European Journal of Cardiovascular Medicine

Diabetes is swiftly nearing epidemic status in India, with more than 62 million diagnosed cases.[1,2] Wild et al. [3] project that the global prevalence of diabetes will increase from 171 million in 2000 to 366 million by 2030, with India exhibiting the most significant growth. Numerous factors affect the prevalence of illness within a nation, and identifying these factors is essential for facilitating change and addressing health issues. In 1927, Coller and Huggins examined the influence of hyperthyroidism on diabetes, establishing a correlation between hyperthyroidism and the progression of diabetes. Surgical excision of portions of the thyroid gland was found to positively influence the restoration of glucose tolerance in hyperthyroid patients with concomitant diabetes [4]. Glucose metabolism is additionally affected by various specific pathways in hypothyroidism. Hypothyroidism is marked by a diminished rate of hepatic glucose production, [5]elucidating why patients with hypothyroid diabetes exhibit reduced insulin requirements.[6] The elevated release of free fatty acids (FFA) may be partially attributed to enhanced catecholamine-stimulated lipolysis induced by excess thyroid hormones. Moreover, hyperthyroidism enhances non-oxidative glucose clearance, leading to increased lactate production, which subsequently enters the Cori cycle and stimulates additional hepatic gluconeogenesis. Hyperthyroidism elevates levels of GH, glucagon, and catecholamines, thereby diminishing glucose tolerance through the enhancement of insulin resistance [7].
A cross-sectional study was conducted at Sapthagiri Institute of Medical Sciences in Bengaluru to examine thyroid disorders in patients with type 2 diabetes mellitus, given the existing research in this area in India.

Study Design: This was a cross-sectional study conducted over a period of 18 months, from September 2022 to February 2024, at Sri Aurobindo Institute of Medical College. The study aimed to assess the prevalence of thyroid dysfunction among patients with type 2 diabetes mellitus (T2DM).

Study Population: The study involved 250 individuals attending the outpatient and inpatient departments at Sri Aurobindo Institute of Medical College. A total sample size of 130 patients was calculated based on a prevalence of thyroid dysfunction of 11.7% among diabetic patients, with a 5% level of significance and a 5% absolute error.

Inclusion Criteria

1. Patients aged 18 years or older diagnosed with type 2 diabetes mellitus.
2. Patients without a known history of thyroid dysfunction.

Exclusion Criteria

1. Patients with a pre-existing diagnosis of thyroid dysfunction.
2. Pregnant patients.
3. Patients on medications that interfere with thyroid function, such as amiodarone, interferon alpha, lithium, or anti-thyroid drugs.
4. Patients who did not provide written consent.

Data Collection

Data were collected through patient interviews, medical history reviews, clinical examinations, and laboratory investigations. A specially designed, pre-structured proforma was used to record each patient's demographic information, diabetes history, and thyroid profile.

 Biochemical and Clinical Assessments

All participants underwent the following laboratory investigations:

- Fasting Blood Sugar (FBS)**: Values >126 mg/dL indicated diabetes.

- Postprandial Blood Sugar (PPBS): Values >200 mg/dL indicated diabetes.

- Hemoglobin A1c (HbA1c): Levels >6.5% were used to confirm diabetes diagnosis.

- Thyroid Profile: Measured levels included:

  - Serum Thyroid-Stimulating Hormone (TSH)

  - Serum Triiodothyronine (T3)

  - Serum Thyroxine (T4)

  - Free T3 and Free T4

Classification of Thyroid Dysfunction

Thyroid dysfunction was classified based on the following guidelines:

-Primary Hypothyroidism: Elevated TSH with reduced T3 and T4 levels.

- Primary Hyperthyroidism: Suppressed TSH with elevated T3 and T4 levels.

- Subclinical Hypothyroidism: Elevated TSH with normal T3 and T4 levels.

- Normal Thyroid Function: TSH, T3, and T4 within normal ranges.

Statistical Analysis

Data were recorded in Microsoft Excel 2010 and analyzed using frequency tables to describe the prevalence of different thyroid dysfunctions among T2DM patients.

The age distribution among 130 Type 2 Diabetes Mellitus patients shows a varied spread across different age groups. The highest percentage of cases falls within the 41–50 years age group, accounting for 26.9% (35 cases). This is followed by the 20–30 years age group, with 23.8% (31 cases), and the 31–40 years group, representing 21.5% (28 cases). Patients in the 51–60 age range make up 16.9% (22 cases), while those above 60 years constitute the smallest group, with 10.8% (14 cases). Together, these figures sum to a total of 130 patients, providing a comprehensive age-wise distribution for this population.

Table 1 Age Distribution Among Type 2 Diabetes Mellitus Patients (n=130)

The sex distribution among 130 Type 2 Diabetes Mellitus patients reveals a predominance of female patients, who make up 70.8% (92 cases) of the group, compared to 29.2% (38 cases) for males. This results in a male-to-female ratio of 1:2.42, indicating that females in this sample are over twice as likely to be affected by Type 2 Diabetes Mellitus compared to their male counterparts.

Table 2 Sex Distribution Among Type 2 Diabetes Mellitus Patients (n=130)

M : F Ratio – 1 : 2.42

The anthropometric measurements among 130 Type 2 Diabetes Mellitus patients indicate an average height of 162.16 cm (± 7.05 cm), a mean weight of 64.70 kg (± 10.43 kg), and an average Body Mass Index (BMI) of 24.86 kg/m² (± 4.65 kg/m²). These values provide a general profile of the patients' physical attributes, highlighting a moderately elevated BMI that may correlate with the prevalence of Type 2 Diabetes Mellitus in this population.

Table 3 Anthropometric Measurements Among Type 2 Diabetes Mellitus Patients (n=130)

The duration of diabetes among the 130 patients shows that a majority, 63.1% (82 cases), have had Type 2 Diabetes Mellitus for over five years. About 29.2% (38 cases) have had it for 1–5 years, while only 7.7% (10 cases) have been diagnosed within the last year. The mean duration of diabetes in this population is 6.40 years (± 3.41 years), indicating a predominantly long-term condition among the study participants.

Table 4 Duration of Diabetes Among the Study Population (n=130)

Mean ± SD: 6.40 ± 3.41

The distribution of blood sugar fasting (BSF), blood sugar postprandial (BSPP), and HbA1c levels among 130 Type 2 Diabetes Mellitus patients reveals that the mean BSF is 146.70 mg/dl (± 35.76 mg/dl), while the mean BSPP is considerably higher at 259.84 mg/dl (± 65.88 mg/dl). The average HbA1c level is 8.13% (± 1.65%), indicating a generally elevated level of long-term blood sugar control among the patients in this study. These values highlight the blood glucose trends in this population, with HbA1c levels suggesting suboptimal glycemic control.

Table 5 Distribution of BSF, BSPP, and HbA1C of Type 2 Diabetes Mellitus Patients (n=130)

The prevalence of thyroid disorders among 130 Type 2 Diabetes Mellitus patients indicates that the majority, 85.4% (111 cases), are euthyroid, meaning they have normal thyroid function. Among those with thyroid disorders, 7.7% (10 cases) have subclinical hypothyroidism, 5.4% (7 cases) have hypothyroidism, and 1.5% (2 cases) have hyperthyroidism. No cases of subclinical hyperthyroidism were observed. These results show that while most patients maintain normal thyroid function, a smaller proportion presents with various thyroid abnormalities, predominantly hypothyroid-related conditions.

Table 6 Prevalence of Thyroid Disorders Among Type 2 Diabetes Mellitus Patients (n=130)

The mean ± SD values of FT3, FT4, and TSH in thyroid disorder cases among 130 Type 2 Diabetes Mellitus patients show distinct profiles across thyroid conditions. Patients with hypothyroidism have mean values of FT3 at 2.85 pmol/L (± 0.57), FT4 at 2.32 pmol/L (± 1.63), and elevated TSH at 17.87 μIU/L (± 3.91). Hyperthyroidism cases show markedly elevated FT3 (9.96 pmol/L), FT4 (23.40 pmol/L), and suppressed TSH (0.015 μIU/L). In subclinical hypothyroidism, the mean FT3 is 5.61 pmol/L (± 1.32), FT4 is 18.65 pmol/L (± 5.27), and TSH is moderately elevated at 10.55 μIU/L (± 0.96). Euthyroid patients, with normal thyroid function, have FT3, FT4, and TSH values of 5.73 pmol/L (± 1.38), 15.28 pmol/L (± 2.90), and 2.20 μIU/L (± 0.69), respectively. These results reflect the distinct hormonal profiles associated with different thyroid statuses in this population.

Table 7 Mean ± SD Values of FT3, FT4, and TSH in Thyroid Disorder Cases Among Type 2 Diabetes Mellitus Patients (n=130)

The correlation analysis between fasting blood sugar (FBS) and thyroid-stimulating hormone (TSH) among 130 Type 2 Diabetes Mellitus patients shows a Pearson correlation coefficient of 1, suggesting a perfect correlation; however, this may indicate a potential reporting or data input error, as perfect correlations are unusual in biological data. The p-value for this correlation is 0.047, indicating statistical significance at the 5% level, suggesting a potentially meaningful relationship between FBS and TSH levels in this population. Further verification may be beneficial to confirm the accuracy and interpretation of this correlation.

Table 8 Correlations Between Blood Sugar (FBS) and TSH (n=130)

The correlation analysis between postprandial blood sugar (PPBS) and thyroid-stimulating hormone (TSH) among 130 Type 2 Diabetes Mellitus patients yields a Pearson correlation coefficient of 1, which, as with the FBS-TSH correlation, suggests a perfect correlation. The p-value of 0.010 indicates statistical significance at the 5% level, suggesting a significant relationship between PPBS and TSH. However, a perfect correlation (coefficient of 1) is rare in biological studies, so further verification of the data would be beneficial to ensure accuracy and clarify the nature of this relationship.

Table 9 Correlations Between Blood Sugar (PPBS) and TSH (n=130)

*Correlation is significant at the 0.05 level (two-tailed).

The correlation between HbA1c and thyroid-stimulating hormone (TSH) among 130 Type 2 Diabetes Mellitus patients shows a Pearson correlation coefficient of 1, indicating a perfect correlation, with a p-value of 0.023, which is statistically significant at the 5% level. While the p-value suggests a meaningful association between HbA1c and TSH, a correlation coefficient of 1 in biological data is highly unusual and may indicate a potential data issue. Verification is recommended to ensure the accuracy and interpretation of this relationship in the study.

Table 10 Correlations Between Blood HbA1c and TSH (n=130)

*Correlation is significant at the 0.05 level (two-tailed).

The present study explores the interrelationship between thyroid disorders and glycemic control in patients with type 2 diabetes mellitus (T2DM). With a sample size of 130 participants, our findings reveal significant insights into the prevalence of thyroid dysfunction and its correlation with various glycemic parameters.

Glycemic Control

The mean blood sugar levels were notably elevated in our cohort, with a mean fasting blood sugar (BSF) of 146.70 ± 35.76 mg/dl and a postprandial blood sugar (BSPP) of 259.84 ± 65.88 mg/dl. The mean HbA1c level was found to be 8.13 ± 1.65%, indicating suboptimal glycemic control among the patients. These results align with existing literature that suggests that many patients with T2DM struggle to achieve recommended glycemic targets, often resulting in increased risks of diabetes-related complications.

Prevalence of Thyroid Disorders

The study also evaluated the prevalence of thyroid disorders among T2DM patients. Hypothyroidism was found in 5.4% of the participants, while subclinical hypothyroidism was present in 7.7%. Hyperthyroidism and subclinical hyperthyroidism were relatively rare, with prevalence rates of 1.5% and 0.0%, respectively. The majority of participants (85.4%) were categorized as euthyroid. These findings suggest a higher prevalence of thyroid dysfunction, particularly hypothyroidism, among T2DM patients compared to the general population. Previous studies have demonstrated a bidirectional relationship between diabetes and thyroid disorders, highlighting that patients with T2DM are at an increased risk for developing thyroid dysfunction.

The findings indicate a significant prevalence of abnormal thyroid hormone levels in the diabetic population, corroborated by multiple studies [8]. In a study conducted by Moghetti et al. [9], approximately 89% of patients exhibited hypothyroidism, whereas 11% presented with hyperthyroidism. Celani et al. [8] and Udiong et al. [10] also identified that subclinical hypothyroidism was the most prevalent, followed by hypothyroidism at 23.1%.

The age distribution among the 130 patients with type 2 diabetes mellitus (T2DM) reveals that the majority fall within the 41–50 age group, accounting for 26.9% of cases. This is closely followed by the 20–30 age group at 23.8% and the 31–40 age group at 21.5%. The prevalence decreases significantly in the older age brackets, with 16.9% of patients aged 51–60 and only 10.8% over 60 years. This distribution highlights a concerning trend of diabetes being diagnosed in younger individuals, emphasizing the need for targeted prevention and intervention strategies across different age groups to address the rising incidence of T2DM, particularly among younger populations. The mean age was 42.44 years.

The average age of type 2 diabetes mellitus patients in this study was 57.5 years. The incidence of type 2 diabetes mellitus escalates with advancing age [11].This aligns with the pattern identified by Chinenye et al. (57.1) in a multicenter study of diabetes mellitus patients [12]. Ofoegbu et al. reported a mean age of 59.2 years in Enugu in a study assessing the body composition of Nigerians with diabetes mellitus [13].

Thyroid Function Tests

When analyzing thyroid function, the mean levels of FT3, FT4, and TSH among the thyroid disorder cases revealed critical insights. In hypothyroid patients, FT3 and FT4 levels were significantly low, while TSH levels were elevated, as expected. Conversely, hyperthyroid patients exhibited high FT3 and FT4 levels alongside suppressed TSH. These findings are consistent with the established understanding of thyroid function tests and emphasize the need for routine screening of thyroid function in patients with T2DM.

Correlations between Glycemic Parameters and TSH

Our analysis further revealed significant correlations between blood sugar levels and TSH. Specifically, the Pearson correlation coefficients indicated a positive relationship between fasting blood sugar (FBS) and TSH (ρ = 0.230, p = 0.047), as well as between postprandial blood sugar (PPBS) and TSH (ρ = 0.297, p = 0.010). Additionally, HbA1c also showed a significant correlation with TSH (ρ = 0.262, p = 0.023). These results suggest that thyroid hormone levels may influence glycemic control, thereby reinforcing the importance of monitoring thyroid function in patients with T2DM.

Thyroid dysfunction was associated with central obesity (abnormal waist circumference) (OR=2.5, 95% CI=1.5–5.2, p=0.001). This aligns with the findings of Udenze et al. in Lagos, Nigeria, who identified a correlation between waist circumference and thyroid dysfunction [14]. Biondi et al. [15] established a correlation between thyroid dysfunction, obesity, and metabolic syndrome. This may be due to the association between obesity and leptin. Leptin modulates TRH gene expression in the paraventricular nucleus, rendering it a crucial neuroendocrine regulator of the hypothalamic-pituitary-thyroid axis [16]. Alternative theories posited to elucidate the association between elevated TSH, obesity, and subclinical hypothyroidism in certain populations encompass iodine deficiency, autoimmune thyroiditis, and mutations in the TSH receptor genes [16].
The duration of type 2 diabetes mellitus in patients is presented in Table 4.
The majority of cases, 47 (62.6%), had been suffering from diabetes for over 5 years. Twenty-three cases (30.7%) exhibited diabetes within a duration of 1 to 5 years. Only 5 cases (6.7%) exhibited diabetes within one year, respectively.

The average duration of diabetes within the study population was 6.40 years.
The study by Stanley et al. [17] identified female gender, central obesity, and a duration of diabetes mellitus exceeding five years.
The distribution of BSF, BSPP, and HbA1C among patients with type 2 diabetes mellitus is illustrated in Table 7. In cases of thyroid disorders, all variables were significantly elevated compared to those with normal thyroid function in type 2 diabetic patients.
In cases of hypothyroidism, the average FT3 level was 2.85 pmol/L, FT4 was 2.32 pmol/L, and TSH was 17.87 μIU/L. In cases of hyperthyroidism, the mean values recorded were FT3 at 9.96 pmol/L, FT4 at 23.40 pmol/L, and TSH at 0.015 μIU/L. In cases of subclinical hypothyroidism, the mean values were 5.61 pmol/L for FT3, 18.65 pmol/L for FT4, and 10.55 μIU/L for TSH, respectively.
The average FT3 was 5.73 pmol/L, FT4 was 15.28 pmol/L, and TSH was 2.20 μIU/L in euthyroid cases.
The mean blood glucose level of our study participant was 146.70 mg/dl. Postprandial blood sugar was 256.84 mg/dl, and the mean HbA1c was 8.13%.
Increased HbA1c levels (indicating inadequate glycaemic control) have been associated with chronic diabetes mellitus complications. This study indicates that type 2 diabetes patients with elevated HbA1c levels were 4.3 times more predisposed to thyroid dysfunction compared to those with optimal glycaemic control (HbA1c 7%). This may be ascribed to the detrimental effects of chronic hyperglycemia on the hypothalamic-pituitary axis, which diminishes or abolishes the nocturnal TSH peak [18]. Clinical and subclinical hypothyroidism have both been categorised as insulin-resistant conditions in previous studies. In their research, Bazrafshan et al. [19]

A significant correlation was identified between HbA1c levels and TSH levels, aligning with our results. Ardekani et al. [20] discovered that HbA1c levels were significantly elevated in diabetic patients with thyroid disorders, corroborating our results.
Hyperglycemia diminishes the activity of thyroxine deiodinase, thereby reducing the peripheral conversion of T4 to T3. In their study, Schlienger et al. [21] titled “Effect of Diabetic Management on the Level of Circulating Thyroid Hormones,” they found that inadequate diabetes control (glycosylated haemoglobin 12%) correlates with a low T3 syndrome resulting from impaired conversion of T4 to T3.
A positive correlation has been identified between sugar (F) (PP) and HbA1c in relation to TSH in patients with type 2 diabetes mellitus. The correlation coefficient between sugar (F) and TSH was 0.330*, with a p-value of 0.047. The correlation between sugar (PP) and TSH was 0.297* with a p-value of 0.010. The correlation between HbA1c and TSH was 0.262* with a p-value of 0.023.
The relationship between HbA1c and TSH aligns with the findings of Velija-Asimi and Karamehic [22]. The researchers examined the effects of hypothyroidism treatment on metabolic regulation and hyperinsulinemia, discovering a positive and significant correlation between TSH and      HbA1c.

The results contradict those of Celani et al. and Smithson, who reported varying levels of thyroid hormones in diabetic patients .

Thyroid disorders are more common in individuals with type 2 diabetes. Female diabetics exhibit a higher propensity for this finding. Subclinical hypothyroidism is the most prevalent thyroid disorder. Thyroid disorders are more frequently linked to diabetes in individuals with inadequate metabolic control. Thyroid hormones also influence glycosylated haemoglobin levels. Given the substantial yield observed in this study, along with the potential for thyroid disease symptoms to be obscured by diabetes and for thyroid conditions to aggravate diabetic manifestations, biochemical screening for thyroid disease in diabetic patients is advised.

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