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Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT

Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT

Published on: January 7, 2018

Hypoglycemia in cystic fibrosis during an extended oral glucose tolerance test

Natasha Armaghanian^1,2,3, Julie Hetherington⁴, Venkat Parameswaran^5,6

¹Academic Department of Adolescent Medicine, Children's Hospital at Westmead, Sydney, Australia.

Pediatric Pulmonology

|September 21, 2020

Insights

Hypoglycemia in cystic fibrosis (CF) is common, especially in those without CF-related diabetes. A 3-hour oral glucose tolerance test revealed delayed insulin release and potential issues with glucagon regulation as contributing factors.

Area of Science:

Endocrinology
Metabolic Disorders
Pulmonology

Background:

Hypoglycemia is a recognized complication in cystic fibrosis (CF) management, yet its underlying causes remain unclear.
Existing research lacks a unifying hypothesis for the etiology of hypoglycemia in CF patients without glucose-lowering treatments.

Purpose of the Study:

To assess glucose, insulin, glucagon, GLP-1, and GIP release patterns during a 3-hour oral glucose tolerance test (OGTT) in individuals with CF.
To determine the prevalence of hypoglycemia during the OGTT in this population.
To investigate the association between hypoglycemia and the release patterns of key hormones.

Main Methods:

A 3-hour OGTT was administered to adult participants attending a CF clinic.
Hormone levels (glucose, insulin, glucagon, GLP-1, GIP) were measured at multiple time points (fasting, 30, 60, 120, 180 minutes).
Hypoglycemia was categorized as mild (3.4-3.9 mmol/L), moderate (3.1-3.3 mmol/L), or severe (≤3.0 mmol/L).

Main Results:

Out of 24 participants, 19 (79%) without CF-related diabetes experienced hypoglycemia during the OGTT.
Participants with hypoglycemia showed higher peak glucose and insulin responses.
Delayed insulin release was observed across all glucose tolerance groups, while glucagon suppression was appropriate.

Conclusions:

Extending the OGTT to 3 hours unmasked postprandial hypoglycemia in a significant portion of the CF cohort.
Delayed insulin secretion and potentially impaired glucagon counter-regulation are implicated in the development of hypoglycemia in CF.
No correlation was found between hypoglycemia and modulator therapy use.

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Abstract

Background:

Hypoglycemia in cystic fibrosis (CF), in the absence of glucose-lowering therapies, has long been identified as an important issue in the management of CF. There is currently still no unifying hypothesis for its etiology.

Aim:

The aims of this study were to perform a 3-h oral glucose tolerance test (OGTT) in participants with CF and (1) document glucose, insulin, glucagon, glucagon-like-peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) release patterns within varying glucose tolerance groups during the OGTT; (2) determine the prevalence of hypoglycemic during the OGTT; and (3) define any association between hypoglycemia and patterns of insulin, glucagon, GLP-1, and GIP release.

Methods:

Eligible participants attending an adult CF clinic completed a 3-h OGTT. Hypoglycemia on OGTT was defined as mild (glucose 3.4-3.9 mmol/L), moderate (glucose 3.1-3.3 mmol/L), and severe (glucose ≤ 3 mmol/L). Hormones were measured at fasting, 30, 60, 120, and 180 min.

Results:

Twenty-four participants completed the study, of which 7 had normal glucose tolerance, 12 had abnormal glucose tolerance, and 5 had cystic fibrosis related diabetes (CFRD). All participants had a delayed insulin response compared with normative data. All glucose tolerance groups showed appropriate and similar suppression of fasting glucagon. Four participants (17%) had mild hypoglycemic, three (13%) had moderate hypoglycemic, and eight (33%) had severe hypoglycemic. No participant with CFRD demonstrated hypoglycemic. Of the 19 participants without CFRD, 15 (79%) experienced hypoglycemic. Participants with hypoglycemic had greater peak glucose and insulin responses than those that did not have hypoglycemic, and this approached significance (p = .0625 for glucose and p = .0862 for insulin). No significant mean differences between GLP-1 and GIP release were found. There was no relationship between hypoglycemic and modulator therapy.

Conclusion:

Postprandial hypoglycemic was unmasked by the extension of an OGTT to 3 h. Delayed and abnormal insulin release, and ineffective counter-regulatory action of glucagon may have a role in its etiology.

Keywords:

abnormal glucose metabolism cystic fibrosis hypoglycemia oral glucose tolerance test

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