What is the correct description of the pathology of diabetes mellitus type 2?

Pathophysiology of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is characterized by relative insulin deficiency with insulin resistance in peripheral tissues. This pathophysiological mechanism distinguishes it from other forms of diabetes and is supported by multiple clinical guidelines 1, 2.

Core Pathophysiological Mechanisms

Type 2 diabetes accounts for 90-95% of all diabetes cases and involves two primary defects:

1. Insulin Resistance:

   • Decreased biological response to insulin in target tissues (muscle, liver, fat)
   • Present even before clinical diagnosis of diabetes
   • Often associated with obesity, particularly visceral adiposity 2

2. Relative Insulin Deficiency:

   • Initially, pancreatic β-cells increase insulin production to compensate for insulin resistance
   • Over time, β-cell function deteriorates, leading to inadequate insulin secretion
   • This creates a state of "relative" insulin deficiency (as opposed to the absolute deficiency seen in type 1 diabetes) 1

Distinguishing from Other Types of Diabetes

This pathophysiology clearly differentiates type 2 diabetes from:

• Type 1 diabetes (option C): Characterized by absolute insulin deficiency due to autoimmune destruction of pancreatic β-cells 1
• Single gene disorders (option A): While genetic factors contribute to type 2 diabetes risk, it is not caused by a single chromosome defect with variable penetrance 1
• Autoimmune processes (option D): Anti-insulin antibodies are not a primary feature of type 2 diabetes 1

Progression of Disease

The pathophysiology follows a typical sequence:

1. Development of insulin resistance in peripheral tissues
2. Initial compensation with increased insulin production (hyperinsulinemia)
3. Progressive β-cell dysfunction leading to inadequate insulin secretion
4. Worsening hyperglycemia as the disease advances 1, 2

Metabolic Consequences

The combination of insulin resistance and relative insulin deficiency leads to:

• Increased hepatic glucose production
• Decreased glucose uptake in muscle and adipose tissue
• Disturbances in carbohydrate, fat, and protein metabolism 1

Risk Factors and Contributors

• Obesity (especially central/visceral)
• Physical inactivity
• Genetic predisposition
• Aging
• Certain ethnicities (higher risk in African Americans, Hispanic/Latino individuals, Native Americans, Asian Americans) 1, 2

Type 2 diabetes is a progressive disease with complex pathophysiology, but its core feature remains the combination of insulin resistance in peripheral tissues coupled with a relative, rather than absolute, deficiency of insulin 1, 2.