Liver disease as risk factor for cystic fibrosis‐related diabetes development

Minicucci, L.; Lorini, Renata; Giannattasio, A.; Colombo, Carla; Iapichino, L.; Reali, M F; Padoan, Rita; Calevo, Maria Grazia; Casciaro, R.; Alessandri, A. De; Haupt, Riccardo

doi:10.1111/j.1651-2227.2007.00250.x

Cited by 41 publications

(33 citation statements)

References 29 publications

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“…Female sex has been noted to be a significant risk factor for diabetes in CF, and we saw evidence of this association in this study, although significance was not achieved, which may be due to insufficient power (13). Other associated CF complications such as lung transplantation (32), markers of chronic inflammation (24), and liver disease (33) were not evaluated.…”

Section: Discussionmentioning

confidence: 48%

Genetic Modifiers Play a Substantial Role in Diabetes Complicating Cystic Fibrosis

Blackman

Hsu

Vanscoy

et al. 2009

The Journal of Clinical Endocrinology &Amp; Metabolism

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Section: Discussionmentioning

confidence: 48%

Genetic Modifiers Play a Substantial Role in Diabetes Complicating Cystic Fibrosis

Blackman

Hsu

Vanscoy

et al. 2009

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…CF liver disease predisposes patients to glucose abnormalities and diabetes (55,56). However, it remains unclear whether neonatal liver pathologies in CF influence glucose and insulin regulation.…”

Section: Discussionmentioning

confidence: 99%

Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets

Olivier¹,

Yi²,

Sun³

et al. 2012

J. Clin. Invest.

120

143

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Diabetes is a common comorbidity in cystic fibrosis (CF) that worsens prognosis. The lack of an animal model for CF-related diabetes (CFRD) has made it difficult to dissect how the onset of pancreatic pathology influences the emergence of CFRD. We evaluated the structure and function of the neonatal CF endocrine pancreas using a new CFTR-knockout ferret model. Although CF kits are born with only mild exocrine pancreas disease, progressive exocrine and endocrine pancreatic loss during the first months of life was associated with pancreatic inflammation, spontaneous hyperglycemia, and glucose intolerance. Interestingly, prior to major exocrine pancreas disease, CF kits demonstrated significant abnormalities in blood glucose and insulin regulation, including diminished first-phase and accentuated peak insulin secretion in response to glucose, elevated peak glucose levels following glucose challenge, and variably elevated insulin and C-peptide levels in the nonfasted state. Although there was no difference in lobular insulin and glucagon expression between genotypes at birth, significant alterations in the frequencies of small and large islets were observed. Newborn cultured CF islets demonstrated dysregulated glucose-dependent insulin secretion in comparison to controls, suggesting intrinsic abnormalities in CF islets. These findings demonstrate that early abnormalities exist in the regulation of insulin secretion by the CF endocrine pancreas. IntroductionCystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) chloride channel. Cystic fibrosisrelated diabetes (CFRD) is a common complication of CF and affects 20%-25% of adolescents and 40%-50% of individuals over 30 years of age (1,2). CFRD is associated with worsening clinical status, including reduced pulmonary function, increased frequency of pulmonary exacerbations, and a decline in nutritional status (3-7). Furthermore, CFRD leads to increased mortality compared with CF patients without diabetes (4,8). Thus, early diagnosis and treatment are vital to improving clinical outcome of CFRD patients.While the pathophysiology of CFRD is multifactorial, delayed insulin secretion appears to be a key hallmark of disease progression (9-12), and the health of CF patients is improved by insulin therapy prior to and following diagnosis of overt diabetes (13,14). Partial insulin deficiency occurs in part due to islet loss associated with exocrine pancreas disease (15-18). However, CF pancreata at CFRD autopsy demonstrate that remaining islets contain roughly half the number of insulin-positive cells found in non-CF controls (17,18), and this degree of β cell loss is thought to be insufficient to explain diabetes (19). Thus, insulin deficiency in CFRD is relative and not absolute. All stages of CFRD are characterized by abnormalities in circulating insulin levels (10,12,20,21). Impaired first-phase insulin (IFPI) responses are common in CFRD patients, but also occur in approximately 50% of CF children with normal glucose tolerance (9). Cu...

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“…Malnutrition associated with portal hypertension is likely multifactorial with decreased nutrient absorption, increased resting energy expenditure, anorexia and decreased caloric intake. There may be a link between CFLD and increased insulin resistance leading to a higher incidence of CF related diabetes [30]. A single center retrospective case–control study showed an odds ratio of 4.8 (95% CI, 2.49, 9.17) for CF related diabetes in those with cirrhosis and portal hypertension, using a surrogate marker (thrombocytopenia) for cirrhosis with portal hypertension [31].…”

Section: Cystic Fibrosis Related Cirrhosis With and Without Portalmentioning

confidence: 99%

Cirrhosis and other liver disease in cystic fibrosis

Flass

Narkewicz

2013

Journal of Cystic Fibrosis

163

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Liver disease as risk factor for cystic fibrosis‐related diabetes development

Abstract: Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance.

Cited by 41 publications

References 29 publications

Genetic Modifiers Play a Substantial Role in Diabetes Complicating Cystic Fibrosis

Genetic Modifiers Play a Substantial Role in Diabetes Complicating Cystic Fibrosis

Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets

Cirrhosis and other liver disease in cystic fibrosis

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