Association of elevated extracellular HSP72 in albuminuria with systemic inflammation and disease progression in type 2 diabetic kidney disease.

BACKGROUND: Sub-clinical inflammation in hyperglycemia is tied to the pathogenesis of diabetic kidney disease (DKD). Though well known for its immunostimulatory function, the significance of extracellular heat shock protein 72 (eHSP72) in DKD is not well studied. We aimed to determine the association of extracellular HSP72 with systemic inflammation and the progression of DKD, and explore its possible clinical significance in DKD. METHODS: 160 type 2 diabetic individuals were enrolled in the study. Their anthropometric data, routine biochemical parameters, urinary renal function parameters, and blood count parameters were estimated. Plasma from patients' blood samples were used to estimate HSP72 and interleukin 1ß (IL-1ß) using sandwich immunoassays. RESULTS: Plasma eHSP72 is elevated in DKD. Pairwise comparisons showed the drastic elevation of eHSP72 in the presence of albuminuria. A significant positive relationship was observed between plasma levels of eHSP72 and IL-1ß. eHSP72 levels did not statistically differ between micro and macro-albuminuric DKD. However, it was inversely associated with estimated glomerular filtration rate, the index of disease severity, independent of age, gender, diabetes duration and absolute monocyte count. At a cutoff of 0.52 ng/ml, with sensitivity of 64.1 % and specificity of 69.2 %, plasma eHSP72 differentiated the presence of DKD in type 2 diabetics with statistical significance. CONCLUSION: The positive relationship of eHSP72 and IL-1ß with worsening DKD likely indicates their participation in immunostimulatory pathways of renal fibrosis. eHSP72 may be closely linked to albuminuria-induced tubular injury and likely contributes to fibrotic changes in the progression of DKD. From our study, we infer the possible clinical significance of eHSP72 as a marker of sub-clinical renal damage in DKD, and the implication of IL-1ß-associated mechanisms in DKD progression.

Circulating 18-Glycosyl Hydrolase Protein Chitiotriosidase-1 is Associated with Renal Dysfunction and Systemic Inflammation in Diabetic Kidney Disease.

Introduction: Chitotriosidase-1 (CHIT-1) is a marker of macrophage activation and recently attributed to type 2 diabetes mellitus (T2DM). However, its role in the development and progression of diabetic kidney disease (DKD) has been sparsely discussed in the recent literature. Materials and Methods: In this cross-sectional exploratory study, 81 participants with T2DM were classified into two groups based on the presence of DKD. Their anthropometric, biochemical, and pathological profiles were estimated. Circulatory CHIT-1 concentration was determined using the enzyme-linked immuno-sorbent assay (ELISA) in plasma. Results: CHIT-1 was significantly elevated in diabetic nephropathy, independent of age and gender. It is associated with severity of kidney disease, as assessed using urinary protein-creatinine ratio (uPCR) in a multiple linear regression model, independent of age, gender, diabetes duration, and insulin resistance. CHIT-1 positively predicted the likelihood of DKD in the study population (area under the curve = 0.724, P < 0.05). The duration of diabetes correlated positively with uPCR and negatively with estimated glomerular-filtration rate. Neutrophil-Lymphocyte ratio was elevated in participants with DKD. This well-established marker of systemic inflammation exhibited significant positive association with CHIT-1. Conclusion: Plasma CHIT-1 protein is elevated in DKD and associated with disease progression. It is capable of reflecting disease severity and is closely related to systemic inflammation possibly caused by pro-inflammatory circulatory immune cells.

Association of serum omentin-1, apelin and chemerin concentrations with the presence and severity of diabetic retinopathy in type 2 diabetes mellitus patients.

Omentin-1 is a novel adipokine with anti-inflammatory functions. Apelin is associated with hyperinsulinemia and pathological angiogenesis. Chemerin has both pro- and anti-inflammatory actions and implicated in insulin resistance and metabolic syndrome. The aim of this study was to assess serum omentin-1, apelin and chemerin concentrations and to investigate their association with the presence and severity of DR in T2DM patients. Serum omentin-1, apelin and chemerin were measured in 112 patients with DR and 56 patients without DR. Bivariate analysis showed omentin-1 correlated negatively with hsCRP and TyG index; while apelin correlated positively with chemerin. Linear regression data showed that apelin and chemerin were independent predictors of DR severity. ROC curve revealed that omentin-1 was the best discriminant for DR while apelin was the best discriminant for vision threatening retinopathy. Serum omentin-1 concentration correlates negatively, while serum apelin and chemerin concentrations correlate positively with DR presence and severity in T2DM patients.

Circulating adropin and vascular endothelial growth factor receptor-2 levels in age-related macular degeneration and T2DM patients-A cross-sectional study.

BACKGROUND: Macular drusen formation and angiogenesis are the two chief processes associated with age-related macular degeneration. Adropin and vascular endothelial growth factor receptor-2 (VEGFR-2) may be involved in these pathologies. By altering lipid metabolism, adropin may contribute in the early stages of age-related macular degeneration (AMD). VEGFR-2 may participate in the later form of AMD, by promoting angiogenesis. This study compared the circulatory levels of adropin and VEGFR-2 in AMD and patients without AMD and assessed their association with disease severity, to understand their possible role in AMD. OBJECTIVES: This study aimed to assess and compare the serum levels of adropin and VEGFR-2 in patients with AMD and type 2 diabetes patients without AMD, and, to investigate the correlation between these two parameters with disease severity. METHODS: Our study involves two groups of 39 each. Group A (age-related macular degeneration) and Group B (diabetes patients without age-related macular degeneration). Routine parameters fasting blood sugar (FBS), lipid profile, and liver function tests (LFT) were estimated by using autoanalyzer. Serum adropin and VEGFR-2 were assessed by ELISA. RESULTS: Among the basic parameters, systolic blood pressure and fasting blood glucose alone were significantly different across the groups. We did not find significant alterations in adropin and VEGFR-2 levels between the study groups. Our lipid profile parameters (triglycerides and total cholesterol) have significant positive association. VEGFR-2 showed a positive correlation with the severity of AMD. Adropin did not exhibit any correlation with disease severity and with VEGFR-2. CONCLUSION: We could not find any observable alterations of statistical significance, in adropin and VEGFR-2 levels. VEGFR-2's correlation with disease severity could be important. Adropin might have subtler roles in AMD, though not evident from our study, and requires a deeper observation at the molecular level to elucidate its function.

Circulating matrix modulators (MMP-9 and TIMP-1) and their association with severity of diabetic retinopathy.

AIMS: Diabetic Retinopathy (DR) is the leading cause of vision loss in the working age population. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1), are molecules involved in extracellular tissue matrix remodelling. They are implicated in the loss of retinal tissue integrity, a major cause of DR, that leads to retinal tissue degradation and apoptosis. This study is therefore, conducted to compare the serum levels of MMP-9 and TIMP-1 in T2DM patients without and with retinopathy, and to evaluate their association with the severity of DR. MATERIALS AND METHODS: Our study comprised of 2 groups of 41 each. Group A (cases) included T2DM patients with retinopathy and Group B (controls) included T2DM patients without retinopathy. Routine parameters, mainly, fasting blood glucose, and lipid profile were measured using autoanalyzer. Serum MMP-9, TIMP-1, and insulin levels were assessed using ELISA method. RESULTS AND CONCLUSION: Statistically significant increase in the levels of MMP-9, insulin, fasting blood glucose and lipid profile were observed in the serum of T2DM patients with retinopathy, as compared with those without retinopathy. These results help to conclude that rise in MMP-9, and associated serum markers promote disease progress in DR. These findings suggest that the elevations of our study markers in the serum of the type 2 diabetic patients with retinopathy, as compared to those without retinopathy, play important roles in aggravating tissue matrix degradation, supporting DR disease progression.