European Journal of Cardiovascular Medicine

Diabetes mellitus (DM) is a group of metabolic illnesses characterized by insulin insufficiency induced hyperglycemia that impairs the metabolism of fat, protein, carbohydrates and causes electrolyte abnormalities ^[1]. In India, the percentage of people with diabetes varies between 4 to 9% in rural areas and between 12 to 19% in urban areas. By 2030, there will be 71.4 million diabetics worldwide, up from 31.7 million in 2000, based on World Health Organization estimates ^[2]. A cross sectional study conducted in India found that the prevalence of thyroid dysfunction was 17.5% among patients with type 2 diabetes mellitus, with hypothyroidism being more common than hyperthyroidism ^[1,5]. Thyroid disorders were significantly more prevalent in patients with diabetes (31%) than in controls (12%)^[5]. 

Thyroxine (T4) and Tri-iodothyronine (T3), two hormones essential for cellular growth and metabolic equilibrium, are produced by the thyroid gland ^[1,2]. The mean annual incidence of autoimmune hypothyroidism is 4 per 1000 women and 1 per 1000 men. Subclinical hypothyroidism affects 6-8% of women and 3% of males ^{[1, 2]}. 60–80% of cases of thyrotoxicosis cases are caused by graves disease, affecting up to 2% of women.

Owing to autoimmune causes, thyroid dysfunction is widespread in type 1 diabetes. However, new research indicates that thyroid dysfunction, particularly hypothyroidism, is also common in type 2 diabetes. Thyroid impairment, primarily subclinical hypothyroidism, affects up to 31.4% of patients with type 2 diabetes ^{[3, 4,5]}. A meta-analysis of prospective observational studies found that thyroid dysfunction was associated with an increased risk of developing type 2 diabetes ^[3] and that there exists a bidirectional association between diabetes and thyroid disorders ^[3,4].

Hypothyroidism in patients with diabetes can lead to an aggravation of dyslipidemia and elevate the risk of cardiovascular disease and hyperthyroidism impairs glycemic control. In patients with diabetes, early detection and treatment of thyroid dysfunction may minimize the risk of cerebrovascular and cardiovascular consequences ^[1,4,8].

Screening for thyroid dysfunction in patients with diabetes is recommended to allow early treatment and prevent the worsening of diabetic complications ^[1,4]. Thyroid dysfunction in diabetes may alter glucose metabolism and affect glycemic control ^[5]. In summary, these recent studies highlight the high prevalence of thyroid dysfunction in type 2 diabetes, its bidirectional association, the importance of screening and treating thyroid disorders in patients with diabetes to optimize their metabolic control and prevent complications.

The purpose of this study was to determine how common thyroid dysfunction occurs in individuals with type 2 diabetes with the following objectives: (i) To determine the different modes of clinical presentation of thyroid dysfunction in patients with type 2 diabetes mellitus and (ii) To assess the thyroid autoimmunity status in patients with type 2 diabetes mellitus.

Ethical Committee and Scientific Board Approval: Taken from the concerned authorized regulatory board prior to the study.

Study Site: This study was conducted at a tertiary care center known for its advanced healthcare services.

Study Population: This study involved retrospective collection of data from patients with type 2 diabetes mellitus (T2DM) admitted to the tertiary care center. Data were collected from inpatient case sheets maintained in the Medical Records Department between October 2018 and February 2020. Patient details, including clinical findings relevant to thyroid dysfunction, were noted based on predefined inclusion and exclusion criteria to ensure reliability and relevance of the study data. Furthermore, this comprehensive recording system allowed access to vital information regarding patient demographics, clinical presentations and diagnostic test results.

Study Design: A retrospective observational study was conducted to investigate the prevalence and characteristics of thyroid dysfunction in patients with type 2 diabetes mellitus (T2DM). In this study, data from medical records were analyzed without direct intervention or follow-up of patients. This approach allowed for the evaluation of clinical outcomes and associations based on existing patient data.

Sample Size with Justification: The sample size for the present study was determined based on the assumption that the prevalence of thyroid dysfunction among patients with type 2 diabetes mellitus (T2DM) in the Indian population is approximately 20%, as observed in previous studies. The following sample size formula was applied to ensure adequate statistical power and precision:

n = Z² P (1-P)/ d²

Where:

n = required sample size

Z = value from the standard normal distribution corresponding to the desired confidence level (Z = 1.96 for 95% confidence interval)

P = expected prevalence or proportion based on previous studies (20% or 0.20)

d =   desired precision, which is half the width of the confidence interval (in this case, 5%)

By applying these values,

n = [(1.96)² x 0.20 x (1-0.20)] ÷ (0.05)² = 245 ~ 250

The calculated sample size was approximately 246, which was rounded to 250 to ensure a sufficient number of participants for an accurate analysis. This sample size allowed for an estimate of the prevalence of thyroid dysfunction in T2DM patients with a 95% confidence level and a 5% margin of error.

The inclusion criteria for the study were patients admitted to the tertiary care center with a confirmed history of type 2 diabetes mellitus (T2DM) and those aged > 30 years. The exclusion criteria were patients diagnosed with gestational diabetes mellitus (GDM) and those with pre-existing hepatic or renal dysfunction, as these conditions could potentially confound the assessment of thyroid dysfunction in the context of type 2 diabetes.

The study commenced after obtaining approval from the Institutional Ethics Committee and the Scientific Review Board. We retrospectively collected data from inpatient case files of patients admitted with a history of type 2 diabetes mellitus (T2DM). These records were maintained in the Medical Records Department and detailed information was recorded in a structured case record form. The following details were extracted for each patient: Age, sex, date of admission, past medical history, family history, drug history, body mass index (BMI) and results of routine investigations. This included diagnostic workups for diabetes, thyroid function tests and lipid profiles, which provided comprehensive data for the analysis of thyroid dysfunction in T2DM patients.

Statistical analysis

After data collection, the data were entered into an MS Excel datasheet and statistical analysis was performed using SPSS version 17.0. Descriptive statistics were used to summarize the data. For quantitative variables, such as age, duration of diabetes, TSH levels, HbA1c and BMI, measures such as mean, standard deviation, standard error of the mean and median were computed. For qualitative variables, such as hypertension and dyslipidemia, percentages and frequencies were used to describe the distribution within the study population.

Definition used in the study: We classified patients as having SCH, overt hypothyroidism, hyperthyroidism and subclinical hyperthyroidism based on the definitions as per American Thyroid Association's (ATA) clinical practice guidelines.

SCH was defined as TSH 4.5 to 10 with normal FT4; Overt hypothyroidism as TSH >10 with low FT4; Hyperthyroidism as < 0.45 TSH with raised FT4; Subclinical hyperthyroidism as < 0.45 TSH with normal FT4; Dyslipidemia as LDL >100 mg/dl or on statin therapy

The study included 111 male patients (44.4 %) and 139 female patients (55.6 %).  The age distribution of the study group was as follows: 37 patients (14.8%) were aged between 35 and 45 years, 112 patients (44.8%) were between 45.1 and 55 years, 76 patients (30.4%) were between 55.1 and 65 years, 22 patients (8.8%) were between 65 and 75 years and 3 patients (1.2%) were older than 75 years. The total number of patients were 250, with a mean age of 54.02 years (±8.7). A standard deviation of 14 reflected a moderate spread from the mean, showing a consistent distribution of gender representation. The coefficient of variation was 11.2%, indicating a relatively low degree of variation in the gender distribution relative to the critical difference at p=0.05, which was approximately 0.93, indicating that any gender difference was statistically insignificant.

Among the 139 female patients, 44 (31.7%) were found to have thyroid dysfunction, including 30 cases of subclinical hypothyroidism (SCH), 12 cases of overt hypothyroidism and 2 cases of overt hyperthyroidism. In contrast, of 111 male patients, 15 (13.5%) had thyroid dysfunction, with 10 cases of SCH, 4 cases of overt hypothyroidism and 1 case of hyperthyroidism. This sex difference in the prevalence of thyroid dysfunction was statistically significant (p = 0.001).

The mean age of diabetic patients with thyroid dysfunction was slightly higher (54.22 ± 8.66 years) compared to those with normal thyroid function (euthyroid), who had a mean age of 53.96 ± 8.75 years. However, the difference in mean age between the two groups was not statistically significant (p = 0.840).

Table 1: Distribution of Thyroid Function in the Study

The distribution of age among diabetic patients based on their thyroid function status shows that the majority of patients, both euthyroid and with thyroid dysfunction, fall within the 45-55 age group. Specifically, 83 patients were euthyroid and 29 had thyroid dysfunction in this age range, totaling 112 patients. In the 55-65 age group, 56 were euthyroid, while 20 had thyroid dysfunction, with a total of 76 patients. Among those aged 35-45 years, 31 were euthyroid and 6 had thyroid dysfunction, resulting in a total of 37 patients. In the older age groups, 65-75 years, 20 were euthyroid and 2 had thyroid dysfunction, while in the >75 age group, one patient was euthyroid and two had thyroid dysfunction. Overall, 59 of the 250 patients (23.6%) had thyroid dysfunction across all age groups.

Table 2 : Distribution of Age and Thyroid Dysfunction

The mean HbA1c level, a marker of long-term glycemic control, was slightly higher in diabetic patients with thyroid dysfunction than in those with normal thyroid function (euthyroid). Patients with thyroid dysfunction had a mean HbA1c of 8.85% ± 1.40, while euthyroid patients had a mean HbA1c of 8.56% ± 1.58. Although HbA1c levels were elevated in both groups, indicating suboptimal glycemic control, the difference between the two groups was relatively small.

The comparison of mean HbA1c levels across different thyroid function groups showed varying degrees of glycemic control among patients with diabetes. Euthyroid patients had a mean HbA1c of 8.56% ± 1.58. Patients with subclinical hypothyroidism (SCH) had a slightly higher mean HbA1c of 8.80% ± 1.34, while those with overt hypothyroidism had the highest mean HbA1c of 8.96% ± 1.42. The hyperthyroid group, consisting of three patients, had a mean HbA1c of 8.80% ± 1.54. These results suggest that glycemic control tends to be poor in patients with thyroid dysfunction, particularly in those with hypothyroidism. However, the differences between the groups were relatively small.

Table 3 : Comparison of Mean HbA1C in each group

The mean duration of diabetes in the study population was 5.36 ± 4.18 years. For euthyroid patients, the mean duration was 5.26 ± 4.14 years, while for those with thyroid dysfunction, it was slightly higher at 5.66 ± 4.34 years. However, this difference was not statistically significant (P = 0.467).

The distribution of patients based on the duration of diabetes and thyroid function showed that the majority were in Group A (0-5 years), with 112 (80%) euthyroid patients and 28 (20%) with thyroid dysfunction, totaling 140 patients. In Group B (5.1-10 years), 58 patients (69.9%) were euthyroid, while 25 (30.1%) had thyroid dysfunction, resulting in a total of 83 patients. In Group C (10.1-15 years), 18 patients (81.8%) were euthyroid and 4 (18.2%) had thyroid dysfunction, with a total of 22 patients. In Group D (>15 years), three patients (60%) were euthyroid and two (40%) had thyroid dysfunction, with five patients in total. Overall, thyroid dysfunction was more common in patients with a longer duration of diabetes, particularly in Groups B and D. Despite the variation in thyroid dysfunction across these groups, there was no significant correlation between the duration of diabetes and the occurrence of thyroid dysfunction (p = 0.254).

Table 4 : Distribution of Patients based on Duration of Diabetes

Table 5 :  Correlation between Duration of Diabetes and Thyroid Dysfunction

Association between Anti-TPO Positivity and Gender

Among the 250 patients with diabetes, 59 were diagnosed with thyroid dysfunction, including 44 females and 15 males. Of the female patients with thyroid dysfunction, 33 had elevated anti-TPO antibody levels, while 6 of the 15 males showed elevated anti-TPO antibodies. This sex-based difference in anti-TPO positivity was statistically significant (p = 0.013).

In this study, we analyzed 250 patients with diabetes, of whom 55.6% were female and 44.4% were male. The mean age of the study population was 54.02 ± 8.7 years, with the majority of patients (44.8%) in the 45-55 year age group, followed by 30.4% in the 55-65 year age group. Nearly half of the patients (47.2%) had hypertension, 38.4% had dyslipidemia and 30% had both hypertension and dyslipidemia. The mean body mass index (BMI) was 24.75 ± 2.44 kg/m². The average fasting blood sugar (FBS) was 132.78 ± 30.33 mg/dl and the postprandial blood sugar (PPBS) averaged 192.68 ± 45.0 mg/dl. The mean HbA1c level in the study group was 8.63 ± 1.54%, indicating suboptimal glycemic control. The mean creatinine level was 0.82 ± 0.11 mg/dl. Though a high BMI is reported to be a risk factor for thyroid dysfunction in patients with T2DM, one of the reported studies did not observe any significant association between BMI and the prevalence of thyroid dysfunction ^[16].

In our study, the prevalence of thyroid dysfunction was 23.6% (CI: 22.49 to 24.70%). Among them, 22.4% had hypothyroidism, 16% had subclinical hypothyroidism and 6.4% had overt hypothyroidism. Additionally, 1.2% of patients had overt hyperthyroidism, while no cases of subclinical hyperthyroidism were identified. Our findings were consistent with those reported by Tomar et al who reported a similar prevalence of thyroid dysfunction in diabetic patients, with 23.75% having hypothyroidism (15% subclinical and 8.75% overt) and 6.25% diagnosed with hyperthyroidism, all of which were overt cases^[5]. Other studies, such as that by Celani et al., reported a higher prevalence of 31.4%^[12], Kiran Babu et al. reported a prevalence of 28%, also comparable to our findings^[13]. These variations in prevalence may be influenced by differences in study populations, methodologies, and geographic factors.

In our study, the mean age of euthyroid diabetic patients was 53.96 ± 8.75 years, while the mean age of those with thyroid dysfunction was slightly higher at 54.22 ± 8.66 years. However, this difference was not statistically significant. Comparatively, in the study by Kim et al., the mean age of euthyroid type 2 diabetic patients was 57.8 ± 11.8 years, whereas the mean age of type 2 diabetics with subclinical hypothyroidism (SCH) was significantly higher at 61.7 ± 9.8 years (p = 0.014)^[10]. This suggests that subclinical hypothyroidism in type 2 diabetes is associated with increasing age, a finding not mirrored in our study. The variation in age-related prevalence may be attributed to differences in study populations and sample sizes.

In our study, 31.7% of female diabetes had thyroid dysfunction compared with 13.5% of males, a statistically significant difference. This aligns with the findings of Yang et al., who studied 371 diabetic patients and diagnosed 22.4% with subclinical hypothyroidism (SCH), with a prevalence of 29.9% in females and 12.1% in males ^[14].

Multiple studies have consistently demonstrated that thyroid disorders, particularly in type 2 diabetes, are more common in females ^[12,13]. The higher prevalence of thyroid dysfunction in women may be linked to hormonal differences, genetic predisposition and autoimmune factors, all of which contribute to their increased vulnerability to thyroid disorders in the context of diabetes. While the mean duration of diabetes in patients with thyroid dysfunction was 5.66 ± 4.34 years, compared to 5.26 ± 4.14 years in euthyroid patients, this difference was not statistically significant. This finding was consistent with the results reported by Diez et al.^[15]

In terms of glycemic control, mean fasting blood sugar (FBS), postprandial blood sugar (PPBS) and HbA1c levels were higher in patients with thyroid dysfunction than in euthyroid patients, however, these differences were not statistically significant^[15]. Furthermore, a study conducted by Kim et al. indicated that patients with type 2 diabetes with subclinical hypothyroidism (SCH) experienced poorer glycemic control and higher insulin resistance, suggesting that thyroid dysfunction may negatively impact diabetes management ^[10].

In our study, 29.2% of patients with dyslipidemia had thyroid dysfunction compared to only 20.1% of those without dyslipidemia, however this difference was not statistically significant. The association between dyslipidemia and thyroid dysfunction was significant for each lipid parameter, except LDL, which did not reach significance, as noted in the study by Chubb et al^[9]. In our analysis, dyslipidemia was defined as statin therapy or LDL levels exceeding 100 mg/dl, which may explain the lack of a significant correlation between dyslipidemia and thyroid dysfunction in our cohort. Ozair et al reported that the thyroid dysfunction was more frequent in females and was significantly associated with dyslipidemia, retinopathy, poor glycemic control (HbA1c ≥7) and a longer duration of diabetes ^[8]. Additionally, Kim et al. found that patients with subclinical hypothyroidism (SCH) had relatively higher mean values of total cholesterol (TC), LDL and HDL than euthyroid subjects, while triglyceride (TG) levels were lower ^[10]. However, none of these lipid parameters showed statistically significant differences between the two groups. Among the 39 patients with elevated anti-TPO antibodies, 84.6% were female and only 15.4% were male, a statistically significant difference. This finding is consistent with those of Celani et al.^[12] and Schroner et al.^[11], highlighting the gender disparity in anti-TPO positivity.

The mean age of the study group was 54.02 years, with a higher representation of females than males. The prevalence of thyroid dysfunction in our study was 23.6% (CI: 22.49 to 24.70%), comprising 16% with subclinical hypothyroidism, 6.4% with overt hypothyroidism and 1.2% with overt hyperthyroidism, while no cases of subclinical hyperthyroidism were identified. Notably, there was a significantly higher prevalence of thyroid dysfunction among females compared than in males. Additionally, thyroid autoimmunity was present in 66.1% of the patients with thyroid dysfunction, with a greater incidence observed in females. Our analysis revealed no correlation between age and the duration of diabetes in euthyroid patients or those with thyroid dysfunction. Lastly, these findings emphasize the importance of routine screening for TSH levels in all patients with type 2 diabetes to facilitate the early detection and management of thyroid dysfunction.

1. 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‑
2. Ogbonna SU, Ezeani IU. Risk factors of thyroid dysfunction in patients with type 2 diabetes mellitus. Front Endocrinol 2019; 10:440.
3. Rong F, Dai H, Wu Y, Li J, Liu G, Chen H, Zhang X. Association between thyroid dysfunction and type 2 diabetes: A meta-analysis of prospective observational studies. BMC Med 2021; 19:257.
4. Biondi B, Kahaly GJ, Robertson RP. Thyroid dysfunction and diabetes mellitus: Two closely associated disorders. Endocr Rev 2019; 40:789‑
5. Tomar MS, Melwani V, Trivedi A. Assessment of thyroid dysfunctions in patients with type II diabetes mellitus in Central India. Asian J Pharm Clin Res 2022; 15:3.
6. Yadav A, Yadav GAM, Narsingrao KK, Kumar LGN, Yadav GSN. Prevalence of thyroid disorders among patients with diabetes in rural South India. Diabetes MetabSyndr 2021; 15:885‑
7. Khassawneh AH, Al-Mistarehi AH, ZeinAlaabdin AM, Khasawneh L, AlQuran TM, Kheirallah KA, et al. Prevalence and predictors of thyroid dysfunction among type 2 diabetic patients: A case-control study. Int J Gen Med 2020; 13:803‑
8. 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;12:3
9. Chubb SA, Davis WA, Inman Z. Prevalence and progression of subclinical hypothyroidism in women with type 2 diabetes: the Fremantle Diabetes Study. ClinEndocrinol (Oxf) 2005; 62:480–6.
10. Kim BY, Kim CH, Jung CH, Mok JO, Suh KI, Kang SK. Association between subclinical hypothyroidism and severe diabetic retinopathy in Korean patients with type 2 diabetes. Endocr J 2011; 58:919‑
11. Schroner Z, Lazurova I, Petrovicova J. Autoimmune thyroid diseases in patients with diabetes mellitus. Bratisl LekListy 2008; 109:125‑
12. Celani MF, Bonati ME, Stucci N. Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus. Diabetes Res 1994; 27:15‑
13. KiranBabu, Kakar A, Byotra SP. Prevalence of thyroid disorder in type 2 diabetes mellitus patients. J Assoc Physicians India 2001; 49:43.
14. Yang JK, Liu W, Shi J, Li YB. An association between subclinical hypothyroidism and sight-threatening diabetic retinopathy in type 2 diabetic patients. Diabetes Care 2010; 33:1018‑
15. Diez JJ, Sanchez P, Iglesias P. Prevalence of thyroid dysfunction in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 2011; 119:201-7.
16. Sawardekar VM, et al. Thyroid dysfunction in patients with T2DM. Natl J Lab Med 2024; 13:PO44‑