scholarly journals Pathogenetic rationale for correction of endothelial dysfunction with quercetin in the complex treatment of non-alcoholic steatohepatitis and diabetic kidney disease in patients with type 2 diabetes mellitus

Author(s):  
O. S. Khukhlina ◽  
A. A. Antoniv ◽  
Z. Ya. Kotsiubiichuk

Objective — to determine effects of therapeutical complex, including metformin, rosuvastatin, essential phospholipids and quercetin, on the state of blood lipid spectrum, endothelial function, fibrinolysis system and platelet hemostasis, which are factors in the progression of nonalcoholic steatohepatitis (NASH) and diabetic kidney disease (DKD). Materials and methods. The investigation was performed in the dynamics of treatment of 60 NASH patients with type 2 diabetes mellitus (DM 2) and DKD of stage I — III. Depending on the prescribed treatment patients were randomized into 2 groups. The comparison group 1 (28 subjects) was administered hypocaloric diet with account of dietary restrictions #9, received essential phospholipids 300 mg 2 caps. 3 times a day) during 30 days for the NASH treatment, and antidiabetic and lipid‑lowering therapy with metformin hydrochloride 1000 mg per day, rosuvastatin (5 mg 1 time per day) for 1 month. Group 2 consisted of 32 patients and in addition to the similar 30 days of dietary recommendations, essential phospholipids, hypoglycemic and hypolipidemic therapy, received quercetin and povidone 500 mg intravenously in 100 ml of isotonic sodium 10 mg for 10 days. The mean age of patients was 53.8 ± 3.52 years. The comparison group consisted of 30 healthy age‑matching subjects. Results. Parameters of endothelial dysfunction, fibrinolysis and platelet hemostasis were determined to check the degree of endothelial‑protective effects of Quercetin against the background of the recommended protocol therapy. As a result of treatment, baseline significantly reduced NO levels (in 1.7 times) in patients of group 1 increased insignificantly (p > 0.05), and significantly raised in 1.5 times (p < 0.05) in group 2. This can be explained by effects of Quercetin as an endothelial protector, as well as by metformin effects, which reduces degree of insulin resistance and promotes body weight reduction, as well as reduction of hyperlipidemia level and probability of deposition of subendothelial proatherogenic fractions. Conclusions. Combined therapy of NASH with DM 2 and diabetic kidney disease with the use of essential phospholipids, statins and metformin with addition of Quercetin was more effective than traditional therapy: it significantly reduced the markers of NASH exacerbation, optimized blood lipid spectrum, restored endothelial functional state, eliminated the phenomena of hypercoagulable syndrome without the additional administration of antiplatelet agents.  

2021 ◽  
Vol 16 (8) ◽  
pp. 622-629
Author(s):  
O.S. Khukhlina ◽  
A.A. Antoniv ◽  
Z.Ya. Kotsiubiichuk

Background. The purpose of the study was to determine the probable effect of a complex of metformin, rosuvastatin, essential phospholipids, and quercetin on the clinical course of non-alcoholic steatohepatitis, diabetic kidney disease, type 2 diabetes mellitus, as well as on the state of blood lipid spectrum, parameters of carbohydrate metabolism compensation which are the factors of the progression of non-alcoholic steatohepatitis and diabetic kidney disease. Materials and methods. The dynamic of treatment was studied in 60 patients with non-alcoholic steatohepatitis with type 2 diabetes mellitus and stage I–III diabetic kidney disease, among whom 48 patients were diagnosed with mild non-alcoholic steatohepatitis and 12 with moderate activity. The comorbid disease in all patients with non-alcoholic steatohepatitis was type 2 diabetes mellitus of moderate severity, among which 15 people were at the stage of compensation, 45 were subcompensated. The state of carbohydrate metabolism was determined by fasting blood glucose and 2 hours after a meal by glucose oxidase method, fasting insulin content (DRG System) by enzyme-linked immunosorbent assay, blood glycosylated hemoglobin content ­using standard sets of reagents “Simko Ltd”. Results. One month after the start of therapy, asthenic syndrome of much lower intensity persisted only in 1 person (3.13 %) of the second group, while in the first group, it remained in 9 patients (32.1 %). At the same time in the majority of patients of the second group, the feeling of heaviness and pain in the right hypochondrium disappeared (in 31 (96.9 %) against 16 (57.1 %) in the first group (p < 0.05), respectively, and almost no dyspeptic symptoms disturbed (in 24 patients of group 2 (75.0 %) against 11 people (39.3 %) in group 1). A month after the start of treatment, no clinical manifestations of cholestasis were registered in 20 (62.5 %) patients of group 2 and only in 10 patients (35.7 %) in group 1 (p < 0.05). Quercetin in a complex treatment was found to have a positive effect on hepatomegaly regression, which remained in 5 patients (15.6 %) in group 2. Conclusions. The complex therapy with essential phospholipids, rosuvastatin, metformin in combination with quercetin in patients with comorbid non-alcoholic steatohepatitis, type 2 diabetes mellitus, and diabetic renal disease helps to eliminate the main clinical and laboratory symptoms of exacerbation of non-alcoholic steatohepatitis, helps to normalize blood glucose. The complex therapy with the addition of quercetin probably helped to increase the effectiveness of treatment of diabetic kidney di­sease against the background of type 2 diabetes mellitus, reduced the incidence of proteinuria, increased glomerular filtration rate, reduced hypercreatininemia.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Magdy ElSharkawy ◽  
Mohamed Mostafa ◽  
Mohamed Ezzat

Abstract Background and Aims Microalbuminuria is one of the early presentations of diabetic kidney disease that may progress to macroalbuminuria, progressive loss of glomerular filtration rate and eventually end stage renal disease. Early recognition and management of microalbuminuria can avert irreversible complications. Antihypertensive medications and antihyperlipidemic medications are medications that have been used to control diabetic nephropathy, but the reports of some side effects limited the usage of some of these drugs in diabetic patients. Pentoxifylline is an anti-inflammatory medication that have been experienced for clinical trials in diabetic patients with diabetic kidney disease. Effect of Pentoxifylline on albuminuria has been evaluated in several studies with different outcomes where a significant decrease in albuminuria in the Pentoxifylline group compared with placebo was the final conclusion. The aim of our study is the assessment of the value of Pentoxifylline addition in diabetic patients. Method Of 90 patients aged between 20 and 55 years old with a history of diabetes mellites type II for more than 5 years with normal serum creatinine and had a spot urinary albumin/creatinine ratio of &gt; 300 mg/g on two consecutive measurements with HBA1C &lt; 7% and lacking any history of glomerular disease, immunological, malignant nor cardiovascular disease in the previous 6 months nor using pentoxifylline for the past 3 month attending Ain Shams University clinics in Egypt from October 2017 to September 2018, 61 patients were eligible and randomly assigned in prospective, randomized, parallel-group, non-blind study after obtaining written informed consent from studied patients into 2 groups either the Pentoxifylline group (n = 30) receiving 400 mg thrice daily for 6 months or Ramipril group (n = 31) receiving 2.5 mg once daily on the same schedule. Blood samples and single first morning void urine samples were collected before breakfast after an 8–12 hours overnight fast. Plasma glucose, HbA1c, serum Creatinine, AST, ALT, and urinary protein / Creatinine levels were measured. All biochemical analyses were performed. Participants were followed up after 1, 3 and 6 months during the treatment period to evaluate the outcome Results Highly Statistically significant differences were noted as regard the reduction of the proteinuria levels at the same measurement points in both groups where the mean ranges of proteinuria in group 1 were found to be 2.2±1, 1.8±0.7, 1.4±0.6 mg\g at the start of the study, 3 and 6 month later respectively while in group 2 the mean range was found to be 2.6±1.2, 2±0.8, 1.6±0.7 mg\g with marked reduction of 20.6% after 3 month and 37.6% after 6 month from the start of the trial in group 1 in contrast to 20.7% and 40.2% respectively in group 2, also the effect of both drugs on the level of HbA1c has been studied in both group, in group 1 there was no reduction in the level of HbA1c after 6 month of drug administration in contrary to group 2 which showed a reduction of 4% where these results were found to be statistically significant in group 2 only. we also found statistically significant differences in both groups as regard the decline in eGFR throughout the trial duration which was 4% in group 1 and 6% in group 2. Conclusion We concluded that Pentoxifylline has a promising role as an antiproteinuric agent in comparison with ACEI from our statistical analysis of the study data with a more decline in eGFR throughout the trial duration in the study population using ACEI in comparison to Pentoxifylline. Due to restrictions of the study design these observations need further confirmation by prospective studies. Figure (1) showing comparison between both groups as regard the level of proteinuria and its reduction rate over 6 months Figure (2) showing eGFR levels at 0, 6 months in both groups Figure (3) showing comparison between both groups as regard HbA1C at baseline and after 6 months.


2021 ◽  
Vol 10 (11) ◽  
pp. 798-802
Author(s):  
Sai Deepika Ram Mohan ◽  
Shashidhar Kurpad Nagaraj ◽  
Raveesha Anjanappa ◽  
Muninarayana Chandrappa

BACKGROUND In addition to diet and nutrition, environmental changes may increase the incidence of diabetes mellitus and microvascular complication leading to ‘diabetic kidney disease (DKD)’. One such factor considered in this study is fluoride. Increased incidence of DKD lead to estimation of fluoride in fluoride endemic areas. Fluoride and advanced glycation end products lead to the development of microvascular complication in patients of diabetes leading to diabetic kidney disease or diabetic nephropathy which in turn leads to increase in expression of sirtuin 1; a regulatory protein mediating deacetylation of histone proteins which was analysed. METHODS Subjects recruited for this cross-sectional study were divided as - group 1 (healthy controls), group 2 (patients with type 2 diabetes) and group 3 (diabetic nephropathy patients) with 50 subjects in each group. Routine parameters were analysed in biochemistry section of central laboratory. RESULTS In patients with diabetic kidney disease, serum and urine fluoride levels were similar (0.2 and 0.28 ppm); whereas, in other two groups, urine fluoride values were more than the serum fluoride values indicating better renal function and fluoride clearance. Least sirtuin 1 median range was observed in group 1 [22.65 (11.78 - 91.10)] and 36.9 (27.38 - 56.23) in group 3 lesser than group 2 with a value of [42.7 (30.17 - 52.93)]. CONCLUSIONS Serum and urine fluoride estimation aids in assessing progression of disorder and hence helps in preventing complications. Fluoride may not be a cause of diabetes but may accelerate its microvascular complications as observed in this study. Sirtuin 1 levels in serum or plasma can be a marker for various damages caused by aging disorders. Sirtuin 1 correlation with diabetic parameters will help in health research to include it as a therapeutic target for various toxic conditions. KEY WORDS Advanced Glycation End product, Fluoride, Diabetic Kidney Disease, Sirtuin 1, Type 2 Diabetes Mellitus


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 443-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
YUKO YAMAZAKI ◽  
KOKA MOTOYAMA ◽  
TOMOAKI MORIOKA ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 539-P
Author(s):  
YOSHINORI KAKUTANI ◽  
MASANORI EMOTO ◽  
KATSUHITO MORI ◽  
YUKO YAMAZAKI ◽  
AKINOBU OCHI ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Randa I. Farah ◽  
Mohammed Q. Al-Sabbagh ◽  
Munther S. Momani ◽  
Asma Albtoosh ◽  
Majd Arabiat ◽  
...  

Abstract Aim Diabetic kidney disease (DKD) is a major long-term complication of diabetes mellitus (DM). Given the paucity of data on DKD in Jordan, we aimed to evaluate the prevalence, characteristics and correlates of DKD in Jordanian patients with type 2 DM. Methods This cross-sectional study included 1398 adult patients with type 2 DM who sought medical advice in the endocrinology clinic between March and September 2019. Demographic, clinical and laboratory data were reviewed. DKD was defined as reduced eGFR, and/or albuminuria. Three regression models were constructed to identify factors associated with CKD stages, albuminuria and DKD. Results Overall, 701 (50.14%) patients had DKD, with a median age of 59.71 ± 11.36  years. Older age, high triglycerides, and low high-density lipoprotein were associated with DKD (multivariable odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03, p < 0.01; OR: 1.1, 95% CI: 1.01–1.2; and OR: 0.98, 95% CI: 0.97–0.99, p < 0.01 respectively). Metformin and renin-angiotensin system blockers were negatively associated with albuminuria and chronic kidney disease stages (p < 0.01). Conclusion Our study demonstrated that approximately one half of patients with type 2 DM had DKD. Further studies are necessary to understand this high prevalence and the underlying factors. Future research are needed to assess implementing targeted community-based intervention.


2019 ◽  
Vol 95 (1) ◽  
pp. 178-187 ◽  
Author(s):  
Guozhi Jiang ◽  
Andrea On Yan Luk ◽  
Claudia Ha Ting Tam ◽  
Fangying Xie ◽  
Bendix Carstensen ◽  
...  

2021 ◽  
Vol 18 (3) ◽  
pp. 17-25
Author(s):  
Stoiţă Marcel ◽  
Popa Amorin Remus

Abstract The presence of albuminuria in patients with type 2 diabetes mellitus is a marker of endothelial dysfunction and also one of the criteria for diagnosing diabetic kidney disease. The present study aimed to identify associations between cardiovascular risk factors and renal albumin excretion in a group of 218 patients with type 2 diabetes mellitus. HbA1c values, systolic blood pressure, diastolic blood pressure were statistically significantly higher in patients with microalbuinuria or macroalbuminuria compared to patients with normoalbuminuria (p <0.01). We identified a statistically significant positive association between uric acid values and albuminuria, respectively 25- (OH)2 vitamin D3 deficiency and microalbuminuria (p <0.01).


2008 ◽  
Vol 11 (4) ◽  
pp. 988-991
Author(s):  
Robert C Atkins ◽  
Paul Zimmet

In 2003, the International Society of Nephrology and the International Diabetes Federation launched a booklet called “Diabetes in the Kidney: Time to act” [1] to highlight the global pandemic of type 2 diabetes and diabetic kidney disease. ration (PZ)


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