Activation markers of the stress system in patients with type 1 diabetes during hypoglycemia

BACKGROUND: Usually, a hypoglycemic episode occurs due to inadequacy of the administered insulin dose in accordance with the current physiological situation. Activated systems aimed at increasing blood glucose levels serve as precursors of hypoglycemia and markers of the severity of hyperinsulinemia. Therefore, determining their components can serve as a more subtle and sensitive approach to assessing the physiological appropriateness of different insulin therapy options.

AIM: To investigate the markers (biochemical, clinical, and morphological) and the degree of activation of the stress system preceding the development of hypoglycemic episodes in patients with type 1 diabetes (T1D) undergoing insulin therapy.

MATERIALS AND METHODS: A cross-sectional observational clinical study was conducted involving 74 patients with type 1 diabetes (T1D). All patients underwent examination, which included assessment of the history of hypoglycemic episodes, quality of life using the SF-36 questionnaire, levels of adrenocorticotropic hormone (ACTH), insulin-like growth factor-1 (IGF-1), cortisol, C-reactive protein (CRP), coagulation profile, and 24-hour urinary cortisol excretion. Evaluation of patients’ sleep characteristics was performed based on the results of completed questionnaires: Sleep Questionnaire and Epworth Sleepiness Scale. Patients underwent overnight polysomnography (PSG) with interpretation according to the AASM 2012 standards.

RESULTS: Patients with a higher frequency of hypoglycemic episodes showed a decrease in IGF-1 levels at all stages (140 [123:162]; 98 [93:121], p=0.005), worse quality of life scores across all domains of the SF-36 questionnaire (95 [88:100]; 84 [77:92], p=0.001). As the frequency of hypoglycemic episodes increased, polysomnography data revealed an increase in the number of awakenings lasting more than 3 minutes (2 [1:3]; 3 [2:4]; p=0.03), increased time spent in bed (493.1 [463.95:513.4]; 536.2 [511.6:551]; p=0.03), increased sleep duration (437.5 [430.05:468]; 489 [471.5:519], p=0.006), and in creased total sleep time (382.5 [321.75:422]; 439 [409.5:486], p=0.008).

CONCLUSION: An increase in the frequency of hypoglycemic episodes should be accompanied by activation of the stress response system; however, repeated episodes of hypoglycemia lead to depletion of the stress response system, as evidenced by a decrease in the level of IGF-1 in patients with frequent hypoglycemic episodes. Hypoglycemic episodes occurring not only during night time but also at other times disrupt the sleep structure by increasing the frequency of nocturnal awaken ings.

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