Search

Aims: Patient-reported outcomes (PROs) are increasingly important for assessing patient satisfaction with diabetes technologies. PROs must be assessed with validated questionnaires in clinical practice and research studies. Our aim was to translate and validate the Italian version of the continuous glucose monitoring (CGM) Satisfaction (CGM-SAT) scale questionnaire. Methods: Questionnaire validation followed MAPI Research Trust guidelines and included forward translation, reconciliation, backward translation, and cognitive debriefing. Results: The final version of the questionnaire was administered to 210 patients with type 1 diabetes (T1D) and 232 parents. The completion rate was excellent, with almost 100% of items answered. The overall Cronbach’s coefficient was 0.71 and 0.85 for young people (patients) and parents indicating moderate and good internal consistency, respectively. Parent–young people agreement was 0.404 (95% confidence interval: 0.391–0.417), indicating moderate agreement between the two assessments. Factor analysis identified that factors assessing the “benefits” and “hassles” of CGM accounted for 33.9% and 12.9% of score variance in young people and 29.6% and 19.8% in parents, respectively. Discussion: We present the successful Italian translation and validation of the CGM-SAT scale questionnaire, which will be useful for assessing satisfaction with Italian T1D patients using CGM systems.

Type 1 diabetes mellitus (T1DM) is a complex metabolic disease characterized by a massive loss of insulin-producing cells due to an autoimmune reaction. Currently, daily subcutaneous administration of exogenous insulin is the only effective treatment. Therefore, in recent years considerable interest has been given to stem cell therapy and in particular to the use of three-dimensional (3D) cell cultures to better reproduce in vivo conditions. The goal of this study is to provide a reliable cellular model that could be investigated for regenerative medicine applications for the replacement of insulin-producing cells in T1DM. To pursue this aim we create a co-culture spheroid of amniotic epithelial cells (AECs) and Wharton’s jelly mesenchymal stromal cells (WJ-MSCs) in a one-to-one ratio. The resulting co-culture spheroids were analyzed for viability, extracellular matrix production, and hypoxic state in both early- and long-term cultures. Our results suggest that co-culture spheroids are stable in long-term culture and are still viable with a consistent extracellular matrix production evaluated with immunofluorescence staining. These findings suggest that this co-culture may potentially be differentiated into endo-pancreatic cells for regenerative medicine applications in T1DM. Type 1 diabetes mellitus (T1DM) is a complex metabolic disease characterized by a massive loss of insulin-producing cells due to an autoimmune reaction. Currently, daily subcutaneous administration of exogenous insulin is the only effective treatment. Therefore, in recent years considerable interest has been given to stem cell therapy and in particular to the use of three-dimensional (3D) cell cultures to better reproduce in vivo conditions. The goal of this study is to provide a reliable cellular model that could be investigated for regenerative medicine applications for the replacement of insulin-producing cells in T1DM. To pursue this aim we create a co-culture spheroid of amniotic epithelial cells (AECs) and Wharton’s jelly mesenchymal stromal cells (WJ-MSCs) in a one-to-one ratio. The resulting co-culture spheroids were analyzed for viability, extracellular matrix production, and hypoxic state in both early- and long-term cultures. Our results suggest that co-culture spheroids are stable in long-term culture and are still viable with a consistent extracellular matrix production evaluated with immunofluorescence staining. These findings suggest that this co-culture may potentially be differentiated into endo-pancreatic cells for regenerative medicine applications in T1DM.

Considerando che la prima definizione strutturata di biomateriali è stata formulata solo 50 anni fa, e che 100 anni fa i biomateriali come li conosciamo ora non esistevano nemmeno, possiamo affermare che rappresentano un punto cruciale del progresso scientifico, rivoluzionando la biomedicina. Molti aspetti della medicina clinica, compreso il trattamento di patologie croniche, il delivery di piccole molecole, la produzione di dispositivi medici e l’ingegneria tissutale non sarebbero gli stessi senza i recenti sviluppi di questa classe di materiali. L’ampia gamma di applicazioni per cui possono essere progettati, le caratteristiche uniche e la possibilità di adattare il costrutto finale ad un’ampia varietà di scopi garantiscono un interesse ancora molto elevato attorno al loro sviluppo. La possibilità di implementare nuovi aspetti e tecnologie e ottenere prodotti più complessi rende i biomateriali validi candidati per affrontare delle sfide aperte nel trattamento di molteplici condizioni patologiche ed espandere i confini della medicina moderna. In questa tesi, viene proposta, per molteplici applicazioni, la derivatizzazione chimica e la formulazione di polimeri sia di origine sintetica sia naturale. La combinazione di diverse classi di polimeri e le loro proprietà, oltre allo sfruttamento del concetto di multivalenza, sono alla base di tutti i progetti presentati. Viene descritto lo sviluppo di nanoparticelle polimeriche multimodali, basate su una combinazione di acido poli-γ-glutammico e chitosano, per la visualizzazione delle isole pancreatiche e delle cellule β derivate da cellule staminali pluripotenti indotte. Questo tipo di strumento potrebbe essere cruciale nella trasposizione in clinica di terapie rigenerative per il diabete di tipo 1, basate sull’utilizzo di pancreas bio-artificiali, dal momento che consente l’imaging di specifiche cellule ad alta sensibilità e quindi il monitoraggio della vitalità all’interno di questi tipi di dispositivi. Queste nanoparticelle sono versatili e, decorandole con diversi agenti di targeting e detecting, è possibile sviluppare nanomateriali adatti al monitoraggio della sopravvivenza, attecchimento, proliferazione e funzione di trapianti cellulari e lo sviluppo e validazione dell’applicazione di tecnologie di imaging all’avanguardia che facilitano l’impiego di nuove terapie rigenerative su modelli preclinici con animali di grandi dimensioni e su pazienti. Inoltre, è stata sviluppato uno scaffold polimerico lineare basata su un polimero sintetico coniugato con un analogo del naturale delle cellule β pancreatiche (exendina-4, Ex4), e può portare a nuovi agenti terapeutici o di diagnostica. Infatti, il polimero presenta più siti disponibili per successiva coniugazione di ulteriori oggetti. I prodotti sintetizzati possono essere utilizzati anche come vettori per il rilascio controllato di Ex4. Un altro coniugato polimerico è stato sviluppato e studiato, in concomitanza con una libreria di piccole molecole basate sul mannosio, per il trattamento del batterio Pseudomonas Aeruginosa. In questo caso, il chitosano è stato scelto come componente polimerica, sfruttando la sua tenue attività antibatterica e la possibilità di essere usato come scaffold, combinato con la capacità di interagire con LecB di solfonati e solfossimmine derivati dal mannosio, che sono stati coniugati al polimero. Infine, un idrogelo ibrido composto da acido ialuronico e gelatina è stato sviluppato per la biostampa 3D con cellule U87. L’idrogelo proposto è reticolato chimicamente e ricorda con le sue specificità la matrice extracellulare naturale cerebrale in composizione e caratteristiche. Questo tipo di materiale può servire come modello 3D di glioblastoma e può essere utilizzato per uno screening più affidabile e conveniente di farmaci antitumorali, anche considerando l’elevata malignità, resistenza verso trattamenti antitumorali e alto tasso di ricorrenza del tumore. Considering that the first structured definition of biomaterials was given only 50 years ago and that 100 years ago biomaterials, as we think about them today, did not even exist, we could claim they have been a crucial point in scientific advances, as they revolutionized many aspects of biomedicine. Thinking about the state-of-the-art of many fields in medicine and biotechnologies, biomaterials are widely employed. Many aspects of clinical medicine, including chronic conditions treatment, drug delivery, medical device manufacturing, and tissue engineering would not be the same without all the recent advances in the development of this class of materials. The wide range of applications they can be designed for, the unique characteristics, and the possibility to tune them and adapt the final construct for an extended variety of cases and purposes ensure a still high hype around their development. Even though much progress has been made, the possibility to implement new aspects and technologies and obtain more smart and complex products makes biomaterials valid candidates to face opening challenges in the treatment of multiple pathological conditions and expand the boundaries of modern medicine. In this thesis, the chemical derivatization and formulation of polymers of both synthetic and natural origin for multiple applications are proposed. The combination of different classes of polymers and so of their properties, and the exploitation of the concept of multivalency, underlie all the presented projects. Hence, we show the development of multimodal polymeric nanoparticles, based on a combination of poly-γ-glutamic acid (γ-PGA) and chitosan, for the imaging of porcine pancreatic islet and induced pluripotent stem cell-derived β-cells. This kind of tool might be crucial in the clinical translation of type 1 diabetes regenerative therapies involving bio-artificial pancreas, since it allows the imaging of specific cell types with high sensitivity and therefore the monitoring of β cells viability inside this kind of device. The proposed nanoparticles are highly versatile, and by decorating different targeting and detecting agents it is possible to develop nanotools suitable for monitoring of survival, engraftment, proliferation, function, and whole-body distribution of the cellular transplants and the development and validation of the application of state-of-the-art imaging technologies facilitating the provision of new regenerative therapies to preclinical large animal models and patients. Furthermore, a linear polymeric scaffold based on a synthetic polymer conjugated to an analogue of natural ligand of pancreatic β-cells (exendin-4, Ex4) has been developed, and can lead to new therapeutics and diagnostics agents. Indeed, the polymer displays more available sites for subsequent conjugation of other entities. The synthesized compounds may function per se as Ex4 controlled release carriers. Another polymeric conjugate, together with a library of mannoside-based small molecules, has been designed and studied for the treatment of Pseudomonas Aeruginosa bacterium. In this case, chitosan has been selected as polymeric component, exploiting its mild antimicrobial activity and its capability to serve as a linear scaffold and combining it with the lectin B targeting capability of mannoside-derived sulfonates and sulfoximines. Lastly, a hybrid hydrogel made of hyaluronic acid and gelatin has been developed for 3D bioprinting with U87 cells. The proposed hydrogel is chemically crosslinked and resembles in its features the natural extracellular matrix (ECM) brain composition and characteristics This kind of material may serve as a model of glioblastoma for 3D cell culture and can be used for more reliable and convenient antitumoral drug screening routes, considering the high malignancy, resistance towards antitumoral treatments and the high recurrence rate.

Context Patients with type 1 diabetes (T1D) have higher cardiovascular disease (CVD) risk than the general population. Objective This observational study aims to evaluate sex-related differences in CVD prevalence and CVD risk estimates in a large cohort of T1D adults. Methods We conducted a multicenter, cross-sectional study involving 2041 patients with T1D (mean age 46 years; 44.9% women). In patients without pre-existing CVD (primary prevention), we used the Steno type 1 risk engine to estimate the 10-year risk of developing CVD events. Results CVD prevalence (n = 116) was higher in men than in women aged ≥55 years (19.2 vs 12.8%, P = .036), but comparable between the 2 sexes in those aged Conclusion Both men and women with T1D are at high CVD risk. The 10-year estimated CVD risk was higher in men aged

Context Poor glucose control has been associated with increased mortality in COVID-19 patients with type 1 diabetes (T1D). Objective This work aimed to assess the effect of prevaccination glucose control on antibody response to the SARS-CoV-2 vaccine BNT162b2 in T1D. Methods We studied 26 patients with T1D scheduled to receive 2 doses, 21 days apart, of BNT162b2, followed prospectively for 6 months with regular evaluation of SARS-CoV-2 antibodies and glucose control. Immunoglobulin G (IgG) to spike glycoprotein were assessed by enzyme-linked immunosorbent assay, and serum neutralization by a live SARS-CoV-2 assay (Vero E6 cells system). Glycated hemoglobin A1c (HbA1c) and continuous glucose monitoring (CGM), including time in range (TIR) and above range (TAR), were collected. The primary exposure and outcome measures were prevaccination glucose control, and antibody response after vaccination, respectively. Results Prevaccination HbA1c was unrelated to postvaccine spike IgG (r = −0.33; P = .14). Of note, the CGM profile collected during the 2 weeks preceding BNT162b2 administration correlated with postvaccine IgG response (TIR: r = 0.75; P = .02; TAR: r = −0.81; P = .008). Patients meeting the recommended prevaccination glucose targets of TIR (≥ 70%) and TAR (≤ 25%) developed stronger neutralizing antibody titers (P < .0001 and P = .008, respectively), regardless of HbA1c. Glucose control along the study time frame was also associated with IgG response during follow-up (TIR: r = 0.93; P < .0001; TAR: r = −0.84; P < .0001). Conclusion In T1D, glucose profile during the 2 weeks preceding vaccination is associated with stronger spike antibody binding and neutralization, highlighting a role for well-controlled blood glucose in vaccination efficacy.

Background: Type 1 diabetes mellitus requires complex skills of self-care that, during adolescence, need to be adapted to continuous major changes. Therefore, adolescents could struggle in performing adequate self-care, with consequences on glycaemic control. Caregivers’ contribution to self-care could be useful for reaching health outcomes. Existing studies lacked a theoretical framework, and tools administered for measuring adolescents’ self-care and caregivers’ contribution to self-care were not theory grounded. Aim: To describe adolescents’ self-care and caregiver contribution to self-care within the theoretical framework of the middle-range theory of self-care of chronic illness. Methods: A cross-sectional observational study was conducted enrolling 153 adolescent-caregiver dyads. The Self-Care of Diabetes Inventory (SCODI), including self-care maintenance, monitoring and management, was administered to adolescents. The Caregiver Contribution to Self-Care of Diabetes Inventory (CC-SCODI), including caregiver contribution to self-care maintenance, monitoring and management, was administered to caregivers. We analysed the differences in caregiver contribution according to adolescents’ self-care level and the differences in caregiver characteristics according to their contribution to self-care level. Results: Adolescents mostly obtained adequate scores for self-care maintenance (74%), monitoring (52%) and management (58%). Caregivers mostly obtained adequate scores for contribution to self-care maintenance (72%) and monitoring (52%), and almost adequate scores for contribution to self-care management (41%). Scores were consistent within the dyads for self-care monitoring and management: high caregiver contribution when adequate adolescent self-care and vice-versa (P < 0.001). Higher caregiver self-efficacy in contributing to patient self-care was associated with higher caregiver contribution to self-care maintenance (P = 0.022), monitoring (P < 0.001) and management (P < 0.001). Conclusion: Caregivers can contribute significantly to the self-care of adolescents with type 1 diabetes. Health professionals could implement interventions aimed at improving caregivers’ contribution through enhancing caregiver self-efficacy in contributing to patient self-care. Researchers could deepen the understanding of the relationship between adolescent self-care and caregiver contribution to self-care, as well as the determinants of caregiver contribution to self-care, and its effects on health outcomes.

Despite type 1 diabetes' (T1D) potential influence on adolescents' physical development, the occurrence of body image problems of adolescents with diabetes remains unclear. No research synthesis has yet addressed this issue. This study aims to systematically evaluate the empirical evidence concerning body image in individuals with T1D in order to provide an overview of the existing literature. Using PRISMA methodology, 51 relevant studies that fulfilled the eligibility criteria were found, the majority of them (N = 48) involving youth. The findings varied across studies: 17 studies indicated that in youth with T1D, body dissatisfaction was common and that body concerns were generally greater in youth with T1D than in controls; nine studies did not find any differences in body image problems between participants with and without T1D; three studies described higher body satisfaction in youth with diabetes than in controls; and three studies reported mixed results. Body concerns in individuals with T1D were often found to be associated with negative medical and psychological functioning. The variability and limits in assessment tools across studies, the overrepresentation of female subjects, and the fact that most research in this field is based on cross-sectional data are stressed in the interpretation of these mixed findings. Future research directions that could improve the understanding of body image concerns and clinical implications are discussed.

Background Cardiovascular risk and body-weight management are both emerging challenges of type 1 diabetes care. We evaluated the association between intraindividual variability of body-weight and risk of cardiovascular events in people with type 1 diabetes. Methods We analyzed 1,398 participants from the DCCT/EDIC studies. Five indices of intraindividual variability of body-weight were calculated for each participant taking into account body-weight measures obtained during the DCCT follow-up (average 6 ± 2 years). The Average Successive Variability (ASV) index, the main variable of interest, was defined as the average absolute difference between successive body-weight measures. The primary outcome was a composite of major adverse cardiovascular events (MACE: nonfatal myocardial infarction or stroke, or cardiovascular death) occurring during the subsequent EDIC follow-up (20 ± 3 years). All-cause death was a secondary outcome. Risk of outcomes were assessed by Cox proportional hazards regression analyses, adjusted for traditional cardiovascular risks factors, including BMI. Results The cumulative incidence of MACE and all-cause death during follow-up were 5.6% (n = 79) and 6.8% (n = 95), respectively. The adjusted Hazard Ratio (HR) for MACE by every increase of 1 standard deviation (SD) of ASV was 1.34 (95% CI, 1.06–1.66), p = 0.01. For all-cause death, the adjusted HR for 1 SD increase of ASV was 1.25 (1.03–1.50), p = 0.03. Similar results were observed when considering the other indices of intraindividual variability of body-weight. Conclusions High body-weight variability (body-weight cycling) is associated with increased risk of MACE and all-cause death in people with type 1 diabetes, independently of the BMI and traditional cardiovascular risk factors.

To explore intraindividual (between-meals) and interindividual (between-subjects) variability of postprandial glucose response (PGR) in type 1 diabetes (T1DM).Data were taken from five cross-over trials in 61 subjects with T1DM on insulin pump wherein the effects of different dietary components or the intraindividual-variability of PGR to the same meal were evaluated by CGM. Predictors (type of meal or nutrient composition) of early (iAUCHigh-glycemic-index (HGI) and low-glycemic-index meals were the best positive and negative predictors of glucose iAUCBeyond the meal characteristics (including glycemic index, fat and fiber content), individual traits significantly influence PGR. Specific interindividual factors should be further identified to properly predict glucose response to meals with different composition in individuals with T1DM.

BACKGROUND Microneurographic recordings of muscle sympathetic nerve activity (MSNA) have shown that sympathetic activation may characterize diabetes mellitus. However, it is recognized that comorbidities and metabolic abnormalities frequently associated with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) diabetes affect MSNA, generating potential confounding effects and making the association between sympathetic activation and diabetes mellitus still a controversial matter. METHODS The present meta-analysis evaluated 11 microneurographic studies enrolling 314 diabetes mellitus patients and healthy controls, and MSNA was chosen as the main variable of interest. Collection of the data included indirect adrenergic markers such as heart rate and venous plasma noradrenaline, together with hemodynamic, anthropometric and metabolic variables. RESULTS A total of 11 microneurographic studies were evaluated including 314 diabetes mellitus patients and controls. Diabetes mellitus displayed MSNA significantly greater than controls (mean difference amounting to 8.1, 95% confidence interval 1.21-15.08, P

Aims/hypothesis: Impaired wound healing significantly impacts morbidity and mortality in diabetic patients, necessitating the development of novel treatments to improve the wound healing process. We here investigated the topical use of acellular embryonic stem cell extracts (EXTs) in wound healing in diabetic db/db mice. Methods: Wounds were induced in diabetic db/db mice, which were subsequently treated with EXTs, with 3T3 fibroblast cell line protein extracts (3T3XTs) or with saline as a control. Pathology and mechanistic assays were then performed. Results: The in vivo topical administration of EXTs facilitates wound closure, contraction and re-epithelialization. Moreover, EXTs reduced the number of wound-infiltrating CD45+ inflammatory cells and increased the rate of repair and of angiogenesis as compared to controls. Interestingly, the EXT effect was partly enhanced by the use of a collagen-based biocompatible scaffold. In vivo, topical administration of EXTs increased the percentage of regulatory T cells in the wounded tissue, while in vitro EXT treatment reduced T cell-mediated IFN-γ production. Proteomic screening revealed 82 proteins differentially segregating in EXTs as compared to 3T3 extracts, with APEX1 identified as a key player for the observed immunomodulatory effect of EXTs. Conclusions: EXTs are endowed with immunoregulatory and anti-inflammatory properties; their use improves wound healing in diabetic preclinical models.

We read with interest the article by Messer et al.1 reporting a significant increase in time in range (TIR, +9%, P

Background and aims: The renin-angiotensin system (RAS), which is a key mediator of cardiovascular homeostasis, has two main axes. The classic one, including angiotensin-converting enzyme (ACE) and Angiotensin (Ang) II, promoting vasoconstriction, and the “alternative” one, including ACE2 and Ang1-7, with opposed actions to AngII. ACE2 has been identified as the main receptor of SARS-CoV2, whereby it enters the cells, leading to the downregulation of surface ACE2 and RAS tissue unbalance. Given that diabetes is associated with an increase in COVID-19 severity and death, we aimed at evaluating RAS expression in patients with type 1 diabetes (T1D). Methods and results: This is a case–control study comparing 39 T1D patients to 33 controls, with a median age of 29 and 32 years, and no comorbidities. ACE and ACE2 gene expression was assessed in peripheral blood mononuclear cells. T1D patients had higher ACE expression and circulating AngII, which were related to glucose levels. T1D patients had lower ACE2 expression. However, ACE2 expression was also related to the sex of participants, being higher in the female group. T1D women did not show the same increase of ACE2 expression that was seen in control women. Conclusion: T1D promotes the increase of ACE, AngII, and ACE/ACE2, which might contribute to the higher cardiovascular risk, as well as to severe tissue injury induced by SARS-CoV2 in these patients. The ratio ACE/ACE2 does not differ between men and women with T1D, which might explain why CVD or COVID-19 do not show substantial gender differences in these patients.

Objective To evaluate the six-month impact of the advanced automated functions of a closed-loop control (CLC) system (Control-IQ) and a virtual educational camp (vEC) on emotions and time in range (TIR) of children and adolescents with type 1 diabetes. Methods Children and their parents participated in a three-day vEC. Clinical, glucose, and emotion data were evaluated before, just after, and six months after the vEC. Emotions were evaluated using adapted Plutchik's and Geneva Emotion Wheels. Results Forty-three children and adolescents (7–16 years) showed significant improvements in positive emotions immediately and six months after the vEC (67% and 65% vs 38%, p < 0.05, respectively), while mixed emotions were reduced (32% and 15% vs 61%, p < 0.05 and p < 0.001, respectively). The median percentage TIR increased from 64% (IQR 54–72) to 75% (IQR 70–82) with Control-IQ (p < 0.001) six months after the vEC. Conclusions Positive emotions (joy, serenity, and satisfaction) significantly improved while mixed emotions were significantly worse six months after the initiation of a CLC system (Control-IQ) and a vEC.

Past studies on altered taste function in individuals with type 1 diabetes have yielded inconsistent results. We therefore evaluated taste recognition and possible association with personal and diseases characteristics in young individuals with type 1 diabetes and healthy controls. Taste recognition and intensity for 6-n-propylthiouracil (PROP), quinine, citric acid, sucrose, and sodium chloride were assessed using a filter paper method in 276 participants with type 1 diabetes and 147 healthy controls. Personal and clinical data were recorded for all participants during a baseline visit. Regression analysis was adjusted for sex, age, and standardized BMI. Overall, 47% of participants with type 1 diabetes vs. 63.5% of healthy controls recognized all tastes (p = 0.006). Moreover, a lower capacity for recognizing the bitter taste of PROP and the sour taste of citric acid was found in participants with type 1 diabetes compared to healthy controls (p = 0.014 and p = 0.003, respectively). While no significant effect of glycemic control on taste recognition was found, an association with lower age at onset emerged. Our findings suggest an impaired taste perception in individuals with type 1 diabetes, possibly linked to age at onset.

Aim/HypothesisTo compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019.MethodsForty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019.ResultsOverall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, pConclusions/InterpretationThere was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks.

The study compares the performance of the European Society of Cardiology (ESC) risk criteria and the Steno Type 1 Risk Engine (ST1RE) in the prediction of cardiovascular (CV) events.456 adults with type 1 diabetes (T1D) were retrospectively studied. During 8.5 ± 5.5 years of observation, twenty-four patients (5.2%) experienced a CV event. The predictive performance of the two risk models was evaluated by classical metrics and the event-free survival analysis.The ESC criteria show excellent sensitivity (91.7%) and suboptimal specificity (64.4 %) in predicting CV events in the very high CV risk group, but a poor performance in the high/moderate risk groups. The ST1RE algorithm shows a good predictive performance in all CV risk categories. Using ESC classification, the event-free survival analysis shows a significantly higher event rate in the very high CV risk group compared to the high/moderate risk group (p 0.0019). Using the ST1RE algorithm, a significant difference in the event-free survival curve was found between the three CV risk categories (p 0.0001).In T1D the ESC classification has a good performance in predicting CV events only in those at very high CV risk, whereas the ST1RE algorithm has a good performance in all risk categories.

Aims Couples living with Type 1 diabetes: co-designing interventions to support them. Methods This is a qualitative study comprising two phases. Phase I represents the exploratory phase, consisting of semi-structured interviews with persons with Type 1 diabetes (N = 16) and partners (N = 6). In the second phase, co-design principles guided workshops with healthcare professionals, persons with Type 1 diabetes, and partners (N = 7) to facilitate discussion of the key themes identified and solutions to engage couples living with Type 1 diabetes in diabetes care. Result The key themes identified from phase I as priorities to target in future interventions were: (i) Emotional impact of diabetes and (ii) Partners’ involvement. Priority (i) captures the impact the emotional burden of diabetes management produces within couples’ relationship. Priority (ii) captures the request from partners to be more involved in diabetes management. Characteristics of the interventions suggested during the co-design phase II focused on engaging patients and partners via a counseling point in healthcare settings and tailored help for couples’ psychological support needs. Conclusions Couples value pro-active intervention and support from their diabetes team or primary care for both the partners to live well with Type 1 diabetes.

N/A

Aim People with type 1 diabetes and celiac disease (T1D&CD) have high blood glucose variability. Processed gluten-free foods have shown to induce a worse metabolic profile whereas naturally gluten-free foods may represent healthier options. On the other hand, dietary fibre has shown to reduce postprandial glycemic excursions in individuals with diabetes. Thus, we evaluated the acute effect of fibre-enriched buckwheat (FBP) and corn pasta (CP) on postprandial blood glucose response (PP-BGR). Methods Ten adult patients with T1D&CD consumed two meals with the same amount of carbohydrate while differing only for pasta type (FBP or CP) preceded by the same insulin bolus. Participants utilized continuous glucose monitoring (CGM) and data over 6 h after meal were analyzed. Results PP-BGR differed between the two meals, being significantly lower in the first period (0–3 h) after the CP than the FBP meal (iAUC: −38 ± 158 vs. 305 ± 209 mmol/L · 180 min, p = 0.040), whereas significantly higher in the second period (3–6 h) after the CP than the FBP meal (iAUC: 432 ± 153 vs. 308 ± 252 mmol/L · 180 min, p = 0.030). Overall, a less variable postprandial profile was observed after FBP than CP consumption. Conclusions In individuals with T1D&CD, the acute consumption of FBP induces significant differences in PP-BGR compared with CP that may be clinically relevant.

Background and aim: Albuminuria and reduced eGFR are hallmarks of Diabetic Kidney Disease in adults. Our aim was to analyze factors associated with albuminuric and non-albuminuric mildly reduced eGFR phenotypes in youths with type 1 diabetes. Methods and results: This multicenter cross-sectional study included 1549 youths (age 5–17 years) with type 1 diabetes enrolled at 14 Italian Pediatric Diabetes Centers. Albuminuria, creatinine, glycosylated hemoglobin (HbA1c), lipids, blood pressure (BP), neutrophils (N) and lymphocytes (L) count were analyzed. Uric acid (UA) was available in 848 individuals. Estimated GFR (eGFR) was calculated using bedside Schwartz's equation. The sample was divided in three phenotypes: 1) normoalbuminuria and eGFR ≥90 mL/min/1.73 m2 (reference category, n = 1204), 2) albuminuric and normal GFR phenotype (n = 106), 3) non-albuminuric mildly reduced GFR (MRGFR) phenotype (eGFR 60–89 mL/min/1.73 m2, n = 239). Albuminuric and non-albuminuric reduced eGFR phenotypes were significantly associated with autoimmune thyroiditis (P =0.028 and P=0.044, respectively). Albuminuric phenotype showed high risk of high HbA1c (P=0.029), high BP (P < 0.001), and low HDL-C (P =0.045) vs reference category. Non-albuminuric MRGFR phenotype showed high risk of high BP (P < 0.0001), low HDL-C (P =0.042), high Triglycerides/HDL-C ratio (P =0.019), and high UA (P < 0.0001) vs reference category. Conclusion: Non albuminuric MRGFR phenotype is more prevalent than albuminuric phenotype and shows a worst cardiometabolic risk (CMR) profile). Both phenotypes are associated with autoimmune thyroiditis. Our data suggest to evaluate both albuminuria and eGFR earlier in type 1 diabetes to timely identify young people with altered CMR profile.

Bone fragility is one of the possible complications of diabetes, either type 1 (T1D) or type 2 (T2D). Bone fragility can affect patients of different age and with different disease severity depending on type of diabetes, disease duration and the presence of other complications. Fracture risk assessment should be started at different stages in the natural history of the disease depending on the type of diabetes and other risk factors. The risk of fracture in T1D is higher than in T2D, imposing a much earlier screening and therapeutic intervention that should also take into account a patient's life expectancy, diabetes complications etc. The therapeutic armamentarium for T2D has been enriched with drugs that may influence bone metabolism, and clinicians should be aware of these effects.Considering the complexity of diabetes and osteoporosis and the range of variables that influ-ence treatment choices in a given individual, the Working Group on bone fragility in patients with diabetes mellitus has identified and issued recommendations based on the variables that should guide screening of bone fragility and management of diabetes and bone fragility: (A) ge, (B)MD, (C)omplications, (D)uration of disease, & (F)ractures (ABCD&F). Consideration of these parameters may help clinicians identify the best time for screening, the appropriate glycaemic target and anti-osteoporosis drug for patients with diabetes at risk of or with bone fragility.(c)& nbsp;2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Background Telemedicine use in chronic disease management has markedly increased during health emergencies due to COVID-19. Diabetes and technologies supporting diabetes care, including glucose monitoring devices, software analyzing glucose data, and insulin delivering systems, would facilitate remote and structured disease management. Indeed, most of the currently available technologies to store and transfer web-based data to be shared with health care providers. Objective During the COVID-19 pandemic, we provided our patients the opportunity to manage their diabetes remotely by implementing technology. Therefore, this study aimed to evaluate the effectiveness of 2 virtual visits on glycemic control parameters among patients with type 1 diabetes (T1D) during the lockdown period. Methods This prospective observational study included T1D patients who completed 2 virtual visits during the lockdown period. The glucose outcomes that reflected the benefits of the virtual consultation were time in range (TIR), time above range, time below range, mean daily glucose, glucose management indicator (GMI), and glycemic variability. This metric was generated using specific computer programs that automatically upload data from the devices used to monitor blood or interstitial glucose levels. If needed, we changed the ongoing treatment at the first virtual visit. Results Among 209 eligible patients with T1D, 166 completed 2 virtual visits, 35 failed to download glucose data, and 8 declined the visit. Among the patients not included in the study, we observed a significantly lower proportion of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) users (n=7/43, 16% vs n=155/166, 93.4% and n=9/43, 21% vs n=128/166, 77.1%, respectively; P Conclusions These findings indicate that the structured virtual visits help maintain and improve glycemic control in situations where in-person visits are not feasible.

This study aims to analyze the correlations and relevance of self-efficacy items in 411 patients with diabetes using network analysis. We found that the self-efficacy items structure is consistent between genders and types of diabetes. However, the strength of item correlations was significantly higher in type 2 diabetes. The items central to the network were following a regular diet in type 2 diabetes and adjusting diet when ill in type 1 diabetes. No significant gender differences were found. Knowledge of the most central aspects of self-efficacy and their interconnections can help clinicians to target psychoeducational interventions aimed at empowering patients.

Purpose This study is aimed at evaluating changes in metrics of glucose control in home-isolated patients with type 1 diabetes and COVID-19 using a continuous glucose monitoring (CGM) system. Methods We included adults aged 18–45 years with type 1 diabetes, using CGM, followed by telemedicine at a Southern Italian University Hospital. Thirty-two home-quarantined subjects with SARS-CoV-2 positive swab constituted the COVID-19 group. Thirty age-matched diabetic individuals without COVID-19 formed the control group. The effects of COVID-19 on glycemic control in patients infected were assessed at different time points [2 weeks before-COVID-19 (Time 1), 2 weeks during-COVID-19 (Time 2) and 2 weeks after COVID-19 (Time 3)] and compared with those without infection. Results A significant reduction of TIR (Time 1 vs Time 2, %, 60.1 ± 16.6 vs 55.4 ± 19.2, P = 0.03), associated with a significant increase of TAR level 2 (10.1 ± 7.3 vs 16.7 ± 12.9, P P P = 0.04), mean glucose values (mg/dL, 160.2 ± 26.5 vs 175.5 ± 32.6, P = 0.001) and standard deviation (59.2 ± 13.1 vs 68.6 ± 17.7, P = 0.001) was observed in patients with COVID-19. No significant change of glycemic metrics was found in the NO COVID-19 group across the time. Conclusion Young home-isolated patients with type 1 diabetes and COVID-19 showed a worsening of glucose control during COVID-19, as compared with age-matched diabetic subjects without the infection.

Aim: To evaluate the impact of a virtual educational camp (vEC) on glucose control in children and adolescents with type 1 diabetes using a closed-loop control (CLC) system. Materials and Methods: This was a prospective multicentre study of children and adolescents with type 1 diabetes using the Tandem Basal-IQ system. Insulin pumps were upgraded to Control-IQ, and children and their parents participated in a 3-day multidisciplinary vEC. Clinical data, glucose metrics and HbA1c were evaluated over the 12 weeks prior to the Control-IQ update and over the 12 weeks after the vEC. Results: Forty-three children and adolescents (aged 7-16 years) with type 1 diabetes and their families participated in the vEC. The median percentage of time in target range (70-180 mg/dL; TIR) increased from 64% (interquartile range [IQR] 56%-73%) with Basal-IQ to 76% (IQR 71%-81%) with Control-IQ (P&nbsp

Objective Arginine vasopressin (AVP) and its surrogate, copeptin, have been implicated in diabetic kidney disease (DKD) pathogenesis, which develops in a subset of people with longstanding type 1 diabetes, but not in others (DKD Resistors). We hypothesized that patients with DKD would exhibit higher copeptin concentrations vs. DKD Resistors. Methods Participants with type 1 diabetes (n = 62, duration ≥50 years) were stratified into 42 DKD Resistors and 20 with DKD (eGFR ≤60 mL/min/1.73m2 or ≥30 mg/day urine albumin), and age/sex-matched controls (HC, n = 74) were included. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were calculated by inulin and p-aminohippurate clearance before and after angiotensin II (ang II) infusion. Renal vascular resistance (RVR) was calculated as mean arterial pressure/renal blood flow. Plasma copeptin, renin, aldosterone, neutrophil gelatinase-associated lipocalin (NGAL), and urea concentrations were measured, along with 24-h urine volume. Results DKD resistors had lower copeptin (95% CI: 4.0 [3.4–4.8] pmol/l) compared to DKD (5.8 [4.5–7.6] pmol/l, p = 0.02) and HC (4.8 [4.1–5.5] pmol/l, p = 0.01) adjusting for age, sex and HbA1c. In type 1 diabetes, higher copeptin correlated with lower GFR (r: −0.32, p = 0.01) and higher renin concentration (r: 0.40, p = 0.002) after multivariable adjustments. These relationships were not evident in HC. Copeptin inversely associated with RVR change following exogenous ang II only in participants with type 1 diabetes (β ± SE: −6.9 ± 3.4, p = 0.04). Conclusions In longstanding type 1 diabetes, copeptin was associated with intrarenal renin–angiotensin–aldosterone system (RAAS) activation and renal hemodynamic function, suggesting interplay between AVP and RAAS in DKD pathogenesis.

Background: Disordered eating behaviors (DEBs), including diagnosable eating disorders, are quite common and can interfere with optimal type 1 diabetes (T1DM) management. We explored DEBs prevalence in youth with T1DM, proposing news diagnostic subscales, to represent the clinical dimensions associated with feeding and eating disorders (ED), Methods: additionally to SCOFF questionnaire and Diabetes Eating Problem Survey&ndash, Revised (DEPS-R), four subscales combined from the original DEPS-R questionnaire were administered to 40 youths with T1DM (15.0 &plusmn, 2.6), Results: females showed higher scores than males in DEPS-R original factor 2 (&ldquo, preoccupations with thinness/weight&rdquo, p = 0.024) and in DEPS-R proposed &ldquo, restriction&rdquo, factor (p = 0.009). SCOFF scores was correlated with original DEPS-R factors 1 (&ldquo, maladaptive eating habits&rdquo, ) and 2 (p &lt, 0.001) and with the newly proposed DEPS-R factors: restriction, disinhibition, compensatory behaviors, diabetes management (all p &lt, 0.02). Diabetes management was the only factor related to glycated hemoglobin level (p = 0.006). Patients with high DEPS-R score (&ge, 20) scored higher than patients with low (&lt, 20) DEPS-R score in DEPS-R original factors 1 (p &lt, 0.001) and 2 (p = 0.002) as well as in the proposed factors including restriction, disinhibition, diabetes management (all p &lt, 0.02), Conclusions: the complicated nature of DEBs calls for the development target specific questionnaires to be used as screening tools to detect cases of DEBs and exclude non cases. Early recognition of DEBs in adolescents with T1DM is essential for effective prevention and successful treatment.

The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), responsible for the coronavirus disease COVID-19, was first identified in Wuhan, China in December 2019. Diabetes, as well as other cardiovascular comorbidities, has been recognized as a major risk factor for outcomes and mortality in adults with COVID19, particularly in the elderly with type 2 diabetes. Based on these conclusions, COVID-19 data on adults have been generalizedto youth with diabetes. Nevertheless, experience from Pediatric Diabetes practices in China (Wuhan), Italy, Spain (Catalonia) and the US (San Francisco Bay Area) consistently report only a single severe case of COVID-19 in a 20-year-old female youth with type 1 diabetes (T1D) that was hospitalized for bilateral pneumonia and was subsequently discharged without complications. In Italy, information on COVID-19 in all children with diabetes is collected on a weekly basis andthose with positive swab test or infection-related symptoms reported to a dedicated national registry. Of a total of 15,500 children tested,11subjects with T1D (age 8-17y) tested positive for COVID-19; 6/11 were asymptomatic and the rest presented with mild symptoms. In the rest of locations, youth with T1D diagnosed with COVID-19 were based on clinical suspicion and a confirmatory PCR test(Wuhan:0; Catalonia-HSJD:3; California-Stanford:2) and all of them were asymptomatic or had a mild course.We suggest that COVID-19 data from adults should not be generalizedto children, adolescents and youth with diabetes as their outcomes and prognosis seem to be similar to their non-diabetic-peers and consistently milder than adults with diabetes. This article is protected by copyright. All rights reserved.

The aims of this paper was to compare the frequency of Diabetic Ketoacidosis (DKA) at diagnosis in 2014–2016 with the one previously reported in 2004–2013; and to assess the association between family socioeconomic status and DKA at type 1 diabetes (T1D) diagnosis in children

Background: No studies have assessed if 2-week of continuous glucose monitoring (CGM) data provide good estimation of long-term glycemic control and glucose variability (GV) in pediatric patients with type 1 diabetes (T1D) as in adults. Methods: Six hundred fifty-four T1D pediatric patients were enrolled and 12-weeks of CGM data, before HbA1c measurement, were collected. Metrics of glycemic control and GV in incremental sampling periods were calculated. The agreement between metrics calculated in the sampling periods and the full 12-week period was assessed with correlation analysis (R2), median relative absolute difference (RAD) or absolute difference in the entire study populations and subjects stratified by age, pubertal status, insulin therapy (MDI,CSII), type of CGM (intermittently scanned [isCGM], real-time [rtCGM]), and HbA1c level. Results: Correlations with metrics of the full 12-week period improved by extending the sampling periods. R2 values close to 0.90 using 4-week period were significantly higher than 2-week period, particularly for coefficient of variation, mean glucose SD, percentage of time below the range

Aims: Various studies have investigated the relationship between depressive symptoms, diabetes distress, low adherence and glycemic control in adolescents with type 1 diabetes. Less is known about the impact of technological devices on diabetes management in young adults and its relationship with psychological well-being. The aim of the study is to investigate psychological health status and glycemic control during a three years period in a population of emerging adults (18-25 years) with type 1 diabetes. The relationship between technology utilization and psychological health status and glycemic control will be then investigated. Design: This is an observational, prospective (3 years) and multi-centric national study. Experimental sites: University of Padova, University of Bologna and University of Verona. Methods: Participant recruitment will be face to face or online. We aim to recruit at least 200 participants. Emerging adults will be recruited in Diabetology Units or in University Faculties. The study will be advertised via social media and posters. Socio-demographic and clinical data will be asked to participants. Glycemic control will be detected with HbA1c test (mmol/mol). Psychological health status will be assessed with generic and diabetes specific self-administered questionnaires, evaluating: depressive symptoms (PHQ-9), anxiety (GAD-7), adult attachment style (ECRR), sleep quality (PSQI), diabetes distress (PAID), self-efficacy in diabetes management (IT-DMSES), fear of hypoglicaemia (HFS-II), and treatment satisfaction (DTSQ). In patients using Continuous Subcutaneous Insulin Infusion (CSII), beneficial and barriers related to technology utilization will be investigated using the Insulin Pump Attitudes questionnaire (IPA) recently developed in Germany. The questionnaire will be firstly translated and adapted from German to Italian and, then, administered with the other questionnaires. With their permission, participants will be contacted after 12, 24 and 36 months to repeat the evaluation with the questionnaires previously used. Planned analysis: Primary endpoint: Descriptive statistics will examine participants’ clinical characteristics at baseline. To analyze the trend of glycemic control and psychological health status over time (T0=baseline, T1=12 months, T2=24 months and T3=36 months), repeated measures mixed models will be used. These models are suitable in the presence of missing data. The effects that will be investigated in these analyses are: the mean effect of technological devices utilization (yes vs. no); the time trend of scores regardless of the technological devices utilization; and the time trend in each group. Secondary endpoint: Psychometric testing included construct validity (principal component analysis), internal consistency (Cronbach’s α coefficient) and convergent/discriminant validity (Spearman’s correlation coefficient) will be performed for the Italian validation of the IPA questionnaire. Expected outcomes:  IPA Questionnaire will be validated in the Italian language in a population of emerging adults with type 1 diabetes.  Prevalence data on psychological health status of emerging adults with type 1 diabetes.  Longitudinal data (3 years) on psychological health status of emerging adults with type 1 diabetes.  Longitudinal data on the relationship between the use of technological device, glycemic control, and psychological health status in emerging adults with type 1 diabetes. Problems/Questions: 1) To include only patients who use technology devices or all patients with type 1 diabetes 2) Would be appropriate to build a questionnaire ad hoc to investigate the prevalence of use of proximal technology such as apps? PSAD

Management of Type 1 Diabetes (T1D) in the context of exercise or sports competition still represents a great challenge for athletes living with this disease, due to the wide excursions in blood glucose level with increased risk of life threatening hypoglycemia. Recently, an algorithm called ECRES has been developed to estimate patient-exercise tailored carbohydrates (CHO) supplement required to maintain safe blood glucose levels during physical activity. This method estimates a CHO supplement based on the patient’s habitual therapy, the specific patient’s insulin sensitivity and the overall amount of CHO oxidized during the specific exercise. The last is based on the glucose pulse relation, i.e. the relation between heart rate (HR) and CHO oxidation rate, already studied in sedentary and moderately-trained subjects, but not in well-trained athletes. This study aimed to model the glucose pulse relation during exercise in type 1 highly trained diabetic patients and in healthy subjects. HR, oxygen consumption and carbon dioxide production were acquired breath-by-breath in seven T1D and seven well-matched healthy highly-trained subjects at four different exercise intensity levels, as well as at rest. Results showed a linear CHOox-HR relation (CHOox = 0.76 · %HRmax - 19.6; n = 70, R2 = 0.78) with no significant difference between the T1D and healthy athletes (p-value = 0.11). In conclusion, results of this study can be implemented in an updated version of the ECRES algorithm allowing an easy estimate of CHO supplement also in highly trained subjects. This useful support system can enhance the self-management of glycaemia during the training sessions of athletic patients throughout mHealth technologies.

Hypoglycemia is a pathological condition characterized by a low plasma glucose concentration associated with typical autonomic and/or neuroglycopenic symptoms, and resolution of these symptoms with carbohydrate consumption. Hypoglycemia is quite common in clinical practice, particularly in insulin-treated patients with diabetes and in other inherited or acquired conditions involving the regulation of glucose metabolism. Beyond symptoms that might strongly affect the quality of life, hypoglycemia can lead to short- and long-term detrimental consequences for health. Hypoglycemia can be prevented by appropriate changes in dietary habits or by relevant modifications of the drug treatment. Several dietary approaches based on the intake of various carbohydrate foods have been tested for hypoglycemia prevention; among them uncooked cornstarch (UCS) has demonstrated a great efficacy. In this narrative review, we have summarized the current evidence on the UCS usefulness in some conditions characterized by high hypoglycemic risk, focusing on some inherited diseases −i.e. glycogen storage diseases and other rare disorders − and acquired conditions such as type 1 diabetes, postprandial hypoglycemia consequent to esophageal-gastric or bariatric surgery, and insulin autoimmune syndrome. We also considered the possible role of UCS during endurance exercise performance. Lastly, we have discussed the dose requirement, the side effects, the limitations of UCS use, and the plausible mechanisms by which UCS could prevent hypoglycemia.

The human figure drawing in children with type 1 diabetes and healthy control individuals: What differences? The purpose of this study was to evaluate the presence of psychological problems in children with type 1 diabetes by using human figure drawings. A total of 81 consecutive patients attending an Southern Italian university pediatric diabetology centre with a diagnosis of type 1 diabetes, along with 219 control subjects matched to the study group for age and gender, were asked to draw human figure drawings according to the Draw a Person: Screening Procedure for Emotional Disturbances (DAP:SPED). The glycosylated hemoglobin (HbA1C) mean value, measured every 3 months over the past year, was used as a measure of metabolic control. No significant differences between the children with type 1 diabetes and controls in the DAP:SPED total scores were observed, even when they were differentiated by gender or by weight An item by item human figure drawings comparison showed that the children with type 1 diabetes drew smaller figures for height and width than the controls, with more frequent presence of pointed fingers and the absence of clothes. Findings indicated the presence of distinctive elements in human figure drawings suggesting the existence of aspects of body image which characterize children with type 1 diabetes and distinguish them from healthy children. The differences observed support the need for monitoring the characteristics of body image in children with type 1 diabetes during the course of the development in order to increase the efficacy of early action to prevent the onset of psychological problems.

Purpose: To describe gender differences concerning glycemic control, cardiovascular risk factors, diabetic complications, concomitant pathologies, and circulating endothelial progenitor cells (EPCs), in a population of young adults with type 1 diabetes. Methods: We collected data from 300 consecutively patients (168 males and 132 females), aged 18–30 years, among those admitted at Diabetes Unit of University of Campania “Luigi Vanvitelli” (Naples, Italy) from March 2012 to January 2017. Circulating levels of seven EPCs phenotypes were determined by flow cytometry. Results: As compared to men, women with type 1 diabetes had a significantly higher HbA1c levels (%, 8.4 ± 1.3 vs. 8.1 ± 1.3, P = 0.020), body mass index (Kg/m2, 24.8 ± 4.2 vs. 23.9 ± 3.9, P = 0.034), HDL-cholesterol (mg/dL, 61.7 ± 13.7 vs. 54.7 ± 13.9, P < 0.001), and a lower count of both CD133+KDR+ and CD34+KDR+CD133+ EPCs (P = 0.022, P < 0.001, respectively). A higher proportion of women had overweight/obesity, and thyroiditis; smoking and sexual dysfunctions were more prevalent in men than in women. Conclusions: Young adults with type 1 diabetes present gender differences with regard to glycemic control, prevalence of some cardiovascular risk factors, sexual dysfunctions and circulating levels of EPCs, most often to the detriment of women.

Aims/hypothesis Microvascular complications in the heart and kidney are strongly associated with an overall rise in inflammation. Annexin A1 (ANXA1) is an endogenous anti-inflammatory molecule that limits and resolves inflammation. In this study, we have used a bedside to bench approach to investigate: (1) ANXA1 levels in individuals with type 1 diabetes; (2) the role of endogenous ANXA1 in nephropathy and cardiomyopathy in experimental type 1 diabetes; and (3) whether treatment with human recombinant ANXA1 attenuates nephropathy and cardiomyopathy in a murine model of type 1 diabetes. Methods ANXA1 was measured in plasma from individuals with type 1 diabetes with or without nephropathy and healthy donors. Experimental type 1 diabetes was induced in mice by injection of streptozotocin (STZ; 45 mg/kg i.v. per day for 5 consecutive days) in C57BL/6 or Anxa1 −/− mice. Diabetic mice were treated with human recombinant (hr)ANXA1 (1 μg, 100 μl, 50 mmol/l HEPES; 140 mmol/l NaCl; pH 7.4, i.p.) or vehicle (100 μl, 50 mmol/l HEPES; 140 mmol/l NaCl; pH 7.4, i.p.). Results Plasma levels of ANXA1 were elevated in individuals with type 1 diabetes with/without nephropathy compared with healthy individuals (66.0 ± 4.2/64.0 ± 4 ng/ml vs 35.9 ± 2.3 ng/ml; p

Purpose: A relationship between thyroid dysfunction and diabetes mellitus has been described by several authors but the role of glycemic variability is still unclear. We planned the present study to evaluate the influence of glycemic variability on thyroid hormones and TSH concentrations in patients with type 1 diabetes mellitus (T1DM).Methods: Seventy-seven young patients with T1DM were enrolled and evaluated for basal glucose concentrations, HbA1c, thyroid hormones and TSH concentrations. Glucose variability was investigated by considering the standard deviation of blood glucose readings and by calculating the mean amplitude of glycemic excursions and continuous overlapping net glycemic action (CONGA). The low (LBGI) and high (HBGI) blood glucose indices were also calculated. The correlations between TSH, thyroid hormones, glycemia and HbA1c were studied in patients and in controls, whereas those between TSH, thyroid hormones and indices of glucose variability only in patients.Results: No correlations were observed in T1DM patients between free thyroid hormones and glycemic values, HbA1c and indices of glucose variability, while an inverse correlation was observed between TSH levels and glycemic values (r = −0.27; p = 0.01), CONGA index (r = −0.35; p = 0.001) and HBGI (r = −0.28; p = 0.01) but not with HbA1c (r = −0.1; p = 0.47). Conclusions: Our results suggest a direct action of glycemic excursions on TSH secretion, regardless of variations of thyroid hormone concentrations. Thus, the evaluation of thyroid function through the assay of TSH concentrations in these patients should be made, if possible, by multiple samples on patients in euglycemic state to avoid underestimation or overestimation of thyroid dysfunction due to a wrong diagnosis of euthyroidism or dysthyroidism with consequent inappropriate choice of therapeutic options.