|
 |
|
|||||||
|
|||||||||
© 2003 by the American Diabetes Association, Inc.
Letters: Comments and Responses |
Clinical and Genetic Heterogeneity of Latent Autoimmune Diabetes in Adults
Response to Fukui et al.
From the 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary
Address correspondence to Nóra Hosszúfalusi, MD, PhD, Budapest Kútvölgyi út 4. H-1125 Hungary. E-mail: hono{at}kut.sote.hu.
We read with interest the comments of Fukui et al. (1) in this issue of Diabetes Care regarding our recent article (2). They claim that patients with latent autoimmune diabetes in adults (LADA) are heterogeneous in their clinical attributes and that the LADA patients in our study represented the LADA type 1 subgroup. Because of this, we observed that their clinical and genetic characteristics resembled patients having rapidly progressive adult-onset type 1 diabetes. We agree that LADA patients may show heterogeneous clinical features, but we feel that our patients with LADA are representative of the whole LADA group: 25% of our LADA patients belonged to the overweight category based on their BMI, and the same percentage of patients had lipid abnormalities. The median of the insulin-free period after the diagnosis of diabetes was 3.0 years (1.0–6.0), despite the fact that we initiated insulin therapy in 23 of our 54 patients with LADA during the first year after diagnosis. The indication of insulin treatment in these patients was their autoantibody positivity and not their metabolic status. We suspect that LADA type 1 and LADA type 2 subgroups may not represent different clinical entities. Instead we think that a certain proportion of patients with LADA, mainly with aging, develop clinical features of metabolic syndrome beside their autoimmune diabetes.
We agree with Palmer and Hirsch (3) that phenotypically there are at least three separate populations of autoimmune diabetes in adults: adult-onset type 1 diabetes, LADA, and obese phenotypic type 2 diabetes with autoantibody positivity. In the study of Fukui et al. (4) anti–GAD-positive type 2 diabetic patients with secondary failure of sulfonylurea therapy (n = 44, we think that these are the LADA patients) showed an increased prevalence of one of the predisposing alleles, while the anti–GAD-positive and well-controlled type 2 diabetic patients (n = 22, we think that they represent type 2 diabetes with autoantibody positivity) were more likely to have protective alleles and less likely to have predisposing alleles compared with type 1 diabetes showing rapid progression. Notably, the type 1 diabetic group from their study instead represents childhood-onset diabetes (age at onset was 14.5 ± 12.9 years). Another explanation could be the ethnic differences between the Japanese and Hungarian populations.
The unexpected high level of fasting C-peptide at onset in the type 1 diabetic group, (median 0.46 nmol/l [range 0.24–1.05]) was also surprising. However, Mallone et al. (5) also reported a wide range of fasting plasma C-peptide levels in newly diagnosed type 1 diabetes, even with childhood onset (median 0.44 ng/ml [0–5.70]). Since the diagnosis of type 1 diabetes was established according to the World Health Organization criteria, and the decision of prompt insulin therapy was based on the clinical picture (presence of ketonuria or ketoacidosis) in our study, we do not think that another subgroup of type 1 diabetic patients should have been formed on the basis of the fasting C-peptide level. As a result of the comments by Fukui et al., we noticed a regrettable typing error in Table 1 of our report (1): fasting C-peptide in adult-onset type 1 diabetes 1–10 years after onset is 0.40 nmol/l (0.24–0.62) instead of 0.40 nmol/l (0.24–1.05).
We reported that the islet cell antibody (ICA) positivity documented earlier disappeared in six patients having LADA with longer disease course. There was a considerable interval between the positive and the negative ICA tests (6–11 years). The data regarding persistence of ICA in LADA are controversial. In the cited study (6), ICA either persisted (n = 18) or disappeared (n = 9) and anti-GAD antibody persisted (n = 10) in patients having type 2 diabetes with further insulin requirement. Further studies are necessary to evaluate the long-term characteristics of ICA in patients with LADA.
Regarding the classification of autoimmune diabetes, we would divide it into two or three subtypes. One subtype would be the childhood-onset type 1 diabetes (age at onset <20 years), showing the highest prevalence of the predisposing genotypes and the most aggressive ß-cell destruction. Another subtype could be adult-onset type 1 diabetes, which has two forms: rapidly and slowly progressive. The latter should be called LADA without age restriction. The problem of obese phenotypic type 2 diabetes with autoantibody positivity remains unsolved; it needs to be decided whether this group belongs to type 1 or type 2 diabetes, represents a mixture of type 1 and type 2 diabetes, represents a distinct clinical entity, or is merely a laboratory bias.
References
- Fukui M, Kitagawa Y, Nakamura N, Yoshikawa T: Clinical and genetic heterogeneity of latent autoimmune diabetes in adults (Letter). Diabetes Care 26:2223, 2003
[Free Full Text]
- Hosszufalusi N, Vatay A, Rajczy K, Prohaszka Z, Pozsonyi E, Horvath L, Grosz A, Gero L, Madacsy L, Romics L, Karadi I, Fust G, Panczel P: Similar genetic features and different islet cell autoantibody pattern of latent autoimmune diabetes in adults (LADA) compared with adult-onset type 1 diabetes with rapid progression. Diabetes Care 26:452–457, 2003
[Abstract/Free Full Text]
- Palmer JP, Hirsch IR: What’s in a name: latent autoimmune diabetes of adults, type 1.5, adult onset, and type 1 diabetes. Diabetes Care 26:536–538, 2003
[Free Full Text]
- Fukui M, Nakano K, Maruya E, Saji H, Obayashi H, Ohta K, Ohta M, Mori H, Kajiyama S, Wada S, Kida Y, Kosaka K, Deguchi M, Shigeta H, Kitagawa Y, Kondo M: HLA-DRB1 alleles contribute to determining the prognosis of Japanese diabetes mellitus positive for antibodies to glutamate decarboxylase. J Clin Immunol 18:89–92, 1998[Medline]
- Mallone R, Ortolan E, Pinach S, Volante M, Zanone MM, Bruno G, Baj G, Lohmann T, Cavallo-Perin P, Malavasi F: Characterisation in new-onset type 1 diabetes and latent autoimmune diabetes of the adult (LADA) and comparison with other islet autoantibodies. Diabetologia 45:1667–1677, 2002[Medline]
- Kobayashi T, Nakanishi K, Okubo M, Murase T, Kosaka K: GAD antibodies seldom disappear in slowly progressive IDDM (Letter). Diabetes Care 19:1031, 1996
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |