Clinical meaning
T2DM features insulin resistance and progressive beta-cell dysfunction. Insulin resistance from TNF-alpha, IL-6, free fatty acids impairs IRS phosphorylation. Beta-cell compensation fails through glucotoxicity and lipotoxicity. First-line: metformin + lifestyle. Second-line based on comorbidities: SGLT2i or GLP-1RA for ASCVD, HF, CKD.
Diagnosis & workup
Diagnostics & workup: - Free T4 and Free T3 for thyroid hormone assessment - Thyroid ultrasound for nodule characterization (TI-RADS scoring) - Fine needle aspiration biopsy of thyroid nodules (Bethesda classification) - Morning cortisol (8 AM) and ACTH for adrenal function - HbA1c for 3-month glycemic control (target <7% for most adults) - Cosyntropin stimulation test for adrenal insufficiency - Fasting glucose and 2-hour OGTT for diabetes diagnosis
Risk factors: - Obesity (BMI >30) with insulin resistance - Chronic kidney disease affecting calcium-phosphorus-PTH axis - Pituitary adenoma causing hormonal hypersecretion or deficiency - Chronic corticosteroid use with HPA axis suppression - Autoimmune disease predisposition (Type 1 DM, Hashimoto's, Addison's) - Iodine deficiency or excess affecting thyroid function - Age-related hormonal decline (menopause, andropause)