Beta-cell Autoantibodies and Diabetes Mellitus Family History in Cystic Fibrosis

Minicucci, L.; Cotellessa, M; Pittaluga, Livia; Minuto, Nicola; d’Annunzio, Giuseppe; Avanzini, Maria Antonietta; Lorini, Renata

doi:10.1515/jpem.2005.18.8.755

Cited by 22 publications

(16 citation statements)

References 11 publications

(7 reference statements)

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“…These results are in accordance with previous findings [24] and may reinforce the hypothesis that CF-related diabetes mellitus is not an autoimmune disease, but may be secondary to both insulin deficiency induced by pancreatic disease and insulin resistance induced by chronic infection [25]. Nevertheless, other studies have suggested that autoimmunity may play a role in the pathogenesis of CF diabetes, in the wake of bacterial hyperimmunisation [11].…”

Section: Discussionsupporting

confidence: 92%

Prevalence and clinical significance of auto-antibodies in adults with cystic fibrosis

Lachenal

Nkana²,

Nové-Josserand³

et al. 2009

European Respiratory Journal

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The aim of this study was to determine the prevalence of different auto-antibodies in adult, French cystic fibrosis (CF) patients and to look for a correlation between autoimmunity, patient characteristics and survival.The sera of 144 patients were screened for a wide range of antibodies. Clinical, biological and bacteriological characteristics and the cystic fibrosis transmembrane conductance regulator genotype were recorded and progression of lung disease was examined.113 (78.5%) patients displayed one or several auto-antibodies, predominantly immunoglobulin (Ig)A anti-Saccharomyces cerevisiae antibodies (ASCA; 43.7%) and antineutrophil cytoplasmic antibodies (ANCA; 40%), of which 59% showed bactericidal/permeability-increasing protein (BPI) specificity. The presence of BPI-ANCA was associated with the number of antibiotic courses, low body mass index, Pseudomonas aeruginosa colonisation, the presence of resistant P. aeruginosa, low forced expiratory volume in 1 s, CF-related liver disease, hypergammaglobulinaemia, male sex and inflammatory syndrome. The presence of ASCA-IgA was correlated with male sex and hypergammaglobulinaemia. 41 patients presented with chronic respiratory failure and/or requested lung transplantation or died during follow-up. These events were more frequent in patients with BPI-ANCA or ASCA-IgA.These findings confirm the high frequency of auto-antibodies in CF, particularly BPI-ANCA and ASCA-IgA, and the link between BPI-ANCA, severity of lung disease and CF prognosis.

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Section: Discussionsupporting

confidence: 92%

Prevalence and clinical significance of auto-antibodies in adults with cystic fibrosis

Lachenal

Nkana²,

Nové-Josserand³

et al. 2009

European Respiratory Journal

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“…Insulin resistance induced by chronic pulmonary infections has been proposed as a possible contributor to the development of CFRD [6] although this is also controversial [2]. Beta cell specific pancreatic autoantibodies are not more frequent in CFRD compared to the background population [7] and autoimmunity is not generally considered to be the mechanism as in type 1 diabetes (T1D). However, one study noticed the presence of islet cell antibodies in CF patients who were genetically predisposed with certain HLA-types with increased risk of developing autoimmune diabetes [8].…”

Section: Introductionmentioning

confidence: 99%

Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus

Hillman

Eriksson

Mared

et al. 2012

Journal of Cystic Fibrosis

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Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.

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“…On one hand, there appears to be less similarity with type 1 diabetes, considering that diabetes incidence increases steadily with age rather than peaking in childhood, and that islet autoimmunity characteristic of type 1A diabetes plays little or no role in CF according to most (e.g. Minicucci et al [9], Lanng et al [10]) but not all (e.g. Nousia-Arvanitakis et al [11]) reports.…”

Section: Introductionmentioning

confidence: 99%

A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis

et al. 2009

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Aims/hypothesis Insulin-requiring diabetes affects 25-50% of young adults with cystic fibrosis (CF). Although the cause of diabetes in CF is unknown, recent heritability studies in CF twins and siblings indicate that genetic modifiers play a substantial role. We sought to assess whether genes conferring risk for diabetes in the general population may play a risk modifying role in CF. Methods We tested whether a family history of type 2 diabetes affected diabetes risk in CF patients in 539 families in the CF Twin and Sibling family-based study. A type 2 diabetes susceptibility gene (transcription factor 7-like 2, or TCF7L2) was evaluated for association with diabetes in CF using 998 patients from the family-based study and 802 unrelated CF patients in an independent case-control study. Results Family history of type 2 diabetes increased the risk of diabetes in CF (OR 3.1; p=0.0009). A variant in TCF7L2 associated with type 2 diabetes (the T allele at rs7903146) was associated with diabetes in CF in the family study (p=0.004) and in the case-control study (p=0.02; combined p=0.0002). In the family-based study, variation in TCF7L2 increased the risk of diabetes about three-fold (HR 1.75 per allele, 95% CI 1.3-2.4; p=0.0006), and decreased the mean age at diabetes diagnosis by 7 years. In CF patients not treated with systemic glucocorticoids, the effect of TCF7L2 was even greater (HR 2.9 per allele, 95% CI 1.7-4.9, p=0.00011). Conclusions/interpretation A genetic variant conferring risk for type 2 diabetes in the general population is a modifier of risk for diabetes in CF.

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Beta-cell Autoantibodies and Diabetes Mellitus Family History in Cystic Fibrosis

Abstract: The investigated factors did not show correlation with the pathogenesis of CFRD.

Cited by 22 publications

References 11 publications

Prevalence and clinical significance of auto-antibodies in adults with cystic fibrosis

Prevalence and clinical significance of auto-antibodies in adults with cystic fibrosis

Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus

A susceptibility gene for type 2 diabetes confers substantial risk for diabetes complicating cystic fibrosis

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