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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 45  |  Issue : 3  |  Page : 135-140

Relationship between serum Fetuin-A and insulin resistance in patients with hyperthyroidism


1 Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt

Date of Submission09-Jan-2017
Date of Acceptance04-May-2017
Date of Web Publication29-Nov-2017

Correspondence Address:
Samar R Ammar
Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, 3333
Egypt
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DOI: 10.4103/tmj.tmj_4_17

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  Abstract 


Background Fetuin-A is a multifunctional hepatic secretory protein that is involved in the pathology of many disorders. Recent epidemiological studies showed that serum Fetuin-A was associated with insulin resistance and its comorbidities, such as metabolic syndrome and type 2 diabetes. Hyperthyroidism involves a significant increase in the level of tissue metabolism and is often accompanied by abnormal glucose tolerance and insulin resistance.
Aim The aim of this work is to study the relationship between serum Fetuin-A and insulin resistance in patients with hyperthyroidism.
Participants and methods Our study was carried out on 35 newly diagnosed patients with hyperthyroidism (group I) and 20 healthy individuals matched for age and sex as controls (group II). Fetuin-A, fasting insulin, fasting blood glucose, free T3, free T4, thyroid stimulating hormone, total serum calcium, and high-sensitivity C-reactive protein were measured before and after euthyroidism was established.
Results Significantly higher levels of serum Fetuin-A were noted in the patient group before treatment compared with the control group. There was a significant decrease in serum Fetuin-A in the patients after treatment in comparison with before treatment. There was an insignificant difference between the patients after treatment and the control group in terms of serum Fetuin-A. Fetuin-A was correlated positively with Homeostasis Model of Assessment-Insulin Resistance, High-sensitivity C-reactive protein, fT3, and fT4, whereas there was a negative correlation between thyroid stimulating hormone and Fetuin-A.
Conclusion This study provides direct evidence for a relationship between serum Fetuin-A and insulin resistance in patients with hyperthyroidism.

Keywords: Fetuin-A, hyperthyroidism, insulin resistance


How to cite this article:
Ammar SR, Elbedewy TA, Nagy HM, Kotb NA. Relationship between serum Fetuin-A and insulin resistance in patients with hyperthyroidism. Tanta Med J 2017;45:135-40

How to cite this URL:
Ammar SR, Elbedewy TA, Nagy HM, Kotb NA. Relationship between serum Fetuin-A and insulin resistance in patients with hyperthyroidism. Tanta Med J [serial online] 2017 [cited 2018 May 26];45:135-40. Available from: http://www.tdj.eg.net/text.asp?2017/45/3/135/219441




  Introduction Top


Hyperthyroidism is a set of disorders that involve excess synthesis and secretion of thyroid hormones by the thyroid gland, which leads to the hyper-metabolic condition of thyrotoxicosis [1]. In approximately 50% of patients with hyperthyroidism, glucose tolerance disorders were observed with increased fasting insulin, C- peptide, and proinsulin concentrations, and 2–3% of patients had diabetes [2],[3]. Insulin resistance in hyperthyroidism patients can be explained by increased glucose absorption through the gastrointestinal tract and elevated hepatic glucose output, as well as decreased hepatic insulin sensitivity [3]. An alternative explanation could be peripheral insulin resistance because of increased secretion of bioactive mediators such as interleukin-6 and tumor necrosis factor-α from the adipose tissue, which exert both proinflammatory and insulin resistance effects [4].

Fetuin-A is a protein secreted from the liver that inhibits arterial calcium deposition. Fetuin-A may be an important link between obesity, hepatosteatosis, and insulin resistance [5],[6],[7]. High levels of circulating Fetuin-A are associated with insulin resistance. Several studies have reported the role of Fetuin-A in the development of type 2 diabetes and its plasma level could predict the incidence of type 2 diabetes independent of other established risk factors [8].

Thus, the aim of our work was to study the relationship between serum Fetuin-A and insulin resistance in patients with hyperthyroidism.


  Participants and methods Top


Participants

Our study was carried out on 35 newly diagnosed patients with hyperthyroidism (group I) and 20 healthy individuals matched for age and sex as controls (group II). They were recruited from outpatient clinics and inwards of Internal Medicine and General Surgery departments of Tanta University Hospitals from October 2014 to April 2015. Informed consent was obtained from all participants after a full explanation of the benefits and risks was provided. The study was approved by the ethics committee of the faculty of medicine, Tanta University.

Patients with diabetes mellitus, atherosclerotic vascular diseases, infections, malignancies, congestive heart disease, hepatic disorders, and renal dysfunction were excluded from our study.

The diagnosis of the cause of hyperthyroidism was made on the basis of clinical examination, laboratory investigations, thyroid ultrasound, radioactive iodine uptake, and thyroid scan.

Methods

All patients and controls were subjected to a full assessment of history and complete clinical examination.

Laboratory investigations

Five milliliters of venous blood was collected from each participant after 8 h of overnight fasting using disposable sterilized plastic syringes. The blood was allowed to clot for half an hour in a water bath at 37°C and then it was centrifuged for 15 min at 3000 rpm for the separation of serum. The following investigations were performed.
  1. Fasting blood glucose using an autoanalyzer with commercially available kits.
  2. Total serum calcium using spectrophotometry.
  3. Free thyroxin (T3), free triiodothyronine (T4), and thyroid stimulating hormone (TSH) using the enzyme-linked immunosorbent assay (ELISA) technique.
  4. Fasting insulin using the DRG-diagnostics Germany (DRG) insulin ELISA kit (a solid-phase ELISA based on the sandwich principle).
  5. High-sensitivity C-reactive protein (hs-CRP) using the DBC kit following a typical two-step capture or sandwich-type assay.
  6. Serum Fetuin-A using an ELISA. The biotechne Fetuin-A enzyme immunoassay kit (Bio-techne Company USA) uses the quantitative sandwich enzyme immunoassay technique.


The Homeostatic Model Assessment (HOMA-IR) was calculated using the following formula: HOMA-IR=fasting blood glucose (mg/dl)×fasting insulin (μIU/ml)/405 [9]. The presence of insulin resistance was considered when the HOMA-IR index was 2.5 or higher.

Laboratory investigations for the patients were performed before hyperthyroidism treatment was initiated and after euthyroidism was achieved. TSH, free T3, and free T4 were evaluated every 6 weeks until euthyroidism was achieved.

Statistical method

The collected data were tabulated and analyzed using SPSS (version 20; SPSS Inc., Chicago, Illinois, USA) software. Categorical data were presented as number and percentages, whereas quantitative data were expressed as range (minimum and maximum), mean, SD, and median. Comparison of continuous data between two groups was made using an unpaired t-test for parametric data and the Mann–Whitney test for nonparametric data. Comparison of continuous data between the same group before and after treatment was made using the Paired t-test for parametric data and the Wilcoxon’s signed ranks test for nonparametric data. χ2-Test and Fisher’s exact test were used for comparison of categorical data. Pearson’s tests for correlations between different parameters (nonparametric and parametric, respectively) were used. The accepted level of significance in this work was 0.05 (P<0.05 was considered significant).


  Results Top


The present study was carried out on 35 newly diagnosed patients with hyperthyroidism before the initiation of any treatment; the mean age of the patients was 34.97±10.52 years. There were 30 women and five men. Totally, 25 patients had Graves’ disease and 10 patients had toxic multinodular goiter. Also, our study included 20 healthy individuals matched for age (30.45±10.31 years) and sex (13 women and seven men). The duration of treatment ranged from 6 to 24 weeks, mean±SD 16.5±6.00 weeks. All patients received carbimazole at a dose that ranged from 20 to 40 mg, mean±SD (28.57±7.23 mg).

There was an insignificant difference between the patients studied and the control group before and after treatment in terms of BMI. There was a significant increase in BMI in the patients studied after treatment compared with before treatment.

Our results showed significantly lower levels of serum TSH in the patient group before treatment compared with the control group. Our results showed significantly higher levels of fT3, fT4, serum calcium, hs-CRP, HOMA-IR, and serum Fetuin-A in the patient group before treatment compared with the control group ([Table 1]).
Table 1 Comparison of the different parameters studied between the patients studied and the control group before and after treatment

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There was a significant increase in TSH in the studied patients after treatment in comparison with before treatment. There was a significant decrease in fT3, fT4, serum calcium, hs-CRP, HOMA-IR, and serum Fetuin-A in the studied patients after treatment in comparison with before treatment ([Table 1]).

There was an insignificant difference between the patients studied after treatment and the control group in terms of TSH, fT3, fT4, serum calcium, hs-CRP, and serum Fetuin-A. Significantly lower levels of HOMA-IR were noted in the patient group after treatment compared with the control group.

There was a significant positive correlation between Fetuin-A and free T3, free T4, hs-CRP, and HOMA-IR before and after treatment and a significant negative correlation between Fetuin-A and TSH before and after treatment ([Table 2] and [Figure 1]).
Table 2 Correlation between Fetuin-A and the different parameters studied before and after treatment

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Figure 1 Comparison of Fetuin-A between studied patients and control group before and after treatment.

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  Discussion Top


Fetuin-A is a multifunctional hepatic secretory protein that is involved in the pathology of many disorders [10]. High levels of circulating Fetuin-A are associated with insulin resistance, the primary underlying abnormality in the pathogenesis of type 2 diabetes mellitus [8].

The aim of this work was to study the relationship between serum Fetuin-A and insulin resistance in patients with hyperthyroidism.

Our study was carried out on 35 patients with hyperthyroidism; there were 30 (85.7%) women and five (14.3%) men, with a female to male ratio of 6 : 1. The age of our patients ranged from 19 to 59 years, with a mean±SD of 34.97±10.52 years. Pamuk et al. [11], in their study, enrolled 42 hyperthyroid patients, 27 (64%) women and 15 (36%) men, with a female : male ratio of 1.8 : 1, with a mean age±SD of 48.5±15.0 years.

In the present study, euthyroidism was achieved in 6.0–24.0 weeks, with a mean±SD of 16.5±6.0 weeks. The results of this work are not in agreement with those of Pamuk et al. [11], who reported that euthyroidism was achieved in 12±2.8 weeks. The longer duration of treatment needed to achieve euthyroidism in our study may be because of the poor compliance of patients to the treatment and follow-up or because of the severity of the disease.

Thyroid hormones regulate the basal energy expenditure through their effect on protein, carbohydrate, and lipid metabolism. Hyperthyroidism is associated with low body weight despite increased appetite because of an increase in the metabolic rate [12].

In the present study, there was a significant increase in BMI in the patients studied after treatment in comparison with before treatment (P<0.001). Our results were in agreement with those of Dutta et al. [13], who found that there was a significant increase in BMI in the patients studied after treatment compared with before treatment (P<0.001). However, Bilgir et al. [14] reported that there was an insignificant difference in BMI in the patients studied after treatment compared with before treatment. This may be because their study was carried out on patients with subclinical hyperthyroidism, which is characterized by unclear signs and symptoms of hyperthyroidism.

In the present study, there was a significant increase in TSH in the patients studied after treatment compared with before treatment (P<0.001). Our results were in agreement with those of Pamuk et al. [11], Dutta et al. [13], and Bilgir et al. [14], who reported that there was a significant increase in TSH in the patients studied after treatment compared with before treatment (P<0.0001, <0.001, =0.001), respectively.

In the present study, there was a significant decrease in fT3 and fT4 in the patients studied after treatment compared with before treatment (P<0.001, <0.001), respectively. Our results were in agreement with those of Pamuk et al. [11] and Dutta et al. [13], who reported that there was a significant decrease in fT3 and fT4 in the patients studied after treatment compared with before treatment (P<0.001, <0.001) (P<0.001, <0.0001), respectively.

In the present study, there was a significant decrease in the calcium level in the patients studied after treatment compared with before treatment (P<0.001). Our results are in agreement with those of Pamuk et al. [11], who reported that there was a significant decrease in the calcium level in patients studied after treatment compared with before treatment (P<0.0001); this can be explained by an increase in bone turnover associated with hyperthyroidism.

In the present study, there was a significant decrease in the hs-CRP level in the patients studied after treatment compared with before treatment (P<0.001). Our results were in agreement with those of Czarnywojtek et al. [15], who reported that the mean hs-CRP concentration was significantly higher among hyperthyroid patients than among the euthyroid patients (P=0.007) [15]. However, Bilgir et al. [14] reported that there was an insignificant difference in hs-CRP between the patients studied before and after treatment (P=0.107) and this can be explained by the short duration of treatment by propyl thiouracil therapy.

In the present study, 30 hyperthyroid patients had HOMA-IR value more than 4 (85.7%). Also, there was a significant decrease in HOMA-IR in the patients studied after treatment compared with before treatment (P<0.001). Our results were in agreement with those of Maratou et al. [16], Mitrou et al. [4], and Dutta et al. [13]. They reported that the mean HOMA-IR was significantly higher in hyperthyroid patients before treatment than among patients after treatment (P<0.05, =0.007, <0.05), respectively.

Thyroid hormones increase bone turnover markers and hyperthyroidism increases bone turnover. Fetuin-A may be increased in hyperthyroidism through a mechanism related to bone metabolism [11]. Also, hypercalcemia is a well-known complication of hyperthyroidism; thus, they believed that stimulating Fetuin-A synthesis may be an adaptation to prevent ectopic tissue calcification in hyperthyroidism [11]. In addition to its functions as an inhibitor of tissue calcification, Fetuin-A is an endogenous inhibitor of the insulin receptor tyrosine kinase [17] and Fetuin-A knockout mice show increased insulin sensitivity [18].

In the present study, there was a significant decrease in Fetuin-A in the patients studied after treatment compared with before treatment (P<0.001). Our results were in agreement with those of Pamuk et al. [11] and Bilgir et al. [14], who reported that the mean Fetuin-A was significantly higher in hyperthyroid patients before treatment than among patients after treatment (P<0.0001, =0.022), respectively.

In the present study, there was a significant negative correlation between Fetuin-A and TSH in the patients studied before and after treatment, whereas there was a significant positive correlation between Fetuin-A and fT3, fT4, hs-CRP, and HOMA-IR in the patients studied before and after treatment. These results were in agreement with those of Bakiner et al. [19], who documented that elevated Fetuin-A levels were associated with decreased TSH levels (P=0.001). Also, these results were in agreement with those of Pamuk et al. [11], who reported that elevated Fetuin-A levels were associated with increased fT3 (P=0.001), fT4 (P=0.002), hs-CRP (P=0.0001), and HOMA-IR (P=0.0001) levels. Also, these results were in agreement with those of Song et al. [20], who documented that there was a significant positive correlation between Fetuin-A and HOMA-IR (P=0.007). Also, these results were partially in agreement with those of Ishibashi et al. [21], who documented that there was a significant positive correlation between Fetuin-A and HOMA-IR (P<0.001), but there was no significant correlation between Fetuin-A and CRP [21]. Also, our results were in agreement with those of Ahmed et al. [22], who reported that there was a significant positive correlation between Fetuin-A and HOMA-IR (P<0.01) and between Fetuin-A and CRP (P<0.01).


  Conclusion Top


This study provides evidence for the significant correlation between serum Fetuin-A and insulin resistance, hs-CRP, and thyroid hormones in hyperthyroid patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Bahn Chair RS, Burch HB, Cooper DS. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract 2011; 21:593–646.  Back to cited text no. 1
    
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