A 21 year-old man with a 7-year history of type 2 diabetes mellitus (T2DM) presents for follow-up. He was diagnosed with T2DM at age 14 years. At that time, his body mass index (BMI) was in the 99th percentile for his age. His mother has a history of gestational diabetes mellitus during her pregnancy with him and was diagnosed with T2DM in her early forties, when he was ten years old. His current BMI is 41 kg/m2 (normal, 18.5 to 24.9 kg/m2). He has been treated with metformin and insulin analogues, but he has not been taking the insulin recently because he feels unwell after he exercises with symptoms of shakiness, sweatiness, and hunger. His glycated hemoglobin (HbA1c) is 9.2% (normal, <5.7%). He wants to know more about diabetes mellitus and asks if there are other medication options for him.
1. The pathophysiology of the diabetes mellitus of this patient is characterized by which of the following?
- Increased glucagon secretion
- Insulin resistance and beta cell dysfunction
- Increased peripheral glucose uptake
- Decreased hepatic gluconeogenesis
- A and B
Correct Answer: E ) A and B
Rationale: Insulin, produced and secreted by beta cells located in clusters of pancreatic cells called the islets of Langerhans, is the most potent anabolic hormone, promoting the uptake, utilization, and storage of both glucose and lipids. T2DM is characterized by resistance to the actions of insulin in target tissues. Pancreatic beta cells compensate by increasing insulin secretion, and patients with insulin resistance initially have high circulating levels of insulin and maintain normal serum levels of glucose. Eventually, however, pancreatic beta cells start to fail. When they can no longer supply enough insulin to meet these increased requirements, T2DM develops. It is believed that the chronic demand for elevated insulin secretion in insulin resistant subjects unmasks a secondary defect in the beta cells, resulting in progressive loss of beta cell function. Thus, both insulin resistance and insufficiency of beta cell function are important features in T2DM pathogenesis. In addition, glucagon secretion by pancreatic alpha cells appears to be inappropriately elevated in many patients with T2DM, and thus, a decreased insulin:glucagon ratio may also contribute to hyperglycemia in these patients.
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