Elevated HDL-bound miR-181c-5p level is associated with diabetic vascular complications in Australian Aboriginal people.

AIMS/HYPOTHESIS: Diabetes is a major burden on Australia's Indigenous population, with high rates of disease and vascular complications. Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. MicroRNAs (miRNAs) are key players in the regulation of angiogenesis. HDL-cholesterol (HDL-c) levels are inversely associated with the risk of developing diabetic complications and HDL can carry miRNAs. HDL-miRNA profiles differ in disease states and may present as biomarkers with the capacity to act as bioactive signalling molecules. Recent studies have demonstrated that HDL becomes dysfunctional in a diabetic environment, losing its vasculo-protective effects and becoming more pro-atherogenic. We sought to determine whether HDL-associated miRNA profiles and HDL functionality were predictive of the severity of diabetic vascular complications in Australia's Indigenous population. METHODS: HDL was isolated from plasma samples from Indigenous participants without diabetes ('Healthy'), with type 2 diabetes mellitus ('T2DM') and with diabetes-associated macrovascular complications (specifically peripheral artery disease, 'T2DM+Comp'). To assess HDL angiogenic capacity, human coronary artery endothelial cells were treated with PBS, reconstituted HDL (rHDL, positive control) or isolated HDL and then exposed to high-glucose (25 mmol/l) conditions. The expression levels of two anti-angiogenic miRNAs (miR-181c-5p and miR-223-3p) and one pro-angiogenic miRNA (miR-27b-3p) were measured in the HDL fraction, plasma and treated human coronary artery endothelial cells by quantitative real-time PCR. In vitro endothelial tubule formation was assessed using the Matrigel tubulogenesis assay. RESULTS: Strikingly, we found that the levels of the anti-angiogenic miRNA miR-181c-5p were 14-fold higher (1454 ± 1346%) in the HDL from Aboriginal people with diabetic complications compared with both the Healthy (100 ± 121%, p < 0.05) and T2DM (82 ± 77%, p < 0.05) groups. Interestingly, we observed a positive correlation between HDL-associated miR-181c-5p levels and disease severity (p = 0.0020). Under high-glucose conditions, cells treated with rHDL, Healthy HDL and T2DM HDL had increased numbers of tubules (rHDL: 136 ± 8%, p < 0.01; Healthy HDL: 128 ± 6%, p < 0.01; T2DM HDL: 124 ± 5%, p < 0.05) and branch points (rHDL: 138 ± 8%, p < 0.001; Healthy HDL: 128 ± 6%, p < 0.01; T2DM HDL: 127 ± 5%, p < 0.01) concomitant with elevations in mRNA levels of the key hypoxia angiogenic transcription factor HIF1A (rHDL: 140 ± 10%, p < 0.01; Healthy HDL: 136 ± 8%, p < 0.01; T2DM HDL: 133 ± 9%, p < 0.05). However, this increase in angiogenic capacity was not observed in cells treated with T2DM + Comp HDL (tubule numbers: 113 ± 6%, p = 0.32; branch points: 113 ± 5%, p = 0.28; HIF1A: 117 ± 6%, p = 0.43), which could be attributed to the increase in cellular miR-181c-5p levels (T2DM + Comp HDL: 136 ± 7% vs PBS: 100 ± 9%, p < 0.05). CONCLUSIONS/INTERPRETATION: In conclusion, HDL from Aboriginal people with diabetic complications had reduced angiogenic capacity. This impairment is associated with an increase in the expression of anti-angiogenic miR-181c-5p. These findings provide the rationale for a new way to better inform clinical diagnosis of disease severity with the potential to incorporate targeted, personalised HDL-miRNA intervention therapies to prevent further development of, or to reverse, diabetic vascular complications in Australian Aboriginal people.

Assessment of the Intention to Use Mobile Health Applications Using a Technology Acceptance Model in an Israeli Adult Population.

Background: Mobile health applications (mHealth apps) have now gained global popularity. However, evaluating the level of their use over time still remains a pertinent challenge. According to the Technology Acceptance Model (TAM), perceived ease of use and usefulness predict attitudes toward technology utilization. Together, these factors serve as determinants of behavioral intention to use the technology, which in turn predicts actual use. Purpose: We sought to elucidate factors affecting behavioral intention to use mHealth apps in an Israeli adult population sample. Methods: A modified TAM Likert Scale questionnaire-based survey was offered to 200 participants, with 168 respondents. Results: Sixty one percent of participants reported using mHealth apps on their smartphones, 81% of whom used mHealth apps from health maintenance organization providers. Generation Y participants displayed more confidence with the use of mHealth apps, and were less concerned about compromising the confidentiality of their health records. Furthermore, answers to TAM-related questions among mHealth apps users were significantly more positive, compared with nonuser TAM components that accounted for 51% of the total variance in the intention to use mHealth apps. Discussion: TAM constructs were related to the behavioral intention to continue to use mHealth apps. Health organizations as providers of mHealth apps were strong determinants of their acceptance and utilization. Generational differences in user competence were observed; however, whether user experience or interface design represents the underlying differentials remains to be elucidated, and developers of health care-related mobile technologies will need to address this question.

High-Energy Diet and Shorter Light Exposure Drives Markers of Adipocyte Dysfunction in Visceral and Subcutaneous Adipose Depots of Psammomys obesus.

Dysfunctional adipose tissue phenotype underpins type 2 diabetes mellitus (T2DM) development. The disruption of circadian rhythms contributes to T2DM development. We investigated the effects of high-energy diet and photoperiod length on visceral and subcutaneous adipose tissue phenotype. Psammomys obesus sand rats exposed to neutral (12 light:12 dark) or short (5 light:19 dark) photoperiod were fed a low- (LE) or high- (HE) energy diet. The HE diet and/or short photoperiod reduced subcutaneous expression of adipocyte differentiation/function markers C/ebpα, Pparδ, Pparγ and Adipoq. Visceral Pparα levels were elevated in the 5:19HE group; however, the HE diet and/or short photoperiod decreased visceral Pparγ and Adipoq expression. 5:19HE animals had elevated Ucp1 yet lower Pgc-1α levels. The HE diet increased visceral Tgf-ß1, Ccl2 and Cd68 levels, suggestive of a pro-inflammatory state. Daily visceral rhythms of these genes were affected by a short photoperiod and/or HE diet. The 12:12HE, 5:19LE or 5:19HE animals had a higher proportion of larger adipocytes, indicating increased adipocyte hypertrophy. Collectively, the HE diet and/or shorter light exposure drives a dysfunctional adipose tissue phenotype. Daily rhythms are affected by a short photoperiod and HE diet in a site-specific manner. These findings provide mechanistic insight on the influence of disrupted circadian rhythms and HE diet on adipose tissue phenotype.

C-reactive protein concentrations are very high and more stable over time than the traditional vascular risk factors total cholesterol and systolic blood pressure in an Australian aboriginal cohort.

BACKGROUND: Stability of circulating high-sensitivity C-reactive protein (hsCRP) concentrations has implications for its utility in assessing cardiovascular disease (CVD) risk. We sought to determine hsCRP reproducibility in an indigenous Australian cohort with a view to use hsCRP as a marker of future CVD in community-based risk-factor screenings. METHODS: Seventy people living in a community on the northern coast of Australia participated in 2 risk-factor screenings over a median (interquartile range) follow-up time of 829 (814-1001) days. hsCRP was measured by high-sensitivity nephelometry. RESULTS: Geometric mean hsCRP concentrations at baseline and follow-up were 4.5 and 5.1 mg/L, respectively (P = 0.220), and Pearson product-moment correlation was 0.775. The proportion of people at high CVD risk (hsCRP >3.0 mg/L) at baseline was 67.1% and remained consistently high (68.6%) at follow-up. Linear regression analysis for follow-up hsCRP as a function of baseline hsCRP, sex, and differences in total and regional body fatness showed that baseline hsCRP was the single predictor in the model, accounting for 63.9% of the total variance in follow-up hsCRP (P(model) < 0.001). Prevalence agreement (95% CI) between baseline and follow-up for the hsCRP >3.0 mg/L category was 84% (73%-92%) (P(McNemar) = not significant), and kappa coefficient was fair (0.64, compared with 0.31 for systolic blood pressure > or =140 mmHg and 0.43 for total cholesterol > or =5.5 mmol/L). CONCLUSIONS: hsCRP concentrations remained consistently reproducible over time across a wide concentration range in an Aboriginal cohort. Correlations between concentrations over time were better than for other traditional CVD risk factors. hsCRP concentration has potential as a marker of future CVD risk.

Agreement between laboratory results and on-site pathology testing using Bayer DCA2000+ and Cholestech LDX point-of-care methods in remote Australian Aboriginal communities.

BACKGROUND: Indigenous Australians experience high risk of diabetes and cardiovascular disease. On-site pathology data can help identify those at risk. We sought to evaluate point-of-care (POC) analysers in remote Australian communities. METHODS: Results obtained from population screening (n=76-118) on the DCA2000+ and Cholestech LDX analysers were compared to laboratory measures. Results were compared using parametric and non-parametric statistical analyses, including the use of conventional cut-off values for pathology markers. RESULTS: Agreements (95% CI) between the two methods for categorising results according to the selected cut-off values ranged from 88% (77-94%) for HDL-C to 99% (92-100%) for glucose, and Kappa coefficients ranged from 0.668 for total cholesterol to 0.945 for glucose. Differences in median values were not clinically meaningful but were statistically significant (P<0.05) for urinary albumin (18.8 [inter-quartile range: 7.5-41.7] vs. 18.0 [5.5-43.2] mg/L), creatinine (12.1 [7.9-17.1] vs. 12.4 [8.1-17.0] mmol/L) and albumin:creatinine ratio (ACR; 1.66 [0.70-3.53] vs. 1.27 [0.46-3.03] mg/mmol), HDL cholesterol (HDL-C; 1.05 [0.95-1.25] vs. 1.00 [0.81-1.20] mmol/L), triglycerides (1.65 [1.12-2.19] vs. 1.49 [1.07-2.36] mmol/L) and glucose (5.2 [4.5-6.0] vs. 5.2 [4.7-5.8] mmol/L), respectively, for POC and laboratory methods. Median HbA1c (5.6% [5.3-6.0%] vs. 5.5% [5.3-6.1%]) and total cholesterol (4.4 [3.8-5.0] vs. 4.4 [3.8-5.1] mmol/L) did not differ significantly. Bland-Altman analyses showed statistically significant (but not clinically meaningful) variation in the measurement difference across analyte concentration for all measures except ACR and total cholesterol. CONCLUSION: POC instruments provided a reliable alternative to conventional laboratory methods for screening for chronic disease risk factors in locations remote from urban centres.

Leanness and type 2 diabetes in a population of indigenous Australians.

OBJECTIVE: To determine the prevalence of type 2 diabetes and its risk factors in a population of indigenous Australians. RESEARCH DESIGN AND METHODS: A cross-sectional study of 332 indigenous community residents aged 15 years and over with fasting blood samples and anthropometric measurements. RESULTS: Almost half of the study population (47.3%) was extremely lean (BMI<22 kg/m(2)). Leanness was particularly pronounced in the youngest age group (15<20 years), 78% of which had a BMI<22 kg/m(2). The prevalence of diabetes was 12%. It was highest in those 45-54 years and declined in older aged people. No cases of diabetes were detected in those aged less than 30 years. Diabetes prevalence was strongly linked to BMI and age (age-adjusted odds ratio=24.1, 95% CI 6.0-96.5, p<0.001) for BMI>or=25 kg/m(2) versus BMI<22 kg/m(2). Those with the lowest diabetes risk profile are lean (BMI<22 kg/m(2)) and/or young (age 15-34 years). CONCLUSIONS: These results highlight that strategies to prevent or delay the onset of diabetes should focus on the maintenance of leanness from adolescence and throughout adult life whilst young people are still in the process of forming lifelong habits.

Contamination in HPLC quantified benzaldehyde is from polypropylene microtubes.

Semicarbazide-sensitive amine oxidase (SSAO; EC 1.4.3.6) is a copper-containing enzyme predominantly expressed by vascular smooth muscle cells. SSAO deaminates primary amines to produce aldehydes and oxygen peroxides, and may thus play a role in vascular damage. SSAO activity can be quantified by assaying benzaldehyde production using fluorescent derivatisation and separation by HPLC. We performed the derivatisation step in polypropylene or borosilicate glass tubes over 45 min at 95 degrees C. High and obstructing background levels of benzaldehyde were found in one batch of polypropylene vials, as opposed to its alternatives. Treatment and handling of product shipment into the country did not account for introduction of contaminant into packaged vials nor did any reagent used in the assay. We conclude that the source of contamination was most likely due to variation in the commercial production process. Use of borosilicate vials for assays based on aldehyde production and derivatisation is recommended.

Low high-density lipoprotein-cholesterol is the most prevalent metabolic abnormality for Australian Aboriginal men and women even when lean.

BACKGROUND: The aim of this study was to investigate the relationship of the prevalence and risk of the metabolic syndrome to body mass index (BMI) in Australian Aboriginal people. DESIGN: It was a cross-sectional, secondary analysis of data obtained from population-based screenings in Aboriginal communities in central and northern Australia (913 participants recruited between 1993 and 1997). RESULTS: Forty-one percent of men and 48% of women conformed to the National Cholesterol Education Program definition for the metabolic syndrome (chi2=3.72, P=0.054). The prevalence of low high-density lipoprotein-cholesterol was high in all BMI categories (89 and 95% in men and women, respectively). The prevalence of all other metabolic abnormalities increased linearly with BMI. CONCLUSION: The metabolic syndrome is highly prevalent in Aboriginal communities and is strongly associated with BMI. Low high-density lipoprotein-cholesterol was the predominant component of the metabolic syndrome across sex groups and BMI strata.