**3. Pilot study: the role of glycemia variability in development of cognitive disorders in patients with type 1 diabetes mellitus**

Design: observational, transverse, and one-stage study. Clinical characteristics of patients is as follows: 30 patients with type 1 diabetes mellitus at the age of 27 (22–31) years and duration of the disease 17 (5–23) years; among them 14 men and 16 women were examined. Patients were divided into two groups: the first group (main)—with the presence of cognitive impairment, and the second group (control)—with normal cognitive functions.

On the constructive praxis in the job, the alternating path is most affected by the CONGA parameter (χ2 = −0.502, p = 0.006) and MAGE (χ2 = −0.555, p = 0.002), and the clock is MEAN (χ2 = −0.379, p= 0.043), LI (χ2 = −0.471, p= 0.010), Gindex (χ2 = −0.497, p= 0.006), LBGI (χ2 = −0.477, p = 0.009), HBGI (χ2 = − 0.384, p = 0.040), MAGE (χ2 = −0.386, p = 0.038), Mvalue (χ2 = −0.446, p = 0.002), and MAG (χ2 = −0.505, p = 0.005). To reduce memory, the MEAN indicator is most important (χ2 = −0.455, p = 0.013). Violation of the task of repeating the phrase depends on the level of HbA1c (χ2 = −0.390, p = 0.036), LI (χ2 = −0.463, p = 0.011), LBGI (χ2 = −0.604, p = 0.001), MAGE χ2 = −0.422, p = 0.031), Mvalue (χ2 = −0.483, p = 0.008), and MAG (χ2 = −0.501, p =0.002).

Cognitive Impairment in Patients with Diabetes Mellitus http://dx.doi.org/10.5772/intechopen.74388 27

The study showed a decrease in cognitive functions in (constructive praxis, repetition, and memory) in patients with type 1 diabetes mellitus. The currently available markers for the control of glycemia-HbA1c do not always reflect an excursion of hyperglycemia and hypoglycemia [19].

The assignment of MoCA test (repeating speech) depends on the level of HbA1c.

**Parameters The main group The control group**

**Table 7.** Characteristics of parameters of the Montreal scale of cognitive functions in the main and control groups.

Alternating path (drawing) 0.26 ± 0.11\* 0.92 ± 0.07 Cube (drawing) 1.00 ± 0.00 1.00 ± 0.00 Clock (drawing) 2.60 ± 0.13\* 2.14 ± 0.09 Naming 3.00 ± 0.00 3.00 ± 0.00 Memory 2.80 ± 0.32\* 3.64 ± 0.24 Number series 1.80 ± 0.10 1.92 ± 0.71 Concentration 1.13 ± 0.13 1.14 ± 0.14 Serial subtraction by 7 2.66 ± 0.18 2.92 ± 0.07 Repeat suggestions 1.46 ± 0.13\* 1.07 ± 0.07 Fluency of speech 0.66 ± 0.12 0.92 ± 0.07 Abstraction 1.53 ± 0.19 1.50 ± 0.13 Orientation 0.26 ± 0.11\* 0.92 ± 0.07 Sum of points 1.00 ± 0.00 1.00 ± 0.00

**Figure 6.** Example of a glycemic profile according to iPro data.

Note: \*

p ≤ 0.05.

For the diagnosis of fluctuations in the glucose level, continuous monitoring of glycemia was conducted using the iPro2 device (Medtronic, USA) and the CareLink iPro™ software, as well as the Medtronic MiniLink and MMT-700 transmitter, and the Medtronic Diabetes CareLink USB device. Fixation of data on the level of glycemia was carried out at a 5-minute interval for 72 hours using a system of constant monitoring of glycemia. We used the EasyGV calculator (version 9.0), proposed by Hill (2011) [26] (**Figure 6**).

The following glucose variability values were assessed: mean glycemic mean (MEAN), standard deviation (SD), mean amplitude of glycemic fluctuation (MAGE), long-term glycemic index (CONGA), glycemia lability index (LI), hypoglycemia risk index (LBGI), an index of risk of hyperglycemia (HBGI), and average hourly rate of change in glycemia (MAG).

The study found that patients with type 1 diabetes mellitus among the main group of cognitive disorders prevailed violation constructive praxis, memory, and attention. The average score in this group was 23.8 ± 0.66, while in the control group, it was 26.4 ± 0.13 points, respectively (t = 3.6, p = 0.001) (**Table 7**). In the study of HbA1c in plasma, the mean level in the main group was 10.5 ± 1.3%, and in the control group 6.7 ± 0.23% (t = −2.5, p = 0.015).

The analysis of the GV indicators is presented in **Table 8**. There is a significant difference in MEAN, SD, CONGA, Gindex, LBGI, HBGI, MAGE, Mvalue, and MAG.

Correlation analysis shows that cognitive functions are generally affected by the level of HbA1c (χ2 = −0.450, p = 0.014), as well as the MEAN variability parameters (χ2 = −0.584, p = 0.001), SD (χ2 = 0.022, p = 0.022), CONGA (χ2 = −0.853, p = 0.001), Gindex (χ2 = −0.504, p = 0.005), LBGI (χ2 = −0.451, p = 0.014), HBGI (χ2 = −0.053, p = 0.003), MAGE (χ2 = −0.480, p = 0.008), Mvalue (χ2 = −0.593, p = 0.001), and MAG (χ2 = −0.573, p = 0.001).

**Figure 6.** Example of a glycemic profile according to iPro data.

**3. Pilot study: the role of glycemia variability in development of cognitive disorders in patients with type 1 diabetes mellitus**

**Table 6.** Characteristics of specificity and sensitivity of signs of magnetic resonance imaging.

**Indicators Sensitivity (%) Specificity (%)**

Arachnoidal changes in the cerebrospinal fluid 92 37 Expansion of convective fluidic spaces 73 26 Expansion of Virchow-Robin spaces 78 34 Gliosis 11 17 Leukoareosis 21 43

26 Cognitive Disorders

ment, and the second group (control)—with normal cognitive functions.

(version 9.0), proposed by Hill (2011) [26] (**Figure 6**).

Design: observational, transverse, and one-stage study. Clinical characteristics of patients is as follows: 30 patients with type 1 diabetes mellitus at the age of 27 (22–31) years and duration of the disease 17 (5–23) years; among them 14 men and 16 women were examined. Patients were divided into two groups: the first group (main)—with the presence of cognitive impair-

For the diagnosis of fluctuations in the glucose level, continuous monitoring of glycemia was conducted using the iPro2 device (Medtronic, USA) and the CareLink iPro™ software, as well as the Medtronic MiniLink and MMT-700 transmitter, and the Medtronic Diabetes CareLink USB device. Fixation of data on the level of glycemia was carried out at a 5-minute interval for 72 hours using a system of constant monitoring of glycemia. We used the EasyGV calculator

The following glucose variability values were assessed: mean glycemic mean (MEAN), standard deviation (SD), mean amplitude of glycemic fluctuation (MAGE), long-term glycemic index (CONGA), glycemia lability index (LI), hypoglycemia risk index (LBGI), an index of

The study found that patients with type 1 diabetes mellitus among the main group of cognitive disorders prevailed violation constructive praxis, memory, and attention. The average score in this group was 23.8 ± 0.66, while in the control group, it was 26.4 ± 0.13 points, respectively (t = 3.6, p = 0.001) (**Table 7**). In the study of HbA1c in plasma, the mean level in the main

The analysis of the GV indicators is presented in **Table 8**. There is a significant difference in

Correlation analysis shows that cognitive functions are generally affected by the level of HbA1c (χ2 = −0.450, p = 0.014), as well as the MEAN variability parameters (χ2 = −0.584, p = 0.001), SD (χ2 = 0.022, p = 0.022), CONGA (χ2 = −0.853, p = 0.001), Gindex (χ2 = −0.504, p = 0.005), LBGI (χ2 = −0.451, p = 0.014), HBGI (χ2 = −0.053, p = 0.003), MAGE (χ2 = −0.480, p = 0.008), Mvalue

risk of hyperglycemia (HBGI), and average hourly rate of change in glycemia (MAG).

group was 10.5 ± 1.3%, and in the control group 6.7 ± 0.23% (t = −2.5, p = 0.015).

MEAN, SD, CONGA, Gindex, LBGI, HBGI, MAGE, Mvalue, and MAG.

(χ2 = −0.593, p = 0.001), and MAG (χ2 = −0.573, p = 0.001).

On the constructive praxis in the job, the alternating path is most affected by the CONGA parameter (χ2 = −0.502, p = 0.006) and MAGE (χ2 = −0.555, p = 0.002), and the clock is MEAN (χ2 = −0.379, p= 0.043), LI (χ2 = −0.471, p= 0.010), Gindex (χ2 = −0.497, p= 0.006), LBGI (χ2 = −0.477, p = 0.009), HBGI (χ2 = − 0.384, p = 0.040), MAGE (χ2 = −0.386, p = 0.038), Mvalue (χ2 = −0.446, p = 0.002), and MAG (χ2 = −0.505, p = 0.005). To reduce memory, the MEAN indicator is most important (χ2 = −0.455, p = 0.013). Violation of the task of repeating the phrase depends on the level of HbA1c (χ2 = −0.390, p = 0.036), LI (χ2 = −0.463, p = 0.011), LBGI (χ2 = −0.604, p = 0.001), MAGE χ2 = −0.422, p = 0.031), Mvalue (χ2 = −0.483, p = 0.008), and MAG (χ2 = −0.501, p =0.002). The assignment of MoCA test (repeating speech) depends on the level of HbA1c.

The study showed a decrease in cognitive functions in (constructive praxis, repetition, and memory) in patients with type 1 diabetes mellitus. The currently available markers for the control of glycemia-HbA1c do not always reflect an excursion of hyperglycemia and hypoglycemia [19].


**Table 7.** Characteristics of parameters of the Montreal scale of cognitive functions in the main and control groups.


Patients with similar levels of HbA1c and average glucose values may have a significantly different daily variability in glycemia. In his study, Rizzo et al. showed that MAGE was associated with impaired cognitive functioning, regardless of the level of HbA1c among patients with diabetes (R = 0.83, p < 0.001) [20]. Although the mechanisms by which the variability of glycemia affects cognitive function are not clear, they can also be associated with oxidative stress. In this context, daily glucose fluctuations, such as peaks and falls, affect the development of oxidative stress more than chronic hyperglycemia. The work of Abbatecola et al. also demonstrated that an increase in postprandial glucose variability is associated with attention impairment [21]

Cognitive Impairment in Patients with Diabetes Mellitus http://dx.doi.org/10.5772/intechopen.74388 29

Thus, the present study demonstrated a link between high HbA1c, glycemic variability, and cognitive function in patients with type 1 diabetes mellitus. Since dysglycemia is a risk factor for both mild to moderate cognitive impairment and dementia, the present data provide opportunities for interventional studies to stabilize glycemia, not only by reducing HbA1c but

The proton magnetic resonance multilocular spectroscopy of the brain was carried out on a MAGNETOM Symphony 1.5 T (Siemens) device with the relaxation time TE = 135, and the voxel volume was 1.5 cm3; the main spectra of choline (Cho), creatine/phosphocreatine (Cr, Cr2), and N-acetylaspartate (NAA) were analyzed [22]. With the help of the regional approach, the data of metabolites Cho (choline), creatine), Cr2 (phosphocreatine), NAA (N-acetylaspartate), localized

The study revealed that the average age of patients with type 1 diabetes mellitus was 26 ± 4.8 years, and the control group was 30 ± 6.4 years. When comparing patients with type 1 diabetes mellitus (30 people) and control group (18 people) in metabolites Cho (choline), Cr (creatine), Cr2 (phosphocreatine), NAA and (N-acetylaspartate), distributed by the method of linear grouping and

When comparing the values obtained for the Cho metabolite, a statistically significant difference in the Cho12 index was found: in patients with type 1 diabetes mellitus, 0.82 (0.75–0.84),

When comparing the tables for the Cr metabolite, statistically significant differences in the

In the study of the metabolite NAA, no significant differences in voxels were found. The

Thus, the main differences in patients with type 1 diabetes mellitus and in the control group were found by the metabolites Cr and Cr2. At the same time, these parameters are energy metabolism markers in their function and promote glycolysis [23, 24]. In addition, it was reported that in the voxel assessment there are significant differences in Cr and Cr2 in the

**4. Pilot study: magnetic resonance spectrometry as a method of estimation of brain metabolism in type 1 diabetes mellitus**

(**Figure 7**).

also leveling out acute glucose fluctuations.

in the hippocampal region on the left and right.

regional approach, no statistically significant differences were found.

compared with a higher value in the control group, 0.87 (0.81–2.02).

study revealed changes in the ratio of metabolites Cho, Cr, Cr2, and NAA.

indices were found: Cr5, Cr10, Cr25, Cr26, Cr28, Cr31, and Cr36.

**Table 8.** Characteristics of VG indicators by groups.

**Figure 7.** Examples of models with the smallest squares indicating a negative relationship between a multi-scale SH, the volumes of regions of the brain, as well as cognitive functions: (A) the ratio between GVC2 and volume of GM in the left island cortex, (B) the ratio between GVC1 and GM volume in the right spindle-shaped gyrus, (C) the ratio between GVC2 and GM volume in the left cingulate gyrus, and (D) the ratio between GVC2 and total cognitive performance (composite T) (SD, triangles; control, circles).

Patients with similar levels of HbA1c and average glucose values may have a significantly different daily variability in glycemia. In his study, Rizzo et al. showed that MAGE was associated with impaired cognitive functioning, regardless of the level of HbA1c among patients with diabetes (R = 0.83, p < 0.001) [20]. Although the mechanisms by which the variability of glycemia affects cognitive function are not clear, they can also be associated with oxidative stress. In this context, daily glucose fluctuations, such as peaks and falls, affect the development of oxidative stress more than chronic hyperglycemia. The work of Abbatecola et al. also demonstrated that an increase in postprandial glucose variability is associated with attention impairment [21] (**Figure 7**).

Thus, the present study demonstrated a link between high HbA1c, glycemic variability, and cognitive function in patients with type 1 diabetes mellitus. Since dysglycemia is a risk factor for both mild to moderate cognitive impairment and dementia, the present data provide opportunities for interventional studies to stabilize glycemia, not only by reducing HbA1c but also leveling out acute glucose fluctuations.
