Plasminogen activator inhibitor 1 and visceral obesity during pronounced weight loss after bariatric surgery

Background and aimsElevated plasminogen activator inhibitor 1 (PAI-1) concentrations are a hallmark of obesity and are considered to contribute to the development of cardiovascular disease. As adipose tissue constitutes a major source for PAI-1 in obesity, we investigated the individual contribution of subcutaneous and intra-abdominal fat on PAI-1 concentrations during pronounced weight loss after bariatric surgery.Methods and resultsThirty-seven obese adults were examined before and 18 months after surgery. Abdominal fat distribution was determined by ultrasound, metabolic parameters and plasma PAI-1 levels by standard methods. BMI was reduced by 9.2 ± 4.9 kg/m², while total fat mass and visceral fat diameter (VFD) decreased by 20.7 ± 11.9 kg and 4.2 ± 2.3 cm, respectively. Concomitantly, PAI-1 levels diminished by 3.2 ± 5.6 ng/ml (all p ≤ 0.015). Change in PAI-1 levels was correlated with change in VFD (r = 0.441, p = 0.008), but not with subcutaneous fat diameter. In stepwise multiple regression analysis change in VFD was an independent predictor of change in PAI-1 concentrations. When adjusted for age and sex or total fat mass associations between PAI-1 and VFD remained significant.ConclusionWe demonstrate that VFD is a major determinant for PAI-1 concentrations during pronounced weight loss after bariatric surgery. Thus, significant reduction of visceral fat mass may contribute to the reduced cardiovascular morbidity and mortality after bariatric surgery by a concomitant decrease in PAI-1 concentrations.     

Evolution of subcutaneous adipose tissue fibrosis after bariatric surgery

AimObesity is associated with the development of metabolic complications such as insulin resistance (IR). The mechanisms leading to IR remain unclear. This study aimed to investigate the relationship between adipose tissue fibrosis and IR in obese patients before and after bariatric surgery.MethodsThirty-five obese patients awaiting bariatric surgery (12 with type 2 diabetes) were included in the study. Non-diabetic patients were classified as either insulin-sensitive (n = 11) or insulin-resistant (n = 12), based on the Matsuda insulin sensitivity index (ISI_Matsuda). Homoeostasis model assessment (HOMA-IR) was used for longitudinal evaluation of insulin resistance. Fibrosis was quantified by Masson's trichrome staining on microscopy, and mRNA levels of fibrosis-related genes were examined in subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies collected during and 6 months after bariatric surgery (SAT only).ResultsDespite their similar age, body mass index and fat mass, SAT fibrosis was significantly higher in diabetic vs insulin-sensitive patients (P < 0.05), and associated with IR as assessed by both ISI_Matsuda (r = −0.417, P = 0.038) and HOMA-IR (r = 0.464, P = 0.007) at baseline, whereas VAT fibrosis was not. Six months after surgery and significant weight loss, fibrosis levels remained unchanged in SAT, although IR was significantly reduced in all groups (P < 0.0001). No correlation was found between SAT fibrosis and IR after surgery.ConclusionOverall, these results show a significant but, most likely, transient association between SAT fibrosis and IR in obese humans.     

Intra-thoracic fat, cardiometabolic risk factors, and subclinical cardiovascular disease in healthy, recently menopausal women screened for the Kronos Early Estrogen Prevention Study (KEEPS)

ObjectiveTo examine the correlations between intra-hepatic and intra-thoracic (total, epicardial, and pericardial) fat deposition with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis burden in healthy, recently postmenopausal women.MethodsWomen screened for the Kronos Early Estrogen Prevention Study (mean age 52.9 years) who underwent electron beam or multidetector computed tomography (CT) imaging for the quantification of intra-hepatic fat and thoracic adipose tissue, and coronary artery calcification (CAC) were included (n = 650).ResultsHigher levels of intra-hepatic and thoracic fat were each associated with CVD risk markers. After adjustment for BMI, the associations for intra-hepatic fat with hs-CRP and insulin persisted (r = 0.21 and 0.19, respectively; P < 0.001), while those between thoracic fat indices and lipids persisted (r for total thoracic fat with HDL, LDL, and triglycerides = ?0.16, 0.11, and 0.11, respectively, P < 0.05). Total thoracic fat was associated with CAC after initial multivariable adjustment (odds ratio [OR] of 2nd, 3rd, and 4th vs. 1st quartile and [95% confidence intervals]: 0.8 [0.4–1.6], 1.5 [0.8–2.9], and 1.8 [1.0–3.4]; p for linear trend = 0.017) and was only slightly attenuated after additional adjustment for BMI. Associations between total thoracic fat and CVD risk markers and CAC appeared due slightly more to associations with epicardial than pericardial fat.ConclusionWhile hepatic fat is related to hs-CRP and insulin, cardiac fat is associated with subclinical atherosclerosis as demonstrated by CAC. Cardiac fat may represent a useful marker for increased CVD risk beyond the standard adiposity measures of BMI and WC.     

Sarcopenic obesity is associated with adverse clinical outcome after cardiac surgery

Background &; aimsBoth undernutrition – low fat free mass (FFM) – and obesity – high fat mass (FM) – have been associated with adverse outcome in cardiac surgical patients. However, whether there is an additional effect on outcome of these risk factors present at the same time, that is sarcopenic obesity (SO), is unknown. Furthermore, the association between SO and muscle function is unidentified.Methods and resultsIn 325 cardiac surgical patients, we prospectively analysed the association between preoperative FFM and FM, measured by bioelectrical impedance spectroscopy, and postoperative adverse outcomes, and their correlation with muscle function – handgrip strength (HGS). SO was associated with postoperative infections (28.2% vs. 5.3%, adj. odds ratio (OR): 7.9; 95% confidence interval (CI): 1.2–54.1; p = 0.04). Further, a low FFM index (FFMI; kg m^?2) was associated with postoperative infections (18.5% vs. 4.7%, adj. OR: 6.6; 95% CI: 1.7–25.2; p = 0.01) while a high FM index (FMI; kg m^?2) was not. Both components of SO, FFMI and FMI, correlated with HGS (FFMI: r = 0.570; p < 0.001, FMI: r = ?0.263; p < 0.001).ConclusionSO is associated with an increased occurrence of adverse outcome after cardiac surgery. Our results suggest an additional risk of a low FFMI and high FMI present at the same time. Furthermore, SO is characterised by less muscle function. We advocate determining body composition in cardiac surgical patients to classify and treat undernourished patients, in particular those who are also obese.     

Differences in the GH-IGF-I axis in children of different weight and fitness status

ObjectiveTo determine if differences in the GH-IGF-I axis exist between children of high and low aerobic fitness who are obese or of normal weight.Design124 children (ages 8–11) divided into four groups based on BMI and VO₂max (mL O₂/kg fat free mass(FFM)/min): normal weight — high-fit (NH), normal weight — low-fit (NL), obese — high-fit (OH), and obese — low-fit (OL). Height, weight, skinfolds, body mass index (BMI), body fat percentage and predicted VO₂max (both ml/kg/min and ml/kg_FFM/min) were assessed. Resting growth hormone (GH), total insulin-like growth factor 1 (total IGF-I), free insulin-like growth factor 1(free IGF-I), and insulin were measured using morning fasting blood samples.ResultsGH was greater in the NH group compared to the OL group only (p < 0.01). No group differences existed for either total IGF-I (p = 0.53) or free IGF-I (p = 0.189). Insulin was greater in the OH and OL groups than the NH and NL groups (p < 0.01). With groups combined (or overall), insulin and free IGF-I were related to fitness (insulin — ml/kg/min: r = ? 0.226, p < 0.05 and ml/kg_FFM/min: r = ? 0.212, p < 0.05; free IGF-I — ml/kg/min: r = ? 0.219, p < 0.01 and ml/kg_FFM/min: r = ? 0.272, p < 0.05).ConclusionsFitness may contribute to the obesity related reduction of GH that may be involved with weight gain.     

Serum IGF-I and C-reactive protein in healthy black and white young men: The CARDIA male hormone study

ObjectiveAnimal and human studies suggest that C-reactive protein (CRP) may be inversely associated with serum insulin-like growth factor-I (IGF-I) concentrations. However, most human studies have not controlled adequately for confounding factors, particularly nutritional intake. This population-based study examined whether CRP is inversely associated with IGF-I and IGFBP-3 concentrations.MethodsIn cross-sectional analysis, multivariable linear regression with adjustment for age, BMI, smoking status, alcohol intake, and nutritional factors was used to relate log CRP, the independent variable, to IGF-I and IGFBP-3 in a sample of black (n = 364) and white men (n = 486) separately by race.ResultsOnly black men had positive findings: log CRP was significantly associated with IGF-I (β = ?13.1 ng/ml, p = 0.02) and the difference in mean IGF-I concentrations between the highest and lowest quartiles of CRP was 26 ng/ml. There was a statistically significant interaction between log CRP and smoking status (p = 0.02); the regression coefficient for IGF-I predicted from log CRP was significant in smokers (β = ?39.8 ng/ml, p = 0.0001), but not in non-smokers. The difference in mean IGF-I concentrations between highest and lowest quartiles of CRP was 100 ng/ml for black smokers. There were no associations for IGFBP-3.ConclusionsIn our study, CRP levels are inversely associated with IGF-I concentrations in black male smokers; however, the causal nature of the association is unclear and should be studied further.     

Ischemia-modified albumin in patients with hyperthyroidism and hypothyroidism

BackgroundThe relationship between ischemia-modified albumin (IMA) and thyroid dysfunction remains uncertain. This study aimed to investigate the influence of overt hypothyroidism (Oho), overt hyperthyroidism (Ohe), and their treatments on serum IMA levels.MethodsA total of 35 untreated patients with Ohe, 35 untreated patients with Oho, and 35 control subjects were enrolled in the study. C-reactive protein (CRP), homocysteine (Hcy), IMA, and lipid profiles were measured and evaluated before and after treatment.ResultsCRP, Hcy, and IMA levels and lipid profiles were higher in patients with Oho than in euthyroid or Ohe subjects (p < 0.05). Basal IMA levels were reduced after treatments in all patients (p < 0.05). In Ohe patients, serum IMA levels were positively correlated with free triiodothyronine (r = 0.424, p = 0.011) and free thyroxine (r = 0.567, p < 0.001) levels. In Oho patients, serum IMA levels were inversely correlated with free triiodothyronine (r = ? 0.555, p = 0.001) and free thyroxine (r = ? 0.457, p = 0.006) but positively correlated with anti-thyroid peroxidase antibody, C-reactive protein, and homocysteine levels (p < 0.05). Linear regression analyses showed that free triiodothyronine was the most important factor affecting serum IMA levels in Ohe (β = 0.694, p = 0.019) and in Oho (β = ? 0.512, p = 0.025).ConclusionsIMA levels are increased in patients with thyroid dysfunction, particularly in overt hypothyroidism. Thyroid dysfunction has a significant impact on the oxidative stress status.     

Reproducibility and validity of ultrasound for the measurement of visceral and subcutaneous adipose tissues

BackgroundUltrasound represents a low-cost and widely available field method for assessing visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) but its measurement properties are uncertain. The aim of the current study was to examine the reproducibility and validity of ultrasound to quantify abdominal fat compartments.MethodsIn two study centers, VAT and SAT thicknesses were quantified by ultrasound two times by two observers each among 127 adults aged 20–70 years. In a separate sample of 30 adults, the ultrasound method was validated by comparing VAT and SAT thicknesses with VAT and SAT areas at vertebrae L2/L3 as obtained by a single magnetic resonance imaging (MRI) slice.ResultsFor VAT, the intra-rater reproducibility values for observers 1 and 2 were r = 0.996 (95% CI = 0.994–0.997) and r = 0.999 (95% CI = 0.999–0.999), respectively. For SAT, the intra-rater reproducibility values were r = 0.992 (95% CI = 0.989–0.994) and r = 0.993 (95% CI = 0.990–0.995), respectively. The inter-rater reproducibility values for VAT and SAT were r = 0.998 (95% CI = 0.997–0.999) and r = 0.990 (95% CI = 0.986–0.993), respectively. For VAT and SAT, the correlation coefficients between ultrasound and MRI measurements were r = 0.898 (P < 0.001) and r = 0.705 (P < 0.001), respectively.ConclusionUltrasound provides reproducible and valid estimates of VAT and SAT and represents a useful method to assess abdominal fat in large scale epidemiologic studies.     

Plasma soluble triggering receptor expressed on myeloid cells-1 in Crohn's disease

BackgroundNo definite conclusions can be drawn from available data on the accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to assess disease activity in Crohn's disease.AimsPlasma sTREM-1 levels were correlated with disease activity markers in Crohn's disease.Methods191 consecutive patients from a single referral centre (Nancy IBD cohort) were prospectively enrolled between June 1, 2005 and December 12, 2008. Plasma sTREM-1 levels were also assessed amongst 20 healthy controls.ResultsThe sTREM-1 was detectable in 87 Crohn's disease patients (46%). Plasma sTREM-1 level was higher in Crohn's disease patients (interquartile range, 0–356) than in healthy controls (interquartile range, 0–15.1; P = 0.01). It was neither correlated with Crohn's disease activity index (r = 0.05, P = 0.56), C-reactive protein (r = 0.06, P = 0.53), nor with albumin (r = −0.041, P = 0.66). Crohn's disease activity index, C-reactive protein and albumin median levels were similar between patients with positive sTREM-1 levels and those with undetectable sTREM-1 levels. Azathioprine (P = 0.06), infliximab (P = 0.68) and methotrexate (P = 0.56) did not influence sTREM-1 levels.ConclusionPlasma sTREM-1 does not appear to be an accurate marker of disease activity in Crohn's disease and cannot be recommended for assessing disease activity in these patients.     

A new device for measuring resting energy expenditure (REE) in healthy subjects

Background and aimLifestyle change targeted towards increasing daily resting energy expenditure (REE) is one of the cornerstones of obesity treatment. Measurements of energy expenditure and substrate utilization are essential to understanding the metabolic basis of obesity, and the physiological responses to perturbations in habitual food intake. REE is the largest part of human energy expenditure (60-70%) and an increase or decrease in REE would have a large impact on total energy. Accurate and easy-to-use methods for measuring REE are needed, to be applied by clinicians in daily clinical settings to assess the validity of a new instrument to estimate REE in normal weight, healthy adults.MethodsNinety-nine subjects (52 females and 47 males) (mean ± SD, age 38 ± 14 years; body mass index (BMI) 23 ± 3 kg/m²) were tested. REE was assessed using a Sensor Medics Vmax metabolic cart with a ventilated canopy and with the SenseWear armband. Body composition, percentage fat mass (%FM) and percentage fat free mass (%FFM) were assessed by skinfold thickness measurements (SF), bio-electrical impedance analysis (BIA) and air displacement plethysmography (BOD-POD).ResultsNo significant difference was found among measurements of FFM using the three different techniques. Both SenseWear and Sensor Medics Vmax showed a high correlation, r = 0.42 and r = 0.40 (p < 0.0001) respectively, with BMI. No significant difference was found in mean REE between SenseWear (1540 ± 280 kcal/day) and Sensor Medics Vmax (1700 ± 330 kcal/day) (p = ns) and the correlation between REE measured by SenseWear and Sensor Medics Vmax was high (r = 0.86, p < 0.0001). Bland–Altman plot showed no difference in REE determination between SenseWear and Sensor Medics Vmax. %FFM determined by BOD-POD correlated with SenseWear (r = 0.42, p < 0.0001) as well as Sensor Medics Vmax (r = 0.38, p < 0.001).ConclusionSF, BIA and BOD-POD provide valid and reliable measurements of FFM. Our results suggest that the SenseWear armband is an acceptable device to accurately measure REE in healthy subjects. Its characteristics have the potential to reduce measurement times and make the SenseWear armband useful for epidemiological studies.     

Short-term growth hormone or IGF-I administration improves the IGF-IGFBP system in arthritic rats

ObjectiveAdjuvant-induced arthritis is an experimental model of rheumatoid arthritis that inhibits the GH-IGF-I axis and decreases body weight gain and muscle mass. Although chronic GH or IGF-I treatment increases body weight gain in arthritic rats, muscle resistance to GH and IGF-I is a very common complication in inflammatory diseases. In this study we examine the effect of short-term administration of rhGH and rhIGF-I on liver and muscle IGF-I, IGFBP-3 and ? 5 as well as on the ubiquitin-ligases MuRF1 and atrogin-1 in the muscle of arthritic rats.DesignArthritis was induced in adult male Wistar rats by an intradermal injection of 4 mg of Freund's adjuvant. Fifteen days after adjuvant injection, 300 μg/kg of rhGH or 200 μg/kg of rhIGF or saline was administrated 18 and 3 h before decapitation. A pair-fed group injected with saline was included in order to discard a possible effect of decreased food intake. Gene expression of IGF-I, GHR, IGFBP-3, IGFBP-5, atrogin-1 and MuRF1 were quantified using RT-PCR. In serum, IGF-I was measured by radioimmunoassay (RIA) and IGFBP-3 by ligand blot.ResultsArthritis decreased serum IGF-I and IGF mRNA in liver (P < 0.05), but not in skeletal muscle. In arthritic rats, rhGH increased serum IGF-I and liver IGF-I mRNA similar to the levels of pair-fed rats. Arthritis increased atrogin-1, MuRF1, IGFBP-3 and IGFBP-5 mRNA in muscle (P < 0.01). IGFBP-3 mRNA was downregulated by rhIGF-I, but not by rhGH, administration in control and arthritic rats (P < 0.05). Administration of rhGH and rhIGF-I increased IGFBP-5 in the gastrocnemius of arthritic rats.ConclusionsShort-term rhGH and rhIGF-I administration was found to increase muscle IGFBP-5 mRNA, whereas only rhIGF-I administration decreased muscle IGFBP-3 mRNA in control and arthritic rats. These data suggest that arthritis does not induce GH or IGF-I resistance in skeletal muscle.     

IGF-I at 9 and 36 months of age — relations with body composition and diet at 3 years — the SKOT cohort

ObjectiveHigh infancy levels of insulin-like growth factor-I (IGF-I) have been associated with increased linear growth and fat-free mass (FFM) but also with risk of obesity. This paper examines how IGF-I at 9 and 36 months relates to diet and body composition.DesignHealthy term infants from the prospective cohort study, SKOT, were examined at 9 and 36 months with anthropometry, bioelectrical impedance (36 months), 7-day food records and blood analysis of IGF-I and IGFBP-3 by chemiluminescent immunometric assay.ResultsIGF-I at 36 months (n = 229) was positively correlated with 9 months values and values were considerably higher in girls (43%). Children breastfed at 9 months had lower IGF-I concentrations at 9 months but reached the same IGF-I concentrations at 36 months as infants not breastfed at 9 months. IGF-I at 36 months was positively associated with height, weight, BMI, predicted FFM and FFM index (FFM/height (kg/m²)). Although there also was a positive association with predicted fat mass (FM) there was no association with FM index (FM/height (kg/m²)). Further, a negative association with skin fold thickness was observed. A change in IGF-I from 9–36 months was positively related to FFM and FFM index but not BMI, FM and FM index. No associations were seen between IGF-I and current intake of milk, meat or protein energy percentage, but both fat and saturated fat energy percentage were negatively associated with IGF-I.ConclusionIGF-I concentrations were positively associated with growth but not with adiposity at this age. However, the higher tempo of growth may influence age at adiposity rebound and thereby later risk of obesity. Milk and protein intake at 36 months did not influence IGF-I but there was a negative association with intake of fat and saturated fat. The implications of this finding for development of obesity need further exploration.     

Relationship between total oxidant status and severity of diabetic nephropathy in type 2 diabetic patients

Background and aimData on oxidative stress in type 2 diabetic patients with diabetic nephropathy is scant. The objective of this study was to investigate possible associations between total oxidant status (TOS) and the severity of diabetic nephropathy in type 2 diabetic patients by using a novel automated measurement method.Methods and resultsThirty-six patients with diabetic nephropathy (group 1), 25 diabetic patients without nephropathy (group 2) and 30 controls (group 3) were enrolled. Serum total antioxidant capacity (TAC), TOS levels and oxidative stress index (OSI) were determined. The severity of the disease was determined with microalbuminuria levels. TAC was lower, while TOS and OSI were higher in group 1 than in group 3 (P < 0.01, P < 0.001, P < 0.001; respectively). There were no statistically significant differences between group 2 and group 3 with respect to TAC, TOS and OSI (all P > 0.05). Group 1 had higher TOS and OSI than group 2 (both P < 0.05), but there was no statistically significant difference with respect to TAC. Significant correlations were observed between microalbuminuria levels, and TAC, TOS and OSI levels (r = −0.616, P < 0.001; r = 0.488, P < 0.01; r = 0.567, P < 0.001; respectively).ConclusionOur results suggest that oxidative stress is increased in patients with diabetic nephropathy compared to diabetic patients without nephropathy and this increase seems to be related to the severity of microalbuminuria levels.     

Diet,body composition,and physical fitness influences on IGF-I bioactivity in women

ObjectiveInsulin-like growth factor I (IGF-I) is a metabolic-regulatory hormone that mediates a variety of physiologic functions. Body composition, fitness status and intake of certain micro- and macronutrients are associated with circulating concentrations of immunoreactive IGF-I. The influence of these factors on IGF-I bioactivity; however, is undetermined. We assessed the relationships between IGF-I bioactivity and lifestyle factors purportedly associated with IGF-I immunoreactivity.DesignIn a cross sectional study, fasted blood samples were obtained from 44 lightly active, college-age (20 ± 2 yrs) women. IGF-I bioactivity was estimated by an assay which determines the ability of serum IGFs to phosphorylate IGF-I receptors in cultured cells; free and total IGF-I were measured by immunoassay. Estradiol and progesterone were measured by immunoassay. Body mass index was calculated from measured height and weight, bone mineral density and body fat percentage measured by dual energy X-ray absorptiometry, and peak oxygen consumption (VO_2peak) determined during a graded treadmill protocol. A food frequency questionnaire measured habitual and a 5-day food record assessed short-term micro- and macronutrient intakes. Associations between bioactive, free and total IGF-I with body composition, sex hormones, VO_2peak, and dietary intake were assessed using univariate and multiple linear regression analyses.ResultsAssociations between bioactive IGF-I with age (r = ?0.36, P < 0.05), body fat percentage (r = ?0.32, P < 0.05), estradiol (r = 0.31, P < 0.05) and progesterone (r = 0.33, P < 0.05) concentrations, habitual alcohol (r = ?0.38, P < 0.05) and selenium intakes (r = 0.41, P < 0.01), free IGF-I with age (r = ?0.34, P < 0.05), estradiol (r = 0.48, P < 0.01) and progesterone (r = 0.52, P < 0.001) concentrations, habitual alcohol (r = ?0.33, P < 0.05) and isoflavone intakes (r = 0.30, P < 0.05) and total IGF-I with age (r = ?0.27, P < 0.05) and habitual alcohol intake (r = ?0.33, P < 0.05) were observed. Habitual alcohol intake was a negative predictor of bioactive, free and total IGF-I in multivariate models.ConclusionOf the lifestyle factors measured, the most robust relationship observed was a negative association between habitual alcohol intake and all measures of IGF-I. This finding suggests that alcohol intake may blunt the physiologic actions of the IGF-I axis.     

Relationship of plasma apolipoprotein M with proprotein convertase subtilisin-kexin type 9 levels in non-diabetic subjects

PurposeApolipoprotein M (apoM) retards atherosclerosis development in murine models, and may be regulated by pathways involved in LDL metabolism. Proprotein convertase subtilisin–kexin type 9 (PCSK9) plays a key role in LDL receptor processing. We determined the extent to which plasma apoM is related to PCSK9 levels in subjects with varying degrees of obesity.MethodsWe sought correlations between plasma apoM and PCSK9, measured using recently developed ELISAs, in 79 non-diabetic subjects.ResultsApoM and PCSK9 levels were both correlated positively with total cholesterol, non-HDL cholesterol, LDL cholesterol and apoB (P < 0.05 to P < 0.001). ApoM correlated positively with PCSK9 in lean individuals (n = 37, r = 0.337, P = 0.041), but not in overweight subjects (n = 32, r = 0.125, P = 0.50) and in obese subjects (n = 10, r = ?0.055, P = 0.88).ConclusionsThe PCSK9 pathway may contribute to plasma apoM regulation in humans. The influence of PCSK9 on circulating apoM appears to be modified by adiposity.     

Racial differences in the association between body fat distribution and lipid profiles among reproductive-age women

AimThe aim of this study was to examine the racial and ethnic differences in the relationship between body fat distribution variables and serum lipid profiles.MethodsSecondary data analyses were conducted on 708 healthy women (204 blacks, 247 whites and 257 Hispanics), aged 16–33 years, seen in an outpatients clinic for contraception. Pearson correlation and multivariable linear regression techniques were used to identify racial/ethnic differences in the relationship between lipid profiles and body fat after adjusting for lean mass as well as demographic and lifestyle variables.ResultsAll body fat distribution variables were significantly associated with total cholesterol (TC) (r = 0.14 to 0.26), triglycerides (TG) (r = 0.13 to 0.46), HDL cholesterol (r = −0.13 to −0.34), cholesterol-to-HDL ratio (r = 0.20 to 0.50) and atherogenic index of plasma (AIP) (r = 0.16 to 0.49). Significant racial/ethnic differences were observed in many associations. After adjusting for lean mass, and other demographic and lifestyle factors, the study showed that black women demonstrated significantly weaker associations than their white and Hispanic counterparts using multivariable linear regression procedures.ConclusionThe relationship between lipid profiles and body fat distribution variables varies by race/ethnicity in reproductive-age women. A better understanding of these racial/ethnic differences has important implications for clinical and public-health efforts in targeting the prevention of cardiovascular disease (CVD).     

Weight change modulates epicardial fat burden: a 4-year serial study with non-contrast computed tomography

IntroductionEpicardial fat volume (EFV) is linked to cardiovascular event risk. We aimed to investigate the relationships between EFV and weight change.MethodsFrom the EISNER (Early Identification of Subclinical Atherosclerosis using Non-invasive Imaging Research) Registry with baseline and follow-up coronary calcium scans (1248 subjects), we selected a cohort of 374 asymptomatic subjects matched using age decade, gender and coronary calcium score (CCS) as a measure of subclinical cardiovascular risk, who underwent 2 scans at an interval of 4.1 ± 0.4 years. Using semi-automated validated software, pericardial contours were generated on all slices by spline interpolation from 5 to 10 control points. EFV was computed as fat volume within the pericardial contours. Weight gain/loss was defined as >5% change.ResultsAt baseline, EFV was moderately correlated to weight, body mass index (BMI) and waist circumference (r = 0.51, 0.41 and 0.50, p < 0.0001). EFV change was weakly correlated to change in weight (r = 0.37, p < 0.0001), BMI (r = 0.39, p < 0.0001) and waist circumference (r = 0.21, p = 0.002). On multivariable linear regression analysis, weight change [β = 1.2, 95% confidence interval (CI) 0.9–1.5, p < 0.001], BMI change (β = 1.2, 95% CI 0.9–1.5, p < 0.001), gender (β = ?6.4, 95% CI ?10.9 to ?1.8, p = 0.006) and hypertension (β = 4.7, 95% CI 0.5–9.0, p = 0.03) predicted EFV change. EFV decreased in 54 subjects with weight loss and increased in 71 subjects with weight gain (?2.3 ± 21.1% vs. 23.3 ± 24.4%, p < 0.001).ConclusionsEFV is related to body weight, BMI and waist circumference. Reduction in weight may stabilize or reduce EFV, while weight gain may promote EFV increase.     

The association of macro- and micronutrient intake with growth hormone secretion

ContextGrowth hormone (GH) is known to be nutritionally regulated, but the effect of dietary composition on detailed GH secretion parameters has not previously been comprehensively evaluated.ObjectiveThe objective of the study was to determine whether specific macro- and micronutrients are associated with discrete parameters of GH secretion among subjects with wide ranges of body mass index.DesignDetailed macro- and micronutrient intake was assessed by 4-day food records while GH secretion was assessed by standard stimulation testing in 108 men and women in one study (Study 1), and by overnight frequent blood sampling in 12 men in another study (Study 2).ResultsPeak stimulated GH was positively associated with vitamin C (r = + 0.29; P = 0.003), dietary fiber (r = + 0.27; P = 0.004), arachidic acid (r = + 0.25; P = 0.008), and behenic acid (r = + 0.30; P = 0.002) intake in univariate analysis. Controlling for age, gender, race/ethnicity, visceral fat, HOMA-IR, total caloric intake and these four dietary factors in step-wise multivariate modeling, peak GH remained significantly associated with vitamin C and visceral fat (both P < 0.05). In addition, vitamin C intake was associated with various parameters of endogenous GH secretion including basal GH secretion (r = + 0.95; P < 0.0001), GH half-life (r = + .75; P = 0.005), total GH production (r = + 0.76; P = 0.004), GH area-under-the-curve (r = + 0.89; P = 0.0001), mean log₁₀ GH pulse area (r = + 0.67; P = 0.02), and overnight maximum (r = + 0.62; P = 0.03), nadir (r = + 0.97; P < 0.0001), and mean GH secretion (r = + 0.89; P = 0.0001).ConclusionsThese results suggest that certain micronutrients such as vitamin C intake are strongly and uniquely associated with stimulated and endogenous spontaneous GH secretion.     

Gender specific associations between matrix metalloproteinases and inflammatory markers in post myocardial infarction patients

ObjectiveAtherothrombotic disease in the coronary arteries leads to myocardial infarction (MI) through plaque rupture or erosion of the endothelium, the former mechanism predominating in men and the latter in women. Inflammation is a key feature of these processes, and the interplay between inflammation and matrix metalloproteinases (MMPs) in this context is not fully understood. In this study, we investigated the association between inflammatory markers and MMPs in men and women.MethodsBlood samples were drawn 3 months after a first MI in 387 patients and 387 sex- and age-matched controls (82% men). C-reactive protein (CRP), interleukin-6 (IL-6), IL-8, -18, tumour necrosis factor-α (TNF-α), macrophage chemoattractant protein-1 (MCP-1), MMP-1, -3 and -9 were measured. Coronary angiography was performed in 243 of the patients, and they were classified into 0-, 1-, 2- or 3-vessel disease groups.ResultsCRP, IL-6, -8, -18 and TNF-α were higher, and MMP-3 and -9 were lower, in patients than in controls. A greater proportion of women (49%) had 0-vessel disease than men (16%, p < 0.0001). A gender specific pattern of associations between inflammatory markers and MMPs was found as IL-6 (r_S = 0.29, p < 0.05), IL-18 (r_S = 0.34, p < 0.01) and MCP-1 (r_S = 0.35, p < 0.01) correlated with MMP-3 in female patients, whereas CRP (r_S = 0.23, p < 0.0001), IL-6 (r_S = 0.13, p < 0.05) and IL-8 (r_S = ?0.21, p < 0.01) correlated with MMP-9 in male patients.ConclusionsThe present study demonstrates different patterns of association between inflammatory markers and MMPs in men and women, strengthening the hypothesis of gender specific differences in pathophysiological mechanisms of MI.     

The effects of the surgical removal of subcutaneous adipose tissue on energy expenditure and adipocytokine concentrations in obese women

ObjectiveTo analyze the effects of the surgical removal of subcutaneous adipose tissue by ultrasound-assisted megalipoplasty (UAM) on energy expenditure and adipocytokine concentrations in obese women.MethodsFifteen premenopausal obese women with BMI 37.5 ± 6.3 kg/m² (range: 30.7–53.6 kg/m²) underwent UAM. Body composition (by DEXA), resting metabolic rate (REE) by indirect calorimetry, insulin resistance (by the HOMA method), leptin, C-reactive protein, interleukin-6, resistin and adiponectin were measured before and 1, 3, 28 and 180 days after the procedure.ResultsUAM significantly reduced fat mass at day 3, without further changes in the following days. REE increased at day 3 after UAM, returned to baseline levels at day 28 and significantly declined at day 180. Leptin levels transiently increased after UAM and then declined according to fat mass reduction. C-reactive protein, interleukin-6 and resistin levels acutely increased after UAM and then returned to the baseline levels. Adiponectin levels acutely declined after the procedure and then stabilized to a plasma level slightly lower than at baseline. Insulin resistance deteriorated in the acute post-operative phase and then improved.ConclusionThe surgical removal of subcutaneous fat was associated to an acute inflammatory reaction with high REE and insulin-resistance. Later on, the metabolic effects of fat mass removal appeared, with a reduction of leptin levels and REE and an improvement of insulin resistance.