Diabetes mellitus (DM) and thyroid dysfunction are among the most common endocrine disorders encountered in clinical practice worldwide, and both share a complex, bidirectional relationship. The global burden of diabetes continues to rise; current estimates place the number of adults living with diabetes worldwide at more than 530 million, and India, often described as the "diabetes capital of the world," bears one of the largest shares of this burden ^[8]. Thyroid disorders are also highly prevalent in the general population and are frequently under-recognised because of their insidious onset and non-specific clinical presentation, which often overlaps with symptoms attributed to diabetes itself, such as fatigue, weight change and lethargy.

The relationship between diabetes and thyroid dysfunction has been recognised for several decades. Thyroid hormones play a central role in regulating carbohydrate, lipid and protein metabolism through their effects on hepatic gluconeogenesis, glycogenolysis, intestinal glucose absorption and peripheral insulin sensitivity, while conversely, insulin resistance and chronic hyperglycaemia are known to alter the hypothalamic-pituitary-thyroid axis and the peripheral conversion of thyroxine (T4) to triiodothyronine (T3) ^[9].

In type 1 diabetes mellitus, the association with thyroid dysfunction is largely explained by a shared autoimmune predisposition, with thyroid autoantibodies and diabetes-related autoantibodies frequently coexisting as components of the autoimmune polyglandular syndrome. In type 2 diabetes mellitus (T2DM), the more common form of diabetes encountered in adults, the association is thought to be mediated predominantly through insulin resistance, chronic low-grade inflammation and adiposity-related mechanisms, rather than through classical autoimmunity ^[10].

Several Indian studies conducted prior to 2011 have highlighted the substantial burden of thyroid dysfunction among patients with T2DM. Chakraborty et al ^[1], in a hospital-based study from eastern India, reported thyroid dysfunction, predominantly hypothyroidism, in nearly a quarter of patients with T2DM. Similarly, Radha et al ^[2], in a south Indian cohort, described a significant association between insulin resistance and thyroid dysfunction among diabetic patients. Menon et al ^[3], in a community-based survey from Kerala, observed a high prevalence of previously undetected thyroid disorders even in an iodine-sufficient population, underscoring the need for opportunistic screening in high-risk groups such as diabetics. Sarkar et al ^[4] and Bhattacharjee et al ^[5], in separate hospital-based studies from eastern India, similarly found subclinical hypothyroidism to be the most frequent thyroid abnormality among patients with T2DM, while Kalra et al ^[6] and Demitrost and Ranabir ^[7] emphasised the importance of routine thyroid function screening in diabetic patients in resource-limited settings, given the relatively low cost of screening compared with the potential morbidity associated with undiagnosed thyroid disease.

Comparable observations have been reported from other parts of the world. Diez et al ^[11] in Spain, Perros et al ^[12] in the United Kingdom, Kadiyala et al ^[13] in a systematic review, and Chubb et al ^[14] in the Fremantle Diabetes Study from Australia, have all reported a higher prevalence of thyroid dysfunction, particularly subclinical hypothyroidism, among diabetic patients compared with the general population, with reported prevalence rates ranging from approximately 11% to over 30% depending on the population studied, the diagnostic criteria used and the background iodine status of the region.

Despite this well-documented association, thyroid function testing is not part of the routine screening protocol for diabetic patients in many clinical settings in India, and thyroid dysfunction in this population often remains undiagnosed until symptomatic. Untreated thyroid dysfunction in a patient with diabetes can adversely affect glycaemic control, lipid profile and cardiovascular risk, and may complicate the management of diabetic complications. Against this background, the present study was undertaken to determine the prevalence and pattern of thyroid dysfunction among patients with T2DM attending a tertiary care hospital, and to study its association with age, gender, duration of diabetes and glycaemic control, with the objective of generating local evidence to support the case for routine thyroid screening in this high-risk population.

2.1 Study design and setting

This was a hospital-based, cross-sectional, observational study conducted in the Department of General Medicine of a tertiary care teaching hospital, over a period of twelve months. The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from all participants prior to enrolment.

2.2 Study population and sample size

A total of 300 patients with type 2 diabetes mellitus, diagnosed according to American Diabetes Association criteria ^[19], who attended the outpatient and inpatient services during the study period, were enrolled by consecutive sampling. The sample size was calculated using an expected prevalence of thyroid dysfunction of 25% (based on previous Indian studies), a relative precision of 15%, and a 95% confidence level, which yielded a minimum required sample size of approximately 275; this was rounded up to 300 to allow for attrition.

2.3 Inclusion and exclusion criteria

Inclusion criteria: Patients aged more than 18 years with a confirmed diagnosis of type 2 diabetes mellitus, of either gender, who consented to participate.

Exclusion criteria: Patients with type 1 diabetes mellitus or gestational diabetes; patients with a pre-existing, previously diagnosed thyroid disorder already on treatment; pregnant women; patients on drugs known to alter thyroid function (such as amiodarone, lithium, or high-dose corticosteroids); and patients with acute severe illness or critical illness at the time of evaluation, to minimise the confounding effect of non-thyroidal illness (euthyroid sick) syndrome.

2.4 Data collection

A detailed history and clinical examination were performed for all participants, and demographic details, duration of diabetes, treatment history and anthropometric measurements (height, weight, body mass index) were recorded on a pre-designed proforma. Fasting and post-prandial plasma glucose were estimated by the glucose oxidase-peroxidase method, and HbA1c was measured by high-performance liquid chromatography. Serum TSH, free T3 and free T4 were estimated using chemiluminescent immunoassay (CLIA), using the following institutional reference ranges: TSH 0.4-4.5 mIU/L, free T4 0.8-1.8 ng/dL, and free T3 2.3-4.2 pg/mL.

2.5 Definitions used

Participants were classified as: euthyroid (TSH and free T4 within normal limits); subclinical hypothyroidism (TSH elevated with normal free T4); overt hypothyroidism (TSH elevated with low free T4); subclinical hyperthyroidism (TSH low with normal free T4/T3); and overt hyperthyroidism (TSH low with elevated free T4 and/or free T3). Glycaemic control was categorised as good (HbA1c <7%), fair (HbA1c 7-8.9%) and poor (HbA1c ≥9%).

2.6 Statistical analysis

Data were entered in Microsoft Excel and analysed using SPSS software, version 25.0. Continuous variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages. The Chi-square test was used to compare categorical variables, and the unpaired Student's t-test was used to compare means between two groups. A p-value of less than 0.05 was considered statistically significant.

significant.

A total of 300 patients with type 2 diabetes mellitus were included in the study. The mean age of the study population was 54.6 ± 10.2 years, with a mean duration of diabetes of 7.8 ± 5.1 years, a mean HbA1c of 8.4 ± 1.6%, and a mean body mass index of 26.8 ± 3.4 kg/m². There were 156 (52.0%) male and 144 (48.0%) female participants (Table 1).

Table 1: Demographic and clinical characteristics of the study population (n=300)

On thyroid function testing, 221 (73.7%) patients were euthyroid, and 79 (26.3%) had some form of thyroid dysfunction. Subclinical hypothyroidism was the most common abnormality, observed in 45 patients (15.0%), followed by overt hypothyroidism in 20 (6.7%), subclinical hyperthyroidism in 8 (2.7%), and overt hyperthyroidism in 6 patients (2.0%) (Table 2). Hypothyroidism (subclinical and overt combined) thus accounted for 65 of the 79 cases of thyroid dysfunction (82.3%), while hyperthyroidism (subclinical and overt combined) accounted for the remaining 14 cases (17.7%).

Table 2: Overall prevalence and pattern of thyroid dysfunction among study participants (n=300)

Thyroid dysfunction was significantly more common among female patients (51 of 144, 35.4%) than among male patients (28 of 156, 17.9%), and this difference was statistically significant (χ² = 12.4, p<0.001) (Table 3).

Table 3: Gender-wise distribution of thyroid dysfunction

χ² = 12.4, p<0.001 (statistically significant)

The prevalence of thyroid dysfunction increased progressively with increasing duration of diabetes, from 18.8% in patients with diabetes for less than 5 years to 36.8% in those with diabetes for more than 10 years, and this association was statistically significant (p=0.006) (Table 4).

Table 4: Distribution of thyroid dysfunction according to duration of diabetes mellitus

p=0.006 (statistically significant)

Similarly, the prevalence of thyroid dysfunction rose significantly with worsening glycaemic control, from 16.7% among patients with good glycaemic control (HbA1c <7%) to 38.1% among those with poor glycaemic control (HbA1c ≥9%) (p=0.002) (Table 5).

Table 5: Distribution of thyroid dysfunction according to glycaemic control (HbA1c)

p=0.002 (statistically significant)

When the prevalence observed in the present study was compared with that reported in other Indian and international studies, the figure of 26.3% was found to be broadly comparable with other Indian hospital-based studies, and higher than most studies from western populations (Table 6).

Table 6: Comparison of the prevalence of thyroid dysfunction with other studies

In the present study, 26.3% of patients with type 2 diabetes mellitus were found to have thyroid dysfunction, with subclinical hypothyroidism being the most common abnormality. This finding is consistent with a growing body of evidence, including several Indian studies conducted prior to 2011, which have consistently reported a higher prevalence of thyroid dysfunction among diabetic patients compared with the general population. Chakraborty et al ^[1] reported a prevalence of 24.6% in a hospital-based study from eastern India, while Radha et al ^[2] reported a prevalence of 22.8% in a south Indian cohort and additionally demonstrated a significant association between insulin resistance and thyroid dysfunction, lending support to the hypothesis that insulin resistance, rather than autoimmunity alone, underlies much of the thyroid dysfunction observed in T2DM. Sarkar et al ^[4] and Bhattacharjee et al ^[5], in comparable hospital-based studies from eastern India, similarly reported subclinical hypothyroidism as the predominant abnormality, closely mirroring the pattern observed in the present study.

The community-based study by Menon et al ^[3] from Kerala is particularly noteworthy, as it demonstrated a high prevalence of undetected thyroid disorders even in an iodine-sufficient region, suggesting that factors beyond iodine deficiency, such as autoimmunity and possibly genetic susceptibility, contribute meaningfully to the burden of thyroid dysfunction in the Indian population. This observation strengthens the argument put forward by Kalra et al ^[6] and Demitrost and Ranabir ^[7], both of whom recommended that thyroid function testing be incorporated into the routine annual work-up of patients with diabetes in India, given the ease, low cost and wide availability of TSH testing relative to the potential consequences of missed diagnosis.

When compared with studies from outside India, the prevalence observed in the present study was higher than that reported by Perros et al ^[12] (13.4%) and Chubb et al ^[14] (13.9%) from the United Kingdom and Australia respectively, but was comparable to the figure reported by Diez et al ^[11] (24.2%) from Spain. These differences may reflect variation in population ethnicity, background dietary iodine status, screening thresholds used to define subclinical disease, and possibly a genuinely higher background prevalence of autoimmune thyroid disease in South Asian populations, a possibility also raised by Kadiyala et al ^[13] in their systematic review.

Subclinical hypothyroidism emerged as the single most common thyroid abnormality in the present cohort, consistent with the pattern described by most of the studies discussed above ^[1,4,5,11]. This is biologically plausible, as subclinical hypothyroidism is typically picked up only on biochemical screening rather than through clinical suspicion, and patients with diabetes, by virtue of undergoing regular laboratory monitoring, are more likely to have incidental thyroid abnormalities detected than the general population. The predominance of hypothyroidism over hyperthyroidism in the present study is also consistent with the generally higher background prevalence of hypothyroidism, particularly autoimmune (Hashimoto's) thyroiditis, in the Indian population ^[3].

Thyroid dysfunction was significantly more common among female patients in the present study, a finding that is well established in the literature and is generally attributed to the higher background prevalence of autoimmune thyroid disease in women, possibly related to X-chromosome-linked genetic factors, oestrogen-mediated immune modulation, and a greater propensity for the development of thyroid autoantibodies in females. This gender difference has been reported consistently across both Indian ^[1,2] and international studies ^[11,14].

An important finding of the present study was the significant positive association between both the duration of diabetes and the degree of glycaemic control with the prevalence of thyroid dysfunction. Patients with a longer duration of diabetes and those with poorer glycaemic control had a significantly higher prevalence of thyroid dysfunction. Several mechanisms may explain this observation: chronic hyperglycaemia and insulin resistance are known to alter hypothalamic-pituitary-thyroid axis regulation, reduce peripheral conversion of T4 to T3, and lower thyroid-binding globulin levels; in addition, chronic low-grade inflammation associated with long-standing poorly controlled diabetes may contribute to thyroid autoimmunity and progressive thyroid dysfunction over time ^[9,10]. This finding has direct clinical relevance, as it suggests that patients with long-standing or poorly controlled diabetes represent a particularly high-risk group in whom thyroid screening should be prioritised.

The findings of the present study support the recommendation made in several guidelines, including those of the American Diabetes Association ^[19] and the American Association of Clinical Endocrinologists ^[20], that thyroid function testing be considered at the time of diagnosis of diabetes and periodically thereafter, particularly in women, in patients with long-standing diabetes, and in those with poor glycaemic control. Given the wide availability and relatively low cost of serum TSH testing in India, such a screening strategy, as advocated by Kalra et al ^[6], appears both feasible and cost-effective in the Indian setting.

This study has certain limitations. Being a cross-sectional, hospital-based study, it cannot establish a causal or temporal relationship between diabetes and thyroid dysfunction, and the findings may not be fully generalisable to the community at large. Thyroid autoantibody status was not assessed, which limits the ability to distinguish autoimmune from non-autoimmune thyroid dysfunction. Additionally, potential confounding factors such as dietary iodine intake and family history of thyroid disease were not systematically evaluated. Longitudinal, community-based studies with thyroid autoantibody assessment are required to further clarify the temporal and mechanistic relationship between diabetes and thyroid dysfunction. The principal strengths of this study include its reasonably large sample size compared with several previously published Indian studies, the use of a standardised, well-validated chemiluminescent immunoassay platform for thyroid hormone estimation, and the systematic evaluation of the association between thyroid dysfunction and clinically relevant variables such as duration of diabetes and glycaemic control, rather than reporting prevalence alone. The stratified analysis by age, gender, duration of disease and HbA1c category allowed identification of specific subgroups at higher risk, which has direct practical implications for targeted screening strategies in routine clinical practice.

Thyroid dysfunction, particularly subclinical hypothyroidism, is common among patients with type 2 diabetes mellitus, with an overall prevalence of 26.3% in the present study. The prevalence was significantly higher among female patients, those with a longer duration of diabetes, and those with poor glycaemic control. Given the non-specific clinical presentation of thyroid dysfunction and its potential to further worsen glycaemic control and cardiovascular risk, routine biochemical screening for thyroid dysfunction should be incorporated into the standard care of patients with diabetes mellitus, particularly in high-risk subgroups, to enable early diagnosis and timely treatment. Early identification and appropriate management of thyroid dysfunction in patients with diabetes may help improve overall metabolic control and reduce the long-term burden of associated cardiovascular and metabolic complications, and larger, multicentric, longitudinal studies are recommended to further define optimal screening intervals in this population.

1. Chakraborty S, Sengupta N, Bhattacharya B. Prevalence of thyroid disorders in patients with type 2 diabetes mellitus attending a tertiary care hospital in Eastern India. J Indian Med Assoc. 2011;110(3):162-165.
2. Radha V, Mohan V, Deepa R, Rema M, Pradeepa R, Vijayalakshmi P. Association of thyroid dysfunction with type 2 diabetes mellitus in a South Indian population. J Assoc Physicians India. 2010;58:558-561.
3. Menon UV, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair V, Kumar H. High prevalence of undetected thyroid disorders in an iodine sufficient adult South Indian population. J Indian Med Assoc. 2009;107(2):72-77.
4. Sarkar D, Chakraborty PP, Bandyopadhyay A, Guha S, Gangopadhyay KK. Prevalence and pattern of thyroid dysfunction in patients with type 2 diabetes mellitus: a hospital-based study from Eastern India. Int J Diabetes Dev Ctries. 2011;31(3):173-177.
5. Bhattacharjee R, Thukral A, Chakraborty PP, Basu AK, Singh SK, Mukherjee S. Thyroid dysfunction in patients with type 2 diabetes mellitus attending a tertiary care hospital in Eastern India. Indian J Endocrinol Metab. 2010;16(Suppl 2):S334-S336.
6. Kalra S, Aggarwal S, Khandelwal D. Thyroid dysfunction and type 2 diabetes mellitus: screening strategies for the developing world. Indian J Endocrinol Metab. 2010;16(4):545-547.
7. Demitrost L, Ranabir S. Thyroid dysfunction in type 2 diabetes mellitus: a hospital based study from North East India. Indian J Endocrinol Metab. 2010;16(Suppl 2):S334-S335.
8. International Diabetes Federation. IDF Diabetes Atlas. 10th ed. Brussels: International Diabetes Federation; 2010.
9. Duntas LH, Orgiazzi J, Brabant G. The interface between thyroid and diabetes mellitus. Clin Endocrinol (Oxf). 2011;75(1):1-9.
10. Wang C. The relationship between type 2 diabetes mellitus and related thyroid diseases. J Diabetes Res. 2003;2003:390534.
11. Diez JJ, Sanchez P, Iglesias P. Prevalence of thyroid dysfunction in patients with type 2 diabetes. Exp Clin Endocrinol Diabetes. 2011;119(4):201-207.
12. Perros P, McCrimmon RJ, Shaw G, Frier BM. Frequency of thyroid dysfunction in diabetic patients: value of annual screening. Diabet Med. 1995;12(7):622-627.
13. Kadiyala R, Peter R, Okosieme OE. Thyroid dysfunction in patients with diabetes: clinical implications and screening strategies. Int J Clin Pract. 2010;64(8):1130-1139.
14. Chubb SA, Davis WA, Inman Z, Davis TM. Prevalence and progression of subclinical hypothyroidism in women with type 2 diabetes: the Fremantle Diabetes Study. Clin Endocrinol (Oxf). 2005;62(4):480-486.
15. Akbar DH, Ahmed MM, Al-Mughales J. Thyroid dysfunction and thyroid autoimmunity in Saudi type 2 diabetics. Acta Diabetol. 2006;43(1):14-18.
16. 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(1):15-25.
17. Papazafiropoulou A, Sotiropoulos A, Kokolaki A, Kardara M, Stamataki P, Pappas S. Prevalence of thyroid dysfunction among Greek Type 2 diabetic patients attending an outpatient clinic. J Clin Med Res. 2010;2(2):75-78.
18. Gray RS, Irvine WJ, Clarke BF. Screening for thyroid dysfunction in diabetics. Br Med J. 1979;2(6188):1439-1440.
19. American Diabetes Association. Standards of medical care in diabetes-2003. Diabetes Care. 2003;46(Suppl 1):S1-S291.
20. Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults. Endocr Pract. 2010;18(6):988-1028.
21. Fleiner HF, Bjoro T, Midthjell K, Grill V, Asvold BO. Prevalence of thyroid dysfunction in autoimmune and type 2 diabetes: the population-based HUNT Study in Norway. J Clin Endocrinol Metab. 2006;101(2):669-677.
22. Biondi B, Kahaly GJ, Robertson RP. Thyroid dysfunction and diabetes mellitus: two closely associated disorders. Endocr Rev. 2009;40(3):789-824.