Orthostatic hypotension in diabetes mellitus: From cardiovascular autonomic neuropathy to clinical management

Orthostatic hypotension (OH) is a common yet often overlooked complication of diabetes mellitus that significantly impacts patients' quality of life and health outcomes. This review explores the relationship between diabetes and OH, covering its prevalence, pathophysiology, clinical implications, diagnostic approach, and management strategies. The pooled prevalence of OH across unselected diabetic populations is approximately 20–24%, notably higher than in the general population, and rises further among patients with established cardiovascular autonomic neuropathy (CAN) or diabetic neuropathy. The pathophysiology is closely linked to CAN, involving impaired baroreflex sensitivity, sympathetic denervation, and endothelial dysfunction. Poor glycemic control accelerates autonomic nerve damage and worsens OH, while hypoglycemic episodes may independently precipitate hemodynamic instability. Clinical implications include increased fall risk, cardiovascular events, postprandial hypotension, cognitive impairment, and elevated mortality. Supine hypertension, coexisting in up to 50% of patients with neurogenic OH, represents a critical therapeutic dilemma. Diagnosis rests on routine lying-and-standing blood pressure measurement and identification of reversible contributors, with autonomic function testing and, in selected cases, plasma norepinephrine measurement or sympathetic imaging reserved for specialist evaluation to distinguish neurogenic from non-neurogenic subtypes. Treatment encompasses non-pharmacological approaches and pharmacological agents, including midodrine, droxidopa, fludrocortisone, and pyridostigmine. This review emphasizes the importance of an individualized, multifaceted approach, including optimized glycemic control, in managing OH in diabetic patients.