Diabetologia

, Volume 40, Issue 1, pp 82-88

Infusion of pramlintide, a human amylin analogue, delays gastric emptying in men with IDDM

  • M.-F. KongAffiliated withDepartment of Diabetes, University Hospital Nottingham, Nottingham, UK
  • , P. KingAffiliated withDepartment of Diabetes, University Hospital Nottingham, Nottingham, UK
  • , I. A. MacdonaldAffiliated withDepartment of Physiology and Pharmacology, University of Nottingham Medical School, Nottingham, UK
  • , T. A. StubbsAffiliated withDepartment of Physiology and Pharmacology, University of Nottingham Medical School, Nottingham, UK
  • , A. C. PerkinsAffiliated withDepartment of Medical Physics, University Hospital Nottingham and University of Nottingham Medical School, Nottingham, UK
  • , P. E. BlackshawAffiliated withDepartment of Medical Physics, University Hospital Nottingham and University of Nottingham Medical School, Nottingham, UK
  • , C. MoysesAffiliated withAmylin Pharmaceuticals, Amylin Europe Ltd, Oxford, UK
  • , R. B. TattersallAffiliated withDepartment of Diabetes, University Hospital Nottingham, Nottingham, UK

Summary

Pramlintide, a human amylin analogue, reduces hyperglycaemia after meals in patients with insulin-dependent diabetes mellitus (IDDM). We investigated whether this was due to delayed gastric emptying. Eight men with uncomplicated IDDM were studied twice in a randomised, double-blind crossover design. Euglycaemia was maintained overnight by intravenous infusion of glucose and/or insulin and the following morning a 5-h infusion of pramlintide 25 μg/h or placebo was started at 08.00 hours. At 08.30 hours the patients injected their normal morning insulin dose subcutaneously and 30 min later ate a meal (600 kcal, 50 % carbohydrate) of which the solid component was labelled with Technetium-99 m and the liquid with Indium-111 to quantify gastric emptying. Gamma-scintigraphic images were obtained every 20 min for the next 4 h. Insulin and glucose were infused as necessary to maintain blood glucose levels within 3 mmol/l of the pre-meal value. Compared to placebo, pramlintide significantly delayed emptying of both liquid (median lag time 69 vs 7.5 min) and solid (median lag time 150 vs 44.5 min) components of the meal. Pramlintide delayed gastric emptying so much that t50 values could not be calculated for solid or liquid. Amylin agonists such as pramlintide may, therefore, be of value in improving glycaemic control in IDDM by modifying gastric emptying. [Diabetologia (1997) 40: 82–88]

Keywords Insulin-dependent diabetes mellitus gastric emptying postprandial hyperglycaemia amylin pramlintide.