type 1 diabetes

Type 1 diabetes is caused by T-cell mediated autoimmune destruction of pancreatic islet beta cells, often associated with HLA-DR3 and HLA-DR4 haplotypes. Autoantibodies commonly detected include anti-GAD65, anti-insulin, anti-islet cell (ICA), and anti-IA-2 antibodies, useful for diagnosis and distinguishing from type 2 diabetes. Unlike type 2 diabetes, T1DM is not typically associated with obesity or insulin resistance, and patients have little to no endogenous insulin production, reflected by low C-peptide levels.

Pathophysiology: Genetic susceptibility combined with environmental triggers (e.g., viral infections such as coxsackievirus B) leads to autoimmune insulitis, progressive beta cell destruction, and insulin deficiency. This results in impaired glucose uptake by tissues, unchecked hepatic gluconeogenesis/glycogenolysis, and lipolysis with ketogenesis due to unopposed glucagon action, predisposing patients to diabetic ketoacidosis (DKA)—a hallmark acute complication presenting with hyperglycemia, anion gap metabolic acidosis, ketonemia/ketonuria, Kussmaul respirations, and fruity breath odor.

Clinical features: Onset is usually in childhood or adolescence (though can occur at any age—'latent autoimmune diabetes of adults,' LADA). Classic symptoms include polyuria, polydipsia, polyphagia, unexplained weight loss, and fatigue. Diagnosis is based on fasting plasma glucose ≥126 mg/dL, random glucose ≥200 mg/dL with symptoms, HbA1c ≥6.5%, or oral glucose tolerance test criteria, supported by presence of autoantibodies and low C-peptide.

Management: Requires exogenous insulin (basal-bolus regimens, insulin pumps) for survival, along with glucose monitoring, dietary management, and monitoring for chronic microvascular (retinopathy, nephropathy, neuropathy) and macrovascular complications (cardiovascular disease). Associated with other autoimmune conditions (Hashimoto thyroiditis, celiac disease, Addison disease) as part of polyglandular autoimmune syndromes.

Key boards distinction: T1DM = absolute insulin deficiency, autoimmune, prone to DKA, normal/low BMI, requires insulin. T2DM = relative insulin deficiency/insulin resistance, associated with obesity/metabolic syndrome, prone to hyperosmolar hyperglycemic state (HHS) rather than DKA, may be managed with lifestyle changes and oral hypoglycemics initially.