Hieronymus Laura, Griffin Stacy
DiabetesCare & Communications, Lexington, KY, USA (Dr Hieronymus)Baptist Health-Lexington, KY, USA (Dr Griffin)
DiabetesCare & Communications, Lexington, KY, USA (Dr Hieronymus)Baptist Health-Lexington, KY, USA (Dr Griffin).
Diabetes Educ. 2015 Dec;41(1 Suppl):47S-56S. doi: 10.1177/0145721715607642. Epub 2015 Sep 30.
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.
糖尿病的病理生理学历来侧重于胰岛素分泌和功能的改变；然而，糖尿病涉及多种激素改变，包括胰淀素调节异常。本综述讨论了胰淀素在葡萄糖稳态中的生理功能以及在1型和2型糖尿病中补充胰淀素的理论依据。还讨论了合成胰淀素类似物普兰林肽的使用。
胰淀素主要在胰岛β细胞中形成，在摄入热量时与胰岛素共同分泌。1型糖尿病患者的基础胰淀素血清浓度较低，且对热量摄入无胰淀素反应。需要胰岛素治疗的2型糖尿病患者对热量摄入的胰淀素反应也减弱，这可能与β细胞损伤程度有关。胰淀素在维持葡萄糖稳态中的关键生理功能包括：对热量摄入作出反应时抑制胰高血糖素释放、延缓胃排空速率以及刺激大脑中的饱腹感中枢以限制热量摄入。普兰林肽适用于尽管接受了最佳胰岛素治疗但血糖控制仍不理想的1型和2型糖尿病成人患者。作为胰岛素治疗的辅助药物，普兰林肽在1型和2型糖尿病患者中显著降低了糖化血红蛋白（A1C）水平，并对体重产生了有利影响。它在每餐主餐前皮下注射。与普兰林肽联合使用时，胰岛素导致低血糖的风险增加。其他不良反应可能包括恶心、呕吐、厌食、食欲减退和头痛。正确选择患者并进行教育对于成功使用普兰林肽至关重要。
