The role of the autonomic nervous system in obesity and insulin-resistant conditions has been largely explored. However, the exact mechanisms involved in this relation have not been completely elucidated yet, since most of these mechanisms display a bi-directional effect. Insulin-resistance, for instance, can be caused by sympathetic activation, but, in turn, the associated hyperinsulinemia can activate the sympathetic branch of the autonomic nervous system. The picture is made even more complex by the implicated neural, hormonal and nutritional mechanisms. Among them, leptin plays a pivotal role, being involved not only in appetite regulation and glucose homeostasis but also in energy expenditure. The purpose of this review is to offer a comprehensive view of the complex interplay between leptin and the central nervous system, providing further insights on the impact of autonomic nervous system balance on adipose tissue and insulin-resistance. Furthermore, the link between the circadian clock and leptin and its effect on metabolism and energy balance will be evaluated.

The advanced and performing technologies of glucose monitoring systems provide a large amount of glucose data that needs to be properly read and interpreted by the diabetology team in order to make therapeutic decisions as close as possible to the patient’s metabolic needs. For this purpose, new parameters have been developed, to allow a more integrated reading and interpretation of data by clinical professionals. The new challenge for the diabetes community consists of promoting an integrated and homogeneous reading, as well as interpretation of glucose monitoring data also by the patient himself. The purpose of this review is to offer an overview of the glycemic status assessment, opened by the current data management provided by latest glucose monitoring technologies. Furthermore, the applicability and personalization of the different glycemic monitoring devices used in specific insulin-treated diabetes mellitus patient populations will be evaluated.

Retinal neurodegeneration (RN), an early marker of diabetic retinopathy (DR), is closely associated with Müller glia cells (MGs) in diabetic subjects. MGs play a pivotal role in maintaining retinal homeostasis, integrity, and metabolic support and respond to diabetic stress. In lower vertebrates, MGs have a strong regenerative response and can completely repair the retina after injuries. However, this ability diminishes as organisms become more complex. The aim of this study was to investigate the gliotic response and reprogramming potential of the human Müller cell line MIO-M1 cultured in normoglycemic (5 mM glucose, NG) and hyperglycemic (25 mM glucose, HG) conditions and then exposed to sustained high-glucose and glucose fluctuation (GF) treatments to mimic the human diabetic conditions. The results showed that NG MIO-M1 cells exhibited a dynamic activation to sustained high-glucose and GF treatments by increasing GFAP and Vimentin expression together, indicative of gliotic response. Increased expression of SHH and SOX2 were also observed, foreshadowing reprogramming potential. Conversely, HG MIO-M1 cells showed increased levels of the indexes reported above and adaptation/desensitization to sustained high-glucose and GF treatments. These findings indicate that MIO-M1 cells exhibit a differential response under various glucose treatments, which is dependent on the metabolic environment. The in vitro model used in this study, based on a well-established cell line, enables the exploration of how these responses occur in a controlled, reproducible system and the identification of strategies to promote neurogenesis over neurodegeneration. These findings contribute to the understanding of MGs responses under diabetic conditions, which may have implications for future therapeutic approaches to diabetes-associated retinal neurodegeneration.

Retinal neurodegeneration (RN) is an early marker of diabetic retinopathy, preceding vascular damage. The aims of our study are to evaluate the three-year progression of neuroretinal structure, the association between early alterations and diabetic neuropathy (DN) and the predictive role of glycaemic variability (GV) in this progression in paediatric type 1 diabetes mellitus (T1DM) subjects. Twenty-five paediatric T1DM patients, using Continuous Glucose Monitoring (CGM) and treated with continuous subcutaneous insulin infusion, without any complication, and eighteen controls (C) were enrolled and followed for three years. All subjects underwent an Optical Coherence Tomography, with analysis of neuroretinal layers. In T1DM patients, metabolic parameters, GV indexes, standardised CGM metric, peripheral and autonomic assessment were investigated. All the data were collected at baseline and every 12 months. Starting from the baseline, Retinal Nerve Fiber Layer thickness and Outer Plexiform Layer (OPL) became significantly thinner in T1DM versus C. In T1DM patients, negative correlations were observed between GV and all the inner retinal layers and positive correlations were observed between TIR and OPL. No significant correlations between HbA1c and macular layer thickness were observed. At V3, positive correlations between the retinal variation and neuropathic indexes were observed. Early morphological alterations of neuroretina are already present in paediatric T1DM patients without complications. There is a possible association between these alterations and early signs of DN. These data corroborate the hypothesis that RN is an early sign of DN and GV should be effectively addressed in the early stage of T1DM.