Home / Archives / Vol 46 No 1 (2020) / Research Articles

Effect of Glycaemic Control on Thyroid Hormones Level in Type 2 Diabetic Patients

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Kamrunnahar Alo
Department of Physiology, Khwaja Yunus Ali Medical College, Enayetpur, Sirajganj, Bangladesh.

Mahmuda Begum
Department of Physiology, Sir Salimullah Medical College, Dhaka, Bangladesh

Md. Mahfuzar Rahman
Department of Community Medicine, Anwer Khan Modern Medical College, Dhaka, Bangladesh.

Keywords: Thyroid stimulating hormone, free thyroxine, free triiodothyronine, Type 2 Diabetes Mellitus, Glycaemic controls

DOI: 10.3329/bmrcb.v46i1.47466

Abstract

Introduction

Diabetes is characterized by chronic hyperglycemia associated with disturbances in protein and lipid metabolism on account of absolute or relative deficiency or inefficiency of insulin.¹ The reduced sensitivity to insulin is often called insulin resistance.² The prevalence of diabetes mellitus is increasing throughout the world due to population growth, aging, urbanization, increase prevalence of obesity and physical inactivity and increased consumption of refined foods globally.^3,4 Long term diabetes mellitus is associated with vascular complications like retinopathy, nephropathy, peripheral and autonomic neuropathy, cardiovascular and cerebrovascular diseases but adequate glycemic control can delay development of diabetic complication.^5,6

Thyroid dysfunction is another common endocrine disorder that is also increasing day by day and manifests either as hyper or hypothyroidism that may occur in type 2 diabetic patients.^7,8 There is great variability in the prevalence of thyroid dysfunction in general population ranging from 6.6% to 13.4% where as in diabetic patients the prevalence is greater and varies from 10 to 24%.⁹ This difference can be explained by different diagnostic criteria of thyroid disease, the degree of iodine intake among different regions, different sensitivities of the TSH assays and the large population diversity.¹⁰ However, in type 2 diabetic patients hypothyroidism is more common than hyperthyroidism.¹¹ Some researchers observed that 28.8% of diabetic patients having abnormal thyroid hormone levels, 22.5% had hypothyroidism and 6.25% had hyperthyroidism.¹² In this country, another researcher found 16.3% thyroid dysfunction among type 2 diabetic patients (9.0% had hypothyroidism and 7.0% had hyperthyroidism).¹³Diabetes mellitus influence thyroid function mainly at two sites; first at the level of hypothalamic control of thyroid stimulating hormone release and second, at the conversion of T₄to T₃¹⁴ especially those with poor glycemic control.¹⁵ Bartalena et al. found that poor glycemic control affects the hypothalamo-pituitary-thyroid axis.¹⁶ It causes impairment of nocturnal TSH secretion, thyroid hormone secretion and their response to TRH stimulation.¹⁷ On the other hand, higher circulating level of insulin associated with insulin resistance causes proliferation of thyroid tissue and formation of thyroid nodules.¹⁸ Moreover, alteration of the secretory activities of thyroid gland causes low thyroid hormone level.¹⁹ Uncontrolled diabetes is also associated with low serum T₃ state and impaired production of T₃ from T₄. Because the activity of thiol dependent hepatic enzyme T₄-5 deiodinase that causes peripheral conversion of thyroxin to triiodothironine via 5 monodeiodination reaction is reduced.²⁰ Besides these, Sahu et al. reported that thyroid peroxidase antibody is responsible for thyroid dysfunction in type 2 diabetic patients.²¹

The relationship between thyroid disorders and type 2 diabetes mellitus is characterized by a complex interdependent interaction. The prevalence of thyroid disorders in type 2 diabetic patients which is further found to be more in uncontrolled diabetic patients.²² Some researchers suggested that, type 2 diabetic patients should measure serum TSH level yearly to detect asymptomatic thyroid dysfunction as it may help to achieve good glycemic control.^23,24 Otherwise, it can aggravate classical risk factors such as dyslipidemia and lead to an increased risk of cardiovascular events and nephropathy in these patients.^6,25

Materials and Methods

This case control study was conducted among 30 diagnosed type 2 diabetic patients age ranged from 40 to 60 years were selected from the Out Patient Department of Endocrinology, Sir Salimullah Medical College (SSMC) and Mitford Hospital, Dhaka. The patients were diagnosed according to American Diabetic Association (ADA) criteria. Thirty apparently healthy subjects with similar age, BMI and socioeconomic status were selected as comparison/Control (Group A). Study group was again subdivided into two groups. Group B₁ included 17 uncontrolled diabetic patients and Group B₂ included 13 controlled diabetic patients. Both control and study groups were selected purposively. The study protocol was approved by Institutional Ethics Committee of SSMC. Diabetic patients with renal disease, known thyroid abnormalities, any other endocrine abnormalities and pregnancy were excluded from this study. After selection, the subjects were thoroughly informed about the aim, objectives and procedure of the study and were encouraged for voluntary participation. An informed written consent was taken from each subject. Data were generated using a standard pre-tested questionnaire. It was filled up by the principal investigator individually. In addition, samples were collected by the principal investigator as well. With all aseptic precautions 7 ml of venous blood was drawn by sterile disposable syringe from ante-cubital vein. Then 2 ml of whole blood was transferred to an EDTA tube for determination of HbA_1c level. The remaining blood was transferred to a clean and dry glass test tube and was kept in slanted position till formation of clot. After centrifugation, supernatant serum was collected in labeled eppendroff test-tube and was used for different biochemical tests. In assessing thyroid function, serum TSH, FT₄ and FT₃ levels were measured by chemiluminescent microparticle immunoassay (CMIA) method in the Department of Biochemistry, BSMMU, Dhaka however, fasting plasma glucose level was estimated by glucose oxidase (GOD) method in the Department of Physiology, SSMC and HbA_1c levels were estimated by ion exchange high performance liquid chromatography (HPLC) method in the Department of Biochemistry, BSMMU to observe participants glycemic status. Correlation of HbA_1c with serum TSH, FT₄ and FT₃ were done to observe its relationship. The data quality control was done using appropriate checklist. The statistical analysis was done by ANOVA test, Bonferroni test and Pearson’s correlation coefficient test by using Statistical Package of Social Science (SPSS) windows.

Results

In this study, the mean fasting blood glucose level was significantly (p<0.001, p≤0.05) higher in uncontrolled and controlled diabetic patients in comparison to that of non-diabetic subjects and it was also significantly (p<0.001) higher in uncontrolled diabetic patients in comparison to that of controlled diabetic patients. Again, the mean HbA_1c level was significantly (p<0.001, p<0.01) higher in uncontrolled and controlled diabetic patients in comparison to that of non-diabetic subjects and it was also significantly (p<0.001) higher in uncontrolled diabetic patients than that of controlled diabetic patients (Table II).

In this study, the mean serum TSH level was significantly (p<0.001, p≤0.05) higher in uncontrolled and controlled diabetic patients than that of non-diabetic subjects and it was also significantly (p<0.01) higher in uncontrolled diabetic patients as compared to controlled diabetic patients. On the other hand, the mean serum FT₄ level was significantly (p<0.01, p≤0.05) lower in uncontrolled diabetic patients than that of non-diabetic subjects and controlled diabetic patients. This level was lower in controlled diabetic patients than that of non-diabetic subjects but the difference was not statistically significant. However, the mean serum FT₃ level was significantly (p≤0.05) lower in uncontrolled diabetic patients in comparison to that of non-diabetic subjects. FT₃ level was lower in controlled diabetic patients than that of non-diabetic subjects but the difference was not statistically significant. Again, this level was lower in uncontrolled diabetic patients than that of controlled diabetic patients but the difference was not statistically significant (table III). Moreover, HbA1c found positively correlated with serum TSH level and negatively correlated with serum FT₄ & FT₃ level (Figure 1), (Figure 2), and (Figure 3).

Again, in this study, among the uncontrolled diabetic patients, 70.6% were euthyroid, 11.8% were hypothyroid and 17.7% were subclinical hypothyroid. Results are shown in (Figure 4).

Discussion

This study observed thyroid function status in uncontrolled and controlled type 2 diabetic patients by measuring thyroid hormone levels. HbA1c level was also estimated to find out its level on diabetic patients and to correlate them with serum TSH, FT₄ and FT₃ levels. Results of this study showed serum TSH level was significantly higher in uncontrolled diabetic patients than that of controlled diabetic patients. This result agrees to other researchers.¹⁷ The exact mechanism that was involved in high TSH level in type 2 diabetic patients was not yet clearly established. However, several investigators of different countries proposed various suggestions on this aspect. Some researchers reported that metabolic control affects the hypothalamo-pituitary-thyroid (HPT) axis and metabolic de-compensation leads to impairment of TSH secretion and TSH response to TRH stimulation was blunted in poorly controlled diabetic patients that cause hypothyroidism in type 2 diabetic patients.^16,17

Whereas the mean serum FT₄ level was significantly lower in uncontrolled diabetic patients than that of controlled diabetic patients. These findings were consistent with that of some other researchers of different countries.¹⁷ Again, the mean serum FT₃ level was non-significantly lower in uncontrolled diabetic patients than that of controlled diabetic patients. Similar finding was observed by Gursoy et al.¹⁷ On the other hand, some researchers found significantly lower serum FT₃ level in uncontrolled diabetic patients than that of controlled diabetic patients.¹⁵ T₄-5’deiodinase enzyme is responsible for deiodination of T₄ to T_3.²⁶ This enzyme activity was decreased in streptozotocin induced diabetic rats that catalyzes peripheral deiodination of T₄ to T₃ and produces low T₃ state.²⁰ Pittman et al reported that, reduced level of tissue glutathione is responsible for lowering deiodination in streptozotocin induced diabetic rats.²⁷ Moreover, thyroid hormone binding inhibitor (THBI), inhibitor of extrathyroidal conversion (IEC) of thyroxine to triiodothyronine and free fatty acid (FFA) are responsible for abnormal thyroid hormone level in uncontrolled diabetic patients.

In the present study, lower levels of thyroid hormones may be due to poor glycemic control. The significant negative correlation of HbA_1c level with FT₃ and FT₄ levels in uncontrolled diabetic patients are in favor of this statement. Again, serum thyroid stimulating hormone level was found significantly higher in uncontrolled diabetic patients than controlled diabetic patients. This may be due to negative feedback regulation resulting in increased TSH secretion from the anterior pituitary gland. The positive correlation of serum TSH level with HbA_1c of the subjects further supports these findings.

Conclusion

Based on the results of this study, it can be concluded that, hypothyroidism occurs in type 2 diabetic patients which was found only in uncontrolled diabetic patients and this may be due to their poor glycaemic control.

Acknowledgement

The authors do acknowledge gratefully to all the faculty members of the Department of Physiology, SSMC for their active support and offer special thanks to all the study population for their kind cooperation in deed

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