Search PubMed⌕ Search

Biomedical subjects

I Deschamps

Publications and source records attributed to I Deschamps.

At least 55 records · Page 3Linked to original sources
PubMed1990

[Epidemiology of juvenile insulin-dependent diabetes in Algeria (Wilaya of Oran)].

In order to precise the prevalence and incidence of IDDM in a well characterized population, we have ascertained between 1979 and 1988 all juvenile diabetic patients living in the department of Oran (Wilaya of Oran), Algeria, aged less than 20 years at the date of Dec. 31th 1988 who had onset of the disease before 15 years old. Cross comparisons of the data obtained both by a IDDM registry and a questionnaire sent to the practitioners show an excellent correlation. A total of 173 families was studied, including 155 Simplex Families (SF), and 18 Multiplex Families (MF). The prevalence was 0.27 p. 1000 among children aged less than 15 years. The annual incidence (mean = 4.4 p. 100,000) increased regularly from 1.6 p. 100,000 in 1981 to 8.1 p. 100,000 in 1988. The prevalence of IDDM among siblings was 3.8%. The birth order of index cases (first affected siblings) was lower in MF (3.0 +/- 0.4) than both in index cases of SF (4.0 +/- 0.3; p less than 0.01) and in secondary affected siblings of MF (4.8 +/- 0.05; p less than 0.001). The frequency of 2nd degree consanguineous marriages (between first cousins) was greater among the IDDM families compared with control families: 25% vs 11% (RR = 2.9; p less than 0.001).

Adolescent↗
PubMed1989

[Increased risk of insulin-dependent diabetes for siblings of diabetic children with the DR 3 haplotype of the mother].

Among 285 caucasoid families genotyped for HLA-A, B, C, DR including at least one insulin-dependent diabetic child, we have studied the effect of the DR3 and DR4 antigens inherited from the father or the mother (DR3p, DR3m, DR4p and DR4m, respectively) on the recurrence of the disease among siblings; families with affected parents being excluded, a total of 37 affected and 200 non affected siblings have been taken into consideration. Among the DR3, DR4 positive siblings, the DR4p/DR3m genotype was observed at a greater frequency than the DR3p/DR4m genotype among affected, but not among unaffected siblings. Comparing the respective frequencies between affected and unaffected siblings, the relative risk was 8.1 (p less than 10(-6) among DR4p/DR3m positive siblings, but is was not significantly increased among DR3p/DR4m positive siblings. The excess of maternal DR3 among affected siblings of diabetic children could be due to a gestational event associated with HLA-DR3, e.g. education of the fetal immune repertoire or the transmission of a viral infection by the mother to the fetus during pregnancy, after reactivation of the latent viral disease.

Diabetes Mellitus, Type 1↗
PubMed1989

[Chronic non-insulin deficient hyperglycemia in children].

We report the clinical records of 45 children with abnormalities regarding glycemic regulation characterized by a non-insulin deficient hyperglycemia (NIDH), known under the different names of chemical diabetes, sub-clinical diabetes and more recently MODY. These 45 children belong to 31 families with 532 relatives comprising 137 cases of NIDH which could have been studied. The symptoms of this biochemical abnormality, the pathophysiology of which is not yet clearly understood, are the following: lack of clinical manifestations, except for a variable and intermittent glycosuria; constant abnormal glucose tolerance tests, above 97 percentiles of the reference value with some variations over time; normal immunoreactive insulin levels; percentage of glycosylated hemoglobin at the upper range of normal; dominant autosomal genetic transmission and no association with HLA markers like in insulin-dependent diabetes; lack of degenerative complications of the micro-angiopathic type, at least on these cases even after more than 30 years of follow-up; finally, no tendency towards insulin-dependent diabetes. The NIDH should not be confused with the slow and progressive beginning of insulin-dependent diabetes for which prolonged delay is needed to affirm the diagnosis. The frequency of the biochemical phenomena is about 1.8% of the cases of authentic diabetes mellitus occurring before the age of 15.

Adolescent↗
PubMed1988

Two distinct HLA-DR3 haplotypes are associated with age related heterogeneity in type 1 (insulin-dependent) diabetes.

Heterogeneity between two haplotypes in linkage disequilibrium with DR3: B8, C4AQOB1,BfS,DR3 and B18,C4A3BQO,BfF1,DR3, with regard to age at onset of Type 1 (insulin-dependent) diabetes mellitus, was investigated in 325 unrelated French patients (146 males and 179 females, age at onset 1 month to 29 years) who were genotyped for HLA-A, B, C, DR and Bf and 225 of whom were typed for the C4A, B complement components. A subgroup of 82 patients and 75 control subjects were tested for DR beta and DQ beta DNA restriction fragment length polymorphism. The distribution according to age at onset and the mean ages at onset were compared between patients bearing B8, DR3 (n = 58), B18,DR3 (n = 62) or other DR3 haplotypes (Bx, DR3, n = 70), the haplotype segments C4AQOB1,DR3 (n = 41) or C4A3BQO,DR3 (n = 52) and the C4 null alleles C4AQO (N = 48) or C4BQO (n = 112) alone. The B8,DR3 haplotype, its smaller segment C4AQOB1,DR3 or C4AQO alone were associated with age at onset after 6 years (p less than 0.01, less than 0.08 and less than 0.02 respectively); on the other hand, the B18,DR3 haplotype, its segment C4A3BQO,DR3 or C4BQO alone were significantly more frequent in patients aged less than 6 years at onset (p less than 0.02, less than 0.01 and less than 0.01 respectively). Accordingly, the mean age of onset was significantly lower in the latter compared with the former patients (p less than 0.02, less than 0.02 and less than 0.01 respectively). No age-related variation was observed in BX,DR3 patients and their mean age of onset was intermediate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Organ-specific autoantibodies in HLA genotyped insulin-dependent diabetes mellitus families.

The prevalence of cytoplasmic islet cell antibodies (ICA) and extrapancreatic antibodies (EPA), (stomach, adrenal and thyroid) was investigated in 132 juvenile onset diabetic patients, without personal or familial history of other autoimmune disease, and their 31 diabetic and 402 non-diabetic first degree relatives. The prevalence of ICA was 59% in index cases and 12% in the non-affected first degree relatives. The frequency of EPA was 23% and 16% respectively. There were no sex-related differences among the patients. However, among the non-affected relatives, an increased frequency of EPA was observed in females (23%) compared to males (8%) (P less than 10-4). There was a higher prevalence of ICA in healthy relatives bearing DR3 and/or DR4 antigen combinations compared to non-DR3 and non-DR4 individuals (14% versus 5%, P less than 0.05). Furthermore, ICA were more frequent in healthy siblings sharing two haplotypes compared with one or no haplotype (21% vs 10%, P less than 0.05). These results support the heterogeneity of the autoantibodies: ICA are related closely to diabetes, decline in frequency with the duration of the disease and show association with DR3 or DR4 and the number of HLA haplotypes shared with the proband; EPA are sex related, independent of the duration of diabetes, non-HLA linked, and clustered in families with parent-offspring overtransmission, reflecting an overlapping autoimmune background.

Adolescent↗
PubMed1988

HLA-DQ rather than HLA-DR region might be involved in dominant nonsusceptibility to diabetes.

Since HLA-DRw15 (a subdivision of the HLA-DR2 specificity previously called DR2 long) is associated with dominant nonsusceptibility to insulin-dependent diabetes mellitus (IDDM), while HLA-DRw16 (another subdivision of HLA-DR2, previously called DR2 short) is positively associated with the disease, we looked for particular characteristics of HLA products encoded by the DR2 haplotypes of IDDM patients. The results show the following: (i) HLA-DQ molecules of HLA-DRw15-positive IDDM patients are different from those of HLA-DRw15-positive controls, suggesting that the HLA-DQ gene of DRw15 haplotypes is involved in a protective effect. (ii) HLA-DR and -DQ products of DRw16-positive IDDM are functionally indistinguishable from those of HLA-DRw16-positive controls. Furthermore, our data provide evidence that the residue at position 57 on the DQ beta chain could play a crucial biological role in antigen presentation to T cells as far as the DRw16 haplotype is concerned. This observation fits with the recent observation of correlation between DQ beta allelic polymorphism at position 57 and both susceptibility and resistance to IDDM.

Amino Acid Sequence↗
PubMed1988

MHC classes I, II, III antigens study in 70 insulin-dependent diabetics with associated auto-immune diseases.

Seventy IDDM patients (insulin-dependent diabetics), 48 females and 22 males, most of them adults at the onset of diabetes, and suffering from at least one other associated autoimmune manifestation (AAM) were studied for HLA A,B,C, DR markers and Bf, C4 complement components. Comparisons were made with 108 normal controls and a series of 287 IDDM patients with juvenile onset (under 25 years) and no patent other autoimmune disease. The increase in frequency of HLA-B8 among IDDM patients with AAM was confirmed (36% versus 20% in controls) (p less than 0.04). The frequency of DR4 among diabetics with AAM (33%) was not significantly different from the normal frequency (27%), and the allelic combination DR3/4 was found in only 13% of IDDM with AAM. Corresponding frequencies in patients with IDDM alone were 66% for DR4 and 34% for DR3/4 (p less than 10(-6) and 10(-3) respectively). These results confirm the heterogeneity of IDDM and support, by genetic arguments, the concept of overlapping entities. The hypothesis of a common background of autoimmunity associated with B8 DR3 can be postulated, while the organ specific target process should be associated with various DR alleles.

Adolescent↗
PubMed1988

Study of cis and trans interactions between extended HLA-haplotypes in insulin-dependent diabetes.

From the study of HLA, A, B, C, DR, Bf and C4A, C4B alleles in 287 insulin-dependent diabetes mellitus patients and 108 controls, comparisons were made between 424 diabetic and 216 normal extended haplotypes. In the "cis" situation (haplotype), the highest relative risks (RR) for IDDM were borne by multiloci allelic associations, mainly DR/complement alleles, rather than by DR3 or DR4 considered alone. Susceptibility was strongly associated with two extended haplotypes (Aw30, Cw5, B18, C4BQ0, C4A3, BfF1, DR3 and A2, Cw3, B15, C4Bx, C4A3, BfS, DR4) or their smaller segments. Two haplotypes, S31 associated with DR2 or DR5 and F31 associated with DRw6 or DR7 had a protective effect. In the "trans" situation (opposite haplotype) the large excess of DR3/DR4 heterozygotes was not the only distortion observed. An excess of DR1 (57%) and of C4BQ0 (40%) was noted among non DR3, non DR4 haplotypes in diabetics compared to normal individuals (26% and 23%, respectively, P less than 0.01, 0.05). Homozygotes for DR3 or DR4 were not increased, and other homozygotes were decreased compared to controls. The protective antigens HLA DR2, DR5 and DR7 seemed not to be distributed randomly: their putative protective effect was not observed in the case of combination with DR1 or a B18, DR3 haplotype. DR2 was never found homozygous or combined with DR5. These results suggest that susceptibility to IDDM is generated by both cis and trans interactions between genes or gene products of the HLA region.

Alleles↗
PubMed1988

A new method to test genetic models in HLA associated diseases: the MASC method.

We propose a new method to analyse data on HLA associated diseases. The method uses the simultaneous information on the marker associations and segregation with the disease. It may also take into account the differential risk of being affected for specific relatives of a patient as well as the differential HLA haplotype sharing according to the marker genotype of the patient. It is based on the principle of minimization of a sum of independent chi-squares. It allows us to test the goodness-of-fit of various models in an easy and economical way. The method is applied to a sample of 269 French IDDM patients and their relatives leading to the rejection of models with one locus closely linked to HLA with two and three alleles.

Alleles↗
PubMed1987

A Gm haplotype study in relation with HLA-DR in 155 insulin-dependent diabetic patients and their affected and non affected siblings.

In order to assess interaction between HLA and Gm for susceptibility to IDDM, the families of 155 IDDM probands were typed for HLA class I, II, III antigens and 16 Gm allotypes (including G2m23). Haplotypes were obtained for both systems. Individuals bearing the equivocal haplotype Gm (formula; see text) were excluded. The frequencies of the 6 Gm haplotypes detected were comparable in IDDM patients, sibling controls and unrelated controls. The number of Gm haplotypes was compatible with random segregation whether or not the HLA genotype was taken into account. However, analysis of the HLA-DR allelic combinations showed an increase of the uncommon haplotype Gm (formula; see text) in IDDM patients bearing DR3 in the absence of DR4 (Gm (formula; see text) phenotype frequency 43% vs 24% in other allelic combinations, p less than 0.04). When 21 diabetic and 154 non diabetic siblings of the probands were compared, the combined presence of DR3/ non 4 and Gm (formula; see text) was observed in 7 (33%) affected and 11 (7%) unaffected siblings (p less than 0.001), conferring a relative risk of 6.4 to siblings who bear both markers. All DR3/non 4 positive affected siblings (7/7) also carried Gm (formula; see text) compared with 27% (11/41) of unaffected siblings (p less than 0.001). This result suggests, that in spite of the absence of segregation distortion, interaction between Gm and HLA gene products may play a role in the familial penetrance of IDDM.

Adolescent↗
PubMed1986

[4 varieties of islet cell antibodies in 74 insulin-dependent diabetics and their families as a function of the HLA genotype].

The sera of 74 diabetic patients and of their first degree relatives were studied for 4 different types of islet cell antibodies (ICA, CFICA, ICSA, ICACT) and the results were compared according to the HLA genotype. Seventy two percent of the patients' sera were positive for at least one type of auto-antibody. Two types of auto-antibodies were observed: anticytoplasmic antibodies (ICA and CFICA), and surface antibodies (ICSA and ICACT). The different types of antibodies were not associated with any HLA-DR. These antibodies were also present in 15% of the healthy relatives. The fact that they were detected in the sera of siblings sharing no haplotype with the proband, some of them bearing neither DR3 nor DR4 antigens, suggests that non HLA linked genes and/or environmental factors partly control their secretion.

Autoantibodies↗
PubMed1986

HLA-DR 3 is associated with a more slowly progressive form of type 1 (insulin-dependent) diabetes.

The presence of HLA-DR 3 was analysed in 745 patients with Type 1 (insulin-dependent) diabetes with age at diagnosis between 1-19 years. HLA-DR 3 and/or 4 was found in 678/745 (91%) of the patients. Presence of DR2 with neither DR 3 nor 4 was demonstrated in 15 patients. Patients with HLA-DR 3 without DR 4 presented with Type 1 diabetes more evenly over the year; they also presented without incidence peaks at 7 years or 10-11 years, as seen especially in DR 3/4 patients. The DR 3 patients more often had mild disease with less ketonuria at diagnosis, less often ketoacidotic symptoms and more often a subsequent partial remission. The apparently more severe disease among diabetic girls may, at least to some extent, be explained by their higher prevalence of HLA-DR 4. The differences found were similar in North America and Europe. The results suggest that Type 1 diabetes is a genetically heterogeneous disease and that HLA-typing may be a useful marker of this heterogeneity.

Adolescent↗
PubMed1986

Interactive effect of HLA and Gm tested in a study of 135 juvenile insulin-dependent diabetic families.

Interaction between HLA and Gm for susceptibility to insulin-dependent diabetes (IDD) has been studied in 135 IDD families comparing HLA and Gm phenotype distributions in patients and sibling controls. The association analysis comparing the 135 index cases to 124 sibling controls did not show any significant interaction, but only a tendency for Gm 4,5 phenotypes to be more frequent in IDD patients, particularly in those who carried DR3/X. The sib pair analysis of 16 pairs of affected sibs did not show any distortion of segregation of Gm. On the other hand, among 98 sib pairs of one affected and one nonaffected sib, there was a significant distortion in favour of sib pairs with non-identical Gm phenotypes. However, no interaction between HLA and Gm was found. These results provide suggestive evidence that Gm or a locus very close to Gm could be involved in susceptibility to IDD.

Adolescent↗
PubMed1986

[Distortion of the maternal segregation of the silent alleles of complement factor 4 in normal and diabetic families].

54 normal Caucasian families and 169 families in whom at least one child had type I diabetes (IDDM) were genotyped for HLA-A, B, C, DR and for the complement factors Bf and C4. The paternal and maternal transmission of the different alleles and of haplotypes and complotypes in linkage desequilibrium have been analysed. No distortion of the paternal transmission has been observed in the offspring of the two series of families. On the contrary, a distortion of the maternal segregation of the silent alleles at the complement factor C4A and B locus was found: mothers transmitted C4AQ0 more often than expected to their male offspring (p less than 0.04 in normal families, p less than 0.001 in IDDM families) while they transmitted C4BQ0 in excess to their female offspring (p less than 0.01 and p less than 0.03 in normal and IDDM families, respectively).

Alleles↗
PubMed1986

[Risk factors in insulin-dependent diabetes].

The relative risks (RR) of the immunogenetic markers of insulin-dependent diabetes mellitus (IDDM) have been calculated in a population of 235 IDDM patients compared with a control population. The highest relative risk was that of subjects heterozygous DR3/DR4 (RR = 47, P less than 0.001) which was still more increased in those who carry this combination associated with the RFLP cluster DQR4 (RR = 72). Further, a sample of 51 secondary affected siblings of IDD index cases has been compared with 265 non affected siblings (one child of each family, excluding index cases). The highest risks have been found in addition to DR3/DR4, for DR3 alone and particularly for the combination C4BQ0, DR3 (RR = 9, p less than 0.001) suggesting a role for this peculiar association in the familial penetrance. In the group of siblings HLA-identical with the index case, only two factors showed some capacity of discriminating between affected and non affected siblings: HLA-DR3 and age (less than or equal to 10 years old at onset of IDDM in the index case) (p less than 0.01). In the group of haploidentical siblings, the combination DR3/DR4 and the associations C4BQ0, DR3 and BfF1, DR3 significantly increased the susceptibility for higher familial occurrence of the disease. If confirmed by additional family series, this scale of risk factors could be helpful in predicting risk of IDDM to siblings of diabetic children.

Diabetes Mellitus, Type 1↗
PubMed1986

[Renal diabetes. Apropos of 103 cases].

Three main concepts came out of this prospective study of 103 cases (51 girls and 52 boys) of renal diabetes followed up from 1955 to 1975 and reviewed in 1984: contrary to what is still sometimes written, renal diabetes does not evolve to diabetes mellitus; renal diabetes does not seem to progress over the years; the mode of genetic transmission, when present, which is rare, is obscure but it seems to occur in a recessive rather than a dominant fashion.

Adolescent↗
PubMed1986

Effects of HLA genotype, age and birth order on empirical risk estimates for insulin-dependent diabetes in siblings of diabetic children. An actuarial evaluation.

The incidence of insulin-dependent diabetes (IDDM) was evaluated as a function of time of follow-up among the 371 siblings of 193 diabetic children using actuarial methods and comparisons were carried out according to HLA genotype, sex, age and birth order. The following parameters appeared to be relevant for empirical discrimination in terms of the risk of recurrence of the disease among siblings: The number of HLA-haplotypes shared with the first affected sibling considered as the proband. Cumulative proportions 15 yr after onset of IDD in the proband were 35%, 20% and 3% in the case of 2, 1 and 0 haplotypes in common, respectively (p less than 0.02). The birth order. Cumulative risk estimates were 26% for sibs born after the proband and 11% for sibs born before the proband (p less than 0.001). The age. Risk estimates were 24% for sibs who were aged less than 10 yr at the time of the proband's onset and 5% in sibs aged greater than 10 yr (p less than 0.001). The joint analysis of birth order or age with HLA genotypes showed significantly higher risks for both identical and haplo-identical sibs with later birth order and/or younger age. Even though these results do not reflect true incidence rates because of retrospective recruitment of part of the material, the comparison of the risk figures points out the important role of some age-related effect, probably environmental, in addition to the genetic susceptibility borne by MHC genes.

Birth Order↗