In adults with obesity and type 2 diabetes, the improvement in insulin sensitivity measured by hyperinsulinemic-euglycemic clamp following marked weight loss is equivalent whether weight loss is achieved through behavioral diet therapy or Roux-en-Y gastric bypass surgery, indicating that the magnitude of weight loss, not the method, is the primary driver of systemic insulin sensitivity.

When a person loses a significant amount of weight, fat tissue around organs and inside muscle cells shrinks, which removes barriers that block insulin from working. This allows insulin to enter muscle tissue more easily, turn on signaling pathways that move glucose transporters to the cell surface, and let glucose enter muscle cells from the blood. This process improves the body's ability to lower blood sugar after eating, regardless of how the weight was lost.