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

Abstract

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.

Glucagon-like peptide-1 receptor agonists inhibit hepatic stellate cell activation by blocking the p38 MAPK signaling pathway

“…Park et al (2007) treated 8-week-old male db/db mice with the long-acting GLP-1R agonist liraglutide for 8 weeks and found that the expression of transforming growth factor-β1 and type IV collagen were significantly decreased. Hillman et al (2012) recently found that GLP-1 levels were significantly reduced in cystic fibrosis patients (P < 0.01) compared with healthy individuals. In an electron microscope study, Tang et al (2008) observed that the endothelial basement membrane thickness of pulmonary capillaries was significantly decreased following treatment with GLP-1 for 8 weeks in the Otsuka-Long-Evans-Tokushima fatty rat model (P < 0.01).…”

Cystic Fibrosis Related Diabetes: A Case Report

“…Toplumda T2DM gelişmesine yol açan bazı genetik varyasyonların ve gen polimorfizmlerin KFİDM gelişmesinde de rol oynayabileceği ve hastalığın daha erken yaşlarda görülmesine yol açabileceği belirtilmiştir (15,16). KFİDM gelişmesinde inkretin hormonlarının rolünün ne olduğu konusunda ise daha fazla çalışmaya ihtiyaç vardır (17,18). Sinsi bir klinik seyre sahip olan KFİDM'un bulguları klasik diyabet belirtileri (poliüri, polidipsi, kilo kaybı), boy uzama hızında yavaşlama, pulmoner fonksiyonlarda açıklanamayan azalma ve protein Yılmaz ve ek olarak multivitamin desteği içeren diyet uygulanmalıdır.…”

A Practical Approach to Glucose Abnormalities in Cystic Fibrosis

“…Patients with CF have also been shown to have decreased GLP-1 activity compared to normal controls, which may contribute to glucose abnormalities [9]. CF is a complex multisystem disease, and multiple defects in nutritional status and metabolism also contribute to observed glucose abnormalities.…”