MARKEDLY DELAYED INSULIN SECRETION AND A HIGH RATE OF UNDETECTED OVERT DIABETES CHARACTERIZE GLUCOSE METABOLISM IN ADULT PATIENTS WITH CYSTIC FIBROSIS AFTER LUNG TRANSPLANTATION.

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/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. 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*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. 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. ABBREVIATIONS: 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.

Impact of nutritional status on pulmonary function after lung transplantation for cystic fibrosis.

BACKGROUND: Nutritional status is an important prognostic factor in patients with cystic fibrosis (CF) prior to lung transplantation. OBJECTIVE: To investigate the impact of nutritional status on pulmonary function in CF transplant recipients. METHODS: Adult double lung transplanted CF patients were consecutively included. The predictive value of nutritional status on lung function - measured by spirometry - was longitudinally assessed by body composition serially evaluated by a three-compartment model bioelectrical impedance analysis (BIA) in comparison to body mass index (BMI). RESULTS: Overall, 147 spirometries and 147 BIAs were performed in 58 patients (59% female, median age: 30.1 years, median BMI: 19.6 kg/m2). Malnourished patients (BMI < 18.5 kg/m2; 27.6%) had a significantly reduced lung function compared to normal/overweight patients (forced expiratory volume in 1 second in percent (FEV1%pred), 57% vs 77%; p = 0.024). BMI, as well as the BIA parameters phase angle, total body water, fat free mass, body cell mass (BCM) and extracellular mass (ECM)/BCM ratio, were univariate predictors of FEV1%pred. When included in a linear mixed model, ECM/BCM ratio remained the only significant predictor of lung function (p = 0.012). CONCLUSION: Nutritional status assessed by BIA predicted lung function in CF transplant recipients. Serial BIA measurements to monitor patients' nutritional status might help to improve or maintain lung function.