Metabolically inactive insulin : friend or foe in the prevention of autoimmune diabetes?

About 20 years ago an American study suggested that daily subcutaneous injections of a metabolically inactive insulin analogue with a single amino acid substitution (aspartic acid instead of phenylalanine) at position 25 of the B chain was as effective as intact insulin in preventing autoimmune diabetes in NOD mice. In this issue of Diabetologia Grnholm et al (DOI: 10.1007/s00125-017-4276-5) report that parenteral administration of the same insulin analogue has no preventive effect whatsoever on the development of diabetes in NOD mice; in fact, high doses of the metabolically inactive insulin accelerated disease development. The authors were also unable to show any tolerogenic effect of an insulin peptide mimetope given via a subcutaneous osmotic pump. These data do not support the use of metabolically inactive insulin for the prevention of autoimmune diabetes and question whether insulin alone, intact or inactivated has any role in preventing progression to symptomatic diabetes. Future and ongoing intervention trials in humans with preclinical type 1 diabetes should indicate whether the administration of oral insulin has any protective, neutral or even predisposing effects on the development of symptomatic diabetes.Peer reviewe

Introduktion : barnens och pediatrikens framtid i Finland

English summar

Typ 1 -diabetes : en autoimmun eller infektionssjukdom?

English summar

Reclassification of asymptomatic beta cell autoimmunity : a critical perspective

Type 1 diabetes is an immune-mediated disease leading to almost total beta cell destruction and permanent exogenous insulin dependency. The appearance of clinical symptoms is preceded by an asymptomatic preclinical period, the duration of which is highly individual. The emergence of diabetes-associated autoantibodies into the peripheral circulation is the first detectable sign of beta cell autoimmunity. If type 1 diabetes is diagnosed in childhood the preclinical period lasts for an average of 2.5-3 years, but clinical symptoms may in some cases appear within a few months or be delayed for more than 20 years. In this issue of Diabetologia, Bonifacio and colleagues (doi:) suggest that asymptomatic beta cell autoimmunity should be considered as a pathological and diagnostic entity. Although such a strategy may have some positive consequences, it might also have serious drawbacks. To label an asymptomatic child that may have 10-20 years of a healthy life ahead of him/her as a patient will most likely affect both the life of the family and the child. Therefore, we think that one should not adapt the new diagnosis before the psychological consequences of such a strategy have been assessed. Instead, since metabolic abnormalities precede the appearance of clinical symptoms of type 1 diabetes, analysis of a combination of immunological and metabolic markers will provide better insight into the likelihood of progression to clinical disease, with a shorter 'sickness' period.Peer reviewe

Kan typ 1-diabetes förebyggas med ett vaccin?

Diabetes. English summary

Lipidomics of human umbilical cord serum : identification of unique sterol sulfates

Aim: There are currently limited lipidomics data for human umbilical cord blood. Therefore, the lipidomes of cord sera from six newborns and sera from six nonpregnant females were compared. Materials & methods: Sera lipidomics analyses were conducted using a high-resolution mass spectrometry analytical platform. Results: Cord serum contained a diverse array of glycerophospholipids, albeit generally at lower concentrations than monitored in adult serum. The unexpected observations were that cord serum contained several neurosteroid sulfates and bile acid sulfates that were not detectable in adult serum. Conclusion: Our data are the first to demonstrate that cord serum contains bile acid sulfates that are synthesized early in the hydroxylase, neutral and acidic pathways of primary bile acid biosynthesis and support previous publications of cord blood perfluoralkyl toxins in newborns. Lay abstract: Umbilical cord blood offers the potential to increase our understanding of fetal development during pregnancy and during development after delivery. Our studies of complex sterols in umbilical cord blood (bile acid sulfates) suggest that with further studies these may be useful biomarkers of abnormal fetal liver development.Peer reviewe

Probiotic intervention in infancy is not associated with development of beta cell autoimmunity and type 1 diabetes

Non peer reviewe

FOXP3+ Regulatory T Cell Compartment Is Altered in Children With Newly Diagnosed Type 1 Diabetes but Not in Autoantibody-Positive at-Risk Children

The dysfunction of FOXP3-positive regulatory T cells (Tregs) plays a key role in the pathogenesis of autoimmune diseases, including type 1 diabetes (T1D). However, previous studies analyzing the peripheral blood Treg compartment in patients with T1D have yielded partially conflicting results. Moreover, the phenotypic complexity of peripheral blood Tregs during the development of human T1D has not been comprehensively analyzed. Here, we used multi-color flow cytometry to analyze the frequency of distinct Treg subsets in blood samples from a large cohort comprising of 74 children with newly diagnosed T1D, 76 autoantibody-positive children at-risk for T1D and 180 age- and HLA-matched control children. The frequency of CD4+CD25+CD127lowFOXP3+ Tregs was higher in children with T1D compared to control children, and this change was attributable to a higher proportion of naïve Tregs in these subjects. Further longitudinal analyses demonstrated that the increase in Treg frequency correlated with disease onset. The frequencies of the minor subsets of CD25+FOXP3low memory Tregs as well as CD25lowCD127lowFOXP3+ Tregs were also increased in children with T1D. Moreover, the ratio of CCR6-CXCR3+ and CCR6+CXCR3- memory Tregs was altered and the frequency of proliferating Ki67-positive and IFN-γ producing memory Tregs was decreased in children with T1D. The frequency of CXCR5+FOXP3+ circulating follicular T regulatory cells was not altered in children with T1D. Importantly, none of the alterations observed in children with T1D were observed in autoantibody-positive at-risk children. In conclusion, our study reveals multiple alterations in the peripheral blood Treg compartment at the diagnosis of T1D that appear not to be features of early islet autoimmunity