Phenotype tailored lifestyle intervention on weight loss and cardiometabolic risk factors in adults with obesity: a single-centre, non-randomised, proof-of-concept study.

Background: Lifestyle interventions for weight loss are currently not individualised to underlying pathophysiology and behavioral traits in obesity. We aim to compare the outcome of a standard lifestyle intervention (SLI) to phenotype-tailored lifestyle interventions (PLI) on weight loss, cardiometabolic risk factors and physiologic variables contributing to obesity. Methods: This 12-week, single-centre non-randomised proof-of-concept clinical trial including men and women aged 18-65 years with a body mass index (BMI) greater than 30 without history of any bariatric procedure, and current use of any medication known to affect weight. Participants lived anywhere in the United States, and underwent in-person testing in Rochester, MN at a teaching hospital. All participants completed in-person phenotype testing at baseline and after 12 weeks. Participants were assigned to their intervention based on their period of enrollment. In the first phase, participants were assigned to SLI with a low-calorie diet (LCD), moderate physical activity, and weekly behavioral therapy sessions. In the second phase, other participants were assigned to PLI according to phenotype: abnormal satiation (time-restricted volumetric LCD); abnormal postprandial satiety (LCD with pre-meal protein supplementation); emotional eating (LCD with intensive behavioral therapy); and abnormal resting energy expenditure (LCD with post-workout protein supplementation and high-intensity interval training). The primary outcome was total body weight loss in kg at 12 weeks using multiple imputation for missing data. Linear models estimated the association of study group allocation and study endpoints adjusting for age, sex, and baseline weight. This study was registered with ClinicalTrials.gov, NCT04073394. Findings: Between July 2020 and August 2021, 211 participants were screened, and 165 were assigned to one of the two treatments in the two phases: 81 SLI (mean [SD] age 42.9 [12] years; 79% women; BMI 38.0 [6.0]) and 84 PLI (age 44.8 [12.2] years; 83% women; BMI 38.7 [6.9]); 146 completed the 12-week programs. The weight loss was -7.4 kg (95%CI, -8.8, -6.0) with PLI vs. -4.3 kg (95%CI, -5.8, -2.7) with SLI (difference, -3.1 kg [95%CI, -5.1 to -1.1]; P = 0.004). No adverse events were reported in any group. Interpretation: Phenotype-tailored lifestyle interventions may result in significant weight loss, but a randomised controlled trial is required to confirm causality. Funding: Mayo Clinic; NIH (K23-DK114460).

Sex as an independent variable in the measurement of satiation: a retrospective cohort study.

BACKGROUND: Satiation is a key component of food intake regulation as it brings an eating episode to an end. The effect of sex on satiation measurement has not been characterized. OBJECTIVE: To assess the effects of biological variables on satiation. DESIGN: Retrospective cohort study. We included 959 participants (mean age 39 [SD 12] years; 70.7% female, and BMI 33 kg/m2 [8]) who had measurements of satiation with a nutrient-drink test to assess volume to fullness (VTF) and maximum tolerated volume (MTV), and/or an ad libitum meal test to assess calories consumed to fullness (CTF). We performed univariate and multiple regression analyses to estimate the contribution of sex to VTF, MTV, and CTF, compared to other biological variables, such as age, weight, height, BMI, waist-to-hip circumference (W/H), and lean mass percentage (LM%), that are known to affect these parameters. RESULTS: Females had higher BMI, W/H, and LM%. VTF, MTV, and CTF were lower in females: 704 [323] vs. 783 [328] mL, p = 0.001; 1226 [384] vs. 1419 [410] mL, p < 0.001; and 871 [291] vs. 1086 [326] kcal, p < 0.001; respectively. Sex was a strong and independent predictor of VTF, MTF and CTF: parameter estimate [PE] = -80.8, p = 0.006; PE = -124.2, p = 0.0007; and PE = -110, p = 0.001; respectively. CONCLUSIONS: Sex has a strong effect on satiation measured by VTF, MTV, and CTF, even after adjusting for other biological factors known to affect these parameters. Females seem to integrate intra-meal inhibition signals to consume fewer calories unrelated to body size or composition. CLINICAL TRIAL REGISTRATION: None.

Association between anxiety and eating behaviors in patients with obesity.

Background: Given the link between eating behavior and obesity, it is critical to identify individuals who have eating behaviors which contribute to obesity etiology. This study aimed to investigate the potential relationship between symptoms of anxiety and eating behaviors in patients with obesity. Methods: This was a cross-sectional study analyzing baseline characteristics of 438 patients with obesity (BMI>30). Patients completed the Hospital Anxiety and Depression Scale (HADS) questionnaire, the Three-Factor Eating Questionnaire R21 (TFEQ-R21), and the Weight Efficacy Lifestyle Questionnaire (WEL). Pearson correlation coefficients were used to evaluate the association between questionnaires. Two-sample independent t-test were conducted to examine differences in the TFEQ-R21 and WEL between low and moderate to severe levels of symptoms of anxiety. Results: Anxiety scores (HADS-A) positively correlated with two factors of the TFEQ, emotional eating (r = 0.36) and uncontrolled eating (r = 0.27). The HADS-A score was negatively correlated with self-efficacy to resist eating in all five situational factors on the WEL (p < 0.01). Patients with symptoms of anxiety additionally showed higher mean scores for emotional eating and uncontrolled eating (p < 0.001, respectively),and lower levels of cognitive restraint (p = 0.04)) on the TFEQ-R21. Conclusion: Patients with obesity who reported having anxiety symptoms had lower self-confidence to manage their eating and more emotional eating than patients with low anxiety symptoms. Clearly more needs to be learned about symtoms of anxiety and eating behaviors.

The effect of culinary interventions (cooking classes) on dietary intake and behavioral change: a systematic review and evidence map.

BACKGROUND: Culinary interventions (cooking classes) have been used to improve the quality of dietary intake and change behavior. The aim of this systematic review is to investigate the effects of culinary interventions on dietary intake and behavioral and cardiometabolic outcomes. METHODS: We conducted a systematic review of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus for comparative studies that evaluated culinary interventions to a control group or baseline values. The intervention was defined as a cooking class regardless of its length or delivery approach. Studies included populations of children, healthy adults or adults with morbidities. The risk of bias was assessed using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale. Outcomes were pooled using the random-effects model and descriptive statistics and depicted in an evidence map. Simple logistic regression was used to evaluate factors associated with intervention success. RESULTS: We included 30 studies (6 were randomized, 7381 patients, average follow up 25 weeks). Culinary interventions were not associated with a significant change in body mass index (- 0.07 kg/m2, 95% CI: -1.53, 1.40), systolic (- 5.31 mmHg, 95% CI: -34.2, 23.58) or diastolic blood pressure (- 3.1 mmHg, 95% CI: -23.82, 17.62) or LDL cholesterol (- 8.09 mg/dL, 95% CI: -84.43, 68.25). Culinary interventions were associated with improved attitudes, self-efficacy and healthy dietary intake in adults and children. We were unable to demonstrate whether the effect of a culinary intervention was modified by various characteristics of the intervention such as its delivery or intensity. Interventions with additional components such as education on nutrition, physical activity or gardening were particularly effective. CONCLUSIONS: Culinary interventions were not associated with a significant change in cardiometabolic risk factors, but were associated with improved attitudes, self-efficacy and a healthier dietary intake in adults and children.

Health Habits of Employees in a Large Medical Center: Time Trends and Impact of a Worksite Wellness Facility.

Worksite health interventions are not novel but their effect remains subject of debate. We examined employer-based wellness program to determine health habits trends, and compare prevalence estimates to national data. We conducted serial surveys (1996 and 2007-10) to employees of a large medical center that included questions measuring outcomes, including obesity, regular exercise, cardiovascular activity, and smoking status. Logistic regression models were estimated to compare data by membership across years, considering p-values ≤ 0.01 as statistically significant. 3,206 employees responded (Response rates 59-68%). Obesity prevalence increased over time in members and nonmembers of the wellness facility, consistent with national trends. Members had a lower prevalence of cigarette smoking compared to nonmembers (overall year-adjusted odds ratio 0.66, P < 0.001). Further, employees had a lower prevalence of cigarette smoking (9.7 vs. 17.3% in 2010, P < 0.001) compared with national data. Wellness facility membership was associated with increased regular exercise and cardiovascular exercise (P < 0.001) compared to nonmembers. In summary, working in a medical center was associated with a decreased prevalence of cigarette smoking, but not with lower prevalence of obesity. Worksite wellness facility membership was associated with increased exercise and decreased cigarette smoking. Employer-based interventions may be effective in improving some health behaviors.

The diagnostic yield of the first episode of a periodic health evaluation: a descriptive epidemiology study.

BACKGROUND: The benefits of a periodic health evaluation remain debatable. The incremental value added by such evaluations beyond the delivery of age appropriate screening and preventive medicine recommendations is unclear. METHODS: We retrospectively collected data on a cohort of consecutive patients presenting for their first episode of a comprehensive periodic health evaluation. We abstracted data on new diagnoses that were identified during this single episode of care and that were not trivial (i.e., required additional testing or intervention). RESULTS: The cohort consisted of 491 patients. The rate of new diagnoses per this single episode of care was 0.9 diagnoses per patient. The majority of these diagnoses was not prompted by patients' complaints (71%) and would not have been identified by screening guidelines (51%). Men (odds ratio 2.67; 95% CI, 1.76, 4.03) and those with multiple complaints at presentation (odds ratio 1.12; 95% CI, 1.05, 1.19) were more likely to receive a clinically relevant diagnosis at the conclusion of the visit. Age was not a predictor of receiving a diagnosis in this cohort. CONCLUSION: The first episode of a comprehensive periodic health evaluation may reveal numerous important diagnoses or risk factors that are not always identified through routine screening.

Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis.

CONTEXT: Vitamin D affects bone and muscle health and likely reduces the risk of falls in the elderly. OBJECTIVE: The aim of this systematic review is to summarize the existing evidence on vitamin D use and the risk of falls. DATA SOURCES: We searched electronic databases from inception through August 2010. STUDY SELECTION: Eligible studies were randomized controlled trials in which the intervention was vitamin D and the incidence of falls was reported. DATA EXTRACTION: Reviewers working in duplicate and independently extracted study characteristics, quality, and outcomes data. DATA SYNTHESIS: Odds ratio and associated 95% confidence interval were estimated from each study and pooled using the random effects model. RESULTS: We found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96). This effect was more prominent in patients who were vitamin D deficient at baseline and in studies in which calcium was coadministered with vitamin D. The quality of evidence was low to moderate because of heterogeneity and publication bias. CONCLUSIONS: Vitamin D combined with calcium reduces the risk of falls. The reduction in studies without calcium coadministration did not reach statistical significance. The majority of the evidence is derived from trials enrolling elderly women.

Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis.

CONTEXT: Several studies found association between vitamin D levels and hypertension, coronary artery calcification, and heart disease. OBJECTIVE: The aim of this study was to summarize the evidence on the effect of vitamin D on cardiovascular outcomes. DESIGN AND METHODS: We searched electronic databases from inception through August 2010 for randomized trials. Reviewers working in duplicate and independently extracted study characteristics, quality, and the outcomes of interest. Random-effects meta-analysis was used to pool the relative risks (RR) and the weighted mean differences across trials. RESULTS: We found 51 eligible trials with moderate quality. Vitamin D was associated with nonsignificant effects on the patient-important outcomes of death [RR, 0.96; 95% confidence interval (CI), 0.93, 1.00; P = 0.08], myocardial infarction (RR, 1.02; 95% CI, 0.93, 1.13; P = 0.64), and stroke (RR, 1.05; 95% CI, 0.88, 1.25; P = 0.59). These analyses were associated with minimal heterogeneity. There were no significant changes in the surrogate outcomes of lipid fractions, glucose, or diastolic or systolic blood pressure. The latter analyses were associated with significant heterogeneity, and the pooled estimates were trivial in absolute terms. CONCLUSIONS: Trial data available to date are unable to demonstrate a statistically significant reduction in mortality and cardiovascular risk associated with vitamin D. The quality of the available evidence is low to moderate at best.

Physician diagnosis of overweight status predicts attempted and successful weight loss in patients with cardiovascular disease and central obesity.

INTRODUCTION: Despite the association of central obesity with adverse outcomes, most patients with cardiovascular disease (CVD) are unable to successfully lose weight. We undertook this analysis to evaluate the effect of motivational factors, and clinical factors, including physician diagnosis of overweight, on weight loss in patients with CVD and central obesity in the United States. METHODS AND RESULTS: We used data from the National Health and Nutrition Examination Survey 1999 to 2004. Waist circumference ≥ 102 cm in men and ≥ 88 cm in women were used to classify central obesity. We examined demographic, motivational and clinical determinants of attempted and successful weight loss using multivariable logistic regression. Successful weight loss was defined as ≥ 5% weight loss in the preceding year. There were 907 respondents with CVD and central obesity of which 78% were aware of their overweight status and 80% were desirous to weigh less. Despite this awareness and desire, only 49% of centrally obese adults had attempted weight loss in the last year. Only 62% (n = 584) reported that they had been informed that they were overweight by a physician. On multivariable analysis, physician diagnosis of overweight was a significant predictor of weight loss attempts (OR 2.42, 95% CI 1.44-4.09, P = .006) and successful weight loss (OR 2.70, 95% CI 1.40-5.19, P = .001). CONCLUSION: In a nationally representative sample of adults with CVD and central obesity, physician diagnosis of overweight status emerged as a significant predictor of attempted and successful weight loss.

Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor?

Vitamin D deficiency is a highly prevalent condition, present in approximately 30% to 50% of the general population. A growing body of data suggests that low 25-hydroxyvitamin D levels may adversely affect cardiovascular health. Vitamin D deficiency activates the renin-angiotensin-aldosterone system and can predispose to hypertension and left ventricular hypertrophy. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. Epidemiologic studies have associated low 25-hydroxyvitamin D levels with coronary risk factors and adverse cardiovascular outcomes. Vitamin D supplementation is simple, safe, and inexpensive. Large randomized controlled trials are needed to firmly establish the relevance of vitamin D status to cardiovascular health. In the meanwhile, monitoring serum 25-hydroxyvitamin D levels and correction of vitamin D deficiency is indicated for optimization of musculoskeletal and general health.

The influence of sex and obesity phenotype on meal fatty acid metabolism before and after weight loss.

BACKGROUND: Regional differences in meal fat storage may explain the preservation of fat accumulation in obese persons. OBJECTIVE: The objective was to determine whether meal fatty acid (FA) metabolism differs by sex and obesity phenotypes before and after weight loss. DESIGN: A [(3)H]triolein-containing meal was given to trace meal FA oxidation ((3)H(2)O generation) and adipose tissue uptake (abdominal subcutaneous and gluteal biopsy samples) in 13 upper-body obese (UOb) men, 9 UOb women, and 8 lower-body obese (LOb) women (study 1). Dual-energy X-ray absorptiometry and abdominal computed tomography were used to measure fat distribution. The subjects participated in a diet and exercise weight-loss program, after which 23 subjects returned for an identical study (study 2). RESULTS: In study 1, the storage of meal FA (mg meal fat/g adipose lipid) was greater in gluteal than in abdominal fat (P = 0.022) in LOb women, but not in UOb women or UOb men. UOb men stored a lesser percentage of meal FAs in both upper- and lower-body subcutaneous fat than did the LOb and UOb women (P = 0.001 and P = 0.044, respectively). The participants who returned for study 2 had lost 14.1 +/- 1.1 kg. Changes in the uptake of meal FAs followed a pattern indicative of obesity phenotype maintenance by group. The uptake of meal FAs increased in upper-body subcutaneous fat (P = 0.028) in weight-reduced UOb women and UOb men (P = 0.046) and decreased in lower-body fat (P = 0.025) in UOb men. CONCLUSION: The differences in meal FA trafficking by obesity phenotype suggest that meal FA storage may play a role in regulating body fat distribution in obese persons.

The impact of a quality improvement program on employee satisfaction in an academic microsystem.

Quality improvement is a potential method to enhance employee satisfaction. This study describes the impact of a program instituted to enhance employee satisfaction using the principles of high-performing microsystems. A shared leadership committee, participatory meetings, suggestion boxes, and quality improvement projects were implemented as part of the program. A follow-up survey 1 year after implementation of the program demonstrated an increase in employee perception of the division's desire to improve service (16%), opportunities to expand skills (17%), involvement in work decisions (25%), and the institution's interest in employee well-being (17%). Key drivers of discretionary effort (4 of 5), job satisfaction (2 of 6), and overall satisfaction (1 of 8) with the institution showed statistically significant improvement in the study division as compared with the other divisions in which no such program was implemented. Further research is needed to study systems changes that enhance employee satisfaction and their impact on patient and financial outcomes.

Markers of inflammation are inversely associated with VO2 max in asymptomatic men.

We investigated whether markers of inflammation, including a cytokine (IL-6), acute-phase reactants [C-reactive protein (CRP) and fibrinogen], and white blood cell (WBC) count are associated with maximal O(2) consumption (Vo(2 max)) in men without coronary heart disease (CHD). In asymptomatic men (n = 172, 51 +/- 9.3 yr old), Vo(2 max) was measured during a symptom-limited graded treadmill exercise test. Physical activity level was assessed by a standardized questionnaire. IL-6 and CRP were measured by immunoassays, fibrinogen by the Clauss method, and WBC count with a Coulter counter. IL-6 and CRP were logarithmically transformed to reduce skewness. Multivariable regression was used to assess whether markers of inflammation were associated with Vo(2 max) after adjustment for age, body mass index, CHD risk factors, and lifestyle variables (physical activity level, percent body fat, and alcohol intake). Vo(2 max) was 34.5 ml.kg(-1).min(-1) (SD 6.1). Log IL-6 (r = -0.38, P < 0.001), log CRP (r = -0.40, P < 0.001), fibrinogen (r = -0.42, P < 0.001), and WBC count (r = -0.22, P = 0.004) were each correlated with Vo(2 max). In separate multivariable linear regression models that adjusted for age, body mass index, CHD risk factors, and lifestyle variables, log IL-6 [beta-coeff = -1.66 +/- 0.63 (SE), P = 0.010], log CRP [beta-coeff = -0.99 +/- 0.33 (SE), P = 0.003], fibrinogen [beta-coeff = -1.51 +/- 0.44 (SE), P = 0.001], and WBC count [beta-coeff = -0.52 +/- 0.30 (SE), P = 0.088] were each inversely associated with Vo(2 max). In conclusion, higher circulating levels of IL-6, CRP, and fibrinogen are independently associated with lower Vo(2 max) in asymptomatic men.

Extreme obesity: a new medical crisis in the United States.

The prevalence of obesity has markedly increased in the past few decades, and this disorder is responsible for more health care expenditures than any other medical condition. The greater the body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters), the greater the risk of comorbidities, including diabetes mellitus, hypertension, obstructive sleep apnea, many cancers, dyslipidemia, cardiovascular disease, and overall mortality. Class III (extreme) obesity, defined as a BMI of 40 kg/m2 or greater, has also increased such that it now affects almost 1 in 20 Americans. The prevalence of extreme obesity is greater among women than among men and greater among blacks than among non-Hispanic whites or Hispanics. The effect of extreme obesity on mortality is greater among young than among older adults, greater among men than among women, and greater among whites than among blacks. The current permissive environment that promotes increased dietary energy intake and decreased energy expenditure through reduced daily physical activity coupled with genetic susceptibility is an important pathogenic factor. The number of bariatric surgical procedures performed annually is relatively small but increasing.

Aortic augmentation index is inversely associated with cardiorespiratory fitness in men without known coronary heart disease.

BACKGROUND: We investigated whether the aortic augmentation index (AIx), a measure of arterial wave reflection and stiffness, is associated with cardiorespiratory fitness in men without known coronary heart disease (CHD). METHODS: Asymptomatic men (n = 201, mean age 51 +/- 9.2 years) referred for a screening exercise electrocardiogram (ECG) underwent applanation tonometry to obtain radial artery pulse waveforms, and an ascending aortic pressure waveform was derived by a transfer function. The AIx is the difference between the first and second systolic peak of the ascending aortic pressure waveform, expressed as a percentage of the pulse pressure. Cardiorespiratory fitness was assessed by maximal oxygen consumption (VO2max mL/min/kg) during a symptom-limited graded exercise test. Multivariable regression analyses were used to identify significant independent determinants of AIx and of VO2 max. RESULTS: Diabetes was present in 2.5% of subjects, 34.8% had history of smoking, and 29% were hypertensive. Mean (+/- SD) AIx was 19.9% +/- 9.0% and mean VO(2 max) was 33.9 +/- 6.4 mL/min/kg. In a multivariable linear regression model, AIx was positively associated with age, hypertension, and history of smoking and inversely with heart rate, height, and body mass index (BMI). The VO2 max was significantly inversely related to AIx after adjustment for age, heart rate, height, and BMI (r = -0.22, P = .002), after further adjustment for CHD risk factors (total cholesterol, HDL-cholesterol, history of smoking, diabetes, hypertension) (P = .006), and after additional adjustment for behavioral factors (physical activity score, alcohol intake, and percent body fat) (P = .022). CONCLUSIONS: These findings indicate that AIx, a measure of arterial wave reflection and stiffness, is inversely associated with cardiorespiratory fitness in men without CHD.

Action on obesity: report of a mayo clinic national summit.

In May 2004, representatives from local, state, and national public and private organizations met in Rochester, Minn, for the Action on Obesity Summit hosted by Mayo Clinic. The overall goal of this summit was to identify creative and effective strategies to Increase the US population's physical activity and improve nutrition to reverse the increasing prevalence of obesity. Ideas generated from selected abstract presentations and breakout sessions were prioritized and incorporated into an action model (available at www.actiononobesity.org) deemed feasible for implementation into most communities. Highlights of the presentations included a company that reported lower than expected health care expenditures secondary to a work site wellness program, a national initiative to increase physical activity (www.americaonthemove.org), and innovative work site nutritional strategies. The implementation model that emerged contained certain themes. Coordinated action at all levels will be required to substantially impact the increasing prevalence of obesity. Educational messages should be simple, consistent, tailored, and linked to benefits. Healthy food options in vending machines and restaurants and increased opportunities for daily physical activity should be available in schools, work sites, and communities. Legislative and policy changes should promote physical activity and improve nutrition. Support for research should be encouraged and outcome measures for interventions documented. A second Action on Obesity Summit is planned for June 9 and 10, 2005, that will review the progress made in the intervening year and continue to refine the implementation model to help address the obesity epidemic, one of the greatest public health problems facing the United States.

Splanchnic lipolysis in human obesity.

Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obesity phenotypes, taken together with healthy, lean women (n = 12) and men (n = 12), were studied. Systemic, splanchnic, and leg FFA kinetics were measured. The results showed that plasma FFA concentrations were approximately 20% greater in obese men and obese women. The contribution of splanchnic lipolysis to hepatic FFA delivery ranged from less than 10% to almost 50% and increased as a function of visceral fat in women (r = 0.49, P = 0.002) and in men (r = 0.52, P = 0.002); the slope of the relationship was greater in women than in men (P < 0.05). Leg and splanchnic tissues contributed a greater portion of systemic FFA release in obese men and women than in lean men and women. We conclude that the contribution of visceral adipose tissue lipolysis to hepatic FFA delivery increases with increasing visceral fat in humans and that this effect is greater in women than in men.