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Journal of Endocrinology & Metabolism

Original Article

Volume 5, Number 1-2, April 2015, pages 179-183

Thyroid Hormones Protect Type 2 Diabetes Obese Patients Against Cardio-Metabolic Risk Factors

The obesity is considered as a risk factor of cardiovascular events and dysfunction of thyroid gland is observed in obese patients. An inverse linear association of anthropometric measurements including waist circumference and body mass index (BMI) with serum thyroid stimulating hormone (TSH) levels was observed in adult [1]. In young women, the higher prevalence of metabolic syndrome was reported significantly in those with a TSH level > 2.5 mIU/L and they had a two-fold greater risk of metabolic syndrome [2].

In obese children, the serum levels of TSH and free triiodothyronine (fT3) were higher than non-obese, and the TSH was positively correlated with total cholesterol (TC), triglycerides (TG), and systolic blood pressure [3]. Another study observed a significant association between TSH levels and impaired fasting glucose, impaired glucose tolerance, high TC, high low-density lipoprotein cholesterol (LDL-c) and high TG [4].

In women, there is a relation between the metabolic syndrome components with TSH and fT3 levels irrespective of the menopausal status [5]. Moreover, non-diabetic non-obese patients who presented with low thyroid function (even in the euthyroid state) were predisposed to have high cholesterol, glucose, insulin, and insulin resistance levels [6].

In T2D, there is non-significant difference between patients with euthyroid and subclinical hypothyroidism in term of serum TG or high-density lipoprotein-cholesterol (HDL-c) and TSH level does not show significant correlation with these parameters [7]. Thyroid dysfunction was reported in diabetes and the hormonal profile showed subclinical or overt hypothyroidism and the level of TSH reduced with oral hypoglycemic agents particularly metformin [8]. Wang et al demonstrated a significant association between acute insulin responses (using arginine stimulating test) withT3 and fT3 indicated the protective effect of thyroid hormones for beta cell function in T2D [9]. There is evidence that the changes in thyroid function (increase TSH and fT4) are related to the adiposity and insulin resistance that present in obese or T2D patients [10]. Further study showed that the components of metabolic syndrome (except HDL-c) correlated with T3 (independent to the insulin resistance) and free T4 (in the presence of insulin resistance status) [11].

This study aimed to demonstrate the gender-based effect of thyroid hormones as well as TSH against the cardio-metabolic risk factors that observed in obese T2D.

This cross-sectional study was conducted in Martyr LaylaQasm Center for Diabetes Mellitus in Erbil, Iraq in cooperation with Department of Pharmacology, College of Medicine at Al-Mustansiriya University in Baghdad, Iraq. The study was conducted according to the guidelines from the Declaration of Helsinki with approval from a local ethical review board. All patients gave written informed consent. The criteria of inclusion are obese patients with T2D using oral hypoglycemic agents. Obesity means a BMI of ≥ 30 kg/m². All the patients were on the glibenclamide (up to 12.5 mg daily) and metformin (up to 1,750 mg daily). The present study excluded the patients with a history of rheumatoid arthritis, hematological, neoplastic, renal, hepatic or thyroid diseases, or patients receiving treatment with anti-inflammatory drugs. Patients with acute or chronic infections and autoimmune disease (e.g. systemic lupus erythematous) were also excluded from the study. Demographic data, medical history and treatment were obtained from the case-sheet data in the center. Modifiable risk factors, events or complications, and current therapy were recorded. A person who reported smoking on admission was defined as current smoker. The following anthropometric measurements are determined: height (m), weight (kg), waist circumference (cm). The BMI and waist/height ratios were calculated taking the cut-off level of BMI ≥ 30 kg/m² and waist to hip ratio ≥ 0.5 as an indication of obesity. The blood pressure (mm Hg) was measured on sitting position and the mean of three readings was taken. The difference between systolic and diastolic blood pressure represented the pulse pressure and the mean arterial blood pressure was equal to diastolic blood pressure + 1/3 pulse pressure.

Peripheral venous blood was drawn immediately after admission into tubes, then the samples were centrifuged at 2,500 rpm for 10 min, and the sera were separated for determination of fasting serum glucose, HbA1_c (%) fasting lipid profile and thyroid hormones: TSH, total thyroxin (T4) and total triiodothyronine (T3).

The determinants of lipid profile included fasting serum TC, TG, and HDL-c. The non-HDL-c lipoprotein (LDL-c) is determined by using the equation that was described by Rungtanapirom et al) [12]

Determined LDL = 0.98 (TC - HDL) - 0.12 TG + 0.1 Age + 2.4 Sex + 0.2 BMI (for male = 1 and for female = 2)

The atherogenic index was calculated by estimating the log of the ratio TG to HDL values. Quantitative determination of serum high sensitive C-reactive protein (hsCRP) was determined using the enzyme-linked immunosorbent assay (ELISA) technique. The following values indicated the level of cardiovascular event risk: < 1.0 mg/L (low risk), 1.0 - 3.0 mg/L (intermediate risk) and > 3.0 mg/L (high risk). The determination of thyroid hormones was carried on using MiniVidas equipment and the kits purchased from bioMerieux, France. The normal ranges of thyroid hormones are TSH: 0.3 - 0.6 mIU/L, T4: 60 - 140 nmol/L, and T3: 0.9 - 2.5 nmol/L.

Data are expressed as number, percent, mean ± SD or median. Unpaired Student’s t-test was used to evaluate differences between the two groups and the simple correlation test was applied for the association between the independent and dependent factors. For all tests, a two-tailed P ≤ 0.05 was considered statistically significant. All calculations were made using Excel 2003 program for Windows.

Table 1 shows the characteristics of patient. There was non-significant difference between men and women regarding the age and the duration of diabetes. Family history was reported in 24% in women compared with 32% in men which did not reach significant level. The results of anthropometric measurements showed significant high body weight and BMI in women compared with men while the waist circumference and waist to height ratio did not show significant differences.

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Table 1. Characteristics of the Patients

Table 2 shows the profile of cardio-metabolic risk factors. The glycemic status that was determined by fasting serum glucose and glycosylated hemoglobin indicated that the patients of both genders were uncontrolled diabetes. There was non-significant difference between men and women with respect to the glycemic status. There was non-significant difference between the blood pressures (systolic, diastolic, mean and pulse) between women and men. The mean values of systolic and diastolic blood pressure exceeded the upper limits of 130 mm Hg systolic and 85 mm Hg diastolic (cut-off values in diabetes). Fasting serum profile indicated that both genders are at risk of cardiovascular events. The mean values of fasting serum TG, atherogenic lipoprotein and atherogenic index exceed the upper normal values. The mean value of HDL-c achieved the level within the normal range. There were non-significant differences between women and men in the mean values of lipid profile. The mean value of hsCRP which amounted more than 3 mg/L indicated that all patients were at high risk of cardiovascular events. Table 3 shows changes in the thyroid function reflected by fluctuation in the thyroid hormone levels. The mean level of TSH was non-significantly higher in women compared with men. Normal range TSH hormone level was reported in 16 out of 100 (16%) women compared with seven out of 50 (14%) men, a difference that did not reach significant level. The low level of TSH was found in higher percent men compared with women (26% versus 18%). The mean levels of T4 and T3 were non-significantly higher in men compared with women. Table 4 shows the correlations between the cardio-metabolic risk factors and the thyroid hormones. TSH was significantly correlated (positively) with BMI, waist circumference, mean arterial blood pressure, and glycosylated hemoglobin, while it correlated inversely with HDL-c. Non-significant correlations were observed with fasting serum glucose and hsCRP. The power of correlation as assessed by correlation coefficient (r) was higher in men compared with women. The opposite pictures were observed with T4 or T3. Both hormones were significantly correlated in an inverse pattern with cardio-metabolic risk factors and positively correlated with HDL-c. Again the higher coefficient factors of these associations were found in men compared with women.

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Table 2. Cardio-Metabolic Risk Factors

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Table 3. Serum Thyroid Hormones

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Table 4. Correlation Coefficient of the Relationship Between Thyroid Hormones and Cardio-Metabolic Risk Factors

The results of this study show fluctuation in the serum TSH, T3 and T4 indicating thyroid gland dysfunction in uncontrolled T2D. Moreover, the higher serum T3 or T4 associated with lower cardio-metabolic risk factors. These changes are well observed in men compared with women indicating the alteration in thyroid gland function in T2D is gender-based effect. Obesity as a cause of insulin resistance may play a role in thyroid dysfunction. There is evidence that low free T4 is associated with insulin resistance [13]. Therefore, it is possible to attribute the findings of this study to the obesity as the BMI value is significantly less in men compared with women. Solanki et al reported significant correlation between BMI and TSH in healthy adults but the authors did not highlight the difference between men and women [14]. As shown in Table 2, there were no significant differences between men and women regarding the cardio-metabolic risk factors which indicated that the results of this study was not biased with variations in the clinical presentation. Low serum T3 and T4, and low TSH levels are presented in high percent in women compared with men and such subclinical hypothyroidism status is presented with cardio-metabolic risk factors as shown in Table 2. This finding confirmed the results reported by Pesic et al but again the authors did not demonstrate the effect of gender [15]. The positive correlation between glycosylated hemoglobin and TSH, and an inverse correlation with T3 or T4 in T2D patients confirmed a previous study carried on non-diabetic subject [16]. This observation may be attributed to the catabolic effect of thyroid hormones as well as the insulin resistant status on the albumin metabolism which reflected on the glycosylated hemoglobin [17]. In this study the hsCRP as an inflammatory biomarker does not significantly correlate with TSH, but an inverse significant correlation with T3 or T4 was observed with a higher coefficient correlation in male. This observation agreed with the previous results that reported an association of higher circulating levels of inflammatory markers with lower levels of free serum T3 in elderly population [18]. A prominent gender-based effect of thyroid hormones and TSH in relation to the HDL-c was observed in this study. Triolo et al observed that plasma glucose interacted positively with free T4 on HDL antioxidative capacity, and that in chronic hyperglycemia, the low free T4 within the euthyroid range involved in the diminished HDL antioxidative capacity [19]. One of the limitations of this study is non-diabetic healthy subjects are not included and thereby the gender-based effect is limited in the T2D. It concludes that there are alterations in the thyroid gland function in obese T2D patients and the levels of thyroid hormones (T3 and T4) were significantly and inversely correlated with cardio-metabolic risk factors which prominently were observed in men.

Conflict of Interest

Nil.

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