scholarly journals Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

2020 ◽  
Author(s):  
Tomoko Okuyama ◽  
Jun Shirakawa ◽  
Takashi Nakamura ◽  
Takayo Murase ◽  
Daisuke Miyashita ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Plasma Insulin ◽  
Surrogate Marker ◽  
Vascular Complications ◽  
The Body ◽  
Xanthine Oxidoreductase ◽  
Fasting Plasma ◽  
Fasting Plasma Insulin

Abstract Xanthine oxidoreductase (XOR) catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species and causes endothelial dysfunction. In this study, we evaluated the association of XOR and its substrate with the vascular complications in 94 Japanese inpatients with type 2 diabetes (T2DM).The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the high density lipoprotein cholesterol. The plasma XOR activity also showed a positive correlation with the serum triglyceride. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. The plasma XOR activity negatively correlated with the duration of diabetes, and positively correlatted with the coefficient of variation of the R-R interval and sensory nerve conduction velocity. Furthermore, the plasma XOR activity was significantly decreased in patients with coronary artery disease.Thus, the plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in T2DM.Trial registration: This study is registered at the UMIN Clinical Trials Registry (UMIN000029970; https://www.umin.ac.jp/ctr/index-j.htm). The study was conducted from Nov 15, 2017.

scholarly journals Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

2021 ◽  
Author(s):  
Tomoko Okuyama ◽  
Jun Shirakawa ◽  
Takashi Nakamura ◽  
Takayo Murase ◽  
Daisuke Miyashita ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Plasma Insulin ◽  
Surrogate Marker ◽  
Vascular Complications ◽  
The Body ◽  
Xanthine Oxidoreductase ◽  
Fasting Plasma ◽  
Fasting Plasma Insulin

Abstract Xanthine oxidoreductase (XOR) catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species and causes endothelial dysfunction. In this study, we evaluated the association of XOR and its substrate with the vascular complications in 94 Japanese inpatients with type 2 diabetes (T2DM). The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the high density lipoprotein cholesterol. The plasma XOR activity also showed a positive correlation with the serum triglyceride. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. The plasma XOR activity negatively correlated with the duration of diabetes, and positively correlated with the coefficient of variation of the R-R interval and sensory nerve conduction velocity. Furthermore, the plasma XOR activity was significantly decreased in patients with coronary artery disease. Thus, the plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in T2DM. Trial registration: This study is registered at the UMIN Clinical Trials Registry (UMIN000029970; https://www.umin.ac.jp/ctr/index-j.htm). The study was conducted from Nov 15, 2017.

scholarly journals Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomoko Okuyama ◽  
Jun Shirakawa ◽  
Takashi Nakamura ◽  
Takayo Murase ◽  
Daisuke Miyashita ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Plasma Insulin ◽  
Surrogate Marker ◽  
Vascular Complications ◽  
The Body ◽  
Xanthine Oxidoreductase ◽  
Fasting Plasma ◽  
Fasting Plasma Insulin

AbstractXanthine oxidoreductase (XOR) catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species and causes endothelial dysfunction. In this study, we evaluated the association of XOR and its substrate with the vascular complications in 94 Japanese inpatients with type 2 diabetes (T2DM). The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the high density lipoprotein cholesterol. The plasma XOR activity also showed a positive correlation with the serum triglyceride. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. The plasma XOR activity negatively correlated with the duration of diabetes, and positively correlated with the coefficient of variation of the R-R interval and sensory nerve conduction velocity. Furthermore, the plasma XOR activity was significantly decreased in patients with coronary artery disease. Thus, the plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in T2DM.Trial registration: This study is registered at the UMIN Clinical Trials Registry (UMIN000029970; https://www.umin.ac.jp/ctr/index-j.htm). The study was conducted from Nov 15, 2017.

scholarly journals Association of the plasma xanthine oxidoreductase activity with the metabolic parameters and vascular complications in patients with type 2 diabetes: a cross-sectional study in a hospital setting

2020 ◽  
Author(s):  
Tomoko Okuyama ◽  
Jun Shirakawa ◽  
Takashi Nakamura ◽  
Takayo Murase ◽  
Daisuke Miyashita ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Uric Acid ◽  
Plasma Levels ◽  
Plasma Insulin ◽  
Vascular Complications ◽  
Xanthine Oxidoreductase ◽  
Fasting Plasma ◽  
Fasting Plasma Insulin

Abstract Background Xanthine oxidoreductase (XOR) is a rate-limiting enzyme that catalyzes the oxidation of hypoxanthine to xanthine, and of xanthine to uric acid. XOR also enhances the production of reactive oxygen species (ROS) and causes endothelial dysfunction. To explore the association of XOR and its substrate with the vascular complications in patients with type 2 diabetes mellitus (hereafter simply, diabetes), we measured the plasma XOR activity and plasma levels of xanthine and hypoxanthine in patients with type 2 diabetes. Materials and Methods Plasma XOR activity and the plasma levels of xanthine and hypoxanthine were measured, and their associations with the clinical parameters and vascular complications were investigated in 94 Japanese inpatients with type 2 diabetes. Results Both the plasma XOR activity and plasma xanthine levels were correlated with the serum uric acid level. The plasma XOR activity was correlated with the plasma xanthine level, but not the plasma hypoxanthine level. The plasma XOR activity and plasma xanthine levels were positively correlated with the body mass index (BMI), serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum γ-GTP, fasting plasma insulin, and the homeostasis model of assessment of insulin resistance (HOMA-IR), and negatively correlated with the serum high density lipoprotein cholesterol levels (HDL-C). The plasma XOR activity also showed a positive correlation with the serum triglyceride (TG) levels. Plasma xanthine was positively correlated with the Fib4-index. Multivariate analyses identified AST, ALT, fasting plasma insulin and HOMA-IR as being independently associated with the plasma XOR activity. In addition, a negative correlation was observed between the plasma XOR activity and the duration of diabetes, and positive correlations were observed between the plasma XOR activity and the coefficient of variation of the R-R interval (CVR-R) and sensory nerve conduction velocity (SCV). Furthermore, the plasma XOR activity was found to be significantly decreased in patients with coronary artery disease. Conclusions The plasma XOR activity might be a surrogate marker for the development of vascular complications, as well as liver dysfunction and insulin resistance, in patients with type 2 diabetes

scholarly journals Potential triggers of atrial fibrillation in type 2 diabetes mellitus

2021 ◽  
Author(s):  
Zulfiya Mirzarakhimova ◽  
Bakhodir Narziev ◽  
Akmal Yakubov ◽  
Oybek Salaev ◽  
Ramesh Hamraev ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Plasma Insulin ◽  
Model Assessment ◽  
Fasting Plasma ◽  
Fasting Plasma Insulin

Abstract Introduction. Atrial fibrillation is an irregular heartbeat that accelerates to form blood clots in the chambers of the heart and leads to stroke, heart failure, and other cardiovascular complications. Diabetes mellitus itself has been identified as a risk factor for atrial fibrillation, but the association between them is unclear. Material and methods. We analyzed 70 patients with type 2 insulin non-dependent diabetes mellitus. All patients were examined in parallel continuous glucose (CGM) and ECG for 14 days. The study population divided into documented atrial fibrillation (AF group, n = 16) and without atrial fibrillation (non-AF group, n = 54) groups. We assessed the relationship between hypoglycemia, fasting plasma insulin, insulin resistance using the homeostatic model assessment (HOMA-IR) equation, and the incidence of atrial fibrillation. Results. We found a total of 46 episodes of documented atrial fibrillation (AF be defined as an arrhythmia lasting ≥ 30 seconds) lasted on the whole 596.9 minute, which was the most significant by the number (2.87 ± 2.05 per patient, p < 0.0001) or the time (31.31 ± 16.57 min per patient, p < 0.0001). We also compared the incident rate of different types of atrial premature complexes between two groups. We found a maximum of 642.6 ± 567.2 single PACs per patient in the AF group, compared to 84.6 ± 87.9, p = 0.002. Despite this, there were significant differences by the following parameters: couplet PACs (p = 0.0015) and triplet or > 3 PACs (p = 0.0007). Over 14 days, a total of 263 hypoglycemic episodes or 5135 min hypoglycemic time were detected, the average number and time of hypoglycemic episodes were 8.0 ± 4.94 per person and 137.0 ± 63.17 min in AF group, and 2.5 ± 4.64 per person (p = 0.0001), 54.5 ± 67.3 min (p = 0.004) in the non-AF group. There was a statistically significant (p < 0.0001) association between FPI and incident AF, more exactly, the mean level of FPI was 31 ± 6.1 mlU/L in the AF group, whereas was 11.3 ± 4.07 in the non-AF group. When we measured the HOMA-IR index by using the homeostasis model, we found significant differences between AF and non-AF groups (11.2 ± 3.88 mmol/l vs. 4.3 ± 1.66 mmol/l, p < 0.0001). Conclusion. The parallel recording of continuous glucose and ECG are necessary to evaluate hypoglycemia-related atrial fibrillation in type 2 diabetes mellitus. Elevated fasting plasma insulin, as well as insulin resistance, are important predictors of atrial fibrillation development, but it needs further studies.

Abstract 18289: New Roles of the Interplay Between Endothelin and Insulin-like Growth Factor 1 in the Regulation of Vascular Redox State in Patients With Type 2 Diabetes and Coronary Atherosclerosis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Ioannis Akoumianakis ◽  
Marios Margaritis ◽  
Fabio Sanna ◽  
Laura Herdman ◽  
Constantinos Psarros ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Growth Factor ◽  
Nadph Oxidase ◽  
Redox State ◽  
Vascular Complications ◽  
Positive Association ◽  
Elevated Plasma ◽  
Enos Uncoupling

Background: Insulin resistance (IR) is associated with increased cardiovascular risk. Given that plasma endothelin (ET) is elevated in IR, we explored whether the variations in ET levels mediate the vascular complications of type 2 diabetes (T2DM), by exploring its links with vascular redox state in human vessels. Methods: The study population consisted of 383 patients undergoing coronary bypass surgery (CABG), 30% with T2DM. Levels of ET, insulin growth factor 1 (IGF1), insulin and glucose (to calculate HOMA-IR as an index of insulin resistance) were measured in plasma, while vascular superoxide (O2) was measured in saphenous vein segments obtained during surgery. Results: Patients with untreated T2DM had elevated plasma ET, contrary to treated patients with T2DM (A). A positive association was observed between plasma endothelin and IGF1 levels in non-T2DM, which was reversed in T2DM (B). Elevated plasma ET was associated with increased NADPH-stimulated O2- (indicative of higher NADPH oxidase activity) and more LNAME inhibitable O2- (suggestive of more eNOS uncoupling) in human vessels (C, D). Conclusions: We demonstrate that circulating ET is elevated in untreated T2DM but its levels are normalised after intensive glycaemic control. We also document a striking effect of DM on the balance between ET and IGF1, and we demonstrate for the first time in humans, that elevated plasma ET is associated with increased O2- generation in the vascular wall through activation of NADPH-oxidase and uncoupling of eNOS. This study shows that ET and its interplay with IGF1 is possibly a key mechanism linking T2DM with its vascular complications in humans

Abstract 015: Increased 20-HETE Levels Contribute to Impaired Glucose Metabolism and Type 2 Diabetes in Cyp4a14 Knockout Mice Fed on High Fat Diet.

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Varunkumar G Pandey ◽  
Lars Bellner ◽  
Victor Garcia ◽  
Joseph Schragenheim ◽  
Andrew Cohen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Weight Gain ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
High Fat ◽  
Plasma Insulin Levels

20-HETE (20-Hydroxyeicosatetraenoic acid) is a cytochrome P450 ω-hydroxylase metabolite of arachidonic acid that promotes endothelial dysfunction, microvascular remodeling and hypertension. Previous studies have shown that urinary 20-HETE levels correlate with BMI and plasma insulin levels. However, there is no direct evidence for the role of 20-HETE in the regulation of glucose metabolism, obesity and type 2 diabetes mellitus. In this study we examined the effect of 20-SOLA (2,5,8,11,14,17-hexaoxanonadecan-19-yl-20-hydroxyeicosa-6(Z),15(Z)-dienoate), a water-soluble 20-HETE antagonist, on blood pressure, weight gain and blood glucose in Cyp4a14 knockout (Cyp4a14-/-) mice fed high-fat diet (HFD). The Cyp4a14-/- male mice exhibit high vascular 20-HETE levels and display 20-HETE-dependent hypertension. There was no difference in weight gain and fasting blood glucose between Cyp4a14-/- and wild type (WT) on regular chow. When subjected to HFD for 15 weeks, a significant increase in weight was observed in Cyp4a14-/- as compared to WT mice (56.5±3.45 vs. 30.2±0.7g, p<0.05). Administration of 20-SOLA (10mg/kg/day in drinking water) significantly attenuated the weight gain (28.7±1.47g, p<0.05) and normalized blood pressure in Cyp4a14-/- mice on HFD (116±0.3 vs. 172.7±4.6mmHg, p<0.05). HFD fed Cyp4a14-/- mice exhibited hyperglycemia as opposed to normal glucose levels in WT on a HFD (154±1.9 vs. 96.3±3.0 mg/dL, p<0.05). 20-SOLA prevented the HFD-induced hyperglycemia in Cyp4a14-/- mice (91±8mg/dL, p<0.05). Plasma insulin levels were markedly high in Cyp4a14-/- mice vs. WT on HFD (2.66±0.7 vs. 0.58±0.18ng/mL, p<0.05); corrected by the treatment with 20-SOLA (0.69±0.09 ng/mL, p<0.05). Importantly, glucose and insulin tolerance tests showed impaired glucose homeostasis and insulin resistance in Cyp4a14-/- mice on HFD; ameliorated by treatment with 20-SOLA. This novel finding that blockade of 20-HETE actions by 20-SOLA prevents HFD-induced obesity and restores glucose homeostasis in Cyp4a14-/- mice suggests that 20-HETE contributes to obesity, hyperglycemia and insulin resistance in HFD induced metabolic disorder. The molecular mechanisms underlying 20-HETE mediated metabolic dysfunction are being currently explored.

scholarly journals Effect of Inulin-Type Carbohydrates on Insulin Resistance in Patients with Type 2 Diabetes and Obesity: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mingyue Rao ◽  
Chenlin Gao ◽  
Ling Xu ◽  
Lan Jiang ◽  
Jianhua Zhu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
The Body ◽  
Obese Patients ◽  
Significant Difference ◽  
Simple Obesity

Background. Insulin resistance (IR) is a physiological condition related to type 2 diabetes mellitus (T2DM) and obesity, which is associated with high blood insulin and glucose. Inulin-type carbohydrate (ITC) is a kind of fermentable fructan that can reduce glucose and ameliorate IR in an animal model, but the effect in clinical trials is controversial. Objective. The authors conducted a systematic literature review to evaluate the effect of ITC supplementation in ameliorating IR in T2DM and obese patients. Methods. Multiple databases were queried for studies before December 25, 2018, which involved supplementation with ITC in ameliorating IR in T2DM and obese patients. Studies that involved meta-analysis of the body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FI), HbA1c, homeostatic model assessment IR (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) of T2DM subjects were included. HOMA-IR and QUICKI were identified as the primary outcomes. A systematic review was performed to evaluate the effect of ITC on IR in obese patients. Results. The database search yielded 25 studies, which met the inclusion criteria; 11 articles were meta-analyzed, and 5 other articles on T2DM and 9 articles on simple obesity were systematically reviewed. Our results did not find ITC supplementation decrease postintervention and reduction data of BMI (P=0.08). However, it can significantly decrease postintervention and reduction data of FPG, FI, HbA1c, and HOMA-IR. Heterogeneity was eliminated by subgroup analysis according to baseline BMI. There was no significant difference in the amelioration of QUICKI between the ITC and control groups. However, the difference was statistically significant and the heterogeneity was eliminated after subgroup analysis according to intakes of ITC. 14 articles for a systematic review found that the results of blood glucose, insulin, and HbA1c were controversial. Only one of the seven studies on simple obesity concluded that ITC intervention significantly ameliorated HOMA-IR, while the other six did not. Conclusion. Supplementation of ITC can ameliorate IR in T2DM, especially in obese T2DM patients, but the effects are controversial in obese patients.

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