Possibilities of the Akabane Test and Cosinor Analysis to Predict the Level of Glycemia and the Individual Selection of Drugs and their Doses in the Treatment of Diabetes

Currently, despite the huge technological advances in the treatment
of diabetes, the mechanism of the formation of glycemia...


Introduction
Currently, despite the huge technological advances in the treatment of diabetes, the mechanism of the formation of glycemia in diabetes is not completely clear. Therefore, maintaining the optimal glycemic value and predicting its level is still very relevant for patients with diabetes. Typical for research in the field of biology and medicine is static representations in the form of correlation and regression dependences of some processes on others by the sum of their results. However, they give only a general point of view on a certain process, smoothing out the sequence of temporary events, which are often crucial for understanding the mechanisms of interaction in the body. Usually, for monitoring patients with diabetes, an assessment of the level of glycemia in the dynamics of observation is used. However, blood glucose is the final product in the multi-link chain of carbohydrate metabolism, where various organs and systems are involved. New possibilities are opened using the Akabane test [1] to monitor these patients, since the test indicators allow you to track the functional activity of various organs and systems involved in digestion [2][3][4][5]. This test also has high correlations with various biochemical parameters of blood, with the level of glycemia [4,6,7]. Thus, according to the test data, one can evaluate the entire chain of carbohydrate metabolism with an assessment of the contribution of each organ or physiological system and with the identification of the level and nature of regulatory failure. Previously, a general model was shown of the relationship between the indices of certain AC and the regulation of glycemia in patients with type T1D, which was in good agreement with the results of subsequent studies [8]. According to this model (Figure 1), on the pancreatic canal, test indices at the SP1 point on the right and left separately reflect the total activity of either B or A pancreatic cells and vary in proportion to their participation in digestion. These changes are cyclical in nature and reflect 2 endogenous biorhythms associated with the activity of A and B cells ( Figure 2). In addition to the pancreas, while maintaining its function, other organs and systems also affect the level of glycemia, and their contribution can be estimated, for example, using a regression model. This model can be represented as 2 scales with a set of channels in each of them with different signs and coefficients of influence on the level of glycemia. At the same time, both scales are in constant motion under the influence of biorhythms, due to which the "corridor of norm" is

Materials and Methods.
To quantitatively evaluate a channel's activity level in TCM, the so-called "sacrificial stick" test was used in ancient times in China.
This test involved a burning sandal stick that was brought in proximity to points at the tips of every finger and toe until the first sensation of pain. At each point, the pulse rate before pain was first felt, was measured. If the number of pulse beats was lower than the average one for all the channels, it proved the hyperactivity of an acupuncture channel and its corresponding organ. Conversely, when the rate was higher, it represented the inactivity of a channel and its corresponding organ. This test was described by the Japanese doctor Koben Akabane in 1956. Since then, the test has carried his name. This test measures the pain thresholds in temperature sensitivity (TS) when heat is applied to the "entrance-exit" points of each channel (LU11, LII1, PC9, TE1, HT9, SI1, SP1, LR1, ST45, GB44, KI1, and BL67) by applying an impulse light-emitting diode (LED) non-coherent infrared radiation (IR)-light onto the skin (f = 1 Hz, λ = 920nM), recording the total energy expenditure in joules [2-4, 9,10]. Each impulse radiates 0.07 joules of thermal energy. These measurements were carried out using a certified device-"Merid", invented by the author of the paper. TS is our bodies' basic reactive system; it is as significant as important indicators such as body temperature, as it gives a very clear representation of functional and psycho-physiological profiles. Their topography is shown in  According to classical Oriental literature as well as according to our study results [3,4], the following channels have different regulatory functions: LU-lungs channel, connected with the function of lungs and tissue breathing. a) Li-large intestine channel, connected with the large intestine function and its microbe flora, it participates in the regulation of arterial pressure, biochemical blood indices. b) PC -pericardium channel, connected with the cardiac muscle trophicity and its structure. In addition, it is connected to muscular activity, arterial blood pressure levels and emotions. i) GB-channel of the gallbladder is connected to the digestion function and peripheral nervous system.

j)
Ki-kidney channel is connected to the kidney function and the adrenal glands.
k) BL-urinary bladder channel is connected to the urogenital system, its functions and its related hormones, it reflects the state of vertebrae column as well. Each channel consists of the left (l) and the right (r) branch between which normal symmetrical activity balance is maintained.

Results
Since group statistics using correlation, regression, and FA smooth out the effects of biorhythms, then for an example of real monitoring of the effect of biorhythms on glycemia, we will give observation of a woman aged 24 years who has suffered from T1D for 12 years. She gats intensive insulin therapy using basal-bolus regimens with a total insulin dose of 14 to 55 units per day, depending on the situation. In this case, glycosylated hemoglobin  a generally ineffective control using these medications. There is also a large range of glycemic values; for example, on the 10th day of monitoring, it changed from 9.1 to 19mmol/l., and on the 14th day of monitoring, it changed from 3.8 to 17.2mmol/l per day. Table   1 shows the correlation of AС with several additional factors that were evaluated during monitoring; such as the temperature in the street, the amount of food eaten, the level of physical activity, the day of the menstrual cycle.  In general, repeated fragments with glycemic level profiles after 5 days are noted. To assess the effect of insulin on АС, consider another stepwise regression model presented in Table 3. This model has 95% explainable variance due to the influence of a larger number of АС. It is interesting to note that insulin in this case mainly affects    [4,19], it was found that a correctly selected medicine or other therapeutic effect should restore the symmetry broken by the disease in the body according to certain systems, which is reflected through the channels in changing their sign of influence or in changing the right or left branch of the channel in comparison with the time of treatment. In this case, the results of comparing two models of the influence of glucose and insulin on the channels show that insulin levels the effect of glycemia due to restoration of symmetry and harmony only in these two body systems. Therefore, in this case, such a treatment is not enough. Moreover, an increase in the dose of insulin, for example, with insulin resistance, can on the contrary, lead to a breakdown of compensation and the appearance of reverse asymmetry, which is fraught with new problems, because the presence of any asymmetry on the right/left level, according to the theory of interaction of 5 primary elements -will strike a bounce on other AC and harmony will be broken in other organs and systems . In this case, the proverb will be true: "Оne is cured, the other is crippled. "With ideally selected therapy, in the regression models of AC connections with glycemia and insulin, the same channels should participate, but with opposite signs of influence or the opposite side. Only in this case, the drug will be as effective as possible. it will restore symmetry and harmony in the body at the level of certain organs and systems affected by pathology.  Table 4. Part of АС are included in the model from Table 1, reflecting several additional external and internal factors influencing the level of glycemia. As in the previous simplified model (Table 2)  *Correlation is significant at the 0.05 level (2-tailed).

If a larger number of AС is introduced into the step-by-step
**Correlation is significant at the 0.01 level (2-tailed).  When comparing models of the effect of insulin on AС ( Table   3)  If you find the biorhythms of these AС, the process of assessing and predicting the level of glycemia will increase significantly, because it will be possible to more accurately predict the rise and fall due to the interference of a larger number of АС.

Discussion
The AS system is the oldest real regulatory system in living nature, including in the human body [20][21][22][23][24]. The whole acupuncture system is built on it, which has existed for many millennia and has proven its effectiveness in practice. There is convincing data on the effect of glycemia on the activity of certain AC. This data cannot be ignored, because they can be a key theoretical basis in creating a new promising monitoring system for patients with diabetes based on new physical principles. In this design, AC act as sensors from which you can read information about the state of certain internal organs and systems and thus monitor in time the entire chain of energy conversion in the body. Typically, such studies are devoted to generalized statistics for a group of people. But then, due to averaging, the truth becomes blurred and does not reflect individual reality. Therefore, it is much more productive, especially to assess the effect of biorhythms, to study one organism with an assessment of its features. In this case, as a rule, a lot of seemingly insignificant nuances are revealed, the combination of which gives new important decisions and conclusions that slip away when assessed at the level of group statistics. In this case, using the example of a specific patient, one can see that many factors influence the level of glycemia, which are reflected in the activity indicators of certain AS. Each AS seems to adsorb strictly defined effects on the body in the mode of selective resonance with several internal and external factors. To illustrate the effect of glycemia, we took 2 regression models, of which only 1 was illustrated by biorhythms of 5 AС, because using this simplified model, we could show more simply and clearly the principle of forecasting based on the analysis of biorhythms. In the second model, already 11 АС were used for analysis and therefore it is much more difficult to evaluate the influence of interference in the manual mode. In this case, computer simulation is already needed to identify crisis periods in time. It would be ideal to assess the impact of all 24 major АС included in the system of five primary elements, since in general, they reflect the whole gamut of internal and external processes affecting our body. Using this AС system as a

Disclosure Statement
The authors declare that they have no conflicts of interest and no financial interests related to the material of this manuscript.