title: Role of glucagon-like peptide-1 analogue versus amylin as an adjuvant therapy in type 1 diabetes in a closed loop setting with ePID algorithm.
abstract: Postprandial hyperglycemia due to paradoxical hyperglucagonemia is a major challenge of diabetes treatment despite the use of the artificial pancreas. We postulated that adjunctive therapy with pramlintide or exenatide would attenuate hyperglycemia in the postprandial phase through glucagon suppression, thereby optimizing the functioning of the closed-loop (CL) system. Subjects with type 1 diabetes (T1DM) on insulin pump therapy were recruited to participate in a 27-hour hospitalized admission on 3 occasions (2-4 weeks apart) and placed on the insulin delivery via CL system in random order to receive (1) insulin alone (control), (2) exenatide 2.5 µg + insulin, (3) pramlintide 30 µg + insulin. Medications were given prior to lunch and dinner, which was a standardized meal of 60 grams of carbohydrates. Insulin delivery was as per the ePID algorithm via the Medtronic CL system and continuous subcutaneous glucose monitoring via Medtronic Sof-sensors. Ten subjects age 23 ± 1 years with a HbA1c of 7.29 ± 0.3% (56 ± 1 mmol/mol) and duration of T1DM 10.6 ± 2.0 years participated in the 3-part study. Exenatide was found to be significantly better in attenuating postprandial hyperglycemia as compared to insulin monotherapy (P < .03) and pramlintide (P > .05). Glucagon suppression was statistically significant with exenatide (P < .03) as compared to pramlintide. Insulin requirements were lower with adjunctive therapy, but statistically insignificant. Insulin monotherapy results in postprandial hyperglycemia in T1DM in the CL setting and adjunctive therapy with exenatide reduces postprandial hyperglycemia effectively and should be considered as adjunctive therapy in T1DM.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Venkat Sasidhar
authors.initials: VS
authors.lastname: Renukuntla
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Neesha
authors.initials: N
authors.lastname: Ramchandani
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Jeniece
authors.initials: J
authors.lastname: Trast
authors.affiliation: Medtronic Minimed, Inc, Northridge, CA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Cantwell
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA rubina.heptulla@einstein.yu.edu.
authors.forename: Rubina A
authors.initials: RA
authors.lastname: Heptulla
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy; D000077270:Exenatide; D005260:Female; D005934:Glucagon / Q000097:blood; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage; D007332:Insulin Infusion Systems; D058228:Islet Amyloid Polypeptide / Q000627:therapeutic use*; D008297:Male; D019397:Pancreas, Artificial; D010455:Peptides / Q000627:therapeutic use*; D014688:Venoms / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D010455:Peptides; D014688:Venoms; D005934:Glucagon; D000077270:Exenatide; C105254:pramlintide
keywords: artificial pancreas; closed loop; ePID algorithm; exenatide; pramlintide; type 1 diabetes