Markedly Delayed Insulin Secretion and a High Rate of Undetected Overt Diabetes Characterize Glucose Metabolism in Adult Patients with Cystic Fibrosis After Lung Transplantation

Abstract

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). Twelve adult CF patients after LT without known diabetes (33.3 ± 11.5 years; body mass index [BMI] 21.5 ± 3.3 kg/m2) and 8 control subjects matched by age (36.0 ± 6.6 years; P>.05), BMI (22.3 ± 1.5 kg/m2; 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. 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*m2*mM), higher in CF-noDM (39.9 ± 23.4 pmol/min*m2*mM), but still significantly lower compared to CON (108.3 ± 53.9 pmol/min*m2*mM; P = .0008). CFRD patients exhibited increased triglyceride levels and decreased high-density lipoprotein levels. 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. AUC = area under the curve; BMI = body mass index; CF = cystic fibrosis; CFRD = cystic fibrosis-related diabetes; CFTR = cystic fibrosis transmembrane-conductance regulator; CF-TX = cystic fibrosis patients who underwent lung transplantation; CGM = continuous glucose monitoring; HbA1c = glycated hemoglobin; HDL = high-density lipoprotein; INDET = indeterminate glycemia; LDL = low-density lipoprotein; LT = lung transplantation; OGIS = oral glucose sensitivity index; OGTT = oral glucose tolerance test; QUICKI = quantitative insulin sensitivity check index.