Type 1 Diabetes Antibody Natural History
Type 1 Diabetes Natural History – The clinical presentation of type 1 diabetes is preceded by an asymptomatic period of highly variable duration (5). Aggressive beta-cell destruction may lead to disease manifestation within a few months in infants and young children, whereas in other individuals, the process may continue for years (in some cases, even for >10 years) before the eventual presentation of overt disease.
The appearance of diabetes-associated autoantibodies is the first detectable sign of emerging beta-cell autoimmunity. There are four disease-related autoantibodies that have been shown to predict clinical type 1 diabetes (6). These include classic islet cell antibodies detected by conventional immunofluorescence, insulin autoantibodies (IAAs), and autoantibodies to the 65-kDa isoform of GAD and the tyrosine phosphatase-related IA-2 molecule. The latter three autoantibodies are measured with specific radiobinding assays.
The number of detectable autoantibodies is unequivocally related to the risk of progression to overt type 1 diabetes both in family studies and also in surveys based on general population cohorts.
In family studies, positivity for three to four autoantibodies is associated with a risk of developing clinical type 1 diabetes in the range of 60–100% over the next 5–10 years. Preliminary studies in the general population indicate that the predictive value of multiple autoantibody positivity is approaching that observed among first-degree relatives (7,8).
Several studies have shown that beta-cell autoimmunity may be induced early in life (9,10). [T]he Finnish Diabetes Prediction and Prevention (DIPP) study shows that the first autoantibodies appear already before the age of 3 months and that ∼9% of these children recruited from the general population based on increased HLA DQB1–conferred genetic risk develop persistent positivity for at least one autoantibody by the age of 5 years, whereas close to 4% seroconvert to persistent positivity for multiple (two or more) antibodies by that age (11). These figures demonstrate that a higher proportion of the population develops signs of beta-cell autoimmunity than those progressing to clinical type 1 diabetes. Data from the DIPP study indicate that the spreading of the humoral [non-cellular] autoimmune response from one epitope [antigenic determinant] to another and from one antibody to another occurs in a relatively short window of time (5,12). If such a spreading does not take place within a year after the appearance of the first autoantibodies, it rarely occurs later. These and other observations imply that positivity for a single autoantibody specificity represents in most cases harmless nonprogressive beta-cell autoimmunity, whereas the presence of two or more autoantibodies reflects a progressive process that only rarely reverts (13).
Accordingly, positivity for multiple autoantibodies can be used as a surrogate marker of clinical type 1 diabetes in prospective studies (in young children in particular), since the overwhelming majority of young children with multiple autoantibodies will eventually present with overt diabetes (14).
The new insights into the natural history of type 1 diabetes have accordingly opened up new possibilities and strategies for assessing the role of environmental factors in the development of diabetes.
We think it is important to test for auto-antibodies in order to better assess the current potential for disease progression. Since we have two boys with type 1 diabetes, we get their other siblings tested each year for antibody markers such as GAD 65, IAA and IA-2. This provides us a means by which to determine how adherent to the Roman Diet we will require our non-diabetic children to be. Consult with your doctor to see if antibody testing would be right for you and your other immediate family members. The earlier risk is detected, the better the chances are that lifestyle changes may aid in prevention of disease progression.
Mapping, monitoring and measuring are a continuous cycle when living with diabetes. You begin with a certain course of treatment in mind, which you mapped out with the help of your medical professional. You monitor your progress and measure it against your goals. Upon evaluation, you may find a new course must be corrected to compensate for successes and challenges. Evaluating progress and results of the Health-e-Solutions lifestyle is essential for mastering diabetes in the healthiest way possible. This downloadable, printable e-publication equips you with the key evaluation tools you need, along with some of the research behind them, to determine where you want to go and how to get there. We give you important tools to help you chart your course and stay on track to reach your destination.
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- LaGasse JM, Brantley MS, Leech NJ, Rowe RE, Monks S, Palmer JP, Nepom GT, McCulloch DK, Hagopian WA: Successful prospective prediction of type 1 diabetes in schoolchildren by multiple defined autoantibodies: eight year follow-up of the Washington State Diabetes Prediction Study. Diabetes Care25 :505 –511,2002 Abstract/FREE Full Text
- Ziegler A-G, Hummel M, Schenker M, Bonifacio E: Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes48 :460 –468,1999 Abstract
- Kimpimäki T, Kupila A, Hämäläinen A-M, Kukko M, Kulmala P, Savola K, Simell T, Muona P, Ilonen J, Simell O, Knip M: The first signs of β-cell autoimmunity appear in infancy in genetically susceptible children from the general population: the Finnish Type 1 Diabetes Prediction and Prevention Study. J Clin Endocrinol Metab86 :4782 –4788,2001 Abstract/FREE Full Text
- Kukko M, Kimpimäki T, Korhonen S, Kupila A, Simell S, Veijola R, Simell T, Ilonen J, Simell O, Knip M: Dynamics of diabetes-associated autoantibodies in young children with HLA-conferred risk of type 1 diabetes recruited from the general population. J Clin Endocrinol Metab90 :2712 –2717,2005 Abstract/FREE Full Text
- Kupila A, Muona P, Ronkainen M, Simell T, Erkkilä S, Arvilommi P, Korhonen S, Kimpimäki T, Sjöroos M, Ilonen J, Knip M, Simell O: Genetic risk determines the emergence of diabetes-associated autoantibodies in young children. Diabetes51 :646 –651,2002 Abstract/FREE Full Text
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