**Core Concept**
Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and impaired insulin secretion, leading to hyperglycemia. The pathophysiology involves a complex interplay between genetic and environmental factors, resulting in impaired glucose metabolism.

**Why the Correct Answer is Right**
The correct answer is related to the concept of insulin resistance, which is a hallmark of T2DM. Insulin resistance occurs when the body's cells become less responsive to insulin, leading to increased glucose levels in the bloodstream. This is primarily due to impaired glucose uptake in peripheral tissues, such as skeletal muscle and adipose tissue. The key enzyme involved in this process is **phosphatidylinositol 3-kinase (PI3K)**, which is crucial for insulin signaling.

**Why Each Wrong Option is Incorrect**
**Option A:** This is incorrect because impaired insulin secretion is a contributing factor to hyperglycemia in T2DM, but it is not the primary cause.
**Option B:** This is incorrect because increased fasting plasma glucose in T2DM is not primarily due to decreased insulin sensitivity in the liver.
**Option C:** This is incorrect because increased fasting plasma glucose in T2DM is not primarily due to decreased glucagon-like peptide-1 (GLP-1) secretion.

**Clinical Pearl / High-Yield Fact**
A key clinical feature of T2DM is the presence of insulin resistance, which can be assessed using the homeostatic model assessment (HOMA) index. This index takes into account fasting glucose and insulin levels to estimate insulin sensitivity.

**Correct Answer:** D.