MD Conference Express ADA 2011 - (Page 8)

n F E A T U R E Diabetes: Beyond Just Type 1 and Type 2 Written by Lori Alexander Defining diabetes has become more complex than a simple classification of type 1 and type 2. As more is learned about the pathophysiology of the disease, subtle distinctions have been found, which have implications for diagnosis and treatment. Diabetes that is linked to another disease, or to organ transplantation, may also require a different management strategy. Latent autoimmune diabetes in adults (LADA) and post-transplant diabetes are two types of so-called "special diabetes" that have become more recognized over the past few years, creating challenges both in appropriate diagnosis and treatment. LADA The concept of LADA began in the early 1970s, when a marker of the autoimmune process in type 1 diabetes mellitus (T1DM) was discovered, said Jerry P. Palmer, MD, Seattle VA Puget Sound Health Care System, Seattle, Washington, USA. LADA is phenotypic type 2 diabetes mellitus (T2DM) but with autoantibodies that are characteristic of T1DM. “One cannot distinguish LADA from type 2 diabetes by looking at the patients; measurement of immune markers is required,” said Dr. Palmer. Other characteristics that distinguish LADA from T2DM (antibody-negative) are early failure of sulfonylureas, more rapid decline in endogenous insulin secretion, and earlier need for insulin treatment. Several other names have been given to the disease, including type 1.5 diabetes and antibody-positive T2DM. Patients with LADA test positively for at least one of the four antibodies that are commonly found in T1DM: islet cell autoantibodies (ICAs), autoantibodies to GAD, IA-2, or insulin. ICAs and GAD antibodies are also common in LADA, but both IA-2 and insulin autoantibodies are much less common in LADA than in T1DM. Some patients with phenotypic T2DM have been shown to have negative antibody testing at diagnosis but positive testing later. In contrast, some patients with positive antibodies have negative testing later. The pathophysiology of T2DM may include β-cell autoimmunity, and that autoimmunity may be transient. Dr. Palmer discussed the importance of immune testing within the context of the increasing number of children (aged >18 years) who are being diagnosed with T2DM. In a study of children with new-onset diabetes, a large proportion of those who were diagnosed with T2DM (14 of 19) tested positively for ICAs [Brooks-Worrell BM 8 August 2011 et al. J Clin Endo Metab 2004]. Similarly, autoantibodies were positive in 11 of 16 children in whom the type of diabetes was classified as “indeterminate” at diagnosis. Some studies have indicated that T-cell reactivity to islet antigens may be a better marker for diabetes. Dr. Palmer and colleagues found that the level of glucagon-stimulated C-peptide correlated more strongly with T-cell positivity than with antibody positivity [Goel A et al. Diabetes 2007]. Their data suggested that measuring T-cell responses to multiple islet proteins in patients with phenotypic type 2 diabetes improves the identification of patients with autoimmune diabetes and distinguishes those who have a more severe β-cell lesion compared with antibody assessment only. These findings were confirmed later, with a significantly lower level of glucagon-stimulated C-peptide found among adults with phenotypic T2DM who had negative antibody testing but T-cell positivity (p<0.02; Figure 1) [BrooksWorrell BM et al. Diabetes Care 2011]. This diabetes variant of negative antibodies but T-cell reactivity represents a new classification of diabetes, one that cannot be detected through autoantibody testing alone. Figure 1. Differences in the Level of GlucagonStimulated C-Peptide According to Antibody Testing and T-Cell Reactivity. Glucagon- Stimulated C- peptide 14 12 10 * * * * ng/ml 8 6 4 2 0 Ab-TAb+TAb-T+ Patient category Ab+T+ *p<0.02 Reproduced with permission from J. Palmer, MD. The term LADA is a misnomer, as the diabetes is not latent and can develop in children as well as adults. LADA, as a specific type of diabetes, may be inappropriate, Dr. Palmer added. The distinct separation of T1 and T2DM may need to be reevaluated. Transplantation-Related Diabetes The development of diabetes after organ transplantation is becoming more prevalent due to the increasing number www.mdconferencexpress.com  http://www.mdconferencexpress.com http://www.mdconferencexpress.com

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