Alessio Mazzieri

Bio: Alessio Mazzieri is an academic researcher. The author has contributed to research in topics: Hypoglycemia & Medicine. The author has an hindex of 1, co-authored 1 publications receiving 1 citations.

Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin?

Abstract: Hypoglycemia represents a dark and tormented side of diabetes mellitus therapy. Patients treated with insulin or drug inducing hypoglycemia, consider hypoglycemia as a harmful element, which leads to their resistance and lack of acceptance of the pathology and relative therapies. Severe hypoglycemia, in itself, is a risk for patients and relatives. The possibility to have novel strategies and scientific knowledge concerning hypoglycemia could represent an enormous benefit. Novel available glucagon formulations, even now, allow clinicians to deal with hypoglycemia differently with respect to past years. Novel scientific evidence leads to advances concerning physiopathological mechanisms that regulated glycemic homeostasis. In this review, we will try to show some of the important aspects of this field.

The role behind the scenes of Tregs and Th17s in Hashimoto’s thyroiditis: Toward a pivotal role of FOXP3 and BACH2

Abstract: In Hashimoto’s thyroiditis (HT), the genetic bases play a central role in determining development of the disease. In particular, the most frequent genes involved in the onset of HT are the Human Leukocyte Antigen (HLA). However, there are other genes and transcription factors in the autoimmune background of HT, both isolated and as part of autoimmune polyendocrine syndromes (APS). Recently more interest is being fueled toward BACH2 (BTB Domain and CNC Homolog 2), that promotes Tregs (T regulators lymphocytes) differentiation and enhances Treg-mediated immunity. The synergistic interaction between environmental agents and the aforementioned genes leads to the onset of autoimmunity and ultimately to damage of the thyroid gland. In this scenario, the role of Th17 (T helper-17 lymphocytes) and Treg cells is still less defined as compared to action of Th1 cells (T helper-1 lymphocytes) and cytotoxic lymphocytes (CD8 + T lymphocytes). Evidences show that an imbalance of Th17/Treg ratio represents a prognostic factor with respect to the gland damage. Moreover, the deficient ability of Treg to inhibit the proliferation of T cells against the self can break the immune balance. In light of these considerations, the use of genetic panels and the progress of immunotherapy could allow for better targeting treatment and preventive interventions in subjects with potential or early stage of HT.

83-LB: Simplifying Insulin Treatment in Persons with T2 DM over 65 Years—Interim Report of the STOP Study

Abstract: This is an interim evaluation of the STOP study, a proof-of-concept observation, whose aim is to test effectiveness and safety of IDegLira in deintensifying diabetes therapy in insulin-treated persons with T2DM aged >65 years. The study, retrospective observational, gathered so far data related to 93 consecutive persons with T2 DM, in whom IDegLira was introduced in therapy, and for whom clinical data were available for at least 6 months after the switch. The 93 persons (42 F, age 76±8 yrs, diabetes duration 20±10 yrs, duration of insulin treatment 13±12 yrs, BMI 28.6±4.9 kg/m2, A1C 7.4±0.9), were for the 75% in basal/bolus insulin therapy. Sixteen % of them, needed caregiver, whereas 53% were in follow up at the Geriatric Clinic for mild/severe cognitive impairment. After 3 months, fasting plasma glucose (PG) decreased (from 138±38 to 117±24 mg/dl, p=0.000036 vs baseline), similarly A1C (from 7.4±0.9 to 7.0±0.6%, p=0.000126). All results showed additional improvement at 6 month (p< 0.005 vs baseline). Rates of hypoglycemia at any time of day (PG <70 mg/dl) were lower after 3 months (0.35±0.94 vs 1.15±2.61, episodes/pt/month, p=0.0057). Episodes with PG <54 mg/dl decreased from 0.56±1.71 to 0.03±0.25, p=0.0093). Accordingly, the proportion of patients with at least one episode of PG <70 mg and 54 mg/dl, felt down from baseline to 3 month (23.7 to 14%;16.1 to 11%, respectively), being zero at 6 months. Rapid acting insulin dose decreased by 80 % at 3, up to 95% at 6 months (from 0.18±0.13 to 0.04±0.06 at 3, and 0.01±0.04 U/kg at 6 months, p< 0.0001). Nearly all patients interrupted it. IDegLira was initiated at a mean dose of 17±5.4 U/die to further increase to 23±9.6 after 6 months. BMI did not change significantly (p=ns). According to our preliminary results, IDegLira seems to offer a relevant option, to more complex insulin regimens, in terms of effectiveness and safety, in a population in whom preventing hypoglycemia and improving quality of life are mandatory and clinical inertia is often present. A. Mazzieri: None. M. De fano: None. F. Mancinetti: None. D. Xenos: None. V. Boccardi: None. C. G. Fanelli: None. F. Porcellati: Board Member; Lilly Diabetes, Sanofi, Consultant; Novo Nordisk.

Molecular Mechanisms in Autoimmune Thyroid Disease

Abstract: The most common cause of acquired thyroid dysfunction is autoimmune thyroid disease, which is an organ-specific autoimmune disease with two presentation phenotypes: hyperthyroidism (Graves-Basedow disease) and hypothyroidism (Hashimoto’s thyroiditis). Hashimoto’s thyroiditis is distinguished by the presence of autoantibodies against thyroid peroxidase and thyroglobulin. Meanwhile, autoantibodies against the TSH receptor have been found in Graves-Basedow disease. Numerous susceptibility genes, as well as epigenetic and environmental factors, contribute to the pathogenesis of both diseases. This review summarizes the most common genetic, epigenetic, and environmental mechanisms involved in autoimmune thyroid disease.

Safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight and obese patients with co-morbidities.

Abstract: AIM To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of the novel long-acting glucagon analogue HM15136 in overweight/obese patients with co-morbidities, with and without type 2 diabetes (T2D). MATERIALS AND METHODS This was a phase 1, double-blind, randomized, placebo-controlled, two-part trial with a 12-week treatment period of once-weekly subcutaneous HM15136 (0.02/0.04/0.06 mg/kg). Part 1 included patients with dyslipidaemia and/or hypertension and no T2D. Part 2 included patients with dyslipidaemia and/or hypertension plus T2D. RESULTS In part 1, 23/27 (85.2%) patients receiving HM15136 and all patients receiving placebo (9/9 [100%]) experienced a treatment-emergent adverse event (TEAE). Five of 27 (18.5%) patients receiving HM15136 developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration and fasting plasma glucose (FPG) were observed, as were dose-dependent weight reductions of 0.5%/2.3%/2.6% at doses of 0.02/0.04/0.06 mg/kg, respectively. In part 2, 8/12 (66.7%) patients receiving HM15136 and all patients receiving placebo (4/4 [100.0%]) reported a TEAE. Two (16.7%) patients developed anti-HM15136 antibodies. Dose-dependent increases in mean HM15136 serum concentration were observed. FPG of more than 200 mg/dL was reported in 4/9 (44.4%) and 2/3 (66.7%) patients receiving 0.02 and 0.06 mg/kg, respectively. The 0.06 mg/kg dose was not tolerated in part 2 because of hyperglycaemia. Patients receiving 0.02 mg/kg showed a 0.9% weight reduction. No serious TEAEs leading to discontinuation were reported in either study part. CONCLUSIONS This study of HM15136 provides a preliminary safety and tolerability profile with initial insights into its efficacy profile.

Integrated safety and efficacy analysis of dasiglucagon for the treatment of severe hypoglycaemia in individuals with type 1 diabetes

Abstract: To perform an integrated analysis of the safety and efficacy of dasiglucagon, a glucagon analogue available in a ready‐to‐use aqueous formulation, to treat severe hypoglycaemia (SH) in type 1 diabetes (T1D).