Age- and sex-dependent distribution of OGTT-related variables in a population of cystic fibrosis patients

Alberto Battezzati, Giorgio Bedogni, Laura Zazzeron, Andrea Mari, Pier Maria Battezzati, Gianfranco Alicandro, Simona Bertoli, Carla Colombo

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Context: Cystic fibrosis (CF) causes an exceptionally high prevalence of diabetes that increases with age, especially in females. The glucose tolerance defect is progressive, but a cystic fibrosis transmembrane conductance regulator-dependent insulin secretory defect cannot be excluded. The age and sex dependence of the secretory defect is unclear. Objective: The objective of the study was to analyze the age and sex dependency of insulin secretory and sensitivity parameters in CF. Design: This was a cross-sectional analysis in an observational ongoing cohort (mean follow-up duration 7.5 y). Setting: The study was conducted at the CF Center of Milan. Patients: The study included 187 patients aged 8-30 years. Intervention: Interventions included 3-hour oral glucose tolerance tests (n = 478) with 30-minute insulin and c-peptide sampling. Main Outcome Measures: Model-derived insulin secretory and sensitivity parameters were measured. Results: Age was associated with a progressive decrement in insulinemia (at 30 min) and a subsequent increment in glycemia (at 60-90 min), returning at or below baseline (at 180 min). These changes are explained by a progressive reduction in β-cell sensitivity to glucose and a progressive increment in insulin clearance. Fasting and postprandial insulin sensitivity do not seem to be involved. Compared with males, females display higher glucose, insulin, and c-peptide responses with greater insulin secretion, β-cell sensitivity to glucose, insulin clearance, and equal insulin sensitivity. Conclusions: A defect in β-cell sensitivity to glucose progressively develops with age, but it is not sex specific and does not explain the worse glucose tolerance reported in females. In contrast, insulin clearance increases with age, especially in females, contributing to the deterioration in glucose tolerance. The effects of age and sex should be considered when evaluating oral glucose tolerance test results in CF patients.

Original languageEnglish
Pages (from-to)2963-2971
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number8
DOIs
Publication statusPublished - Aug 1 2015

Fingerprint

Sex Distribution
Glucose Tolerance Test
Cystic Fibrosis
Insulin
Glucose
Insulin Resistance
Population
Defects
Cystic Fibrosis Transmembrane Conductance Regulator
Peptides
Fasting
Cross-Sectional Studies
Outcome Assessment (Health Care)
Medical problems
Deterioration
Sampling

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Age- and sex-dependent distribution of OGTT-related variables in a population of cystic fibrosis patients. / Battezzati, Alberto; Bedogni, Giorgio; Zazzeron, Laura; Mari, Andrea; Battezzati, Pier Maria; Alicandro, Gianfranco; Bertoli, Simona; Colombo, Carla.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 8, 01.08.2015, p. 2963-2971.

Research output: Contribution to journalArticle

Battezzati, Alberto ; Bedogni, Giorgio ; Zazzeron, Laura ; Mari, Andrea ; Battezzati, Pier Maria ; Alicandro, Gianfranco ; Bertoli, Simona ; Colombo, Carla. / Age- and sex-dependent distribution of OGTT-related variables in a population of cystic fibrosis patients. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 8. pp. 2963-2971.
@article{89dfd6c7be3a4cb2a2772325ca943cbc,
title = "Age- and sex-dependent distribution of OGTT-related variables in a population of cystic fibrosis patients",
abstract = "Context: Cystic fibrosis (CF) causes an exceptionally high prevalence of diabetes that increases with age, especially in females. The glucose tolerance defect is progressive, but a cystic fibrosis transmembrane conductance regulator-dependent insulin secretory defect cannot be excluded. The age and sex dependence of the secretory defect is unclear. Objective: The objective of the study was to analyze the age and sex dependency of insulin secretory and sensitivity parameters in CF. Design: This was a cross-sectional analysis in an observational ongoing cohort (mean follow-up duration 7.5 y). Setting: The study was conducted at the CF Center of Milan. Patients: The study included 187 patients aged 8-30 years. Intervention: Interventions included 3-hour oral glucose tolerance tests (n = 478) with 30-minute insulin and c-peptide sampling. Main Outcome Measures: Model-derived insulin secretory and sensitivity parameters were measured. Results: Age was associated with a progressive decrement in insulinemia (at 30 min) and a subsequent increment in glycemia (at 60-90 min), returning at or below baseline (at 180 min). These changes are explained by a progressive reduction in β-cell sensitivity to glucose and a progressive increment in insulin clearance. Fasting and postprandial insulin sensitivity do not seem to be involved. Compared with males, females display higher glucose, insulin, and c-peptide responses with greater insulin secretion, β-cell sensitivity to glucose, insulin clearance, and equal insulin sensitivity. Conclusions: A defect in β-cell sensitivity to glucose progressively develops with age, but it is not sex specific and does not explain the worse glucose tolerance reported in females. In contrast, insulin clearance increases with age, especially in females, contributing to the deterioration in glucose tolerance. The effects of age and sex should be considered when evaluating oral glucose tolerance test results in CF patients.",
author = "Alberto Battezzati and Giorgio Bedogni and Laura Zazzeron and Andrea Mari and Battezzati, {Pier Maria} and Gianfranco Alicandro and Simona Bertoli and Carla Colombo",
year = "2015",
month = "8",
day = "1",
doi = "10.1210/jc.2015-1512",
language = "English",
volume = "100",
pages = "2963--2971",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "8",

}

TY - JOUR

T1 - Age- and sex-dependent distribution of OGTT-related variables in a population of cystic fibrosis patients

AU - Battezzati, Alberto

AU - Bedogni, Giorgio

AU - Zazzeron, Laura

AU - Mari, Andrea

AU - Battezzati, Pier Maria

AU - Alicandro, Gianfranco

AU - Bertoli, Simona

AU - Colombo, Carla

PY - 2015/8/1

Y1 - 2015/8/1

N2 - Context: Cystic fibrosis (CF) causes an exceptionally high prevalence of diabetes that increases with age, especially in females. The glucose tolerance defect is progressive, but a cystic fibrosis transmembrane conductance regulator-dependent insulin secretory defect cannot be excluded. The age and sex dependence of the secretory defect is unclear. Objective: The objective of the study was to analyze the age and sex dependency of insulin secretory and sensitivity parameters in CF. Design: This was a cross-sectional analysis in an observational ongoing cohort (mean follow-up duration 7.5 y). Setting: The study was conducted at the CF Center of Milan. Patients: The study included 187 patients aged 8-30 years. Intervention: Interventions included 3-hour oral glucose tolerance tests (n = 478) with 30-minute insulin and c-peptide sampling. Main Outcome Measures: Model-derived insulin secretory and sensitivity parameters were measured. Results: Age was associated with a progressive decrement in insulinemia (at 30 min) and a subsequent increment in glycemia (at 60-90 min), returning at or below baseline (at 180 min). These changes are explained by a progressive reduction in β-cell sensitivity to glucose and a progressive increment in insulin clearance. Fasting and postprandial insulin sensitivity do not seem to be involved. Compared with males, females display higher glucose, insulin, and c-peptide responses with greater insulin secretion, β-cell sensitivity to glucose, insulin clearance, and equal insulin sensitivity. Conclusions: A defect in β-cell sensitivity to glucose progressively develops with age, but it is not sex specific and does not explain the worse glucose tolerance reported in females. In contrast, insulin clearance increases with age, especially in females, contributing to the deterioration in glucose tolerance. The effects of age and sex should be considered when evaluating oral glucose tolerance test results in CF patients.

AB - Context: Cystic fibrosis (CF) causes an exceptionally high prevalence of diabetes that increases with age, especially in females. The glucose tolerance defect is progressive, but a cystic fibrosis transmembrane conductance regulator-dependent insulin secretory defect cannot be excluded. The age and sex dependence of the secretory defect is unclear. Objective: The objective of the study was to analyze the age and sex dependency of insulin secretory and sensitivity parameters in CF. Design: This was a cross-sectional analysis in an observational ongoing cohort (mean follow-up duration 7.5 y). Setting: The study was conducted at the CF Center of Milan. Patients: The study included 187 patients aged 8-30 years. Intervention: Interventions included 3-hour oral glucose tolerance tests (n = 478) with 30-minute insulin and c-peptide sampling. Main Outcome Measures: Model-derived insulin secretory and sensitivity parameters were measured. Results: Age was associated with a progressive decrement in insulinemia (at 30 min) and a subsequent increment in glycemia (at 60-90 min), returning at or below baseline (at 180 min). These changes are explained by a progressive reduction in β-cell sensitivity to glucose and a progressive increment in insulin clearance. Fasting and postprandial insulin sensitivity do not seem to be involved. Compared with males, females display higher glucose, insulin, and c-peptide responses with greater insulin secretion, β-cell sensitivity to glucose, insulin clearance, and equal insulin sensitivity. Conclusions: A defect in β-cell sensitivity to glucose progressively develops with age, but it is not sex specific and does not explain the worse glucose tolerance reported in females. In contrast, insulin clearance increases with age, especially in females, contributing to the deterioration in glucose tolerance. The effects of age and sex should be considered when evaluating oral glucose tolerance test results in CF patients.

UR - http://www.scopus.com/inward/record.url?scp=84939142834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939142834&partnerID=8YFLogxK

U2 - 10.1210/jc.2015-1512

DO - 10.1210/jc.2015-1512

M3 - Article

C2 - 26057180

AN - SCOPUS:84939142834

VL - 100

SP - 2963

EP - 2971

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 8

ER -