Effect of Hyperglycemia on Gastric Emptying Interactions With Pramlintide
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      • To examine the influence of acute glycaemia (normoglycaemia and hyperglycaemia) on gastric
      emptying kinetics in patients with type 1 diabetes and non diabetic subjects when treated
      with subcutaneous (SC) injections of pramlintide.
    

Detailed description: 
      Postprandial increases in plasma glucose concentrations are mainly determined by the degree
      of postprandial suppression of endogenous glucose production and the rate of appearance of
      the ingested glucose. The latter is predominantly determined by the amount of glucose taken
      up by the splanchnic bed. Because nutrient absorption depends on gastric nutrient delivery,
      gastric emptying rate is a key determinant of the early rise of plasma glucose
      postprandially. At mealtime, the faster the stomach empties the more rapid the rise in plasma
      glucose. Yet, plasma glucose concentration is a determinant of gastric emptying rate. In
      non-diabetic subjects, as plasma glucose rises and approaches the upper limit of the normal
      range (~140 mg/dl), gastric emptying slows. This likely represents a physiological brake
      mechanism to limit excess delivery of nutrients, thus avoiding excessive appearance of
      glucose in plasma. In diabetes, abnormally accelerated gastric emptying as well as delayed
      gastric emptying have been reported. These conflicting data may be explained by differences
      of ambient glycaemia. In most of these studies undertaken in diabetic subjects these patients
      were severely hyperglycaemic, thus the reported delayed gastric emptying may be explained by
      the effect of hyperglycaemia on gastric motility. Indeed, a small number of studies
      controlled for ambient glycaemia found acceleration of gastric emptying in diabetes and
      suggest that diabetes manifests with a maladaptive acceleration of gastric emptying likely
      contributing to excessive postprandial plasma glucose excursions.

      The amylin analog pramlintide is a potential new therapeutic that elicits a potent glucose
      lowering effect in the postprandial period thought to be due to both a suppression of plasma
      glucagon and a delay of gastric emptying. It is not clear, however, to what extent the
      pramlintide-induced delay of gastric emptying offsets a potential maladaptive acceleration of
      gastric emptying in diabetes patients studied under controlled glycemic conditions. In
      theory, every drug that reduces hyperglycaemia should accelerate gastric emptying and,
      thereby, minimize its potential effect on postprandial hyperglycaemia. Thus, the drug-induced
      effect of amylin on gastric motility may be of great advantage by offset the effects of
      glycemic induced acceleration on gastric emptying.
    

Intervention name(s): placebo; pramlintide; placebo; pramlintide
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): placebo SC during euglycemia; pramlintide SC during eglycemia; placebo during hyperglycemia; pramlintide SC during hyperglycemia
Intervention MeSH terms: Pramlintide; Islet Amyloid Polypeptide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Diagnostic
Keywords: pramlintide; gastric emptying; T1DM; postprandial