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Elevated Serum Levels of Soluble TNF Receptors and Adhesion Molecules Are Associated with Diabetic Retinopathy in Patients with Type-1 Diabetes.

Sharma S, Purohit S, Sharma A, Hopkins D, Steed L, Bode B, Anderson SW, Caldwell R, She JX - Mediators Inflamm. (2015)

Bottom Line: The levels of sTNFR-I, sTNFR-II, CRP, SAA, sgp130, sIL6R, sVCAM1, and sICAM1 were significantly higher in the T1D patients with DR as compared to T1D patients with no complications.The circulating markers of inflammation, endothelial injury, and TNF signaling are significantly associated with DR in patients with T1D.TNFR-I and TNFR-II receptors are highly correlated, but DR associated more strongly with TNFR-I in these patients.

View Article: PubMed Central - PubMed

Affiliation: Center for Biotechnology and Genomic Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.

ABSTRACT

Aims: To examine the association of the serum levels of TNF receptors, adhesion molecules, and inflammatory mediators with diabetic retinopathy (DR) in T1D patients.

Methods: Using the multiplex immunoassay, we measured serum levels of eight proteins in 678 T1D subjects aged 20-75 years. Comparisons were made between 482 T1D patients with no complications and 196 T1D patients with DR.

Results: The levels of sTNFR-I, sTNFR-II, CRP, SAA, sgp130, sIL6R, sVCAM1, and sICAM1 were significantly higher in the T1D patients with DR as compared to T1D patients with no complications. Multivariate logistic regression analysis revealed significant association for five proteins after adjustment for age, sex, and disease duration (sTNFR-I: OR = 1.57, sgp130: OR = 1.43, sVCAM1: OR = 1.27, sICAM1: OR = 1.42, and CRP: OR = 1.15). Conditional logistic regression on matched paired data revealed that subjects in the top quartile for sTNFR-I (OR = 2.13), sTNFR-II (OR = 1.66), sgp130 (OR = 1.82), sIL6R (OR = 1.75), sVCAM1 (OR = 1.98), sICAM1 (OR = 2.23), CRP (OR = 2.40) and SAA (OR = 2.03), had the highest odds of having DR.

Conclusions: The circulating markers of inflammation, endothelial injury, and TNF signaling are significantly associated with DR in patients with T1D. TNFR-I and TNFR-II receptors are highly correlated, but DR associated more strongly with TNFR-I in these patients.

No MeSH data available.


Related in: MedlinePlus

Strong association of increasing protein levels with DR. Conditional logistic regression was performed on matched paired data using cases (T1D with DR) and controls (T1D without complication) matched for age, sex, and T1D duration (183 pairs). Subjects were divided into four quartiles based on individual protein levels. The odds ratios and 95% confidence intervals (CI) were computed for each protein using lowest quartile as referent. Compared with subjects in the bottom quartile, subjects in the top quartile had the highest risk of DR for all eight proteins. Also, an increased trend in the risk for DR was observed from quartile-2 to quartile-4 of protein concentrations.
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fig3: Strong association of increasing protein levels with DR. Conditional logistic regression was performed on matched paired data using cases (T1D with DR) and controls (T1D without complication) matched for age, sex, and T1D duration (183 pairs). Subjects were divided into four quartiles based on individual protein levels. The odds ratios and 95% confidence intervals (CI) were computed for each protein using lowest quartile as referent. Compared with subjects in the bottom quartile, subjects in the top quartile had the highest risk of DR for all eight proteins. Also, an increased trend in the risk for DR was observed from quartile-2 to quartile-4 of protein concentrations.

Mentions: Since there was a significant effect of age, sex, and T1D duration on the protein concentrations, a paired dataset of 183 matched pairs was generated using multivariate and propensity score matching software [14]. Matching was performed with respect to age, sex, and duration of diabetes and each T1D patient with DR was paired with closest T1D patient without complication. The demographic information and baseline characteristics of the samples after matching are presented in Table 3. Conditional logistic regression was performed to estimate the risk of DR at different protein concentrations. Protein levels were used as categorical variable after dividing into 4 quartiles. The odds ratios of having DR were computed for quartile-2, quartile-3, and quartile-4 using quartile-1 as reference. Subjects in the top quartile had the highest risk of DR compared with subjects in the bottom quartile for all eight proteins: sTNFR-I (OR = 2.13), sTNFR-II (OR = 1.66), CRP (OR = 2.40), SAA (OR = 2.03), sgp130 (OR = 1.83), sIL6R (OR = 1.75), sVCAM1 (OR = 1.98), and sICAM1 (OR = 2.23). Also, for all proteins, an increased trend in the risk for DR was observed from quartile-2 to quartile-4 of protein concentrations as shown in Figure 3.


Elevated Serum Levels of Soluble TNF Receptors and Adhesion Molecules Are Associated with Diabetic Retinopathy in Patients with Type-1 Diabetes.

Sharma S, Purohit S, Sharma A, Hopkins D, Steed L, Bode B, Anderson SW, Caldwell R, She JX - Mediators Inflamm. (2015)

Strong association of increasing protein levels with DR. Conditional logistic regression was performed on matched paired data using cases (T1D with DR) and controls (T1D without complication) matched for age, sex, and T1D duration (183 pairs). Subjects were divided into four quartiles based on individual protein levels. The odds ratios and 95% confidence intervals (CI) were computed for each protein using lowest quartile as referent. Compared with subjects in the bottom quartile, subjects in the top quartile had the highest risk of DR for all eight proteins. Also, an increased trend in the risk for DR was observed from quartile-2 to quartile-4 of protein concentrations.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539119&req=5

fig3: Strong association of increasing protein levels with DR. Conditional logistic regression was performed on matched paired data using cases (T1D with DR) and controls (T1D without complication) matched for age, sex, and T1D duration (183 pairs). Subjects were divided into four quartiles based on individual protein levels. The odds ratios and 95% confidence intervals (CI) were computed for each protein using lowest quartile as referent. Compared with subjects in the bottom quartile, subjects in the top quartile had the highest risk of DR for all eight proteins. Also, an increased trend in the risk for DR was observed from quartile-2 to quartile-4 of protein concentrations.
Mentions: Since there was a significant effect of age, sex, and T1D duration on the protein concentrations, a paired dataset of 183 matched pairs was generated using multivariate and propensity score matching software [14]. Matching was performed with respect to age, sex, and duration of diabetes and each T1D patient with DR was paired with closest T1D patient without complication. The demographic information and baseline characteristics of the samples after matching are presented in Table 3. Conditional logistic regression was performed to estimate the risk of DR at different protein concentrations. Protein levels were used as categorical variable after dividing into 4 quartiles. The odds ratios of having DR were computed for quartile-2, quartile-3, and quartile-4 using quartile-1 as reference. Subjects in the top quartile had the highest risk of DR compared with subjects in the bottom quartile for all eight proteins: sTNFR-I (OR = 2.13), sTNFR-II (OR = 1.66), CRP (OR = 2.40), SAA (OR = 2.03), sgp130 (OR = 1.83), sIL6R (OR = 1.75), sVCAM1 (OR = 1.98), and sICAM1 (OR = 2.23). Also, for all proteins, an increased trend in the risk for DR was observed from quartile-2 to quartile-4 of protein concentrations as shown in Figure 3.

Bottom Line: The levels of sTNFR-I, sTNFR-II, CRP, SAA, sgp130, sIL6R, sVCAM1, and sICAM1 were significantly higher in the T1D patients with DR as compared to T1D patients with no complications.The circulating markers of inflammation, endothelial injury, and TNF signaling are significantly associated with DR in patients with T1D.TNFR-I and TNFR-II receptors are highly correlated, but DR associated more strongly with TNFR-I in these patients.

View Article: PubMed Central - PubMed

Affiliation: Center for Biotechnology and Genomic Medicine, Georgia Regents University, 1120 15th Street, Augusta, GA 30912, USA.

ABSTRACT

Aims: To examine the association of the serum levels of TNF receptors, adhesion molecules, and inflammatory mediators with diabetic retinopathy (DR) in T1D patients.

Methods: Using the multiplex immunoassay, we measured serum levels of eight proteins in 678 T1D subjects aged 20-75 years. Comparisons were made between 482 T1D patients with no complications and 196 T1D patients with DR.

Results: The levels of sTNFR-I, sTNFR-II, CRP, SAA, sgp130, sIL6R, sVCAM1, and sICAM1 were significantly higher in the T1D patients with DR as compared to T1D patients with no complications. Multivariate logistic regression analysis revealed significant association for five proteins after adjustment for age, sex, and disease duration (sTNFR-I: OR = 1.57, sgp130: OR = 1.43, sVCAM1: OR = 1.27, sICAM1: OR = 1.42, and CRP: OR = 1.15). Conditional logistic regression on matched paired data revealed that subjects in the top quartile for sTNFR-I (OR = 2.13), sTNFR-II (OR = 1.66), sgp130 (OR = 1.82), sIL6R (OR = 1.75), sVCAM1 (OR = 1.98), sICAM1 (OR = 2.23), CRP (OR = 2.40) and SAA (OR = 2.03), had the highest odds of having DR.

Conclusions: The circulating markers of inflammation, endothelial injury, and TNF signaling are significantly associated with DR in patients with T1D. TNFR-I and TNFR-II receptors are highly correlated, but DR associated more strongly with TNFR-I in these patients.

No MeSH data available.


Related in: MedlinePlus