|
Diabetes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
These results indicate that CFRD is caused by β cell loss and intraislet inflammation in the setting of a complex pleiotropic disease and not by intrinsic islet dysfunction from CFTR mutation.
|
29669939 |
2018 |
|
Diabetes
|
0.100 |
Biomarker
|
disease |
BEFREE |
The results reveal that by potentiating KATP channels, CFTR acts as a glucose-sensing negative regulator of glucagon secretion in α cells, a defect of which may contribute to glucose intolerance in CF and other types of diabetes.
|
28977595 |
2017 |
|
Diabetes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Despite the increasing understanding of CFTR functioning, several aspects of CF need still to be clarified, e.g., the worse outcome in females, the risk of malignancies, the pathophysiology, and best treatment of comorbidities, such as CF-related diabetes or CF-related bone disorder.
|
27709245 |
2017 |
|
Diabetes
|
0.100 |
Biomarker
|
disease |
BEFREE |
However, the emergence of CFTR corrector and potentiator drugs may offer a personalised approach to treating diabetes in the CF population.
|
27033560 |
2016 |
|
Diabetes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Genotype impacted both mortality and diabetes risk: adults with severe CFTR genotypes experienced greater mortality at every age older than 32 years than those with mild genotypes (P = 0.002), and the risk of developing CFRD was also greatly increased in those with severe genotypes (prevalence 60% in adult patients with severe vs. 14% in adults with mild mutations).
|
25479583 |
2015 |
|
Diabetes
|
0.100 |
Biomarker
|
disease |
BEFREE |
How CFTR deficiency predisposes to diabetes is unknown.
|
26283735 |
2015 |
|
Diabetes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Pancreatic exocrine disease caused by CF transmembrane conductance regulator (CFTR) dysfunction underlies the high rate of diabetes in CF patients; however, only a subset develops this complication, indicating that other factors are necessary.
|
19126627 |
2009 |
|
Diabetes
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The proposed mechanism is supported by several pieces of evidence including: (1) the absolute essentiality of an intact unfolded protein response (UPR) machinery for survival of pancreatic beta-cells, (2) the high susceptibility of beta-cells to prolonged ER stress leading to induction of pro-apoptotic factors and apoptosis pathways in beta-cells, (3) CF patients with mutations in CFTR gene that are engaging the ER quality control system (ERAD) and hence UPR signalling are twenty time more likely to develop diabetes than those with other types of CF-causing mutations, and (4) the high levels of CFTR gene expression in pancreatic islet cells.
|
18851900 |
2009 |
|
Diabetes
|
0.100 |
Biomarker
|
disease |
BEFREE |
In a multivariate model of 377 cases of 3,275 patients, CFTR class (relative risk 1.70 [95% CI 1.16-2.49], class I or II versus others), increasing age, female sex, worse pulmonary function, liver dysfunction, pancreatic insufficiency, and corticosteroid use were independently associated with incident diabetes.
|
18535191 |
2008 |
|
Diabetes
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In idiopathic chronic pancreatitis patients with one or more CFTR gene mutations, exocrine and endocrine insufficiency (diabetes and steatorrhoea) were rare or delayed events.
|
12779072 |
2003 |