The greater impediment to orphan drug access appears to be funding, particularly in publicly sponsored health-care systems. Redundancies in federal and provincial reviews of orphan drugs can result in significant delays in access to new drugs. Clearly, more must be done to accelerate access to the treatments so desperately needed by patients. Public payers must be held accountable for their process and decisions--especially for rare disease therapies.

Atherogenic low density lipoprotein phenotype in long-term survivors of childhood acute lymphoblastic leukemia.

Survivors of childhood acute lymphoblastic leukemia (ALL) have an increased risk of cardiovascular disease. Small density lipoproteins are atherogenic but have not been studied in this population. We conducted a cross-sectional analysis of 110 ALL survivors (mean age, 24.3 years) to determine prevalence of small dense LDL (pattern B) phenotype in ALL survivors and identify associated factors. Lipid subfractions were measured using Vertical Auto Profile-II. Participants with greater than 50% of LDL-cholesterol (LDL-c) in small dense LDL fractions (LDL(3+4)) were classified as LDL pattern B. Visceral and subcutaneous adipose tissue (VAT, SAT) volumes were also measured by computed tomography. While the mean LDL-c level of ALL survivors was 108.7 ± 26.8 mg/dl, 36% (40/110) of survivors had atherogenic LDL pattern B. This pattern was more common in males (26/47; 55%) than in females (14/63; 22%, P = 0.001) and more common in survivors treated with cranial radiotherapy (15/33; 45%) than in those who were treated with chemotherapy alone (25/77; 33%; P = 0.04, adjusted for age, gender, history of hypertension, and smoking history). VAT was associated with atherogenic lipids: LDL pattern B and LDL(3+4) levels. This association was independent of other measures of body fat. We conclude that a substantial proportion of ALL survivors had an atherogenic LDL phenotype despite normal mean LDL-c levels. An atherogenic LDL phenotype may contribute to the increase in cardiovascular mortality and morbidity in this population.

Acute exercise increases adiponectin levels in abdominally obese men.

Objective. To examine the effect of acute and short-term (~1 week) aerobic exercise training on plasma adiponectin levels in inactive, abdominally obese men. Materials and Methods. Inactive and abdominally obese men (n = 38, waist circumference ≥102 cm) recruited from Kingston, Canada were randomly allocated to perform three bouts of aerobic treadmill exercise at either low (50% VO(2) peak) or high (75% VO(2) peak) intensity during a 1-week period. Blood samples were taken before and after the first exercise session and 24-72 hours following the completion of the final exercise session. Results. Adiponectin levels were elevated immediately following an acute bout of exercise at both high and low intensities (High: 5.79 ± 0.42 versus 5.05 ± 0.41 ug/mL; Low: 5.24 ± 0.44 versus 4.37 ± 0.44 ug/mL, P < 0.05) and remained elevated following 30 minutes of rest. In comparison to baseline, adiponectin levels were also elevated 24-72 hours following the final exercise session (High: 5.47 ± 0.48 versus 4.88 ± 0.48 ug/mL; Low: 5.18 ± 0.49 versus 4.47 ± 0.49 ug/mL, P < 0.05). Conclusion. Both acute and short-term aerobic exercise result in a significant increase in plasma adiponectin levels in inactive, abdominally obese men independent of intensity.

Adipokines, body fatness, and insulin resistance among survivors of childhood leukemia.

BACKGROUND: Following our previous reports of an increased prevalence of insulin resistance and adiposity among acute lymphoblastic leukemia (ALL) survivors, particularly women treated with cranial radiotherapy (CRT), we aimed to (1) assess the relationships between adipokines (leptin and adiponectin), CRT, and measures of body fatness and (2) determine correlates of insulin resistance, by gender. METHODS: We conducted cross-sectional evaluation of 116 ALL survivors (median age: 23.0 years; range: 18-37; average time from treatment: 17.5 years), including fasting laboratory testing (adiponectin, leptin, insulin, and glucose), anthropometric measurements (weight, height, and waist circumference), DXA (total body fat and truncal-to-lower-body-fat ratio), and abdominal CT (visceral fat). We estimated insulin resistance using the homeostasis model for assessment of insulin resistance (HOMA-IR). Analytic approaches included regression models and Wilcoxon rank sum testing. RESULTS: Mean leptin per kilogram fat mass was higher for females (0.7 ng/ml/kg) than males (0.4 ng/ml/kg, P < 0.01), and among subjects who had received CRT compared to those who had not received CRT (females CRT =0.9 ng/ml/kg, no CRT = 0.7 ng/ml/kg; P = 0.1; males CRT = 0.5 ng/ml/kg, no CRT = 0.3 ng/ml/kg; P < 0.01). Elevated HOMA-IR was nearly uniformly present, even among subjects with BMI < 25 kg/m(2), and was associated with higher leptin:adiponectin ratio (LA ratio; P < 0.01). CONCLUSIONS: Among survivors of childhood leukemia, higher leptin levels were associated with measures of body fat and insulin resistance. Anthropomorphic and metabolic changes many years after ALL treatment remain a major health problem facing survivors and may be related to central leptin resistance.

Hypertriglyceridemia and waist circumference predict cardiovascular risk among HIV patients: a cross-sectional study.

BACKGROUND: Although half of HIV-infected patients develop lipodystrophy and metabolic complications, there exists no simple clinical screening tool to discern the high from the low-risk HIV-infected patient. Thus, we evaluated the associations between waist circumference (WC) combined with triglyceride (TG) levels and the severity of lipodystrophy and cardiovascular risk among HIV-infected men and women. METHODS: 1481 HIV-infected men and 841 HIV-infected women were recruited between 2005 and 2009 at the metabolic clinic of the University of Modena and Reggio Emilia in Italy. Within each gender, patients were categorized into 4 groups according to WC and TG levels. Total and regional fat and fat-free mass were assessed by duel-energy x-ray absorptiometry, and visceral adipose tissue (VAT) and abdominal subcutaneous AT (SAT) were quantified by computed tomography. Various cardiovascular risk factors were assessed in clinic after an overnight fast. RESULTS: The high TG/high WC men had the most VAT (208.0 ± 94.4 cm(2)), as well as the highest prevalence of metabolic syndrome (42.2%) and type-2 diabetes (16.2%), and the highest Framingham risk score (10.3 ± 6.5) in comparison to other groups (p<0.05 for all). High TG/high WC women also had elevated VAT (150.0 ± 97.9 cm(2)) and a higher prevalence of metabolic syndrome (53.3%), hypertension (30.5%) and type-2 diabetes (12.0%), and Framingham risk score(2.9 ± 2.8) by comparison to low TG/low WC women (p<0.05 for all). CONCLUSIONS: A simple tool combining WC and TG levels can discriminate high- from low-risk HIV-infected patients.

Effects of weight loss among metabolically healthy obese men and women.

OBJECTIVE: Weight loss among metabolically healthy obese (MHO) individuals may be unnecessary or result in elevated cardio-metabolic risk. We studied the effects of exercise- or diet-induced weight loss on cardio-metabolic risk among MHO and metabolically abnormal obese (MAO) adults. RESEARCH DESIGN AND METHODS: Participants were 63 MHO and 43 MAO adults who took part in 3 to 6 months of exercise- or diet-induced weight loss intervention. Changes in anthropometry, adipose tissue distribution, and cardio-metabolic risk factors were assessed. RESULTS: Body weight, waist circumference, and total abdominal and visceral adipose tissue were reduced in all subjects (P < 0.05). Improvements in insulin sensitivity were observed in MHO and MAO men and women (P < 0.05), but were greater in the MAO individuals (P < 0.05). Fasting insulin was the only other cardio-metabolic improvement among MHO individuals (P < 0.05). CONCLUSIONS: Lifestyle-induced weight loss among MHO subjects is associated with a reduction in total and abdominal obesity and improvement in selected cardio-metabolic risk factors.

Breast volume is an independent predictor of visceral and ectopic fat in premenopausal women.

It is suggested that a large breast size among women may predict type 2 diabetes risk independent of BMI and waist circumference (WC). The purpose of this study was to determine the independent associations of breast volume with cardiometabolic risk factors and regional fat distribution. A total of 92 overweight or obese premenopausal women (age = 39.9 +/- 6.8 years) underwent full-body magnetic resonance imaging (MRI) for the assessment of breast volume, visceral adipose tissue (VAT), abdominal and lower-body subcutaneous AT (SAT), and intermuscular AT (IMAT), a 2-h oral glucose tolerance test (OGTT), and fasting phlebotomy for assessment of triglyceride, total, high-density lipoprotein-, and low-density lipoprotein-cholesterol levels. Breast volume was not associated with any of the cardiometabolic risk factors assessed (P > 0.05). However, VAT was consistently associated with a number of cardiometabolic risk factors (OGTT glucose, OGTT insulin, and triglyceride levels) after controlling for age, BMI, WC, breast volume, and the other AT depots. In univariate models, breast volume was positively associated with VAT, IMAT, and abdominal and lower-body SAT (P < 0.05). After controlling for age, BMI, and WC level, breast volume remained positively associated with VAT and IMAT (P < 0.05), such that women with the highest breast volume had approximately 1.1 and 1.3 kg more VAT and IMAT, respectively, but no more abdominal or lower-body SAT, by comparison to women with the smallest breast volume. Thus, the previously documented association between breast size and type 2 diabetes risk may be in part explained by excess VAT and/or IMAT deposition.

The utility of physical activity in the management of global cardiometabolic risk.

Major health organizations promote the adoption of a healthy lifestyle, composed of sufficient daily physical activity and a balanced diet for the prevention and management of type 2 diabetes (T2D) and cardiovascular disease risk. In particular, it is recommended that adults accumulate 30 min of moderate-intensity aerobic physical activity on most days of the week. Despite these recommendations, a physically active lifestyle is seldom adopted, and the majority of the North American population remains sedentary. Although the optimal strategy for promoting physical activity in today's environment remains elusive, the evidence for the utility of physical activity in the management of risk factors for T2D and cardiovascular disease is overwhelming. This review examines the influence of aerobic-type physical activity on components of global cardiometabolic risk, that is, the traditional and emerging risk factors for cardiovascular disease and T2D, including visceral obesity, insulin resistance, hypertension, atherogenic dyslipidemia, thrombosis, inflammation, and cardiorespiratory fitness. Where possible, specific consideration is given to the independent effects of an acute bout of physical activity vs. chronic physical activity with weight loss vs. chronic physical activity without weight loss.

Insulin resistance and risk factors for cardiovascular disease in young adult survivors of childhood acute lymphoblastic leukemia.

PURPOSE: To determine the prevalence of insulin resistance and other risk factors for cardiovascular disease (CVD) in young adult survivors of childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: In this cross-sectional evaluation of 118 survivors of childhood ALL (median age, 23.0 years; range, 18 to 37 years), insulin resistance was estimated using the homeostasis model for assessment of insulin resistance (HOMA-IR). Sex-specific comparisons were made with a cohort of 30- to 37-year-old individuals from the same region participating in the Dallas Heart Study (DHS, N = 782). ALL survivors were stratified by treatment with and without cranial radiotherapy (CRT). RESULTS: Female ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.6, 95% CI, 3.6 to 5.7; no CRT, mean 3.3, 95% CI, 2.8 to 3.8) in comparison with DHS women (mean 2.4, 95% CI, 2.2 to 2.7). Eighty percent of women treated with CRT had at least three of six CVD risk factors, and they were significantly more likely to have three or more risk factors compared with DHS women (odds ratio [OR], 5.96; 95% CI, 2.15 to 16.47). Male ALL survivors had a significantly higher HOMA-IR (CRT, mean 4.0, 95% CI, 2.8 to 5.6; no CRT, mean 3.4, 95% CI, 2.9 to 3.9) in comparison with DHS men (mean 2.3, 95% CI, 2.1 to 2.6), but were not more likely to have multiple CVD risk factors. CONCLUSION: ALL survivors had an increased prevalence of insulin resistance in comparison with a cohort of older individuals from the same community. Importantly, women treated with CRT seem to have an increased prevalence of multiple CVD risk factors, warranting close monitoring and risk-reducing strategies.

Associations of the limb fat to trunk fat ratio with markers of cardiometabolic risk in elderly men and women.

BACKGROUND: The ratio of limb fat to trunk fat (LF/TF) is associated with markers of cardiometabolic risk in elderly men and women. It is unknown if LF/TF is associated with cardiometabolic risk beyond that explained by LF and TF independently. METHODS: Participants included abdominally obese men (n = 58) and women (n = 78) between 60 and 80 years of age. Regional adiposity was quantified using magnetic resonance imaging. Insulin resistance, fasting glucose, high-density lipoprotein (HDL) cholesterol, plasma triglycerides, and adiponectin were determined using standard procedures. RESULTS: After control for potential confounders, TF was positively associated with fasting glucose, insulin resistance, and plasma triglycerides and negatively associated with HDL cholesterol and adiponectin (p < or = .05). These associations were strengthened after further control for LF (p < .05), with the exception of adiponectin in men (p > .05). After control for potential confounders, LF was negatively associated with adiponectin in men (p < .05) but not with any other marker of cardiometabolic risk (p > .05). After further control for TF, LF was negatively associated with plasma triglycerides and positively associated with HDL cholesterol in both genders combined (p < .05) and with adiponectin in women (p < .05) but not in men (p > .05). LF/TF was not associated with any marker of cardiometabolic risk after control for LF and TF. CONCLUSION: These results suggest that it is the absolute, rather than relative, amounts of LF and TF that have the greatest influence on cardiometabolic risk in elderly men and women.

Abdominal obesity and physical inactivity are associated with erectile dysfunction independent of body mass index.

INTRODUCTION: Erectile dysfunction (ED) is common among men with an elevated body mass index (BMI). However, a high waist circumference (WC) and low levels of physical activity may predict ED independently of BMI. AIM: We investigated the independent relationships between BMI, WC, and physical activity with ED. METHODS: Subjects consisted of 3,941 adult men (age > or = 20 years) with no history of prostate cancer from the 2001-2004 National Health and Nutrition Examination Survey. Logistic regression analyses were used to examine the relative odds of ED association with categories of BMI, WC, and physical activity. MAIN OUTCOME MEASURES: Established thresholds were used to divide subjects into three WC and BMI categories. Physical activity level was divided into active (> or =150 min/week), moderately active (30-149 min/week), and inactive (<30 min/week) categories. A single survey question was used to assess the presence of ED. RESULTS: After control for potential confounders, men with either a high WC or an obese BMI had an approximately 50% higher odds of having ED compared with men with a low WC or a normal BMI, respectively. Further, moderately active or inactive men had an approximately 40-60% greater odds of ED compared with active men. When all three predictors (WC, BMI, and physical activity level) were entered into the same logistic regression model, both a high WC and low physical activity level (moderately active and inactive) were independently associated with a greater odds of ED, whereas BMI level was not. CONCLUSION: Maintaining a WC level below 102 cm and achieving the recommended amount of moderate-intensity physical activity (>or =150 min/week) is associated with the maintenance of proper erectile function, regardless of BMI level. These findings suggest that the clinical screening for ED risk should include the assessment of WC and physical activity level in addition to BMI.

Effects of exercise modality on insulin resistance and functional limitation in older adults: a randomized controlled trial.

BACKGROUND: Authorities advocate that resistance and aerobic exercise are essential for reducing risk factors for chronic disease and disability in older adults. However, the incremental effects of combined resistance and aerobic exercise compared with either modality alone on risk factors for disease and disability is generally unknown. METHODS: Participants were 136 sedentary, abdominally obese older men and women recruited from September 30, 2002, through November 15, 2006, at Queen's University. Participants were randomized to 1 of the following 4 groups for 6 months: resistance exercise, aerobic exercise, resistance and aerobic exercise (combined exercise), or nonexercise control. Primary outcomes were analyzed by an intent-to-treat model and included changes in insulin resistance by hyperinsulinemic-euglycemic clamp and functional limitation using the average change in 4 tests combined (average z score). RESULTS: After controlling for age, sex, and baseline value, insulin resistance improved compared with controls in the aerobic exercise and the combined exercise groups but not in the resistance exercise group. Improvement (mean [SE]) in the combined exercise group was greater than in the resistance exercise group (9.2 [1.3] vs 1.8 [1.3] mg/mL/microIU per kilogram of skeletal muscle per minute x100 [P < .001]) but not in the aerobic exercise group (9.2 [1.3] vs 6.5 [1.3] mg/mL/microIU per kilogram of skeletal muscle per minute x100 [P = .46]). Functional limitation improved significantly in all groups compared with the control group. Improvement in the combined exercise group was greater than in the aerobic exercise group (0.5 [0.1] vs -0.0 [0.1]; standard units, z score [P = .003]) but not in the resistance exercise group. Improvement in the resistance exercise group was not different from the aerobic exercise group. CONCLUSION: The combination of resistance and aerobic exercise was the optimal exercise strategy for simultaneous reduction in insulin resistance and functional limitation in previously sedentary, abdominally obese older adults. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00520858.

Is weight loss the optimal target for obesity-related cardiovascular disease risk reduction?

In the present review, it is argued that while weight loss is associated with substantial reduction in obesity-related cardiovascular disease risk and remains a desired outcome of relevant treatment strategies, increasing physical activity is associated with marked reduction in waist circumference, visceral fat and cardiometabolic risk factors, concurrent with an increase in cardiorespiratory fitness despite minimal or no change in body weight. Failure to recognize the benefits of exercise independent of weight loss masks opportunities to counsel and educate patients whose sole criteria for gauging obesity reduction success is the bathroom scale.

Does waist circumference predict diabetes and cardiovascular disease beyond commonly evaluated cardiometabolic risk factors?

OBJECTIVE: While the measurement of waist circumference (WC) is recommended in current clinical guidelines, its clinical utility was questioned in a recent consensus statement. In response, we sought to determine whether WC predicts diabetes and cardiovascular disease (CVD) beyond that explained by BMI and commonly obtained cardiometabolic risk factors including blood pressure, lipoproteins, and glucose. RESEARCH DESIGN AND METHODS: Subjects consisted of 5,882 adults from the 1999-2004 National Health and Nutrition Examination Survey, which is nationally representative and cross-sectional. Subjects were grouped into sex-specific WC and BMI tertiles. Blood pressure, triglycerides, LDL and HDL cholesterol, and glucose were categorized using standard clinical thresholds. Logistic regression analyses were used to calculate the odds for diabetes and CVD according to WC tertiles. RESULTS: After controlling for basic confounders, the medium and high WC tertiles were more likely to have diabetes and CVD compared with the low WC tertile (P < 0.05). After inclusion of BMI and cardiometabolic risk factors in the regression models, the magnitude of the odds ratios were attenuated (i.e., for diabetes the magnitude decreased from 6.54 to 5.03 for the high WC group) but remained significant in the medium and high WC tertiles for the prediction of diabetes, though not for CVD. CONCLUSIONS: WC predicted diabetes, but not CVD, beyond that explained by traditional cardiometabolic risk factors and BMI. The findings lend critical support for the recommendation that WC be a routine measure for identification of the high-risk, abdominally obese patient.

Abdominal obesity, liver fat, and muscle composition in survivors of childhood acute lymphoblastic leukemia.

CONTEXT: Survivors of childhood acute lymphoblastic leukemia (ALL) become obese, and are at increased risk for morbidity and mortality post therapy. OBJECTIVE: We determined the association of cranial radiotherapy (CRT) and/or sex with levels of total, regional, and ectopic fat storage, metabolic risk, IGF-I, and leptin in adult ALL survivors. DESIGN, SETTING, PATIENTS: A cross-sectional analysis of 52 male (15 CRT treated) and 62 female (24 CRT treated) young adult ALL survivors was conducted. MAIN OUTCOMES: We assessed levels of visceral fat, sc abdominal and thigh fat, and liver and muscle fat using computed tomography, total fat and lean body mass using dual-energy x-ray absorptiometry, and IGF-I and leptin levels by radioimmunoassay. RESULTS: Controlled for age and race, ALL survivors treated with CRT had higher levels of abdominal and visceral fat, body fat percentage, metabolic risk (insulin resistance and dyslipidemia), and leptin but lower lean mass and IGF-I levels than non-CRT survivors (P 0.1). CONCLUSION: Among young adult ALL survivors, CRT is a risk factor for elevated total, abdominal, and visceral adiposity, a reduced fat-free mass, elevated metabolic risk, and altered IGF-I and leptin levels.