In the UK, populations of Black African and Caribbean (BAC) ethnicity suffer higher rates of cardiometabolic disease than White Europeans (WE). Obesity, leading to increased visceral adipose tissue (VAT) and intrahepatic lipid (IHL), has long been associated with cardiometabolic risk, driving insulin resistance and defective fatty acid/lipoprotein metabolism. These defects are compounded by a state of chronic low-grade inflammation, driven by dysfunctional adipose tissue. Emerging evidence has highlighted associations between central complement system components and adipose tissue, fatty acid metabolism and inflammation; it may therefore sit at the intersection of various cardiometabolic disease risk factors. However, increasing evidence suggests an ethnic divergence in pathophysiology, whereby current theories fail to explain the high rates of cardiometabolic disease in BAC populations. Lower fasting and postprandial TAG has been reported in BAC, alongside lower VAT and IHL deposition, which are paradoxical to the high rates of cardiometabolic disease exhibited by this ethnic group. Furthermore, BAC have been shown to exhibit a more anti-inflammatory profile, with lower TNF-α and greater IL-10. In contrast, recent evidence has revealed greater complement activation in BAC compared to WE, suggesting its dysregulation may play a greater role in the high rates of cardiometabolic disease experienced by this population. This review outlines the current theories of how obesity is proposed to drive cardiometabolic disease, before discussing evidence for ethnic differences in disease pathophysiology between BAC and WE populations.

The precision nutrition paradigm is based on the premise that substantial variation exists between human subjects in terms of diet-related disease risk and response to dietary interventions. In terms of better defining, ‘the right diet for the right person at the right time’ may be more appropriate than ‘one-diet-fits-all’. This review will explore how systems biology and nutrigenomics approaches have advanced the precision nutrition paradigm. We will draw upon a number of elegant mechanistic studies that have enhanced our understanding with respect to the complex biology and inter-organ crosstalk, relating to inflammation and metabolism, that underpin cardio-metabolic health. Also, this review will explore the extent to which more targeted, precision nutrition approaches may attenuate adverse risk factors associated with cardio-metabolic disease. We will focus on the key characteristics or ‘metabotypes’ of high- v. low-risk individuals and response v. non-response to interventions, to generate greater insights with respect to risk stratification and therapeutic interventions to enhance disease prevention. The goal is to utilise systems biology to enhance understanding by underpinning more targeted nutritional approaches, which may improve efficacy of personalised nutrition interventions.

Assessments of visceral adipose tissue (VAT) are critical in preventing metabolic disorders; however, there are limited measurement methods that are accurate and accessible for VAT. The purpose of this cross-sectional study was to evaluate the association between VAT estimates from consumer-grade devices and traditional anthropometrics and VAT and subcutaneous adipose tissue (SAT) from dual-energy X-ray absorptiometry (DXA). Data were collected from 182 participants (female = 114; White = 127; Black/African-American (BAA) = 48) which included anthropometrics and indices of VAT produced by near-infrared reactance spectroscopy (NIRS), visual body composition (VBC) and multifrequency BIA (MFBIA). VAT and SAT were collected using DXA. Bivariate and partial correlations were calculated between DXAVAT and DXASAT and other VAT estimates. All VAT indices had positive moderate–strong correlations with VAT (all P < 0·001) and SAT (all P < 0·001). Only waist:hip (r = 0·69), VATVBC (r = 0·84), and VATMFBIA (r = 0·86) had stronger associations with VAT than SAT (P < 0·001). Partial associations between VATVBC and VATMFBIA were only stronger for VAT than SAT in White participants (r = 0·67, P < 0·001) but not female, male, or BAA participants individually. Partial correlations for waist:hip were stronger for VAT than SAT, but only for male (r = 0·40, P < 0·010) or White participants (r = 0·48, P < 0·001). NIRS was amongst the weakest predictors of VAT which was highest in male participants (r = 0·39, P < 0·010) but non-existent in BAA participants (r = –0·02, P > 0·050) after adjusting for SAT. Both anthropometric and consumer-grade VAT indices are consistently better predictors of SAT than VAT. These data highlight the need for a standardised, but convenient, VAT estimation protocol that can account for the relationship between SAT and VAT that differs by sex/race.

Obesity and dyslipidaemia are strongly associated with the development of cardiometabolic diseases including CVD, stroke, type 2 diabetes, insulin resistance and non-alcoholic fatty liver disease. While these conditions are preventable, they are leading causes of mortality globally. There is now overwhelming clinical and experimental evidence that these conditions are driven by chronic systemic inflammation, with a growing body of data suggesting that this can be regulated by increasing levels of physical activity and reducing sedentary time. In this review we address the role of macrophage-mediated inflammation on the development of cardiometabolic diseases in individuals with overweight and obesity and how reducing sedentary behaviour and increasing physical activity appears to lessen these pro-inflammatory processes, reducing the risk of developing cardiometabolic diseases. While loss of subcutaneous and visceral fat mass is important for reducing chronic systemic inflammation, the mediating effects of increasing physical activity levels and lowering sedentary time on the development of inflamed adipose tissue also occur independently of changes in adiposity. The message that weight loss is not necessary for the benefits of physical activity in lowering chronic inflammation and improving health should encourage those for whom losing weight is difficult. Additionally, while the health benefits of meeting the recommended physical activity guidelines are clear, simply moving more appears to lower chronic systemic inflammation. Reducing sitting time and increasing light physical activity may therefore provide an alternative, more approachable manner for some with overweight and obesity to become more active, reduce chronic inflammation and improve cardiometabolic health.

To investigate the association between the Metabolic Score for Visceral Fat (METS-VF) and risk of type 2 diabetes mellitus (T2DM) and compare the predictive value of the METS-VF for T2DM incidence with other obesity indices in Chinese people. A total of 12 237 non-T2DM participants aged over 18 years from the Rural Chinese Cohort Study of 2007–2008 were included at baseline and followed up during 2013–2014. The cox proportional hazards regression was used to calculate hazard ratios (HR) and 95 % CI for the association between baseline METS-VF and T2DM risk. Restricted cubic splines were used to model the association between METS-VF and T2DM risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the ability of METS-VF to predict T2DM incidence. During a median follow-up of 6·01 (95 % CI 5·09, 6·06) years, 837 cases developed T2DM. After adjusting for potential confounding factors, the adjusted HR for the highest v. lowest METS-VF quartile was 5·97 (95 % CI 4·28, 8·32), with a per 1-sd increase in METS-VF positively associated with T2DM risk. Positive associations were also found in the sensitivity and subgroup analyses, respectively. A significant nonlinear dose–response association was observed between METS-VF and T2DM risk for all participants (Pnonlinearity = 0·0347). Finally, the AUC value of METS-VF for predicting T2DM was largest among six indices. The METS-VF may be a reliable and applicable predictor of T2DM incidence in Chinese people regardless of sex, age or BMI.

The purpose of this study was to determine if the mixed evidence of almond consumption on HbA1c stems from testing people with different body fat distributions (BFD) associated with different risks of glucose intolerance. A 6-month randomised controlled trial in 134 adults was conducted. Participants were randomly assigned to the almond (A) or control (C) group based on their BFD. Those in the almond group consumed 1·5 oz of almonds with their breakfast and as their afternoon snack daily. Those in the control group continued their habitual breakfast and afternoon snack routines. Body weight and composition were measured and blood samples were collected for determination of HbA1c, glycaemia and lipaemia at 0 and 6 months. Appetite ratings, energy intake and diet quality were collected at 0, 2, 4 and 6 months. Participants consuming almonds ingested 816 (sem 364) kJ/d more than participants in the control group (P = 0·03), but this did not result in any differences in body weight (A: –0·3 (sem 0·4), C: –0·4 (sem 0·4); P > 0·3). Participants in the almond, high android subcutaneous adipose tissue (SAT) group had a greater reduction in android fat mass percentage (A: –1·0 (sem 0·6), C: 1·1 (sem 0·6); P = 0·04), preserved android lean mass percentage (A: 0·9 (sem 0·6), C: –1 (sem 0·6); P = 0·04) and tended to decrease android visceral adipose tissue mass (A: –13 (sem 53) g, C: 127 (sem 53) g; P = 0·08) compared with those in the control, high SAT group. There were no differences in HbA1c between groups (A: 5·4 (sem 0·04), C: 5·5 (sem 0·04); P > 0·05). Thus, BFD may not explain the mixed evidence on almond consumption and HbA1c. Long-term almond consumption has limited ability to improve cardiometabolic health in those who are overweight and obese but otherwise healthy.

Nut-based products may aid low-glycaemic dietary strategies that are important for diabetes prevention in populations at increased risk of dysglycaemia, such as Asian Chinese. This randomised cross-over trial assessed the postprandial glycaemic response (0–120 min) of a higher-protein nut-based (HP-NB) snack formulation, in bar format (1009 kJ, Nutrient Profiling Score, NPS, −2), when compared with an iso-energetic higher-carbohydrate (CHO) cereal-based bar (HC-CB, 985 kJ, NPS +3). It also assessed the ability to suppress glucose response to a typical CHO-rich food (white bread, WB), when co-ingested. Ten overweight prediabetic Chinese adults (mean, sd: age 47⋅9, 15⋅7 years; BMI 25⋅5, 1⋅6 kg/m2), with total body fat plus ectopic pancreas and liver fat quantified using dual-energy X-ray absorptiometry and magnetic resonance imaging and spectroscopy, received the five meal treatments in random order: HP-NB, HC-CB, HP-NB + WB (50 g available CHO), HC-CB + WB and WB only. Compared with HC-CB, HP-NB induced a significantly lower 30–120 min glucose response (P < 0⋅05), with an approximately 10-fold lower incremental area under the glucose curve (iAUC0–120; P < 0⋅001). HP-NB also attenuated glucose response by approximately 25 % when co-ingested with WB (P < 0⋅05). Half of the cohort had elevated pancreas and/or liver fat, with 13–21 % greater suppression of iAUC0–120 glucose in the low v. high organ fat subgroups across all five treatments. A nut-based snack product may be a healthier alternative to an energy equivalent cereal-based product with evidence of both a lower postprandial glycaemic response and modulation of CHO-induced hyperglycaemia even in high-risk, overweight, pre-diabetic adults.

The present study aimed to investigate the association of the Chinese visceral adiposity index (CVAI) and its 6-year change with hypertension risk and compare the ability of CVAI and other obesity indices to predict hypertension based on the Rural Chinese Cohort Study. Study participants were randomly recruited by a cluster sampling procedure, and 10 304 participants ≥18 years were included. Modified Poisson regression was used to derive adjusted relative risks (RR) and 95 % CI. We identified 2072 hypertension cases during a median of 6·03 years of follow-up. The RR for the highest v. lowest CVAI quartile were 1·29 (95 % CI 1·05, 1·59) for men and 1·53 (95 % CI 1·22, 1·91) for women. Per-sd increase in CVAI was associated with hypertension for both men (RR 1·09, 95 % CI 1·02, 1·16) and women (RR 1·14, 95 % CI 1·06, 1·22). Also, the area under the receiver operating characteristic curve value for hypertension was higher for CVAI than the four other obesity indices for both sexes (all P < 0·05). Finally, per-sd increase in CVAI change was associated with hypertension for both men (RR 1·26, 95 % CI 1·16, 1·36) and women (RR 1·23, 95 % CI 1·15, 1·30). Similar results were observed in sensitivity analyses. CVAI and its 6-year change are positively associated with hypertension risk. CVAI has better performance in predicting hypertension than other visceral obesity indices for both sexes. The current findings suggest CVAI as a reliable and applicable predictor of hypertension in rural Chinese adults.

Sugar-sweetened beverage (SSB) consumption has been associated with visceral fat partitioning in adults; however, the underlying mechanisms in childhood remain unclear and warrant exploration. This cross-sectional study aimed to investigate the association between SSB consumption and body fat in children aged 9–13 years and the potential modifying effect of children’s sex and serum cortisol levels. A sample of 2665 Greek schoolchildren participated in the ‘Healthy Growth Study’, and anthropometric, body composition, dietary intake and serum cortisol data were assessed. SSB consumption was defined as low (<1 serving/d), medium (1–2 servings/d) or high (>2 servings/d). We used linear regression models to assess the association between SSB consumption and measures of adiposity and to assess effect modification; models were stratified by sex and tertiles of morning serum cortisol. A significant positive association was observed between high SSB consumption and visceral adipose tissue (VAT) (β = 1·4, 95 % CI 0·4, 2·3, P = 0·01) but not BMI or BMI z-score. When stratified by sex, the association was observed in boys (β = 1·8, 95 % CI 0·3, 3·4, P = 0·02) but not in girls. When stratified by cortisol levels, SSB consumption was associated with VAT in children with cortisol levels in the lowest tertile (β = 2·8, 95 % CI 1·0, 4·6, P < 0·01). These results indicate that increased SSB consumption is associated with visceral adiposity in schoolchildren and this association may be modified by sex and morning serum cortisol. To prevent VAT accumulation and concomitant disease risk, dietary interventions should target SSB consumption during childhood.

Subcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.

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.

Although the first description of a syndrome defined by the co-existence of atherogenic and diabetogenic metabolic abnormalities is debated in the literature, it was Gerald Reaven who proposed, in his landmark 1988 Banting award lecture, that a significant proportion of individuals (with diabetes or not) were characterised by insulin resistance causing prejudice to cardiovascular health. However, Reaven was influenced by seminal observations made more than 50 years earlier by Himsworth who proposed that there were two forms of diabetes (insulin resistant v. insulin sensitive). Reaven went further in proposing the theory that insulin resistance was the most prevalent cause of CVD associated with metabolic abnormalities that he named syndrome X. Because there was a syndrome X documented in cardiology, the term evolved to insulin resistance syndrome. As Reaven could also find insulin-resistant individuals in non-obese subjects, he did not include obesity as a feature of syndrome X. Imaging studies then revealed that excess adipose tissue in the abdominal cavity, a condition described as visceral obesity, was the form of overweight/obesity associated with insulin resistance and its related abnormalities. As obesity risk assessment and management remain largely based on body weight (BMI) and weight loss, it is proposed that our clinical approaches and public health messages should be revisited. First, patients should be educated about the importance of monitoring their waistline as a crude index of abdominal adiposity. Secondly, public health approaches focussing on ‘lifestyle vital signs’ including achieving healthy waistlines rather than healthy body weights should be developed.

Type 2 diabetes (T2D) is a global public health priority, particularly for populations of black African-Caribbean ethnicity, who suffer disproportionately high rates of the disease. While the mechanisms underlying the development of T2D are well documented, there is growing evidence describing distinctions among black African-Caribbean populations. In the present paper, we review the evidence describing the impact of black African-Caribbean ethnicity on T2D pathophysiology. Ethnic differences were first recognised through evidence that metabolic syndrome diagnostic criteria fail to detect T2D risk in black populations due to less central obesity and dyslipidaemia. Subsequently more detailed investigations have recognised other mechanistic differences, particularly lower visceral and hepatic fat accumulation and a distinctly hyperinsulinaemic response to glucose stimulation. While epidemiological studies have reported exaggerated insulin resistance in black populations, more detailed and direct measures of insulin sensitivity have provided evidence that insulin sensitivity is not markedly different to other ethnic groups and does not explain the hyperinsulinaemia that is exhibited. These findings lead us to hypothesise that ectopic fat does not play a pivotal role in driving insulin resistance in black populations. Furthermore, we hypothesise that hyperinsulinaemia is driven by lower rates of hepatic insulin clearance rather than heightened insulin resistance and is a primary defect rather than occurring in compensation for insulin resistance. These hypotheses are being investigated in our ongoing South London Diabetes and Ethnicity Phenotyping study, which will enable a more detailed understanding of ethnic distinctions in the pathophysiology of T2D between men of black African and white European ethnicity.

High overall nutritional quality (NQ) is an important component of ideal cardiovascular health, a concept introduced in 2010 by the American Heart Association. However, data on the independent contribution of overall NQ to the variation in the cardiometabolic risk (CMR) profile are limited. This observational study aimed to investigate the association between overall NQ and the CMR profile in 4785 participants (65⋅4 % of men, age 43⋅3 (sd 10⋅8) years) who underwent a cardiometabolic health evaluation, including lifestyle habits, anthropometric measurements, blood pressure, lipid profile and HbA1c concentrations. In addition, a submaximal exercise test was conducted to assess cardiorespiratory fitness (CRF). Using a standardised NQ questionnaire (twenty-five items food-based questionnaire), participants were classified into three subgroups: (1) low, (2) moderate or (3) high NQ and variance and multiple linear regression analyses were performed. Results showed that less than 15 % of participants presented a high NQ. A high NQ was associated with a healthier lifestyle habits and a more favourable CMR profile (lower values of waist circumference and cholesterol:HDL-cholesterol ratio, lower concentrations of non-HDL-cholesterol, TAG and HbA1c). Some of these associations were independent of age, physical activity level (PAL) and CRF. A better NQ was also associated with a lower proportion of participants presenting the hypertriacylglycerolaemic waist phenotype independently of both PAL and CRF. The present study suggests that overall NQ can be assessed with a short food-based questionnaire and should be considered in clinical practice as a new ‘vital sign’ associated with other health behaviours and cardiometabolic health.

It has been established that ingestion of a high-fat diet increases the blood levels of lipopolysaccharides (LPS) from Gram-negative bacteria in the gut. Obesity is characterised by low-grade systemic and adipose tissue inflammation. This is suggested to be implicated in the metabolic syndrome and obesity. In the present review, we hypothesise that LPS directly and indirectly participates in the inflammatory reaction in adipose tissue during obesity. The experimental evidence shows that LPS is involved in the transition of macrophages from the M2 to the M1 phenotype. In addition, LPS inside adipocytes may activate caspase-4/5/11. This may induce a highly inflammatory type of programmed cell death (i.e. pyroptosis), which also occurs after infection with intracellular pathogens. Lipoproteins with or without LPS are taken up by adipocytes. Large adipocytes are more metabolically active and potentially more exposed to LPS than small adipocytes are. Thus, LPS might be involved in defining the adipocyte death size and the formation of crown-like structures. The adipocyte death size is reached when the intracellular concentration of LPS initiates pyroptosis. The mechanistic details remain to be elucidated, but the observations indicate that adipocytes are stimulated to cell death by processes that involve LPS from the gut microbiota. There is a complex interplay between the composition of the diet and microbiota. This influences the amount of LPS that is translocated from the gut. In particular, the lipid content of a meal may correlate with the amount of LPS built in to chylomicrons.

Androgen deprivation therapy (ADT) is used widely as part of a combined modality for the treatment of prostate cancer. However, ADT has also been associated with the development of cardiometabolic complications that can increase mortality from cardiovascular events. There is emerging evidence to suggest that ADT-related cardiometabolic risk can be mitigated by diet and lifestyle modification. While the clinical focus for a nutritional approach for achieving this effect is unclear, it may depend upon the timely assessment and targeting of dietary changes to the specific risk phenotype of the patient. The present review aims to address the metabolic origins of ADT-related cardiometabolic risk, existing evidence for the effects of dietary intervention in modifying this risk, and the priorities for future dietary strategies.

Faster eating rates are associated with increased energy intake, but little is known about the relationship between children’s eating rate, food intake and adiposity. We examined whether children who eat faster consume more energy and whether this is associated with higher weight status and adiposity. We hypothesised that eating rate mediates the relationship between child weight and ad libitum energy intake. Children (n 386) from the Growing Up in Singapore Towards Healthy Outcomes cohort participated in a video-recorded ad libitum lunch at 4·5 years to measure acute energy intake. Videos were coded for three eating-behaviours (bites, chews and swallows) to derive a measure of eating rate (g/min). BMI and anthropometric indices of adiposity were measured. A subset of children underwent MRI scanning (n 153) to measure abdominal subcutaneous and visceral adiposity. Children above/below the median eating rate were categorised as slower and faster eaters, and compared across body composition measures. There was a strong positive relationship between eating rate and energy intake (r 0·61, P<0·001) and a positive linear relationship between eating rate and children’s BMI status. Faster eaters consumed 75 % more energy content than slower eating children (Δ548 kJ (Δ131 kcal); 95 % CI 107·6, 154·4, P<0·001), and had higher whole-body (P<0·05) and subcutaneous abdominal adiposity (Δ118·3 cc; 95 % CI 24·0, 212·7, P=0·014). Mediation analysis showed that eating rate mediates the link between child weight and energy intake during a meal (b 13·59; 95 % CI 7·48, 21·83). Children who ate faster had higher energy intake, and this was associated with increased BMI z-score and adiposity.