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

Introduction. The relevance of carbohydrate metabolism studying in patients with Cushing disease 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 the 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.

Methods. A total of 20 patients with Cushing disease were included, (19 female and 1 male), the mean age was 37.5 years (18-69). All of the patients were diagnosed with Cushing disease for the first time (using urinary free cortisol levels and MRI-data); none of them had a history of previous drug therapy, radiotherapy or pituitary surgery. The mean HbA1c level was 5,8% (5,3-6,2). All patients underwent OGTT, during which glucose, glucagon, GLP1, GLP2, GIP, ghrelin were measured at 0, 30 and 120 min respectively. The control group included 21 patients without previous history of carbohydrate metabolism disturbances. After OGTT 57% were presented without any carbohydrate metabolism disturbances, 28,57% presented with prediabetes and 14,43% were diagnosed with diabetes.

Results. After glucose levels analyzing 40% of patients were diagnosed with early carbohydrate metabolism disturbances ,15% were diagnosed with diabetes. After glucose intake a slight inrease in glucagon levels with a peak by 30’ (p=0,001) compared to gradually decreasing levels in controls was observed . The levels of GIP during OGTT were not significantly different compared to control group. GLP-1 and GLP-2 levels were significantly higher compared to controls (p=0,017 and p<0,001 respectively) with peak levels at 30’. Ghrelin levels were also significantly higher compared to controls (p=0,013)

Conclusion. Incretins levels can be possible markers of specific carbohydrate metabolism disturbances in patients with Cushing disease and presumably will help to differentiate steroid diabetes from T2DM. Further investigations needed to prove these speculations.