EFFECTIVENESS OF "NEO-INULIN" IN THE COMPREHENSIVE TREATMENT OF PATIENTS WITH TYPE 2 DIABETES MELLITUS

Abbreviated Version
Original Report: DOWNLOAD

Katamanova E.V., Kazakova P.V., Kudaeva I.V., Kuks A.N., Ushakova O.V. FGBNU "East Siberian Institute of Medical and Ecological Research" (665827, Angarsk, 12a microdistrict, 3, Russia) Corresponding Author: Katamanova Elena Vladimirovna

SUMMARY
Diabetes mellitus (DM) is one of the most serious medical, social, and economic healthcare problems worldwide. The incidence of DM doubles every 10–15 years, taking on the character of a non-infectious epidemic. Therefore, the search for new medicinal products that normalize glycemia, prevent DM complications, and improve patients' quality of life is extremely relevant. One such product is "Neo-Inulin," which exhibits hypoglycemic, antioxidant, hepatoprotective, and angioprotective effects.

Objective of the Study
To evaluate the effectiveness of "Neo-Inulin" in the comprehensive treatment of patients with type 2 diabetes mellitus.

Materials and Methods
The study included 18 women (mean age – 64.5 ± 8.7 years, mean weight – 77.8 ± 11.4 kg) and 3 men (mean age – 54.6 ± 12.4 years, mean weight – 114 ± 40.2 kg) with type 2 diabetes mellitus. The average disease duration was 11.0 (7.0–12.0) years. "Neo-Inulin" was administered at a dosage of 2 capsules per day for 12 weeks, in addition to the basic diabetes therapy. The effectiveness of the therapy was evaluated through health-related quality of life surveys, biochemical blood tests (glycated hemoglobin), clinical minimum (CBC, urinalysis, ECG, blood glucose), tissue blood flow functional characteristics, and ankle-brachial index (ABI). Statistical analysis was performed using Statistica 6.0 (StatSoft Inc., USA), with p < 0.05 considered statistically significant.

Results
Statistically significant differences were found in all health-related quality of life scale indicators before and after treatment with "Neo-Inulin," including the physical and mental component summaries. There was an improvement in the functioning of microcirculation regulation mechanisms, confirmed by a statistically significant increase in ABI (right – 1.0 and 0.8; left – 0.9 and 0.8 respectively; p < 0.05) and microcirculation variation coefficient (9.2 and 8.3 respectively; p < 0.05). Glycated hemoglobin normalization was achieved in 57.1% of cases (12 patients).

Conclusion
The treatment regimen including "Neo-Inulin" contributes to increased treatment effectiveness and improved quality of life for patients with type 2 diabetes mellitus.
Keywords: diabetes mellitus, "Neo-Inulin," quality of life, ankle-brachial index, fluorimetry

JUSTIFICATION
Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by both insulin resistance and impaired insulin secretion. T2DM is the leading cause of hyperglycemia, with its incidence catastrophically increasing in all countries, doubling every 15–20 years. Chronic hyperglycemia is not the only component of T2DM. It is accompanied by visceral obesity, arterial hypertension, increased low-density lipoproteins, triglycerides, and decreased high-density lipoproteins. The main complication of DM is microangiopathy, endothelial damage due to excessive glycated blood proteins. The endothelium plays a key role in controlling vascular tone, regulating vessel lumen depending on blood flow rate and blood pressure on the vessel wall, and tissue metabolic needs. Therefore, the search for means that normalize glycemia, improve blood lipid profile, restore the endothelium, and normalize microcirculation is extremely relevant. One such means is "Neo-Inulin," containing inulin, dihydroquercetin, lipoic acid, chromium, and bilberry shoot extract, which exhibits hypoglycemic, antioxidant, hepatoprotective, and angioprotective effects.

OBJECTIVE OF THE STUDY
To evaluate the effectiveness of "Neo-Inulin" in the comprehensive treatment of patients with type 2 diabetes mellitus.

MATERIALS AND METHODS
The study included 18 women (mean age – 64.5 ± 8.7 years; mean weight – 77.8 ± 11.4 kg) and 3 men (mean age – 54.6 ± 12.4 years; mean weight – 114 ± 40.2 kg) with type 2 diabetes mellitus. The average disease duration was 11.0 (7.0–12.0) years. Inclusion criteria were age 40 and older; presence of type 2 diabetes; voluntary participation with written informed consent. Exclusion criteria included pregnancy and lactation; decompensation of cerebrovascular, cardiovascular diseases, malignant tumors, kidney, liver, thyroid diseases, active tuberculosis or other infectious diseases; drug or alcohol dependence; systemic steroid or immunosuppressive therapy; sensitization and hypersensitivity to dietary supplement components; current participation in any clinical trial or any other non-interventional drug or device study.
Overall, the group registered the following diabetes complications: nephropathy – 6 patients (28.6%), macroangiopathy – 12 (57.1%), retinopathy – 14 (66.7%), and polyneuropathy – 100% of cases.
Patients took glucose-lowering drugs according to standardized treatment regimens included in first-line drugs with dosages indicated in clinical guidelines. The groups of drugs included: biguanides (metformin) as monotherapy at a dose of 1000 mg twice a day – 6 patients (28.6%); sulfonylurea derivatives (gliclazide) 60 mg in combination with metformin 1000 mg per day – 9 patients (42.8%); DPP-4 inhibitor (sitagliptin) 50 mg in combination with metformin 1000 mg per day – 6 patients (28.6%). "Neo-Inulin" was administered at a dosage of 2 capsules per day for 12 weeks, in addition to basic diabetes therapy.
The effectiveness of the therapy was assessed using social frustration scales as risk factors for mental adaptation disorders. Health-related quality of life was assessed using the SF-36 method, determining the physical component summary (including physical functioning, role-physical functioning, general health, and bodily pain) and the mental component summary (including social functioning, role-emotional functioning, vitality, and mental health). The total score from 0 to 30 corresponded to a low quality of life, 30–60 to a medium quality, and over 61 to a high quality of life. The maximum score for each scale was 100 points.
Biochemical blood samples were analyzed on the Labio 200 biochemical analyzer. ABI was measured using the portable ultrasound Doppler angiological screening system Angiodin-PC, and microcirculation indicators were assessed using the laser analyzer "LACC-01."
In accordance with the requirements of the Biomedical Ethics Committee, the examination was conducted with the written informed consent of patients, did not infringe on the rights or endanger the welfare of the research subjects, in accordance with the requirements of biomedical ethics approved by the Helsinki Declaration of the World Medical Association (2000) and the conclusion of the Local Ethics Committee (No. 7 of 27.11.2020).

STATISTICAL PROCESSING
Statistical processing was performed using the Statistica 6 (StatSoft Inc., USA) software package. Intergroup comparison of quantitative indicators was performed using the non-parametric Wilcoxon test. Values are presented as the mean and standard error, as well as the median (Me), upper (Q25), and lower (Q75) quartiles. The relative frequency of the binary sign is presented with the boundaries of the 95% confidence interval. Fisher's F-test was used to test the statistical hypothesis about differences in the frequencies of a qualitative sign in dependent samples. In all cases, differences were considered statistically significant at p < 0.05.

RESULTS
The study of subjective sensations regarding daily and social activities in the group of examined individuals revealed statistically significant differences in the values of all health-related quality of life scales in patients with type 2 diabetes in the groups before and after treatment with "Neo-Inulin," including physical and mental component summaries.
It should be noted that in the "before treatment" group, patients had reduced indicators of all health-related quality of life scales, including integral components of physical and mental health, indicating the negative impact of physical condition on daily duties, the presence of pain, emotional problems, fatigue, and reduced work capacity most of the time, limiting life activities, and characterizing a decrease in mood and positive emotions, as well as purposefulness, motivation, and initiative in social relationships.
After treatment with "Neo-Inulin," patients showed a statistically significant increase in all health-related quality of life scales, including physical and mental component summaries.
An overall satisfaction index (1.3 ± 0.1 points) was obtained, characterizing a high level of satisfaction according to specified gradations of signs (considering intermediate levels). It should be noted that only 12% of patients in the "before treatment" group showed no social frustration, while after treatment in the patient group – 94%, indicating the absence of social frustration in the form of frustration tension in the areas of social functioning of patients.
Fasting hyperglycemia was recorded in all examined individuals (100%) before treatment, and after a course of "Neo-Inulin" therapy, this indicator was 66.7% (14 patients). When analyzing the target level of glycated hemoglobin against the background of treatment with "Neo-Inulin," it was found that the target level of glycated hemoglobin was not achieved in 9 (42.9%) cases, while 12 patients (57.1%) achieved target levels of this indicator.
ABI indicators before treatment were less than 1.0 in 76% of the examined individuals, with ABI values less than 0.9 noted in 10 people, indicating the presence of peripheral artery disease of the lower extremities. After taking "Neo-Inulin" for three months, ABI values less than 1.0 were observed in 38%, less than 0.9 in 2 out of 21 individuals, indicating an improvement in the state of the vascular wall.

DISCUSSION
The main goals in the treatment of diabetes mellitus are the elimination of symptoms, optimal metabolic control, prevention of acute and chronic complications, and achieving the highest possible quality of life. Our results on reducing glycemia levels in individuals with type 2 diabetes mellitus using "Neo-Inulin" in complex therapy indicate the pathogenic effect of its components. There is evidence that chromium picolinate positively affects blood glucose levels and helps reduce insulin resistance in diabetes patients. Another component with a potentially positive effect on normalizing blood glucose levels is the primary component of the drug – inulin. Studies have shown that taking this supplement reduces major glycemic indicators, including glycated hemoglobin levels and fasting blood glucose concentrations, particularly in patients with prediabetes and type 2 diabetes, which can have potential clinical value as adjuvant therapy for this pathology.
In recent years, much attention has been paid to quercetin and its derivative dihydroquercetin due to their potential capabilities in treating metabolic diseases. These flavonoids have many pharmacological properties, such as hypoglycemic, hypolipidemic, cardiovascular, anti-inflammatory, and others. Alpha-lipoic acid, another component of "Neo-Inulin," has been shown to have beneficial effects on the prevention and treatment of diabetes. It is a powerful antioxidant with insulin-mimetic and anti-inflammatory effects, playing an essential role in mitochondrial bioenergetic reactions, making it an attractive treatment option for diabetes-related complications such as retinopathies, neuropathies, and vascular damage.
The quality of life issue for diabetes patients concerns specialists worldwide. In diabetes, many aspects of quality of life are affected: psychological, professional, family, and social. Quality of life determines the psychological and physical condition of patients. The treatment regimen including "Neo-Inulin" significantly improved physical, role, social, and psychological functioning.
The main complication of diabetes is microangiopathy, endothelial damage due to excessive glycated blood proteins. The statistically significant data obtained in the study on increasing ABI and perfusion constant indicates improved vascular wall condition and microcirculation processes in peripheral vessels.

CONCLUSION
Thus, the treatment regimen including "Neo-Inulin" improves health-related quality of life, leading to increased psychosocial adaptation levels and treatment effectiveness. "Neo-Inulin" treatment for up to three months in the comprehensive therapy of type 2 diabetes mellitus normalizes some microcirculation indicators: ABI and microcirculation variation coefficient statistically significantly increased, and statistically significant decreases in glycated hemoglobin and fasting glucose were observed.

Funding Funding within the framework of exploratory scientific research.
Conflict of Interest The authors declare no potential conflicts of interest.

REFERENCES

1. Algorithms of specialized medical care for diabetes patients: clinical recommendations, 10th edition. Ed. I.I. Dedov, M.V. Shestakova, A.Yu. Mayorov. Moscow, 2021.
2. Ahmed W, Rashid S. Functional and therapeutic potential of inulin: A comprehensive review. Crit Rev Food Sci Nutr. 2019; 59(1): 1-13. doi: 10.1080/10408398.2017.1355775
3. Gao T, Jiao Y, Liu Y, Li T, Wang Z, Wang D. Protective effects of konjac and inulin extracts on type 1 and type 2 diabetes. J Diabetes Res. 2019; 2019: 3872182. doi: 10.1155/2019/3872182
4. Wan X, Guo H, Liang Y, Zhou C, Liu Z, Li K, et al. The physiological functions and pharmaceutical applications of inulin: A review. Carbohydr Polym. 2020; 246: 116589. doi: 10.1016/j.carbpol.2020.116589
5. Sunil C, Xu B. Phytochemistry. An insight into the health-promoting effects of taxifolin (dihydroquercetin). Phytochemistry. 2019; 166: 112066. doi: 10.1016/J.phytochem.2019.112066
6. Shu Z, Yang Y, Yang L, Jiang H, Yu X, Wang Y. Cardioprotective effects of dihydroquercetin against ischemia reperfusion injury by inhibiting oxidative stress and endoplasmic reticulum stress-induced apoptosis via the PI3K/Akt pathway. Food Funct. 2019; 10(1): 203-215. doi: 10.1039/c8fo01256c
7. Zhang Y, Yu J, Dong XD, Ji HY. Molecules. Research on characteristics, antioxidant and antitumor activities of dihydroquercetin and its complexes. Molecules. 2017; 23(1): 20. doi: 10.3390/molecules23010020
8. Yeh G, Eisenberg D, Kaptchuk T, Philips R. Systematic review of herbs and dietary supplements for glycemic control in diabetes. Diabetes Care. 2003; 26(4): 1277-1294. doi: 10.2337/diacare.26.4.1277
9. Vasserman L.I. Risk factors for mental maladaptation in teachers of mass schools: a guide for doctors and psychologists. Saint Petersburg, 1997.
10. Ware JE, Sherbour CD. The MOS 36-item short form health survey: conceptual framework and item selection. Medical Care. 1992. 30: 473-483.
11. Landgraf R, Aberle J, Birkenfeld AL, Gallwitz B, Kellerer M, Klein H, et al. Therapy of type 2 diabetes. Exp Clin Endocrinol Diabetes. 2019; 127(S 01): S73-S92. doi: 10.1055/a-1018-9106
12. Suksomboon N, Poolsup N, Yuwanakorn A. Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther 2014; 39(3): 292-306. doi: 10.1111/jcpt.12147
13. Ashoush S, Abou-Gamrah A, Bayoumy H, Othman N. Chromium picolinate reduces insulin resistance in polycystic ovary syndrome: Randomized controlled trial. J Obstet Gynaecol Res. 2016; 42(3): 279-285. doi: 10.1111/jog.12907
14. Wang L, Yang H, Huang H, Zhang C, Zuo HX, Xu P, et al. Inulin-type fructans supplementation improves glycemic control for the prediabetes and type 2 diabetes populations: RESULTS from a GRADE-assessed systematic review and dose-response meta-analysis of 33 randomized controlled trials. J Transl Med. 2019; 17(1): 410. doi: 10.1186/s12967-019-02159-0
15. Maalik A, Khan FA, Mumtaz A, Mehmood A, Azhar S, Atif M, et al. Pharmacological applications of quercetin and its derivatives: A short review. Trop J Pharm Res. 2014; 13(9): 1561-1566. doi: 10.4314/tjpr.v13i9.26
16. Rochette L, Ghibu S, Muresan A, Vergely C. Alpha-lipoic acid: Molecular mechanisms and therapeutic potential in diabetes. Can J Physiol Pharmacol. 2015; 93(12): 1021-1027. doi: 10.1139/cjpp-2014-0353
17. Ovchinnikov A.A., Sultanova A.N., Yakupova A.R. Features of psychoemotional state and quality of life of patients with diabetes mellitus. Journal of Siberian Medical Sciences. 2016; (3): 3.
18. Qiu S, Cai X, Yin H, Sun Z, Zügel M, Steinacker JM, et al. Exercise training and endothelial function in patients with type 2 diabetes: a meta-analysis. Cardiovasc Diabetol. 2018; 17(1): 64. doi: 10.1186/s12933-018-0711-2