Update on diagnosis and monitoring of cystic fibrosis-related diabetes mellitus (CFRD)

Abstract

Cystic fibrosis (CF) is the most common recessive autosomal disease among Caucasian. Children with CF have benefitted from advances in medical and nutritional treatments, and this can be gleaned from the improvement in the survival of these patients. The increase in the survival rate brought with it the appearance of co-morbidities related to CF. Nowadays cystic fibrosis-related diabetes (CFRD) is considered the most common complication associated with CF. It can appear as early as infancy or adolescence, and its prevalence can be as high as 50% in adult patients. Because of its high prevalence, difficulties in early detection and the risks involved, in recent years several studies and consensuses have focused on this condition, adding information about the epidemiology, pathophysiology, prognosis and treatment of CFRD. The main aspects of these new concepts, as well as the current recommendations for its diagnosis and follow-up, will be presented in this study.

Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR

“…Isolated islets from DF508 mice also exhibited significant reductions in insulin secretion compared with the wild-type with greater difference observed at 5 min (around 80%) than that at 60 min (around 30%) after glucose challenge (Fig. 4b), which is consistent with the lack of the first phase response to glucose challenge in CFRD patients424. We also performed in vivo glucose tolerance test.…”

“…Although the cause of insulin insufficiency is generally considered to be a result of β-cell damage by autoimmunity, a high percentage of diabetic patients with insulin insufficiency show negative of those autoantibodies3. Notably, whereas most CFRD cases exhibit insulin insufficiency45, the exact cause remains elusive although destruction of the insulin-secreting pancreatic islets secondary to the obstruction of the pancreatic duct due to defective CFTR has long been considered the underlying cause67. Interestingly, CFTR expression in the pancreatic islet has been reported8; however, its exact role in islet function remains unexplored.…”

Cystic Fibrosis-Related Diabetes in Adults: Inpatient Management of 121 Patients during 410 Admissions

“…2 Advances in medical and nutritional treatment of CF have dramatically improved the life expectancy of affected individuals. [3][4][5] Survival into their 5th and 6th decades of life is no longer a medical miracle but a realistic expectation for many individuals with CF.…”

“…6,7 It is estimated that approximately half of CF adult patients develop CFRD. [3][4][5] The pathogenesis of CFRD is incompletely understood. 3,8 Clearly, insulin insufficiency, particularly in the postprandial state, plays a principal role in the pathogenesis of CFRD.…”

Diagnosis and treatment of endocrine comorbidities in patients with cystic fibrosis

“…Furthermore, fasting and 2-h postprandial plasma glucose levels of CF patients with acute pulmonary exacerbation requiring intravenous antibiotics and/or systemic glucocorticoids should be monitored at least in the first 48 hours. A diagnosis of diabetes should be made if the FPG concentration is greater than or equal to 126 mg/dL or postprandial plasma glucose levels are greater than or equal to 200 mg/dL [28, 32, 36]. …”