Relation of C-reactive protein to body fat distribution and features of the metabolic syndrome in Europeans and South Asians.

OBJECTIVE: To investigate the association between circulating C-reactive protein (CRP) concentrations and indices of body fat distribution and the insulin resistance syndrome in South Asians and Europeans. DESIGN: : Cross-sectional study. SUBJECTS: A total of 113 healthy South Asian and European men and women in West London (age 40-55 y, body mass index (BMI) 17-34 kg/m(2)). MEASUREMENTS: Fatness and fat distribution parameters (by anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan); oral glucose tolerance test with insulin response; modified fat tolerance test; and CRP concentration by sensitive ELISA. RESULTS: Median CRP level in South Asian women was nearly double that in European women (1.35 vs 0.70 mg/1, P=0.05). Measures of obesity and CRP concentration were significantly associated in both ethnic groups. The correlation to CRP was especially strong among South Asians (P0.15). CONCLUSION: We suggest that adiposity and in particular visceral adipose tissue is a key promoter of low-grade chronic inflammation. This observation may in part account for the association of CRP with markers of the metabolic syndrome. Future studies should confirm whether CRP concentrations are elevated in South Asians and whether losing weight by exercise or diet, or reduction in visceral fat mass, is associated with reduction in plasma CRP concentrations

Risk for rheumatic disease in relation to ethnicity and admixture

Risk of systemic lupus erythematosus (SLE) is high in west Africans compared with Europeans, and risk of rheumatoid arthritis (RA) is high in Native Americans compared with Europeans. These differences are not accounted for by differences in allele or haplotype frequencies in the human leucocyte antigen (HLA) region or any other loci known to influence risk of rheumatic disease. Where there has been admixture between two or more ethnic groups that differ in risk of disease, studies of the relationship of disease risk to proportionate admixture can help to distinguish between genetic and environmental explanations for ethnic differences in disease risk and to map the genes underlying these differences

Diabetes risk and amino acid profiles: cross-sectional and prospective analyses of ethnicity, amino acids and diabetes in a South Asian and European cohort from the SABRE (Southall And Brent REvisited) Study.

Aims/hypothesis: South Asian individuals have an increased risk of diabetes compared with Europeans that is unexplained by obesity and traditional or established metabolic measures. Circulating amino acids (AAs) may provide additional explanatory insights. In a unique cohort of European and South Asian men, we compared cross-sectional associations between AAs, metabolic and obesity traits, and longitudinal associations with incident diabetes. / Methods: Nuclear magnetic spectroscopy was used to measure the baseline (1988–1991) levels of nine AAs in serum samples from a British population-based cohort of 1,279 European and 1,007 South Asian non-diabetic men aged 40–69 years. Follow-up was complete for 19 years in 801 European and 643 South Asian participants. / Results: The serum concentrations of isoleucine, phenylalanine, tyrosine and alanine were significantly higher in South Asian men, while cross-sectional correlations of AAs with glycaemia and insulin resistance were similar in the two ethnic groups. However, most AAs were less strongly correlated with measures of obesity in the South Asian participants. Diabetes developed in 227 (35%) South Asian and 113 (14%) European men. Stronger adverse associations were observed between branched chain and aromatic AAs and incident diabetes in South Asian men. Tyrosine was a particularly strong predictor of incident diabetes in South Asian individuals, even after adjustment for metabolic risk factors, including obesity and insulin resistance (adjusted OR for a 1 SD increment, 1.47, 95% CI 1.17,1.85, p = 0.001) compared with Europeans (OR 1.10, 0.87, 1.39, p = 0.4; p = 0.045 for ethnicity × tyrosine interaction). / Conclusions/interpretation: Branched chain and aromatic AAs, particularly tyrosine, may be a focus for identifying novel aetiological mechanisms and potential treatment targets for diabetes in South Asian populations and may contribute to their excess risk of diabetes

Risk of severe COVID-19 in patients with inflammatory rheumatic diseases treated with immunosuppressive therapy in Scotland

Objective: To investigate the association of severe coronavirus disease 2019 (COVID-19) in patients with inflammatory rheumatic diseases (IRDs) treated with immunosuppressive drugs. Method: A list of 4633 patients on targeted – biological or targeted synthetic – DMARDs in March 2020 was linked to a case– control study that includes all cases of COVID-19 in Scotland. Results: By 22 November 2021, 433 of the 4633 patients treated with targeted DMARDS had been diagnosed with COVID-19, of whom 58 had been hospitalized. With all those in the population not on DMARDs as the reference category, the rate ratio for hospitalized COVID-19 associated with DMARD treatment was 2.14 [95% confidence interval (CI) 2.02–2.26] in those on conventional synthetic (cs) DMARDs, 2.01 (95% CI 1.38–2.91) in those on tumour necrosis factor (TNF) inhibitors as the only targeted agent, and 3.83 (95% CI 2.65–5.56) in those on other targeted DMARDs. Among those on csDMARDs, rate ratios for hospitalized COVID-19 were lowest at 1.66 (95% CI 1.51–1.82) in those on methotrexate and highest at 5.4 (95% CI 4.4–6.7) in those on glucocorticoids at an average dose > 10 mg/day prednisolone equivalent. Conclusion: The risk of hospitalized COVID-19 is elevated in IRD patients treated with immunosuppressive drugs compared with the general population. Of these drugs, methotrexate, hydroxychloroquine, and TNF inhibitors carry the lowest risk. The highest risk is associated with prednisolone. A larger study is needed to estimate reliably the risks associated with each class of targeted DMAR

Use of personalised risk-based screening schedules to optimise workload and sojourn time in screening programmes for diabetic retinopathy:A retrospective cohort study

Background: National guidelines in most countries set screening intervals for diabetic retinopathy (DR) that are insufficiently informed by contemporary incidence rates. This has unspecified implications for interval disease risks (IDs) of referable DR, disparities in ID between groups or individuals, time spent in referable state before screening (sojourn time), and workload. We explored the effect of various screening schedules on these outcomes and developed an open-access interactive policy tool informed by contemporary DR incidence rates. Methods and findings: Scottish Diabetic Retinopathy Screening Programme data from 1 January 2007 to 31 December 2016 were linked to diabetes registry data. This yielded 128,606 screening examinations in people with type 1 diabetes (T1D) and 1,384,360 examinations in people with type 2 diabetes (T2D). Among those with T1D, 47% of those without and 44% of those with referable DR were female, mean diabetes duration was 21 and 23 years, respectively, and mean age was 26 and 24 years, respectively. Among those with T2D, 44% of those without and 42% of those with referable DR were female, mean diabetes duration was 9 and 14 years, respectively, and mean age was 58 and 52 years, respectively. Individual probability of developing referable DR was estimated using a generalised linear model and was used to calculate the intervals needed to achieve various IDs across prior grade strata, or at the individual level, and the resultant workload and sojourn time. The current policy in Scotland—screening people with no or mild disease annually and moderate disease every 6 months—yielded large differences in ID by prior grade (13.2%, 3.6%, and 0.6% annually for moderate, mild, and no prior DR strata, respectively, in T1D) and diabetes type (2.4% in T1D and 0.6% in T2D overall). Maintaining these overall risks but equalising risk across prior grade strata would require extremely short intervals in those with moderate DR (1–2 months) and very long intervals in those with no prior DR (35–47 months), with little change in workload or average sojourn time. Changing to intervals of 12, 9, and 3 months in T1D and to 24, 9, and 3 months in T2D for no, mild, and moderate DR strata, respectively, would substantially reduce disparity in ID across strata and between diabetes types whilst reducing workload by 26% and increasing sojourn time by 2.3 months. Including clinical risk factor data gave a small but significant increment in prediction of referable DR beyond grade (increase in C-statistic of 0.013 in T1D and 0.016 in T2D, both p < 0.001). However, using this model to derive personalised intervals did not have substantial workload or sojourn time benefits over stratum-specific intervals. The main limitation is that the results are pertinent only to countries that share broadly similar rates of retinal disease and risk factor distributions to Scotland. Conclusions: Changing current policies could reduce disparities in ID and achieve substantial reductions in workload within the range of IDs likely to be deemed acceptable. Our tool s

Investigation of genetically regulated gene expression and response to treatment in rheumatoid arthritis highlights an association between IL18RAP expression and treatment response.

This article has been accepted for publication in Annals of the Rheumatic Diseases, 2020 following peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/annrheumdis-2020-217204OBJECTIVES: In this study, we sought to investigate whether there was any association between genetically regulated gene expression (as predicted using various reference panels) and anti-tumour necrosis factor (anti-TNF) treatment response (change in erythrocyte sedimentation rate (ESR)) using 3158 European ancestry patients with rheumatoid arthritis. METHODS: The genetically regulated portion of gene expression was estimated in the full cohort of 3158 subjects (as well as within a subcohort consisting of 1575 UK patients) using the PrediXcan software package with three different reference panels. Estimated expression was tested for association with anti-TNF treatment response. As a replication/validation experiment, we also investigated the correlation between change in ESR with measured gene expression at the Interleukin 18 Receptor Accessory Protein (IL18RAP) gene in whole blood and synovial tissue, using an independent replication data set of patients receiving conventional synthetic disease modifying anti-rheumatic drugs, with directly measured (via RNA sequencing) gene expression. RESULTS: We found that predicted expression of IL18RAP showed a consistent signal of association with treatment response across the reference panels. In our independent replication data set, IL18RAP expression in whole blood showed correlation with the change in ESR between baseline and follow-up (r=-0.35, p=0.0091). Change in ESR was also correlated with the expression of IL18RAP in synovial tissue (r=-0.28, p=0.02). CONCLUSION: Our results suggest that IL18RAP expression is worthy of further investigation as a potential predictor of treatment response in rheumatoid arthritis that is not specific to a particular drug type

The role of childhood social position in adult type 2 diabetes: Evidence from the English Longitudinal Study of Ageing

Copyright @ 2014 Pikhartova et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background: Socioeconomic circumstances in childhood and early adulthood may influence the later onset of chronic disease, although such research is limited for type 2 diabetes and its risk factors at the different stages of life. The main aim of the present study is to examine the role of childhood social position and later inflammatory markers and health behaviours in developing type 2 diabetes at older ages using a pathway analytic approach. Methods. Data on childhood and adult life circumstances of 2,994 men and 4,021 women from English Longitudinal Study of Ageing (ELSA) were used to evaluate their association with diabetes at age 50 years and more. The cases of diabetes were based on having increased blood levels of glycated haemoglobin and/or self-reported medication for diabetes and/or being diagnosed with type 2 diabetes. Father's job when ELSA participants were aged 14 years was used as the measure of childhood social position. Current social characteristics, health behaviours and inflammatory biomarkers were used as potential mediators in the statistical analysis to assess direct and indirect effects of childhood circumstances on diabetes in later life. Results: 12.6 per cent of participants were classified as having diabetes. A disadvantaged social position in childhood, as measured by father's manual occupation, was associated at conventional levels of statistical significance with an increased risk of type 2 diabetes in adulthood, both directly and indirectly through inflammation, adulthood social position and a risk score constructed from adult health behaviours including tobacco smoking and limited physical activity. The direct effect of childhood social position was reduced by mediation analysis (standardised coefficient decreased from 0.089 to 0.043) but remained statistically significant (p = 0.035). All three indirect pathways made a statistically significantly contribution to the overall effect of childhood social position on adulthood type 2 diabetes. Conclusions: Childhood social position influences adult diabetes directly and indirectly through inflammatory markers, adulthood social position and adult health behaviours. © 2014Pikhartova et al.; licensee BioMed Central Ltd.Economic and Social Research Council-funded International Centre for Life Course Studies in Society and Health (RES-596-28-0001)