Change of visfatin, C-reactive protein concentrations, and insulin sensitivity in patients with hyperthyroidism

doi:10.1016/j.metabol.2008.05.006

Metabolism

Volume 57, Issue 10, October 2008, Pages 1380-1383

https://doi.org/10.1016/j.metabol.2008.05.006 Get rights and content

Abstract

The present study was undertaken to evaluate the change of circulating visfatin, C-reactive protein (CRP) concentrations, and insulin sensitivity in patients with hyperthyroidism. We studied 19 adult patients (14 women and 5 men aged 32.6 ± 1.8 years) with hyperthyroidism due to Graves disease and 19 age- and sex-matched euthyroid controls (17 women and 2 men aged 36.7 ± 2.7 years). All hyperthyroid patients were treated with 1 of 2 antithyroid drugs and were reevaluated after thyroid function normalized. Before antithyroid treatment, the hyperthyroid group had significantly higher visfatin plasma concentration (mean ± standard error of the mean, 20.7 ± 1.8 ng/mL) than the control group (16.2 ± 1.3 ng/mL, P = .044); but the visfatin level dropped significantly after treatment (12.0 ± 1.4 ng/mL, P < .001). The reciprocal index of homeostasis model assessment of insulin resistance (HOMA–IR) in the hyperthyroid group was higher before treatment (2.06 ± 0.26 mmol mU/L*L) than after treatment (1.21 ± 0.16 mmol mU/L*L, P = .027). There was no significant difference in serum glucose, high-sensitivity CRP, and insulin levels between hyperthyroid and control groups and in the hyperthyroid group before and after treatment. Body mass index–adjusted visfatin levels were significantly elevated in the hyperthyroid group. Pearson correlation revealed that visfatin, glucose, insulin, and HOMA-IR values positively correlated with triiodothyronine and free thyroxine levels. However, visfatin did not correlate with insulin and HOMA-IR levels. The results indicated that plasma visfatin concentration was elevated in hyperthyroidism due to Graves disease, but serum CRP levels were not. Plasma visfatin levels were not associated with indicators of insulin resistance in hyperthyroid patients.

Introduction

Hyperthyroidism has been linked to reduced lean and fat body mass, resulting in lower-than-normal body weight. Patients with hyperthyroidism often have disrupted intermediary metabolism and thyrotoxicosis that has been associated with insulin resistance [1], [2], [3]. Abnormal levels of adipocytokines (eg, leptin, adiponectin, and resistin) in patients with thyroid dysfunction have been reported [4], [5], [6], [7]. Visfatin, an adipose tissue–derived protein, is known to have insulin-like metabolic effects [8]. The molecule was previously identified as a growth factor for early B-lymphocytes and named as pre-B cell colony-enhancing factor [9]. The gene for visfatin is expressed and regulated in adipocytes [10], [11]. Visfatin gene expression in visceral fat is increased in obese subjects, and the plasma concentration of visfatin has been associated more strongly with the amount of visceral fat than subcutaneous fat [8].

The plasma levels of visfatin in patients with hyperthyroidism due to Graves disease have not been studied. The insulin-like effects of visfatin, such as stimulating glucose transport into muscle cells and adipocytes and inhibiting glucose production in hepatocytes, are dependent on the plasma concentration [8]. Intravenous injection of recombinant visfatin in mice decreases plasma glucose in a dose-dependent fashion [8]. Visfatin appears to play a role in glucose homeostasis and may contribute to the pathogenesis of insulin resistance in hyperthyroidism. In addition, proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor–α (TNF-α) are elevated in Graves disease [12], [13], [14], which may affect insulin sensitivity and interact with visfatin.

The objective of this study was to compare plasma visfatin concentrations in subjects with hyperthyroidism due to Graves disease before and after antithyroid treatment and in euthyoid control subjects. The relationships among visfatin, serum inflammatory marker C-reactive protein (CRP), insulin concentrations, and homeostasis model assessment of insulin resistance index (HOMA-IR) were evaluated.

Section snippets

Subjects

The study enrolled 19 patients with hyperthyroidism due to Graves disease (14 women and 5 men) and 19 age- and sex-matched euthyroid controls (17 women and 2 men). The diagnosis of Graves disease was made by the presence of circulating thyrotropin receptor antibody (TRAB) in patients with hyperthyroidism. Informed consents were obtained from all subjects after thorough explanation of the procedures. All subjects were free of diabetes mellitus and hypertension. Of the 19 hyperthyroid patients, 8

Results

The demographic and clinical characteristics of the study population are shown in Table 1. The mean ± SEM age was 32.6 ± 1.8 years for hyperthyroid subjects and 36.7 ± 2.7 years for matching control subjects. As expected, subjects in the hyperthyroid group before treatment had lower TSH and higher T3 and FT4 serum concentrations than they did after treatment or the control group. The hyperthyroid group before treatment also had higher visfatin plasma concentrations (20.7 ± 1.8 ng/mL) than they

Discussion

Adipocytokines play a crucial role in the regulation of energy homeostasis, insulin sensitivity, lipid and carbohydrate metabolism, and inflammatory and atherogenic reactions [16], [17], [18], [19], [20], [21], [22]. The adipocytokine visfatin has metabolic effects quantitatively similar to those of insulin [8]. However, the relationship between visfatin and insulin resistance remains inconclusive. One study assessed the association between serum visfatin concentrations and levels of

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Hormonal regulation of visfatin gene in avian Leghorn male hepatoma (LMH) cells
2020, Comparative Biochemistry and Physiology -Part A : Molecular and Integrative Physiology
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Visfatin levels in hypo-and hyperthyroidism patients as well as the effects of T3 on the expression of visfatin system have been reported with controversial results. In patients with Graves' disease, circulating visfatin levels were found to be elevated and positively correlated with serum T3 (Chu et al., 2008). On the other side, MacLaren et al. (MacLaren et al., 2007) demonstrated that T3 treatment down regulated visfatin gene expression in 3 T3-L1 adipocytes.
Visfain has been extensively studied in mammals and has been shown to play an important role in obesity and insulin resistance. However, there is a paucity of information on visfatin regulation in non-mammalian species. After characterization of chicken visfatin gene, we undertook this study to determine its hormonal regulation in avian (non-mammalian) liver cells. Addition of 5 ng/mL TNFα, 100 ng/mL leptin, 1, 3, 10 or 100 ng/mL T3 for 24 h upregulated visfatin gene expression by 1.2, 1.8, 1.95, 1.75, 1.80, and 2.45 folds (P < .05), respectively, compared to untreated LMH cells. Administration of 10 ng/mL of orexin A significantly down regulated visfatin gene expression by 1.35 folds compared to control cells. In contrast, treatment with IL-6 or orexin B for 24 h did not influence visfatin mRNA abundance. These pro-inflammatory cytokines and obesity-related hormones modulate the expression of CRP, INSIG2, and nuclear orphan receptors. Hepatic CRP gene expression was significantly upregulated by IL-6, TNFα, orexin B, and T3 and down regulated by leptin and orexin A. LXR mRNA abundances were increased by orexin A, decreased by orexin B, and T3, and did not affected by IL6, TNFα, or leptin. The expression of FXR gene was induced by IL-6, leptin, and T3, but it was not influenced by TNFα, orexin A or B. CXR gene expression was up regulated by TNFα, leptin, orexin B, and T3, down regulated by 5 ng/mL orexin A, and did not affected by IL-6. INSIG2 mRNA levels were increased by TNFα (5 ng/mL), leptin (100 ng/mL), and T3 (1, 3, 10, and 100 ng/mL), decreased by orexin A, and remained unchanged with IL-6 or orexin B treatment.
Together, this is the first report showing hormonal regulation of visfatin in avian hepatocyte cells and suggesting a potential role of CRP, INSIG2, and nuclear orphan receptor LXR, FXR, and CXR in mediating these hormonal effects.
Pre-B cell colony enhancing factor (PBEF), a cytokine with multiple physiological functions
2013, Cytokine and Growth Factor Reviews
Citation Excerpt :
Oleate and sex hormones did not have any effect on adipocyte expression of PBEF, but TNF-α and PPAR-γ agonists decreased its expression. The inhibitory effects of T3 on PBEF were confirmed in patients with Graves's disease [29] by measuring PBEF levels before and after antithyroid treatment. Before treatment, the PBEF level was 20.7 ng/ml, which is higher than in normal subjects (16.2 ng/ml).
Pre-B cell colony enhancing factor (PBEF) is regarded as a proinflammatory cytokine. Named for its first discovered function as a pre-B cell colony enhancing factor, it has since been found to have many other functions relating to cell metabolism, inflammation, and immune modulation. It has also been found to have intracellular and extracellular forms, with the two overlapping in function. Most of the intracellular functions of PBEF are due to its role as a nicotinamide phosphoribosyltransferase (Nampt). It has been found in human endothelial cells, where it is able to induce angiogenesis through upregulation of VEGF and VEGFR and secretion of MCP-1. In human umbilical endothelial cells, PBEF increases levels of the protease MMP 2/9. PBEF has also been found in a variety of immune cells other than B cells and has been shown to inhibit apoptosis of macrophages. Extracellular PBEF has been shown to increase inflammatory cytokines, such as TNF-α, IL-1β, IL-16, and TGF-β1, and the chemokine receptor CCR3. PBEF also increases the production of IL-6, TNF-α, and IL-1β in CD14⁺ monocyctes, macrophages, and dendritic cells, enhances the effectiveness of T cells, and is vital to the development of both B and T lymphocytes. The purpose of this review is to summarize the recent advances in PBEF research.
Ischemia-modified albumin in patients with hyperthyroidism and hypothyroidism
2012, European Journal of Internal Medicine
Citation Excerpt :
However, no significant differences were found in serum CRP levels among different thyroid function groups [19,26]. Although CRP levels were higher in hyperthyroid patients than in euthyroid subjects, the difference did not reach statistical significance [27,28]. Even though patients with Hashimoto's thyroiditis were euthyroid, 8.6% had CRP levels greater than 10 mg/L [29].
The relationship between ischemia-modified albumin (IMA) and thyroid dysfunction remains uncertain. This study aimed to investigate the influence of overt hypothyroidism (Oho), overt hyperthyroidism (Ohe), and their treatments on serum IMA levels.
A total of 35 untreated patients with Ohe, 35 untreated patients with Oho, and 35 control subjects were enrolled in the study. C-reactive protein (CRP), homocysteine (Hcy), IMA, and lipid profiles were measured and evaluated before and after treatment.
CRP, Hcy, and IMA levels and lipid profiles were higher in patients with Oho than in euthyroid or Ohe subjects (p < 0.05). Basal IMA levels were reduced after treatments in all patients (p < 0.05). In Ohe patients, serum IMA levels were positively correlated with free triiodothyronine (r = 0.424, p = 0.011) and free thyroxine (r = 0.567, p < 0.001) levels. In Oho patients, serum IMA levels were inversely correlated with free triiodothyronine (r = − 0.555, p = 0.001) and free thyroxine (r = − 0.457, p = 0.006) but positively correlated with anti-thyroid peroxidase antibody, C-reactive protein, and homocysteine levels (p < 0.05). Linear regression analyses showed that free triiodothyronine was the most important factor affecting serum IMA levels in Ohe (β = 0.694, p = 0.019) and in Oho (β = − 0.512, p = 0.025).
IMA levels are increased in patients with thyroid dysfunction, particularly in overt hypothyroidism. Thyroid dysfunction has a significant impact on the oxidative stress status.
Visfatin is upregulated in type-2 diabetic rats and targets renal cells
2010, Kidney International
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In addition, plasma visfatin concentrations have been correlated with endothelial dysfunction in type-2 diabetic patients and patients with CKD.15,16 Furthermore, several studies have failed to identify an association between circulating levels of visfatin and insulin sensitivity.26–29 Collectively, these results suggest a new physiological role of visfatin in organ injury.
Visfatin (also known as pre-B cell colony-enhancing factor) is a newly discovered adipocytokine that is preferentially produced by visceral fat and regulated by cytokines promoting insulin resistance. Here we determined its renal synthesis and physiology in a genetic model of type 2 diabetes in rats. These rats had higher levels of visfatin synthesis in both glomeruli and tubulointerstitium compared to control rats. Plasma visfatin levels were significantly increased in the early stages of diabetic nephropathy and positively correlated with body weight, fasting plasma glucose, and microalbuminuria. Interestingly, visfatin synthesis was found to occur in podocytes and proximal tubular cells, as well as in adipocytes in vitro. Further, in both renal cells, visfatin synthesis was significantly increased by high glucose in the media but not by angiotensin II. Additionally, visfatin treatment induced rapid uptake of glucose and was associated with increased translocation of GLUT-1 to the cellular membrane of both renal cell types. Furthermore, visfatin induced tyrosine phosphorylation of the insulin receptor, activated downstream insulin signaling pathways such as Erk-1, Akt, and p38 MAPK, and markedly increased the levels of TGFβ1, PAI-1, type I collagen, and MCP-1 in both renal cells. Thus, our results suggest that visfatin is produced by renal cells and has an important paracrine role in the pathogenesis of diabetic nephropathy.
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Change of visfatin, C-reactive protein concentrations, and insulin sensitivity in patients with hyperthyroidism

Abstract

Introduction

Section snippets

Subjects

Results

Discussion

Metabolism

Biochem Biophys Res Commun

Immunol Lett

J Biol Chem

Graves' disease

N Engl J Med

Thyroid disease and lipids

Thyroid

Thyroid hormone excess and glucose intolerance

Exp Clin Endocrinol Diabetes

Changes in adipocyte hormones leptin, resistin, and adiponectin in thyroid dysfunction

J Cell Biochem

Role of thyroid hormones on serum leptin levels

Eur J Endocrinol

Serum concentrations of adipocytokines in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function