Kistik Fibrozis Tanılı Hastalarda Glukoz Metabolizmasının Değerlendirilmesi

Abstract

Cystic fibrosis is a multisystemic disease that affects all exocrine tissues including lung, digestive system (liver, biliary tract, pancreas, intestines), reproductive system (epididymis) and sweat glands. With the prolongation of life expectancy of cystic fibrosis patients, disease-related complications have started to be seen more frequently. Recently, due to increased awareness and widespread application of screening tests these complications are more commonly observed. Glucose homeostasis disorders are among these complications. In patients with glucose homeostasis disorder, impaired glucose tolerance or cystic fibrosis related diabetes is seen. After sinus diseases, asthma and reflux, cystic fibrosis related diabetes, which is among the “other causes of diabetes” in current diabetes classification, is the most common complication in cystic fibrosis. Due to worsening of clinical condition, reduction of lung functions, deterioration in nutritional status, and decreased expectation of life these disorders have to be recognized and treated. Previous studies and national reports have shown that the incidence of cystic fibrosis-related diabetes is increased in patients aged 10 years and older. In the early period, cystic fibrosis related diabetes may have a clinical silent course. Therefore current guidelines recommend the evaluation of glucose metabolism annually in cystic fibrosis patients aged 10 years or older. In this study, 94 patients aged between 10 and 18 years who were followed-up in the outpatient clinic of Hacettepe University, Faculty of Medicine, Pediatric Pulmonology Department between November 15, 2018 and March 15, 2019 were included. Oral glucose tolerance test was applied all patients and the results show that, 74 (78.7%) of the patients had normal glucose tolerance, 16 (17%) had impaired glucose tolerance and 4 (4.3%) had cystic fibrosis related diabetes. Patients with normal glucose tolerance and abnormal glucose tolerance were compared in terms of clinical features and laboratory parameters. In 25 (33.8%) of the patients with normal glucose tolerance, 14 (70%) of the patients with abnormal glucose tolerance had a family history of diabetes, and there was a statistically significant difference between these two groups (p=0,004). The median (quartile interval) number of antibiotics given for acute pulmonary exacerbation in the last year in patients with normal glucose tolerance was 2 (2,5) and it was 3 (3,5) in patients with abnormal glucose tolerance; there was a statistically significant difference between the two groups (p=0,004). Mean FEV1 percentage in normal glucose tolerance patients was 88.8 (± 24.4) and in abnormal glucose tolerance patients was 74.1 (± 26.3). There was a statistically significant difference between the two groups (p=0,021). Liver disease was present in 21 (30%) of the patients with normal glucose tolerance and 11 (57.9%) of patients with abnormal glucose tolerance; there was a statistically significant difference between the two groups (p = 0.025). The percentage of HbA1c was significantly different between patients with normal glucose tolerance and abnormal glucose tolerance (p <0.001). A moderate positive correlation was found between oral glucose tolerance test 120th minute plasma glucose level and HbA1c percentage. The diagnostic value of HbA1c percentage in predicting abnormal glucose tolerance was found as AUC: 0.716 (95%, 0.57 - 0.86, p = 0.003), and the diagnostic performance was moderate. When the diagnostic performance measurements were evaluated, the cut-off point was determined to be >5,7. Sensitivity for this value was 75% (95%CI 50,9 - 91,3), and its specifity was 63,5% (95%CI 51,5 - 74,4). When the percentage of HbA1c >5,7 was used as a diagnostic criterion, 4 (20%) of 20 patients with cystic fibrosis related diabetes could not be diagnosed. Considering the effects of cystic fibrosis related diabetes on pulmonary functions, nutritional status and mortality, the rate of false negativity was considered to be clinically high. In conclusion, patients with abnormal glucose tolerance had a history of diabetes more frequently in their families. The number of acute pulmonary exacerbations they had in the last year was higher, the percentage of FEV1 was lower, and the incidence of liver disease was higher in both univariate and multivariate analyzes. When the percentage of HbA1c> 5,7 was used as a diagnostic criterion, the rate of false negativity was high. Low HbA1c percentages could not exclude abnormal glucose tolerance. Therefore, it should be recommended to use oral glucose tolerance test in screening of cystic fibrosis related diabetes until an easily applicable, cost-effective, sensitive and specific method that can be used widely for screening in all patients is developed.