Alpha₂-Macroglobulin and Proliferative Retinopathy in Type 1 Diabetes

Abstract

Serum alpha 2-macroglobulin (alpha 2m) and total glycosylated haemoglobin (HbA1) concentrations were measured in 110 insulin dependent Type 1 diabetics with minimal or no fundoscopic retinopathy, referred to as non-retinopaths, and in 52 proliferative retinopaths. Proteinuria was recorded in 8 (7%) non-retinopaths and 29 (56%) retinopaths and was accompanied by elevated alpha 2m concentrations in both groups of diabetics but only significantly so in the non-retinopaths. Diabetics without proteinuria showed a significant correlation between alpha 2m concentration and duration of diabetes, HbA1 and age (being higher at extremes of age). Alpha 2m concentrations were significantly higher in retinopaths than in non-retinopaths without proteinuria when allowance was made for the influence of age and duration of diabetes on alpha 2m. This difference may be attributed to the higher HbA, levels found in retinopaths than in non-retinopaths and was no longer evident when account was taken of the prevailing HbA1 concentration in individual patients.

Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease

“…In patients with NAFLD we previously demonstrated a very significant association between A2M and insulin levels, a hallmark of insulin resistance [25]. Other studies have observed an increase of A2M in diabetic patients [41]. Insulin is covalently bound to A2M [42] in plasma and A2M is a binding protein of Insulin-like Growth Factor Binding Protein-1 (IGFBP-1) which modifies the IGFBP-1/IGF interaction [43].…”

Reference distributions for alpha2‐macroglobulin: A practical, simple and clinically relevant approach in a large cohort

“…It has been observed that induced hyperglycemia in normal nondiabetic persons results in increased serum concentrations of a 2 M (14). Furthermore, evidence is mounting that elevated a 2 M levels are seen in diabetics with increased risk of microangiopathic complication, retinopathy, and nephropathy (58)(59)(60)(61). An interesting observation has been made suggesting that patients with prostate cancer and bone metastases had extremely low levels of a 2 M (62-64).…”

Vitreous Fibronectin and Fibrinogen Expression Increased in Eyes With Proliferative Diabetic Retinopathy After Intravitreal Anti-VEGF Therapy

“…Of note, we found increased expression of several proteins, including a2-macroglobulin, vitamin D-binding protein, and prostaglandin-H2 Disomerase, which have been proposed as biomarkers for diabetes mellitus. [22][23][24][25][26][27] In recent years, there has been accumulating evidence showing that IVI increases the risk of TRD in patients with severe PVR. 9,[14][15][16][17][18] However, the molecular mechanism underlying the profibrotic effects of anti-VEGF drugs is not fully understood.…”

“…We also found differential expression in a2-macroglobulin, vitamin D-binding protein, and prostaglandin-H2 D-isomerase, which were previously referred to as biomarkers for diabetes mellitus. [22][23][24][25][26][27] In addition, the proteins ceruloplasmin, a-synuclein, flavin reductase, glutathione peroxidase-3, catalase, and peroxiredoxin-2 were differentially expressed among the three groups. The signal intensities for the differentially expressed proteins are shown in Supplementary Table S3.…”