title: Adjunct therapy for type 1 diabetes mellitus.
abstract: Insulin replacement therapy in type 1 diabetes mellitus (T1DM) is nonphysiologic. Hyperinsulinemia is generated in the periphery to achieve normal insulin concentrations in the liver. This mismatch results in increased hypoglycemia, increased food intake with weight gain, and insufficient regulation of postprandial glucose excursions. Islet amyloid polypeptide is a hormone synthesized in pancreatic beta cells and cosecreted with insulin. Circulating islet amyloid polypeptide binds to receptors located in the hindbrain and increases satiety, delays gastric emptying and suppresses glucagon secretion. Thus, islet amyloid polypeptide complements the effects of insulin. T1DM is a state of both islet amyloid polypeptide and insulin deficiency. Pramlintide, a synthetic analog of islet amyloid polypeptide, can replace this hormone in patients with T1DM. When administered as adjunctive therapy to such patients treated with insulin, pramlintide decreases food intake and causes weight loss. Pramlintide therapy is also associated with suppression of glucagon secretion and delayed gastric emptying, both of which decrease postprandial plasma glucose excursions. Pramlintide therapy improves glycemic control and lessens weight gain. Agents that decrease intestinal carbohydrate digestion (alpha-glucosidase inhibitors) or decrease insulin resistance (metformin) might be alternative adjunctive therapies in T1DM, though its benefits are marginally supported by clinical data.
authors.affiliation: Department of Medicine, Division of Endocrinology, State University of New York Health Science Center at Brooklyn, 450 Clarkson Avenue, New York, NY 11203, USA. hlebovitz1@hotmail.com
authors.forename: Harold E
authors.initials: HE
authors.lastname: Lebovitz
mesh_terms: D000682:Amyloid / Q000627:therapeutic use*; D050260:Carbohydrate Metabolism / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology; D004063:Digestion / Q000187:drug effects; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism; D058228:Islet Amyloid Polypeptide; D008687:Metformin / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000682:Amyloid; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D008687:Metformin; C105254:pramlintide; D005947:Glucose
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