Pathophysiology of Diabetes

Type 1 diabetes results from autoimmune destruction of pancreatic islet β cells. Infiltrating immune cells produce inflammatory agents that destroy these cells. Exposure to viruses or environmental factors stimulates this autoimmune cellular destruction in genetically susceptible individuals. When approximately 80% of β cells are destroyed, hyperglycemia develops and clinical diagnosis occurs.

Type 2 diabetes stems from heterogeneous causes including impaired β cell function, reduced insulin secretion, and insulin resistance in skeletal muscles, adipose tissue, and liver. Excessive glucagon production and hepatic insulin resistance dysregulate glucose metabolism, elevating blood glucose in fasting and post-meal states. Unlike type 1, type 2 involves gradual onset with strong genetic predisposition and is typically associated with obesity.

Insulin resistance impedes glucose transport from circulation into target tissues. This dysfunction in skeletal muscles, adipose tissue, and liver prevents efficient glucose uptake, causing blood glucose to accumulate. Elevated fasting insulin levels and dysregulated glucagon secretion further complicate glucose homeostasis, contributing to the hyperglycemia characteristic of type 2 diabetes.

Other specific types include monogenic forms such as MODY and neonatal diabetes, which arise from mutations affecting key genes in glucose regulation. Secondary diabetes can result from diseases like pancreatitis or cystic fibrosis, or from endocrinopathies that disrupt normal glucose metabolism. Gestational diabetes occurs during pregnancy due to placental hormones causing insulin resistance, typically resolving after childbirth.

Gestational diabetes develops when the mother's pancreas cannot produce sufficient insulin to compensate for placental hormone-induced insulin resistance during pregnancy. Although gestational diabetes typically resolves after childbirth, it significantly increases the risk for type 2 diabetes in both mother and child in the future, indicating a lasting metabolic vulnerability.

Type 1 diabetes involves a complex interplay between genetics and environment. Certain genes increase susceptibility, yet many affected individuals lack family history. Environmental factors such as viral exposure or inflammatory responses trigger autoimmune destruction in genetically predisposed individuals, with the autoimmune process progressing over months to years before clinical onset.

In type 2 diabetes, the liver becomes resistant to insulin action, impairing its ability to regulate glucose metabolism appropriately. Combined with excessive glucagon production, this hepatic insulin resistance dysregulates glucose output from the liver, increasing blood glucose levels in both fasting and post-prandial states and perpetuating hyperglycemia.