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: - HbA1c for 3-month glycemic control (target <7% for most adults) - Fine needle aspiration biopsy of thyroid nodules (Bethesda classification) - Plasma metanephrines for pheochromocytoma screening - Dexamethasone suppression test (1mg overnight) for Cushing screening - Fasting glucose and 2-hour OGTT for diabetes diagnosis - Prolactin level for pituitary evaluation - Morning cortisol (8 AM) and ACTH for adrenal function
Risk factors: - Autoimmune disease predisposition (Type 1 DM, Hashimoto's, Addison's) - Pituitary adenoma causing hormonal hypersecretion or deficiency - Eating disorders with hypothalamic amenorrhea - Prior radiation to head/neck affecting thyroid or pituitary - Age-related hormonal decline (menopause, andropause) - Metabolic syndrome (waist circumference, triglycerides, HDL, BP, glucose) - Chronic corticosteroid use with HPA axis suppression