Objective: Cystic fibrosis-related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT). Methods: Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index [BMI] 21.5 ± 3.3 kg/m 2 ) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m 2 ; P>.05), and gender (CON group) underwent a 3-hour OGTT with glucose, insulin, and C-peptide measurements. Parameters of insulin secretion and sensitivity as well as lipid profiles were assessed. Results: In the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values >200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*m 2 *mM), higher in CF-noDM (39.9 ± 23.4 pmol/ min*m 2 *mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/ min*m 2 *mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels. Conclusion: Adult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism

Markedly delayed insulin secretion and a high rate of undetected overt diabetes characterize glucose metabolism in adult patients with cystic fibrosis after lung transplantation

Tura A;Pacini G;
2019

Abstract

Objective: Cystic fibrosis-related diabetes (CFRD) is associated with adverse clinical outcomes and should be screened for by an annual oral glucose tolerance test (OGTT). Since pathophysiologic studies have mainly been performed in a pediatric/adolescent, nontransplanted collective, we aimed to assess parameters of insulin secretion and sensitivity in adult cystic fibrosis (CF) patients after lung transplantation (LT). Methods: Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index [BMI] 21.5 ± 3.3 kg/m 2 ) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m 2 ; P>.05), and gender (CON group) underwent a 3-hour OGTT with glucose, insulin, and C-peptide measurements. Parameters of insulin secretion and sensitivity as well as lipid profiles were assessed. Results: In the CF group, 4 patients were diagnosed with overt diabetes (CFRD) compared to CF patients without diabetes (CF-noDM), of whom 6 had indeterminate glycemia with 1-h glucose values >200 mg/dL. The insulin peak after glucose load occurred after 30 minutes in CON, after 90 minutes in CF-noDM, and was missing in CFRD. Insulin sensitivity was comparable between the groups. Beta-cell glucose sensitivity was markedly reduced in CFRD (10.7 ± 5.8 pmol/min*m 2 *mM), higher in CF-noDM (39.9 ± 23.4 pmol/ min*m 2 *mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/ min*m 2 *mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels. Conclusion: Adult CF patients after LT have profound disturbances in glucose metabolism, with a high rate of undetected diabetes and markedly delayed insulin secretion. Curbed beta-cell glucose sensitivity rather than insulin resistance explains postprandial hyperglycemia and is accompanied by abnormalities in lipid metabolism
2019
Istituto di Neuroscienze - IN -
C peptide
calcineurin inhibitor
cystic fibrosis transmembrane conductance regulator
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14243/391834
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