title: Effect of pramlintide on prandial glycemic excursions during closed-loop control in adolescents and young adults with type 1 diabetes.
abstract: OBJECTIVE
  Even under closed-loop (CL) conditions, meal-related blood glucose (BG) excursions frequently exceed target levels as a result of delays in absorption of insulin from the subcutaneous site of infusion. We hypothesized that delaying gastric emptying with preprandial injections of pramlintide would improve postprandial glycemia by allowing a better match between carbohydrate and insulin absorptions.
  
  
  METHODS
  Eight subjects (4 female; age, 15-28 years; A1C, 7.5 ± 0.7%) were studied for 48 h on a CL insulin-delivery system with a proportional integral derivative algorithm with insulin feedback: 24 h on CL control alone (CL) and 24 h on CL control plus 30-μg premeal injections of pramlintide (CLP). Target glucose was set at 120 mg/dL; timing and contents of meals were identical on both study days. No premeal manual boluses were given. Differences in reference BG excursions, defined as the incremental glucose rise from premeal to peak, were compared between conditions for each meal.
  
  
  RESULTS
  CLP was associated with overall delayed time to peak BG (2.5 ± 0.9 vs. 1.5 ± 0.5 h; P < 0.0001) and reduced magnitude of glycemic excursion (88 ± 42 vs. 113 ± 32 mg/dL; P = 0.006) compared with CL alone. Pramlintide effects on glycemic excursions were particularly evident at lunch and dinner, in association with higher premeal insulin concentrations at those mealtimes.
  
  
  CONCLUSIONS
  Pramlintide delayed the time to peak postprandial BG and reduced the magnitude of prandial BG excursions. Beneficial effects of pramlintide on CL may in part be related to higher premeal insulin levels at lunch and dinner compared with breakfast.
authors: Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA. stuart.weinzimer@yale.edu
authors: Stuart A
authors: SA
authors: Weinzimer
authors: Jennifer L
authors: JL
authors: Sherr
authors: Eda
authors: E
authors: Cengiz
authors: Grace
authors: G
authors: Kim
authors: Jessica L
authors: JL
authors: Ruiz
authors: Lori
authors: L
authors: Carria
authors: Gayane
authors: G
authors: Voskanyan
authors: Anirban
authors: A
authors: Roy
authors: William V
authors: WV
authors: Tamborlane
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide / Q000627:therapeutic use*; D008297:Male; D062407:Meals; D019397:Pancreas, Artificial; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; C105254:pramlintide