Qibin Qi, Jing Wang, Huaixing Li, Zhijie Yu, Xingwang Ye, Frank B Hu, Oscar H Franco, An Pan, Yong Liu and Xu Lin
Resistin increases insulin resistance (IR) in mice. However, the role of resistin in human disease remains controversial. We aimed to assess plasma resistin levels and their associations with inflammatory and fibrinolytic markers, IR and metabolic syndrome (MetS) among Chinese.
Design and methods
Plasma resistin was measured in a population-based cross-sectional survey of 3193 Chinese aged from 50 to 70 years in Beijing and Shanghai.
The median resistin concentration was 8.60 ng/ml (interquartile range, 5.78–14.00) among all participants, and it was higher in women than in men (P=0.008). Resistin was correlated weakly with body mass index, waist circumference, high-density lipoprotein (HDL) cholesterol (negatively), homeostatic model assessment of IR and tumor necrosis factor-α receptor 2 (TNFR2; r=0.04, 0.07, –0.09 and 0.06 respectively, all P<0.05), and more highly with C-reactive protein (CRP), interleukin (IL)6 and plasminogen activator inhibitor (PAI)1 (r=0.12, 0.12 and 0.21 respectively, all P<0.001), but only HDL cholesterol, CRP, IL6, TNFR2, and PAI1 remained significantly associated with resistin in multiple regression analysis (all P<0.05). Furthermore, elevated resistin levels were associated with the higher prevalence of IR and MetS. However, the significant relationships disappeared after adjustment for inflammatory and fibrinolytic markers especially PAI1.
This study suggests that resistin is more strongly associated with inflammatory and fibrinolytic markers than with obesity or IR status. The associations of resistin with IR and MetS could largely be explained by inflammatory and fibrinolytic markers especially PAI1 levels.
Layal Chaker, Sanaz Sedaghat, Ewout J Hoorn, Wendy P J Den Elzen, Jacobijn Gussekloo, Albert Hofman, M Arfan Ikram, Oscar H Franco, Abbas Dehghan and Robin P Peeters
Thyroid dysfunction has been associated with kidney function decline, but mainly in cross-sectional studies. Therefore, we aimed to determine the association between thyroid and kidney function in a prospective population-based cohort study longitudinally.
Prospective cohort study.
Participants aged ≥45 years from the Rotterdam Study with thyroid and kidney function assessment were included. Kidney function and new onset chronic kidney disease (CKD) were defined using estimated glomerular filtration ate (eGFR), with CKD defined as eGFR <60 mL/min/1.73 m2 according to the CKD-EPI formula.
We included 5103 participants (mean age of 63.6 years) with a mean follow-up of 8.1 years. Cross-sectionally, higher TSH levels were associated with lower eGFR (Beta (β): −1.75 mL/min; 95% confidence interval (CI): −2.17, −1.33), in multivariable models adjusting for several cardiovascular risk factors including smoking, hypertension and history of coronary heart disease among others. In contrast, longitudinally, higher TSH levels were associated with less annual eGFR decline (β: −0.06 mL/min; CI: −0.11, −0.01) and lower CKD incidence (odds ratio 0.85, CI; 0.75, 0.96). Compared with euthyroid participants, subclinical hyperthyroid individuals had an increased risk for CKD whereas hypothyroid individuals had a decreased risk (P for trend = 0.04).
Hyperactive thyroid function is associated with increased risk of kidney function decline while hypothyroidism is associated with a decreased CKD risk. More insight is needed in the pathophysiological pathways connecting high thyroid function and kidney function decline.
Samer R Khan, Arjola Bano, Marlies Wakkee, Tim I M Korevaar, Oscar H Franco, Tamar E C Nijsten, Robin P Peeters and Layal Chaker
Autoimmune thyroid disease (AITD) and psoriatic disease share auto-immunological components. Few studies have investigated the link between both, yielding inconclusive results.
We assessed the association of AITD with psoriatic disease in a prospective cohort study and performed a systematic review and meta-analysis.
8214 participants of the Rotterdam Study (RS) with thyroid peroxidase antibodies (TPO-Abs), thyroid-stimulating hormone (TSH) and/or free thyroxine (FT4) measurements and information on psoriatic disease were included. We performed logistic and Cox regression analyses and a systematic literature search in several electronic databases on AITD and psoriatic disease. We pooled odds ratios (ORs) of included studies using the Mantel-Haenszel method, while adding RS data on prevalent psoriatic disease.
Within the RS, we found no association between TPO-Ab positivity and psoriatic disease. There was a positive trend between TSH and prevalent psoriatic disease, and between FT4 and incident psoriatic disease, although not significant. Out of 1850 articles identified, seven were included in the systematic review and four in the meta-analysis. The risk of psoriatic disease (pooled OR) was 1.71 (confidence interval (CI): 1.27–2.31) for TPO-Ab positivity, 1.25 (CI: 1.14–1.37) for AITD and 1.34 (CI: 1.16–1.54) respectively, and 1.17 (CI: 1.03–1.32) for hypothyroidism and hyperthyroidism.
Our meta-analysis suggests that TPO-Ab positivity, hypothyroidism and hyperthyroidism might be associated with prevalent psoriatic disease. However, there are only few studies with large heterogeneity regarding psoriatic disease definition and indication of publication bias. Additional prospective data are needed to assess the association of AITD with incident psoriatic disease.
Vincent L Wester, Jan W Koper, Erica L T van den Akker, Oscar H Franco, Ronald P Stolk and Elisabeth F C van Rossum
An excess of glucocorticoids (Cushing’s syndrome) is associated with metabolic syndrome (MetS) features. Several single-nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR) gene influence sensitivity to glucocorticoids and have been associated with aspects of MetS. However, results are inconsistent, perhaps due to the heterogeneity of the studied populations and limited samples. Furthermore, the possible association between functional GR SNPs and prevalence of MetS remains unexplored.
Cross-sectional population-based cohort study.
MetS presence and carriage of functional GR SNPs (BclI, N363S, ER22/23EK, GR-9beta) were determined in 12 552 adult participants from Lifelines, a population-based cohort study in the Netherlands. GR SNPs were used to construct GR haplotypes.
Five haplotypes accounted for 99.9% of all GR haplotypes found. No main effects of functional GR haplotypes on MetS were found, but the association of GR haplotype 4 (containing N363S) with MetS was influenced by interaction with age, sex and education status (P < 0.05). Stratified analysis revealed that haplotype 4 increased MetS presence in younger men (at or below the median age of 47; odds ratio 1.77, P = 0.005) and in people of low education status (odds ratio 1.48, P = 0.039).
A glucocorticoid receptor haplotype that confers increased sensitivity to glucocorticoids appears to increase the risk of metabolic syndrome, but only among younger men and less educated individuals, suggesting gene–environment interactions.
Blerim Mujaj, Daniel Bos, Maryam Kavousi, Aad van der Lugt, Jan A Staessen, Oscar H Franco and Meike W Vernooij
To investigate the association between fasting serum insulin and glucose levels with atherosclerotic plaque composition in the carotid artery. Impaired insulin and glucose levels are implicated in the etiology of cardiovascular disease; however, their influence on the formation and composition of atherosclerotic plaque remains unclear.
In 1740 participants (mean age 72.9 years, 46% women, 14.4% diabetes mellitus) from the population-based Rotterdam Study, we performed carotid MRI to evaluate the presence of calcification, lipid core, and intraplaque hemorrhage in carotid atherosclerosis. All participants also underwent blood sampling to obtain information on serum insulin and glucose levels. Using logistic regression models, we assessed the association of serum insulin and glucose levels (per s.d. and in tertiles) with the different plaque components, while adjusting for sex, age, intima-media thickness, and cardiovascular risk factors.
Serum insulin levels were associated with the presence of intraplaque hemorrhage (adjusted odds ratio (OR): 1.42 (95% CI: 1.12–1.7)) We found no association with the presence of calcification or lipid core. Sensitivity analyses restricted to individuals without diabetes mellitus yielded similar results. No associations were found between serum glucose levels and any of the plaque components.
Serum insulin levels are associated with the presence of vulnerable components of carotid plaque, specifically with intraplaque hemorrhage. These findings suggest a complex role for serum insulin in the pathophysiology of carotid atherosclerosis and in plaque vulnerability.