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ORIGINAL ARTICLE
Year : 2020  |  Volume : 9  |  Issue : 8  |  Page : 4277-4281  

Thyroid dysfunction in patients with type 2 diabetes mellitus and its association with diabetic complications


1 Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
2 Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
3 Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India

Date of Submission11-May-2020
Date of Decision14-Jun-2020
Date of Acceptance24-Jun-2020
Date of Web Publication25-Aug-2020

Correspondence Address:
Dr. Vadivelan Mehalingam
Department of Medicine, JIPMER, Dhanvantari Nagar, Puducherry - 605 006
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jfmpc.jfmpc_838_20

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  Abstract 


Background and Aims: Patients with type 2 diabetes mellitus are more prone to thyroid disorders. Hypothyroidism in them leads to an aggravation of microvascular complications. Diabetic patients with hypothyroidism also are at an increased risk of cardiovascular disease. Screening for thyroid dysfunction in diabetic patients will allow early treatment of hypothyroidism. The aim of this study was to assess the level of thyroid dysfunction in patients with type 2 diabetes mellitus and to identify the association of thyroid dysfunction with diabetic complications. Methods: This is a cross-sectional study that was conducted at departments of Medicine & Endocrinology in JIPMER, Pondicherry, between June 2016 and May 2019. 331 patients with type 2 diabetes mellitus attending the out-patient department without any prior history of thyroid disease, chronic liver disease or acute illness were recruited for the study. All subjects were screened for diabetic complications (nephropathy, neuropathy, retinopathy & cardiovascular disease). Thyroid function test was done in all subjects using chemiluminescent immunoassay method. Results: Hypothyroidism was seen in 13.9%, while hyperthyroidism was observed in 3.6% of the study subjects. Thyroid dysfunction was more common among females than males. No correlation was seen between thyroid dysfunction and diabetic complications in the study subjects. Conclusion: The prevalence of thyroid dysfunction is 17.5% in patients with type 2 diabetes mellitus. Thyroid dysfunction did not have any correlation with diabetic complications.

Keywords: Diabetic complications, thyroid dysfunction, type 2 diabetes mellitus


How to cite this article:
Mehalingam V, Sahoo J, Bobby Z, Vinod KV. Thyroid dysfunction in patients with type 2 diabetes mellitus and its association with diabetic complications. J Family Med Prim Care 2020;9:4277-81

How to cite this URL:
Mehalingam V, Sahoo J, Bobby Z, Vinod KV. Thyroid dysfunction in patients with type 2 diabetes mellitus and its association with diabetic complications. J Family Med Prim Care [serial online] 2020 [cited 2020 Sep 22];9:4277-81. Available from: http://www.jfmpc.com/text.asp?2020/9/8/4277/293099




  Introduction Top


Patients with type 2 diabetes mellitus are more prone to develop thyroid disorders. Many diabetic patients show features of thyroid dysfunction over a period of time.[1] Insulin resistance plays an important role in the development of hypothyroidism in patients with type 2 diabetes mellitus. Hypothyroidism in diabetic patients leads to an aggravation of dyslipidemia, hypertension and cardiovascular disease.[2] Thus, it is necessary to recognize and treat hypothyroidism in diabetic patients to prevent worsening of diabetic complications.[3] Hypothyroidism can be diagnosed with the help of a simple blood test which is readily and easily available. This can be performed by the primary care physician involved in treating diabetic patients. Early treatment of thyroid dysfunction in diabetic patients will help in normalizing their glycemic status and lipid profile.

Diabetic patients with sub-clinical hypothyroidism have been reported to be associated with an increased risk of nephropathy and cardiovascular disease.[4],[5] Micro-angiopathic complications of diabetes like retinopathy and neuropathy can worsen in the presence of co-existing hypothyroidism due to dyslipidemia. Screening for thyroid abnormalities in diabetic patients will allow early treatment of sub-clinical and overt thyroid dysfunction.[6] This study was done to estimate the prevalence of thyroid dysfunction in a south Indian population with type 2 diabetes mellitus and examine its association with diabetic complications.


  Aims and Objectives Top


  1. To estimate the prevalence of thyroid dysfunction in patients with type 2 diabetes mellitus
  2. To study the association of thyroid dysfunction with diabetic complications.



  Methods Top


This cross-sectional study was conducted in the Medicine and Endocrinology OPDs of a tertiary care teaching hospital in southern India from June 2016 to May 2019 after obtaining clearance from the Institutional Ethics Committee (IEC Ref. No. JIP/IEC/SC/2014/1/1508).

Considering a prevalence of 32% of thyroid dysfunction in diabetic patients seen in a previous study with an absolute precision of 5% at 5% level of significance, the sample size was calculated to be 331 (using the sample size formula for proportions)[1] Convenient sampling technique was used to include diabetic patients attending the Medicine and Endocrinology OPDs of the hospital. Patients with known thyroid disease, acute illness and chronic liver disease were excluded from the study.

Data regarding age and duration of diabetes were noted in the proforma of the study subjects. Assessment of body mass index (BMI) was done in all the subjects. Body weight was measured using an electronic scale to the nearest 0.1 kg. Subjects were asked to stand straight and relaxed with minimum clothing. Height was measured to the nearest 0.1 cm by using the wall-mounted stadiometer. The height of the subjects was taken in the standing position, without footwear keeping head in the Frankfurt plane. BMI was subsequently calculated dividing the body weight in kilograms by the square of height in meters. BMI between 25 and 29.9 kg/m 2 was taken as overweight while BMI above 30 kg/m 2 was taken as obesity for the purpose of this study. Blood pressure was measured in the study subjects with the help of a digital BP instrument. Subjects with BP above 140/90 mm Hg were considered to be hypertensive for the purpose of this study.

The laboratory investigations that were performed were glycosylated hemoglobin, fasting lipid profile and urine albumin. Screening for diabetic retinopathy was done by dilated fundus examination. Diabetic retinopathy was classified as non-proliferative (NPDR) or proliferative (PDR) in the study subjects. NPDR was further sub-divided into mild, moderate and severe categories. Twelve lead electrocardiogram (ECG) was taken for evaluation of cardiovascular disease. Study subjects with changes suggestive of ischemia on ECG were considered to have ischemic heart disease. Vibration perception threshold (VPT) was performed in subjects clinically suspected to have diabetic neuropathy. Based on VPT findings, the study subjects were defined as not having neuropathy, mild or severe neuropathy. Diabetic nephropathy was considered to be present if there was albuminuria. Microalbuminuria was defined as urinary albumin excretion of 30-300 mg/day while macroalbuminuria was defined as presence of urinary albumin of more than 300 mg/day. Microalbuminuria was estimated with the help of nephelometry technique in the biochemistry laboratory.

Biochemical analysis

Serum TSH (Thyroid Stimulating Hormone), free T3(Triiodothyronine) and free T4 (Thyroxine) were assessed in the fasting serum samples of the study subjects using chemiluminescent immunoassay method technology (ADVIA Centaur XP, Siemens Healthcare Global, USA). The normal range of TSH was 0.35-5.5 mU/L, 2.3-4.2 pg/ml for free T3 and 0.89-1.76 ng/dL for free T4. Sub-clinical hypothyroidism was defined as subjects with TSH value between 5-10 mU/L and normal free T3& T4 levels. Overt hypothyroidism was present in subjects with TSH value above 10 mU/L and low free T3& T4 levels. Sub-clinical hyperthyroidism was defined as low TSH with normal free T3& T4 levels. Overt hyperthyroidism was defined as low TSH with high free T4 levels. Serum creatinine was estimated by using enzymatic Jaffe's method. Lipid profile was also done for all the study subjects. Dyslipidemia was considered to be present if total serum cholesterol was above 200 mg/dL. Glycosylated hemoglobin was done in all study subjects by high performance liquid chromatography (HPLC) technique in the laboratory.

Statistical analysis

Data on continuous variables like age, duration of diabetes, BMI, HbA1c and lipid profile were expressed as mean with standard deviation (SD). Independent student's t test was done to compare continuous variables between two independent groups. Categorical variables like proportion of subjects having thyroid dysfunction, hypertension, dyslipidemia, obesity and diabetic complications were expressed as a percentage and were analyzed by Chi-square test (χ2). All statistical analysis was carried out at 5% level of significance and P value below 0.05 was considered as significant.


  Results Top


A total of 331 participants were included in this study. The baseline characteristics of the study subjects are given in [Table 1]. The mean duration of diabetes was 6.37 ± 2.41 years and the mean glycosylated hemoglobin was 9.3 ± 2.66% among the study population.
Table 1: Baseline characteristics of study participants

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The age and gender of the study subjects are given in [Table 2]. The maximum number of diabetic patients included in this study were in the age group of 41-70 years.
Table 2: Age and gender distribution of study participants

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[Table 3] shows the result of thyroid function test in the study subjects. A majority of study subjects (> 80%) had normal TSH, free T3 and free T4 values. Hypothyroidism was seen in 13.9% while hyperthyroidism was seen in only 3.6% of subjects.
Table 3: Thyroid function test results of study participants

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Diabetic nephropathy in study subjects was based on the presence of albuminuria. This was further classified into microalbuminuria (<300 mg albumin/gram of creatinine) and macroalbuminuria (>300 mg albumin/gram of creatinine). [Table 4], [Table 5], [Table 6], [Table 7] depict the presence of thyroid dysfunction in the study population according to age, gender, duration of diabetes and glycemic status. Both types of thyroid dysfunction (hypothyroidism & hyperthyroidism) were more common in females as compared to males.
Table 4: Thyroid dysfunction in study subjects according to gender

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Table 5: Thyroid dysfunction in study subjects according to age

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Table 6: Thyroid dysfunction in study subjects according to duration of diabetes

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Table 7: Thyroid dysfunction in study subjects according to glycemic status

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[Table 8] shows that there was no correlation of thyroid dysfunction with diabetic nephropathy in the study subjects. Similarly, there was no correlation of thyroid dysfunction in diabetic patients with cardiovascular disease, neuropathy and retinopathy. [Table 9], [Table 10], [Table 11].
Table 8: Correlation of thyroid dysfunction with diabetic nephropathy in study participants

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Table 9: Correlation of thyroid dysfunction with cardiovascular disease in study participants

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Table 10: Correlation of thyroid dysfunction with diabetic neuropathy in study participants

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Table 11: Correlation of thyroid dysfunction with diabetic retinopathy in study participants

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Summary

  1. The prevalence of thyroid dysfunction among diabetic patients was 17.5% in this study. Hypothyroidism was more common in the study subjects as compared to hyperthyroidism
  2. Thyroid dysfunction was more common among females in this study
  3. Hypothyroidism was more common among study subjects having diabetes for more than 5 years
  4. There was no correlation of thyroid dysfunction with diabetic complications among the study subjects



  Discussion Top


Insulin resistance that is typically seen in patients with type 2 diabetes mellitus plays a major role in the development of thyroid dysfunction in such patients. Thyroid dysfunction can occur in the form of hypothyroidism and hyperthyroidism. Sub-clinical hypothyroidism can also occur in diabetic patients and can contribute to diabetic complications like retinopathy, neuropathy and cardiovascular disease.[7]

The prevalence of thyroid dysfunction among diabetic patients in our study was found to be 17.5%. Hypothyroidism was more common among the study subjects. This is similar to a study done in south India by Jali MV et al. that showed the prevalence of thyroid dysfunction among diabetic patients to be 16.2%.[8] Another study done in north India showed that prevalence of sub-clinical hypothyroidism in diabetic patients was 18.8%. This study also found that prevalence of thyroid dysfunction was more among females, patients with dyslipidemia and retinopathy and patients with poor glycemic control & long duration of diabetes.[9] A retrospective study done by Demitrost L et al. showed that hypothyroidism was seen in 11.4% of type 2 diabetic patients while hyperthyroidism was seen in only 1.5% of the cases.[1] A study to assess the prevalence of thyroid dysfunction in patients with type 2 diabetes mellitus was done by Diez JJ et al. and it was found that 15.1% of the patients had overt hypothyroidism while overt hyperthyroidism was seen in 3.5% of the patients. The study also showed that thyroid dysfunction was not linked to the duration of diabetes, glycosylated hemoglobin and the presence of diabetic complications.[10] The study findings are in line with the present study which did not show a correlation between thyroid dysfunction and diabetic complications in the study subjects. However, another study done in Egypt showed that prevalence of thyroid dysfunction increased with an increase in glycosylated hemoglobin which suggests that poor glycemic control could play a role in the occurrence of thyroid dysfunction in diabetic patients.[11]

Our study showed that duration of diabetes (more than 5 years) was an important factor in patients with hypothyroidism. However, this was not found in diabetic patients having hyperthyroidism. A study that was done by Metab Al-Geffari et al. showed that duration of diabetes (more than 10 years) was an important risk factor for the development of thyroid dysfunction among type 2 diabetic patients in their study population.[12]

Apart from insulin resistance, autoimmunity may also have a role in the development of thyroid dysfunction in patients with type 2 diabetes mellitus. A study done by Radaideh AR et al., showed that 12.5% of diabetic patients were found to have thyroid disease. Among the diabetic patients with thyroid dysfunction, thyroid peroxidase antibody was found to be positive in 8.3% of cases. This study showed that screening for asymptomatic thyroid dysfunction may be helpful in diagnosing thyroid disease among diabetic patients.[13]

Hypothyroidism can be associated with an increased risk of nephropathy and cardiovascular disease among diabetic patients. This was shown in a study done by Chen HS et al. that found sub-clinical hypothyroidism to be a risk factor for nephropathy and cardiovascular disease among type 2 diabetic patients.[4] However, our study showed that there was no correlation of thyroid dysfunction with nephropathy and cardiovascular disease in patients with type 2 diabetes mellitus.

Thyroid dysfunction is a common occurrence among patients with type 2 diabetes mellitus. It is more pronounced in patients with long-standing diabetes and female gender. Treatment of thyroid dysfunction in diabetic patients can improve their morbidity and prevent worsening of diabetic complications.

Limitation of the study

Anti-thyroid peroxidase (anti TPO) antibody estimation was not done in our study. Thus, the role of thyroid auto-immune antibody in patients developing thyroid dysfunction among type 2 diabetic patients could not be assessed.


  Conclusion Top


The prevalence of thyroid dysfunction was 17.5% among patients with type 2 diabetes mellitus in this study. Hypothyroidism was more common among the study subjects than hyperthyroidism. There was no correlation of thyroid dysfunction with diabetic complications.

Acknowledgements

The authors gratefully acknowledge the financial support provided by JIPMER, Puducherry for conducting this study.

Financial support and sponsorship

JIPMER Intramural Research Grant.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Demitrost L, Ranabir S. Thyroid dysfunction in type 2 diabetes mellitus: A retrospective study. Indian J Endocrinol Metab 2012;16:S334-5.  Back to cited text no. 1
    
2.
Donckier JE. Endocrine diseases and diabetes. In: Pickup JC, Williams G, editors. Textbook of Diabetes Mellitus. Chicester, U.K.: Blackwell Publishing Company; 2003. p. 21-7.  Back to cited text no. 2
    
3.
Ghazali SM, Abbiyesuku FM. Thyroid dysfunction in type 2 diabetics seen at the University College Hospital, Ibadan, Nigeria. Niger J Physiol Sci 2010;25:173-9.  Back to cited text no. 3
    
4.
Chen HS, Wu TE, Jap TS, Lu RA, Wang ML, Chen RL, et al. Subclinical hypothyroidism is a risk factor for nephropathy and cardiovascular diseases in type 2 diabetic patients. Diabet Med 2007;24:1336-44.  Back to cited text no. 4
    
5.
Walsh JP, Bremner AP, Bulsara MK, O'Leary P, Leedman PJ, Feddema P, et al. Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med 2005;165:2467-72.  Back to cited text no. 5
    
6.
Perros P, McCrimmon RJ, Shaw G, Frier BM. Frequency of thyroid dysfunction in diabetic patients: Value of annual screening. Diabet Med 1995;12:622-7.  Back to cited text no. 6
    
7.
Wang C. The relationship between type 2 diabetes mellitus and related thyroid diseases. J Diabetes Res 2013;2013:390534.  Back to cited text no. 7
    
8.
Jali MV, Kambar S, Jali SM, Pawar N, Nalawade P. Prevalence of thyroid dysfunction among type 2 diabetes mellitus patients. Diabetes Metab Syndr 2017;11(Suppl 1):S105-8.  Back to cited text no. 8
    
9.
Ozair M, Noor S, Raghav A, Siddiqi SS, Chugtai AM, Ahmad J. Prevalence of thyroid disorders in north Indian type 2 diabetic subjects: A cross sectional study. Diabetes Metab Syndr 2018;12:301-4.  Back to cited text no. 9
    
10.
Diez JJ, Sanchez P, Iglesias P. Prevalence of thyroid dysfunction in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 2011;119:201-7.  Back to cited text no. 10
    
11.
Elgazar EH, Esheba NE, Shalaby SA, Mohamed WF. Thyroid dysfunction prevalence and relation to glycemic control in patients with type 2 diabetes mellitus. Diabetes Metab Syndr 2019;13:2513-7.  Back to cited text no. 11
    
12.
Al-Geffari M, Ahmad NA, Al-Sharqawi AH, Youssef AM, Alnaqeb D, Al-Rubeaan K. Risk factors for thyroid dysfunction among type 2 diabetic patients in a highly diabetes mellitus prevalent society. Int J Endocrinol 2013;2013:417920.  Back to cited text no. 12
    
13.
Radaideh AR, Nusier MK, Amari FL, Bateiha AE, El-Khateeb MS, Naser AS, et al. thyroid dysfunction in patients with type 2 diabetes mellitus in Jordan. Saudi Med J 2004;25:1046-50.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]



 

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