Validation of the vitronectin knockout mouse as a model for studying myocardial infarction: Vitronectin appears to influence left ventricular remodelling following myocardial infarction

BACKGROUND:

Vitronectin (VN) is an abundant acute-phase plasma protein that regulates cell adhesion and migration as well as interactions with components of the plasminogen activator/plasmin system, specifically plasminogen activator inhibitor type 1. This system plays a major role in tissue remodelling regulating wound healing after myocardial infarction.

OBJECTIVES:

To investigate the feasibility of using VN knockout mice (VN^−/−) to study the role of VN on ventricular remodelling following myocardial infarction.

METHODS:

Specifically bred VN^−/− mice and normal wild-type (VN^+/+) mice underwent coronary artery ligation and were assessed 28 days postligation using echocardiography and morphometric histology.

RESULTS:

No difference was observed between VN^−/− mice and VN^+/+ mice with respect to gross phenotype, weight, coronary anatomy or echocardiographically measured ejection fraction (56%). Following myocardial infarction, VN^−/− mice exhibited less ventricular dilation and less impairment in echocardiographic ejection fraction compared with VN^+/+ mice (48% versus 41%; P=0.01). VN^−/− mice also exhibited smaller infarcts on morphometric analysis.

CONCLUSIONS:

The results of the present study confirmed the feasibility of using coronary artery ligation in VN knockout mice to investigate the role of VN in post-myocardial infarction remodelling. The absence of VN appears to result in favourable effects on wound healing. These data suggest that this model may offer novel insights into the role of VN in the regulation of myocardial remodelling.     

Comparing the Performance of the Optical Glucose Assay Based on Glucose Binding Protein with High-Performance Anion-Exchange Chromatography with Pulsed Electrochemical Detection: Efforts to Design a Low-Cost Point-of-Care Glucose Sensor

Background

The glucose binding protein (GBP) is one of many soluble binding proteins found in the periplasmic space of gram-negative bacteria. These proteins are responsible for chemotactic responses and active transport of chemical species across the membrane. Upon ligand binding, binding proteins undergo a large conformational change, which is the basis for converting these proteins into optical biosensors.

Methods

The GBP biosensor was prepared by attaching a polarity-sensitive fluorescent probe to a single cysteine mutation at a site on the protein that is allosterically responsive to glucose binding. The fluorescence response of the resulting sensor was validated against high-performance anion-exchange chromatography (HPAEC) with pulsed electrochemical detection. Finally, a simple fluorescence reader was built using a lifetime-assisted ratiometric technique.

Results

The GBP assay has a linear range of quantification of 0.100–2.00 μM and a sensitivity of 0.164 μM⁻¹ under the specified experimental conditions. The comparison between GBP and HPAEC readings for nine blind samples indicates that there is no statistical difference between the analytical results of the two methods at the 95% confidence level. Although the methods of fluorescence detection are based on different principles, the response of the homemade device to glucose concentrations was comparable to the response of the larger and more expensive tabletop fluorescence spectrophotometer.

Conclusions

A glucose binding protein labeled with a polarity-sensitive probe can be used for measuring micromolar amounts of glucose. Using a lifetime-assisted ratiometric technique, a low-cost GBP-based micromolar glucose monitor could be built.     

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.     

Noninvasive Ultrasonic Glucose Sensing with Large Pigs (～200 Pounds) Using a Lightweight Cymbal Transducer Array and Biosensors

Background

To prevent complications in diabetes, the proper management of blood glucose levels is essential. Since conventional glucose meters require pricking fingers or other areas of the skin, a noninvasive method for monitoring blood glucose levels is desired. Using a lightweight cymbal transducer array, this study was conducted to noninvasively determine the glucose levels of pigs having a similar size to humans.

Method

In vivo experiments using eight pigs (∼200 pounds) were performed in five groups. A cymbal array with four biosensors was attached to the axillary area of the pig. The array was operated at 20 kHz at special peak–temporal peak intensity (I_sptp) equal to 50 or 100 mW/cm² for 5, 10, or 20 minutes. After the ultrasound exposure, glucose concentrations of the interstitial fluid were determined using biosensors. For comparison, glucose levels of blood samples collected from the ear vein were measured by a commercial glucose meter.

Result

In comparison, glucose levels determined by a cymbal array and biosensor system were close to those measured by a glucose meter. After a 20-minute ultrasound exposure at I_sptp = 100 mW/cm², the average glucose level determined by the ultrasound system was 175 ± 7 mg/dl, which is close to 166 ± 5 mg/dl measured by the glucose meter.

Conclusion

Results indicate the feasibility of using a cymbal array for noninvasive glucose sensing on pigs having a similar size to humans. Further studies on the ultrasound conditions, such as frequency, intensity, and exposure time, will be continued for effective glucose sensing.     

Female rats are relatively more sensitive to reduced lipid versus reduced carbohydrate availability

Objectives:

Because females have blunted counterregulatory responses to hypoglycemia relative to males, we hypothesized that females would have greater sensitivity to changes in lipid availability.

Design and subjects:

To assess this, we examined the feeding response to glucoprivation (2-deoxyglucose; 2DG) and lipoprivation (mercaptoacetate; MA) in age-matched male and female Long-Evans rats.

Results:

Males versus females had significantly greater food intake after 250 mg kg⁻¹ of 2DG, but there were no sex differences with the 750 mg kg⁻¹ dose of 2DG. Glucose responses to 250 mg kg⁻¹ of 2DG were also significantly greater in males versus females. In contrast, females had a significant increase in food intake with all doses of MA versus saline, and had significantly greater food intake compared with males at the lowest and highest doses of MA with a trend towards significance with the intermediate dose. To determine whether estradiol (E2) is the mechanism underlying this sexual dimorphism, ovariectomized females were injected with vehicle or 2 μg of E2 every fourth day to mimic the variations in across the estrous cycle. Ovariectomized females significantly increased feeding and glucose after 250 mg kg⁻¹ of 2DG over intact females and E2 had no effect on these responses. Although the feeding response to 2DG was not different, the glucose response to 2DG was still significantly greater in males versus ovariectomies females. However, ovariectomized females also did not increase food intake after MA, regardless of E2 treatment.

Conclusions:

These data collectively suggest that males are relatively more sensitive to glucose deprivation and females are relatively more sensitive to lipid deprivation. Further, these data rule out a role for cyclic changes in E2 in these sex differences.     

Clinical Correlates of Insulin Sensitivity and Its Association with Mortality among Men with CKD Stages 3 and 4

Background and objectives

Insulin resistance participates in the pathogenesis of multiple metabolic and cardiovascular diseases. CKD patients have impaired insulin sensitivity, but the clinical correlates and outcome associations of impaired insulin sensitivity in this vulnerable population are not well defined.

Design, setting, participants, & measurements

The prospective cohort study was from the third examination cycle of the Uppsala Longitudinal Study of Adult Men, a population-based survey of elderly men ages 70–71 years; insulin sensitivity was assessed by glucose disposal rate as measured with euglycemic clamps. Inclusion criterion was eGFR<60 ml/min per 1.73 m² (n=543). Exclusion criteria were incomplete data on euglycemic clamp and diabetes (n=97), leaving 446 men with CKD stages 3 and 4 (eGFR median=51.9 ml/min per 1.73 m²; range=20.2–59.5 ml/min per 1.73 m²).

Results

The mean of glucose disposal rate was 5.4±1.9 mg/kg per minute. In multivariable analysis, the independent clinical correlates of glucose disposal rate were eGFR (slope, 0.02; 95% confidence interval, 0.01 to 0.04), hypertension (−0.48; 95% confidence interval, −0.86 to −0.11), hyperlipidemia (−0.51; 95% confidence interval, −0.84 to −0.18), and body mass index (−0.32; 95% confidence interval, −0.37 to −0.27). During follow-up (median=10.0 years; interquartile range=8.7–11.0 years), 149 participants died. In Cox regression models, glucose disposal rate was not associated with all-cause or cardiovascular mortality. Multiplicative interactions (P<0.05) were observed between glucose disposal rate and physical activity or smoking in total mortality association. After subsequent stratification, glucose disposal rate was an independent correlate of all-cause mortality in smokers (adjusted hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.96 per 1 mg/kg per minute glucose disposal rate increase) and physically inactive individuals (hazard ratio, 0.77; 95% confidence interval, 0.61 to 0.97) but not their counterparts.

Conclusion

eGFR, together with various components of the metabolic syndrome, contributed to explain the variance of insulin sensitivity in men with CKD stages 3 and 4. Insulin sensitivity was associated with a lower mortality risk in individuals who smoked and individuals who were physically inactive.     

Effectiveness of phosphodiesterase-5 inhibitor therapy for portopulmonary hypertension

BACKGROUND:

Portopulmonary hypertension is associated with significant morbidity and mortality. Phosphodiesterase-5 inhibitor therapy is efficacious in other causes of WHO group I pulmonary arterial hypertension.

OBJECTIVE:

To evaluate the efficacy and safety of phosphodiesterase-5 inhibitor therapy in patients with portopulmonary hypertension.

METHODS:

A single-centre retrospective cohort study that included patients with a diagnosis of portopulmonary hypertension was performed. The primary outcome was change in pulmonary vascular resistance after six months of phosphodiesterase-5 inhibitor therapy. A secondary evaluation investigated the effect on other hemodynamic measurements, 6 min walk distance, functional class, safety outcomes and survival.

RESULTS:

Of 1385 patients screened, 25 patients with portopulmonary hypertension were identified, of whom 20 received a phosphodiesterase-5 inhibitor. After six months, there was a significant decrease in pulmonary vascular resistance (−236 dyn·s·cm⁻⁵ [95% CI −343 dyn·s·cm⁻⁵ to −130 dyn·s·cm⁻⁵]; P<0.001), mean pulmonary artery pressure (−8.9 mmHg [95% CI −13.7 mmHg to −4.2 mmHg]; P=0.001) and an increase in Fick cardiac output (0.9 L/min [95% CI 0.1 L/min to 1.6 L/min]; P=0.02). There was no change in 6 min walk distance. The proportion of subjects with a WHO functional class III or IV was significantly reduced at six months compared with baseline (18% versus 61%; P=0.002). Safety outcomes did not reveal any adverse events.

CONCLUSIONS:

Phosphodiesterase-5 inhibitor therapy improved hemodynamics and functional class at six months in a cohort of patients with portopulmonary hypertension.     

Effect of phosphorus supplementation on weight gain and waist circumference of overweight/obese adults: a randomized clinical trial

Background:

Phosphorus status is inversely correlated with body weight; however, the effect of phosphorus supplementation on body weight in a controlled design has not been studied.

Methods:

This is a double-blind, randomized, placebo-controlled trial of 63 adults aged 18–45 years with a body mass index (BMI) of ⩾25 kg m⁻² and normal kidney function at the American University of Beirut. Participants were randomly assigned to the placebo or phosphorus group where daily placebo or phosphorus supplements were ingested with three main meals (breakfast, lunch and dinner) for a period of 12 weeks. Primary outcomes were changes in anthropometric measures, blood metabolites (including lipid profile, glucose and insulin) and subjective appetite scores. The trial is registered with Clinical Trial.gov, {"type":"clinical-trial","attrs":{"text":"NCT02329990","term_id":"NCT02329990"}}NCT02329990.

Results:

Body weight was significantly lower in the phosphorus group when compared with the placebo group (−0.65 kg (95% confidence interval (CI) −1.69 to 0.40) vs 1.13 kg (95% CI 0.19 to 2.06), P=0.01). Similarly, BMI and waist circumference were significantly lower in the phosphorus group when compared with the placebo group (−0.24 kg m⁻² (95% CI −0.59 to 0.12) vs 0.42 kg m⁻² (95% CI 0.05 to 0.78), P=0.01; −3.62 cm (95% CI−4.90 to −2.33) vs 0.38 cm ( 95% CI−0.44 to 1.20), P<0.001; respectively). Several parameters of subjective appetite scores were decreased in the phosphorus-supplemented group.

Conclusions:

Phosphorus supplementation for 12 weeks significantly decreases body weight, BMI, waist circumference and subjective appetite scores. These findings support a promising role of the mineral phosphorus in the prevention and management of obesity, especially abdominal adiposity. The exact mechanisms of action and longer-term effects still need to be elucidated.     

The effect of bitter melon (Mormordica charantia) in patients with diabetes mellitus: a systematic review and meta-analysis

Background:

Mormordica charantia (bitter melon) has been investigated for lowering plasma glucose in patients with diabetes mellitus (DM). Previous data has offered inconclusive and inconsistent results about the benefits of bitter melon in patients with DM. Our current project aims to determine whether bitter melon has a favorable effect in lowering plasma glucose in patients with DM.

Methods:

We searched PubMed, EMBASE and the Cochrane Library from inception to July 2013 without any language restrictions for randomized controlled trials (RCTs) evaluating bitter melon to no treatment in patients with type 1 or type 2 diabetes. Study selection, data extraction and validity of each article were independently assessed by two investigators. Articles were appraised for proper random sequence generation, allocation concealment, blinding, selective reporting and completeness of outcomes reporting to assess the risk for biases. The glycemic results of each RCT were analyzed to yield weighted mean differences (WMDs) and 95% confidence intervals (CIs).

Results:

A total of four RCTs, each with 40–66 participants, followed between 4 and 12 weeks were identified in this meta-analysis. Overall risk of bias for each article included was determined to be unclear. In total, 208 participants with type 2 DM (mean age of 56.5 years) were evaluated. Compared with no treatment, bitter melon did not significantly lower A1C (WMD −0.13%, 95% CI −0.41 to 0.16) nor fasting plasma glucose (FPG) 47 (WMD 2.23 mg dl⁻¹, 95% CI −14.91 to 19.37).

Conclusions:

Bitter melon supplementation compared with no treatment did not show significant glycemic improvements on either A1c or FPG.     

A novel criterion for identifying metabolically obese but normal weight individuals using the product of triglycerides and glucose

Objectives:

Metabolically obese but normal weight (MONW) individuals constitute a subgroup of normal weight individuals that display impaired insulin sensitivity with a higher risk of developing diabetes, cardiovascular disease and mortality. We aimed to propose a novel criterion for defining MONW by examining the usefulness and the cutoff value of the TyG index, a product of the levels of triglycerides and glucose, in identifying MONW individuals. In addition, the performance of this criterion in predicting the future incidence of diabetes was assessed.

Subjects/methods:

A total of 7541 non-diabetic, normal weight (body mass index ⩾18.5 and <25 kg m⁻²) subjects were selected from the Korea National Health and Nutrition Examination Survey conducted in 2009–2010. Another 3185 participants with follow-up studies were selected from a prospective community-based cohort study. The TyG index was calculated as ln(fasting triglycerides (mg dl⁻¹) × fasting glucose (mg dl⁻¹)/2).

Results:

The levels of the TyG index paralleled the prevalence of metabolic syndrome and its components. The cutoff value of the TyG index that reflected MONW based on the receiver operating characteristics analysis was 8.82 for men and 8.73 for women, with the area under the curve values being 0.855 and 0.868, respectively. The sensitivity and the specificity were 84.2 and 77.6% in men and 69.1 and 89.4% in women, respectively. Individuals designated as MONW, who have a normal weight and TyG levels higher than cutoff, displayed a metabolically unhealthy phenotype and an approximately twofold higher risk of developing diabetes compared with metabolically healthy normal weight subjects.

Conclusions:

We propose a simple diagnostic criterion of MONW, which might be used to discriminate subjects with a higher risk of metabolic diseases.     

Yacon diet (Smallanthus sonchifolius,Asteraceae) improves hepatic insulin resistance via reducing Trb3 expression in Zucker fa/fa rats

Objective:

Yacon is a perennial plant forming a clump of >20 big, edible underground tubers. Yacon, which originates from South America, has become increasingly popular in the Japanese diet for tubers have a lower caloric value and a high fiber content. Recent studies have suggested that yacon feeding ameliorates diabetes as indicated by reduced blood glucose.

Methods:

We fed male Zucker fa/fa rats for 5 weeks with isocaloric normal chow diet containing from 6.5% control aroid or 6.5% yacon. Insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp study.

Results:

Body weight was comparable between yacon- and aroid-fed rats. In the basal state, yacon feeding had an effect to lower fasting glucose levels from 184.1±4.1 to 167.8±2.7 mg dl⁻¹ (P<0.01), as well as basal hepatic glucose output (HGO) from 9.9±0.4 to 7.4 ± 0.2 mg kg⁻¹ per min (P<0.01). During the clamp studies, the glucose infusion rate required to maintain euglycemia was increased by 12.3% in yacon-fed rat. The insulin suppression of HGO was also increased in yacon-fed rats compared with control rats (85.3±2.4% vs 77.0±3.0% P<0.05), whereas the glucose disposal rate was not different between the two groups. Consistent with the clamp data, the insulin-stimulated phosphorylation of Akt was significantly enhanced in liver but not in skeletal muscle. Furthermore, tribbles 3 (Trb3) expression, which is a negative regulator of Akt activity, was markedly reduced in the liver of yacon-fed rats compared with control rats.

Conclusion:

These results indicate that the effect of yacon feeding to reduce blood glucose is likely due to its beneficial effects on hepatic insulin sensitivity in the insulin resistant state.     

Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice

Background:

Obesity is associated with reduced levels of circulating high-density lipoproteins (HDLs) and its major protein, apolipoprotein (apo) A-I. As a result of the role of HDL and apoA-I in cellular lipid transport, low HDL and apoA-I may contribute directly to establishing or maintaining the obese condition.

Methods:

To test this, male C57BL/6 wild-type (WT), apoA-I deficient (apoA-I^−/−) and apoA-I transgenic (apoA-I^tg/tg) mice were fed obesogenic diets (ODs) and monitored for several clinical parameters. We also performed cell culture studies.

Results:

ApoA-I^−/− mice gained significantly more body weight and body fat than WT mice over 20 weeks despite their reduced food intake. During a caloric restriction regime imposed on OD-fed mice, apoA-I deficiency significantly inhibited the loss of body fat as compared with WT mice. Reduced body fat loss with caloric restriction in apoA-I^−/− mice was associated with blunted stimulated adipose tissue lipolysis as verified by decreased levels of phosphorylated hormone-sensitive lipase (p-HSL) and lipolytic enzyme mRNA. In contrast to apoA-I^−/− mice, apoA-I^tg/tg mice gained relatively less weight than WT mice, consistent with other reports. ApoA-I^tg/tg mice showed increased adipose tissue lipolysis, verified by increased levels of p-HSL and lipolytic enzyme mRNA. In cell culture studies, HDL and apoA-I specifically increased catecholamine-induced lipolysis possibly through modulating the adipocyte plasma membrane cholesterol content.

Conclusions:

Thus, apoA-I and HDL contribute to modulating body fat content by controlling the extent of lipolysis. ApoA-I and HDL are key components of lipid metabolism in adipose tissue and constitute new therapeutic targets in obesity.     

Casual Blood Pressure and Neurocognitive Function in Children with Chronic Kidney Disease: A Report of the Children with Chronic Kidney Disease Cohort Study

Summary

Background and objectives

Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP.

Design, setting, participants, & measurements

This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project.

Results

Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90^th percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject''s BP/95^th percentile BP) correlated inversely with Performance IQ score (systolic, r = −0.13, P = 0.01; diastolic, r = −0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = −3.7, 95% confidence interval [CI]: −7.3 to −0.06; systolic BP index, β = −1.16 to 95% CI: −2.1, −0.21; diastolic BP index, β = −1.17, 95% CI: −1.8 to −0.55).

Conclusions

Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.     

Inferior Vena Cava Diameter and Left Atrial Diameter Measure Volume but Not Dry Weight

Summary

Background and objectives

Hypervolemia is an important and modifiable cause of hypertension. Hypertension improves with probing dry weight, but its effect on echocardiographic measures of volume is unknown.

Design, setting, participants, & measurements

Shortly after dialysis, echocardiograms were obtained at baseline and longitudinally every 4 weeks on two occasions. Among 100 patients in the additional ultrafiltration group, 198 echocardiograms were performed; among 50 patients in the control group, 104 echocardiograms were performed.

Results

Baseline inferior vena cava (IVC)_insp diameter was approximately 5.1 mm/m²; with ultrafiltration, change in IVC_insp diameter was −0.95 mm/m² more compared with the control group at 4 weeks and −1.18 mm/m² more compared with the control group at 8 weeks. From baseline IVC_exp diameter of approximately 8.2 mm/m², ultrafiltration-induced change at 4 weeks was −1.06 mm/m² more and at 8 weeks was −1.07 mm/m² more (P = 0.044). From a baseline left atrial diameter of 2.1 cm/m², ultrafiltration-induced change at 4 weeks was −0.14 cm/m² more and at 8 weeks was −0.15 cm/m² more. At baseline, there was no relationship between interdialytic ambulatory BP and echocardiographic parameters of volume. The reduction in interdialytic ambulatory BP was also independent of change in the echocardiographic volume parameters.

Conclusions

The inferior vena cava and left atrial diameters are echocardiographic parameters that are responsive to probing dry weight; thus, they reflect excess volume. However, echocardiographic volume parameters are poor determinants of interdialytic BP, and their change does not predict the BP response to probing dry weight.     

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.     

Comparison of the effects of 52 weeks weight loss with either a high-protein or high-carbohydrate diet on body composition and cardiometabolic risk factors in overweight and obese males

Background:

A high-protein (HP), low-fat weight-loss diet may be advantageous for improving cardiometabolic health outcomes and body composition. To date, only limited research has been conducted in male participants.

Objective:

To evaluate the medium to long-term effects of two, low-fat, hypocaloric diets differing in carbohydrate:protein ratio on body composition and cardiometabolic health outcomes in overweight and obese males.

Design:

One hundred and twenty males (age 50.8±9.3 (s.d.) years, body mass index 33.0±3.9 kg m⁻²) were randomly assigned and consumed a low-fat, isocaloric, energy-restricted diet (7 MJ per day) with either HP (protein:carbohydrate:fat %energy, 35:40:25) or high carbohydrate (HC; 17:58:25). Body weight, body composition and cardiometabolic risk factors were assessed at baseline and after 12 and 52 weeks.

Results:

Sixty-eight participants completed the study (HP, n=33; HC, n=35). At 1 year both the groups experienced similar reductions in body weight (HP, −12.3±8.0 kg (−12%); HC, −10.9±8.6 kg (−11%); P=0.83 time × group interaction) and fat mass (−9.9±6.0 kg (−27%) vs −7.3±5.8 kg (−22%); P=0.11). Participants who consumed the HP diet lost less fat-free mass (−2.6±3.7 kg (−4%) vs −3.8±4.7 kg (−6%); P<0.01). Both groups experienced similar increases in high-density lipoprotein cholesterol (8%) and reductions in total cholesterol (−7%), low-density lipoprotein cholesterol (−9%), triglycerides (−24%), glucose (−3%), insulin (−38%), blood pressure (−7/−12%) and C-reactive protein (−29%), (P⩾0.14).

Conclusion:

In overweight and obese men, both a HP and HC diet reduced body weight and improved cardiometabolic risk factors. Consumption of a HP diet was more effective for improving body composition compared with an HC diet.     

Hypertrophy of the non-embolized liver after chemotherapy

Background:

Neoadjuvant chemotherapy (NC⁺) and portal vein embolization (PVE) enables curative resection in more patients with colorectal-liver metastases (CRLM). However, after NC⁺, structural alterations have been reported with the risk of post-operative hepatic failure. We undertook to determine if NC⁺ toxicity limits future remnant liver (FRL) hypertrophy after PVE.

Methods:

PVE was performed in 20 patients, 13 (65%) of whom previously received a mean FOLFIRI (5-fluorouracil + leucovorin + irinotecan) regimen (NC⁺) of 6.6 cycles. The seven remaining patients served as the control group without NC (NC⁻).

Results:

CRLM were bilateral in 69% (NC⁺) and 57% (NC⁻), and synchronous in 84% (NC⁺) and 14% (NC⁻). The FRL hypertrophy rate was 54.1% (NC⁺) and 43.7% (NC⁻) (P= 0.3). CRLM were unresectable in four of our 20 patients, i.e. group NC⁺: one insufficient FRL hypertrophy and one severe steatosis; and group NC⁻: two tumoral progressions. In both groups, the operative parameters were comparable except for pedicular clamping: 8 (NC⁺) and 36 min (NC⁻), respectively (P < 0.05). Also, the surgical outcome rate and hospital stay were comparable. No significant pathological difference was observed between the two groups. No mortality occurred in either group.

Conclusion:

In view of our limited experience, we conclude that hypertrophy of the non-embolized liver (FRL) is not altered after FOLFIRI-based NC.     

Adipocyte fatty acid-binding protein levels are associated with left ventricular diastolic dysfunction in morbidly obese subjects

Objectives:

This study aimed to examine the association of adipocyte fatty acid-binding protein (FABP4) levels with left ventricular diastolic dysfunction (LVDD) in obese subjects with varying degrees of the metabolic syndrome (MetS).

Methods:

Fifty morbidly obese subjects with LVDD were selected at random and matched by age (±5 years) and sex with 50 morbidly obese with normal left ventricular (LV) function. In addition, 24 healthy lean subjects were included as controls.

Results:

Median FABP4 levels (interquartile range) in obese subjects with LVDD were significantly higher (42 ng ml⁻¹ (32–53)) than in obese with normal LV function (24 ng ml⁻¹ (36–43), P=0.036), and in normal weight controls (13 ng ml⁻¹ (10–20), P<0.0001). Increasing FABP4 tertiles were significantly associated with parameters of LVDD, the number of LVDD components, physical performance and epicardial fat thickness. In multivariate regression analysis adjusting for age, sex and adiposity, FABP4 levels remained significantly associated with parameters of diastolic function. The association of FABP4 levels with LVDD was mainly observed in subjects with metabolic complications, but not in metabolically healthy obese.

Conclusions:

FABP4 levels are significantly associated with LVDD in obese subjects, when the MetS is present. Thus, FABP4 may be a link between obesity and cardiometabolic disorders.     

Acylation stimulating protein reduction precedes insulin sensitization after BPD-DS bariatric surgery in severely obese women

Objective:

The mechanisms involved in early resolution of insulin resistance and type 2 diabetes mellitus after biliopancreatic diversion with duodenal switch (BPD-DS) surgery are still unknown. We evaluated early effects of BPD-DS on plasma acylation stimulating protein (ASP), an adipokine involved in lipid and glucose metabolism.

Subjects:

32 non-diabetic and 22 diabetic severely obese women (BMI⩾40 kg m⁻²) were evaluated for body composition and plasma parameters before, 24 h, 5 days, 6 and 12 months after surgery.

Results:

Within the early postoperative period (24 h), ASP decreased 25 and 30% in non-diabetic and diabetic women, respectively (P<0.001). Twenty-four hours after surgery, triglyceride, cholesterol, HDL-Chol, LDL-Chol and C3 also decreased, while glucose, insulin and high-sensitivity C-reactive protein (hsCRP) increased (all P<0.001). By 5 days, without significant weight loss, the decreases in ASP, cholesterol, HDL-Chol and LDL-Chol levels were all maintained. At this time, glucose, insulin and HOMA-IR also decreased 11 to 52% (all P<0.001). At 6 and 12 months, with pronounced weight loss and decreased per cent fat mass, there were further decreases in ASP (maximal −56% non-diabetic, −61% diabetic, P<0.001), as well as in glucose, insulin, HOMA-IR, triglyceride, cholesterol, LDL-Chol, HDL-Chol and hsCRP levels. Improved insulin resistance/diabetes at 5 days was predicted by 24 h changes as follows: per cent change ASP, HDL-Chol, hsCRP and total cholesterol predicted HOMA-IR (5 days) (r²=0.454, P<0.001), and per cent change ASP, HDL-Chol and hsCRP predicted change (5 days vs baseline) in HOMA-IR (r²=0.351, P<0.001).

Conclusion:

Acute postoperative decreases in ASP are associated with early improvement of insulin resistance/diabetes after BPD-DS surgery.