An Update in Cystic Fibrosis-Related Diabetes in Children and Adolescents

Abstract

This paper delineates several aspects of cystic fibrosis-related diabetes (CFRD)—a common complication of cystic fibrosis (CF). CFRD exhibits a predilection for older individuals with CF, yet it also extends its influence on children and adolescents. Scientific insights postulate a potential link between CFRD and the aberrant mucus production within the pancreas, thereby culminating in pancreatic insufficiency. This, in turn, perturbs the synthesis of insulin, a pivotal endocrine hormone responsible for the regulation of glycemic levels. Standardized protocols advocate for the systematic screening of CFRD among all individuals with CF, commencing at the age of 10 years using the oral glucose tolerance test (OGTT). Therapeutic modalities encompass insulin therapy, dietary adjustments, and the vigilant monitoring of glycemic parameters. The overarching objective is to maintain blood glucose levels within a targeted range to mitigate the advent of diabetic complications. Untreated or sub-optimally managed CFRD can precipitate a spectrum of deleterious health ramifications, encompassing cardiovascular afflictions, neuropathy, renal dysfunction, and ocular complications.

The Role of Continuous Glucose Monitoring in Detecting Early Dysglycemia and Clinical Outcomes in Patients with Cystic Fibrosis

“…Several risk factors have been associated with the development of CFRD including organ insufficiency (lung, liver, exocrine pancreas), growth delay, sex (female), residual CFTR function-related factors (residual function, genotype, genetic modifiers), history of solid organ transplantation, abnormal glucose tolerance (impaired fasting glucose, impaired glucose tolerance, indeterminate), and medication use (corticosteroids, calcineurin inhibitors) [ 12 ].…”

“…These hormones stimulate insulin release into the circulation, inhibit pancreatic glucagon and somatostatin secretion, delay gastric emptying, and suppress appetite. There is some evidence that patients with CFRD have significantly lower levels of GIP and GLP-1 when compared to healthy controls [ 12 , 36 ]. Therefore, the secretion of incretins and the responsiveness to incretins is diminished in the pancreatic insufficiency that arises in CF [ 4 ].…”

“…Patients with CF have various epidemiological, genetic, therapeutic, and clinical features that may impact glycemia and lead to bidirectional changes in glycemic status, which have been observed using both OGTT and CGM [ 12 , 35 , 40 ]. In addition, β-cell responsiveness is a dynamic process [ 45 ], which makes it difficult to define dysglycemia, irrespective of the screening test used.…”

“…Insulin is currently the primary treatment modality for CFRD and possibly prediabetes; however, CFRD is a heterogeneous disease, and not all patients with CFRD need insulin therapy. Insulin has effects beyond blood glucose control, including improving respiratory function and enhancing body mass index (BMI) by repleting muscle mass and protein reserves [ 12 , 13 ]. Several insulin regimens are available, and the choice of regimen should be based on the patient’s blood glucose variability and disease severity (e.g., basal insulin only, multiple daily injections like basal–bolus therapy, or an insulin pump).…”

“…Nutritive support is of utmost importance in the treatment of CFRD. As opposed to patients with type 1 and type 2 diabetes, optimal management for usually undernourished CF patients involves a high-caloric diet, aiming for a caloric intake 20–100% higher than that of healthy peers [ 11 , 12 ]. Physical activity is useful in maintaining blood glucose control and reducing insulin requirements but may be accompanied by an increased risk of hypoglycemia [ 12 , 15 ].…”