[en] We investigated inaugural disease phenotype in relation to the presence or absence of diabetes-associated autoantibodies and human leukocyte antigen (HLA) DQ risk genotypes in adult-onset diabetic patients. Blood samples and questionnaires were obtained from 1584 recent-onset Belgian Caucasian patients (age 15-39 yr at diagnosis of primary diabetes) who were recruited by the Belgian Diabetes Registry over an 11-yr period. At clinical diagnosis, antibody-positive patients (n = 1198) were on average younger and had more symptoms, a more acute disease onset, lower body mass index, and random C-peptide levels, but higher insulin needs, glycemia, and prevalence of ketonuria, HLA-DQ, and 5' insulin gene susceptibility genotypes (P < 0.001 vs. antibody-negative patients; n = 386). In antibody-positive patients, these characteristics did not differ according to HLA-DQ genotype. However, in antibody-negative subjects, we found that patients were younger (P = 0.001); had a lower body mass index (P < 0.001), higher insulin needs (P = 0.014), and amylasemia (P = 0.001); and tended to have a higher glycemia and lower C-peptide in the presence of susceptible HLA-DQ genotypes. Differences according to HLA-DQ genotype subsisted after careful age-matching. In conclusion, we found no relation between initial disease phenotype and HLA-DQ genotype in antibody-positive diabetic young adults. In contrast, antibody-negative patients displayed more type I-like features when carrying susceptible HLA-DQ genotypes known to promote the development of antibody-positive diabetes. The overrepresentation of these susceptibility genotypes in antibody-negative patients suggests the existence of an immune-mediated disease process with as yet unidentified immune markers in a subgroup of seronegative patients.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Weets, Ilse; Vrije Universiteit Brussel - VUB > Diabetes Research Center (I.W., B.K., F.C.S., B.V.D.A., M.R., P.D.P., F.K.G.)
Siraux, Valérie; Cliniques Universitaires de Bruxelles - Hôpital Erasme > Department of Endocrinology (V.S., F.F.)
Daubresse, Jean-Claude ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
De Leeuw, Ivo H.; Universitair Ziekenhuis Antwerpen - UZA > Department of Endocrinology (I.H.D.L., L.V.G.)
Féry, Françoise; Cliniques Universitaires de Bruxelles - Hôpital Erasme > Department of Endocrinology (V.S., F.F.)
Keymeulen, Bart; Vrije Universiteit Brussel - VUB > Diabetes Research Center (I.W., B.K., F.C.S., B.V.D.A., M.R., P.D.P., F.K.G.)
Krzentowski, Georges; Centre Hospitalier Universitaire Charleroi > Department of Endocrinology (J.-C.D., G.K.)
Letiexhe, Michel ; Centre Hospitalier Universitaire de Liège - CHU > Maladies infectieuses et médecine interne générale
Mathieu, Chantal; Universitair Ziekenhuizen Leuven - UZ Leuven > Department of Endocrinology (C.M.)
Nobels, Frank; OLV Ziekenhuis Aalst > Department of Endocrinology (F.N.)
Rottiers, Raoul; Universitair Ziekenhuis Gent - UZ > Department of Endocrinology (R.R.)
Scheen, André ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladie métaboliques - Médecine interne générale
Van Gaal, Luc; Universitair Ziekenhuis Antwerpen > Department of Endocrinology (I.H.D.L., L.V.G.)
Schuit, Frans C.; Vrije Universiteit Brussel - VUB > Diabetes Research Center (I.W., B.K., F.C.S., B.V.D.A., M.R., P.D.P., F.K.G.)
Van Der Auwera, Bart; Vrije Universiteit Brussel - VUB > Diabetes Research Center (I.W., B.K., F.C.S., B.V.D.A., M.R., P.D.P., F.K.G.)
Rui, Mao; Vrije Universiteit Brussel - VUB > Diabetes Research Center (I.W., B.K., F.C.S., B.V.D.A., M.R., P.D.P., F.K.G.)
De Pauw, Peter; Vrije Universiteit Brussel - VUB > Diabetes Research Center (I.W., B.K., F.C.S., B.V.D.A., M.R., P.D.P., F.K.G.)
Kaufman, Leonard; Vrije Universiteit Brussel - VUB > Department of Biostatistics (L.K.)
Gorus, F. K.; Vrije Universiteit Brussel - VUB > Diabetes Research Center (I.W., B.K., F.C.S., B.V.D.A., M.R., P.D.P., F.K.G.)
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