BackgroundRecent studies have shown that an artificial-pancreas system can improve glucosecontrol and reduce nocturnal hypoglycemia. However, it is not known whether suchresults can be replicated in settings outside the hospital.MethodsIn this multicenter, multinational, randomized, crossover trial, we assessed the shorttermsafety and efficacy of an artificial pancreas system for control of nocturnalglucose levels in patients (10 to 18 years of age) with type 1 diabetes at a diabetescamp. In two consecutive overnight sessions, we randomly assigned 56 patients to receivetreatment with an artificial pancreas on the first night and a sensor-augmentedinsulin pump (control) on the second night or to the reverse order of therapies on thefirst and second nights. Thus, all the patients received each treatment in a randomlyassigned order. The primary end points were the number of hypoglycemic events(defined as a sensor glucose value of (63 mg per deciliter [3.5 mmol per liter] forat least 10 consecutive minutes), the time spent with glucose levels below 60 mgper deciliter (3.3 mmol per liter), and the mean overnight glucose level for individualpatients.ResultsOn nights when the artificial pancreas was used, versus nights when the sensoraugmentedinsulin pump was used, there were significantly fewer episodes ofnighttime glucose levels below 63 mg per deciliter (7 vs. 22) and significantlyshorter periods when glucose levels were below 60 mg per deciliter (P = 0.003 andP = 0.02, respectively, after adjustment for multiplicity). Median values for the individualmean overnight glucose levels were 126.4 mg per deciliter (interquartilerange, 115.7 to 139.1 [7.0 mmol per liter; interquartile range, 6.4 to 7.7]) with theartificial pancreas and 140.4 mg per deciliter (interquartile range, 105.7 to 167.4[7.8 mmol per liter; interquartile range, 5.9 to 9.3]) with the sensor-augmentedpump. No serious adverse events were reported.ConclusionsPatients at a diabetes camp who were treated with an artificial-pancreas systemhad less nocturnal hypoglycemia and tighter glucose control than when theywere treated with a sensor-augmented insulin pump.
COBISS.SI-ID: 1271980
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a recessive disorder resulting from mutations in the autoimmune regulator (AIRE). The patients' autoantibodies recognize not only multiple organ-specific targets, but also many type I interferons (IFNs) and most T helper type 17 (Th17) cell-associated cytokines, whose biological actions theyneutralize in vitro. These anti-cytokine autoantibodies are highly disease-specific: otherwise, they have been found only in patients with thymomas, tumours of thymic epithelial cells that fail to express AIRE. Moreover, autoantibodies against Th17 cell-associated cytokines correlate withchronic mucocutaneous candidiasis in both syndromes. Here, we demonstrate that the immunoglobulin (Ig)Gs but not the IgAs in APECED sera are responsiblefor neutralizing IFN-Ž, IFN-Ž2a, interleukin (IL)-17A and IL-22. Their dominant subclasses proved to be IgG1 and, surprisingly, IgG4 without IgE, possibly implicating regulatory T cell responses and/or epithelia in their initiation in these AIRE-deficiency states. The epitopes on IL-22 and IFN-Ž2a appeared mainly conformational. We also found mainly IgG1 neutralizingautoantibodies to IL-17A in aged AIRE-deficient BALB/c mice - the first report of any target shared by these human and murine AIRE-deficiency states. We conclude that autoimmunization against cytokines in AIRE deficiencyis not simply a mere side effect of chronic mucosal Candida infection, but appears to be related more closely to disease initiation.
COBISS.SI-ID: 757676
Donohue syndrome (leprechaunism; OMIM *246200) is a rare, recessively inherited disorder of extreme insulin resistance due to mutations in the insulin receptor gene (INSR) causing either defects in insulin binding or receptor autophosphorylation and tyrosine kinase activity. We report a patientwith pronounced clinical picture of leprechaunism who developed severe progressive hypertrophic obstructive cardiomyopathy (HOCM) and renal tubular dysfunction which improved on continuous subcutaneous infusion of recombinant human insulin-like growth factor-1 (rhIGF-I). INSR gene molecular analysis andinsulin receptor (IR) autophosphorylation on cultured fibroblasts were performed. A novel homozygous missense mutation p.Leu795Pro was found, locatedin the extracellular portion of the Ž subunit of the insulin receptor. The post-binding defect of the insulin receptor signaling in cultured fibroblasts demonstrated decreased insulin receptor autophosphorylation. Conclusion: Treatment with rhIGF-I partially reversed severe progressive HOCM and renal tubular dysfunction in a patient with Donohue syndrome associated with a novel p.Leu795Pro INSR gene mutation causing a severe decrease in IR autophosphorylation.
COBISS.SI-ID: 688044