Antioxidant biomarkers and cardiometabolic risk markers in an Aboriginal community in remote Australia: a cross-sectional study.

OBJECTIVE: High-quality diets, characterised by nutrient-rich foods, are one of the foundations for health and well-being. Indicators of diet quality, antioxidants, are associated with protection against cardiometabolic diseases. The current study explores relationships between plasma antioxidants and cardiometabolic risk among Aboriginal people in Australia. DESIGN: As part of a community-driven health promotion programme, we conducted a cross-sectional study including a health-behaviour questionnaire, plasma antioxidants and cardiometabolic risk markers (anthropometric, blood pressure measurements, fasting glucose, glycated Hb (HbA1c), lipids, C-reactive protein and albumin-creatinine-ratio) continuous and categorised into population-specific cut-offs. Antioxidants (ß-carotene, ß-cryptoxanthin, lycopene, lutein-zeaxanthin, retinol and α-tocopherol measured using HPLC) were applied to a principal component analysis, which aggregated these into a single component. Linear regression models were applied to investigate associations between the antioxidant component and cardiometabolic risk markers. SETTING: Community in a remote area in Northern Territory, Australia. PARTICIPANTS: A total of 324 Aboriginal people, mean age 35·5 (range 15-75) years. RESULTS: Antioxidant component levels were higher among individuals with higher self-reported vegetable intake (P < 0·01), higher among individuals with higher self-reported fruit intake (P = 0·05) and lower among current smokers (P = 0·06). Linear regression revealed an inverse association between the antioxidant component and C-reactive protein (ß = -0·01, P < 0·01) after adjusting for confounders. CONCLUSION: Higher plasma antioxidant levels, indicators of diet quality, were associated with lower levels of high-sensitivity C-reactive protein in this Aboriginal population in remote Australia. This association suggests plasma antioxidants may be protective against inflammation; however, longitudinal studies are needed to examine this potentially protective relationship.

Erratum: Higher glomerular filtration rate is related to insulin resistance but not to obesity in a predominantly obese non-diabetic cohort.

This corrects the article DOI: 10.1038/srep45522.

Higher glomerular filtration rate is related to insulin resistance but not to obesity in a predominantly obese non-diabetic cohort.

Glomerular hyperfiltration has been associated with obesity, insulin resistance, and systolic blood pressure (SBP). However, previous studies are limited by confounders such as pre-existing diabetes or hypertension, or have used indirect measures of adiposity and insulin sensitivity (IS). Therefore, we examined the relationship between estimated glomerular filtration rate (eGFR) and IS measured by the hyperinsulinaemic euglycaemic clamp in a healthy population on no medications. We performed oral glucose tolerance test (OGTT) and measured % body fat (DEXA), BMI, blood pressure and M-value (hyperinsulinaemic euglycaemic clamp) in 104 individuals (44 females and 60 males). The majority of the study population (n = 89, 85.6%) were classified on their BMI as overweight/obese. eGFR was related to age, BMI, M-value (IS), 2-hour glucose levels post OGTT and white blood cell count (WBC) (all p < 0.05); but not to SBP (p = 0.1) or fasting glucose levels (p = 0.2). After adjustment for gender, BMI, SBP and WBC, the inverse association between eGFR and M-value (p = 0.001), and 2-hour glucose post OGTT (p = 0.02) persisted. In conclusion, although eGFR has been associated with BMI and blood pressure in previous studies, in our healthy population, eGFR was more closely related to markers of glucose metabolism (IS and 2-hour glucose post OGTT) than to BMI and blood pressure.

Bisphenol A and the risk of cardiometabolic disorders: a systematic review with meta-analysis of the epidemiological evidence.

Bisphenol A (BPA) is suspected to be associated with several chronic metabolic diseases. The aim of the present study was to review the epidemiological literature on the relation between BPA exposure and the risk of cardiometabolic disorders. PubMed and Embase databases were searched up to August 2014 by two independent investigators using standardized subject terms. We included observational studies (cohort, case-control and cross-sectional studies) carried out in children or adults, measuring urinary BPA (uBPA), including at least 100 participants and published in English. The health outcomes of interest were diabetes, hyperglycemia, measures of anthropometry, cardiovascular disease (CVD) and hypertension. Data were extracted and meta-analyzed when feasible, using a random-effects model. Thirty-three studies with sample size ranging from 239 to 4811 met the inclusion criteria, including five with a prospective design. Twelve studies reported on diabetes or hyperglycemia, 16 on anthropometry, 6 on CVD and 3 on hypertension. Evidence for a positive association between uBPA concentrations and diabetes, overweight, obesity, elevated waist circumference (WC), CVD and hypertension was found in 7/8, 2/7, 6/7, 5/5, 4/5 and 2/3 of the cross-sectional studies, respectively. We were able to conduct outcome-specific meta-analyses including 12 studies. When comparing the highest vs. the lowest uBPA concentrations, the pooled ORs were 1.47 (95% CI: 1.21-1.80) for diabetes, 1.21 (95% CI: 0.98-1.50) for overweight, 1.67 (95% CI: 1.41-1.98) for obesity, 1.48 (95% CI: 1.25-1.76) for elevated WC, and 1.41 (95% CI: 1.12-1.79) for hypertension. Moreover, among the five prospective studies, 3 reported significant findings, relating BPA exposure to incident diabetes, incident coronary artery disease, and weight gain. To conclude, there is evidence from the large body of cross-sectional studies that individuals with higher uBPA concentrations are more likely to suffer from diabetes, general/abdominal obesity and hypertension than those with lower uBPA concentrations. Given the potential importance for public health, prospective cohort studies with proper adjustment for dietary characteristics and identification of critical windows of exposure are urgently needed to further improve knowledge about potential causal links between BPA exposure and the development of chronic disease.

Lower levels of high-density lipoprotein cholesterol in urban Africans presenting with communicable versus non-communicable forms of heart disease: the 'Heart of Soweto' hospital registry study.

OBJECTIVES: To investigate if urban Africans displayed lower levels of atheroprotective high-density lipoprotein cholesterol (HDLC) when presenting with communicable versus non-communicable forms of heart disease (HD) as both acute infection and chronic inflammation reduce HDLC levels. DESIGN: Hospital registry of 5328 de novo cases of HD over a 3-year period. SETTING: Cardiology Unit, Baragwanath Hospital in Soweto, South Africa. PARTICIPANTS: A total of 1199 patients of African descent (59% women; 57.0±13.4 years) had fasting blood lipid levels (total cholesterol (TC), triglyceride, HDLC and low-density lipoprotein cholesterol (LDLC)) documented on admission. Serum inflammatory marker C reactive protein (CRP) was measured in a subset of 367 patients (31% of cases). MAIN OUTCOME MEASURES: Lipid profiles were compared according to prespecified classification of non-communicable (eg, hypertensive HD) versus communicable (eg, rheumatic HD) HD. Low HDLC was defined as <1.0 mmol/L for men and <1.2 mmol/L for women, according to applicable South African Clinical Guidelines. RESULTS: Overall 694 (58%) of those presenting with HD had low HDLC levels; 344 of 678 (51%) and 350 of 521 (67%) for non-communicable and communicable, respectively (p<0.001). Comparatively, overall prevalence of high TC was 32% and high LDLC was 37%. On an adjusted basis, those with non-communicable HD were more likely to record a low HDLC relative to non-communicable presentations (odds ratio (OR) 1.91, 95% CI 1.42 to 2.57; p<0.001). There was a strong relationship between low HDLC and higher levels of CRP, but only in women. CONCLUSIONS: Despite largely favourable lipid profiles, there are clear differences according to aetiology of underlying HD in urban Africans, with younger patients with communicable HD having particularly low levels of HDLC. Appropriate prospective evidence is needed to determine if persistent low levels of HDLC expose patients to increased, long-term risk of atherosclerotic forms of HD. The women-only inverse association between HDLC and CRP warrants further investigation.

Evidence for low high-density lipoprotein cholesterol levels in Australian indigenous peoples: a systematic review.

BACKGROUND: Low plasma high-density lipoprotein cholesterol (HDL-C) levels are a strong, independent, but poorly understood risk factor for cardiovascular disease (CVD). Although this atherogenic lipid abnormality has been widely reported in Australia's Indigenous peoples, Aboriginal and Torres Strait Islanders, the evidence has not come under systematic review. This review therefore examines published data for Indigenous Australians reporting 1) mean HDL-C levels for both sexes and 2) factors associated with low HDL-C. METHODS: PubMed, Medline and Informit ATSI Health databases were systematically searched between 1950 and 2012 for studies on Indigenous Australians reporting mean HDL-C levels in both sexes. Retrieved studies were evaluated by standard criteria. Low HDL-C was defined as: <1.0 mmol/L. Analyses of primary data associating measures of HDL-C with other CVD risk factors were also performed. RESULTS: Fifteen of 93 retrieved studies were identified for inclusion. These provided 58 mean HDL-C levels; 29 for each sex, most obtained in rural/regional (20%) or remote settings (60%) and including 51-1641 participants. For Australian Aborigines, mean HDL-C values ranged between 0.81-1.50 mmol/L in females and 0.76-1.60 mmol/L in males. Two of 15 studies reported HDL-C levels for Torres Strait Islander populations, mean HDL-C: 1.00 or 1.11 mmol/L for females and 1.01 or 1.13 mmol/L for males. Low HDL-C was observed only in rural/regional and remote settings--not in national or urban studies (n = 3) in either gender. Diabetes prevalence, mean/median waist-to-hip ratio and circulating C-reactive protein levels were negatively associated with HDL-C levels (all P < 0.05). Thirty-four per cent of studies reported lower mean HDL-C levels in females than in males. CONCLUSIONS: Very low mean HDL-C levels are common in Australian Indigenous populations living in rural and remote communities. Inverse associations between HDL-C and central obesity, diabetes prevalence and inflammatory markers suggest a particularly adverse CVD risk factor profile. An absence of sex dichotomy in HDL-C levels warrants further investigation.

Advanced glycation end products (AGEs) are cross-sectionally associated with insulin secretion in healthy subjects.

It has been postulated that chronic exposure to high levels of advanced glycation end products (AGEs), in particular from dietary sources, can impair insulin secretion. In the present study, we investigated the cross-sectional relationship between AGEs and acute insulin secretion during an intravenous glucose tolerance test (IVGTT) and following a 75 g oral glucose tolerance test (OGTT) in healthy humans. We report the cross-sectional association between circulating AGE concentrations and insulin secretory function in healthy humans (17 F: 27 M, aged 30 ± 10 years) with a wide range of BMI (24.6-31.0 kg/m(2)). Higher circulating concentrations of AGEs were related to increased first phase insulin secretion during IVGTT (r = 0.43; p < 0.05) and lower 2-h glucose concentrations during OGTT (r = -0.31; p < 0.05). In addition, fasting (r = -0.36; p < 0.05) and 2-h glucose concentrations were negatively related to circulating levels of soluble receptor for AGE (RAGE) isoforms (r = -0.39; p < 0.01). In conclusion, in healthy humans, we show a cross-sectional association between advanced glycation end products and acute insulin secretion during glucose tolerance testing.

Plasma advanced glycation end products (AGEs) and NF-κB activity are independent determinants of diastolic and pulse pressure.

BACKGROUND: High levels of circulating advanced glycation end products (AGEs) can initiate chronic low-grade activation of the immune system (CLAIS) with each of these factors independently associated with cardiovascular (CV) morbidity and mortality. Therefore, our objective was to characterize the relationship between serum AGEs, CLAIS and other risk factors for CV disease in normotensive non-diabetic individuals. METHODS: We measured body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, lipid and glucose profile in 44 non-diabetic volunteers (17 female, 27 males). Carboxymethyl-lysine (CML) was measured by ELISA as a marker for circulating AGEs and NF-κB p65 activity as an inflammatory marker by DNA-binding in peripheral blood mononuclear cells lysates (PBMC). RESULTS: Plasma CML concentrations were related to diastolic blood pressure (r=-0.51, p<0.01) independently of age, sex, BMI and WHR (p<0.05). Diastolic blood pressure was also related to NF-κB activity in PBMC (r=0.47, p<0.01) before and after adjustment for age, sex, BMI and WHR (p<0.05). Plasma CML concentrations were related to the pulse pressure before (r=0.42; p<0.05) and after adjustment for age, sex, BMI and waist (p<0.05). Neither CML nor NF-κB activity were related to systolic blood pressure (both p=ns). Plasma CML concentrations were not associated with plasma lipid or glucose concentrations (all p=ns). CONCLUSIONS: Plasma AGE levels and NF-κB activity in PBMC were independent determinants of diastolic and pulse pressure in healthy normotensive individuals. This association suggests a role for AGEs in the etiology of hypertension, possibly via the initiation of CLAIS and aortic stiffening.

Different lipid profiles according to ethnicity in the Heart of Soweto study cohort of de novo presentations of heart disease.

BACKGROUND: Historically, sub-Saharan Africa has reported low levels of atherosclerotic cardiovascular disease (CVD). However as these populations undergo epidemiological transition, this may change. METHODS: This was an observational cohort study performed at Chris Hani Baragwanath Hospital in Soweto, South Africa. As part of the Heart of Soweto study, a clinical registry captured detailed clinical data on all de novo cases of structural and functional heart disease presenting to the Cardiology unit during the period 2006 to 2008. We examined fasting lipid profiles in 2 182 patients (of 5 328 total cases) according to self-reported ethnicity. The study cohort comprised 1 823 patients of African descent (61% female, aged 56 ± 16 years), 142 white Europeans (36% female, aged 57 ± 13 years), 133 Indians (51% female, aged 59 ± 12 years) and 87 of mixed ancestry (40% female, aged 56 ± 12 years). RESULTS: Consistent with different patterns in heart disease aetiology, there were clear differences in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides across ethnicities (p < 0.001): patients of African descent had the lowest TC and LDL-C levels and Indians the highest. However, there were no significant differences in high-density lipoprotein cholesterol (HDL-C) levels between ethnicities (p = 0.20). Adjusting for age, gender and body mass index, patients of African descent were significantly less likely to record a TC of > 4.5 mmol/l (OR 0.33, 95% CI: 0.25-0.41) compared to all ethnic groups (all p < 0.001). CONCLUSIONS: These data confirm important blood lipid differentials according to ethnicity in patients diagnosed with heart disease in Soweto, South Africa. Such disparities in CVD risk factors may justify the use of specialised prevention and management protocols.

c-Jun NH2-terminal kinase activity in subcutaneous adipose tissue but not nuclear factor-kappaB activity in peripheral blood mononuclear cells is an independent determinant of insulin resistance in healthy individuals.

OBJECTIVE: Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK) pathways-two pathways proposed as the link between CLAIS and insulin resistance. RESEARCH DESIGN AND METHODS: Adiposity (dual-energy X-ray absorptiometry), waist-to-hip ratio (WHR), and insulin sensitivity (M, hyperinsulinemic-euglycemic clamp) were measured in 22 healthy nondiabetic volunteers (aged 29 +/- 11 years, body fat 28 +/- 11%). NF-kappaB activity (DNA-binding assay) and JNK1/2 activity (phosphorylated JNK) were assessed in biopsies of the vastus lateralis muscle and subcutaneous adipose tissue and in peripheral blood mononuclear cell (PBMC) lysates. RESULTS: NF-kappaB activities in PBMCs and muscle were positively associated with WHR after adjustment for age, sex, and percent body fat (both P < 0.05). NF-kappaB activity in PBMCs was inversely associated with M after adjustment for age, sex, percent body fat, and WHR (P = 0.02) and explained 16% of the variance of M. There were no significant relationships between NF-kappaB activity and M in muscle or adipose tissue (both NS). Adipose-derived JNK1/2 activity was not associated with obesity (all P> 0.1), although it was inversely related to M (r = -0.54, P < 0.05) and explained 29% of its variance. When both NF-kappaB and JNK1/2 were examined statistically, only JNK1/2 activity in adipose tissue was a significant determinant of insulin resistance (P = 0.02). CONCLUSIONS: JNK1/2 activity in adipose tissue but not NF-kappaB activity in PBMCs is an independent determinant of insulin resistance in healthy individuals.