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Analysis of serum inflammatory mediators in type 2 diabetic patients and their influence on renal function.

ABSTRACT: AIM:To evaluate the serum concentrations of inflammatory mediators in patients with type 2 diabetes mellitus (T2DM) with or without renal alteration (RA) function. METHODS:Serum samples from 76 patients with T2DM and 24 healthy individuals were selected. Patients with T2DM were divided into two groups according to eGFR (> or < 60mL/min/1.73m2). Cytokines, chemokines and adipokines levels were evaluated using the Multiplex immunoassay and ELISA. RESULTS:TNFR1 and leptin were higher in the T2DM group with RA than in the T2DM group without RA and control group. All patients with T2DM showed increased resistin, IL-8, and MIP-1? compared to the control group. Adiponectin were higher and IL-4 decreased in the T2DM group with RA compared to the control group. eGFR positively correlated with IL-4 and negatively with TNFR1, TNFR2, and leptin in patients with T2DM. In the T2DM group with RA, eGFR was negatively correlated with TNFR1 and resistin. TNFR1 was positively correlated with resistin and leptin, as well as resistin with IL-8 and leptin. CONCLUSION:Increased levels of TNFR1, adipokines, chemokines and decrease of IL-4 play important role in the inflammatory process developed in T2DM and decreased renal function. We also suggest that TNFR1 is a strong predictor of renal dysfunction in patients with T2DM.

SUBMITTER: Araujo LS

PROVIDER: S-EPMC7055870 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Analysis of serum inflammatory mediators in type 2 diabetic patients and their influence on renal function.

Araújo Liliane Silvano LS da Silva Marcos Vinícius MV da Silva Crislaine Aparecida CA Borges Maria de Fátima MF Palhares Heloísa Marcelina da Cunha HMDC Rocha Laura Penna LP Corrêa Rosana Rosa Miranda RRM Rodrigues Júnior Virmondes V Dos Reis Marlene Antônia MA Machado Juliana Reis JR

PloS one 20200304 3

<h4>Aim</h4>To evaluate the serum concentrations of inflammatory mediators in patients with type 2 diabetes mellitus (T2DM) with or without renal alteration (RA) function.<h4>Methods</h4>Serum samples from 76 patients with T2DM and 24 healthy individuals were selected. Patients with T2DM were divided into two groups according to eGFR (> or < 60mL/min/1.73m2). Cytokines, chemokines and adipokines levels were evaluated using the Multiplex immunoassay and ELISA.<h4>Results</h4>TNFR1 and leptin were ...[more]

PMID: 32130282

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Project description:BACKGROUND:Albuminuria is the early manifestation of the pathogenesis of diabetic nephropathy (DN). The current study was to investigate the relationship of pulmonary function with albuminuria in type 2 diabetic patients with preserved renal function to evaluate the role of pulmonary function in the early stage of DN. METHODS:A total of 326 patients with type 2 diabetes mellitus (T2DM) including 270 without albuminuria and 56 with albuminuria, and 265 non-diabetic patients were enrolled. The patients' general information, and the parameters of pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1?s (FEV1), FEV1/FVC, total lung capacity (TLC), diffusion capacity for carbon monoxide of lung (DLCO) were compared between T2DM and control groups, as well as T2DM patients with and without albuminuria groups. All pulmonary function parameters were expressed as a percentage of those predicted (%pred). Logistic regression models were constructed to test the association of albuminuria and pulmonary function. RESULTS:The values of FVC%pred, FEV1%pred, TLC%pred and DLCO%pred were lower, and the proportion of subjects with FVC%pred <?80, FEV1%pred <?80, and DLCOc%pred <?80 was higher in T2DM subjects than controls (all P?<?0.05). Subgroup analysis of diabetic patients showed that the values of FVC%pred, FEV1%pred, TLC%pred, and DLCOc%pred (97.18?±?13.45, 93.95?±?14.51, 90.64?±?9.97, 87.27?±?13.13, respectively) were significantly lower in T2DM subjects with albuminuria than those without albuminuria (103.94?±?14.12, 99.20?±?14.25, 93.79?±?10.36, 92.62?±?13.45, all P?<?0.05). There was a significantly negative correlation between the urine albumin-to-creatinine ratio (UACR) and DLCOc%pred (r =?-?0.143, P =?0.010) in spearman linear correlation test. In logistic regression analysis, the FVC%pred (OR 0.965, 95%CI 0.944-0.988), FEV1%pred (OR 0.975, 95%CI 0.954-0.996), and DLCOc%pred (OR 0.974, 95%CI 0.951-0.998) were independently associated with albuminuria after adjustments for smoking index, duration, HbA1c, FBG, and TG. CONCLUSION:Our results demonstrated albuminuria is associated with a restrictive pulmonary function as well as pulmonary diffusion function in T2DM with preserved renal function, which remind us to be alert of the pulmonary function decline even in the early stage of DN.

Project description:Correlation of vascular endothelial function and coagulation factors with renal function and inflammatory factors in patients with diabetic nephropathy was analyzed. A total of 86 patients diagnosed with diabetes mellitus (DM) and admitted to the 89th Hospital of the People's Liberation Army (Weifang, China) from March 2014 to May 2017 were selected. Among them, 38 patients complicated with nephropathy were divided into the observation group and 48 patients without nephropathy into the control group. The general data of patients were collected, and the relevant biochemical indexes, vascular endothelial function, coagulation factors and renal function indicators and the levels of inflammatory factors were determined. In the observation group, the duration of DM was longer than that in the control group, and the levels of glycated hemoglobin (HbA1c), fasting plasma glucose (FPG) and fasting insulin (FINS), level of fibrinogen (FIB) were higher than those in the control group (p<0.05). Homocysteine (Hcy) and brachial artery blood flow in the observation group were higher than those in the control group. The levels of nitric oxide (NO) and flow-mediated dilation (FMD) were lower than those in the control group (p<0.05). Activated partial thromboplastin time (APTT) in the observation group was shorter than that in the control group (p<0.05). The levels of cystatin-C (Cys-C), serum creatinine (SCr), urea and ?2-microglobulin, levels of C-reactive protein (CRP), tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) in peripheral serum in the observation group were greatly higher than those in the control group (p<0.05). It was concluded via the correlation analysis of vascular endothelial function and coagulation factor with renal function and inflammatory factors that SCr and CRP were negatively correlated with NO, and SCr and CRP were positively correlated with FIB. Serum inflammatory factors, coagulation function and vascular endothelial function are closely related to diabetic nephropathy, which are good reference indexes for the assessment of diabetic nephropathy.

Project description:BackgroundInfection with, and treatment of HIV is associated with effects on glycaemia and renal function. The purpose of this study was therefore to compare glycaemic control and albuminuria in HIV-positive and HIV-negative type 2 diabetic patients.Materials and methodsDiabetic patients with and without HIV infection were recruited from a diabetic clinic at Chris Hani Baragwanath Hospital in Soweto, South Africa. Data was collected on weight, height, HbA1c, fasting glucose, urine albumin:creatinine ratio, HIV status, CD4 counts, viral load and concomitant therapies. Multivariable regression analysis was used to isolate the determinants of fasting glucose and HbA1c levels and risk factors for albuminuria.ResultsData were collected from 106 HIV-positive and 214 HIV-negative diabetics. All HIV infected subjects were receiving anti-retroviral therapy. The determinants of fasting glucose levels (log) were HIV infection (β = 0.04, p = 0.01) and use of anti-hypertensive agents (β = 0.07, p = 0.0006), whilst for HbA1c levels (log) they were HIV infection (β = -0.03, p = 0.03), BMI (β = 0.004, p = 0.0005), statin use (β = 0.04, p = 0.002) and glucose levels (β = 0.01, p<0.0005). In HIV-positive subjects, CD4 counts were negatively associated with glucose levels (β = -0.0002, p = 0.03). The risk factors for albuminuria were (odds ratio [95% CIs]) dyslipidaemia (1.94 [1.09, 3.44], p = 0.02) and HbA1c levels (1.24 [1.12, 1.38], p<0.0001).DiscussionThese data suggest that glycaemic control is worse in type 2 diabetic subjects with HIV infection and that HbA1c underestimates glycaemia in these patients. Albuminuria was not associated with HIV-positivity. The negative relationship of CD4 counts with glucose levels may reflect viral removal and easing of the associated inflammatory response. It is possible that the association of statin and anti-hypertensive therapies with high HbA1c and glucose levels, respectively, is due to such therapies being given largely to subjects with poor glycaemic control.

Project description:Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p=0.027 and p=0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p=0.01) and the decrease correlates with chemokine levels (p=0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations. A total of 65 immune and inflammatory mediators were profiled in serum samples derived from early Lyme disease patients and age- and sex-matched controls. These samples have been generated as part of a prospective cohort study that includes a well-defined cohort of patients with acute Lyme disease enrolled from a Lyme endemic area of the mid-Atlantic United States. Only patients with untreated, confirmed early Lyme disease manifesting an active EM skin lesion at the time of enrollment, as defined by CDC case criteria are eligible. Patients with a history of prior Lyme disease or the presence of confounding preexisting medical conditions associated with prolonged fatigue, pain or neurocognitive symptoms are excluded. Controls are nonhospitalized age- and sex-matched and have no prior history of Lyme disease or any exclusionary medical conditions including lack of inflammatory disorders.

Project description:Diabetic nephropathy (DN) is one of the major complications of diabetes and contributes significantly towards end-stage renal disease. Previous studies have identified the gene encoding carnosinase (CN-1) as a predisposing factor for DN. Despite this fact, the relationship of the level of serum CN-1 and the progression of DN remains uninvestigated. Thus, the proposed study focused on clarifying the relationship among serum CN-1, indicators of renal function and tissue injury, and the progression of DN. A total of 14 patients with minimal changes disease (MCD) and 37 patients with DN were enrolled in the study. Additionally, 20 healthy volunteers were recruited as control. Further, DN patients were classified according to urinary albumin excretion rate into two groups: DN with microalbuminuria (n = 11) and DN with macroalbuminuria (n = 26). Clinical indicators including urinary protein components, serum carnosine concentration, serum CN-1 concentration and activity, and renal biopsy tissue injury indexes were included for analyzation. The serum CN-1 concentration and activity were observed to be the highest, but the serum carnosine concentration was the lowest in DN macroalbuminuria group. Moreover, within DN group, the concentration of serum CN-1 was positively correlated with uric acid (UA, r = 0.376, p = 0.026) and serum creatinine (SCr, r = 0.399, p = 0.018) and negatively correlated with serum albumin (Alb, r = - 0.348, p = 0.041) and estimated glomerular filtration rate (eGRF, r = - 0.432, p = 0.010). Furthermore, the concentration of serum CN-1 was discovered to be positively correlated with indicators including 24-h urinary protein-creatinine ratio (24 h-U-PRO/CRE, r = 0.528, p = 0.001), urinary albumin-to-creatinine ratio (Alb/CRE, r = 0.671, p = 0.000), urinary transferrin (TRF, r = 0.658, p = 0.000), retinol-binding protein (RBP, r = 0.523, p = 0.001), N-acetyl-glycosaminidase (NAG, r = 0.381, p = 0.024), immunoglobulin G (IgG, r = 0.522, p = 0.001), cystatin C (Cys-C, r = 0.539, p = 0.001), beta-2-microglobulin (β2-MG, r = 0.437, p = 0.009), and alpha-1-macroglobulin (α1-MG, r = 0.480, p = 0.004). Besides, in DN with macroalbuminuria group, serum CN-1 also showed a positive correlation with indicators of fibrosis, oxidative stress, and renal tubular injury. Taken together, our data suggested that the level of CN-1 was increased as clinical DN progressed. Thus, the level of serum CN-1 might be an important character during the occurrence and progression of DN. Our study will contribute significantly to future studies focused on dissecting the underlying mechanism of DN.

Dataset Information

Analysis of serum inflammatory mediators in type 2 diabetic patients and their influence on renal function.

Publications

Analysis of serum inflammatory mediators in type 2 diabetic patients and their influence on renal function.

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