Association between age, IL-10, IFNγ, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Revisiting infant growth prior to childhood onset type 1 diabetes.

OBJECTIVE: 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. DESIGN: 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. PATIENTS: 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. RESULTS: 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. CONCLUSION: 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.

Reduced frequency of blood group Lewis a-b- in female Type 1 diabetes patients.

AIMS: To examine a disputed association between the Lewis(a(-)b(-)) phenotype and Type 1 diabetes (T1D). METHODS: 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. RESULTS: 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). CONCLUSIONS: The Lewis(a(-)b(-)) phenotype occurs less frequently in T1D compared with healthy control subjects with a strong female gender bias.

Prevalence of coronary artery disease and plaque morphology assessed by multi-slice computed tomography coronary angiography and calcium scoring in asymptomatic patients with type 2 diabetes.

OBJECTIVE: The purpose of the study was to evaluate the prevalence of CAD as well as plaque morphology in asymptomatic patients with type 2 diabetes using multi-slice computed tomography (MSCT). In addition, the relation between calcium score and MSCT findings was explored. DESIGN: In 70 patients, coronary calcium scoring and non-invasive coronary angiography were performed. Angiograms showing atherosclerosis were further classified as obstructive (> or =50% luminal narrowing) CAD or not. Plaque type (non-calcified, mixed and calcified) was determined. Finally, the relation between calcium score and MSCT findings was explored. RESULTS: A calcium score <10 was observed in 31 (44%) patients. A calcium score of 10-100 was observed in 14 (20%) patients while a score of 101-400 or >400 was identified in 12 (17%) and 13 (19%) patients respectively. Non-invasive coronary angiography showed CAD in 56 (80%) patients. 322 coronary segments with plaque were identified, of which 132 (41%) contained non-calcified plaques, 65 (20%) mixed plaques and 125 (39%) calcified plaques. The percentage of patients with obstructive CAD paralleled increasing calcium score. The presence of CAD was noted in 17 (55%) patients with no or minimal calcium (score <10). CONCLUSIONS: MSCT angiography detected a high prevalence of CAD in asymptomatic patients with type 2 diabetes. A relatively high proportion of plaques were non-calcified (41%). Importantly, a calcium score <10 did not exclude CAD in these patients. MSCT might be a useful technique to identify CAD in asymptomatic patients with type 2 diabetes with incremental value over calcium scoring.

Association of interferon-gamma and interleukin 10 genotypes and serum levels with partial clinical remission in type 1 diabetes.

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

[Epoetin-induced pure red-cell aplasia]. / Door epoëtine geïnduceerde erytrocytaire aplasie.

A 73-year-old man, a 73-year-old woman, and a 57-year-old man with anaemia due to renal insufficiency were treated with epoetin. After 6-12 months, the haemoglobin level decreased despite dosage increases, after which the patients became dependent on regular transfusions of concentrated erythrocytes. The older man died from peritonitis following diagnostic examination because of the anaemia. The woman died from septic shock, even though epoetin had been replaced by darbepoetin. The haemoglobin level in the younger man returned to normal after the presence of antibodies against epoetin had been demonstrated, he had stopped using the drug, and he had started on immunosuppressive therapy following kidney transplantation. Since 1998, the number of patients with epoetin resistance due to the development of antibodies against the drug (epoetin-induced pure red-cell aplasia) has increased. This complication should be considered in every patient treated with epoetin who experiences unexplained transfusion-dependent anaemia.