Prevention of type 1 diabetes in NOD mice by 1,25-dihydroxyvitamin D 3 [1␣,25(OH) 2 D 3 ] is accompanied by a T-helper (Th) 1/Th2 cytokine shift in the pancreas. The aim of this study was to investigate whether this immune shift also occurs outside of the pancreas and whether it is limited to autoantigen-specific immune responses. NOD mice treated with 1␣,25(OH) 2 D 3 (5 µg/kg every 2 days) or control vehicle were immunized with GAD65 (p524-543) or ovalbumin (OVA) in the rear footpads. First, we examined T-cell proliferation and cytokine production (via enzyme-linked immunosorbent assay) of draining lymph node cells in vitro with or without peptide rechallenge. Although no differences in proliferation were measured between control and 1␣,25(OH) 2 D 3 -treated mice after in vitro GAD65 rechallenge, a marked shift in cytokine secretion profile was seen in 1␣,25(OH) 2 D 3 -treated mice: interleukin-4 was increased (37 ± 5 vs. 21 ± 12 pg/ml in controls, P < 0.005), whereas ␥-interferon levels were decreased (6 ± 3 vs. 9 ± 3 ng/ml in controls, P < 0.05). This shift was absent in OVA-primed mice. Second, we measured cytokine profiles by reverse transcriptase-polymerase chain reaction in popliteal lymph nodes at different time points after priming with GAD65 or OVA in vivo. A marked Th1/Th2 shift occurred in 1␣,25(OH) 2 D 3 -treated mice after in vivo priming with GAD65. Again, this shift was absent after OVA immunization. Finally, we measured cytokine profiles after rechallenge with a panel of autoantigens (GAD65, heat shock protein 65, insulin Bchain) and control antigens (OVA, keyhole limpet hemocyanine, myelin proteolipid protein, tetanus toxin) and confirmed the Th1/ Th2 shift in autoantigen-injected mice but not in control antigen-injected mice. In conclusion, the immune deviation induced by 1␣,25(OH) 2 D 3 in NOD mice can also be induced in the peripheral immune system but is limited to pancreatic autoantigens.

Background Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control. Objective To examine the frequency of pump usage in T1D children treated in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI. Methods This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized diabetes patient registry. Datasets were aggregated over the most recent year of treatment for each patient. Data were collected until March 2016. To assess the organization of pump therapy a survey was carried out. Results Overall, 44.4% of T1D children were treated with CSII. The proportion of patients with pump usage varied between centers and decreased with increasing age compared with children treated with MDI. In a logistic regression analysis adjusting for age, gender and diabetes duration, the use of pump was associated with both: center size [odd ratio 1.51 (1.47‐1.55), P < .0001) and the diabetes‐related expenditure per capita [odd ratio 1.55 (1.49‐1.61), P < .0001]. Linear regression analysis, adjusted for age, gender, and diabetes duration showed that both HbA1c and daily insulin dose (U/kg/d) remained decreased in children treated with CSII compared to MDI (P < .0001). Conclusions Insulin pump therapy is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age.

IntroductionBody temperature measurement in children is of clinical relevance. Although rectal measurement is the gold standard, less invasive tools have become available. We aimed to describe the accuracy of tympanic, infrared skin, or temporal artery scan thermometers compared with rectal measurement to reflect core temperature.MethodsRectal (Filac 3000; Covidien, Mechelen, Belgium), tympanic (AccuSystem Genius2 Typmanic Infrared Ear Thermometer, Covidien, Mechelen, Belgium), temporal artery scan (Exergen, Exergen Corp, Watertown, Massachusetts), and infrared (ThermoFlash Contactless Medical Electronic Thermometer, Visiomedlab, Paris, France) body temperature measurements were randomly performed and readings were collected once. Temperature readings were described as median and range, and observations were compared with rectal temperature readings (using Wilcoxon, Bland-Altman, sensitivity, and specificity tests). The child’s comfort was assessed by the child, parent, and nurse (using Likert scales) and ease of use was assessed by nurses (using visual analog scale).ResultsBased on observations in 294 (median age = 3.2 years, range = 0.02–17 years) children, the mean difference was 0.49°C (tympanic scan; P < 0.0001), 0.34°C (infrared skin scan; P < 0.0001), and 0°C (temporal artery scan; P = 0.9288), respectively, when compared with rectal temperature readings. Based on visual inspection of Bland-Altman plots, all tools overestimated the temperature at lower body temperature and underestimated the temperature at higher body temperature, resulting in a sensitivity of 22% to 41% and a specificity of 98% to 100% for rectal temperatures above 38°C. The Likert scale scores and the visual analog scale scores for rectal measurement were only slightly higher when compared with the other methods.ConclusionsAll noninvasive techniques underperformed compared with rectal measurement. The temporal artery scan deviations were smallest, but all noninvasive techniques overestimate lower temperatures and underestimate higher temperatures compared with rectal measurement. In our hands, temporal artery scan measurement seems to be second best, but not yet ideal.

KH1060, an analog of 1,25(OH)2D3, delays autoimmune disease recurrence after syngeneic islet transplantation in NOD mice, both alone and especially in combination with CsA, possibly restoring tolerance to beta cells in 30% of cases.