oxyntomodulin and Cystic-Fibrosis

In spite of the evidence that inadequately controlled glycemia is associated with worse clinical outcomes, cystic fibrosis-related diabetes (CFRD) is not well controlled in a majority of patients. The objective of this report is to demonstrate the effect of the addition of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), to basal insulin to control glycemia in one such patient.. The replacement of rapidly acting prandial insulin with semaglutide weekly with continuation of basal insulin. Glycated hemoglobin A1c (HbA1c) was measured and continuous glucose monitoring (CGM) was conducted.. There was a significant improvement in glycemic control, reduction in HbA1c from 9.1% to 6.7% and stable euglycemic pattern on CGM (mean glucose, 142 mg/dL; SD, 51) within 3 months of starting treatment. There was no increase in plasma pancreatic enzyme concentrations.. Semaglutide at a low dose was able to replace prandial insulin and control glycemia in combination with basal insulin.

Topics: Blood Glucose; Cystic Fibrosis; Diabetes Mellitus; Drug Therapy, Combination; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptides; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Treatment Outcome; Young Adult

Pancreatic and gut hormone responses to oral glucose, and insulin sensitivity were studied in cystic fibrosis patients with normal (N = 14), impaired (N = 4), and diabetic (N = 12) glucose tolerance, and in 10 control subjects, and beta cell responses to oral glucose and intravenous glucagon were compared. Compared to control subjects, initial insulin and C-peptide responses to oral glucose were lower in all patient groups, and decreased with decreasing glucose tolerance. Insulin sensitivity in patients with impaired and diabetic glucose tolerance was lower than in control subjects. The 6 min post-glucagon C-peptide concentration was positively correlated with the initial insulin response to oral glucose. Fasting levels of pancreatic polypeptide, pancreatic glucagon, total glucagon, glucagon-like peptide-1 7-36 amide, and gastric inhibitory polypeptide were normal in all patient groups. Following oral glucose, pancreatic polypeptide responses were absent in all patients, suppressibility of pancreatic glucagon secretion was increasingly impaired with decreasing glucose tolerance, and gut hormone levels were normal. In conclusion, at cystic fibrosis (a) insulin secretion is impaired even when glucose tolerance and insulin sensitivity are within the normal range, (b) the glucagon test gives valid estimates of residual beta cell function, (c) pancreatic polypeptide response to oral glucose is absent, (d) glucagon suppressibility decreases with decreasing glucose tolerance, and (e) the enteroinsular axis is intact.

Topics: Administration, Oral; Adult; C-Peptide; Cystic Fibrosis; Diabetes Complications; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose; Glucose Tolerance Test; Hormones; Humans; Injections, Intravenous; Insulin; Intestinal Mucosa; Intestines; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Peptide Fragments; Proinsulin; Protein Precursors; Time Factors

Intestinal dysmotility may be an important factor contributing to various gastrointestinal complications associated with cystic fibrosis. Motilin, enteroglucagon, neurotensin, and peptide YY may each play a role as endocrine hormones influencing gastrointestinal motor activity. Fasting children with cystic fibrosis (N = 8) and controls (N = 18) received a liquid nutrient test meal (fat 4 g/100 ml, protein 4 g/100 ml, carbohydrate 20 g/100 ml, 125 kcal/100 ml; 200 ml/m2) containing lactulose (5 g/100 ml), and the plasma concentrations of these peptides were studied. Mouth-to-cecum transit time was simultaneously studied using the breath H2 technique. Fasting levels of peptide YY and the postprandial response of all four peptides were significantly increased in those with cystic fibrosis. In repeat studies on those with cystic fibrosis after a period of altered pancreatic enzyme supplementation, no significant changes in peptide concentrations were observed. A rise in breath H2 permitting estimation of mouth-to-cecum transit time was noted in 17 control subjects (70-220 min, median 140). In contrast, a rise occurred in only two with cystic fibrosis after low-dose enzyme (70 and 180 min), and four after high-dose enzyme replacement (120-230 min, median 155). Altered gut hormone secretion may play a role in the pathophysiology of intestinal dysmotility in patients with cystic fibrosis.

Topics: Adolescent; Breath Tests; Child; Cystic Fibrosis; Fasting; Food; Gastrointestinal Motility; Glucagon-Like Peptides; Humans; Hydrogen; Motilin; Neuropeptides; Neurotensin; Peptide YY; Peptides