Type 1 diabetes (T1D) is an immune-mediated chronic disease accounting for 5-10% of the total cases of diabetes and its incidence is growing worldwide. As a result of the autoimmune process, inducing the failure of insulin-producing cells, intensive insulin therapy represents the gold standard treatment to maintain blood glucose homeostasis. In 1993, the effectiveness of intensive insulin therapy in T1D has been widely established in Diabetes Control and Complications Trial (DCCT). Moreover, it was affirmed that optimal glycaemic control is directly related to the reduction of incidence and progression of long-term diabetes complications. Therefore, tight glycaemic control is overall recommended for T1D patients with near-normalization of blood glucose levels and an HbA1c <7.0% as the treatment goals. However, a great number of T1D patients have a suboptimal glycaemic control and 60% of people with T1D monitor less frequently than American Diabetes Association (ADA) recommendations of =3 tests daily. On the other hand, benefits of intensive insulin treatment observed in the DCCT came with a three times higher risk of severe hypoglycaemia compared to the conventional therapy with one or two daily insulin injections and the fear of hypoglycaemia keeps many patients away from intensive treatment and achievement of recommended glycaemic goals. Furthermore, treatment goals should be achieved safely and effectively by maintaining daily flexibility to fit individual lifestyle and without major variations in eating behaviours and physical activity promoting patients' compliance and their overall quality of life. Therefore, to reduce these main limiting factors supporting long-term diabetes management the newer technologies and adjuvant treatments represent areas of investigation with important clinical applications. The overall aim of my PhD was to find out if new technologies and adjuvant treatments may improve glycaemic control and patients compliance, reducing glucose variability in T1D patients. This thesis includes two sections: the first one section is focused on the effectiveness of a bolus advisor calculator on glycaemic control in T1D patients undergoing intensive insulin therapy; the second section evaluates the hypothesis that D-Chiro-Inositol (DCI) plus Folic Acid oral supplementation can act as adjuvant treatments to insulin therapy in overweight or obese T1D patients, reducing insulin resistance. 1st section: in order to achieve an optimal glycaemic control in insulin-treated T1D patients the rationale of this part of the thesis has been the higher frequency of errors with empirical calculations of mealtime insulin doses. In fact, 42% diabetic patients administer an uncorrected dose of prandial insulin and the few studies carried-out on bolus calculator systems have been published with controversial results. At the same time, we tested effectiveness and feasibility of a wirelessly meter integrated with a bolus calculator working with a telemedicine system. Furthermore, we investigated the efficacy of this automated bolus calculator (ABC) and wirelessly communicated blood glucose measurement on glucose variability, by the use of a continuous glucose monitoring system (CGMS). The rationale is clearly established from the DCCT results suggesting that glycaemic variability may be an additional risk factor for the long- term diabetes complications and the new treatment strategies are increasingly focusing on reducing post-prandial glycaemic excursions. The results of this section have demonstrated that an ABC system is a friendly wirelessly meter that helps to improve glycaemic control and patients compliance to SMBG. Moreover, patients using an ABC showed a significant reduction of time spent in hypoglycaemic range compared to the control subjects. 2nd section: The rationale of this section of the thesis was based on the worldwide rise of obesity in childhood and adolescence with the consequent increase of insulin resistance also in young patients with T1D. In fact suboptimal glucose control is often due to the higher insulin doses causing an increased risk of hypoglycaemic events, weight gain and poor glycaemic control. On this basis, the second part of this thesis was focused on a research project evaluating the hypothesis that D-Chiro-Inositol (DCI) plus Folic Acid oral supplementation may improve glucose control reducing insulin resistance in overweight or obese T1D patients. In fact, D-Chiro-Inositol (DCI), as putative mediator of intracellular insulin action can accelerate glucose disposal and act as insulin sensitizer. Moreover, folic acid administration seems to improve glycaemic control reducing insulin resistance in other insulin resistant conditions. Therefore, we carried-out a 24 weeks, prospective, randomized, control trial in 26 overweight or obese T1D patients, undergoing intensive insulin therapy. The results of this trial demonstrated for the first time that the DCI plus Folic Acid oral supplementation can improve glycaemic control in overweight T1D patients, as showed by the significant reduction of HbA1c at the end of the study period.

New technologies and adjuvant treatments for the management of type 1 diabetes / Anna Rita Maurizi , 2017 Oct 30. 26. ciclo

New technologies and adjuvant treatments for the management of type 1 diabetes

2017-10-30

Abstract

Type 1 diabetes (T1D) is an immune-mediated chronic disease accounting for 5-10% of the total cases of diabetes and its incidence is growing worldwide. As a result of the autoimmune process, inducing the failure of insulin-producing cells, intensive insulin therapy represents the gold standard treatment to maintain blood glucose homeostasis. In 1993, the effectiveness of intensive insulin therapy in T1D has been widely established in Diabetes Control and Complications Trial (DCCT). Moreover, it was affirmed that optimal glycaemic control is directly related to the reduction of incidence and progression of long-term diabetes complications. Therefore, tight glycaemic control is overall recommended for T1D patients with near-normalization of blood glucose levels and an HbA1c <7.0% as the treatment goals. However, a great number of T1D patients have a suboptimal glycaemic control and 60% of people with T1D monitor less frequently than American Diabetes Association (ADA) recommendations of =3 tests daily. On the other hand, benefits of intensive insulin treatment observed in the DCCT came with a three times higher risk of severe hypoglycaemia compared to the conventional therapy with one or two daily insulin injections and the fear of hypoglycaemia keeps many patients away from intensive treatment and achievement of recommended glycaemic goals. Furthermore, treatment goals should be achieved safely and effectively by maintaining daily flexibility to fit individual lifestyle and without major variations in eating behaviours and physical activity promoting patients' compliance and their overall quality of life. Therefore, to reduce these main limiting factors supporting long-term diabetes management the newer technologies and adjuvant treatments represent areas of investigation with important clinical applications. The overall aim of my PhD was to find out if new technologies and adjuvant treatments may improve glycaemic control and patients compliance, reducing glucose variability in T1D patients. This thesis includes two sections: the first one section is focused on the effectiveness of a bolus advisor calculator on glycaemic control in T1D patients undergoing intensive insulin therapy; the second section evaluates the hypothesis that D-Chiro-Inositol (DCI) plus Folic Acid oral supplementation can act as adjuvant treatments to insulin therapy in overweight or obese T1D patients, reducing insulin resistance. 1st section: in order to achieve an optimal glycaemic control in insulin-treated T1D patients the rationale of this part of the thesis has been the higher frequency of errors with empirical calculations of mealtime insulin doses. In fact, 42% diabetic patients administer an uncorrected dose of prandial insulin and the few studies carried-out on bolus calculator systems have been published with controversial results. At the same time, we tested effectiveness and feasibility of a wirelessly meter integrated with a bolus calculator working with a telemedicine system. Furthermore, we investigated the efficacy of this automated bolus calculator (ABC) and wirelessly communicated blood glucose measurement on glucose variability, by the use of a continuous glucose monitoring system (CGMS). The rationale is clearly established from the DCCT results suggesting that glycaemic variability may be an additional risk factor for the long- term diabetes complications and the new treatment strategies are increasingly focusing on reducing post-prandial glycaemic excursions. The results of this section have demonstrated that an ABC system is a friendly wirelessly meter that helps to improve glycaemic control and patients compliance to SMBG. Moreover, patients using an ABC showed a significant reduction of time spent in hypoglycaemic range compared to the control subjects. 2nd section: The rationale of this section of the thesis was based on the worldwide rise of obesity in childhood and adolescence with the consequent increase of insulin resistance also in young patients with T1D. In fact suboptimal glucose control is often due to the higher insulin doses causing an increased risk of hypoglycaemic events, weight gain and poor glycaemic control. On this basis, the second part of this thesis was focused on a research project evaluating the hypothesis that D-Chiro-Inositol (DCI) plus Folic Acid oral supplementation may improve glucose control reducing insulin resistance in overweight or obese T1D patients. In fact, D-Chiro-Inositol (DCI), as putative mediator of intracellular insulin action can accelerate glucose disposal and act as insulin sensitizer. Moreover, folic acid administration seems to improve glycaemic control reducing insulin resistance in other insulin resistant conditions. Therefore, we carried-out a 24 weeks, prospective, randomized, control trial in 26 overweight or obese T1D patients, undergoing intensive insulin therapy. The results of this trial demonstrated for the first time that the DCI plus Folic Acid oral supplementation can improve glycaemic control in overweight T1D patients, as showed by the significant reduction of HbA1c at the end of the study period.
30-ott-2017
type 1 diabetes glycaemic control
New technologies and adjuvant treatments for the management of type 1 diabetes / Anna Rita Maurizi , 2017 Oct 30. 26. ciclo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/68846
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