Role of Amylin in Type 1 and Type 2 Diabetes

The pathophysiology of diabetes has historically focused on alterations in insulin secretion and function; however, diabetes involves multiple hormonal alterations, including abnormal regulation of amylin. This review discusses the physiologic functions of amylin in glucose homeostasis and the rationale for amylin replacement in type 1 and 2 diabetes. The use of pramlintide, a synthetic amylin analog, is also discussed.

Amylin, formed primarily in pancreatic islet β cells, is cosecreted with insulin in response to caloric intake. Patients with type 1 diabetes have lower baseline amylin serum concentrations, and amylin response to caloric intake is absent. Patients with type 2 diabetes requiring insulin also have a diminished amylin response to caloric intake, potentially related to the degree of β-cell impairment. Key physiologic functions of amylin in maintaining glucose homeostasis include suppressing glucagon release in response to caloric intake, delaying the rate of gastric emptying, and stimulating the satiety center in the brain to limit caloric intake. Pramlintide is indicated for adults with type 1 and 2 diabetes who have not achieved adequate glucose control despite optimal insulin therapy. As an adjunct to insulin therapy, pramlintide demonstrated significant reductions in A1C in patients with type 1 and 2 diabetes, with favorable effects on body weight. It is administered subcutaneously before each major meal. There is an increased risk of hypoglycemia with insulin when used in combination with pramlintide. Other adverse effects may include nausea, vomiting, anorexia, reduced appetite, and headache. Proper patient selection and education are essential to successful pramlintide use.