Background
Inflammation is involved in the pathogenesis of cardiovascular disease and cognitive decline. Interleukin‐6 (IL‐6) has a role in cardiovascular disease, but the association of IL‐6 ...concentration and the functional IL‐6 ‐174 polymorphism with cognitive decline has not been demonstrated unequivocally. The objective of this study was to investigate the associations between both high concentration of IL‐6 and the ‐174 promoter polymorphism, and increased cognitive decline in old age.
Methods
Over 5000 participants of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) with a mean age of 75 years and a history of cardiovascular disease or its risk factors were included in this study. We determined baseline concentrations of IL‐6 and genotype of the IL‐6 ‐174 polymorphism, of which the C allele was previously shown to be associated with higher circulating concentrations of IL‐6. A cognitive test battery was administered at baseline and repeatedly during follow‐up (mean 39 months).
Results
In the cross‐sectional analysis of 5653 participants, higher IL‐6 concentration was associated with worse executive cognitive function (P < 0.001), independent of cardiovascular disease status and risk factors. No association was found between IL‐6 concentration and memory function (P > 0.14). In the prospective analysis, higher IL‐6 concentration was associated with an increased rate of cognitive decline in both executive function (P = 0.002) and memory function (P = 0.002), again independent of cardiovascular disease status and risk factors. Although not associated with IL‐6 concentrations, the IL‐6 ‐174 CC genotype was associated with worse performance on the Stroop test (P = 0.045).
Conclusions
Higher circulating levels of IL‐6 were associated with worse cognitive function and steeper cognitive decline and provide preliminary genetic evidence for a potential causal association. The findings support the importance of the need for further investigation of the IL‐6 pathway in cognitive decline.
We examined prospectively whether measured risk factors can explain the higher CHD mortality in South Asians compared with Europeans.
Conventional CHD risk factors and those associated with insulin ...resistance were measured in 1,787 European and 1,420 South Asian men aged 40 to 69 years at baseline in the population-based Southall and Brent studies (London) between 1988 and 1990. Participants were followed up for mortality.
By February 2006, there were 202 CHD deaths (108 Asian, 94 European). South Asian men had double the CHD mortality of European men in Cox regression analyses adjusted for age, smoking, and cholesterol (hazard ratio HR 2.14, 95% CI 1.56-2.94, p<0.001). Nearly half of all South Asian CHD deaths versus 13% of deaths among Europeans were among persons with diabetes. Asian men had greater CHD mortality than Europeans, both in the with- and the without-diabetes categories at baseline. CHD mortality remained significantly higher in South Asian men in multivariable models that adjusted for conventional risk factors and diabetes and/or impaired glucose regulation, features of insulin resistance, or the metabolic syndrome (HR 1.6-1.9). Accounting for co-morbidity and socio-economic status did not materially alter the findings.
These data confirm that South Asian men have significantly higher CHD mortality than their European counterparts, while indicating that neither conventional risk factors, nor insulin resistance parameters or metabolic syndrome criteria as currently defined can account for this excess risk. The contribution of unmeasured factors to the elevated vascular risk in South Asians should be addressed in future studies.
Aims/hypothesis
This study aimed to determine the extent to which increased insulin resistance and fasting glycaemia in South Asian men, compared with white European men, living in the UK, was due to ...lower cardiorespiratory fitness (maximal oxygen uptake
V
˙
O
2
max
) and physical activity.
Methods
One hundred South Asian and 100 age- and BMI-matched European men without diagnosed diabetes, aged 40–70 years, had fasted blood taken for measurement of glucose concentration, HOMA-estimated insulin resistance (HOMA
IR
), plus other risk factors, and underwent assessment of physical activity (using accelerometry),
V
˙
O
2
max
, body size and composition, and demographic and other lifestyle factors. For 13 South Asian and one European man, HbA
1c
levels were >6.5% (>48 mmol/mol), indicating potential undiagnosed diabetes; these men were excluded from the analyses. Linear regression models were used to determine the extent to which body size and composition, fitness and physical activity variables explained differences in HOMA
IR
and fasting glucose between South Asian and European men.
Results
HOMA
IR
and fasting glucose were 67% (
p
< 0.001) and 3% (
p
< 0.018) higher, respectively, in South Asians than Europeans. Lower
V
˙
O
2
max
, lower physical activity and greater total adiposity in South Asians individually explained 68% (95% CI 45%, 91%), 29% (11%, 46%) and 52% (30%, 80%), respectively, and together explained 83% (50%, 119%) (all
p
< 0.001) of the ethnic difference in HOMA
IR
. Lower
V
˙
O
2
max
and greater total adiposity, respectively, explained 61% (9%, 111%) and 39% (9%, 76%) (combined effect 63% 8%, 115%; all
p
< 0.05) of the ethnic difference in fasting glucose.
Conclusions/interpretation
Lower cardiorespiratory fitness is a key factor associated with the excess insulin resistance and fasting glycaemia in middle-aged South Asian, compared with European, men living in the UK.
The gluten strength and the composition of high- and low-molecular-weight glutenin subunits (HMWGSs and LMWGSs) of fifty-one durum wheat genotypes were evaluated using sodium dodecyl sulfate (SDS) ...sedimentation testing and SDS polyacrylamide gel electrophoresis (SDS-PAGE). This study examined the allelic variability and the composition of HMWGSs and LMWGSs in
wheat genotypes. SDS-PAGE was proven to be a successful method for identifying HMWGS and LMWGS alleles and their importance in determining the dough quality. The evaluated durum wheat genotypes with HMWGS alleles 7+8, 7+9, 13+16, and 17+18 were highly correlated with improved dough strength. The genotypes containing the LMW-2 allele displayed stronger gluten than those with the LMW-1 allele. The comparative in silico analysis indicated that Glu-A1, Glu-B1, and Glu-B3 possessed a typical primary structure. The study also revealed that the lower content of glutamine, proline, glycine, and tyrosineand the higher content of serine and valine in the Glu-A1 and Glu-B1 glutenin subunits, and the higher cysteine residues in Glu-B1 and lower arginine, isoleucine, and leucine in the Glu-B3 glutenin, are associated with the suitability of durum wheat for pasta making and the suitability of bread wheat with good bread-making quality. The phylogeny analysis reported that both Glu-B1 and Glu-B3 had a closer evolutionary relationship in bread and durum wheat, while the Glu-A1 was highly distinct. The results of the current research may help breeders to manage the quality of durum wheat genotypes by exploiting the allelic variation in glutenin. Computational analysis showed the presence of higher proportions of glutamine, glycine, proline, serine, and tyrosine than the other residues in both HMWGSs and LMWGSs. Thus, durum wheat genotype selection according to the presence of a few protein components effectively distinguishes the strongest from the weakest types of gluten.
Aims/hypothesis
Current drug labels for thiazolidinediones (TZDs) warn of increased fractures, predominantly for distal fractures in women. We examined whether exposure to TZDs affects hip fracture ...in women and men and compared the risk to that found with other drugs used in diabetes.
Methods
Using a nationwide database of prescriptions, hospital admissions and deaths in those with type 2 diabetes in Scotland we calculated TZD exposure among 206,672 individuals. Discrete-time failure analysis was used to model the effect of cumulative drug exposure on hip fracture during 1999–2008.
Results
There were 176 hip fractures among 37,479 exposed individuals. Hip fracture risk increased with cumulative exposure to TZD: OR per year of exposure 1.18 (95% CI 1.09, 1.28;
p
= 3 × 10
−5
), adjusted for age, sex and calendar month. Hip fracture increased with cumulative exposure in both men (OR 1.20; 95% CI 1.03, 1.41) and women (OR 1.18; 95% CI 1.07, 1.29) and risks were similar for pioglitazone (OR 1.18) and rosiglitazone (OR 1.16). The association was similar when adjusted for exposure to other drugs for diabetes and for other potential confounders. There was no association of hip fracture with cumulative exposure to sulfonylureas, metformin or insulin in this analysis. The 90-day mortality associated with hip fractures was similar in ever-users of TZD (15%) and in never-users (13%).
Conclusions/interpretation
Hip fracture is a severe adverse effect with TZDs, affecting both sexes; labels should be changed to warn of this. The excess mortality is at least as much as expected from the reported association of pioglitazone with bladder cancer.
Aims
To investigate whether metformin therapy alters circulating aromatic and branched‐chain amino acid concentrations, increased levels amino acid concentrations, increased levels of which have been ...found to predict Type 2 diabetes.
Methods
In the Carotid Atherosclerosis: Metformin for Insulin Resistance (CAMERA) study (NCT00723307), 173 individuals without Type 2 diabetes, but with coronary disease, were randomized to metformin (n=86) or placebo (n=87) for 18 months. Plasma samples, taken every 6 months, were analysed using quantitative nuclear magnetic resonance spectroscopy. Ten metabolites consisting of eight amino acids three branched‐chain (isoleucine, leucine, valine), three aromatic (tyrosine, phenylalanine, histidine) and two other amino acids (alanine, glutamine), lactate and pyruvate were quantified and analysed using repeated‐measures models. On‐treatment analyses were conducted to investigate whether amino acid changes were dependent on changes in weight, fat mass or insulin resistance estimated using homeostasis model assessment (HOMA‐IR).
Results
Tyrosine decreased −6.1 μmol/l (95% CI −8.5, ‐3.7); P<0.0001, while alanine 42 umol/l (95% CI 25, 59); P<0.0001 increased in the metformin‐treated group compared with the placebo‐treated group. Decreases in phenylalanine −2.0 μmol/l (95% CI −3.6, −0.3); P=0.018 and increases in histidine 2.3 μmol/l (95% CI 0.1, 4.6); P=0.045 were also observed in the metformin group, although these changes were less statistically robust. Changes in these four amino acids were not accounted for by changes in weight, fat mass or HOMA‐IR values. Levels of branched‐chain amino acids, glutamine, pyruvate and lactate were not altered by metformin therapy.
Conclusions
Metformin therapy results in a sustained and specific pattern of changes in aromatic amino acid and alanine concentrations. These changes are independent of any effects on weight and insulin sensitivity. Any causal link to metformin's unexplained cardiometabolic benefit requires further study.
What's new?
Aromatic and branched‐chain amino acids have been shown to predict both the development of diabetes and cardiovascular disease in several recent epidemiological studies.
Some studies have suggested that metformin may alter amino acid concentrations but these studies have been small with a short duration of follow‐up, limiting the inferences that could be made about long‐term treatment.
In the CAMERA trial of 173 individuals without diabetes, daily metformin therapy led to sustained reductions in phenylalanine and tyrosine and sustained increases in alanine and histidine concentrations over 18 months.
Graphene (G) has been a game-changer for conductive optical devices and has shown promising aspects for its implementation in the power industry due to its diverse structures. Graphene has played an ...essential role as electrodes, hole transport layers (HTLs), electron transport layers (ETLs), and a chemical modulator for perovskite layers in perovskite solar cells (PSCs) over the past decade. Nitrogen-doped graphene (N-DG) derivatives are frequently evaluated among the existing derivatives of graphene because of their versatility of design, easy synthesis process, and high throughput. This review presents a state-of-the-art overview of N-DG preparation methods, including wet chemical process, bombardment, and high thermal treatment methods. Furthermore, it focuses on different structures of N-DG derivatives and their various applications in PSC applications. Finally, the challenges and opportunities for N-DG derivatives for the continuous performance improvement of PSCs have been highlighted.
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