Pathophysiology
Clinical meaning
Type 1 diabetes results from autoimmune destruction of pancreatic beta cells by CD4+ and CD8+ T lymphocytes, with autoantibodies (GAD65, IA-2, ZnT8, insulin antibodies) detectable months to years before clinical onset. This leads to absolute insulin deficiency requiring exogenous insulin for survival. Type 2 diabetes develops from progressive insulin resistance in skeletal muscle, liver, and adipose tissue, followed by beta cell dysfunction and relative insulin deficiency. The pathophysiology involves the 'ominous octet': decreased insulin secretion, increased glucagon, increased hepatic glucose output, increased lipolysis, decreased incretin effect, increased renal glucose reabsorption, neurotransmitter dysfunction, and decreased muscle glucose uptake. Chronic hyperglycemia causes microvascular complications (retinopathy, nephropathy, neuropathy) through polyol pathway activation, advanced glycation end-product (AGE) formation, protein kinase C activation, and hexosamine pathway flux. Macrovascular complications (CAD, CVD, PAD) result from accelerated atherosclerosis.