Central obesity in males affected by a dyslipidemia-associated genetic polymorphism on APOA1/C3/A4/A5 gene cluster

Background:

Central obesity is a rising epidemic, and often occurs in parallel with dyslipidemia. Furthermore, enhancement of ectopic fat deposition has been observed in both human studies and animal models of altered lipidemic control. Though APOA1/C3/A4/A5 genetic polymorphisms are associated with dyslipidemia, their effect on central obesity is less known.

Method:

The anthropometric and metabolic parameters were taken from obese (body mass index (BMI) ⩾25 kg m⁻²) and non-obese healthy (BMI <25) Taiwanese patients at the initiation weight-loss intervention and 6 months later. The effects of APOA1/C3/A4/A5 genetic polymorphisms were analyzed cross-sectionally and longitudinally. Gender contributions were specifically examined.

Patients:

Three hundred and ninety-eight participants (obese n=262; non-obese healthy n=136) were recruited in total, and 130 obese patients underwent weight-loss treatments.

Results:

APOA5 rs662799 minor allele carriage was associated with unfavorable metabolic profiles in obese but not non-obese individuals at baseline. Further analysis identified gender–genotype interactions in waist-hip ratio (WHR), and that one rs662799 minor allele increased 0.032 WHR unit in obese males as analyzed by linear regression adjusted for age, BMI and plasma triglyceride (TG) (95% confidence interval (CI)=0.014–0.050, P=0.001). The rs662799-associated WHR elevation resulted in increased frequency of central obesity (WHR ⩾1.0) in rs662799 carrying obese males as analyzed by binary logistic regression adjusted for age, BMI and plasma TG (odds ratio=6.52, 95% CI=1.87–22.73, P=0.003). In contrast, APOA5 rs662799 and central obesity were no longer correlated 6 months into weight-loss treatments, owing to significant WHR reductions in male rs662799 minor allele carriers (P=0.001). Meanwhile, hypertriglyceridemia was more prevalent in both male and female obese rs662799 minor allele carriers at baseline (males, P=0.034, females, P=0.007).

Conclusion:

This study highlights the gender-specific and weight-sensitive effects of APOA5 rs662799 on central obesity in Taiwanese individuals, and that these effects are dyslipidemia-independent and weight-loss responsive.     

Impact of vitamin D supplementation on adiposity in African-Americans

Background:

African-Americans have higher rates of obesity-associated chronic diseases. Serum 25-hydroxyvitamin D (25(OH)D) shows an inverse association with obesity status. We investigated whether vitamin D supplementation changes body mass index (BMI).

Subjects:

In total, 328 overweight African-Americans were enrolled over three consecutive winter periods (2007–2010) into a randomized, double-blind, placebo-controlled trial to receive cholecalciferol supplementation (0, 1000 international units (IU), 2000 IU or 4000 IU per day) for 3 months. Plasma concentrations of 25(OH)D and anthropometric measurements were done at baseline, 3 and 6 months.

Results:

At 3 months, vitamin D supplementation in three dose groups (1000 IU, 2000 IU or 4000 IU per day) did not cause any significant changes in BMI as compared with placebo group 3-month change in BMI per 1000 IU per day estimate (SE): 0.01 (0.039); P=0.78.

Conclusions:

In overweight African-Americans, short-term high-dose vitamin D supplementation did not alter BMI.     

Effect of trans fatty acid intake on abdominal and liver fat deposition and blood lipids: a randomized trial in overweight postmenopausal women

Background:

Intake of industrially produced trans fatty acids (TFAs) is, according to observational studies, associated with an increased risk of cardiovascular disease, but the causal mechanisms have not been fully elucidated. Besides inducing dyslipidemia, TFA intake is suspected to promote abdominal and liver fat deposition.

Objective:

We examined the effect of a high intake of TFA as part of an isocaloric diet on whole-body, abdominal and hepatic fat deposition, and blood lipids in postmenopausal women.

Methods:

In a 16-week double-blind parallel intervention study, 52 healthy overweight postmenopausal women were randomized to receive either partially hydrogenated soybean oil providing 15.7 g day⁻¹ of TFA or a control oil with mainly oleic and palmitic acid. Before and after the intervention, body composition was assessed by dual-energy X-ray absorptiometry, abdominal fat by magnetic resonance (MR) imaging, and liver fat by ¹H MR spectroscopy.

Results:

Compared with the control fat, TFA intake decreased plasma high-density lipoprotein (HDL)-cholesterol by 10%, increased low-density lipoprotein (LDL)-cholesterol by 18% and resulted in an increased LDL/HDL-cholesterol ratio (baseline adjusted mean (95% CI) difference between diet groups 0.41 (0.22; 0.60); P<0.001). TFA tended to increase the body fat (0.46 (−0.20; 1.17) kg; P=0.16) and waist circumference (1.1 (−0.1; 2.4) cm; P=0.08) more than the control fat, whereas neither abdominal nor liver fat deposition was affected by TFA.

Conclusion:

The adverse effect of dietary TFA on cardiovascular disease risk involves induction of dyslipidemia, and perhaps body fat, whereas weight gain-independent accumulation of ectopic fat could not be identified as a contributory factor during short-term intake.     

Can a relatively low-intensity intervention by health professionals prevent weight gain in mid-age women? 12-Month outcomes of the 40-Something randomised controlled trial

Background:

Weight gain in perimenopausal women results in increased visceral adipose tissue, leading to metabolic syndrome and associated comorbidities. Despite a high prevalence of weight gain at this life stage, interventions to prevent menopausal obesity are lacking.

Aim:

To test the effectiveness of an intervention delivered by health professionals using a motivational interviewing (MI) counselling style in preventing weight gain in non-obese (body mass index (BMI) 18.5 and 29.9 kg m⁻²) women in late premenopause.

Methods:

In a randomised controlled trial, 54 women (mean (s.d.) age 47.3 (1.8) years; BMI 25.1 (2.4) kg m⁻²) who had menstruated within the preceding 3 months were randomly assigned to an MI intervention (n=28) (five health professional MI counselling sessions) or a self-directed intervention (SDI) (print materials only) (n=26). The primary outcome, body weight (kg) and secondary outcomes (blood lipids, glucose, body fat %, lean mass % and waist circumference) were measured at baseline and postintervention (12 months), and intention-to-treat analysis was conducted.

Results:

Forty women completed all measures and adhered to all protocols. The weight at 12 months for the MI group of 65.6 kg (95% CI: 64.5; 66.8) was significantly different (P=0.034) from the SDI group of 67.4 kg (95% CI: 66.2; 68.6). When stratified by baseline BMI category, the MI group lost significantly more weight (−2.6 kg; 95% CI: −3.9; −1.2) than the SDI group (−0.1 kg; 95% CI: −1.2; 1.0, P=0.002) for the healthy weight women. The overweight women lost weight regardless of the intervention group, with no between-group difference (−3.5 kg; 95% CI: −6.1, −1.0 and −2.3; 95% CI: −4.1, −0.5, P=0.467).

Conclusion:

This relatively low-intensity intervention, incorporating MI into health professional counselling, not only effectively prevented weight gain but also achieved significant weight loss and decreased diastolic blood pressure. Further refinements are required to optimise outcomes for overweight women.     

Serum S-adenosylmethionine,but not methionine,increases in response to overfeeding in humans

Background:

Plasma concentration of the methyl donor S-adenosylmethionine (SAM) is linearly associated with body mass index (BMI) and fat mass. As SAM is a high-energy compound and a sensor of cellular nutrient status, we hypothesized that SAM would increase with overfeeding.

Methods:

Forty normal to overweight men and women were overfed by 1250 kcal per day for 28 days.

Results:

Serum SAM increased from 106 to 130 nmol/l (P=0.006). In stratified analysis, only those with weight gain above the median (high-weight gainers; average weight gain 3.9±0.3 kg) had increased SAM (+42%, P=0.001), whereas low-weight gainers (weight gain 1.5±0.2 kg) did not (P_interaction=0.018). Overfeeding did not alter serum concentrations of the SAM precursor, methionine or the products, S-adenosyl-homocysteine and homocysteine. The SAM/SAH (S-adenosylhomocysteine) ratio was unchanged in the total population, but increased in high-weight gainers (+52%, P=0.006, P_interaction =0.005). Change in SAM correlated positively with change in weight (r=0.33, P=0.041) and fat mass (r=0.44, P=0.009), but not with change in protein intake or plasma methionine, glucose, insulin or low-density lipoprotein (LDL)-cholesterol.

Conclusion:

Overfeeding raised serum SAM in proportion to the fat mass gained. The increase in SAM may help stabilize methionine levels, and denotes a responsiveness of SAM to nutrient state in humans. The role of SAM in human energy metabolism deserves further attention.     

Altered functional connectivity within the central reward network in overweight and obese women

Background/Objectives:

Neuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network.

Subjects/Methods:

Fifty healthy, premenopausal women, 19 overweight and obese (high BMI=26–38 kg m⁻²) and 31 lean (BMI=19–25 kg m⁻²) were selected from the University of California Los Angeles'' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined.

Results:

GMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band.

Conclusions:

Overweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors.     

Effectiveness of a Physical Activity and Weight Loss Intervention for Middle-Aged Women: Healthy Bodies,Healthy Hearts Randomized Trial

BACKGROUND

Physical inactivity is a significant risk factor for cardiovascular disease and remains highly prevalent in middle-aged women.

OBJECTIVE

We hypothesized that an interventionist-led (IL), primary-care–based physical activity (PA) and weight loss intervention would increase PA levels and decrease weight to a greater degree than a self-guided (SG) program.

DESIGN

We conducted a randomized trial.

PARTICIPANTS

Ninety-nine inactive women aged 45–65 years and with BMI ≥ 25 kg/m² were recruited from three primary care clinics.

INTERVENTIONS

The interventionist-led (IL) group (n = 49) had 12 weekly sessions of 30 min discussions with 30 min of moderate-intensity PA. The self-guided (SG) group (n = 50) received a manual for independent use.

MAIN MEASURES

Assessments were conducted at 0, 3, and 12 months; PA and weight were primary outcomes. Weight was measured with a standardized protocol. Leisure PA levels were assessed using the Modifiable Activity Questionnaire. Differences in changes by group were analyzed with a t-test or Wilcoxon rank-sum test. Mixed models were used to analyze differences in changes of outcomes by group, using an intention-to-treat principle.

KEY RESULTS

Data from 98 women were available for analysis. At baseline, mean (SD) age was 53.9 (5.4) years and 37 % were black. Mean weight was 92.3 (17.7) kg and mean BMI was 34.7 (5.9) kg/m². Median PA level was 2.8 metabolic equivalent hours per week (MET-hour/week) (IQR 0.0, 12.0). At 3 months, IL women had a significantly greater increase in PA levels (7.5 vs. 1.9 MET-hour/week; p = 0.02) than SG women; there was no significant difference in weight change. At 12 months, the difference between groups was no longer significant (4.7 vs. 0.7 MET-hour/week; p = 0.38). Mixed model analysis showed a significant (p = 0.048) difference in PA change between groups at 3 months only.

CONCLUSIONS

The IL intervention was successful in increasing the physical activity levels of obese, inactive middle-aged women in the short-term. No significant changes in weight were observed.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-014-3077-5) contains supplementary material, which is available to authorized users.KEY WORDS: physical activity, exercise, clinical trial, intervention     

Impact of body mass index on diastolic function in patients with normal left ventricular ejection fraction

Background:

Obesity is a major public health epidemic and is associated with increased risk of heart failure and mortality. We evaluated the impact of body mass index (BMI) on the prevalence of diastolic dysfunction (DD).

Methods:

We reviewed clinical records and echocardiogram of patients with baseline echocardiogram between 1996 and 2005 that showed normal left ventricular ejection fraction (LVEF). Diastolic function was labeled as normal, stage 1, stage 2 or stage 3/4 dysfunction. Patients were categorized as normal weight (BMI <25 kg m⁻²), overweight (25–29.9 kg m⁻²), obese (30–39.9 kg m⁻²) and morbidly obese (⩾40 kg m⁻²). Multivariable ordinal and ordinary logistic regression were performed to identify factors associated with DD, and evaluate the independent relationship of BMI with DD.

Results:

The cohort included 21 666 patients (mean (s.d.) age, 57.1 (15.1); 55.5% female). There were 7352 (33.9%) overweight, 5995 (27.6%) obese and 1616 (7.4%) morbidly obese patients. Abnormal diastolic function was present in 13 414 (61.9%) patients, with stage 1 being the most common. As BMI increased, the prevalence of normal diastolic function decreased (P<0.0001). Furthermore, there were 1733 patients with age <35 years; 460 (26.5%) and 407 (23.5%) were overweight and obese, respectively, and had higher prevalence of DD (P<0.001). Using multivariable logistic regression, BMI remained significant in both ordinal (all stages of diastolic function) and binary (normal versus abnormal). Also, obesity was associated with increased odds of DD in all patients and those aged <35 years.

Conclusions:

In patients with normal LVEF, higher BMI was independently associated with worsening DD.     

Medical Student Perceptions of Cost-Conscious Care in an Internal Medicine Clerkship: A Thematic Analysis

Background

Although as much as 87 % of all healthcare spending is directed by physicians, studies have demonstrated that they lack knowledge about the costs of medical care. Similarly, learners have not traditionally received instruction on cost-conscious care.

Objective

To examine medical students'' perceptions of healthcare delivery as it relates to cost consciousness

Design

Retrospective qualitative analysis of medical student narratives

Participants

Third-year medical students during their inpatient internal medicine clerkship

Main Measures

Students completed a reflective exercise wherein they were asked to describe a scenario in which a patient experienced lack of attention to cost-conscious care, and were asked to identify solutions and barriers. We analyzed these reflections to learn more about students’ awareness and perceptions regarding the practice of cost-conscious care within our medical center.

Key Results

Eighty students submitted the assignment between July and December 2012. The most common problems identified included unnecessary tests and treatments (n = 69) and duplicative tests and treatments (n = 20.) With regards to solutions, students described 82 scenarios, with 125 potential solutions identified. Students most commonly used discussion with the team (speak up, ask why) as the process they would use (n = 28) and most often wanted to focus lab testing (n = 38) as the intervention. The most common barriers to high-value care included increased time and effort (n = 19), ingrained practices (n = 17), and defensive medicine or fear of missing something (n = 18.)

Conclusions

Even with minimal clinical experience, medical students were able to identify instances of lack of attention to cost-conscious care as well as potential solutions. Although students identified the hierarchy in healthcare teams as a potential barrier to improving high value care, most students stated they would feel comfortable engaging the team in discussion. Future efforts to empower learners at all levels to question value decisions and to develop and implement solutions may result in improved healthcare.     

Asian women have greater abdominal and visceral adiposity than Caucasian women with similar body mass index

Background:

In the Multiethnic Cohort Study, Japanese Americans (JA) have lower mean body mass index (BMI) compared with Caucasians, but show a higher waist-to-hip ratio at similar BMI values and a greater risk of diabetes and obesity-associated cancers.

Objective:

We investigated the abdominal, visceral and hepatic fat distribution in these Asian and Caucasian Americans.

Design:

A cross-sectional sample of 60 female cohort participants (30 JA and 30 Caucasians), of ages 60–65 years and BMIs 18.5–40 kg m⁻², underwent anthropometric measurements and a whole-body dual energy X-ray absorptiometry (DXA) scan: a subset of 48 women also had abdominal magnetic resonance imaging (MRI).

Results:

By design, JA women had similar BMIs (mean 26.5 kg m⁻²) to Caucasian women (27.1 kg m⁻²). JA women were found to have a significantly smaller hip circumference (96.9 vs 103.6 cm; P=0.007) but not a significantly lower DXA total fat mass (25.5 vs 28.8 kg; P=0.16). After adjusting for age and DXA total fat mass, JA women had a greater waist-to-hip ratio (0.97 vs 0.89; P<0.0001), DXA trunk fat (15.4 vs 13.9 kg; P=0.0004) and MRI % abdominal visceral fat (23.9 vs 18.5% P=0.01) and a lower DXA leg fat mass (8.2 vs 10.0 kg; P=<.0001). Their MRI % subcutaneous fat (33.4 vs 30.2% P=0.21) and % liver fat (5.8 vs 3.8% P=0.06) did not significantly differ from that of Caucasian women.

Conclusions:

Our findings build on limited past evidence, suggesting that Asian women carry greater abdominal and visceral fat when compared with Caucasian women with similar overall adiposity. This may contribute to their elevated metabolic risk for obesity-related diseases.     

Body mass index and health status in diabetic and non-diabetic individuals

Background/Objectives:

There is controversy regarding the existence of a body mass index (BMI) mortality paradox in diabetes, whereby the optimal BMI category is higher than it is in non-diabetic persons. To explore possible pathways to a mortality paradox, we examined the relationship of BMI with physical and mental health status in diabetic and non-diabetic persons.

Subjects/Methods:

We examined adjusted SF-12 Physical and Mental Component Summary (PCS-12 and MCS-12) scores by BMI (kg m⁻²) category (underweight, <20; normal weight, 20 to <25; overweight, 25 to <30; obese, 30 to <35; severely obese ⩾35) in adult diabetic and non-diabetic respondents to the 2000–2011 United States national Medical Expenditure Panel Surveys (N=119 161). Adjustors were age, sex, race/ethnicity, income, health insurance, education, smoking, comorbidity, urbanicity, geographic region and survey year.

Results:

In non-diabetic persons the adjusted mean PCS-12 score was highest (that is, most optimal) in the normal-weight category, whereas for diabetic persons the optimal adjusted mean PCS-12 score was in the overweight category (adjusted difference between non-diabetic and diabetic persons in the difference in PCS-12 means for overweight versus normal-weight category=0.8 points, 95% confidence interval; CI 0.1, 1.6; P=0.03). This paradoxical pattern was not evident for the MCS-12, and the adjusted difference between non-diabetic and diabetic persons in the difference in MCS-12 means for overweight versus obese persons was not significant (−0.3 points, 95% CI −0.9, 0.4; P=0.43). The findings were not significantly moderated by smoking status, cancer diagnosis or time period.

Conclusions:

The optimal BMI category for physical health status (but not mental health status) was higher among diabetic than non-diabetic persons. The findings are consistent with a BMI physical health status paradox in diabetes and, in turn, a mortality paradox.     

Measures of body fat in South Asian adults

Background:

South Asian people who originate from the Indian subcontinent have greater percent body fat (%BF) for the same body mass index (BMI) compared with white Caucasians. This has been implicated in their increased risk of type 2 diabetes and cardiovascular disease. There is limited information comparing different measures of body fat in this ethnic group.

Objectives:

The objectives of this study were: (1) to investigate the correlation of %BF measured by a foot-to-foot bioelectrical impedance analysis (FF-BIA) against the BOD POD, a method of air-displacement plethysmography, and (2) to determine the correlations of simple anthropometric measures, (that is, BMI, body adiposity index (BAI), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR)) against the BOD POD measure of body fat.

Methods:

Eighty apparently healthy South Asian men and women were recruited from the community, and measurements of height, weight, WC, HC and body composition using Tanita FF-BIA and BOD POD were taken.

Results:

The mean±s.d. age of participants was 27.78±10.49 years, 42.5% were women, and the mean BMI was 22.68±3.51 kg m⁻². The mean body fat (%BF) calculated by FF-BIA and BOD POD was 21.94±7.88% and 26.20±8.47%, respectively. The %BF calculated by FF-BIA was highly correlated with the BOD POD (Pearson''s r=0.83, P<0.001), however, FF-BIA underestimated %BF by 4.3%. When anthropometric measures were compared with % BF by BOD POD, the BAI showed the strongest correlation (r=0.74) and the WHR showed the weakest (r=0.33). BAI generally underestimated %BF by 2.6% in comparison with %BF by BOD POD. The correlations of BOD POD with other measures of %BF were much stronger in subjects with a BMI >21 kg m⁻² than those with a BMI ⩽21 kg m⁻².

Conclusion:

The FF-BIA and BAI estimates of %BF are highly correlated with that of BOD POD among people of South Asian origin, although both methods somewhat underestimate % BF. Furthermore, their correlations with % BF from BOD POD are significantly weakened among men and women with a BMI ⩽21 kg m⁻².     

The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity

Background:

Cannabinoid type-1 (CB1) receptor inverse agonists improve type 2 diabetes and dyslipidaemia but were discontinued due to adverse psychiatric effects. Δ⁹-Tetrahydrocannabivarin (THCV) is a neutral CB1 antagonist producing hypophagia and body weight reduction in lean mice. We investigated its effects in dietary-induced (DIO) and genetically (ob/ob) obese mice.

Methods:

We performed two dose-ranging studies in DIO mice; study 1: 0.3, 1, 2.5, 5 and 12.5 mg kg⁻¹, oral twice daily for 30 days and study 2: 0.1, 0.5, 2.5 and 12.5 mg kg⁻¹, oral, once daily for 45 days. One pilot (study 3: 0.3 and 3 mg kg⁻¹, oral, once daily) and one full dose-ranging (study 4: 0.1, 0.5, 2.5 and 12.5 mg kg⁻¹, oral, once daily) studies in ob/ob mice for 30 days. The CB1 inverse agonist, AM251, oral, 10 mg kg⁻¹ once daily or 5 mg kg⁻¹ twice daily was used as the positive control. Cumulative food and water intake, body weight gain, energy expenditure, glucose and insulin levels (fasting or during oral glucose tolerance tests), plasma high-density lipoprotein and total cholesterol, and liver triglycerides were measured. HL-5 hepatocytes or C₂C₁₂ myotubes made insulin-resistant with chronic insulin or palmitic acid were treated with 0, 1, 3 and 10 μℳ THCV or AM251.

Results:

THCV did not significantly affect food intake or body weight gain in any of the studies, but produced an early and transient increase in energy expenditure. It dose-dependently reduced glucose intolerance in ob/ob mice and improved glucose tolerance and increased insulin sensitivity in DIO mice, without consistently affecting plasma lipids. THCV also restored insulin signalling in insulin-resistant hepatocytes and myotubes.

Conclusions:

THCV is a new potential treatment against obesity-associated glucose intolerance with pharmacology different from that of CB1 inverse agonists/antagonists.     

Circulating sCD36 is associated with unhealthy fat distribution and elevated circulating triglycerides in morbidly obese individuals

Background:

The recently identified circulating sCD36 has been proposed to reflect tissue CD36 expression, and is upregulated in case of obesity, insulin resistance and hepatic steatosis. The aim of this study was to explore the effect of weight loss secondary to bariatric surgery in relation to sCD36 among morbidly obese individuals. Furthermore, we investigated the levels of sCD36 in relation to obesity-related metabolic complications, low-grade inflammation and fat distribution.

Methods:

Twenty morbidly obese individuals (body mass index (BMI) 43.0±5.4 kg m⁻²) with a referral to Roux-en-Y gastric bypass were included. Anthropometric measurements and fasting blood samples were collected at a preoperative baseline visit and 3 months after surgery. sCD36 was measured by an in-house assay, whereas insulin sensitivity and the hepatic fat accumulation were estimated by the homeostasis model assessment (HOMA-%S) and liver fat percentage (LF%), respectively.

Results:

Postoperatively, BMI was reduced by 20% to 34.3±5.2 kg m⁻² (P<0.001). sCD36 was reduced by 31% (P=0.001) and improvements were observed in the amount of fat mass (P<0.001), truncal fat mass (P<0.001), circulating triglycerides (P=0.001), HOMA-%S (P=0.007), LF% (P=0.001) and the inflammatory marker high-sensitive C-reactive protein (P=0.005). sCD36 correlated with triglycerides (ρ=0.523, P=0.001) and truncal fat mass (ρ=0.357, P=0.026), and triglycerides were found to be an independent predictor of sCD36. At baseline, participants with the metabolic syndrome had a higher LF% and higher levels of the inflammatory biomarker YKL-40 (P=0.003 and P=0.014) as well as a tendency towards higher levels of sCD36.

Conclusion:

sCD36 was reduced by weight loss and associated with an unhealthy fat accumulation and circulating triglycerides, which support the proposed role of sCD36 as a biochemical marker of obesity-related metabolic complications and risks.     

A simple scoring method using cardiometabolic risk measurements in pregnancy to determine 10-year risk of type 2 diabetes in women with gestational diabetes

Objective:

To examine if clustering of cardiometabolic risk factors in pregnancy predicts type 2 diabetes and cardiovascular disease (CVD) risk at 10 years in women with gestational diabetes mellitus (GDM).

Study design and subjects:

A prospective case–control study in 150 GDM and 72 overweight women with normal glucose tolerance (NGT) measured cardiometabolic risk factors (body mass index (BMI), systolic blood pressure (SBP), fasting glucose, insulin, and triglycerides and high-density lipoprotein (HDL) cholesterol) at 28 weeks gestation and 6 months and 10 years after pregnancy. Cluster analysis of cardiometabolic risk factors in pregnancy was used to stratify GDM as ‘high'' and ‘low risk'' for diabetes and CVD risk at 10 years. The data in pregnancy were used to determine a simple method for assessing risk of future diabetes.

Results:

BMI in the 150 GDM at study entry was similar to NGT, but 35% of GDM fell into a ‘high-risk cluster'' with elevated BMI, SBP, glucose, insulin and triglycerides and lower HDL levels. At 10 years, type 2 diabetes was sixfold higher in ‘high-risk'' GDM (odds ratio (OR)=6.75, confidence interval (CI)=2.0, 22.7, P=0.002) compared with ‘low-risk'' GDM and was not reported in NGT. The ‘high-risk'' cluster predicted type 2 diabetes better than BMI>30 (OR=2.13, CI=0.71, 6.4, P=0.179) or fasting glucose >5.5 mmol l^–1, (OR=4.56, CI=1.50, 13.85, P=0.007). We determined that GDM with any four of the cardiometabolic risk factors (BMI>30 kg m^–2, fasting glucose>5.0 mmol l^–1, insulin>7.8 mU l^–1, triglycerides >2.4 mmol l^–1, HDL<1.6 mmol l^–1 or SBP>105 mm Hg) in pregnancy would be in a ‘high-risk'' cluster.

Conclusions:

A metabolic syndrome-like cluster in pregnant GDM identifies risk for type 2 diabetes providing an opportunity to focus on rigorous lifestyle interventions after delivery to reduce the burden of disease attributed to this condition.     

The origin of circulating CD36 in type 2 diabetes

Objective:

Elevated plasma levels of the fatty acid transporter, CD36, have been shown to constitute a novel biomarker for type 2 diabetes mellitus (T2DM). We recently reported such circulating CD36 to be entirely associated with cellular microparticles (MPs) and aim here to determine the absolute levels and cellular origin(s) of these CD36+MPs in persons with T2DM.

Design:

An ex vivo case-control study was conducted using plasma samples from 33 obese individuals with T2DM (body mass index (BMI)=39.9±6.4 kg m⁻²; age=57±9 years; 18 male:15 female) and age- and gender-matched lean and obese non-T2DM controls (BMI=23.6±1.8 kg m⁻² and 33.5±5.9 kg m⁻², respectively). Flow cytometry was used to analyse surface expression of CD36 together with tissue-specific markers: CD41, CD235a, CD14, CD105 and phosphatidyl serine on plasma MPs. An enzyme-linked immunosorbent assay was used to quantify absolute CD36 protein concentrations.

Results:

CD36+MP levels were significantly higher in obese people with T2DM (P<0.00001) and were primarily derived from erythrocytes (CD235a+=35.8±14.6%); although this did not correlate with haemoglobin A_1c. By contrast, the main source of CD36+MPs in non-T2DM individuals was endothelial cells (CD105+=40.9±8.3% and 33.9±8.3% for lean and obese controls, respectively). Across the entire cohort, plasma CD36 protein concentration varied from undetectable to 22.9 μg ml⁻¹ and was positively correlated with CD36+MPs measured by flow cytometry (P=0.0006) but only weakly associated with the distribution of controls and T2DM (P=0.021). Multivariate analysis confirmed that plasma CD36+MP levels were a much better biomarker for diabetes than CD36 protein concentration (P=0.009 vs P=0.398, respectively).

Conclusions:

Both the levels and cellular profile of CD36+MPs differ in T2DM compared with controls, suggesting that these specific vesicles could represent distinct biological vectors contributing to the pathology of the disease.     

Electronic Tools to Assist with Identification and Counseling for Overweight Patients: a Randomized Controlled Trial

Background

Physicians often do not recognize when their patients are overweight and infrequently counsel them about weight loss.

Objective

To evaluate a set of electronic health record (EHR)-embedded tools to assist with identification and counseling of overweight patients.

Design

Randomized controlled trial.

Participants

Physicians at an academic general internal medicine clinic were randomized to activation of the EHR tools (n = 15) or to usual care (n = 15). Patients of these physicians were included in analyses if they had a body mass index (BMI) between 27 and 29.9 kg/m².

Intervention

The EHR tool set included: a physician point-of-care alert for overweight (BMI 27–29. 9 kg/m²); a counseling template to help physicians counsel patients on action plans; and an order set to facilitate entry of overweight as a diagnosis and to order relevant patient handouts.

Main Measures

Physician documentation of overweight as a problem; documentation of weight-specific counseling; physician perceptions of the EHR tools; patient self-reported progress toward their goals and perspectives about counseling received.

Key Results

Patients of physicians receiving the intervention were more likely than those of usual care physicians to receive a diagnosis of overweight (22% vs. 7%; p = 0.02) and weight-specific counseling (27% vs. 15%; p = 0.02). Most patients receiving counseling in the intervention group reported increased motivation to lose weight (90%) and taking steps toward their goal (93%). Most intervention physicians agreed that the tool alerted them to patients they did not realize were overweight (91%) and improved the effectiveness of their counseling (82%); more than half (55%) reported counseling overweight patients more frequently (55%). However, most physicians used the tool infrequently because of time barriers.

Conclusions

EHR-based alerts and management tools increased documentation of overweight and counseling frequency; the majority of patients for whom the tools were used reported short-term behavior change.KEY WORDS: overweight, counseling, electronic health record     

Omentin-1 plasma levels and cholesterol metabolism in obese patients with diabetes mellitus type 1: impact of weight reduction

Background:

Omentin-1 is an anti-inflammatory adipokine produced preferentially by visceral adipose tissue. Plasma levels of omentin-1 are decreased in obesity and other insulin-resistant states. Insulin resistance contributes to the changes of cholesterol synthesis and absorption as well. The aim of this study was to characterise omentin-1 plasma levels in obese patients with diabetes mellitus type 1 during weight reduction, and to elucidate the relationship between cholesterol metabolism and omentin-1.

Methods:

Plasma levels of omentin-1 were measured in obese type 1 diabetics (n=14, body mass index >30 kg m⁻², age 29–62 years) by enzyme-linked immunosorbent assay (BioVendor). Gas chromatography with flame ionisation detector (Fisons Plc.,) was used to measure squalene and non-cholesterol sterols—markers of cholesterol synthesis and absorption (phase I). Measurements were repeated after 1 month (phase II; 1 week of fasting in the hospital setting and 3 weeks on a diet containing 150 g saccharides per day) and after 1 year (phase III) on a diet with 225 g saccharides per day.

Results:

Omentin-1 plasma levels were stable during phases I and II, but significantly increased (P<0.001) during phase III. Omentin-1 plasma dynamics were significantly associated with plasma levels of high-density lipoprotein (P=0.005) and triacylglycerols (P=0.01), as well as with lathosterol (P=0.03).

Conclusion:

Omentin-1 plasma levels significantly increased during the weight reduction programme. Omentin-1 plasma dynamics suggest a close relationship with cholesterol metabolism.     

Specific appetite,energetic and metabolomics responses to fat overfeeding in resistant-to-bodyweight-gain constitutional thinness

Background:

Contrasting with obesity, constitutional thinness (CT) is a rare condition of natural low bodyweight. CT exhibits preserved menstruation in females, no biological marker of undernutrition, no eating disorders but a bodyweight gain desire. Anorexigenic hormonal profile with high peptide tyrosine tyrosine (PYY) was shown in circadian profile. CT could be considered as the opposite of obesity, where some patients appear to resist diet-induced bodyweight loss.

Objective:

The objective of this study was to evaluate appetite regulatory hormones in CTs in an inverse paradigm of diet-induced weight loss.

Methods:

A 4-week fat overfeeding (2640 kJ excess) was performed to compare eight CT women (body mass index (BMI)<17.5 kg m⁻²) to eight female controls (BMI 18.5–25 kg m⁻²). Appetite regulatory hormones profile after test meal, food intake, bodyweight, body composition, energy expenditure and urine metabolomics profiles were monitored before and after overfeeding.

Results:

After overfeeding, fasting total and acylated ghrelin were significantly lower in CTs than in controls (P=0.01 and 0.03, respectively). After overfeeding, peptide tyrosine tyrosine (PYY) and glucagon-like-peptide 1 both presented earlier (T15 min vs T30 min) and higher post-meal responses (incremental area under the curve) in CTs compared with controls. CTs failed to increase bodyweight (+0.22±0.18 kg, P=0.26 vs baseline), contrasting with controls (+0.72±0.26 kg, P=0.03 vs baseline, P=0.01 vs CTs). Resting energy expenditure increased in CTs only (P=0.031 vs baseline). After overfeeding, a significant negative difference between total energy expenditure and food intake was noticed in CTs only (−2754±720 kJ, P=0.01).

Conclusion:

CTs showed specific adaptation to fat overfeeding: overall increase in anorexigenic hormonal profile, enhanced post prandial GLP-1 and PYY and inverse to controls changes in urine metabolomics. Overfeeding revealed a paradoxical positive energy balance contemporary to a lack of bodyweight gain, suggesting yet unknown specific energy expenditure pathways in CTs.