Aim
To study prospectively the ethnic‐specific risks of cardiovascular disease, end‐stage renal disease and all‐cause mortality in patients with Type 2 diabetes mellitus among native Asian ...subpopulations.
Methods
A total of 2337 subjects with Type 2 diabetes (70% Chinese, 17% Malay and 13% Asian Indian) were followed for a median of 4.0 years. Time‐to‐event analysis was used to study the association of ethnicity with adverse outcomes.
Results
Age‐ and gender‐adjusted hazard ratios for cardiovascular disease in ethnic Malay and Asian Indian subjects were 2.01 (1.40–2.88; P<0.0001) and 1.60 (1.07–2.41; P=0.022) as compared with Chinese subjects. Adjustment for conventional cardiovascular disease risk factors, including HbA1c, blood pressure and lipid profile, slightly attenuated the hazards in Malay (1.82, 1.23–2.71; P=0.003) and Asian Indian subjects (1.47, 0.95–2.30; P=0.086); However, further adjustment for baseline renal function (estimated GFR) and albuminuria weakened the cardiovascular disease risks in Malay (1.48, 0.98–2.26; P=0.065) but strengthened that in Asian Indian subjects (1.81, 1.14–2.87; P=0.012). Competing‐risk regression showed that the age‐ and gender‐adjusted sub‐distribution hazard ratio for end‐stage renal disease was 1.87 (1.27–2.73; P=0.001) in Malay and 0.39 (0.18–0.83; P=0.015) in Asian Indian subjects. Notably, the difference in end‐stage renal disease risk among the three ethnic groups was abolished after further adjustment for baseline estimated GFR and albuminuria. There was no significant difference in risk of all‐cause mortality among the three ethnic groups.
Conclusions
Risks of cardiovascular and end‐stage renal diseases in native Asian subjects with Type 2 diabetes vary substantially among different ethnic groups. Differences in prevalence of diabetic kidney disease may partially explain the ethnic disparities.
What's new?
This is the first prospective study to examine ethnic disparities in cardiovascular disease, end‐stage renal disease and all‐cause mortality risks among native South‐East Asian people with Type 2 diabetes.
Ethnic Malay and Asian Indian subjects had a higher risk of cardiovascular disease as compared with Chinese subjects. The risk of end‐stage renal disease was significantly higher in Malay subjects, whereas it trended lower in Asian Indian as compared with Chinese subjects.
The disparity in cardiovascular disease and end‐stage renal disease risks among ethnic subpopulations might be partially explained by difference in the prevalence of diabetic kidney disease.
Our data highlight the importance of primary prevention of diabetic kidney disease in Asian people with Type 2 diabetes.
Temperature-dependent in-plane vibration of functionally graded (FGM) circular arches based on the two-dimensional theory of elasticity is investigated. An analytical solution using the state space ...formulation and Fourier series expansion is obtained for a simply supported circular arch. For such functionally graded arches, the state equation has variable coefficients. Because a definite, continuously varying FG model through the thickness is impractical if not impossible, an approximate laminate model is constructed to derive an asymptotic solution through the thickness direction. The transfer relationship between the state vectors at the inner and outer surfaces is ultimately obtained by considering the continuity conditions at the artificial interfaces. The new formulation is validated by comparing some numerical solutions with established results in open literature, such as functionally graded straight beams, curved sandwich beams and laminated thick circular arches. Effective material properties are predicted using the Mori–Tanaka model and taken as temperature-dependent. Effects of the gradient index, temperature and geometric parameters, i.e. the curvature, length-to-thickness ratio, subtended angle, on the vibration frequency are analyzed and discussed.
•Patients with young-onset type 2 diabetes had a high risk of glycemic progression in 3-year follow-up•A low generic risk score of beta cell dysfunction was associated with low risk of glycemic ...progression•Genetic risk score of beta cell dysfunction does not interact with young-onset age in association with glycemic progression•High risk of glycemic progression in young-onset type 2 diabetes is independent of genetic risk of beta cell dysfunction
To study the relationship between genetic risk of beta cell dysfunction, young onset age and glycaemic progression in individuals with type 2 diabetes (T2D).
1385 T2D outpatients were included in cross-sectional sub-study and 730 insulin-naïve outpatients were followed for 3 years in prospective sub-study. Genetic risk score (GRS) was derived from 24 beta cell dysfunction-related single nucleotide polymorphisms, with lower and upper 25 percentiles defined as low and high genetic risk. Glycaemic progression was defined as requirement for sustained insulin therapy.
388 participants in cross-sectional and 128 in prospective sub-study experienced glycaemic progression. Young onset age (T2D diagnosis below 40 year-old) was associated with high risk of glycaemic progression as compared to usual-onset counterparts (adjusted OR 1.64 95% CI 1.14−2.36, and 2.92 95% CI 1.76−4.87 in cross-sectional and prospective sub-study, respectively). As compared to those with intermediate risk, a low GRS was associated with lower risk for glycaemic progression (adjusted OR 0.72 95% CI 0.49−1.06, and 0.51 95% CI 0.29−0.90) whereas a high GRS was not significantly associated with glycaemic progression. Notably, the association of young-onset T2D with high risk of glycaemic progression was independent of known clinical risk factors and beta cell dysfunction GRS (P interaction > 0.10).
Young onset age and low genetic risk of beta cell dysfunction are independently associated with risk of glycaemic progression. Our data do not support that genetic risk modulates the risk of glycaemic progression in individuals with young-onset T2D.
The aims of the present study were to determine whether Allium sativum (garlic) extract has any effect on the morphology transformation of Candida albicans, and to investigate whether it could alter ...the gene expression level of SIR2, a morphogenetic control gene and SAP4, a gene encoding secreted aspartyl proteinase. Candida albicans cells were incubated with a range of concentrations of fresh garlic extract, and the morphology was monitored via light microscopy. Garlic extract treatment caused the transition of yeast form to hyphal form to be obviated. The expression of SIR2 was down-regulated from 1·2- to 2·5-fold with increasing concentration of the garlic extract, as determined from relative quantitative reverse transcription-polymerase chain reaction. There was no difference in the SAP4 expression in control vs treated cultures. Garlic and its bioactive components have the ability to suppress hyphae production and to affect the expression level of SIR2 gene. Hyphal production is an essential virulence determinant of C. albicans for invasive infections, therefore garlic and its constituents can be effective not only against colonizing C. albicans strains present in mucosal infections, but also virulent strains causing systemic or invasive candidiasis.
Solid and dissolved organic matter (DOM) compositions were investigated in a pristine and a deforested tropical peat forest in Brunei Darussalam. A combination of elemental (%C, %N, C/N), isotopic ...(δ15N, δ13C, Δ14C), molecular (lignin phenol biomarkers) and optical (Specific UV Absorbance at 280nm (SUVA280), fluorescence index (FI)) analyses were performed to characterize DOM in porewater and river water. The DOM composition was compared to vegetation and peat to assess DOM origin and transformations in the ecosystem. Significant relationships were observed between optical properties (SUVA280, FI) and bulk (Δ14C) and molecular (ratio of cinnamyl to vanillyl phenols, C/V) composition of DOM.
The radiocarbon content of DOM shows that it is modern at both sites for both surface and deep (to 4.5m) samples (Δ14C=74.58±8.53‰ at the pristine site and Δ14C=87.84±4.5‰ at the deforested site for the first 2 meters), indicating transport of young DOM to deeper layers. Stable carbon-13 content of vegetation, peat and DOM showed only slight fractionation and ranged from −32.2‰ to −28.3‰. Nitrogen showed a greater shift between ecosystem pools. Nitrogen-15 content was higher in the solid peat (δ15N=−0.92±0.49‰ in the pristine site, δ15N=−1.22±1.37‰ in the deforested site) than in DOM (δ15N=−4.2±2.5‰ in the pristine site, δ15N=−4.1±2.3‰ in the deforested site). This difference in δ15N is significantly correlated with the C/N values of peat and DOM and attributable to higher microbial degradation in the peat compared to DOM. Porewater DOM contains less lignin (λ8=1.10±0.27mg100mgdw−1 in the pristine site and λ8=1.38±0.46mg100mgdw−1 in the deforested site) than does the solid peat (λ8=5.66±2.14mg100mgdw−1 in the pristine site and λ8=10.29±4.69mg100mgdw−1 in the deforested site). All indicators of lignin degradation (P/(V+S), 3,5Bd/V, (Ad/Al)V, (Ad/Al)S) are significantly higher in DOM than in the solid peat. This shows that lignin can be processed rapidly in the porewater of upper layers of tropical peatlands.
Logging activity affected the composition of organic matter at the deforested site. Higher lignin content (λ8) was observed in the solid peat, and the composition of DOM differed greatly in the deforested site: Δ14C, FI, 3,5Bd/V, (Ad/Al)V are significantly different from the pristine site. Thus it appears that the composition of DOM is more sensitive than the solid phase to the effects of land use change on organic matter dynamic in tropical peatlands.
Over the past 20 years, we have seen significant improvements in product titres from 50 mg/l to 5–10 g/l, a more than 100‐fold increase. The main methods that have been employed to achieve this ...increase in product titre have been through the manipulation of culture media and process control strategies, such as the optimization of fed‐batch processes. An alternative means to increase productivity has been through the engineering of host cells by altering cellular processes. Recombinant DNA technology has been used to over‐express or suppress specific genes to endow particular phenotypes. Cellular processes that have been altered in host cells include metabolism, cell cycle, protein secretion and apoptosis. Cell engineering has also been employed to improve post‐translational modifications such as glycosylation. In this article, an overview of the main cell engineering strategies previously employed and the impact of these strategies are presented. Many of these strategies focus on engineering cell lines with more efficient carbon metabolism towards reducing waste metabolites, achieving a biphasic production system by engineering cell cycle control, increasing protein secretion by targeting specific endoplasmic reticulum stress chaperones, delaying cell death by targeting anti‐apoptosis genes, and engineering glycosylation by enhancing recombinant protein sialylation and antibody glycosylation. Future perspectives for host cell engineering, and possible areas of research, are also discussed in this review.
In a recent study, we showed that in response to high fat feeding C57BL/6, 129X1, DBA/2 and FVB/N mice all developed glucose intolerance, while BALB/c mice displayed minimal deterioration in glucose ...tolerance and insulin action. Lipidomic analysis of livers across these five strains has revealed marked strain-specific differences in ceramide (Cer) and sphingomyelin (SM) species with high-fat feeding; with increases in C16-C22 (long-chain) and reductions in C>22 (very long-chain) Cer and SM species observed in the four strains that developed HFD-induced glucose intolerance. Intriguingly, the opposite pattern was observed in sphingolipid species in BALB/c mice. These strain-specific changes in sphingolipid acylation closely correlated with ceramide synthase 2 (CerS2) protein content and activity, with reduced CerS2 levels/activity observed in glucose intolerant strains and increased content in BALB/c mice. Overexpression of CerS2 in primary mouse hepatocytes induced a specific elevation in very long-chain Cer, but despite the overall increase in ceramide abundance, there was a substantial improvement in insulin signal transduction, as well as decreased ER stress and gluconeogenic markers. Overall our findings suggest that very long-chain sphingolipid species exhibit a protective role against the development of glucose intolerance and hepatic insulin resistance.
•Diet-induced changes in hepatic sphingolipid acyl profile vary markedly between different mouse strains.•The balance between long-chain and very long-chain sphingolipid species is a key determinant of glucose homeostasis and insulin action.•Increasing hepatic content of very long-chain ceramides improves insulin action and reduces ER stress, despite higher total ceramide content.
Diabet. Med. 29, e304–e307 (2012)
Aim Screening for peripheral arterial disease, a complication among patients with diabetes, is performed by periodic assessment of ankle–brachial index. We aimed to ...study the degree of ankle–brachial index change over time and factors associated with significant change.
Method We assessed difference between two ankle–brachial index measurements over time in a consecutive series of 82 patients with Type 2 diabetes. All patients had ankle–brachial index > 0.9 but ≤ 1.3 for the first measurement, and significant ankle–brachial index decrease was defined as a decrease of > 0.1 in the follow‐up measurement compared with the baseline.
Results The mean follow‐up duration was 27.6 (median 30.0) months. Significant ankle–brachial index decrease was seen in 20.7% of patients, including 5% with follow‐up ankle–brachial index of ≤ 0.9, consistent with the diagnosis of peripheral arterial disease. After adjusting for age and gender, higher baseline HbA1c and serum creatinine levels, increase in follow‐up serum LDL cholesterol levels compared with baseline and history of retinopathy were predictors of significant ankle–brachial index decrease.
Conclusions Our study suggests that, within two years, one in five patients with diabetes and a normal ankle–brachial index may have significant progression of peripheral arterial disease. Annual ankle–brachial index assessment and better control of hyperlipidaemia may thus be required for at‐risk patients with poor glycaemic control, renal impairment and retinopathy.
The role of the orbitofrontal cortex (OFC) in value processing is a focus of research. Conventional imaging analysis, where smoothing and averaging are employed, may not be sufficiently sensitive in ...studying the OFC, which has heterogeneous anatomical structures and functions. In this study, we employed representational similarity analysis (RSA) to reveal the multi-voxel fMRI patterns in the OFC associated with value processing during the anticipatory and the consummatory phases. We found that multi-voxel activation patterns in the OFC encoded magnitude and partial valence information (win vs. loss) but not outcome (favourable vs. unfavourable) during reward consummation. Furthermore, the lateral OFC rather than the medial OFC encoded loss information. Also, we found that OFC encoded values in a similar way to the ventral striatum (VS) or the anterior insula (AI) during reward anticipation regardless of motivated response and to the medial prefrontal cortex (MPFC) and the VS in reward consummation. In contrast, univariate analysis did not show changes of activation in the OFC. These findings suggest an important role of the OFC in value processing during reward anticipation and consummation.
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