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Corresponding author. Department of Medicine, Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Plot No. 1-2, II-B, Nazimabad No2, Karachi, 74600, Pakistan.
Affiliations
Department of Medicine, Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, Pakistan
Department of Biochemistry, Baqai Medical University, Karachi, PakistanResearch Departments, Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, Pakistan
Genetic factors are involved in the development of T1D and studies have shown that the development of T1D also increases the risk of development of other autoimmune diseases.
Objective
To assess the frequency of thyroid dysfunction in subjects with type 1 diabetes.
Methodology
This study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), a tertiary care diabetes center of Karachi Pakistan from January 2005 to March 2017. Subject with type 1 diabetes (T1D) of all ages and both genders were included in the study. T1D was diagnosed on the basis of History, physical examination and relevant laboratory tests. The data of all registered patients was entered in a specially designed software. Thyroid stimulating hormone (TSH) was used as a screening test to assess thyroid dysfunction in subjects with type 1 diabetes. Further evaluation included FT4, T3 and thyroid antibodies where indicated. The data was analyzed on SPSS version 20.
Results
A total of 153 T1D subjects (67 male and 86 female) were included in the study. Out of 153 subjects, 23 (15.0%) had thyroid dysfunction of which 17 (11.1%) were found to have hypothyroidism (subclinical or clinical), 6 (3.9%) were hyperthyroid while 130(84.96%) subjects were having normal thyroid function. Statistical differences were found in body mass index and serum creatinine level among the different categories of thyroid dysfunction. The required dose of insulin was higher (but not significant) in subjects having hypothyroidism as compared to hyperthyroid or subjects with normal thyroid function.
Conclusion
High frequency of thyroid dysfunction was observed in subjects with T1D. Hypothyroidism was more common than hyperthyroidism. All subjects with T1D should be screened with TSH to evaluate for thyroid dysfunction.
There are significant differences in the incidence of T1D among different countries, highest rates reported from Finland and Sardinia (37 per 100000 people per year) and lowest rates reported from China and Venezuela (0–1 per 100000 people per year).
The exact prevalence of T1D is largely unknown, however according to an old Pakistan based study, conducted in 2002, the prevalence of hyperthyroidism and subclinical hyperthyroidism was 5.1 and 5.8% respectively while the prevalence of hypothyroidism and subclinical hyperthyroidism was 4.1 and 5.4% respectively. Both hyperthyroidism and hypothyroidism had a female predominance.
The pathophysiology of T1D is associated with autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency. Additionally, genetic factors have also been postulated to be involved in the development of T1D and studies have shown that the development of T1D also increases the risk of development of other autoimmune diseases. The most frequent co-morbid conditions in T1D include auto immune thyroid diseases
Relationships between thyroid function and autoimmunity withmetabolic derangement at the onset of type 1 diabetes: a cross sectional and longitudinal study.
Autoimmune thyroid diseases (ATD) are the most common autoimmune manifestations in children and adolescents with T1D6,7. Several genetic risk factors have been associated with T1DM, ATD and other autoimmune disorders.
There are multiple links between diabetes and thyroidal dysfunction. American diabetes association (ADA) currently recommends for screening TSH after stabilization at onset of T1D and every one to two years thereafter.
There is scarcity of data regarding thyroid dysfunction and its association with type 1 diabetes in Pakistan. Therefore, the aim of this study was to assess the frequency of thyroid dysfunction in subjects with T1D attending a tertiary care unit of Karachi, Pakistan.
2. Methodology
It is a cross sectional retrospective study conducted at Baqai Institute of Diabetology and Endocrinology (BIDE), a tertiary care unit of Baqai Medical University from January 2010 to March 2017. We include the subjects with T1D, visiting the outpatient department of BIDE and electronic database were taken and analyzed without any breach of confidentiality regarding their identification. T1D was labeled with reference to the ADA guidelines 2017 by retrieving information from the subject's records. None of the subject was having any prior history of using thyroid medication.
Thyroid stimulating hormone (TSH), was used as a screening test to assess thyroid dysfunction in subjects with T1D. Anti-thyroid antibodies have been done in only few cases where it was a special requirement. Sample selection process was described in Fig. 1. TSH values of range 0.4–4.5 was taken as a standard as determined by immune analysis (ELISA). Subjects were divided into 3 groups i.e. with normal thyroid function, with hypothyroidism and with hyperthyroidism. The relationship of thyroid dysfunction with T1D was also assessed with subject age, gender, body mass index (BMI), glycated hemoglobin (HbA1c) and the dose of insulin required for all 3 groups.
Fig. 1Frequency of patient with hopothyroid and hyperthyroid.
The data was analyzed on SPSS version 20. Chi-square Test, Independent t-test and analysis of variance (ANOVA) were used, where appropriate, to test for any statistically significant differences. P-value of <0.05 was considered to be statistically significant.
3. Results
The study included 153 subjects with type 1 diabetes, 67(43.8%) were males and 86(56.2%) were females. Baseline characteristics of studied subjects stratified by thyroid status is shown in Table 1. Most of the subjects had age of ≤20 years. Positive family history of diabetes was found in 36.6% subjects with mean body mass index was 19.83 ± 5.3 kg/m2. Mean serum creatinine and HbA1c level was 0.95 ± 0.58 mg/dl and 10.89 ± 2.72%, respectively. It was observed that hyperthyroid patients had significantly lower BMI and higher serum creatinine level than subjects with normal thyroid or hypothyroid (P-value<0.05). However, no significant differences were seen in terms of age, gender, marital status, family history of diabetes, blood pressure, and HbA1c level.
Table 1Thyroidal dysfunction with respect to baseline characteristics of patients.
Parameter
Thyroid-stimulating hormone (TSH)
P-value
Overall
normal
hyperthyroid
Hypothyroid
N
130(84.96%)
6(3.9%)
17(11.1%)
–
153
Age (years)
≤20
74(56.9%)
4(66.7%)
10(58.9%)
0.889
88(57.5%)
>20
56(43.1%)
2(33.3%)
7(41.2%)
65(42.5%)
Gender
Male
60(46.2%)
1(16.7%)
6(35.3%)
0.274
67(43.8%)
Female
5(83.3%)
70(53.8%)
11(64.7%)
86(56.2%)
Marital Status
Single
97(77.6%)
5(83.3%)
10(66.7%)
0.592
112(76.7%)
Married
28(22.4%)
1(16.7%)
5(33.3%)
34(23.3%)
Family history of diabetes
No
83(63.8%)
5(83.3%)
9(52.9%)
0.399
97(63.4%)
Yes
47(36.2%)
1(16.7%)
8(47.1%)
56(36.6%)
BMI (kg/m2)
19.51 ± 4.78
16.88 ± 3.25
22.88 ± 7.94
0.024
19.83 ± 5.3
Systolic BP (mmHg)
106.39 ± 15.63
100 ± 20
107.19 ± 12.64
0.644
106.26 ± 15.42
Diastolic BP (mmHg)
71.89 ± 9.48
69 ± 10.25
70 ± 9.13
0.623
71.58 ± 9.43
Serum Creatinine (mg/dl)
0.9 ± 0.44
1.9 ± 2.08
0.93 ± 0.28
0.003
0.95 ± 0.58
HbA1c (%)
11 ± 2.67
10.4 ± 4.22
10.15 ± 2.61
0.5
10.89 ± 2.72
Data presented as mean ± SD or n(%).
P-value <0.05 was considered statistically significant.
Mean dose of insulin to control hyperglycemia was found to be higher in hypothyroid subjects as compare to hyperthyroid and normal thyroid subjects but this difference was not statistically significant (P-value>0.05) as shown in Table 2.
Table 2Insulin dose requirements with respect to thyroidal status.
Parameter
Thyroid-stimulating hormone (TSH)
Normal
Hyperthyroid
Hypothyroid
P-value
Overall
n
130
6
17
–
153
Total insulin dose per day
55.1 ± 28.22
55.6 ± 23.25
66.62 ± 26.12
0.180
56.40 ± 27.91
Data presented as mean ± SD.
P-value <0.05 was considered statistically significant.
Frequency of thyroid dysfunction as shown in Fig. 1. Twenty-three (15.0%) subjects had thyroid dysfunction, 17 (11.1%) subjects were found to have hypothyroidism (subclinical or clinical), 6 (3.9%) subjects were hyperthyroid while 130 (84.96%) subjects were having normal thyroid function.
4. Discussion
In this study thyroid dysfunction was observed in 23 (15%) subjects who suffer from T1D and associated with a higher level of HbA1c at presentation and required higher doses of insulin to control diabetes compared to subjects with TID who had normal thyroid function.
Prevalence of thyroid dysfunction in diabetics varies in different studies, a large clinic based study of 1310 type1 and type 2 diabetics in adults reported 13.4% thyroid dysfunction, 8.8% in men and 16.8% in women.
NHANES 111 reports the prevalence of hypothyroidism in 4.6% and hyperthyroidism in 1.3% in U.S population. Similarly another published study reported a frequency of thyroid dysfunction as 14.6% in both type 1 and type 2 subjects with diabetes. Additionally, in diabetics 13% subjects were found to have subclinical hypothyroidism.
The largest reported study on thyroid dysfunction and subjects with type 1 diabetes has reported a prevalence of 9.5% among 7097 children and adolescents.
We observed similar trends in our study participants.
A small study from North India reported a prevalence of 17.4% hypothyroidism and 13.1% subclinical hypothyroidism, in girls with type 1 diabetes and 4.2% subclinical hypothyroidism in boys with type1 diabetes.
Out of many reasons postulated for this high prevalence of autoimmune thyroid disease in T1D is common sharing of autoimmune etiology. Various genetic and environmental factors interact with each other to produce immune dysfunction in various susceptible organs including pancreas and thyroid. It has been reported that despite the presence of anti-thyroid antibodies in blood majority of patients do not present with symptoms of thyroid dysfunction.
Therefore, as per the guidelines of American Diabetes Association (ADA) and the international society of pediatrics and adolescent diabetes (ISPAD) assessment of thyroid function and thyroid antibodies in children with T1D should be performed at the time of diagnosis or if are normal the test should be repeated every two years or more frequently if symptoms of thyroid disorder appears.
In this study hypothyroidism was associated with a more aggressive disease in pediatric subjects with TID, they had higher HbA1c levels and required higher insulin doses for achieving good glycemic control. In a study by Fatourechi et al., it was documented that children who had both TID and hypothyroidism had significantly higher HbA1c levels at enrollment, presented at younger age and most of them experienced DKA as the first presentation.
Balsamo et al., and Lin et al., also observed the association of severe metabolic derangement and impaired thyroid function in subjects with newly diagnosed TID.
Relationships between thyroid function and autoimmunity withmetabolic derangement at the onset of type 1 diabetes: a cross sectional and longitudinal study.
There are many interpretations to explain the disease severity of T1D with thyroid dysfunction. The effect of hypothyroidism on increasing insulin resistance and glucose metabolism is well documented
The strength of our study is the proper documentation of a large number of T1D subjects, however limitation of our study is that this is a single center study and antibody status was not checked in every subject due to financial constraints.
In this study we have observed association of thyroid dysfunction with type 1 diabetes, hypothyroidism (either clinical or subclinical) was found to be more common rather than hyperthyroidism with female predominance. Further long term studies are needed to validate our findings.
Authors contribution
N Sajid: Concept and design, Interpretation of data, wrote and reviewed the manuscript.
M Riaz: Concept and design, interpretation of data, edit and reviewed the manuscript.
A Fawwad: Interpretation of data, edit and reviewed the manuscript.
A Basit: Concept and design, edit and reviewed the manuscript.
Declaration of competing interests
Nothing to declare.
Acknowledgment
We acknowledge the Research Department of BIDE for its support.
References
Umpierrez G.E.
Latif K.A.
Murphy M.B.
et al.
Thyroid dysfunction in patients with type 1 diabetes: a longitudinal study.
Relationships between thyroid function and autoimmunity withmetabolic derangement at the onset of type 1 diabetes: a cross sectional and longitudinal study.
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