Diabetic Autoimmune Markers in Children and Adolescents With  Type 2 Diabetes

Hathout, Eba; Thomas, Wendy; El-Shahawy, Mohamed; Nahab, Fadi; Mace, John

doi:10.1542/peds.107.6.e102

Cited by 133 publications

(104 citation statements)

References 21 publications

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“…In support of these findings, Hathout et al (40) evaluated the prevalence of islet cell antibodies and GAD and insulin AAs at clinical diagnosis of type 2 diabetes in a group of white and Hispanic children and adolescents. They found that none of the Hispanic children with type 2 diabetes exhibited signs of humoral islet cell autoimmunity.…”

Section: Discussionmentioning

confidence: 93%

Islet Cell Autoimmunity in a Triethnic Adult Population of the Third National Health and Nutrition Examination Survey

et al. 2004

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Markers of humoral islet cell autoimmunity, such as autoantibodies (AAs) against the 65-kDa isoform of GAD (GAD65), serve as determinants of risk for autoimmune diabetes. Despite the high prevalence of diabetes in U.S. racial and ethnic minority adult populations, little is known concerning the prevalence of GAD65 AA in these groups. We estimated the prevalence of GAD65 AA in 1,064 diabetic and 1,036 nondiabetic participants who were 40 -90 years of age from the Third National Health and Nutrition Examination Survey (NHANES III), which provides a representative ethnic sample of the U.S. diabetic population. The prevalence of GAD65 AA was higher in diabetic participants compared with nondiabetic participants in non-Hispanic whites (n ‫؍‬ 920; 6.3% vs. 2.0%; P ‫؍‬ 0.001) and non-Hispanic blacks (n ‫؍‬ 534; 3.7% vs. 1.3%; P ‫؍‬ 0.08) but not in Mexican Americans (n ‫؍‬ 646; 1.2% vs. 2.6%; P ‫؍‬ 0.18). Among diabetic non-Hispanic whites and non-Hispanic blacks, being GAD65 AA positive was associated with lower BMI and C-peptide (P < 0.05). These results may reflect the outcome of an autoimmune process leading to ␤-cell destruction/dysfunction in non-Hispanic white and nonHispanic black adult diabetic patients as it occurs in a similar manner in type 1 diabetes. Among diabetic Mexican Americans, the lower prevalence of GAD65 AA suggests a lower frequency of autoimmune-related diabetes.

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Section: Discussionmentioning

confidence: 93%

Islet Cell Autoimmunity in a Triethnic Adult Population of the Third National Health and Nutrition Examination Survey

et al. 2004

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“…Evidence for the coexistence of insulin resistance and insulin deficiency caused by autoimmune ␤-cell destruction was expanded in this population and proven by the performance of insulin-glucose clamps in a subset of subjects (24,25). A recent study from Hathout et al (26) found that among children and adolescents diagnosed with type 2 diabetes, almost 35% had at least one conventional AA. Case reports have also been published describing adolescents who present with features of both type 1 and type 2 diabetes (27).…”

Section: Follow-up Therapymentioning

confidence: 99%

Evidence for Heterogeneous Pathogenesis of Insulin-Treated Diabetes in Black and White Children

Libman

Pietropaolo²,

Arslanian³

et al. 2003

Diabetes Care

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OBJECTIVE -We have previously reported differences in the prevalence of ␤-cell autoantibodies (AAs) in black and white children with insulin-treated diabetes, suggesting that the disease pathogenesis may be more heterogeneous among racial groups than previously thought. To further explore this issue, we compared clinical, biochemical, and autoimmune characteristics at disease diagnosis and follow-up treatment in an expanded number of black and white children with and without the presence of AAs.RESEARCH DESIGN AND METHODS -The study cohort of 130 black children and adolescents, aged Ͻ19 years, diagnosed with diabetes and treated with insulin at time of diagnosis (January 1979 to December 1998) were matched with an equal number of white children by age at onset, sex, and year of diagnosis.RESULTS -The black children had a higher prevalence of obesity (43 vs. 11%) and acanthosis nigricans (21 vs. 1%) than white children and a lower prevalence of AAs. Compared with black children who had AAs, those with no AAs were older and had a higher prevalence of obesity, acanthosis nigricans, and parental diabetes. However, one of four of the black children with AAs was obese and/or had acanthosis nigricans. Among white children, the absence of AAs was not associated with any differences in terms of obesity or acanthosis nigricans compared with those with AAs. Similar to their black counterparts, white children without antibodies were older and had a higher prevalence of parental diabetes. Although treatment with an insulin sensitizer was used, insulin therapy was rarely discontinued on follow-up.CONCLUSIONS -These pediatric subjects, irrespective of autoimmunity, often showed characteristics associated with type 2 diabetes. These characteristics were more frequently displayed in black than in white children. Our data suggest that childhood diabetes may constitute a spectrum of pathogenic mechanisms that may overlap, including those typically associated with both type 1 and type 2 diabetes. This finding could have therapeutic implications. Diabetes Care 26:2876 -2882, 2003I mmune-mediated type 1 diabetes is the most prevalent type of diabetes among children, and until recently only 1-2% of diabetic children were considered to have type 2 diabetes or other rare forms of the disease. However, recent reports have suggested that 8 -45% of children with newly diagnosed diabetes have type 2 diabetes or another nonclassical type of diabetes (1-10). The majority of these children are classified as having type 2 diabetes according to clinical criteria, but increasingly more children are being identified with other types of diabetes. In particular, diagnoses of atypical diabetes and type 1.5 diabetes have been reported, especially in the black population, who seem to be disproportionately represented in this heterogeneous group (11). We and others reported an increase in the incidence of insulin-treated diabetes in black adolescents in the 1990s, based on the results of population-based studies (1-3). This observation raises the questi...

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“…Ö rtqvist et al (63) demonstrated independent correlations between age, sex, and ICA positivity with duration of partial remission. In a study of DAAs in children with clinical diagnosis of type 2 diabetes, all of the children who were ICA positive were on insulin therapy 1 year after diagnosis (64). In addition, in DAA ϩ adult diabetic patients, ICAs predict a decline in C-peptide (R.A. Jensen, L.K.G., C. Tö rn, M. Landin-Olsson, F.A.…”

Section: Do Autoantibodies Predict Clinical Course?mentioning

confidence: 99%

Autoantibodies in Diabetes

et al. 2005

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Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens-GAD65, IA-2, or insulin-signals an autoimmune pathogenesis of ␤-cell killing. A ␤-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to ␤-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitopespecific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally. Diabetes 54 (Suppl. 2):S52-S61, 2005

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Diabetic Autoimmune Markers in Children and Adolescents With Type 2 Diabetes

Cited by 133 publications

References 21 publications

Islet Cell Autoimmunity in a Triethnic Adult Population of the Third National Health and Nutrition Examination Survey

Islet Cell Autoimmunity in a Triethnic Adult Population of the Third National Health and Nutrition Examination Survey

Evidence for Heterogeneous Pathogenesis of Insulin-Treated Diabetes in Black and White Children

Autoantibodies in Diabetes

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