ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 22 of 61
JMBS 2018, 3(5): 110–114
Clinical Medicine

Endogenous Intoxication Syndrome in Patients with Diabetes Mellitus in Combination with Nonalcoholic Fatty Liver Disease

Maykova T. V., Voloshin O. I., Shklyar S. P., Vlasenko E. O.

The progressive proliferation of diabetes mellitus is a real threat to the quality of life of patients, aggravating the condition of other organs and systems of the body, which requires attention not only of endocrinologists, but also of specialists of other specialties. The importance of clinicians is increasly attracted by the peculiarities of the clinical course of non-alcoholic fatty liver disease (NAFLD) in combination with diabetes mellitus (DM), causal relationships, structural changes in the organs of the hepatobiliary zone and pathways to therapeutic tactics. Metabolic disturbances accompanying diabetes are associated with the accumulation of pathologically high concentrations of carbohydrate and lipid metabolism products, intermediate metabolites and abnormal compounds: oxidized lipoproteins, glycosylated proteins, products of vital functions of hypoxic tissues, and the like. Their toxic properties can lead to depletion of the detoxifying system with the further development of endogenous intoxication (EI). Since one of the parts of the detoxifying system is the liver, it is interesting to study the presence of endotoxemia and its role in the course of NSCLC in patients with diabetes mellitus. Material and methods. While examining 66 patients with diabetes mellitus in combination with nonalcoholic fatty liver disease, endogenous intoxication syndrome was detected in 83.8% of patients with type I diabetes and 74.3% of patients with type II diabetes mellitus. In the examination of patients in Group I, diabetic microangiopathy, manifested by proliferative retinopathy and/ or nephropathy, was established in 80.6% of the cases, macroangiopathy – 32.3%, neuropathy – 67.7%. Results and discussion. Among patients in group ІІ, diabetic microangiopathy was observed in 62.9%, macrogangiopathy – 20.0%, neuropathy – in 62.9% of patients whose frequency was associated with the duration of diabetes mellitus (r = 0.51; p <0.04 ) The level of MSM in patients with Group I increased by 27.1% (p <0.001), MDA in the plasma – by 29.0% (p <0.01), in red blood cells – by 28.1% (p <0.001). Moreover, the increase in the level of MSM in plasma occurred with an increase in HbA1c (r = 0.68; p <0.001) and glycemia (r = 0.86; p <0.001). On the other hand, with the increase in the content of MSM, the incidence of retinopathy (r = 0.74; p <0.001) and neuropathy (r = 0.68; p <0.001) increased. It was with MSM in patients of this group that correlated the degree of liver fibrosis (r = 0.93; p <0.001). The content of MSM directly correlated plasma levels of MDA (r = 0.89; p <0.001) and erythrocytes (r = 0.86; p <0.001), which confirms its known role in the development of ES syndrome. In turn, the concentration of MDA in both plasma and erythrocytes increased with increasing glycemia (r = 0.77; p <0.001 and r = 0.86; p <0.001), and excessive accumulation of MDA in erythrocytes was more characteristic of patients with DD with unsatisfactory glycemic control (r = 0.65; p <0.007). The degree of liver fibrosis increased (r = 0.72; p <0.001) with increasing MDA, and the incidence of microangiopathy (r = 0.48; p <0.03) and neuropathy (r = 0.67; p <0.002) did the same. In patients of group II, the incidence of MSM occurred at 29.8% (p <0.001), MDA of the blood plasma – by 32.2% (p <0.001), MDA in erythrocytes by 21.4% (p <0.001). Endotoxemia was shown to be a burden on the progression of liver fibrosis and the development of complications of diabetes mellitus, in particular, microangiopathy and neuropathy. Conclusions. The revealed pathogenetic features of diabetes mellitus in combination with non-alcoholic fatty liver disease allowed solving the problem of therapeutic tactics. Excessive levels of MDA in erythrocytes in patients with unsatisfactory glycemic control indicated a decrease in erythrocytic buffer in the neutralization of endotoxins, requiring appropriate therapeutic tactics. Prospects for further research. In the future it is planned to develop approaches for treatment tactics of patients with diabetes in combination with NADH, aimed at overcoming endotoxemia.

Keywords: diabetes mellitus, non-alcoholic fatty liver disease, liver fibrosis, endotoxemia

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  1. Bakulyn YG, Sandler YuG, Vynnytskaya EV, Keyyan VA, Rodyonova SV, Rotyn DL. Sakharnyy dyabet y nealkogolnaya zhyrovaya bolezn pecheny: grany sopryazhennosty. Terapevtycheskyy arkhyv. 2017; 89 (2): 59-65. [Russian]
  2. Biokhimichni ta biofizychni metody otsinky porushen okyslyuvalnogo gomeostazu v osib, shcho zaznaly radiotsiynogo vplyvu vnaslidok avariyi na ChAES: metod rekomendatsiyi. Ukladachi: Ovsyannykova MM, Alokhina SM, Drobinska OV, ta in. K, 1999. 6 s. [Ukrainian]
  3. Botsyurko VI, Gryb VA, Gerasymchuk RD, Erstenyuk AM. Endogenna intoksykatsiya ta oksydatyvnyy stres u khvorykh na tsukrovyy diabet 2 typu, uskladnenyy poli nevropatiyeyu. Arkhiv klinichnoyi medytsyny. 2010; 1: 22-5. [Ukrainian]
  4. Nykolaychuk VV, Moyn VM, Kyrkovskyy LY. Sposob opredelenyya «srednykh molekul». Lab delo. 1991; 4: 13-8. [Russian]
  5. Tkachenko VI. Analiz poshyrenosti ta zakhvoryuvanosti na tsukrovyy diabet sered naselennya svitu ta Ukrayiny za 2003–2013 rr. Liky Ukrayiny. 2014; 14 (21): 55-9. [Ukrainian]
  6. Ahmed A, Perumpail RB, Harrison SA. High prevalence of hepatic fibrosis in the setting of coexisting diabetes and hepatic steatosis: A case for selective screening in the general population? Hepatology. 2016; 63 (1): 20-2.
  7. International Diabetes Federation. IDF Diabetes Atlas, 7th edn. Brussels, Belgium: International Diabetes Federation, 2015. Available from:
  8. Definition, Diagnosis and Classification of Diabetes Mellitus
  9. and its Complications. Report of a WHO Consultation. Part 1: Diagnosis and Classification of Diabetes Mellitus. World Health Organization
  10. Department of Noncommunicable Disease Surveillance.
  11. Geneva, 1999. 59 р.
  12. Doycheva I, Cui J, Nguyen P, Costa EA, Hooker J, Hofflich H, Bettencourt R, Brouha S, Sirlin CB, Loomba R. Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE. Aliment Pharmacol Ther. 2016; 43 (1): 83-95.
  13. Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S, Hultcrantz R. Fibrosis Stage is the strongest predictor for disease-specific mortality in NAFLD After Up to 33 Years of Follow-Up. Hepatology. 2015 May; 61 (5): 1547-54.
  14. Januszewski AS, Thomas MC, Chung SJ, Karschimkus CS, Rowley KG, Nelson C, O'Neal D, Wang Z, Best JD, Jenkins AJ. Plasma low-molecular weight fluorescence in type 1 diabetes mellitus. Ann N Y Acad Sci. 2005 Jun; 1043: 655-61.
  15. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006 Nov; 3 (11): e442.
  16. Sharp PS, Rainbow S, Mukherjee S. Serum levels of low molecular weight advanced glycation end products in diabetic subjects. Diabet Med. 2003; 20 (7): 575-9.
  17. Williamson RM, Price JF, Glancy S, Perry E, Nee LD, Hayes PC, Frier BM, Van Look LA, et al. Prevalence of and risk factors for hepatic steatosis and nonalcoholic fatty liver disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes Care. 2011; 34 (5): 1139-44.