RESUMEN
AIMS: We investigated the prevalence of diabetes autoantibodies (Abs) in Cameroonian patients and controls, assessed their contribution in disease classification and compared results with data from Belgium. METHODS: Abs against GAD (GADA), IA-2 (IA-2A) and zinc transporter 8 (ZnT8A) were assessed in 302 recently diagnosed Cameroonian patients with diabetes and 184 control subjects without diabetes aged below 40 years. RESULTS: Only 27 (9%) Cameroonian patients were younger than 15 years. Overall, 29% of patients presented at least one diabetes-associated antibody vs 9% in healthy controls (24% vs 7% for GADA (p<0.001), 10% vs 3% for IA-2A (p<0.006), 4% vs 2% for ZnT8A). Ab(+) patients had lower C-peptide levels (p<0.001), were more often insulin-treated (p<0.002) and were as frequently diagnosed with type 1 diabetes as Ab(-) patients. Only 43% of Ab(+) patients aged 15-39 years were clinically classified as having type 1 diabetes in Cameroon vs 96% in Belgium (p<0.001). Not one Ab(+) Cameroonian patient carried HLA-DQ2/DQ8 genotype vs 23% of Belgian Ab(+) patients (p<0.001). Younger age at diagnosis and antibody positivity were independent predictors of insulin therapy. Ab(+) Cameroonian patients were older (p<0.001), had higher BMI (p<0.001) and lower Ab titers than Belgian Ab(+) patients. In ketonuric patients, prevalence of autoantibodies was similar as in non-ketonuric patients. CONCLUSIONS: In Cameroonian patients with diabetes aged under 40 years, antibody-positivity is not clearly related to disease phenotype, but may help predict the need for insulin treatment.
Asunto(s)
Autoanticuerpos/sangre , Biomarcadores/sangre , Proteínas de Transporte de Catión/inmunología , Diabetes Mellitus Tipo 1/inmunología , Glutamato Descarboxilasa/inmunología , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/inmunología , Adolescente , Adulto , Bélgica/epidemiología , Camerún/epidemiología , Estudios de Casos y Controles , Niño , Preescolar , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Prevalencia , Adulto Joven , Transportador 8 de ZincRESUMEN
OBJECTIVE: We investigated whether measuring autoantibodies against zinc transporter 8 (ZnT8A) and IA-2ß (IA-2ßA) may improve classification of new-onset type 1 diabetic patients based on detection of autoantibodies against insulin (IAA), GAD (GADA), and IA-2 (IA-2A). In addition, we studied the correlation of IA-2ßA and ZnT8A with other biological and demographic variables. RESEARCH DESIGN AND METHODS: Circulating autoantibodies were determined by liquid-phase radiobinding assays from 761 healthy control subjects and 655 new-onset (<1 week insulin) diabetic patients (aged 0-39 years) with clinical type 1 diabetes phenotype consecutively recruited by the Belgian Diabetes Registry. RESULTS: At diagnosis, IA-2ßA and ZnT8A prevalences were 41 and 58%, respectively. In IAA-negative, GADA-negative, and IA-2A-negative patients, one IA-2ßA-positive and eleven ZnT8A-positive individuals were identified at the expense of eight and seven additional positive control subjects (1%), respectively, for each test. ZnT8A or IA-2ßA screening increased (P < 0.001; McNemar) the number of patients with ≥2 antibodies both under (from 78 to 87% for ZnT8A and 82% for IA-2ßA) and above age 15 (from 51 to 63% for ZnT8A and 56% for IA-2ßA) versus 0% in control subjects. IA-2ßA and ZnT8A were preferentially associated with IA-2A, and with younger age at diagnosis. Unlike ZnT8A, IA-2ßA levels were positively correlated with HLA-DQ8 and negatively with HLA-DQ2. ZnT8A could replace IAA for classification of patients above age 10 without loss of sensitivity or specificity. CONCLUSIONS: ZnT8A, and to a lesser degree IA-2ßA, may usefully complement GADA, IA-2A, and IAA for classifying insulin-treated diabetes under age 40 years.