One of the most prevalent and rapidly expanding illnesses worldwide is diabetes. This chronic metabolic disorder is brought on by either absolute or relative insulin insufficiency in conjunction with either insulin resistance (IR), β-cell malfunction, or both. According to research from the International Diabetes Federation (IDF), over 536 million persons worldwide would have diabetes in 2021 [1]. Type 2 diabetes mellitus (T2DM) affects over 90% of diabetics [2]. In general, diabetic patients who receive inadequate care or have poor dietary control may develop life-threatening chronic complications, such as microvascular problems like diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), and diabetic nephropathy (DN), as well as macrovascular problems like cardiovascular disease (CVD). Damage to the macrovascular system, particularly the coronary and cerebrovascular arteries, brought on by hyperglycemia is one of the reasons why diabetes people die [3]. Nonetheless, it is more frequent for hyperglycemia to harm the kidney, eyes, and nerves' microvascular networks [4]. In addition, it has a significant effect on mortality. About 14.1% of people with type 2 diabetes in India have subclinical hypothyroidism [5]. Diabetes mellitus is linked to subclinical hypothyroidism [6]. In patients with type 2 diabetes, hypothyroidism raises the risk of microvascular problems [7]. Thyroid hormone levels have been linked to microvascular problems, even in euthyroid T2 DM patients [8]. Two of the most important metabolic disorders with a well-established correlation are diabetes mellitus and thyroid-related ailments [9]. Changes in circulating thyroid hormone levels can play a role in the onset and course of vascular disease because the vascular endothelium tissue contains thyroid hormone receptors [10]. As a result, more emphasis is being paid to how thyroid function affects diabetic microvascular problems. The pituitary and hypothalamus, feedback mechanisms, and the unique traits and activities of the thyroid are only a few of the many complex elements that go into controlling thyroid function. Thyroid stimulating hormone (TSH), which is produced and released by the pituitary gland, causes the thyroid gland to release more thyroxine. Between its accessible free form, known as free thyroxine (FT4), and its isolated protein-bound form, thyroxine circulates throughout the body in a balanced condition. The circulating FT3:FT4 ratio can be used to measure the conversion of FT4 to the active form of triiodothyronine (FT3) in the thyroid and peripheral tissues [11]. The purpose of this study was to ascertain if microvascular problems in T2 DM patients in a tertiary care facility were related to thyroid-stimulating hormone (TSH) levels.

Aim: To investigate the relationship between Type 2 DM's microvascular problems and TSH levels.

This was a cross-sectional hospital based study conducted on patients with Type 2 DM visiting in our hospital over a period of 1 year from January 2024 to December 2024.  This study was conducted following the Declaration of Helsinki. All patients provided written informed consent.

Inclusion criteria:

• Patients aged ≥ 18 years old with both male and female
• Patients diagnosed as T2DM according to the criteria of the American Diabetes Association [12].
• Patients provide written informed consent for the study

Exclusion criteria

• Patients <18 years of age or patients with T1 DM
• Past history of thyroid diseases, treatment with levothyroxine or antithyroid drugs,
• Pregnancy, acute or chronic infection, malignancy, chronic kidney disease (CKD), patients on hemodialysis and critically ill patients
• Patients not provide consent for the study

Demographic and anthropometric information was gathered on factors such as age, sex, length of T2DM, medicinal interventions, family history of T2DM, history of hypertension, and body mass index (BMI). The following venous blood laboratory values were obtained following an overnight fast: TSH, FT3, FT4, HbA1c, and lipid profile values. The study group was divided into three categories for further analysis according to the TSH levels: 0.27–2.49 mIU/L; 2.5–4.2 mIU/L; and >4.2 mIU/L. All subjects were assessed for microvascular complications of diabetes such as diabetic nephropathy, neuropathy, and retinopathy.

Diabetic kidney disease (DKD) was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 (calculated by CKD-EPI formula) or presence of microalbuminuria/ microalbuminuria. Fundoscopy was done to detect diabetic retinopathy (DR). Diabetic neuropathy was assessed by testing for vibration sense using 128Hz tuning fork. The association between TSH levels and microvascular complications of T2 DM was studied.

Statistical analysis:

IBM SPSS Statistic for Windows, version 24 (IBM Corp., Armonk, N.Y., USA) was used to calculate the frequency, percentage, mean, standard deviation, and probability value after the gathered data was imported into Microsoft Excel Worksheet-2010. P<0.05 is regarded as significant.

The total number of 100 type 2 diabetes mellitus patients fulfilled inclusion criteria were enrolled in this research. Majority of them (43%) were more than 60 years age group, predominantly males (64%). Most of them (65%) resided in urban area and 78% belong to upper-middle class. Maximum of the patients (65%) had education up to or above secondary school.

Table 1: Demographic profile among study participants

Among patients with their HbA1c 7-8%, two had their TSH between 0.27–2.49, four had their TSH in the range of 2.5–4.2, and none had TSH >4.2. Patients with HbA1c values 8.1-9%, six had their TSH between 0.27-2.49, eight had their TSH between 2.5-4.2, and five had TSH >4.2. Patients having HbA1c value 9.1–10%, 15% had their TSH in the range of 0.27–2.49, 14% had their TSH between 2.5-4.2, and 11% had their TSH >4.2. Among patients with their HbA1c value of >10%, 13% had their TSH between 0.27-2.49, 12% had their TSH between 2.5-4.2, and 9% patients had their TSH >4.2. No significant association was found between TSH level and HbA1c (P>0.05) [Table 2].

Table 2: Association between HbA1c and TSH level

At the time of the investigation, 72% (n=72) of the patients had microvascular disease; 35% (n = 35) had only one complication; 25% (n = 25) had two types of microvascular complications and 12% (n = 12) had three types of microvascular complications [Graph: 1].

Graph 1: Frequency of diabetic microvascular complications

The association between TSH levels and microvascular complications were studied. No significant association was found between TSH levels with retinopathy and neuropathy (P>0.05). No statistically significant association was found between higher TSH levels and presence of microalbuminuria and Macroalbuminuria (P>0.05). A significant association was found between higher TSH levels with low GFR and higher TSH levels with Diabetic Kidney Disease with P<0.05)

Table 3: Association between TSH levels and microvascular complications among type 2 DM

In the present study majority of the patients were elderly (>60 years) age group and predominantly males, similar findings were reported by Li H, et al [13].

In our study no statistically significant association was found between TSH level and HbA1c level among type 2 diabetes mellitus subjects, in agreement with the Bingi, et al [14].

We have found that most of the (72%) type 2 DM patients had microvascular disease; among microvascular complications majority of the patients had only one complication; followed by two types and three types of microvascular complications, our results comparable with the Yonghui Hu, et al [15].

TSH levels and diabetic retinopathy were not found to be related in our investigation. Similarly, there was no discernible link between thyroid malfunction and DR in a research by Kassawneh et al. [16] and Ramis JN, et al. [17]. Nonetheless, a research by Hejrat et al. [18] discovered a link between DR and high TSH levels.

According to Kim et al. [19], the current investigation found no significant correlation between TSH levels and diabetic peripheral neuropathy, which contradicts our findings. According to Allam et al. [20], SCH was discovered to be extremely common in diabetic peripheral neuropathy and to be independently correlated with its severity.

The present study showed a significant association between high TSH levels and low GFR. Similarly in a study conducted by Yang et al [21], a negative correlation was found between TSH levels and GFR.

The current investigation found a strong correlation between elevated TSH levels and diabetic nephropathy. Similar conclusions were drawn from studies by Gao et al. [22] and Lin J. et al. [23], which found that elevated TSH was linked to DKD in patients with type 2 diabetes. Renal hemodynamic, endothelial dysfunction, peripheral vascular resistance, and cardiac dysfunction all contribute to overt and subclinical hypothyroidism's impact on kidney function.

No significant association was found between albuminuria and higher TSH levels in the present study, in contrast to current study, Najmaldin et al [24], reported that T2 DM patients with SCH patients had a higher rate of albuminuria as compared to euthyroid patients and increasing TSH values were associated with increasing urine ACR.

We came to the conclusion that there was a strong correlation between diabetic kidney disease and high TSH levels and low GFR. Nevertheless, there was no discernible correlation between TSH levels and albuminuria, diabetic neuropathy, or diabetic retinopathy. Thus, a correlation between TSH levels and microvascular problems of type 2 diabetes was established. To ascertain whether there is a real correlation between TSH levels and the risk of microvascular problems in patients with type 2 diabetes, a sizable randomized controlled clinical trial ought to be conducted.

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