title: Effects of delayed gastric emptying on postprandial glucose kinetics, insulin sensitivity, and β-cell function.
abstract: Controlling meal-related glucose excursions continues to be a therapeutic challenge in diabetes mellitus. Mechanistic reasons for this need to be understood better to develop appropriate therapies. To investigate delayed gastric emptying effects on postprandial glucose turnover, insulin sensitivity, and β-cell responsivity and function, as a feasibility study prior to studying patients with type 1 diabetes, we used the triple tracer technique C-peptide and oral minimal model approach in healthy subjects. A single dose of 30 μg of pramlintide administered at the start of a mixed meal was used to delay gastric emptying rates. With delayed gastric emptying rates, peak rate of meal glucose appearance was delayed, and rate of endogenous glucose production (EGP) was lower. C-peptide and oral minimal models enabled the assessments of β-cell function, insulin sensitivity, and β-cell responsivity simultaneously. Delayed gastric emptying induced by pramlintide improved total insulin sensitivity and decreased total β-cell responsivity. However, β-cell function as measured by total disposition index did not change. The improved whole body insulin sensitivity coupled with lower rate of appearance of EGP with delayed gastric emptying provides experimental proof of the importance of evaluating pramlintide in artificial endocrine pancreas approaches to reduce postprandial blood glucose variability in patients with type 1 diabetes.
authors: Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, Minnesota;
authors: Ling
authors: L
authors: Hinshaw
authors: Department of Information Engineering, University of Padua, Padua, Italy;
authors: Michele
authors: M
authors: Schiavon
authors: Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, Minnesota;
authors: Ashwini
authors: A
authors: Mallad
authors: Department of Information Engineering, University of Padua, Padua, Italy;
authors: Chiara Dalla
authors: CD
authors: Man
authors: Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, Minnesota;
authors: Rita
authors: R
authors: Basu
authors: Division of Gastroenterology, Mayo Medical School, Rochester, Minnesota; and.
authors: Adil E
authors: AE
authors: Bharucha
authors: Department of Information Engineering, University of Padua, Padua, Italy;
authors: Claudio
authors: C
authors: Cobelli
authors: Department of Health Sciences Research, Mayo Medical School, Rochester, Minnesota.
authors: Rickey E
authors: RE
authors: Carter
authors: Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, Minnesota;
authors: Ananda
authors: A
authors: Basu
authors: Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, Minnesota; Kudva.Yogish@mayo.edu.
authors: Yogish C
authors: YC
authors: Kudva
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D005260:Female; D005502:Food; D005746:Gastric Emptying / Q000502:physiology*; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007004:Hypoglycemic Agents; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D058228:Islet Amyloid Polypeptide; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D005934:Glucagon; C105254:pramlintide; D005947:Glucose
keywords: gastric emptying; insulin action; pramlintide