Association of insulin resistance with the accumulation of saturated intramyocellular lipid: A comparison with other fat stores.

It has been shown using proton magnetic resonance spectroscopy (1H MRS) that, in a group of females, whole-body insulin resistance was more closely related to accumulation of saturated intramyocellular lipid (IMCL) than to IMCL concentration alone. This has not been investigated in males. We investigated whether age- and body mass index-matched healthy males differ from the previously reported females in IMCL composition (measured as CH2:CH3) and IMCL concentration (measured as CH3), and in their associations with insulin resistance. We ask whether saturated IMCL accumulation is more strongly associated with insulin resistance than other ectopic and adipose tissue lipid pools and remains a significant predictor when these other pools are taken into account. In this group of males, who had similar overall insulin sensitivity to the females, IMCL was similar between sexes. The males demonstrated similar and even stronger associations of IMCL with insulin resistance, supporting the idea that a marker reflecting the accumulation of saturated IMCL is more strongly associated with whole-body insulin resistance than IMCL concentration alone. However, this marker ceased to be a significant predictor of whole-body insulin resistance after consideration of other lipid pools, which implies that this measure carries no more information in practice than the other predictors we found, such as intrahepatic lipid and visceral adipose tissue. As the marker of saturated IMCL accumulation appears to be related to these two predictors and has a much smaller dynamic range, this finding does not rule out a role for it in the pathogenesis of insulin resistance.

Validation of the Fatty Liver Index for identifying non-alcoholic fatty liver disease in a Kenyan population.

BACKGROUND AND AIM: Fatty Liver Index (FLI) is a simple clinical scoring system estimating non-alcoholic fatty liver disease (NAFLD). It is validated in European-descent and Asian populations, but not in sub-Saharan Africans. The aim of this study is to evaluate the validity of the FLI for predicting NAFLD in a population from Kenya. METHODS: Participants were recruited from a community-based study conducted in Kenya. NAFLD was diagnosed using hepatic ultrasonography. Clinical, anthropometrical, biochemical and lifestyle data were obtained. The accuracy and cut-off point of the FLI to detect NAFLD were evaluated by area under the receiver operator characteristic curve and the maximum Youden index analysis. RESULTS: A total of 640 participants (94 with NAFLD) were included. Mean age was 37.4 ± 0.4 years and 58.7% were women. Mean body mass index (BMI) was 22.3 ± 0.2 kg/m2 and waist circumference (WC) 79.1 ± 0.4 cm. A total of 15 (2.3%) participants were diagnosed with type 2 diabetes and 65 (10.2%) with obesity (BMI ≥ 30 kg/m2 ). AUROC of FLI for predicting NAFLD was 0.80 (95% CI 0.74-0.85), which was significantly higher compared to individual components gamma-glutamyl transferase and triglycerides (p < 0.05), but not compared to anthropometric parameters BMI (AUROC of 0.83, 95% CI 0.79-0.88) and WC (AUROC of 0.81, 95% CI 0.76-0.87). CONCLUSIONS: FLI is a simple valid scoring system to use in rural and urban Kenyan adults. However, this index might not be superior to BMI or WC to predict NAFLD, and those measurements might therefore be more appropriate in limited settings.

Joint associations between objectively measured physical activity volume and intensity with body fatness: the Fenland study.

BACKGROUND/OBJECTIVES: Physical activity energy expenditure (PAEE) represents the total volume of all physical activity. This can be accumulated as different underlying intensity profiles. Although volume and intensity have been studied in isolation, less is known about their joint association with health. We examined this association with body fatness in a population-based sample of middle-aged British adults. METHODS: In total, 6148 women and 5320 men from the Fenland study with objectively measured physical activity from individually calibrated combined heart rate and movement sensing and DXA-derived body fat percentage (BF%) were included in the analyses. We used linear and compositional isocaloric substitution analysis to examine associations of PAEE and its intensity composition with body fatness. Sex-stratified models were adjusted for socio-economic and dietary covariates. RESULTS: PAEE was inversely associated with body fatness in women (beta = -0.16 (95% CI: -0.17; -0.15) BF% per kJ day-1 kg-1) and men (beta = -0.09 (95% CI: -0.10; -0.08) BF% per kJ day-1 kg-1). Intensity composition was significantly associated with body fatness, beyond that of PAEE; the reallocation of energy to vigorous physical activity (>6 METs) from other intensities was associated with less body fatness, whereas light activity (1.5-3 METs) was positively associated. However, light activity was the main driver of overall PAEE volume, and the relative importance of intensity was marginal compared to that of volume; the difference between PAEE in tertile 1 and 2 in women was associated with 3 percentage-point lower BF%. Higher vigorous physical activity in the same group to the maximum observed value was associated with 1 percentage-point lower BF%. CONCLUSIONS: In this large, population-based cohort study with objective measures, PAEE was inversely associated with body fatness. Beyond the PAEE association, greater levels of intense activity were also associated with lower body fatness. This contribution was marginal relative to PAEE. These findings support current guidelines for physical activity which emphasise that any movement is beneficial, rather than specific activity intensity or duration targets.

Hepatic steatosis is associated with anthropometry, cardio-metabolic disease risk, sex, age and urbanisation, but not with ethnicity in adult Kenyans.

OBJECTIVE: We aimed to determine the associations of non-alcoholic fatty liver disease (NAFLD) with cardio-metabolic risk factors for diabetes in adult Kenyans. METHODS: A cross-sectional study was undertaken among rural and urban Kenyans of different ethnic origin. Ultrasonography scanning (USS) methods were used for the assessment of hepatic fat accumulation for NAFLD assessment and abdominal fat distribution, and simple anthropometry measurements were performed. All participants underwent a 2-h oral glucose tolerance test, and biochemical, haemodynamic and lifestyle data were obtained. Multivariate logistic regression analyses were used to assess sex, age, residency and ethnic differences in the association between NAFLD and various metabolic parameters. RESULTS: In total, 743 individuals (59.1% women) with a mean age of 38.0 (range 18-68) years participated in the study. Overall, 118 individuals (15.9%) had NAFLD, of whom 94.1% had mild steatosis. Age >40 years was significantly associated with having NAFLD compared with <30 years of age with no difference found in NAFLD between ethnic groups (Luo, Kamba, Maasai). All body composition and clinical measurements were associated with NAFLD (p < 0.045 for OR). CONCLUSION: Finding lower odds for NAFLD in men was unexpected, as was the lack of differences in NAFLD among the ethnic groups, while higher odds for NAFLD with increasing age and in urban vs. rural populations was expected. Especially the sex-specific results warrant further studies in black African populations on biology of body composition for having NAFLD, and whether this translates into insulin resistance and higher risk of diabetes and consequently cardiovascular disease in black African women.

The association between adherence to the Mediterranean diet and hepatic steatosis: cross-sectional analysis of two independent studies, the UK Fenland Study and the Swiss CoLaus Study.

BACKGROUND AND AIMS: The risk of hepatic steatosis may be reduced through changes to dietary intakes, but evidence is sparse, especially for dietary patterns including the Mediterranean diet. We investigated the association between adherence to the Mediterranean diet and prevalence of hepatic steatosis. METHODS: Cross-sectional analysis of data from two population-based adult cohorts: the Fenland Study (England, n = 9645, 2005-2015) and CoLaus Study (Switzerland, n = 3957, 2009-2013). Habitual diet was assessed using cohort-specific food frequency questionnaires. Mediterranean diet scores (MDSs) were calculated in three ways based on adherence to the Mediterranean dietary pyramid, dietary cut-points derived from a published review, and cohort-specific tertiles of dietary consumption. Hepatic steatosis was assessed by abdominal ultrasound and fatty liver index (FLI) in Fenland and by FLI and non-alcoholic fatty liver disease (NAFLD) score in CoLaus. FLI includes body mass index (BMI), waist circumference, gamma-glutamyl transferase, and triglyceride; NAFLD includes diabetes, fasting insulin level, fasting aspartate-aminotransferase (AST), and AST/alanine transaminase ratio. Associations were assessed using Poisson regression. RESULTS: In Fenland, the prevalence of hepatic steatosis was 23.9% and 27.1% based on ultrasound and FLI, respectively, and in CoLaus, 25.3% and 25.7% based on FLI and NAFLD score, respectively. In Fenland, higher adherence to pyramid-based MDS was associated with lower prevalence of hepatic steatosis assessed by ultrasound (prevalence ratio (95% confidence interval), 0.86 (0.81, 0.90) per one standard deviation of MDS). This association was attenuated [0.95 (0.90, 1.00)] after adjustment for body mass index (BMI). Associations of similar magnitude were found for hepatic steatosis assessed by FLI in Fenland [0.82 (0.78, 0.86)] and in CoLaus [0.85 (0.80, 0.91)], and these were also attenuated after adjustment for BMI. Findings were similar when the other two MDS definitions were used. CONCLUSIONS: Greater adherence to the Mediterranean diet was associated with lower prevalence of hepatic steatosis, largely explained by adiposity. These findings suggest that an intervention promoting a Mediterranean diet may reduce the risk of hepatic steatosis.

Associations of types of dairy consumption with adiposity: cross-sectional findings from over 12 000 adults in the Fenland Study, UK.

Evidence from randomised controlled trials supports beneficial effects of total dairy products on body weight, fat and lean mass, but evidence on associations of dairy types with distributions of body fat and lean mass is limited. We aimed to investigate associations of total and different types of dairy products with markers of adiposity, and body fat and lean mass distribution. We evaluated cross-sectional data from 12 065 adults aged 30-65 years recruited to the Fenland Study between 2005 and 2015 in Cambridgeshire, UK. Diet was assessed with an FFQ. We estimated regression coefficients (or percentage differences) and their 95 % CI using multiple linear regression models. The medians of milk, yogurt and cheese consumption were 293 (interquartile range (IQR) 146-439), 35·3 (IQR 8·8-71·8) and 14·6 (IQR 4·8-26·9) g/d, respectively. Low-fat dairy consumption was inversely associated with visceral:subcutaneous fat ratio estimated with dual-energy X-ray absorptiometry (-2·58 % (95 % CI -3·91, -1·23 %) per serving/d). Habitual consumption per serving/d (200 g) of milk was associated with 0·33 (95 % CI 0·19, 0·46) kg higher lean mass. Other associations were not significant after false discovery correction. Our findings suggest that the influence of milk consumption on lean mass and of low-fat dairy consumption on fat mass distribution may be potential pathways for the link between dairy consumption and metabolic risk. Our cross-sectional findings warrant further research in prospective and experimental studies in diverse populations.

Association of Genetic Variants Related to Gluteofemoral vs Abdominal Fat Distribution With Type 2 Diabetes, Coronary Disease, and Cardiovascular Risk Factors.

Importance: Body fat distribution, usually measured using waist-to-hip ratio (WHR), is an important contributor to cardiometabolic disease independent of body mass index (BMI). Whether mechanisms that increase WHR via lower gluteofemoral (hip) or via higher abdominal (waist) fat distribution affect cardiometabolic risk is unknown. Objective: To identify genetic variants associated with higher WHR specifically via lower gluteofemoral or higher abdominal fat distribution and estimate their association with cardiometabolic risk. Design, Setting, and Participants: Genome-wide association studies (GWAS) for WHR combined data from the UK Biobank cohort and summary statistics from previous GWAS (data collection: 2006-2018). Specific polygenic scores for higher WHR via lower gluteofemoral or via higher abdominal fat distribution were derived using WHR-associated genetic variants showing specific association with hip or waist circumference. Associations of polygenic scores with outcomes were estimated in 3 population-based cohorts, a case-cohort study, and summary statistics from 6 GWAS (data collection: 1991-2018). Exposures: More than 2.4 million common genetic variants (GWAS); polygenic scores for higher WHR (follow-up analyses). Main Outcomes and Measures: BMI-adjusted WHR and unadjusted WHR (GWAS); compartmental fat mass measured by dual-energy x-ray absorptiometry, systolic and diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, fasting glucose, fasting insulin, type 2 diabetes, and coronary disease risk (follow-up analyses). Results: Among 452 302 UK Biobank participants of European ancestry, the mean (SD) age was 57 (8) years and the mean (SD) WHR was 0.87 (0.09). In genome-wide analyses, 202 independent genetic variants were associated with higher BMI-adjusted WHR (n = 660 648) and unadjusted WHR (n = 663 598). In dual-energy x-ray absorptiometry analyses (n = 18 330), the hip- and waist-specific polygenic scores for higher WHR were specifically associated with lower gluteofemoral and higher abdominal fat, respectively. In follow-up analyses (n = 636 607), both polygenic scores were associated with higher blood pressure and triglyceride levels and higher risk of diabetes (waist-specific score: odds ratio [OR], 1.57 [95% CI, 1.34-1.83], absolute risk increase per 1000 participant-years [ARI], 4.4 [95% CI, 2.7-6.5], P < .001; hip-specific score: OR, 2.54 [95% CI, 2.17-2.96], ARI, 12.0 [95% CI, 9.1-15.3], P < .001) and coronary disease (waist-specific score: OR, 1.60 [95% CI, 1.39-1.84], ARI, 2.3 [95% CI, 1.5-3.3], P < .001; hip-specific score: OR, 1.76 [95% CI, 1.53-2.02], ARI, 3.0 [95% CI, 2.1-4.0], P < .001), per 1-SD increase in BMI-adjusted WHR. Conclusions and Relevance: Distinct genetic mechanisms may be linked to gluteofemoral and abdominal fat distribution that are the basis for the calculation of the WHR. These findings may improve risk assessment and treatment of diabetes and coronary disease.

Impact of Early Infant Growth, Duration of Breastfeeding and Maternal Factors on Total Body Fat Mass and Visceral Fat at 3 and 6 Months of Age.

BACKGROUND: Accelerated gain in fat mass in the first months of life is considered to be a risk factor for adult diseases, given the tracking of infancy fat mass into adulthood. Our objective was to assess the influence of early growth, type of feeding and maternal variables on fat mass in early life. METHODS: In 300 healthy term infants, we longitudinally measured fat mass percentage (FM%) by air-displacement-plethysmography at 1, 3, and 6 months and abdominal visceral and subcutaneous fat measured by ultrasound at 3 and 6 months. RESULTS: Both gain in FM% and weight-for-length in the first 3 months were positively associated with FM% at 6 months of age and visceral fat at 3 months of age. Gain in FM% and weight-for-length between 3 and 6 months were both positively associated with visceral fat at 6 months. Breastfeeding duration associated positively with subcutaneous fat but not with visceral fat at 3 and 6 months. Maternal characteristics did not associate with FM% or visceral fat at 3 or 6 months. CONCLUSION: Higher gain in FM% or in weight-for-length in the first postnatal months leads not only to higher FM% but also more to accumulation of visceral fat. Exclusive breastfeeding appears to promote subcutaneous but not visceral fat in the first 6 months.

Visceral and subcutaneous abdominal adiposity and pulmonary function in 30-year-old adults: a cross-sectional analysis nested in a birth cohort.

BACKGROUND: Several studies have verified body fat distribution in association with pulmonary function (PF), mainly waist circumference, but few have used measures able to distinguish abdominal fat compartments. The present study aims to verify the association of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with PF measures. METHODS: In 1982, all hospital births occurring in Pelotas, Brazil, were identified and those livebirths have been followed. In 2012-13, the cohort participants were evaluated and VAT and SAT measured using ultrasound; forced expiratory volume in the first second (FEV1) or forced vital capacity (FVC) were patronized in z-scores stratified by sex. The associations were verified using crude and adjusted linear regressions. RESULTS: The present analyses comprised 3438 individuals (1721 women). VAT was inversely associated with spirometric parameters, in both crude and adjusted models. SAT showed inverse associations in the crude analyzes in males and a positive trend after adjustment, except for SAT and FVC in males. To each centimeter of VAT, mean adjusted FEV1 z-scores decreased 0.072 (95% CI -0.107; -0.036) in men and 0.127 (95% CI -0.164; -0.090) in women, and FVC z-scores decreased -0.075 (95% CI -0.111; -0.039) and 0.121 (95% CI -0.158; -0.083), in men and women, respectively. CONCLUSIONS: VAT has a consistent inverse association with FEV1 and FVC in both sexes. On the other hand, SAT showed inconsistent results with PF parameters.

Abdominal fat depots associated with insulin resistance and metabolic syndrome risk factors in black African young adults.

BACKGROUND: Individuals of black African ethnicity tend to have less visceral adipose tissue (VAT) but more subcutaneous-abdominal adipose tissue (SCAT) than white Caucasians. However, it is unclear whether such distribution of abdominal fat is beneficial for metabolic disease risk in black individuals. Here we compared the associations between these specific abdominal fat depots, insulin sensitivity and metabolic syndrome risk. METHODS: A cross-sectional analysis of 76 black South African young adults (36 men; 40 women) aged 18-19 years participating in the Birth to Twenty Cohort Study had VAT and SCAT measured by MRI. The metabolic syndrome traits (blood pressure, lipid profile, fasting glucose and insulin) were measured and the values were combined into a metabolic syndrome risk score. Fasting glucose and insulin were used to derive the HOMA-index of insulin resistance (HOMA-IR). RESULTS: Compared to men, women had greater VAT (mean: 16.6 vs. 12.5 cm(2)) and SCAT (median 164.0 vs. 59.9 cm(2)). In men, SCAT (r = 0.50) was more strongly correlated to the metabolic syndrome score (MetS) than was VAT (r = 0.23), and was associated with both MetS (P = 0.001) and HOMA-IR (P = 0.001) after adjustment for VAT and total fat mass. In women, both abdominal fat compartments showed comparable positive correlations with MetS (r = 0.26 to 0.31), although these trends were weaker than in men. CONCLUSIONS: In young black South African adults, SCAT appears to be more relevant than VAT to metabolic syndrome traits.

Newborn body composition and child cardiovascular risk markers: a prospective multi-ethnic Asian cohort study.

BACKGROUND: Early epidemiological studies have associated low birthweight with increased cardiovascular risk. We aimed to examine whether the fat and fat-free components of birthweight have differing relationships with childhood cardiovascular risk markers. METHODS: In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort, air displacement plethysmography was conducted within 24 h after delivery in 290 naturally conceived singletons. We investigated associations of newborn cohort-specific standardized z-score of fat mass, fat-free mass, body fat percentage and birthweight on child (at 6 years of age) carotid intima-media thickness, pulse wave velocity, blood pressure, prehypertension/hypertension (>110/70 mmHg) and standardized systolic and diastolic blood pressure (SBP and DBP) trajectories (at 3-6 years of age), taking account of maternal education, height, tobacco exposure, parity, ethnicity, child's sex, gestational age, age at follow-up, and other maternal factors. RESULTS: Clear inverse associations were seen for blood pressure with z-score of fat mass [SBP, ß (95% CI): -1.31 mmHg (-2.57, -0.06); DBP: -0.79 mmHg (-1.74, 0.15)] and body fat percentage [SBP: -1.46 mmHg (-2.73, -0.19); DBP: -0.80 mmHg (-1.75, 0.16)], but not with fat-free mass [SBP: 0.27 mmHg (-1.29, 1.83)]; DBP: -0.14 mmHg (-1.30, 1.03)]. Being in the lowest tertile of fat mass or body fat percentage was associated with higher blood pressure trajectories and prehypertension/hypertension risk [OR (95% CI), fat mass: 4.23 (1.41, 12.68); body fat percentage: 3.22 (1.09, 9.53)] without concomitantly higher overweight/obesity risk. CONCLUSIONS: At birth, low adiposity was associated with increased childhood blood pressure. Low newborn adiposity might serve as a marker of poor fetal growth or suboptimal intrauterine conditions associated with hypertension risk later in life.

Reference Values for DXA-Derived Visceral Adipose Tissue in Adults 40 Years and Older from a European Population: The Tromsø Study 2015-2016.

Background: Reference values for visceral adipose tissue (VAT) are needed and it has been advocated that body composition measures depend on both the technique and methods applied, as well as the population of interest. We aimed to develop reference values for VAT in absolute grams (VATg), percent (VAT%), and as a kilogram-per-meters-squared index (VATindex) for women and men, and investigate potential differences between these measures and their associations with cardiometabolic risk factors (including metabolic syndrome (MetS)). Methods: In the seventh survey of the population-based Tromsø Study, 3675 participants (aged 40-84, 59% women) attended whole-body DXA scans (Lunar Prodigy GE) from where VAT was derived. We used descriptive analysis, correlations, receiver operating characteristics (ROC), and logistic regression to propose reference values for VAT and investigated VAT's association with cardiometabolic risk factors, MetS and single MetS components. Further, Youden's index was used to suggest threshold values for VAT. Results: VATg and VATindex increased until age 70 and then decreased, while VAT% increased with age across all age groups. VAT (all measurement units) was moderate to highly correlated and significantly associated with all cardiometabolic risk factors, except for total cholesterol. Associations between MetS, single MetS components, and VATg and VATindex were similar, and VAT% did not contribute any further to this association. Conclusion: These VAT reference values and thresholds, developed in a sample of adults of Norwegian origin, could be applied to other studies with similar populations using the same DXA device and protocols. The associations between VAT and cardiometabolic risk factors were similar across different measurement units of VAT.

Anthropometry-based prediction of body composition in early infancy compared to air-displacement plethysmography.

BACKGROUND: Anthropometry-based equations are commonly used to estimate infant body composition. However, existing equations were designed for newborns or adolescents. We aimed to (a) derive new prediction equations in infancy against air-displacement plethysmography (ADP-PEA Pod) as the criterion, (b) validate the newly developed equations in an independent infant cohort and (c) compare them with published equations (Slaughter-1988, Aris-2013, Catalano-1995). METHODS: Cambridge Baby Growth Study (CBGS), UK, had anthropometry data at 6 weeks (N = 55) and 3 months (N = 64), including skinfold thicknesses (SFT) at four sites (triceps, subscapular, quadriceps and flank) and ADP-derived total body fat mass (FM) and fat-free mass (FFM). Prediction equations for FM and FFM were developed in CBGS using linear regression models and were validated in Sophia Pluto cohort, the Netherlands, (N = 571 and N = 447 aged 3 and 6 months, respectively) using Bland-Altman analyses to assess bias and 95% limits of agreement (LOA). RESULTS: CBGS equations consisted of sex, age, weight, length and SFT from three sites and explained 65% of the variance in FM and 79% in FFM. In Sophia Pluto, these equations showed smaller mean bias than the three published equations in estimating FM: mean bias (LOA) 0.008 (-0.489, 0.505) kg at 3 months and 0.084 (-0.545, 0.713) kg at 6 months. Mean bias in estimating FFM was 0.099 (-0.394, 0.592) kg at 3 months and -0.021 (-0.663, 0.621) kg at 6 months. CONCLUSIONS: CBGS prediction equations for infant FM and FFM showed better validity in an independent cohort at ages 3 and 6 months than existing equations.

Antenatal Determinants of Childhood Obesity in High-Risk Offspring: Protocol for the DiGest Follow-Up Study.

Childhood obesity is an area of intense concern internationally and is influenced by events during antenatal and postnatal life. Although pregnancy complications, such as gestational diabetes and large-for-gestational-age birthweight have been associated with increased obesity risk in offspring, very few successful interventions in pregnancy have been identified. We describe a study protocol to identify if a reduced calorie diet in pregnancy can reduce adiposity in children to 3 years of age. The dietary intervention in gestational diabetes (DiGest) study is a randomised, controlled trial of a reduced calorie diet provided by a whole-diet replacement in pregnant women with gestational diabetes. Women receive a weekly dietbox intervention from enrolment until delivery and are blinded to calorie allocation. This follow-up study will assess associations between a reduced calorie diet in pregnancy with offspring adiposity and maternal weight and glycaemia. Anthropometry will be performed in infants and mothers at 3 months, 1, 2 and 3 years post-birth. Glycaemia will be assessed using bloodspot C-peptide in infants and continuous glucose monitoring with HbA1c in mothers. Data regarding maternal glycaemia in pregnancy, maternal nutrition, infant birthweight, offspring feeding behaviour and milk composition will also be collected. The DiGest follow-up study is expected to take 5 years, with recruitment finishing in 2026.

Computed tomography-based validation of abdominal adiposity measurements from ultrasonography, dual-energy X-ray absorptiometry and anthropometry.

Large-scale aetiological studies of obesity and its pathological consequences require accurate measurements of adipose mass, distribution and subtype. Here, we compared the validity of three abdominal obesity assessment methods (dual-energy X-ray absorptiometry (DXA), ultrasound and anthropometry) against the gold-standard method of computed tomography (CT) in twenty-nine non-diseased middle-aged men (BMI 26.5 (sd 3.1) kg/m(2)) and women (BMI 25.5 (sd 3.2) kg/m(2)). Assessments of adipose mass (kg) and distribution (total subcutaneous (TSAT), superficial subcutaneous (SSAT), deep subcutaneous (DSAT) and visceral (VAT)) were obtained. Spearman's correlations were performed adjusted for age and sex. VAT area that was assessed using ultrasound (r 0.79; P < 0.0001) and waist circumference (r 0.85; P < 0.0001) correlated highly with VAT from CT, as did BMI (r 0.67; P < 0.0001) and DXA (r 0.70; P < 0.0001). DXA (r 0.72; P = 0.0004), BMI (r 0.71; P = 0.0003), waist circumference (r 0.86; P < 0.0001) and ultrasound (r 0.52; P = 0.015) were less strongly correlated with CT TSAT. None of the comparison measures of DSAT was strongly correlated with CT DSAT (all r approximately 0.50; P < 0.02). BMI (r 0.76; P < 0.0001), waist circumference (r 0.65; P = 0.002) and DXA (r 0.75; P < 0.0001) were all fairly strongly correlated with the CT measure of SSAT, whereas ultrasound yielded a weaker yet statistically significant correlation (r 0.48; P = 0.03). Compared with CT, visceral and subcutaneous adiposity can be assessed with reasonable validity using waist circumference and BMI, respectively. Ultrasound or DXA does not generally provide substantially better measures of these traits. Highly valid assessments of DSAT do not appear to be possible with surrogate measures. These findings may help guide the selection of measures for epidemiological studies of obesity.

Dietary Intervention in Pregnant Women with Gestational Diabetes; Protocol for the DiGest Randomised Controlled Trial.

Gestational diabetes mellitus (GDM) annually affects 35,000 pregnancies in the United Kingdom, causing suboptimal health outcomes to the mother and child. Obesity and excessive gestational weight gain are risk factors for GDM. The Institute of Medicine recommends weight targets for women that are overweight and obese, however, there are no clear guidelines for women with GDM. Observational data suggest that modest weight loss (0.6-2 kg) after 28 weeks may reduce risk of caesarean section, large-for-gestational-age (LGA), and maternal postnatal glycaemia. This protocol for a multicentre randomised double-blind controlled trial aims to identify if a fully controlled reduced energy diet in GDM pregnancy improves infant birthweight and reduces maternal weight gain (primary outcomes). A total of 500 women with GDM (National Institute of Health and Care Excellence (NICE) 2015 criteria) and body mass index (BMI) ≥25 kg/m2 will be randomised to receive a standard (2000 kcal/day) or reduced energy (1200 kcal/day) diet box containing all meals and snacks from 28 weeks to delivery. Women and caregivers will be blinded to the allocations. Food diaries, continuous glucose monitoring, and anthropometry will measure dietary compliance, glucose levels, and weight changes. Women will receive standard antenatal GDM management (insulin/metformin) according to NICE guidelines. The secondary endpoints include caesarean section rates, LGA, and maternal postnatal glucose concentrations.

Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis.

BACKGROUND: In parallel to the increasing prevalence of metabolic syndrome, the prevalence of hepatic steatosis has also increased dramatically worldwide. Hepatic steatosis is a major risk factor of hepatic cirrhosis, cardiovascular disease and type 2 diabetes. Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) have been positively associated with the metabolic syndrome. However, the association between PCSK9 and the liver function is still controversial. OBJECTIVE: The objective of this study is to investigate the association between circulating PCSK9 levels and the presence of hepatic steatosis, as well as with liver biomarkers in a cohort of healthy individuals. METHODS: Total PCSK9 levels were measured by an in-house ELISA using a polyclonal antibody. Plasma albumin, alkaline phosphatase, ALT, AST, total bilirubin and GGT were measured in 698 individuals using the COBAS system. The presence of hepatic steatosis was assessed using ultrasound liver scans. RESULTS: In a multiple regression model adjusted for age, sex, insulin resistance, body mass index and alcohol use, circulating PCSK9 level was positively associated with albumin (ß = 0.102, P = 0.008), alkaline phosphatase (ß = 0.201, P < 0.0001), ALT (ß = 0.238, P < 0.0001), AST (ß = 0.120, P = 0.003) and GGT (ß = 0.103, P = 0.007) and negatively associated with total bilirubin (ß = -0.150, P < 0.0001). Tertile of circulating PCSK9 was also associated with hepatic steatosis (OR 1.48, 95% CI 1.05-2.08, P = 0.02). CONCLUSION: Our data suggest a strong association between PCSK9 and liver biomarkers as well as hepatic steatosis. Further studies are needed to explore the role of PCSK9 on hepatic function.

Associations of physical activity and sedentary time with body composition in Brazilian young adults.

The findings of studies on the association between physical activity and adiposity are not consistent, and most are cross-sectional and used only self-reported measures. The aims of this study were to evaluate: 1) independent and combined cross-sectional associations of objectively-measured physical activity and sedentary time with body composition outcomes at 30 years, and 2) prospective associations of changes in self-reported physical activity from 23 to 30 years with the same outcomes in participants from the 1982 Pelotas (Brazil) Birth Cohort. Body mass index, waist circumference, visceral abdominal fat, fat mass index, and android/gynoid fat ratio were the outcomes. 3,206 participants were analysed. In cross-sectional analyses, higher objectively-measured moderate-to-vigorous physical activity was associated with lower body mass index (ß = 0.017, 95%CI: -0.026; -0.009), waist circumference (ß = -0.043, 95%CI: -0.061; -0.025), visceral abdominal fat (ß = -0.006, 95%CI: -0.009; -0.003), and fat mass index (ß = -0.015, 95%CI: -0.021; -0.009), independent of sedentary time. Sedentary time was independently associated only with higher fat mass index (ß = 0.003, 95%CI: 0.001; 0.005). In longitudinal analyses, using self-reported measure, adiposity was lower among those who were consistently active or who became active. Adiposity was similar among the "became inactive" and "consistently inactive" subjects. Our findings suggest metabolic benefits from engagement in physical activity throughout young adulthood, with stronger associations on concurrent levels.

Associations of stunting in early childhood with cardiometabolic risk factors in adulthood.

Early life stunting may have long-term effects on body composition, resulting in obesity-related comorbidities. We tested the hypothesis that individuals stunted in early childhood may be at higher cardiometabolic risk later in adulthood. 1753 men and 1781 women participating in the 1982 Pelotas (Brazil) birth cohort study had measurements of anthropometry, body composition, lipids, glucose, blood pressure, and other cardiometabolic traits at age 30 years. Early stunting was defined as height-for-age Z-score at age 2 years below -2 against the World Health Organization growth standards. Linear regression models were performed controlling for sex, maternal race/ethnicity, family income at birth, and birthweight. Analyses were stratified by sex when p-interaction<0.05. Stunted individuals were shorter (ß = -0.71 s.d.; 95% CI: -0.78 to -0.64), had lower BMI (ß = -0.14 s.d.; 95%CI: -0.25 to -0.03), fat mass (ß = -0.28 s.d.; 95%CI: -0.38 to -0.17), SAFT (ß = -0.16 s.d.; 95%CI: -0.26 to -0.06), systolic (ß = -0.12 s.d.; 95%CI: -0.21 to -0.02) and diastolic blood pressure (ß = -0.11 s.d.; 95%CI: -0.22 to -0.01), and higher VFT/SAFT ratio (ß = 0.15 s.d.; 95%CI: 0.06 to 0.24), in comparison with non-stunted individuals. In addition, early stunting was associated with lower fat free mass in both men (ß = -0.39 s.d.; 95%CI: -0.47 to -0.31) and women (ß = -0.37 s.d.; 95%CI: -0.46 to -0.29) after adjustment for potential confounders. Our results suggest that early stunting has implications on attained height, body composition and blood pressure. The apparent tendency of stunted individuals to accumulate less fat-free mass and subcutaneous fat might predispose them towards increased metabolic risks in later life.

Validity of ultrasonography to assess hepatic steatosis compared to magnetic resonance spectroscopy as a criterion method in older adults.

BACKGROUND: The rising prevalence of obesity has made hepatic steatosis an increasingly common issue. Ultrasound is generally used in clinical practice to assess steatosis, but its accuracy has been inconsistent across studies. We aimed to determine the validity of ultrasound to diagnose hepatic steatosis when compared to the criterion method proton magnetic resonance spectroscopy (MRS) in older individuals. METHODS: A total of 72 healthy white European individuals (n = 42 men; n = 30 women aged 67-76 years) participating in the Hertfordshire Birth Cohort Physical Activity trial had hepatic steatosis assessed by ultrasound and MRS. The ultrasound scans were graded as normal, mild, moderate and severe steatosis, while hepatic fat content above 5.5% by MRS was used as a cut-off for steatosis. RESULTS: 18 participants (25%) had a level of hepatic fat measured by MRS consistent with diagnosis of steatosis. The sensitivity and specificity of ultrasound in diagnosing hepatic steatosis (mild/moderate/severe vs normal) were 96% (95% CI: 87-99.6%) and 94% (95% CI: 73-100%) respectively, although overlap in MRS hepatic fat content was observed between the ultrasound categories. CONCLUSIONS: Ultrasound is a valid method for detecting the presence or absence of hepatic steatosis in older adults and can be used as an alternative tool in both clinical investigations and epidemiological studies, when other imaging techniques are not feasible.