Endocrine Abstracts (2017) 49 S5.3 | DOI: 10.1530/endoabs.49.S5.3

Carbohydrate metabolism in patients with Cushing disease: a glance at the incretin system

Lubov Matchekhina


Russia.


The relevance of carbohydrate metabolism studying in patients with Cushing disease (CD) and acromegaly can be explained by frequent occurrence of glucose metabolism disturbances on the one hand, and difficulties in glucose-lowering therapy in these patients on the other. The effectiveness of hyperglycaemia treatment may be reduced due to difficulties in remission/cure of the underlying disease, as well as to the use of specific drug-therapy, leading to hyperglycaemia. There is a growing interest in research aimed at studying the role of incretin system in the pathogenesis of secondary hyperglycemia associated with neuroendocrine diseases recently.

Aim of the study: To analyze the rhythm and levels of incretins and neuropeptides secretion in patients with CD and acromegaly and therefore to specify the pathogenesis of carbohydrate metabolism disturbances.

Methods: 42 patients with Cushing disease and acromegaly were included; the mean age was 37.5 years. All of the patients were newly diagnosed with Cushing disease (using urinary free cortisol levels, evening saliva cortisol levels and low-dose dexamethasone suppression test) and acromegaly (in absence of GH suppression during OGTT and high IGF1 levels); none of them had a history of previous drug therapy, radiotherapy or pituitary surgery. All patients underwent OGTT, during which glucose, glucagon, GLP1, GLP2, GIP, ghrelin were measured at 0, 30 and 120 min respectively.

Results: During OGTT glucose levels were not significantly different in all groups. The mean HbA1c level was 5.8% (5.3–6.2). However the relevance of prediabetes was higher in CD patients. In CD patients glucagon levels were significantly higher at all cut off points compared to controls (P=0.001). In acromegaly patients, no significant differences were found. GIP secretion was slightly lower in CD patients; in acromegaly patients, no differences were found. Acromegaly group was characterized by inverse rhythm of GIP secretion, with no peak level at 30’: GIP 0 min – 194.2 pg/ml, GIP 30 min – 178.8 pg/ml. GLP-1 levels were significantly higher in CD patients (P=0.047). In acromegaly group, no significant differences in GLP-1 secretion were found. GLP-2 levels were significantly higher in CD patients compared to acromegaly and controls (P=0.001). Ghrelin levels were significantly higher in CD (P=0.013) and acromegaly (P=0.023) patients.

Conclusion: More pleotropic actions of glucocorticoids can possibly explain higher relevance of carbohydrate metabolism disturbances in CD patients. This can be also explained by higher levels of glucagon secretion, which does not depend on type of carbohydrate metabolism disorder and is stimulated by a direct action of glucocorticoids on glucagon receptor. GIP and GLP-1 secretion in CD and acromegaly patients are characterized by inverse rhythm with no peak levels which means that these hormones are not playing the crucial role in carbohydrate disturbances development in these patients. On the contrary, GLP-2 and ghrelin seem to influence and potentially regulate glucose homeostasis in CD and acromegaly patients.

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