Metabolic and immune parameters at clinical onset of insulin-dependent diabetes: A population-based study

Pozzilli, Paolo; Visalli, N; Buzzetti, Raffaella; Cavallo, Maria Gisella; Marietti, G.; Hawa, M.; Leslie, R. D. G.

doi:10.1016/s0026-0495(98)90324-9

Cited by 57 publications

(48 citation statements)

References 32 publications

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“…the more rapid disappearance of autoantibodies, and of ICA in particular, after clinical onset (11,12) coincides with the complete loss of ␤-cells observed in the pancreases of young type 1 diabetic patients who died soon after diagnosis (under 7 years of age) (14) and with the rapid decline in C-peptide levels after diagnosis described in initially ICA-positive patients in that age-group (10,33). This may suggest that the presence of ␤-cell antigens drives the ongoing production of ICA.…”

Section: Decochez and Associatessupporting

confidence: 66%

High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. The Belgian Diabetes Registry.

et al. 2000

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OBJECTIVE -To study the presence and levels of GAD65 antibodies (GADA), IA-2 antibodies (IA-2-A), and islet cell antibodies (ICA) during the first years after clinical onset of type 1 diabetes in relation to age at diagnosis.RESEARCH DESIGN AND METHODS -Type 1 diabetic patients (n = 194) Ͻ40 years of age were consecutively recruited at the time of diagnosis by the Belgian Diabetes Registry and followed during the first 4 years of insulin treatment. ICA were determined by indirect immunofluorescence assay and IA-2-A, GADA, and insulin autoantibodies by a radioligand assay.RESULTS -Overall, 94% of initially antibody-positive patients (n = 180) remained positive for at least 1 antibody type 4 years after diagnosis. In the case of diagnosis after 7 years of age, GADA, IA-2-A, and ICA persisted in 91, 88, and 71%, respectively, of the initially antibody-positive patients. Antibody persistence was lower in those diagnosed at Ͻ7 years of age, amounting to 60% for GADA, 71% for IA-2-A, and 39% for ICA. In 57% of the initially antibody-positive patients, at least 1 type of autoantibody reached peak values after diagnosis. This occurred more frequently for clinical onset after 7 years of age and more often for GADA (49%) than for IA-2-A (29%) or ICA (19%). Of the patients, 24% that were negative for GADA at onset became GADApositive during the following 4 years. Among the 7% initially antibody-negative patients, 2 of 14 subjects developed antibodies after clinical onset.CONCLUSIONS -In particular, for diagnosis after 7 years of age, islet cell-specific autoantibodies generally persist for many years after diagnosis. There is also a high frequency of increasing antibody levels and of conversion to antibody positivity in the first 4 years after diagnosis and start of insulin treatment. Thus, determination of antibodies at diagnosis can underestimate the number of cases with autoimmune type 1 diabetes, in particular with assays of lower sensitivity. The divergent temporal patterns of ICA, GADA, and IA-2-A suggest that the ICA test recognizes other antibody specificities besides GADA and IA-2-A and reflects other autoimmune processes; it also indicates that GADA assays have a higher diagnostic sensitivity in the period after clinical onset.

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Section: Decochez and Associatessupporting

confidence: 66%

High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. The Belgian Diabetes Registry.

et al. 2000

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“…Type 1 diabetes patients (n = 245) from the Lazio region of Italy were collected by the IMDIAB study group [13]. Clinical criteria for inclusion in the IMDIAB study were based on American Diabetes Association guidelines [14].…”

Section: Patientsmentioning

confidence: 99%

Type 1 diabetes risk for human leukocyte antigen (HLA)-DR3 haplotypes depends on genotypic context: Association of DPB1 and HLA class I loci among DR3- and DR4-matched Italian patients and controls

Noble¹,

Martin²,

Valdes³

et al. 2008

Human Immunology

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Patients with high-risk HLA-DR-DQ genotypes for type 1 diabetes (T1D) were compared to HLAmatched controls to evaluate T1D risk for other HLA loci, including HLA-A, -B, -Cw, and DPB1. Patients (n=133) with high-risk genotypes (DR3/DR3, DR3/DR4, DR4/DR4) were selected from the Lazio (Rome) region of Italy. Screening of more than 9000 subjects from the Lazio region and northern Italy yielded 162 controls with high-T1D-risk haplotypes. Although the overall distributions were not significantly different, allele frequency differences were discovered between the controls from Lazio and those from Northern Italy for some alleles previously shown to affect T1D risk, such as A*3002, DPB1*0301, and DPB1*0402. Therefore, Lazio patient data were compared both to the Lazio subset of controls (n=53) and to the entire group of controls for association analyses. Significant allele frequency differences between patients and DR-DQ-matched controls were found for specific alleles at all loci. Data for the DR3/DR3 subset of patients and controls showed an increase of Cw*0702 in patients. Reduced patient, compared to control, frequencies were seen for several alleles, including A*0101, B*0801, and Cw*0701, all found on the highly-conserved, extended DR3 haplotype known as 8.1 in DR3/DR3, but not DR3/DR4, subgroup. DPB1*0101, often found on 8.1 haplotypes, was also less frequent in DR3/DR3 patients than controls. Analysis of family-based data from the HBDI repository was consistent with the observed results from the Italian subjects, suggesting the presence of a T1D-protective locus at or near A*0101 and a second T1D-protective locus at or near DPB1*0101. These data suggest that T1D risk conferred by the 8.1 haplotype is genotype dependent.

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“…Insulin secretory capacity is less compromised in adults at diagnosis than in children, and after diagnosis it deteriorates less rapidly. A study of 235 consecutive cases with newly diagnosed type 1 diabetes found that those aged Ͻ7 years had the lowest baseline residual insulin secretion and required the highest insulin dose for optimal control, whereas the older the age at diagnosis, the higher the basal C-peptide level (61). Decreased insulin sensitivity in puberty and in adulthood could also be relevant to metabolic decompensation, leading to frank diabetes (Fig.…”

Section: Implications For Disease Pathogenesismentioning

confidence: 99%

Age-Dependent Influences on the Origins of Autoimmune Diabetes

Leslie

Castelli

2004

Diabetes

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Metabolic and immune parameters at clinical onset of insulin-dependent diabetes: A population-based study

Cited by 57 publications

References 32 publications

High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. The Belgian Diabetes Registry.

High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. The Belgian Diabetes Registry.

Type 1 diabetes risk for human leukocyte antigen (HLA)-DR3 haplotypes depends on genotypic context: Association of DPB1 and HLA class I loci among DR3- and DR4-matched Italian patients and controls

Age-Dependent Influences on the Origins of Autoimmune Diabetes

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