David_S
11-14-2006, 04:03 PM
Yes I saved the articles. We read so much on this before the appt.
Autoimmune type 1 diabetes: resolved and unresolved issues -- Notkins and Lernmark 108 (9): 1247 -- Journal of Clinical Investigation (http://www.jci.org/cgi/content/full/108/9/1247)
from page 4 when printed
Autoantibodies as predictors of type 1 diabetes
Hundreds of studies have now been carried out in laboratories around the world to determine the relationship between autoantibodies to GAD/IA-2/insulin and type 1 diabetes (16, 23-27). Approximately 70–80% of newly diagnosed type 1 diabetes patients have autoantibodies to GAD65. Nearly the same number or slightly less have autoantibodies to IA-2. Overall, fewer patients appear to have insulin autoantibodies, but this is due to a pronounced age effect: children with newly diagnosed type 1 diabetes have a markedly higher frequency of autoantibodies to insulin than teenagers or young adults (23). Some patients carry autoantibodies to only one of the major autoantigens, but others may react to all three. In newly diagnosed subjects, up to 90% have autoantibodies to one or more of these antigens. The percent positivity depends on a variety of factors, including not only the age of the subjects, but also the duration of the disease and, in some cases, their ethnic origins. Some intrinsic variability is also seen in the assay, particularly at the limit of its range of detection. In general, GAD65 autoantibody positivity tends to be stable, whereas IA-2 autoantibodies tend to decrease with duration of disease, and insulin autoantibodies cannot be usefully measured after initiation of insulin therapy. Extensive analyses of these autoantibodies in normal controls suggest that about 1.0% have autoantibodies to IA-2, GAD65, or insulin.
So one could assume up to 10% do not have antibodies... and
and from page 9 when printed
Clinical trials.
The discovery of autoantibodies and their value as predictors of type 1 diabetes is making it possible to identify subjects for clinical intervention trials long before their ß cell reserve is lost. The majority of these ongoing and proposed trials (6, 29, 30) are designed to induce immunological tolerance or to suppress the immune response. These approaches are promising but face obstacles. The fact that there are three major autoantigens in type 1 diabetes makes it difficult to know whether one, two, or all three major autoantigens are needed to induce immunological tolerance. It is also uncertain whether there is a single triggering autoantigen and whether the development of the autoantibodies to secondary autoantigens results from epitope spread or a bystander response (see Wucherpfennig, this Perspective series, ref. 43). Indeed, despite innumerable studies, it is not absolutely clear whether autoimmunity in type 1 diabetes is the cause or the result of the disease process. It remains possible that a still-unrecognized combination of genes or environmental factors triggers the destruction of ß cells and that the autoimmune response is secondary to this process. Also of concern is the fact that 10–20% of newly diagnosed type 1 diabetes patients and an even higher percentage of African and Hispanic patients do not carry autoantibodies to any of the major autoantigens (7). These findings suggest either that the autoantibodies are present in very low titer or that other still-unidentified autoantigens are involved. Alternatively, a fraction of type 1 diabetes may not be autoimmune in nature (44). More precise information about the mechanisms involved in the pathogenesis of human type 1 diabetes is needed for designing effective clinical trials.
AND ALSO: I had low c-peptides.
American Journal of Therapeutics - Abstract: Volume 11(4) July/August 2004 p 308-311 The Role of C-Peptide Levels in Screening for Latent Autoimmune Diabetes in Adults. (http://www.americantherapeutics.com/pt/re/ajt/abstract.00045391-200407000-00011.htm;jsessionid=FhYLBn1qQt646g6NgK2PkG1fR1K0m XqNcPSzBYtnD17XZ4TFpBQ2!-1640309041!-949856145!8091!-1)
The mean C-peptide level in the LADA group was 1.0 +/- 0.2 ng/mL and 5.1 +/- 0.4 ng/mL in the group with type 2 diabetes. Only 1 LADA subject had a C-peptide level above the normal range, and all subjects with type 2 diabetes had a C-peptide level within or above the normal range. LADA can be ruled out in adult-onset diabetes by the presence of elevated C-peptide. The more expensive testing for anti-GAD antibodies to definitively diagnose LADA should be reserved for patients who on screening have a low or normal random C-peptide level.
Autoimmune type 1 diabetes: resolved and unresolved issues -- Notkins and Lernmark 108 (9): 1247 -- Journal of Clinical Investigation (http://www.jci.org/cgi/content/full/108/9/1247)
from page 4 when printed
Autoantibodies as predictors of type 1 diabetes
Hundreds of studies have now been carried out in laboratories around the world to determine the relationship between autoantibodies to GAD/IA-2/insulin and type 1 diabetes (16, 23-27). Approximately 70–80% of newly diagnosed type 1 diabetes patients have autoantibodies to GAD65. Nearly the same number or slightly less have autoantibodies to IA-2. Overall, fewer patients appear to have insulin autoantibodies, but this is due to a pronounced age effect: children with newly diagnosed type 1 diabetes have a markedly higher frequency of autoantibodies to insulin than teenagers or young adults (23). Some patients carry autoantibodies to only one of the major autoantigens, but others may react to all three. In newly diagnosed subjects, up to 90% have autoantibodies to one or more of these antigens. The percent positivity depends on a variety of factors, including not only the age of the subjects, but also the duration of the disease and, in some cases, their ethnic origins. Some intrinsic variability is also seen in the assay, particularly at the limit of its range of detection. In general, GAD65 autoantibody positivity tends to be stable, whereas IA-2 autoantibodies tend to decrease with duration of disease, and insulin autoantibodies cannot be usefully measured after initiation of insulin therapy. Extensive analyses of these autoantibodies in normal controls suggest that about 1.0% have autoantibodies to IA-2, GAD65, or insulin.
So one could assume up to 10% do not have antibodies... and
and from page 9 when printed
Clinical trials.
The discovery of autoantibodies and their value as predictors of type 1 diabetes is making it possible to identify subjects for clinical intervention trials long before their ß cell reserve is lost. The majority of these ongoing and proposed trials (6, 29, 30) are designed to induce immunological tolerance or to suppress the immune response. These approaches are promising but face obstacles. The fact that there are three major autoantigens in type 1 diabetes makes it difficult to know whether one, two, or all three major autoantigens are needed to induce immunological tolerance. It is also uncertain whether there is a single triggering autoantigen and whether the development of the autoantibodies to secondary autoantigens results from epitope spread or a bystander response (see Wucherpfennig, this Perspective series, ref. 43). Indeed, despite innumerable studies, it is not absolutely clear whether autoimmunity in type 1 diabetes is the cause or the result of the disease process. It remains possible that a still-unrecognized combination of genes or environmental factors triggers the destruction of ß cells and that the autoimmune response is secondary to this process. Also of concern is the fact that 10–20% of newly diagnosed type 1 diabetes patients and an even higher percentage of African and Hispanic patients do not carry autoantibodies to any of the major autoantigens (7). These findings suggest either that the autoantibodies are present in very low titer or that other still-unidentified autoantigens are involved. Alternatively, a fraction of type 1 diabetes may not be autoimmune in nature (44). More precise information about the mechanisms involved in the pathogenesis of human type 1 diabetes is needed for designing effective clinical trials.
AND ALSO: I had low c-peptides.
American Journal of Therapeutics - Abstract: Volume 11(4) July/August 2004 p 308-311 The Role of C-Peptide Levels in Screening for Latent Autoimmune Diabetes in Adults. (http://www.americantherapeutics.com/pt/re/ajt/abstract.00045391-200407000-00011.htm;jsessionid=FhYLBn1qQt646g6NgK2PkG1fR1K0m XqNcPSzBYtnD17XZ4TFpBQ2!-1640309041!-949856145!8091!-1)
The mean C-peptide level in the LADA group was 1.0 +/- 0.2 ng/mL and 5.1 +/- 0.4 ng/mL in the group with type 2 diabetes. Only 1 LADA subject had a C-peptide level above the normal range, and all subjects with type 2 diabetes had a C-peptide level within or above the normal range. LADA can be ruled out in adult-onset diabetes by the presence of elevated C-peptide. The more expensive testing for anti-GAD antibodies to definitively diagnose LADA should be reserved for patients who on screening have a low or normal random C-peptide level.