Klotho and SIRT1 changes from pre-diabetes to diabetes and pre-hypertension to hypertension

Abstract Background Hypertension and diabetes are among the most important risk factors of cardiovascular diseases. Klotho and SIRT1 are known as anti-aging factors with beneficial effects on cardiovascular system. In this study we investigated the serum Klotho and SIRT1 levels in pre-diabetic and pre-hypertensive individuals and then in diabetic and hypertensive patients to see their relationship with these diseases. Method 229 individuals divided into six groups with similar gender and age distribution 1—Control (normal BP and FBS) 2—pre-diabetic (FBS between 100 and 125 mg/dl) 3—diabetic (FBS ≥ 126 mg/dl), 4—pre-hypertensive (SBP 120–139 or DBP 80–89 mm Hg) 5—hypertensive (SBP ≥ 140 or DBP ≥ 90 mm Hg), and 6—patients with combined hypertension/diabetes. Serum levels of Klotho and SIRT1 were measured by ELISA method. Results Serum Klotho and STRT1 levels decreased in pre-diabetes and returned to normal in diabetic patients. Their concentration increased in pre-hypertension and recovered to normal in hypertension. In the physiologic range of FBS there is a negative correlation between Klotho and SIRT1 with FBS. When pathologic ranges of FBS added to analysis, the negative correlation abolished/U shaped. Also an inverse U shape correlation observed between Klotho and SIRT1 with MAP in the range of normal to hypertensive BP levels. There was an overall positive relationship between the serum levels of Klotho and SIRT1 themselves. Conclusion The serum levels of the anti-aging proteins Klotho and SIRT1 increases or reduces at the onset of the disease, as a compensatory mechanism, but as the disease progresses their level recovers.

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Non-traditional Risk Factors of Cardiovascular Disease and Coenzyme Q10 Therapy in Hemodialysis Patients

Nephro-Urology Monthly ◽

10.5812/numonthly.107889 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Elham Shahraki ◽

Batool Shahraki ◽

AliReza Dashipour

Keyword(s):

Serum Albumin ◽

Coenzyme Q10 ◽

Antioxidant Properties ◽

Serum Levels ◽

Cardiovascular Complications ◽

Hemodialysis Patients ◽

Diabetic Patients ◽

Beneficial Effects ◽

Significant Difference ◽

Coq10 Supplementation

Background: Inflammatory markers increase in end-stage renal disease (ESRD), especially in diabetic patients, and are positively correlated with cardiovascular mortality. Coenzyme Q10 (CoQ10), an agent with antioxidant properties, may be effective in reducing cardiovascular complications in hemodialysis patients. This study aimed to investigate the effects of CoQ10 supplementation on plasma C-reactive protein (CRP), homocysteine, and albumin in hemodialysis patients. Methods: Forty diabetic ESRD patients on hemodialysis for at least six months were evaluated in a double-blinded randomized clinical trial. The patients were randomly assigned to one of the two groups to receive either CoQ10 100 mg daily or placebo. In all patients, the serum levels of homocysteine, albumin, and CRP were measured before and after six months. Results: The mean age of the patients was 60.3 ± 9.1 years, and 57.5% of the participants were female. There was no statistical difference between the two groups at baseline. Furthermore, no significant difference was observed in serum albumin (P = 0.843), CRP (P = 0.214), and homocysteine (P = 0.21) at the end of the intervention between the groups. Conclusions: This study showed that in patients with ESRD, using CoQ10 supplementation has minimal beneficial effects on serum albumin, CRP, and homocysteine levels.

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SURVEY IN SERUM ADH CONCENTRATION IN TRAUMATIC BRAIN INJURY PATIENTS

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2014.4_5.11 ◽

2014 ◽

pp. 83-89

Author(s):

Dung Ngo ◽

Thi Nhan Nguyen ◽

Khanh Hoang

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Osmotic Pressure ◽

Negative Correlation ◽

Closed Head Injury ◽

Serum Levels ◽

Sodium Concentration ◽

Plasma Sodium ◽

Plasma Sodium Concentration ◽

Closed Head

Objective: Study on 106 patients with closed head injury, assessment of serum ADH concentration, correlation with Glasgow score, sodium and plasma osmotic pressure. Patients and methods: Patients with closed head injuries were diagnosed determined by computerized tomography, admitted to the Hue Central Hospital 72 hours ago. Results: (i) Serum concentration of ADH 42.21 ± 47.80 pg/ml. (ii) There is a negative correlation between serum levels of ADH with: (1) Glasgow point r = -0.323, p <0.01; (2) Plasma sodium concentration r = - 0.211, p > 0.05; (3) Plasma osmotic pressure r = - 0.218, p> 0.05. Conclusion: There is a negative correlation between serum levels of ADH with Glasgow scale, plasma sodium concentration and osmotic pressure in plasma. Key words: ADH traumatic brain injury.

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Negative Correlation Between Serum Levels of Homocysteine and Apolipoprotein M

Current Molecular Medicine ◽

10.2174/1566524019666190308115624 ◽

2019 ◽

Vol 19 (2) ◽

pp. 120-126

Author(s):

J. Wei ◽

Y. Yu ◽

Y. Feng ◽

J. Zhang ◽

Q. Jiang ◽

...

Keyword(s):

Negative Correlation ◽

Hepg2 Cells ◽

Serum Levels ◽

Significant Negative Correlation ◽

Mrna Levels ◽

Rt Pcr ◽

Apolipoprotein M ◽

Protein Mass ◽

Protein Levels ◽

Phosphoinositide 3 Kinase

Background: Homocysteine (Hcy) has been suggested as an independent risk factor for atherosclerosis. Apolipoprotein M (apoM) is a constituent of the HDL particles. The goal of this study was to examine the serum levels of homocysteine and apoM and to determine whether homocysteine influences apoM synthesis. Methods: Serum levels of apoM and Hcy in 17 hyperhomocysteinemia (HHcy) patients and 19 controls were measured and their correlations were analyzed. Different concentrations of homocysteine (Hcy) and LY294002, a specific phosphoinositide 3- kinase (PI3K) inhibitor, were used to treat HepG2 cells. The mRNA levels were determined by RT-PCR and the apoM protein mass was measured by western blot. Results: We found that decreased serum apoM levels corresponded with serum HDL levels in HHcy patients, while the serum apoM levels showed a statistically significant negative correlation with the serum Hcy levels. Moreover, apoM mRNA and protein levels were significantly decreased after the administration of Hcy in HepG2 cells, and this effect could be abolished by addition of LY294002. Conclusions: resent study demonstrates that Hcy downregulates the expression of apoM by mechanisms involving the PI3K signal pathway.

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Role of Inflammatory Markers in Elderly Type 2 Diabetic Patients with Mild Cognitive Impairment

Current Diabetes Reviews ◽

10.2174/1573399814666180423113341 ◽

2019 ◽

Vol 15 (3) ◽

pp. 247-253 ◽

Cited By ~ 2

Author(s):

Salwa S. Hosny ◽

Ahmed M. Bahaaeldin ◽

Mohamed S. Khater ◽

Meram M. Bekhet ◽

Hayam A. Hebah ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Elderly Patients ◽

Vascular Disease ◽

Plasma Glucose ◽

Serum Levels ◽

Diabetic Patients ◽

Hs Crp ◽

And Control

Background: Type 2 diabetes (T2DM) is a risk factor for Alzheimer’s disease and mild cognitive impairment. The etiology of cognitive impairment in people with T2DM is uncertain but, chronic hyperglycemia, cerebral micro vascular disease, severe hypoglycemia, and increased prevalence of macro vascular disease are implicated. Objectives: To determine the serum levels of soluble vascular adhesion molecule (sVCAM-1) and highly sensitive C-reactive protein (hs-CRP) in elderly type 2 diabetics with mild cognitive impairment (MCI). Methods: Our study was conducted on 90 elderly subjects (aged 60 years old or more). They were divided into Group І, 30 patients with T2DM and mild cognitive impairment, group ІІ, 30 patients with T2DM without cognitive impairment and group III, 30 healthy subjects as a control group. They were subjected to history taking, full clinical examination, anthropometric measurement, the Addenbrooke’s Cognitive Examination III (ACE---III 2012), Fasting plasma glucose, 2 hours plasma glucose, HbA1c, lipid profile, protein/creatinine ratio, serum sVCAM-1 and hs-CRP. Results: Serum levels of sVCAM-1 in diabetic elderly patients with MCI were significantly higher (946.7 ± 162.01 ng/ml) than diabetic elderly patients without cognitive impairment (479.06 ± 65.27 ng/ml) and control (263.7 ± 72.05 ng/ml) with (P=0.002). Serum levels of Hs-CRP in diabetic elderly patients with MCI were significantly higher than as diabetic elderly patients without cognitive impairment and control with (P=0.005). Conclusion: Elderly diabetic patients with mild cognitive impairment have higher levels of soluble adhesion molecules and markers of low-grade systemic inflammation than other groups.

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QT Prolongation in Dialysis Patients: An Epidemiological Study with a Focus on Malnutrition

Blood Purification ◽

10.1159/000512961 ◽

2021 ◽

pp. 1-8

Author(s):

Masanori Shibata ◽

Isao Ito ◽

Hisae Tawada ◽

Shinkichi Taniguchi

Keyword(s):

Risk Index ◽

Bioelectrical Impedance ◽

Impedance Analysis ◽

Serum Levels ◽

Qt Prolongation ◽

Fat Free Mass ◽

Nutritional Risk ◽

Diabetic Patients ◽

Qtc Interval ◽

Nutritional Risk Index

Background/Aims: QT prolongation is a known risk factor for ventricular fibrillation and ventricular tachycardia. Therefore, more refined management is necessary to reduce sudden cardiac death secondary to such arrhythmias. Methods: Electrocardiographic findings were reviewed in 224 patients, and the associations of QT prolongation with various clinical parameters were examined, including the nutritional state. Correlations were also examined between QT prolongation and body composition measurements determined by multifrequency bioelectrical impedance analysis. Results: Prolongation of the corrected QT (QTc) interval over 0.44 s was seen in 140 patients (62.5%). QT prolongation was independent of age and dialysis therapy duration and was more frequent in diabetics (70.1%) than in nondiabetics (54.2%, p = 0.014) and more frequent in women (78.8%) than in men (53.5%, p < 0.001). Serum levels of albumin (p < 0.001) and Cr (p < 0.001) and the Geriatric Nutritional Risk Index (GNRI, p < 0.001) were negatively correlated with QTc interval; no significant correlation was noted with total protein, urea nitrogen, or uric acid. Negative correlations with QTc interval were found for BMI(p < 0.01), percent total body water (%TBW; p < 0.05), and percent intracellular water (%ICW; p < 0.01) but not with the percent extracellular water/TBW ratio or edema ratio. The longer the QTc interval, the lower the fat-free mass (FFM; p < 0.01) and muscle mass (MM; p < 0.01), but there was no significant correlation with percent fat. Conclusion: These results suggest that QT prolongation is a common complication and is more frequent in women and diabetic patients. The decreases in serum albumin and Cr levels, GNRI, BMI, %TBW, %ICW, FFM, and MM together coincided with malnutrition and thus suggest a close relationship of QT prolongation with malnutrition. Management of QT prolongation may be achieved better in the future by understanding these biochemical and biophysical changes, particularly those regarding malnutrition.

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FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00542-2 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Dezhong Wang ◽

Yuan Yin ◽

Shuyi Wang ◽

Tianyang Zhao ◽

Fanghua Gong ◽

...

Keyword(s):

Diabetic Cardiomyopathy ◽

Metabolic Regulation ◽

Cardiac Injury ◽

Serum Levels ◽

Ros Generation ◽

Dependent Manner ◽

Cardiac Tissues ◽

Beneficial Effects

AbstractAs a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5’ AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

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Insulin treatment improves liver histopathology and decreases expression of inflammatory and fibrogenic genes in a hyperglycemic, dyslipidemic hamster model of NAFLD

Journal of Translational Medicine ◽

10.1186/s12967-021-02729-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Victoria Svop Jensen ◽

Christian Fledelius ◽

Christina Zachodnik ◽

Jesper Damgaard ◽

Helle Nygaard ◽

...

Keyword(s):

Cell Activation ◽

Insulin Treatment ◽

Stellate Cell ◽

Control Diet ◽

Diabetic Patients ◽

Liver Pathology ◽

Hamster Model ◽

Alcoholic Fatty Liver ◽

Beneficial Effects ◽

Liver Histopathology

Abstract Background Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent comorbidities in patients with Type 2 diabetes. While many of these patients eventually will need treatment with insulin, little is known about the effects of insulin treatment on histopathological parameters and hepatic gene expression in diabetic patients with co-existing NAFLD and NASH. To investigate this further, we evaluated the effects of insulin treatment in NASH diet-fed hamsters with streptozotocin (STZ) -induced hyperglycemia. Methods Forty male Syrian hamsters were randomized into four groups (n = 10/group) receiving either a NASH-inducing (high fat, fructose and cholesterol) or control diet (CTRL) for four weeks, after which they were treated with STZ or sham-injected and from week five treated with either vehicle (CTRL, NASH, NASH-STZ) or human insulin (NASH-STZ-HI) for four weeks by continuous s.c. infusion via osmotic minipumps. Results NASH-STZ hamsters displayed pronounced hyperglycemia, dyslipidemia and more severe liver pathology compared to both CTRL and NASH groups. Insulin treatment attenuated dyslipidemia in NASH-STZ-HI hamsters and liver pathology was considerably improved compared to the NASH-STZ group, with prevention/reversal of hepatic steatosis, hepatic inflammation and stellate cell activation. In addition, expression of inflammatory and fibrotic genes was decreased compared to the NASH-STZ group. Conclusions These results suggest that hyperglycemia is important for development of inflammation and profibrotic processes in the liver, and that insulin administration has beneficial effects on liver pathology and expression of genes related to inflammation and fibrosis in a hyperglycemic, dyslipidemic hamster model of NAFLD.

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Evaluation of serum adropin and irisin levels and its association with anthropometric obesity indices and biochemical parameters in Type 2 diabetic patients

Nutrition and Healthy Aging ◽

10.3233/nha-200110 ◽

2021 ◽

pp. 1-8

Author(s):

Foad Alzoughool ◽

Huda Al Hourani ◽

Manar Atoum ◽

Sajedah Bateineh ◽

Hanan Alsheikh ◽

...

Keyword(s):

Negative Correlation ◽

Biochemical Parameters ◽

Significant Positive Correlation ◽

Glycosylated Hemoglobin ◽

Significant Negative Correlation ◽

Diabetic Patients ◽

Positive Correlation ◽

Obesity Indices ◽

Group Serum

BACKGROUND/AIM: The newly described proteins adropin and irisin are a highly conserved polypeptide that plays essential roles in metabolic and energy homeostasis, insulin resistance, and fat browning. The aim of this study is to evaluate the circulating levels of serum adropin and irisin in type 2 diabetes mellitus (T2DM) patients and also to elucidate possible relationships between serum adropin and irisin levels with anthropometric obesity indices and biochemical parameters. SUBJECTS AND METHODS: Single-center prospective observational study included 90 T2DM patients referred to the diabetes outpatient clinic. Height, weight, and waist circumference (WC) were measured. Body mass index (BMI) and waist to height ratio (WHtR) were calculated. Fasting blood glucose, glycosylated hemoglobin, serum lipids, creatinine, urea, and blood urea nitrogen were evaluated. Estimated glomerular filtration rate (GFR) was calculated, serum adropin and irisin were evaluated. RESULTS: The results showed a significant positive correlation between adropin and irisin in females but not in males (r = 0.311; P = 0.042). In males’ group, serum adropin levels showed significant negative correlation with serum glucose (–0.423, P = < 0.05), HbA1C (–0.364, P = < 0.05), and GFR (–0.355, P = < 0.05). In contrast, creatinine was showed a significant positive correlation with adropin in males (0.381, P = < 0.05). In females’ group, adropin showed a significant negative correlation with weight (–0.371, P = < 0.05), BMI (–0.349, P = < 0.05), WC (–0.402, P = < 0.01), and WHtR (–0.398, P = < 0.01). Contrary, in males’ group, serum irisin levels showed significant positive correlation with weight (0.338, P = < 0.05), BMI (0.332, P = < 0.05), WC (0.409, P = < 0.01), and WHtR (0.432, P = < 0.01). CONCLUSION: This study demonstrated that, in T2DM patients, circulating serum adrpoin correlated negatively with anthropometric obesity indices of obesity in females, while serum irisin was positively correlated with anthropometric obesity indices of obesity in males.

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Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17β-oestradiol

British Journal Of Nutrition ◽

10.1017/s0007114517000344 ◽

2017 ◽

Vol 117 (4) ◽

pp. 479-489 ◽

Cited By ~ 4

Author(s):

Youri Jin ◽

Myoungsook Lee ◽

Yongsoon Park

Keyword(s):

Transcription Factor ◽

Bone Loss ◽

Protective Efficacy ◽

Recovery Period ◽

Serum Levels ◽

Protective Mechanism ◽

Beneficial Effects ◽

Combined Use ◽

Related Transcription Factor ◽

Turnover Markers

AbstractOestrogen and n-3 PUFA, especially EPA and DHA, have been reported to have beneficial effects on bone loss. Thus, the purpose of the present study was to investigate the synergistic bone-protective mechanism of combined treatments of EPA+DHA supplementation and oestrogen injection in ovariectomised rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0 %, 1 % or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and after a 1-week recovery period rats were injected with either 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Combined use of n-3 PUFA and E2 synergistically increased femoral cortical bone volume, bone mineral content and the bone expression of runt-related transcription factor 2 (RUNX2), but decreased the bone expression of IL-1β. Both n-3 PUFA and E2 decreased the bone expressions of IL-7, TNF-α and PPAR-γ, and increased the bone expression of oestrogen receptor-α. n-3 PUFA in the presence of E2 and E2 alone significantly decreased the bone expressions of IL-1β and IL-6 and increased the bone expression of RUNX2. E2 significantly decreased the serum levels of bone turnover markers and the bone expression of receptor activator of NF-κB ligand, but decreased the bone expression of osteoprotegerin. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective efficacy through up-regulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1β.

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Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00543.2007 ◽

2008 ◽

Vol 294 (3) ◽

pp. R811-R818 ◽

Cited By ~ 31

Author(s):

Chao-Hung Wang ◽

Wen-Jin Cherng ◽

Ning-I Yang ◽

Chia-Ming Hsu ◽

Chi-Hsiao Yeh ◽

...

Keyword(s):

Critical Role ◽

Serum Levels ◽

Blood Levels ◽

Short Term ◽

Endothelial Progenitor ◽

Beneficial Effects ◽

Dpp Iv ◽

Before And After ◽

Cell Mobilization

Cyclosporin A (CsA) improves the success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57BL/6 mice were divided into control and CsA-treated groups. Before and after hindlimb ischemia was induced, circulating EPC number and serum levels of different cytokines were measured. Compared with the controls, CsA treatment significantly increased the blood levels of stroma-derived factor-1α and stem cell factor after ischemic stress ( P < 0.001). The CsA group displayed a significant increase in the number of circulating EPCs (sca-1+KDR+ and c-kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the numbers of EPCs incorporated into the Matrigel and ischemic limbs ( P < 0.05). In the peripheral blood, CsA significantly decreased CD26+ cell numbers and attenuated the plasma CD26/DPP IV activity ( P < 0.001). Furthermore, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In summary, CsA manipulates the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.

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