Loss of incretin effect contributes to postprandial hyperglycaemia in cystic fibrosis‐related diabetes

Abstract

Aim To investigate the incretin axis in people with cystic fibrosis. Methods Adults with cystic fibrosis‐related diabetes, cystic fibrosis without diabetes, and controls (adults without cystic fibrosis and without diabetes) underwent an oral glucose tolerance test and then a closely matched isoglycaemic i.v. glucose infusion. On each occasion, glucose, insulin, C‐peptide, total and active glucagon‐like peptide‐1 and gastric inhibitory polypeptide responses were recorded and incremental areas under curves were calculated for 60 and 240 min. Results Five adults with cystic fibrosis‐related diabetes, six with cystic fibrosis without diabetes and six controls, matched for age and BMI, completed the study. Glucose during oral glucose tolerance test closely matched those during isoglycaemic i.v. glucose infusion. The calculated incretin effect was similar in the control group and the cystic fibrosis without diabetes group (28% and 29%, respectively), but was lost in the cystic fibrosis‐related diabetes group (cystic fibrosis‐related diabetes vs control group: –6% vs 28%; p=0.03). No hyposecretion of glucagon‐like peptide‐1 or gastric inhibitory polypeptide was observed; conversely, 60‐min incremental area under the curve for total glucagon‐like peptide‐1 was significantly higher in the cystic fibrosis‐related diabetes group than in the control group [1070.4 (254.7) vs 694.97 (308.1); p=0.03] Conclusions The incretin effect was lost in cystic fibrosis‐related diabetes despite adequate secretion of the incretin hormones. These data support the concept that reduced incretin hormone insulinotropic activity contributes significantly to postprandial hyperglycaemia in cystic fibrosis‐related diabetes.

Bone metabolism and incretin hormones following glucose ingestion in young adults with pancreatic insufficient cystic fibrosis

“…Experimental studies suggest that consumption of macronutrients results in acute anti-resorptive effects on bone, and that hormones involved in nutrient metabolism, such as the gut-derived incretins GIP and GLP-1, as well as insulin contribute to these effects [9] , [30] , [31] , [32] . Cystic fibrosis is associated with a unique form of diabetes that involves deranged incretin and insulin responses to macronutrient consumption [33] , [34] . Deficits in bone density and increased fracture risk are reported in patients with CF [35] , [36] ; thus, invoking disruption to the “gut-bone axis” as a plausible contributor to CF related bone disease.…”

Gut microbiota and oleoylethanolamide in the regulation of intestinal homeostasis

“…A recent study conducted in normal subject exposed to 6-week exercise intervention and a validation cohort ( 96 ) revealed that at baseline, eCB and paracannabinoid levels were associated with higher microbiome diversity, negatively associated with Escherichia/Shigella and Collinsella , whose increased levels are found in type 2 and gestational diabetes ( 97 ), and negatively associated with weight loss and insulin sensitivity ( 98 ). Levels of endo- and paracannabinoids were also associated with higher levels of the microbiota-produced SCFA butyrate, along with increases in the anti-inflammatory cytokine IL-10 and decreases in pro-inflammatory cytokines like IL-8 and TNFα ( 96 ).…”

Cystic fibrosis being a polyendocrine disease (Review)

“…Тем не менее альтернативные мнения исследователей [ 32 ] и данные систематического Кокрановского обзора [ 35 ] о методах оптимальной коррекции гликемии, ввиду отсутствия убедительных доказательств преимуществ инсулинов длительного или короткого действия перед пероральными гипогликемическими препаратами в контроле клинических исходов МВСД, также заслуживают внимания. Изучаются возможности применения ингибиторов дипептидилпептидазы-4 [ 7 ], агонистов рецепторов глюкагоноподобного пептида-1 [ 36 ] для улучшения секреции инсулина, сохранения массы β-клеток.…”