GAD-65 autoantibodies and their role as biomarkers of type 1 diabetes and latent autoimmune diabetes in adults (LADA)

Abstract

Summary One of the hallmarks of autoimmune diabetes is the presence of adaptive responses directed to neuroendocrine proteins. One of these proteins is glutamic acid decarboxylase (GAD). While GAD is widely distributed in neuroendocrine tissues, its specific significance in diabetes has paralleled the advances in understanding humoral and cellular immunity in Type 1 diabetes (T1D) and in a subset of Type 2 diabetes (T2D), going from the seminal discoveries of islet autoantibodies to the development and standardization of bioassays as diagnostic tools, to studies on the structure of GAD and its antigenic determinants. GAD65 autoantibodies can accurately predict T1D development in combination with other surrogate humoral biomarkers and they are considered the most sensitive and specific biomarker which identifies a subset of clinically diagnosed T2D termed Latent Autoimmune Diabetes in Adults (LADA). We and others provided evidence indicating that GAD65 autoantibody detection should be part of the diagnostic assessment for clinically diagnosed T2DM mainly because it predicts the rate of progression to insulin requirement in patients affected by LADA. More recently GAD has been used as a “tolerogenic vaccine” to preserve beta cell function in autoimmune diabetes. While the results of Phase III clinical trials did not substantiate the earlier promise of Phase I and II trials, there are still many unanswered questions and approaches that need to be investigated in the applications of GAD in the therapy of T1D and LADA.

Diabetes-Related Autoantibodies in Diabetic Gastroparesis

“…This study supports previous studies that indicate that GADA appears to be a good immunologic antibody for the detection of T1DM [2][3][4][5]. This was the only antibody that was positive in our study.…”

“…Islet autoantibody testing is not routinely performed and is usually reserved to cases that pose a clinical challenge in differentiating between T1DM and T2DM. Others, however, have suggested diabetes-related autoantibody testing as part of the diagnostic assessment for clinically diagnosed & Henry P. Parkman henry.parkman@temple.edu T2DM because it can predict the rate of progression to insulin requirement in patients with LADA [2][3][4][5].…”

Carvedilol can Replace Insulin in the Treatment of Type 2 Diabetes Mellitus

“…Carvedilol acts on the sympathetic nervous system (SNS), which is overstimulated in diabetes mellitus, and the SNS works in tandem with the parasympathetic nervous system (PSNS) [18][19][20].…”

“…Carvedilol works on the kidneys and reduces microalbuminuria and insulin resistance in patients with diabetes mellitus. Inflammatory markers such as interleukin and tumor necrosis factor are affected by the tone of the SNS, which is blocked by carvedilol [18,30].…”

The Prediction of Atherosclerotic Cardiovascular Disease in Type 1 Diabetes Mellitus

“…Not infrequently, type 2 diabetes mellitus results in insulinopenia with inadequate basal insulin secretion (low C-peptide) and the need for insulin therapy, 6 and GAD65-positive autoantibodies alone are less diagnostic for T1D than the presence of 2 to 4 autoantibodies. 7 In addition, an inquiry relates to the reliability of spot versus 24 urine collections to assess the quantity of proteinuria. Although a spot urine is reasonably accurate in the microalbuminuric range, the reliability becomes less when protein excretion is in the higher range 8 ; herein, 5.2% of the cohort had macroalbuminuria.…”