Clinical and In-Silico Analysis of Thyroid Dysfunction and Type 2 Diabetes Risk in Non-Diabetic Iraqi Patients with Subclinical Hypothyroidism

Thyroid dysfunction and type 2 diabetes mellitus (T2DM) are interconnected endocrine disorders, yet their causal relationship remains unclear. This study investigates the impact of subclinical hypothyroidism (SCH) on the risk of developing insulin resistance, prediabetes, and T2DM in non-diabetic Iraqi subjects. A total of 300 SCH patients and 200 healthy controls were assessed for fasting blood glucose (FBG), fasting insulin (FI), glycosylated hemoglobin (HbA1c), thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3) at baseline and after 16 months without treatment. Insulin resistance was evaluated using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The interaction between thyroid hormones and the insulin receptor tyrosine kinase was investigated using molecular docking methodologies. Results showed that 49 % of SCH patients developed clinical hypothyroidism, while all participants exhibited insulin resistance by the follow-up period. After the follow-up period, 73 % of the patients developed prediabetes, and 27 % progressed to T2DM. Molecular docking analyses revealed direct interactions between T3, T4, and the insulin receptor, suggesting a modulatory role of thyroid hormones in insulin signaling. It is concluded that untreated SCH significantly increases the risk of metabolic disorders, supporting thyroid dysfunction as a causative factor in diabetes development. Early detection and management of SCH could be critical in preventing T2DM onset. HIGHLIGHTS The study demonstrates that untreated subclinical hypothyroidism significantly increases the risk of insulin resistance, prediabetes, and type 2 diabetes mellitus in non-diabetic individuals. Computational analysis shows direct interactions between T3, T4, and the insulin receptor tyrosine kinase, supporting the potential modulatory role of thyroid hormones in insulin signaling and glucose metabolism. The findings highlight the importance of early detection and management of subclinical hypothyroidism to prevent metabolic disorders, supporting the role of thyroid dysfunction as a causative factor in diabetes development rather than a consequence. GRAPHICAL ABSTRACT