A V Kharagjitsingh

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (6)18.66 Total impact

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    ABSTRACT: The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFNγ) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes. Two hundred and twenty-seven patients from the Hvidoere Study Group were classified in four different progression groups as assessed by change in stimulated C-peptide from 1 to 6 months. CA repeat variants of the IL-10 and IFNγ gene were genotyped and serum levels of IL-10 and IFNγ were measured at 1, 6 and 12 months. IL-10 decreased (P < 0.001) by 7.7% (1 month), 10.4% (6 months) and 8.6% (12 months) per year increase in age of child, while a twofold higher C-peptide concentration at 1 month (p = 0.06), 6 months (P = 0.0003) and 12 months (P = 0.02) was associated with 9.7%, 18.6% and 9.7% lower IL-10 levels, independent of each other. IL-10 concentrations did not associate with the disease progression groups. By contrast, IFNγ concentrations differed between the four progression groups at 6 and 12 months (P = 0.02 and P = 0.01, respectively); patients with rapid progressing disease had the highest levels at both time points. Distribution of IL-10 and IFNγ genotypes was equal among patients from the progression groups. IL-10 serum levels associate inversely with age and C-peptide. As age and C-peptide also associate, a triangular association is proposed. Genetic influence on IL-10 production seems to be masked by distinct disease mechanisms. Increased serum IFNγ concentrations associate with rapid disease progression. Functional genetic variants do not associate with a single progression pattern group, implying that disease processes override genetically predisposed cytokine production.
    Diabetic Medicine 12/2011; 29(6):734-41. · 3.24 Impact Factor
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    ABSTRACT: Background: Major defects in the IGF1 gene are associated with severely reduced cranial and linear growth. The association between IGF1 promoter polymorphisms and growth is uncertain. Aims: To test the effect of the IGF1 192-bp allele on cranial and linear growth and body mass index (BMI) from birth until age 5 years, and on IQ and serum IGF-1 at age 19 years. Methods: In a birth cohort, including 285 individuals born at a gestational age <32 weeks from the Project On Preterm and Small-for-gestational age infants (POPS), cohort anthropometric measurements were analyzed. At age 19 years IGF1 genotype, serum IGF-1 level and IQ were determined. Regression analyses were performed with mixed models. Results: Homozygotes for the 192-bp allele had a slower cranial growth from birth until age 5 years, and a tendency towards less brain sparing and a slower linear growth compared to the other 2 genotype groups. IGF1 genotype was not associated with IQ or BMI development. Head circumference SDS at age 5 years was positively associated with IQ at age 19 years. Conclusion: Homozygosity for the IGF1 192-bp allele is associated with a slower cranial growth from birth until age 5 years in individuals born very preterm.
    Hormone Research in Paediatrics 03/2011; 76(1):27-34. · 1.55 Impact Factor
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    ABSTRACT: Accelerated early growth prior to childhood type 1 diabetes onset is associated with an increased risk for type 1 diabetes (T1D). We aimed to study early growth, correcting for the previously neglected confounder of familial effects. Infant growth was studied in a retrospective family case-control study of diabetic children in which siblings acted as matched familial controls allowing correction for confounders related to family particulars. Weight and height data were collected from 213 juvenile onset type 1 diabetic children and their 255 healthy siblings. Growth in the first 4 years of life was studied using repeated measurement. The degree of early overgrowth was correlated with age of clinical onset. Birth weight and length did not differ between later diabetic children and their siblings. In the first year of life, weight standard deviation score (SDS) differed between patients and sibs (P = 0.0001). After the first year, both diabetic children and sibs showed parallel enhanced weight and height gain SDS until age 4 years. Earlier onset diabetes was associated with a higher weight SDS at 6 months of age. In this family case-control study the association of increased growth with development of T1D is limited to the first year of life implying that increased growth beyond the first year can be attributed to familial growth patterns, rather than predisposition to T1D per se. Age at disease onset correlated with increased weight in the first 6 months of life, indicating importance of features very early in life on later development of T1D.
    Clinical Endocrinology 10/2009; 72(5):620-4. · 3.35 Impact Factor
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    ABSTRACT: To examine a disputed association between the Lewis(a(-)b(-)) phenotype and Type 1 diabetes (T1D). Lewis red blood cell phenotyping was performed for 97 T1D White patients and 100 control subjects using monoclonal antibodies. Two historical cohorts were also included as a control population. T1D patients had a lower frequency (4.1%) of Lewis(a(-)b(-)) blood group compared with simultaneously tested healthy control subjects (10.0%) and the historical control group (11.1%, P = 0.02). Male T1D patients showed a Lewis(a(-)b(-)) frequency of 8.0%, which was similar to both matched healthy male donors (9.8%) and historical (9.5%) male control subjects. Unexpectedly, none of the female T1D patients displayed Lewis(a(-)b(-)) phenotype, vs. 10.3% and 10.8% of female control subjects (P = 0.039 and 0.017). The Lewis(a(-)b(-)) phenotype occurs less frequently in T1D compared with healthy control subjects with a strong female gender bias.
    Diabetic Medicine 03/2008; 25(2):236-8. · 3.24 Impact Factor
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    ABSTRACT: We studied whether serum interferon (IFN)-gamma or interleukin (IL)-10 levels and their corresponding functional polymorphic genotypes are associated with partial remission of type 1 diabetes (T1D). A multi-centre study was undertaken in patients with newly diagnosed T1D and matched controls. T1D patients were followed for 3 months and characterized for remission status. Partial clinical remission was defined as a daily insulin dose <or= 0.38 units/kg/24 h with an HbA1c <or= 7.5%. Thirty-three patients and 32 controls were phenotyped for serum concentrations of IFN-gamma and IL-10 and genotyped for functional polymorphisms of the IFN-gamma and IL-10 genes. Sixteen of 25 informative patients (63%) remitted. Serum IFN-gamma concentrations were significantly decreased in remitters but increased in non-remitters compared to controls, and did not change over time in any group. IFN-gamma genotypes corresponded with serum levels in controls and non-remitters, but not in remitters who displayed the lowest serum IFN-gamma levels despite more often carrying high-producing IFN-gamma genotypes. Neither the frequency of IL-10 genotypes nor serum IL-10 concentration differed between patients and controls. The combination of high-producing IFN-gamma genotype together with low serum IFN-gamma concentration at the time of diagnosis provided a strong positive predictive value for remission. Serum IFN-gamma concentrations predicted by genotype and observed serum levels were discordant in remitters, suggestive of regulation overruling genetic predisposition. Although high-producing genotypes were less frequent in remitters, they were predictive of remission in combination with low serum IFN-gamma levels. These data imply that remission is partially immune-mediated and involves regulation of IFN-gamma transcription.
    Clinical & Experimental Immunology 10/2006; 145(3):480-4. · 3.28 Impact Factor
  • Clinical Immunology 01/2006; 119. · 3.99 Impact Factor