1. ABSTRACT
1.1. Background
Type 1 diabetes (T1D) is one of the most common chronic diseases of the childhood. Poor glycaemic control influences the brain function. Studies show lower intelligence quotient (IQ) scores in verbal and cognitive area in T1D and type 2 diabetes (T2D) patients during acute hyperglycaemic episodes. The cause of cognitive demise in T1D patients is not clear; however, it could be related to oxidative stress and inflammation. It is also not clear which areas of the brain are the most affected.
1.2. Objective
The goals of the study are studying the influence of 120 – minute hyperglycaemia on:
the function of cognitive areas in the brain by performing functional magnetic resonance imaging (fMRI),
inflammation (interleukin-6 (IL-6), fibrinogen)
1.3. Methods
Twenty T1D patients, aged between 11 and 19 years, without chronic complication of T1D, similar values of glycated haemoglobin (HbA1c) in the last 3 years among the group, normal body mass index (BMI) for age and gender, non-smokers, on insulin pump treatment or treated with multiple daily injections (MDI), without diabetic ketoacidosis or severe hypoglycaemia in the last year, 5-10 years since T1D diagnosis, and 20 healthy volunteers matched for age participated in the study.
T1D patients were subjected to euglycaemic and hyperglycaemic clamp. During both fMRI (Flanker task, Tower of London task, working memory capacity) and magnetic resonance spectroscopy (MRS) studies were performed using Philips MR. Blood samples were obtained in fasting state and after 120-minut of hyperglycaemia in order to measure inflammatory markers (IL-6,fibrinogen).
The healthy volunteers performed the same fMRI and MRS studies as T1D patients twice in a row (on the same day) without any interventions regarding blood glucose levels.
1.4. Hypotheses
We expected that:
more cognitive areas in the brain would be activated during planning task (Tower of London) in acute hyperglycaemia as compared to euglycaemic state
more cognitive areas in the brain would be activated during spatial memory task in acute hyperglycaemia as compared to euglycaemic state
the inhibition control would decrease during acute hyperglycaemia as compared to euglycaemic state
neurotransmitter levels (glucose, myoinositol, N- acetylaspartate, choline) would change in the brain (thalamus, frontal brain cortex, frontalna white matter) during acute hyperglycaemia, marking the change in signal transmission, increased cell membrane disintegration and dysfunction
the level of markers of inflammation in blood would increase during acute hyperglycaemia
1.5. Relevance
To our knowledge no data describing fMRI during acute hyperglycaemia was published to date, apart from an abstract reporting increased activation in the brain in the resting state during acute hyperglycaemia, which is why the results of our research are completely original. Assessing the possible deleterious consequence of acute hyperglycaemia on cognitive function is relevant for future guidelines on insulin therapy and glucose control and may place the acute hyperglycaemia among clinically important acute complications of diabetes.
1.6. Results
Lower spatial working memory (sWM) capacity during acute hyperglycaemia and significant differences in activation of regions of interest during different stages of the spatial working memory task (p=0.014) were observed. Grey matter volume (GMV) (p<0.005) and cortical surface area were significantly reduced (p<0.05) in participants withT1D. Fractional anisotropy (FA) was significantly increased (p<y0.05), radial (RD) and axial diffusivity (AD) were significantly decreased (p<0.05) in participants with T1D. Brain connectivity was significantly increased (p<0.002) in group with T1D. However, during acute hyperglycaemia, it was reduced (p<0.002) as compared to euglycaemia.
1.7. Conclusions
Acute hyperglycaemia negatively affected sWM capacity in adolescents with T1D, which is relevant for daily functioning and academic performance.
The proposed compensatory mechanism of increased brain connectivity in adolescents with T1D fails during acute hyperglycaemia, with possible deleterious effect on executive functions.
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