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Fozza C.,University of Sassari | Contini S.,University of Sassari | Corda G.,University of Sassari | Virdis P.,University of Sassari | And 8 more authors.
Immunobiology | Year: 2012

Several data suggest that stochastic rearrangements of the TCR could play a pathogenic role in both disease predisposition and protection in type 1 diabetes (T1D). As twin sets offer an enormous potential in evaluating the role of genetic and environmental factors in susceptibility to disease, the main goal of this study was to assess whether the degree of sharing of the expressed TCR repertoire of twin pairs discordant for T1D differs from that of disease concordant pairs. We performed our analysis in 5 pairs of monozygotic twins, 3 of which were concordant and 2 discordant for T1D, by combining flow cytometry and CDR3 spectratyping on both CD4+ and CD8+ T-cells. Our data show that TCR repertoires show increased level of concordance within each twin pair, especially in CD8+ cells, in terms of mean BV expression levels on flow cytometry as well as of CDR3 patterns and frequencies of skewed or oligoclonal BV subfamilies on spectratyping. It is worth noting that the degree of similarity among twins seems to be independent of concordance or discordance for T1D. Our findings seem to suggest that in monozygotic twins with T1D the TCR repertoire is influenced by genetic factors more than by the presence of the autoimmune disorder itself. © 2012 Elsevier GmbH. Source


Girelli A.,Unita Operativa di Diabetologia
Giornale Italiano di Diabetologia e Metabolismo | Year: 2015

Physical activity frequently causes hypoglycemia in patients with type 1 diabetes mellitus (T1DM), and the fear of hypoglycemia is their main barrier to exercise. T1DM patients lack the neuroendocrine mechanisms that lead to the adjustment of insulin, and their blood sugar levels depend on their ability to adapt insulin therapy and nutrition. Other causal mechanisms involved in hypoglycemic episodes during and after exercise are the increased absorption of insulin, increased peripheral sensitivity, and impairment of the counter-regulation system. Different types of exercise have different effects on blood sugar and it is therefore essential to establish what kind of activity the patient does (aerobic, anaerobic, intermittent, resistance). Preventive measures can involve both a change of insulin therapy and glucose integration. The algorithms in the literature mainly refer to the management of rapid insulin (if exercise is planned and done in the hours after a meal), and the baseline level; CSII therapy, providing a more physiological, flexible mode of insulinization, is often used by diabetic athletes. As regards glucose integration, patients have to assess the quality, quantity and timing of carbohydrate intake based on insulin dosage, initial glycemia, and the type, intensity and duration of exercise. To reduce the risk of hypoglycemia linked to exercise, glycemic control must be closely monitored through either frequent SBGM or systems for continuously monitoring blood glucose. For safe physical activity with the least possible risk of hypoglycemia, the patient must be properly prepared through a “trial-and-error approach” supported by therapeutic recommendations that are as personalized as possible. © 2015 UTET Periodici Scientifici srl. All rights reserved. Source


Girelli A.,Unita Operativa di Diabetologia
Giornale Italiano di Diabetologia e Metabolismo | Year: 2016

Sport has always been essential to humans and for a person with type 1 diabetes it plays a crucial role in terms of health and quality of life. Until a few years ago some sports were definitely not recommended – often even forbidden – for type 1 diabetics on account of the potential for glycemic disorders and the risks of acute complications (especially hypoglycemia). However, the literature now tells us that exercise brings benefits in type 1 diabetes, reducing cardiovascular risk, while the data on effects on glycemic control tend to vary. The findings of several meta-analyses are conflicting. This might be explained by various factors, including the fact that HbA1c may not be the best parameter for evaluating the effects of exercise: it does not detect blood glucose fluctuations due to exercise, and exercise tested under experimental conditions may not fully reflect real-life scenarios. When treating a person with type 1 diabetes who wants to start a sport, the diabetologist must have the knowledge and skills for an overall clinical evaluation to rule out any complications and establish which sports are suitable. The optimization of therapy over the last 20 years has been enriched by increasingly effective tools, but it still requires thorough knowledge and well-thought-out therapeutic strategies to customize algorithms for different workout or competition schedules. Access to CSII before and continuous glucose monitoring systems afterwards has been a huge step in ensuring safe sport with good glycemic control. Each sport differs not only in energy metabolism but also involves different types of exercise, technical moves, climate, and numerous other factors that must all be taken into account in planning treatment. Modern technology has made all sports much easier from the point of view of the patient’s satisfaction and safety. © 2016, UTET Periodici Scientifici srl. All rights reserved. Source


Cappelli C.,University of Brescia | Pirola I.,University of Brescia | Formenti A.M.,University of Brescia | Zarra E.,Unita Operativa di Diabetologia | And 2 more authors.
Giornale Italiano di Diabetologia e Metabolismo | Year: 2012

Metformin may lower or even suppress serum levels of thyroidstimulating hormone (TSH), mimicking sub-clinical hyperthyroidism (SHT), but the clinical significance of this effect remains controversial. Although commonly asymptomatic, SHT involves an increased risk of cardiac arrhythmias, mostly atrial fibrillation, morphological and functional cardiac alterations, resulting in increased cardiovascular morbidity and mortality. The present study retrospectively evaluated changes in several electrocardiographic indices in euthyroid diabetic patients who, after starting metformin treatment, had lower serum TSH than patients with SHT resulting from an underlying thyroid disease or TSH suppressive treatment with L-thyroxine. Electrocardiographic parameters (heart rate, P-wave duration, P-wave dispersion, QTmax, QTmin and QT-dispersion) were assessed in 23 patients with diabetes treated with metformin before and after six months of TSH-suppression and in 31 control patients with SHT. There were no significant changes in electrocardiographic parameters from baseline to the TSHsuppression measurements. By contrast, there were significant differences in P wave duration (102.9 ± 7.4 vs 92.1 ± 5.8 ms, p < 0.001), P wave dispersion (13.1 ± 3.4 vs 7.1 ± 3.5 ms, p < 0.001), QTmax (399 ± 18 vs 388 ± 16 ms, p = 0.024), QTmin (341 ± 14 vs 350 ± 17 ms, p = 0.038), and QT dispersion (49.9 ± 9.6 vs 30.9 ± 9.2 ms, p < 0.001) between the control patients with SHT and the diabetic patients with similarly low serum TSH. These findings indicate that the TSH-suppressive effect observed in some patients with diabetes taking metformin is not associated with peripheral markers of thyroid hormone excess, at least at the cardiac level. The metformin-induced biochemical condition does not appear to be indicative of SHT, suggesting there is no need for close thyroid function surveillance in diabetic patients starting metformin. Source


Bonfadini S.,Unita Operativa di Diabetologia | Girelli A.,Unita Operativa di Diabetologia | Magri A.,Unita Operativa di Diabetologia | Zarra E.,Unita Operativa di Diabetologia | And 2 more authors.
Giornale Italiano di Diabetologia e Metabolismo | Year: 2014

Intensive insulin therapy management can prevent and/or delay the microvascular complications associated with type 1 diabetes. However, this approach requires the patient’s real commitment and there is a higher risk of hypoglycemia. Recent studies have focused on the development of a sensor-augmented pump (SAP) which combines real-time continuous glycemia monitoring (CGM) with continuous subcutaneous insulin infusion (CSII). However, there are still no official guidelines or clinical trials on the clinical benefits of SAP compared to GCM or CSII alone. This study evaluated the continuity of use, efficacy and clinical safety of SAP systems in 37 patients with type-1 diabetes followed up at the hospital diabetes unit (UOD) of the Spedali Civili Di Brescia; patients had begun this therapy in 2008-2012. The indications for the use of SAP were as follows: 48% severe metabolic instability, 29% inadequate metabolic control and 24% severe hypo-glycemia and/or loss of sensitivity to hypoglycemia. Within one year, 10/37 (27%) who had started using the SAP stopped using CGM, after a mean of 4.7 ± 3.9 months. They gave as their reasons: complexity of use (4 patients), lack of efficacy (2), disturbing alarms (2), difficulty in portability (1) and a request to return to multiple daily injections (MDI, 1). The factors predicting stopping therapy were: using CGM less than half the time (p = 0.000) and lower educational level (p = 0.026). The average period of use of CGM differed significantly, from 11.1 ± 4.55 days/month in the group that stopped to 22.71 ± 7.44 days/month in the group that continued using it (p = 0.001). At one year glycated hemoglobin (HbA1c) had dropped significantly in the 27 patients who continued using the SAP (7.90 ± 0.93% vs. 7.45 ± 0.7%, p < 0.001). Predictive factors for this reduction were higher HbA1c at starting using the SAP (p = 0.013), the use of a bolus calculator (p = 0.025) and older age at starting the SAP (p = 0.05). There were significant reductions in both the percentage of patients and the number of episodes/year of severe hypoglycemia, which decreased during the use of SAP from 14.3% to 7.1% (p < 0.001), and from 2.4 episodes/year/patient to 1 episode/year/patient. Significantly fewer patients reported episodes of ketoacidosis (3 vs. 1). These findings indicate that SAP offered a safe and effective option for the treatment of type 1 diabetes in this population. Further studies are required not only to confirm the clinical efficacy but also to identify the best strategies and tools for the selection, training and follow-up of candidates for the use of integrated systems. © 2014 UTET Periodici Scientifici srl.All rights reserved. Source

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