Sexual precocity after immigration from developing countries to Belgium: Evidence of previous exposure to organochlorine pesticides

in Human Reproduction (2001), 16(103), 1020-1026

In a retrospective auxological study of 145 patients seen in Belgium during a 9-year period for treatment of precocious puberty, 28% appeared to be foreign children (39 girls, one boy) who immigrated 4 to ... [more ▼]

In a retrospective auxological study of 145 patients seen in Belgium during a 9-year period for treatment of precocious puberty, 28% appeared to be foreign children (39 girls, one boy) who immigrated 4 to 5 years earlier from 22 developing countries, without any link to a particular ethnic or country background. The patients were either adopted (n = 28) or non-adopted (n = 12), the latter having normal weight and height at immigration and starting early puberty without evidence of earlier deprivation. This led to the hypothesis that the mechanism of precocious puberty might involve previous exposure to oestrogenic endocrine disrupters. A toxicological plasma screening for eight pesticides detected p,p′-DDE, which is derived from the organochlorine pesticide DDT. Median p,p′-DDE concentrations were respectively 1.20 and 1.04 ng/ml in foreign adopted (n = 15) and non-adopted (n = 11) girls with precocious puberty, while 13 out of 15 Belgian native girls with idiopathic or organic precocious puberty showed undetectable concentrations (<0.1 ng/ml). A possible relationship between transient exposure to endocrine disrupters and sexual precocity is suggested, and deserves further studies in immigrant children with non-advanced puberty. [less ▲]

Geographical variation of presentation at diagnosis of type 1 diabetes in children: the EURODIAB Study

in Diabetologia (2001), 44(3), 75-80

We aimed to describe the frequency and degree of diabetic ketoacidosis in children across Europe at the time of diagnosis of Type I (insulin-dependent) diabetes mellitus and to determine if factors such ... [more ▼]

We aimed to describe the frequency and degree of diabetic ketoacidosis in children across Europe at the time of diagnosis of Type I (insulin-dependent) diabetes mellitus and to determine if factors such as age and geographical region contribute to the risk of diabetic ketoacidosis. METHODS: The study was part of the EURODIAB project. A total of 24 centres, covering a population at risk of more than 15 million children below 15 years of age, recruited 1,260 children at the time of clinical diagnosis. RESULTS: Polyuria, by far the most frequent symptom, was observed in 96% of the children. In only 25% of the children was the duration of symptoms less than 2 weeks and this proportion was larger in the under 5 year age-group (37 vs 22%; p < 0. 001). Of the 11 centres that recorded diabetic ketoacidosis status, the overall proportion with diabetic ketoacidosis (pH < 7.3) was 40% (95%-CI: 36-44%) in at least 90 % of cases. After stratification by centre, the odds ratio for diabetic ketoacidosis in the under 5 age-group was 1.02 (95%-CI:0.69-1.49) relative to the older children. There was significant variation between the 11 centres in the frequency of diabetic ketoacidosis which ranged from 26 to 67% (p = 0.002). An inverse correlation between the frequency of diabetic ketoacidosis and the background incidence rate was found in these centres (Spearman's rank correlation, rs = -0.715;p = 0.012). CONCLUSION/INTERPRETATION: Rising standards of medical information and greater awareness concurrent with an overall increase in incidence could have resulted in changes in the clinical presentation at onset of Type I childhood diabetes in Europe. [less ▲]

Variation and trends in incidence of childhood diabetes in Europe

in Lancet (2000), 355

BACKGROUND: To study the epidemiology of childhood-onset type 1 insulin-dependent diabetes in Europe, the EURODIAB collaborative group established in 1988 prospective geographically-defined registers of ... [more ▼]

BACKGROUND: To study the epidemiology of childhood-onset type 1 insulin-dependent diabetes in Europe, the EURODIAB collaborative group established in 1988 prospective geographically-defined registers of new cases diagnosed under 15 years of age. This report is based on 16 362 cases registered during the period 1989-94 by 44 centres representing most European countries and Israel and covering a population of about 28 million children. METHODS: Multiple sources of ascertainment were used in most centres to validate the completeness of registration by the capture-recapture method. Trends in incidence during the period were analysed by Poisson regression, the data from centres within each country being pooled. FINDINGS: The standardised average annual incidence rate during the period 1989-94 ranged from 3.2 cases per 100000 per year in the Former Yugoslav Republic of Macedonia to 40.2 cases per 100000 per year in two regions of Finland. By pooling over all centres, the annual rate of increase in incidence was 3.4% (95% CI 2.5-4.4%), but in some central European countries it was more rapid than this. Pooled over centres and sexes, the rates of increase were 6.3% (4.1-8.5%) for children aged 0-4 years, 3.1% (1.5-4.8%) for 5-9 years, and 2.4% (1.0-3.8%) for 10-14 years. INTERPRETATION: The results confirm a very wide range of incidence rates within Europe and show that the increase in incidence during the period varied from country to country. The rapid rate of increase in children aged under 5 years is of particular concern. PMID: 10752702 [PubMed - indexed for MEDLI [less ▲]

The Eurodiab Substudy 2 study group. Infections and vaccinations as risk factors for childhood type1(insulin dependent) diabetes mellitus: a multicentre case control investigation

in Diabetologia (2000), 43

Aims/hypothesis. To determine if vaccinations and infections are associated with the subsequent risk of Type I (insulin-dependent) diabetes mellitus in childhood. Method. Seven centres in Europe with ... [more ▼]

Aims/hypothesis. To determine if vaccinations and infections are associated with the subsequent risk of Type I (insulin-dependent) diabetes mellitus in childhood. Method. Seven centres in Europe with access to population-based registers of children with Type I diabetes diagnosed under 15 years of age participated in a case-control study of environmental risk factors. Control children were chosen at random in each centre either from population registers or from schools and policlinics. Data on maternal and neonatal infections, common childhood infections and vaccinations were obtained for 900 cases and 2302 control children from hospital and clinic records and from parental responses to a questionnaire or interview. Results. Infections early in the child's life noted in the hospital record were found to be associated with an increased risk of diabetes, although the odds ratio of 1.61 (95% confidence limits 1.11, 2.33) was significant only after adjustment for confounding variables. None of the common childhood infectious diseases was found to be associated with diabetes and neither was there evidence that any common childhood vaccination modified the risk of diabetes. Pre-school day-care attendance, a proxy measure for total infectious disease exposure in early childhood, was found, however, to be inversely associated with diabetes, with a pooled odds ratio of 0.59 (95% confidence limits 0.46, 0.76) after adjustment for confounding variables. Conclusion/interpretation. It seems likely that the explanation for these contrasting findings of an increased risk associated with perinatal infections coupled with a protective effect of pre-school day care lies in the age-dependent modifying influence of infections on the developing immune system [less ▲]

The EURODIAB Substudy 2 Study Group Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus

in Diabetologia (1999), 42(1), 51-55

The initiation of the immunopathogenetic process that can lead to Type I (insulin-dependent) diabetes mellitus in childhood probably occurs early in life. Studies in vitro have shown that vitamin D3 is ... [more ▼]

The initiation of the immunopathogenetic process that can lead to Type I (insulin-dependent) diabetes mellitus in childhood probably occurs early in life. Studies in vitro have shown that vitamin D3 is immunosuppressive or immunomodulating and studies in experimental models of autoimmunity, including one for autoimmune diabetes, have shown vitamin D to be protective. Seven centres in Europe with access to population-based and validated case registers of insulin-dependent diabetes patients participated in a case-control study focusing on early exposures and risk of Type I diabetes. Altogether data from 820 patients and 2335 control subjects corresponding to 85% of eligible patients and 76% of eligible control subjects were analysed. Questions focused on perinatal events and early eating habits including vitamin D supplementation. The frequency of vitamin D supplementation in different countries varied from 47 to 97% among control subjects. Vitamin D supplementation was associated with a decreased risk of Type I diabetes without indication of heterogeneity. The Mantel-Haenszel combined odds ratio was 0.67 (95% confidence limits: 0.53, 0.86). Adjustment for the possible confounders: a low birth weight, a short duration of breast feeding, old maternal age and study centre in logistic regression analysis did not affect the significant protective effect of vitamin D. In conclusion, this large multicentre trial covering many different European settings consistently showed a protective effect of vitamin D supplementation in infancy. The findings indicate that activated vitamin D might contribute to immune modulation and thereby protect or arrest an ongoing immune process initiated in susceptible people by early environmental exposures. [less ▲]

Familial risk of type 1 diabetes in European children

in Diabetologia (1998), 41

Fluctuations in GAD65 antibodies after clinical diagnosis of IDDM in young children

in Diabetes Care (1997), 20(4), 642-644

OBJECTIVE - To investigate whether the presence of GAD antibodies at onset of IDDM correlates to a more aggressive rate of β-cell destruction after clinical onset. RESEARCH DESIGN AND METHODS - We studied ... [more ▼]

OBJECTIVE - To investigate whether the presence of GAD antibodies at onset of IDDM correlates to a more aggressive rate of β-cell destruction after clinical onset. RESEARCH DESIGN AND METHODS - We studied GAD antibodies at onset of disease, after 1 year, and after 6 years in 33 consecutively referred children (mean age 8.08, range 1.7-16.3). In a subset of 11 patients, GAD antibodies were studied very frequently. The correlation between GAD antibodies and clinical parameters, including glycosylated hemoglobin, residual insulin secretion, and insulin dosage, was evaluated. RESULTS - GAD antibody titers were highly variable. Four patients became GAD antibody positive weeks to years after clinical onset. Other patients switched between testing positive and negative for GAD antibodies shortly after clinical onset. No correlation was found between the presence of GAD antibodies and the rate of β-cell destruction, but patients with high GAD antibody indexes at onset had significantly higher glycosylated hemoglobin levels. CONCLUSIONS - GAD antibodies at clinical onset do not predict the rate of β-cell destruction in young children with newly diagnosed IDDM. The highly variable GAD antibody levels suggest variation of the autoimmune process. [less ▲]

A review of the recent epidemiological data on the worldwide incidence of type 1 (insulin dependent) diabetes mellitus

in Diabetologia (1993), 36

Nearly 70 registries from more than 40 countries have collected and published incidence data of childhood Type 1 (insulin-dependent) diabetes mellitus up to the end of the 1980s. The majority of incidence ... [more ▼]

Nearly 70 registries from more than 40 countries have collected and published incidence data of childhood Type 1 (insulin-dependent) diabetes mellitus up to the end of the 1980s. The majority of incidence data comes from regions of high incidence i.e. from Europe and North America. All these published data facilitate the descriptive comparison of incidence and variation of the occurrence of Type 1 diabetes roughly throughout the northern hemisphere. The aim of this paper is to review and compare the most recent epidemiology data on the incidence of Type 1 diabetes among children under the age of 15 years. A clear difference in incidence appeared between northern and southern hemisphere with no countries below the equator having an incidence greater than 15.0 per 100,000. In contrast above the equator the disease is common. Between continents the variation in incidence showed that the lowest incidences were found in Asia, followed by Oceania (Australia and New Zealand), South and North America, and the highest rates were in Europe. The incidence varied from 0.6 per 100,000 in Korea and Mexico to 35.3 per 100,000 in Finland showing prominent worldwide variation in incidence of Type 1 diabetes. The largest intracontinental variation in incidence appeared in Europe, varying from the highest in Finland to the lowest (4.6 per 100,000) in northern Greece. The highest incidence in the world was in northern Europe, but within the continent scale there were some striking exceptions from the overall level of incidence.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

Insulin autoantibodies and immune response to human insulin therapy in 24 type 1 (insulin-dependent) diabetic children: superiority of radio binding assay over solid phase assay

in Diabetes Research and Clinical Practice (1993), 21(1), 19-24

To evaluate the immunization pattern against human insulin, 24 newly diagnosed diabetic children (12 females, 12 males; mean age: 7 ± 4 years) were treated from diagnosis onwards with semisynthetic human ... [more ▼]

To evaluate the immunization pattern against human insulin, 24 newly diagnosed diabetic children (12 females, 12 males; mean age: 7 ± 4 years) were treated from diagnosis onwards with semisynthetic human insulin (NOVO). Informed consent was obtained from all parents. Blood samples were taken before, 1, 2, 3, 4, 6 and 8 weeks after the start of therapy and, thereafter, at monthly intervals for 2 years. Insulin (auto) antibodies (I(A)A) were measured by radio binding assay (RBA) and by enzyme-linked immunosorbent assay (ELISA). IAA, determined by RBA, were detected in eight children. Using ELISA, IgM IA were not detected after onset of therapy. By contrast, IgG IA were found in 8 children after 2 weeks of treatment and in 12 after 1 month. Using RBA, all children had IA after 2 months of therapy, whereas with ELISA, IA remained undetectable during the study period in 8 out of 24 patients. These results confirm previous observations suggesting that the 2 methods are not interchangeable and yield different estimations of the insulin immune reaction, not only before but also after the start of insulin therapy. In addition, the detection of IA by RBA in all treated patients unambiguously demonstrates that human insulin is immunogenic in man. © 1993. [less ▲]

Nicotinamid

in Diabetes, prevention and therapy (1992), 6