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The main cause of morbidity and mortality in diabetes mellitus (DM) is cardiovascular complications. Diabetic cardiomyopathy (DCM) remains incompletely understood. Animal models have been crucial in exploring DCM pathophysiology while identifying potential therapeutic targets. Streptozotocin (STZ) has been widely used to produce experimental models of both type 1 and type 2 DM (T1DM and T2DM). Here, we compared these two models for their effects on cardiac structure, function and transcriptome. Different doses of STZ and diet chows were used to generate T1DM and T2DM in C57BL/6J mice. Normal euglycemic and nonobese sex- and age-matched mice served as controls (CTRL). Immunohistochemistry, RT-PCR and RNA-seq were employed to compare hearts from the three animal groups. STZ-induced T1DM and T2DM affected left ventricular function and myocardial performance differently. T1DM displayed exaggerated apoptotic cardiomyocyte (CM) death and reactive hypertrophy and fibrosis, along with increased cardiac oxidative stress, CM DNA damage and senescence, when compared to T2DM in mice. T1DM and T2DM affected the whole cardiac transcriptome differently. In conclusion, the STZ-induced T1DM and T2DM mouse models showed significant differences in cardiac remodeling, function and the whole transcriptome. These differences could be of key relevance when choosing an animal model to study specific features of DCM.

Three new equations for calculating the estimated basal serum creatinine (ebSCr) in hospitalized children have been developed: the simplified acute kidney injury (AKI) baseline creatinine (ABC) equation which considered only age in the formula; the equation including age and minimum creatinine (Crmin) within the initial 72 h from hospitalization (ABC-cr); and the equation including Crmin and height, weight, and age as squared values (ABC-advanced). We aimed to test the diagnostic performance of the ABC, ABC-cr and ABC-advanced equations in diagnosing AKI in 163 prospectively enrolled children with type 1 diabetes mellitus (T1DM) onset. We considered measured basal serum creatinine (mbSCr), the creatinine measured 14 days after T1DM onset. AKI was defined by the highest/basal serum creatine (HC/BC) ratio > 1.5. On the basis of the mbSCr, the AKI was diagnosed in 66/163 (40.5%) patients. This prevalence was lower than the prevalence of AKI diagnosed on the basis of ABC ebSCr (122/163 patients; 74.8%) (p < 0.001) and similar to the prevalence of AKI diagnosed on the basis of ABC-cr ebSCr (72/163 patients; 44.2%) (p = 0.5) and to the prevalence of AKI diagnosed on the basis of ABC-advanced ebSCr (69/163; 42.3%) (p = 0.73). AKI determined using ABC ebSCr, ABC-cr ebSCr and ABC-advanced ebSCr showed, respectively, 63.5% (kappa = 0.35; p < 0.001), 87.7% (kappa = 0.75; p < 0.001), and 87.1% (kappa = 0.74; p < 0.001) agreement with AKI determined using mbSCr. Using the HC/BC ratio calculated on the basis of mbSCr as gold standard, for Bland–Altman plots the HC/BC ratio calculated on the basis of ABC formula presented higher bias and wider limits of agreement compared with the HC/BC ratio calculated on the basis of ABC-cr and ABC-advanced formulas. In the receiver–operating characteristics (ROC) curve analysis the HC/BC ratio calculated on the basis of ABC ebSCr presented lower area under the ROC curve (AUROC) (AUROC = 0.89; 95%CI: 0.85–0.95; p < 0.001) compared with HC/BC ratio calculated on the basis of ABC-cr (AUROC = 0.94; 95%CI: 0.91–0.98; p < 0.001) or ABC-advanced ebSCr (AUROC = 0.914; 95%CI: 0.91–0.97; p < 0.001). In both Bland–Altman plots and ROC curve analysis, the ABC-cr and ABC-advanced formulas performed similarly. In conclusion, the ABC-cr and ABC-advanced formulas present very good diagnostic performance toward AKI identification in a population of children with T1DM onset.

Highlights A stable or even improved glycemic control was found in adolescents with T1DM using hybrid closed loop system not only during COVID-19 lockdown but also in the weeks after, when daily activities slowly resumed. Although the slowing down of routine daily activities might still have an influence, we believe that the continuation of the health care professional assistance through telemedicine during lockdown might have led to a "dragging effect" in these patients also after its suspension.

Measuring self-care behaviors is crucial in diabetes research worldwide. Having a common measure of self-care represents an unmet need limiting the development of the science. The Self-Care of Diabetes Inventory was developed to address limitations of previous tools that were not theoretically grounded, strong in psychometrics, and clinically validated. However, the generalizability and comparability of the Self-Care of Diabetes Inventory has not been tested across cultures and languages. The aim of this study was to test the invariance of the Self-Care of Diabetes Inventory measurement model between Italy and the United States. Data from two multicenter cross-sectional studies were used. Two diabetes clinics and two hospitals in Italy and the United States were involved. We enrolled 200 adults in Italy and 226 in the United States, all with a confirmed diagnosis of type 1 or type 2 diabetes. The Self-Care of Diabetes Inventory was used to measure self-care maintenance, monitoring, and management behaviors as described in the middle range theory of self-care of chronic illness. Configural, metric, scalar, and strict invariance were tested for each scale. Three of the four measurement equivalence levels were supported in the three Self-Care of Diabetes Inventory Scales, whereas strict invariance—the highest level—was reached only by the Self-Care Maintenance and Self-Care Monitoring Scales. Clear support for the use of the Self-Care of Diabetes Inventory in diabetes research was provided. Cross-national comparisons of self-care between groups of Italian and U.S. patients are supported, based on the invariance of the measurement model. Aggregation of research data obtained using the Self-Care of Diabetes Inventory across countries could support knowledge development in the field of diabetes self-care.

Aims: To describe self-care maintenance, monitoring, and management behaviors in adults with type 1 diabetes (T1DM), and to identify clinical and socio-demographic determinants of inadequate self-care. Methods: A cross-sectional study was conducted in two diabetes outpatient clinics in Italy. Clinical and socio-demographic characteristics were collected from the medical records of 181 consecutively enrolled T1DM patients. The Self-Care of Diabetes Inventory was used to measure self-care maintenance, self-care monitoring, self-care management and self-care confidence. A standardized 0–100 score was used for each self-care dimension. A score < 70 was considered inadequate self-care. Three multiple logistic regression models were run to find determinants of inadequate self-care maintenance, monitoring, and management. Results: The majority of patients had adequate self-care maintenance (74%; n = 134), self-care monitoring (68.5%; n = 124) and self-care confidence (87.3%; n = 158), while self-care management was adequate for only a minority (34.8%; n = 63). The odds of inadequate self-care maintenance increased by 4.5 times when self-care confidence was inadequate (OR adjusted 4.589; 95% CI 1.611–13.071; p = 0.004). The odds of inadequate self-care monitoring increased four times when patients had inadequate self-care confidence (OR adjusted 4.116; 95% CI 1.457–11.628; p = 0.008). Inadequate self-care confidence increased the odds of performing inadequate self-care management more than five times (OR adjusted 5.313; 95% CI 1.143–24.686; p = 0.033). Conclusions: Self-care management is commonly inadequate in adults with T1DM. Self-care confidence is the most important determinant of self-care behaviors in this population. Educational interventions are recommended to improve self-care confidence in adults with T1DM.

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In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Type 1 diabetes mellitus (T1D) is a complex disorder characterized by an autoimmune response against human pancreatic beta-cells. Patients with T1D can also develop a response toward one or more other factors, such as in autoimmune thyroiditis (AITD) and celiac disease (CD). In the presence of T1D + AITD, the patient is diagnosed with autoimmune polyglandular syndrome type III (APSIII); patients with APSIII may also present with CD. These diseases have a strong genetic component and share many susceptibility genes, suggesting potentially overlapping pathogenic pathways. Polymorphisms in the TNF-α(rs1800629), CTLA-4 (rs231775), and PTPN22 (rs2476601) genes have been previous associated with T1D; however, there is no consensus regarding their role in T1D and scarce literature focusing on AIDT and/or CD. Thus, we analyzed these genetic variants in 205 Northeast Brazilian patients with T1D and with/without AITD and/or CD, and in 308 healthy controls. The PTPN22 gene variants were associated with T1D susceptibility and APSIII [odds ratio (OR) = 2.57 and 2.77, respectively]. CTLA4 rs231775 and TNF-αrs1800629 were not associated with T1D onset in the Brazilian population. However, when comparing APSIII individuals in the T1D only group, we observed an association of the TNF-αSNP in the allelic (P = 0.0442; OR = 0.44) and dominant models (P = 0.0387; OR = 0.40). This study reinforces the importance of CTLA-4 and other variants in unraveling the pathogenic mechanisms of T1D in different populations and in understanding their relationships with the development of other T1D-related autoimmune diseases.

Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence β-cell function, insulin sensitivity, and systematic inflammation-all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

Objective: To identify the role of the family's socio-economic and clinical characteristics on metabolic control in children and adolescents with type 1 diabetes. Methods: In this cross-sectional, multicentre study, 768 subjects with type 1 diabetes under 18 years of age were consecutively recruited from January 2008 to February 2009. Target condition was considered for HbA1c values

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily, which plays an important role in regulating cell death and inflammation. Beyond its anti-tumor activity, increasing evidence in animal studies suggests that TRAIL plays a role in the control of autoimmune diseases, and in particular in type 1 diabetes mellitus (T1DM) [1, 2]. In this context, in a previous study carried out in a retrospective cohort of T1DM pediatric patients, we found significant lower levels of circulating TRAIL in T1DM patients with respect to healthy age-matched controls [3]. However, a limitation of our previous study was as follows: (1) the lack of serial serum samples harvested from the same patients at different time post onset and (2) the lack of information about concurrent metabolic status at time of blood sampling. On these bases, the aim of the present study was to analyze the evolution of circulating TRAIL levels in a pilot group of pediatric patients admitted at Emergency Department for T1DM, from the time of hospital admission throughout the re-establishment of a normal metabolic balance and up to 18 months of clinical follow-up. Moreover, the serum levels of TRAIL in T1DM patients were analyzed in relation to the metabolic status determined at the same times.

Type 1 diabetes mellitus may be associated with many autoimmune diseases with the common autoimmune pathogenesis. We describe the case of a girl suffering from Type 1 diabetes mellitus and autoimmune Hashimoto's thyroiditis since the childhood and, due to the onset of Juvenile Idiopathic Arthritis during adolescence, for three years practiced therapy with an anti-TNF drug, etanercept . Currently her inflammatory markers are normal, arthritis is inactive and diabetes is well controlled. During the treatment with anti-TNF drug we observed a significative reduction of insulin dose, probably due to an increased tissue sensitivity secondary to the suppression of the activity of TNF-alpha. Several clinical trials that have evaluated the effect of immunomodulatory agents in diabetic patients, especially in those with recent onset of disease, were already performed but further studies of longer duration on a larger population are needed to assess the role of biologic drugs and immunotherapy in this group of patients.

Interleukin 18 (IL-18) is a cytokine that plays an important role in the Th1 response, by its ability to induce IFN-γ production in T cells and natural killer cells. Functional variants of IL18 gene has been reported as associated with type 1 diabetes (T1D). In the present study were analyzed three promoter single nucleotide polymorphisms (SNPs), at −656 (rs1946519), −607 (rs1946518) and −137 (rs187238) position, in 181 children and adolescents with T1D and 122 healthy individuals, both from metropolitan area of Recife, Northeast of Brazil. T1D patients were stratified according to the presence autoimmune thyroiditis and celiac disease. Allele and genotype frequencies of IL18 SNPs were Hardy–Weinberg equilibrium in patients and controls. The allele −137G and the haplotype −656G/−607C/−137G were more frequent in T1D patients (OR=1.82 and 1.97, respectively) then in healthy controls. However, those SNPs were not associated with the age of T1D onset as well as with the insurgence of AITD and/or CD in concomitant with T1D patients. Our findings suggest an association between IL18 promoter SNPs and susceptibility to T1D in Brazilian patients.

We have read with interest the original article by Picarelli et al. [1] describing metabolic control and selected hemocoagulative/anticoagulant parameters in patients with isolated type 1 diabetes mellitus (T1DM) and in those affected by celiac disease (CD) too. According to our experience at Pediatric Endocrinology Unit of Trieste, we respectfully disagree with Picarelli’s conclusion and otherwise support the importance of a gluten-free diet (GFD). Picarelli et al. emphasize a better metabolic and glycolipidic control in patients with both DM1 and CD not following a GFD and suggest a protective role of CD in the prothrombotic state of DM1. In our opinion, their study has three critical points. First, all patients presented a glycosylated hemoglobin level (HbA1c)\7.5%. These inclusion criteria could be a selection bias that could influence the results. Second, in accord with literature, we believe that a single variable (glycosylated hemoglobin) is not sufficient to evaluate glycemic control: daily insulin dosages, hypoglycemia frequency, and glycemic variability should be also considered. Glycemic variability, specially, is considered an independent risk factor for complications [2]. Third, they do not analyze the effect of CD on the anthropometric variables nor investigate the presence of other autoimmunities. We followed up 74 patients with diabetes to evaluate the prevalence of celiac disease (CD) in a cohort of children with type 1 diabetes (T1DM) and to investigate the influence of CD on growth and metabolic control, before and after gluten-free diet (GFD). A total of 17 celiac-positive subjects (group 1) and 57 celiac-negative subjects (group 2) were examined. Data on growth and metabolic control were collected retrospectively at three different moments (diabetes diagnosis, CD diagnosis, and 6–12 months after a GFD was started). Prevalence of CD accounts for 13% of our cohort, which is comparable with prevalence in Picarelli’s cohort (13.8%). In most of cases (70%), screening test led to the diagnosis. In 70% of CD-positive patients, HbA1c levels were\8% before GFD (vs 54% of CD negative), but only in 42% of them after GFD. In CD-positive cases, good HbA1c levels were often associated with glycemic variability (65%) before GFD, while quite rarely after 6–12 months of diet (28.5%). These results allow us to suppose that before GFD was started, metabolic control was apparently good, but it really improved after GFD (reduction in glycemic variability). Besides, in our cohort, we observed that the co-occurrence of both disease compromises growth, and meanwhile, it improves after that GFD is started (BMI of CD-positive subjects rises from 46 percentile before GFD, to 54 after GFD, P \ 0.05). In our cohort, CD remains asymptomatic in the most of cases (70%), and then, the diagnosis would have been missed if the screening had not been performed, as confirmed by Picarelli’s study too. This result accords with literature [3–10] and supports importance of serological screening in diabetic population. In conclusion, we believe that serological screening is useful for diagnosing asymptomatic CD and GFD in CDpositive diabetic patients can allow growth and diabetes control comparable with patients with T1DM alone. P. Pascolo (&) E. Faleschini G. Tonini A. Ventura Institute for Child Health IRCCS Burlo Garofolo, Trieste, Italy e-mail: paolapascolo@gmail.com