Associations of fruit intake with adiposity and cardiometabolic biomarkers in UK Biobank.

BACKGROUND: Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress. METHODS: The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake. RESULTS: Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations. CONCLUSIONS: We observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.

Associations between dietary patterns and incident colorectal cancer in 114,443 individuals from the UK Biobank: a prospective cohort study.

BACKGROUND: Diet-disease association studies increasingly use dietary patterns (DPs) to account for the complexity of the exposure. We assessed if a DP associated with type 2 diabetes mellitus, CVD, and all-cause mortality is also associated with colorectal cancer (CRC). METHODS: We used reduced rank regression on 24-h recall data to identify DPs explaining the maximum variation in four nutrient-response variables: energy density, saturated fatty acids, free sugars and fibre density. Cox-proportional hazards models examined prospective associations between DP adherence (coded in a continuous scale as z-scores as well as in quintiles) and incident CRC. Subgroup analyses were conducted for tumour site, age, and sex. RESULTS: Post-exclusions, 1,089 CRC cases occurred in 114,443 participants over a median follow-up of 8.0 years. DP1 was characterised by increased intake of chocolate and confectionery, butter, low-fibre bread, red and processed meats and alcohol, as well as low fruit, vegetable, and high-fibre cereal intake. After accounting for confounders, including body mass, there were positive linear associations between DP1 and incident overall CRC (HR of quintile 5 vs. 1: 1.34, 95%CI 1.16-1.53, PTrend=0.005) and rectal cancer (HR of quintile 5 vs. 1: 1.58, 95%CI 1.27-1.96, PTrend=0.009), but not for proximal or distal colon cancers. No DP2-CRC association was observed. CONCLUSION: A DP previously associated with cardio-metabolic disease is also associated with incident CRC, especially rectal cancers. IMPACT: These consistent associations of particular food groups with both cardiometabolic disease and this diet-related cancer strengthen the evidence base for holistic population dietary guidelines to prevent ill-health.

Body fat distribution and bone mineral density in a multi-ethnic sample of postmenopausal women in The Malaysian Cohort.

In this study of postmenopausal women in Malaysia, total adiposity was inversely associated with total BMD, while regional associations varied. No differences were detected across Malay, Chinese, and Indian ethnicities. Low BMD contributes substantially to morbidity and mortality, and increasing adiposity levels globally may be contributing to this. PURPOSE: To investigate associations of total and regional adiposity with bone mineral density (BMD) among a multi-ethnic cohort of postmenopausal women. METHODS: Dual X-ray absorptiometry (DXA) imaging was undertaken for 1990 postmenopausal women without prior chronic diseases (30% Malay, 53% Chinese, and 17% Indian) from The Malaysian Cohort (TMC). The strength of the associations between standardized total and regional body fat percentages with total and regional BMD was examined using linear regression models adjusted for age, height, lean mass, ethnicity, education, and diabetes. Effect modification was assessed for ethnicity. RESULTS: Women with a higher total body fat percentage were more likely to be Indian or Malay. Mean (SD) BMD for the whole-body total, lumbar spine, leg, and arm were 1.08 (0.11), 0.96 (0.15), 2.21 (0.22), and 1.36 (0.12) g/cm2, respectively. Total body and visceral fat percentage were inversely associated with total BMD (- 0.02 [95% CI - 0.03, - 0.01] and - 0.01 [- 0.02, - 0.006] g/cm2 per 1 SD, respectively). In contrast, subcutaneous and gynoid fat percentages were positively associated with BMD (0.007 [0.002, 0.01] and 0.01 [0.006, 0.02] g/cm2, respectively). Total body fat percentage showed a weak positive association with lumbar BMD (0.01 [0.004, 0.02]) and inverse associations with leg (- 0.04 [- 0.06, - 0.03]) and arm (- 0.02 [- 0.03, - 0.02]) BMD in the highest four quintiles. There was no effect modification by ethnicity (phetero > 0.05). CONCLUSION: Total adiposity was inversely associated with total BMD, although regional associations varied. There was no heterogeneity across ethnic groups suggesting adiposity may be a risk factor for low BMD across diverse populations.

Linking haploinsufficiency of the autism- and schizophrenia-associated gene Cyfip1 with striatal-limbic-cortical network dysfunction and cognitive inflexibility.

Impaired behavioural flexibility is a core feature of neuropsychiatric disorders and is associated with underlying dysfunction of fronto-striatal circuitry. Reduced dosage of Cyfip1 is a risk factor for neuropsychiatric disorder, as evidenced by its involvement in the 15q11.2 (BP1-BP2) copy number variant: deletion carriers are haploinsufficient for CYFIP1 and exhibit a two- to four-fold increased risk of schizophrenia, autism and/or intellectual disability. Here, we model the contributions of Cyfip1 to behavioural flexibility and related fronto-striatal neural network function using a recently developed haploinsufficient, heterozygous knockout rat line. Using multi-site local field potential (LFP) recordings during resting state, we show that Cyfip1 heterozygous rats (Cyfip1+/-) harbor disrupted network activity spanning medial prefrontal cortex, hippocampal CA1 and ventral striatum. In particular, Cyfip1+/- rats showed reduced influence of nucleus accumbens and increased dominance of prefrontal and hippocampal inputs, compared to wildtype controls. Adult Cyfip1+/- rats were able to learn a single cue-response association, yet unable to learn a conditional discrimination task that engages fronto-striatal interactions during flexible pairing of different levers and cue combinations. Together, these results implicate Cyfip1 in development or maintenance of cortico-limbic-striatal network integrity, further supporting the hypothesis that alterations in this circuitry contribute to behavioural inflexibility observed in neuropsychiatric diseases including schizophrenia and autism.

Associations of general and central adiposity with hypertension and cardiovascular disease among South Asian populations: a systematic review and meta-analysis.

BACKGROUND: The relevance of measures of general and central adiposity for cardiovascular disease (CVD) risks in populations of European descent is well established. However, it is less well characterised in South Asian populations, who characteristically manifest larger waist circumferences (WC) for equivalent body mass index (BMI). This systematic review and meta-analysis provide an overview of the literature on the association of different anthropometric measures with CVD risk among South Asians. METHODOLOGY: MEDLINE and Embase were searched from 1990 to the present for studies in South Asian populations investigating associations of two or more adiposity measures with CVD. Random-effects meta-analyses were conducted on the associations of BMI, WC and waist-to-hip ratio (WHR) with blood pressure, hypertension and CVD. Quality assessment was performed using the Newcastle-Ottawa scale. RESULTS: Titles and abstracts were screened for 7327 studies, yielding 147 full-text reviews. The final sample (n=30) included 2 prospective, 5 case-control and 23 cross-sectional studies. Studies reported generally higher risks of hypertension and CVD at higher adiposity levels. The pooled mean difference in systolic blood pressure (SBP) per 5 kg/m2 higher BMI was 3 mmHg (2.90 (95% CI 1.30 to 4.50)) and 6 mmHg (6.31 (95% CI 4.81 to 7.81) per 13 cm larger WC. The odds ratio (OR) of hypertension per 5 kg/m2 higher BMI was 1.33 (95% CI 1.18 to 1.51), 1.45 (95% CI 1.05 to 1.98) per 13 cm larger WC and 1.22 (95% CI 1.04 to 1.41) per 0.1-unit larger WHR. Pooled risk of CVD for BMI-defined overweight versus healthy-weight was 1.65 (95% CI 1.55 to 1.75) and 1.48 (95% CI 1.21 to 1.80) and 2.51 (95% CI 0.94 to 6.69) for normal versus large WC and WHR, respectively. Study quality was average with significant heterogeneity. CONCLUSIONS: Measures of both general and central adiposity had similar, strong positive associations with the risk of CVD in South Asians. Larger prospective studies are required to clarify which measures of body composition are more informative for targeted CVD primary prevention in this population.