What is the pathophysiology of type 1 diabetes mellitus?

• A. Autoimmune destruction of pancreatic beta cells, resulting in absolute insulin deficiency.
• B. Insulin resistance in skeletal muscle, liver, and adipose tissue.
• C. Excess insulin production by beta cells.
• D. Autoimmune destruction of pancreatic alpha cells.

Answer: (A)

Type 1 diabetes mellitus is driven by autoimmune destruction of the pancreatic beta cells that make insulin, leading to an absolute deficiency of endogenous insulin. Immune attack—driven by autoreactive T cells and autoantibodies against beta-cell antigens (like GAD65, IA-2, ZnT8, or insulin itself)—reduces or eliminates insulin production. Without insulin, glucose can’t enter most tissues, so blood glucose rises even though insulin is absent rather than ineffective. The lack of insulin also promotes fat breakdown and ketone production, which can cause diabetic ketoacidosis if not treated. This differs from type 2 diabetes, where the main problem is insulin resistance with relative, not absolute, insulin deficiency. The other options don’t fit because they describe insulin resistance, excess insulin production, or autoimmune destruction of alpha cells, none of which define type 1 diabetes.