Proteomic Insight Reveals Elevated Levels of Albumin in Circulating Immune Complexes in Diabetic Plasma

Bhat, Shweta; Jagadeeshaprasad, Mashanipalya G.; Patil, Yugendra R.; Shaikh, Mahemud L.; Regin, Bhaskaran; Mohan, Viswanathan; Giri, Ashok P.; Balasubramanyam, Muthuswamy; Boppana, Ramanamurthy; Kulkarni, Mahesh J.

doi:10.1074/mcp.m116.058008

Cited by 17 publications

(17 citation statements)

References 44 publications

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“…These autoantibodies with their antigen form circulating immune complexes which are predominantly cleared [35]. Albumin has been recently shown to be elevated in these complexes isolated from humans with impaired glucose tolerance and T2D [36], and clearance of these complexes would further lower albumin levels. Glycated albumin was not measured in this study, so its role could not be evaluated.…”

Section: Discussionmentioning

confidence: 99%

Reduced plasma albumin predicts type 2 diabetes and is associated with greater adipose tissue macrophage content and activation

Chang

Ferrante

et al. 2019

Diabetol Metab Syndr

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BackgroundPlasma albumin is reduced during inflammation. Obesity, a strong risk factor for type 2 diabetes (T2D), is associated with adipose tissue inflammation. However, whether albumin is associated with adipose tissue inflammation and whether it predicts T2D are unclear.MethodsAdults (predominantly American Indian) from a longitudinal study were included. Macrophage content and gene expression related to recruitment/activation were measured from subcutaneous adipose tissue (n = 51). The relationship between plasma albumin and adiposity (dual-energy X-ray absorptiometry or hydrodensitometry), glucose (oral glucose tolerance test), insulin action (hyperinsulinemic-euglycemic clamp), and insulin secretion (intravenous glucose tolerance test) were evaluated (n = 422). Progression to T2D was evaluated by Cox regression (median follow-up 8.8 years; 102 progressors).ResultsAlbumin was associated with macrophage markers including C1QB (r = − 0.30, p = 0.04), CSF1R (r = − 0.30, p = 0.03), and CD11b (r = − 0.36, p = 0.01). Albumin was inversely associated with body fat percentage (r = − 0.14, p = 0.003), fasting plasma glucose (r = − 0.17, p = 0.0003), and 2 h plasma glucose (r = − 0.11, p = 0.03), and was reduced in impaired glucose regulation compared with normal glucose regulation (mean ± SD: 39.4 ± 3.6 g/l and 40.1 ± 3.9 g/l, respectively; p = 0.049). Albumin predicted T2D, even after adjustment for confounders (HR, 0.75; 95% CI 0.58–0.96; p = 0.02; per one SD difference in albumin).ConclusionsReduced albumin is associated with an unfavorable metabolic profile, characterized by increased adipose tissue inflammation, adiposity, and glucose, and with an increased risk for T2D.

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Section: Discussionmentioning

confidence: 99%

Reduced plasma albumin predicts type 2 diabetes and is associated with greater adipose tissue macrophage content and activation

Chang

Ferrante

et al. 2019

Diabetol Metab Syndr

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“…Serum and plasma have become the most widely used sample for diabetic biomarker studies212223. Depletion of serum prior to proteomic analysis by immunoaffinity subtraction of specific proteins through the use of targeted polyclonal antibody columns and spin filters has recently emerged as a promising tool for serum prefractionation19.…”

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confidence: 99%

2D-DIGE as a strategy to identify serum biomarkers in Mexican patients with Type-2 diabetes with different body mass index

Gómez-Cardona

Hernández-Domínguez

Velarde‐Salcedo

et al. 2017

Sci Rep

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Obesity and type 2 diabetes(T2D) are the most prevalent and serious metabolic diseases affecting people worldwide. However racial and ethnic disparities seems to be a risk factor for their development. Mexico has been named as one of the largest populations with the highest prevalence of diabetes and obesity. The aim of this study was to identify novel T2D-associated proteins in Mexican patients. Blood samples were collected from 62 Mexican patients with T2D and they were grouped according to their body mass index(BMI). A panel of 10 diabetes and obesity serum markers was determined using MAGPIX. A comparative proteomics study was performed using two-dimensional difference in-gel electrophoresis(2D-DIGE) followed by mass spectrometry(LC-MS/MS). We detected 113 spots differentially accumulated, in which 64 unique proteins were identified, proteins that were involved in metabolism pathways, molecular transport, and cellular signalling. Four proteins(14-3-3, ApoH, ZAG, and OTO3) showing diabetes-related variation and also changes in relation to obesity were selected for further validation by western blotting. Our results reveal new diabetes related proteins present in the Mexican population. These could provide additional insight into the understanding of diabetes development in Mexican population and may also be useful candidate biomarkers.

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“…Proteins with advanced glycation are known to form immune complexes with immunoglobulin (IgG), as demonstrated by elevated levels of glycated serum albumin in circulating immune complexes in diabetic plasma and the formation of immune complexes between AGE‐modified low‐density lipoprotein and IgG . These immune complexes elicit immune responses and release pro‐inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Glycated Plasma Proteins as More Sensitive Markers for Glycemic Control in Type 1 Diabetes

Zhang

2020

Proteomics Clinical Apps

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Purpose Glycated hemoglobin (HbA1c) is used clinically for diagnosis and therapeutic management of diabetes. However, HbA1c reflects average blood glucose level over a long period. The aim of this study is to look for short period, more sensitive protein markers that correlate better with glycemic level. Experimental Design The glycated proteome of human plasma from type 1 diabetic individuals with good and poor (n = 20 each) glycemic control are analyzed using an online two‐dimensional proteomics approach. Selected glycated peptides are further validated for their potential as candidate biomarkers using parallel reaction monitoring. Results 305 glycated peptides are quantified and 290 are significantly increased in samples with poor glycemic control. 76 of the 88 selected glycated peptides have receiver operating characteristic area under curve (AUC) values greater than 0.8. Six validated glycated peptides with high AUC show high correlation with HbA1c and have higher fold changes between poor and good glycemic control than HbA1c. The parent proteins have half‐lives shorter than HbA1c. Conclusions and Clinical Relevance Using an advanced proteomics platform for protein glycation analysis, glycated peptides and proteins are identified that are promising as more sensitive, shorter term indicators of glycemic control in diabetic patients than the commonly used HbA1c.

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Proteomic Insight Reveals Elevated Levels of Albumin in Circulating Immune Complexes in Diabetic Plasma

Cited by 17 publications

References 44 publications

Reduced plasma albumin predicts type 2 diabetes and is associated with greater adipose tissue macrophage content and activation

Reduced plasma albumin predicts type 2 diabetes and is associated with greater adipose tissue macrophage content and activation

2D-DIGE as a strategy to identify serum biomarkers in Mexican patients with Type-2 diabetes with different body mass index

Glycated Plasma Proteins as More Sensitive Markers for Glycemic Control in Type 1 Diabetes

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