Diabetes mellitus (DM) remains one of the most consequential global health challenges of the 21st century. Projections estimate that global diabetes prevalence will rise from 11.11% in 2024 to 12.96% by 2050, with the number of affected adults aged 20–79 years increasing from approximately 580 million to nearly 900 million [1]. China and India currently account for the largest proportion of this burden and are expected to maintain this position in the coming decades [1]. The majority of cases comprise Type 2 Diabetes Mellitus (T2DM) [2], a chronic metabolic disorder characterized by progressive insulin resistance and β-cell dysfunction. Beyond persistent hyperglycemia, T2DM is clinically significant for its microvascular and macrovascular complications, which substantially increase morbidity, premature mortality, and healthcare expenditure. [1,2] Thyroid dysfunction is among the most prevalent endocrine disorders worldwide and frequently coexists with diabetes mellitus [3]. Conversely, disturbances in glucose metabolism are common in individuals with thyroid disease, underscoring the close physiological interplay between thyroid function and metabolic regulation. Multiple studies have reported a higher prevalence of both overt and subclinical hypothyroidism in patients with T2DM, with reported associations particularly in diabetic nephropathy [4]. Subclinical hypothyroidism (SCH) is defined by elevated serum thyroid-stimulating hormone (TSH) concentrations in the presence of normal circulating free thyroxine (FT4) and free triiodothyronine (FT3) levels [5]. Although often asymptomatic, SCH represents an early stage of thyroid failure with clinically relevant metabolic consequences. Its prevalence in the general population ranges from 1% to 11%, increasing with age and female sex [5]. Population-based data estimate a prevalence of approximately 6.1% in women and 3.4% in men, rising to nearly 22% among postmenopausal women [5, 6]. Thyroid hormones play a fundamental role in regulating basal metabolic rate, lipid metabolism, vascular tone, and glucose homeostasis. Even mild thyroid dysfunction has been associated with insulin resistance, dyslipidemia, endothelial dysfunction, arterial stiffness, and adverse cardiovascular outcomes [7, 8]. Such alterations are particularly consequential in T2DM, a disorder intrinsically defined by insulin resistance and heightened cardiometabolic risk. The interaction between T2DM and SCH appears complex and bidirectional. Chronic hyperglycemia and insulin resistance may disrupt hypothalamic–pituitary–thyroid axis regulation, alter TSH dynamics, and impair peripheral thyroid hormone metabolism [5]. Conversely, SCH may further exacerbate insulin resistance and adversely influence lipid profiles, potentially worsening glycemic control and accelerating the progression of diabetic microvascular and macrovascular complications [9]. Independent associations between thyroid dysfunction and increased systemic vascular resistance, arterial stiffness, and cardiovascular risk further suggest that SCH may amplify vascular burden in individuals with T2DM [11, 12]. Despite growing evidence linking thyroid dysfunction with T2DM, data directly comparing the prevalence of SCH in complicated versus uncomplicated T2DM remain limited and methodologically heterogeneous, particularly within region-specific populations. Whether the presence of established diabetic complications confers an additional risk of SCH remains insufficiently clarified. Furthermore, consensus regarding routine thyroid screening in patients with T2DM has not been established. Clarifying the burden of SCH in T2DM—especially in relation to established diabetic complications—may improve risk stratification and inform targeted screening strategies, particularly in resource-constrained settings where endocrine disorders frequently remain underdiagnosed [13, 14]. Therefore, this study was aimed to determine the prevalence of subclinical hypothyroidism among patients with Type 2 Diabetes Mellitus and to compare its occurrence between those with established diabetic complications and those without.

Study Design and Setting This hospital-based cross-sectional analytical study was conducted to determine the prevalence of subclinical hypothyroidism (SCH) among patients with Type 2 Diabetes Mellitus (T2DM) and to compare its prevalence between uncomplicated and complicated cases. The study was carried out in the Department of General Medicine at a tertiary care teaching hospital in India. The study included 227 patients with T2DM. The protocol was approved by the Institutional Ethics Committee, and written informed consent was obtained from all participants. Study Period The study was conducted over two years, from January 2022 to December 2023. Study Population and Sampling Eligible adult patients with T2DM attending outpatient and inpatient services were enrolled consecutively. Inclusion Criteria • Age ≥ 18 years • Known or newly diagnosed T2DM • Willingness to provide written informed consent Exclusion Criteria • Type 1 Diabetes Mellitus or other specific types of diabetes • Chronic renal failure • Acute systemic illnesses (e.g., sepsis, acute myocardial infarction, severe heart failure, ICU admission) • Known liver dysfunction • Pregnancy • Use of medications affecting thyroid function (e.g., amiodarone, corticosteroids, propranolol, oral contraceptive pills) Data Collection Procedure Data were collected using a structured predesigned proforma. Recorded variables included age, sex, duration of diabetes, body weight, BMI, blood pressure, medical and family history, and presence of diabetic complications. Body weight was measured using a calibrated analog scale with 0.5 kg precision. Clinical records and laboratory investigations were reviewed to confirm complications. Biochemical Assessment After overnight fasting (≥ 8 hours), venous blood samples were collected under aseptic conditions. The following parameters were measured: • Fasting plasma glucose (FPG) • Glycated hemoglobin (HbA1c) • Fasting lipid profile • Liver function tests (LFTs) • Kidney function tests (KFTs) • Thyroid profile (TSH, free T3, free T4) Thyroid function tests were analyzed using enhanced chemiluminescence immunoassay in the hospital’s central laboratory, following standard operating procedures and quality control protocols. SCH was defined as serum TSH > 5.0 µIU/mL with normal free T3 and free T4 levels according to laboratory reference ranges. Outcome Measures • Primary outcome: Prevalence of SCH among T2DM patients • Secondary outcomes: o Comparison of SCH prevalence between uncomplicated and complicated T2DM o Association between SCH and demographic or clinical variables Statistical Analysis Data were analyzed using SPSS v28. Categorical variables are presented as n (%) and continuous variables as mean ± SD or median (IQR). Normality was assessed with the Shapiro–Wilk test. Group comparisons used Chi-square/Fisher’s exact or t-test/Mann–Whitney U tests, as appropriate. SCH prevalence was reported with 95% confidence intervals (CI). Multivariate logistic regression identified independent predictors (adjusted for age, sex, diabetes duration, BMI, and complications) with adjusted odds ratios (AOR) and 95% CI. A p-value < 0.05 was considered significant. Missing data were handled using complete-case analysis.

Table 1: Demographic Profile of the Study Population. Variable Category No. of Cases Percentage (%) Age Group (years) 18–30 26 11.45 31–40 42 18.50 41–50 66 29.07 51–60 58 25.55 >60 35 15.42 Mean Age ± SD 46.83 ± 12.53 Gender Male 120 52.86 Female 107 47.14 Table 1 summarizes the demographic characteristics of the study population comprising 227 patients with type 2 diabetes mellitus. The majority of patients belonged to the middle-aged group, with the highest proportion observed in the 41–50 years age group (29.07%), followed by those aged 51–60 years (25.55%). Patients aged over 60 years constituted 15.42% of the study population, while younger age groups (18–30 and 31–40 years) accounted for 11.45% and 18.50% respectively. The mean age of the participants was 46.83 ± 12.53 years. Gender distribution showed a slight male predominance, with 120 males (52.86%) and 107 females (47.14%). This demographic profile reflects the typical age and sex distribution of patients with type 2 diabetes mellitus. Graph-1: Thyroid Function Status in Type 2 Diabetes Mellitus. Graph 1 depicts the distribution of thyroid function status among patients with type 2 diabetes mellitus. The majority of patients were euthyroid, accounting for 194 cases (85.46%). Subclinical hypothyroidism was identified in 25 patients, representing a prevalence of 11.01%, while overt hypothyroidism was present in 8 patients (3.52%). These findings indicate that subclinical hypothyroidism is a relatively common thyroid abnormality among patients with type 2 diabetes mellitus, emphasizing the need for routine thyroid function screening in this population. Grap-2:: Age-wise Distribution of Thyroid Function Status. Grap-2 illustrates the age-wise distribution of thyroid function status in the study population. Subclinical hypothyroidism was most frequently observed in the 41–50 years age group (36.00%), followed by the 51–60 years age group (28.00%). Euthyroid status was also predominantly seen in the 41–50 years age group (28.87%). Overt hypothyroidism showed a higher proportion in older age groups, particularly among patients aged 51–60 years (37.50%) and those above 60 years (25.00%). These findings suggest an increasing tendency toward thyroid dysfunction with advancing age in patients with type 2 diabetes mellitus. Grph-3: Gender-wise Distribution of Thyroid Function Status. GRAPH Graph 3 presents the distribution of thyroid function status according to gender. Among female patients, subclinical hypothyroidism was observed in 16.67% compared to 4.67% among male patients, and this difference was found to be statistically significant (p = 0.0026). Normal thyroid function was more commonly seen in males (93.46%) than females (78.33%). Although overt hypothyroidism was slightly more prevalent in females (5.00%) compared to males (1.87%), this difference was not statistically significant. These results indicate a significantly higher prevalence of subclinical hypothyroidism among female patients with type 2 diabetes mellitus, suggesting a possible gender-related susceptibility. Table 2: Association Between Body Mass Index and Thyroid Function Status. Comparison BMI (Mean ± SD) P-value Euthyroid vs SCH 28.01 ± 4.12 vs 29.97 ± 4.85 0.029* Euthyroid vs Overt Hypothyroid 28.01 ± 4.12 vs 26.44 ± 3.74 0.291 SCH vs Overt Hypothyroid 29.97 ± 4.85 vs 26.44 ± 3.74 0.069 *=Significant Table 2 compares body mass index (BMI) across different thyroid function categories. Patients with subclinical hypothyroidism had a significantly higher mean BMI (29.97 ± 4.85 kg/m²) compared to euthyroid patients (28.01 ± 4.12 kg/m²), with the difference being statistically significant (p = 0.029). while no statistically significant difference in BMI was observed between other two groups ie. euthyroid vs overt hypothyroid and sub-clinical hypothyroid vs overt hyperthyroid groups. Table 3: Comparison of Subclinical Hypothyroidism in Complicated and Uncomplicated T2DM. Parameter (Mean ± SD) With Complications Without Complications Duration of DM (years) 11.56 ± 3.42 7.23 ± 1.39 TSH (µIU/ml) 6.28 ± 2.10 9.11 ± 14.25 Table 3 shows that the mean duration of diabetes was higher in patients with complications (11.56 ± 3.42 years) compared to those without complications (7.23 ± 1.39 years). Although the mean TSH level was 6.28 ± 2.10 µIU/ml in patients with complications and 9.11 ± 14.25 µIU/ml in those without complications, the difference was not statistically significant. This indicates that subclinical hypothyroidism was not significantly associated with diabetic complications in this study.

This hospital-based cross-sectional study evaluated thyroid dysfunction among 227 patients with Type 2 Diabetes Mellitus (T2DM), focusing on subclinical hypothyroidism (SCH) in complicated and uncomplicated cases. SCH prevalence was 11.01% and overt hypothyroidism 3.52%, yielding a combined thyroid dysfunction prevalence of 14.5%, consistent with previous reports (8–17%) [5]. Asuti et al. (2023) [15] reported a higher prevalence (23.6%), with SCH comprising 67.79% of cases, while Sharma et al. (2020) [14] and Javeedh et al. (2021) [16] reported similar findings. Differences may reflect variations in TSH cut-offs, iodine status, ethnicity, sample size, and study design. The moderate prevalence in this cohort likely reflects its hospital-based and regional characteristics, yet one in nine patients with SCH highlights its clinical relevance. Age-stratified analysis showed SCH was most frequent in the 41–50-year group (36%) and 51–60 years (28%), whereas overt hypothyroidism peaked at 51–60 years (37.5%). This indicates that SCH can occur in middle-aged patients rather than being confined to older adults, consistent with Chaudhary et al. (2025) [5] and Stott et al. (2017) [17]. Chronic metabolic stress, insulin resistance, low-grade inflammation, and autoimmune predisposition may contribute to hypothalamic–pituitary–thyroid axis dysregulation. A significant female predominance was observed (16.67% vs 4.67%, p = 0.0026), likely due to hormonal influences, X-chromosome–linked immune modulation, and higher susceptibility to autoimmune thyroid disease [18–20], supporting targeted screening for female T2DM patients. Patients with SCH had higher BMI (29.97 ± 4.85 vs 28.01 ± 4.12 kg/m², p = 0.029), consistent with Wang et al. (2021) [21] and Kumari et al. (2021) [22]. The relationship appears bidirectional: adiposity may elevate TSH via leptin and inflammatory cytokines, while SCH may worsen weight gain, dyslipidemia, and insulin resistance. Although patients with complications had longer diabetes duration (11.56 ± 3.42 vs 7.23 ± 1.39 years, p < 0.0001), HbA1c (p = 0.94) and TSH (p = 0.09) were similar between groups, suggesting SCH was not independently associated with glycemic control or established complications. Reported associations between thyroid dysfunction and microvascular or cardiovascular outcomes are inconsistent, likely due to heterogeneity in study design, sample size, disease duration, and confounder adjustment. The cross-sectional design limits causal inference. Mechanistically, SCH and T2DM share pathways including insulin resistance, low-grade inflammation, oxidative stress, and altered deiodinase activity. SCH may exacerbate lipid abnormalities and endothelial dysfunction, increasing cardiovascular vulnerability, particularly in females and those with higher BMI. Strengths and Limitations Strengths include a well-defined cohort, standardized biochemical assessment, and comparison between complicated and uncomplicated T2DM, enhancing internal validity. Limitations include the cross-sectional, single-center design, absence of thyroid autoantibody testing, and lack of longitudinal follow-up, limiting causal inference, etiological characterization, and evaluation of SCH progression. Clinical Implications Approximately one in nine T2DM patients had SCH, particularly middle-aged females with elevated BMI. In the absence of universal screening guidelines, targeted screening of high-risk subgroups may be pragmatic. Early detection may facilitate metabolic and cardiovascular monitoring; however, the benefit of treating mild SCH requires validation in prospective longitudinal studies.

In this hospital-based cross-sectional study of 227 patients with Type 2 Diabetes Mellitus (T2DM), subclinical hypothyroidism (SCH) was detected in 11.01%, and overt hypothyroidism in 3.52%. SCH was most prevalent in the 41–50 years age group (36.0%) and significantly higher among females (16.67% vs 4.67%, p = 0.0026). Patients with SCH had a higher mean BMI compared to euthyroid patients (29.97 ± 4.85 vs 28.01 ± 4.12 kg/m², p = 0.029). No significant differences in HbA1c or serum TSH were observed between patients with complicated and uncomplicated T2DM. These findings indicate that SCH is relatively common among middle-aged, female, and overweight T2DM patients, underscoring the importance of routine thyroid function screening in this population. REASON AND EXPLAINATION: Thyroid disorders are more common in females primarily due to hormonal and immunological factors. Estrogen influences immune system activity and increases susceptibility to autoimmune diseases such as Hashimoto’s thyroiditis, which is a common cause of hypothyroidism. Females also have a stronger immune response compared to males, making them more prone to autoimmune thyroid dysfunction. Additionally, physiological changes during puberty, pregnancy, and menopause further affect thyroid regulation in women.

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