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BackgroundThe chronic care model was proven effective in improving clinical outcomes of diabetes in developed countries. However, evidence in developing countries is scarce. The objective of this study was to evaluate the effectiveness of EMPOWER-PAR intervention (based on the chronic care model) in improving clinical outcomes for type 2 diabetes mellitus using readily available resources in the Malaysian public primary care setting.MethodsThis was a pragmatic, cluster-randomised, parallel, matched pair, controlled trial using participatory action research approach, conducted in 10 public primary care clinics in Malaysia. Five clinics were randomly selected to provide the EMPOWER-PAR intervention for 1 year and another five clinics continued with usual care. Patients who fulfilled the criteria were recruited over a 2-week period by each clinic. The obligatory intervention components were designed based on four elements of the chronic care model i.e. healthcare organisation, delivery system design, self-management support and decision support. The primary outcome was the change in the proportion of patients achieving HbA1c < 6.5%. Secondary outcomes were the change in proportion of patients achieving targets for blood pressure, lipid profile, body mass index and waist circumference. Intention to treat analysis was performed for all outcome measures. A generalised estimating equation method was used to account for baseline differences and clustering effect.ResultsA total of 888 type 2 diabetes mellitus patients were recruited at baseline (intervention: 471 vs. control: 417). At 1-year, 96.6 and 97.8% of patients in the intervention and control groups completed the study, respectively. The baseline demographic and clinical characteristics of both groups were comparable. The change in the proportion of patients achieving HbA1c target was significantly higher in the intervention compared to the control group (intervention: 3.0% vs. control: −4.1%, P < 0.002). Patients who received the EMPOWER-PAR intervention were twice more likely to achieve HbA1c target compared to those in the control group (adjusted OR 2.16, 95% CI 1.34–3.50, P < 0.002). However, there was no significant improvement found in the secondary outcomes.ConclusionsThis study demonstrates that the EMPOWER-PAR intervention was effective in improving the primary outcome for type 2 diabetes in the Malaysian public primary care setting.Trial registrationRegistered with: ClinicalTrials.gov.: NCT01545401. Date of registration: 1st March 2012. Electronic supplementary materialThe online version of this article (doi:10.1186/s12875-016-0557-1) contains supplementary material, which is available to authorized users.

Objectives To evaluate the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2-I) dapagliflozin on endothelial function in patients with high-risk type 2 diabetes mellitus (T2DM). Methods This was a prospective, double-blind, randomized, placebo-controlled, clinical trial of patients with T2DM with underlying ischemic heart disease who were receiving metformin and insulin therapy (n = 81). After 12-weeks of additional therapy with either dapagliflozin (n = 40) or placebo (n = 41), systemic endothelial function was evaluated by change in flow-mediated dilation (ΔFMD), change in nitroglycerin-mediated dilation (ΔNMD) and surrogate markers including intercellular adhesion molecule 1 (ICAM-1), endothelial nitric oxide synthase (eNOS), high-sensitivity C-reactive protein (hs-CRP), and lipoprotein(a) (Lp[a]). Glycemic and lipid profiles were also measured. Results The dapagliflozin group demonstrated significant reductions of hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) compared to the placebo group (ΔHbA1c –0.83 ± 1.47% vs –0.16 ± 1.25%, P = 0.042 and ΔFBG vs –0.73 ± 4.55 mmol/L vs –1.90 ± 4.40 mmol/L, P = 0.015, respectively). The placebo group showed worsening of ΔFMD while the dapagliflozin group maintained similar measurements pre- and posttherapy (P = not significant). There was a reduction in ICAM-1 levels in the dapagliflozin group (–83.9 ± 205.9 ng/mL, P &lt; 0.02), which remained unchanged in the placebo group (–11.0 ± 169.1 ng/mL, P = 0.699). Univariate correlation analysis revealed a significant negative correlation between HbA1c and ΔFMD within the active group. Conclusion A 12-week therapy with dapagliflozin, in addition to insulin and metformin therapies, in high-risk patients resulted in significant reductions in HbA1c, FBG, and surrogate markers of the endothelial function. Although the dapagliflozin group demonstrated a significant association between reduction in HbA1c and improvement in FMD, there was no significant difference in FMD between the 2 groups.

Background: Autosomal dominant hypercholesterolaemia (ADH) is a genetic disorder that is mainly resulted from defects in the lowdensity lipoprotein receptor (LDLR) and apolipoprotein B-100 (APOB-100) genes. Few studies of familial hypercholesterolaemia (FH) have been conducted in Malaysia, that makes the underlying main defect remains not well understood.Objectives: This study was aimed to describe the molecular aspects of FH among Malaysian subjects. Methods and Findings:We studied a group of 74 familial hypercholesterolaemic patients and 77 healthy control subjects. The promoter region and the 18 exons of the low-density lipoprotein receptor gene were screened by denaturing high-performance liquid chromatography (DHPLC) to detect small deletions, insertions and nucleotide substitutions, while DNA sequencing was applied to look for gene variants in amplicons of exon 26 and 29 in the APOB-100 gene. A total of five gene sequence variants in the LDLR gene were reported in 54.1% of the studied patients. P.Arg471Arg variant has the highest frequency of 20.3% among the study subjects. One intronic mutation (c.313+1G>A) and one missense mutation (p.Arg 385Try) were found to be pathogenic, while the other three variants were reported to be non-pathogenic by the in silico analyses. Nine variants were reported in the APOB-100 gene among familial hypercholesterolaemic patients with a non-significant difference in their frequency from the control subjects.

Tropical indigenous peoples in Asia (TIA) attract much attention for their unique appearance, while their genetic history and adaptive evolution remain mysteries. We conducted a comprehensive study to characterize the genetic distinction and connection of broad geographical TIAs. Despite the diverse genetic makeup and large inter-area genetic differentiation between the TIA groups, we identified a basal Asian ancestry (bASN) specifically shared by these populations. The bASN ancestry was relatively enriched in ancient Asian human genomes dated as early as ∼50,000 years before the present, and diminished in more recent history. Notably, the bASN ancestry is unlikely to be derived from archaic hominins. Instead, we suggest it may be better modeled as a survived lineage of the initial peopling of Asia. Shared adaptations inherited from the ancient Asian ancestry were detected among the TIA groups (e.g., LIMS1 for hair morphology, and COL24A1 for bone formation), and they are enriched in neurological functions either at an identical locus (e.g., NKAIN3), or different loci in an identical gene (e.g., TENM4). The bASN ancestry could also have formed the substrate of the genetic architecture of the dark pigmentation observed in the TIA peoples. We hypothesize that phenotypic convergence of the dark pigmentation in TIAs could have resulted from parallel (e.g., DDB1/DAK) or genetic convergence driven by admixture (e.g., MTHFD1 and RAD18), new mutations (e.g., STK11), or notably purifying selection (e.g., MC1R). Our results provide new insights into the initial peopling of Asia and an advanced understanding of the phenotypic convergence of the TIA peoples.

Abstract-Aim:This study is designed to investigate the effects of tocotrienol-tocopherol mixed fraction (TTMF), vitamin C and combined TTMF-vitamin C supplementations on serum lipids and biochemical markers of inflammation and endothelial activation in hypercholesterolemic subjects in the low-risk category. Materials and Methods: 78 hypercholesterolaemic subjects (total cholesterol of  5.2 mmol/L and low-density lipoprotein 3.4 -4.9 mmol/L) in the low cardiovascular risk category according to the NCEP-ATP3 criteria were recruited. They were randomized into four treatment combination groups for a period of twelve months; (1) receiving TTMF and vitamin C, (2) receiving TTMF and placebo, (3) receiving vitamin C and placebo, and (4) receiving placebo for both. Serum fasting lipid profiles and levels of high-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor-, intercellular adhesion molecule, vascular cell adhesion molecule, E-selectin and homocysteine were measured at entry and multiple time points post-randomisation. Results: There were no significant differences in percentage changes of lipid profiles and inflammatory markers between treated and placebo groups for either single or combined antioxidants supplementations. Conclusion: TTMF, vitamin C and combined TTMF-vitamin C supplementations have neutral effects on lipid profiles and biochemical markers of inflammation and endothelial activation in low risk subjects, suggesting that they offer no added advantage in the low cardiovascular risk group.

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