Calorie restriction promotes longevity in several animal models. Compounds that modulate nutrient sensing pathways have been suggested to reproduce some of the beneficial effect of calorie restriction on aging. However, none of the commonly studied calorie restriction mimetics actually produce a decrease in calories.
Sodium glucose cotransporter 2 inhibitors (SGLT2i) are a class of drugs that lower glucose by promoting its elimination through the urine, thus inducing a net loss of calories. This effect promotes a metabolic rearrangement at a systemic level, encouraging the use of ketones and fatty acids as alternative substrates to glucose, and is accompanied by a modulation of the main pathways believed to be responsible for aging.
There is a wealth of data from clinical trials, observational studies and meta-analyses that suggest a tangible effect on age-associated pathologies, such as cardiovascular disease, heart failure, kidney disease, and all-cause mortality even in patients without diabetes, in addition to the protective effect against the progression of prediabetes and the development of liver disease. Consequently, we propose here a hypothesis in which at least part of the benefit provided by SGLT-2i is mediated by their ability to attenuate the drivers of aging. If confirmed and extended, the available evidence could suggest the design of studies that test the potential use of this class as preventive drugs in a progressively larger audience of patients.

KEY WORDS calorie restriction; sodium glucose cotransporter 2 inhibitors; aging.

In recent times we observed a portentous acceleration of therapeutic options in the pharmacological management of type 2 diabetes mellitus. The main basic research lines showed three specific pathophysiological rational pathways: 1) the mechanism of insulin-resistance, 2) the glycosuric effect SGLT2-mediated and 3) incretin axis.The De Fronzo “Banting Lecture” documented in a meticulous manner the new holistic vision of pathophysiological mechanisms involved in diabetes, with the individuation of the celebrated “omnious octet”. In this report we showed a hystorical research since the primordial scientific experiments of the Seventeenth Century by Johann Conrad Brunner, the first individuation of the secretin in 1902 by Byliss and Sterling, the absolutely first hormone described, the identification and the molecular characterization of incretins and GIP in 1970s, with the prominent role of John Carvin Brown’s research, and next elucidation of the metabolic pathways of entero-insular axis. Our intention is to offer a rational contribution and a hystorical perspective to better understand this topic, perhaps the most exciting and controversial in the last decades.

KEY WORDS incretins; GIP; entero-insular axis; hystorical perspective; pathophysiologycal mechanisms; glucose control.

AIM Glucose monitoring in subjects with diabetes is increasingly based on the use of sensors (i.e. intermittent or continuous systems) that detect glucose values in the interstitial fluid. Certain substances, such as some drugs can influence the readings of these devices. Considering the remarkable impact these interferences can have on the therapeutic management of diabetes, in this article we have summarised the available data on possible interferences between drugs and sensors.

MATERIAL AND METHODS We have performed a literature research in order to retrieve studies in which glucose sensors were tested with commonly used substances. Furthermore, information from the data sheets and user manuals of the devices were examined.

RESULTS The main interfering substances with glucose monitoring systems are acetaminophen (Guardian 4, Dexcom G4 and G5, FreeStyle Libre PRO, Glunovo Flash I3, Dexcom G6 and ONE only if taken in higher than recommended doses), ascorbic acid (FreeStyle Libre 2 and 3 if taken in doses > 500 mg/day) and hydroxyurea (Enlite, Guardian 3, Dexcom G4, G5, G6 and ONE). New generations of sensors have less susceptibility to exogenous substances due to low voltage technologies (FreeStyle Libre) or due to the presence of semi-permeable membranes on the sensor surface that inhibit the passage of possible interferents (Dexcom G6).

CONCLUSION Knowing which substances and how they interfere with the glucose levels detected by the sensors is crucial, both for stand-alone glucose monitoring systems and for sensors integrated with insulin pumps, in order to avoid hypoglycaemia/ hyperglycaemia not detected by the sensor and consequent therapeutic errors.

KEY WORDS interference; medications; continuous glucose monitoring; intermittent glucose monitoring; diabetes.

In recent decades, there has been a significant increase in the prevalence of diabetes worldwide. One of the most relevant challenges for the diabetologist is to optimise glycemic control in pregnancy. Metformin represents a promising therapeutic option during pregnancy, as it allows maintaining adequate glycemic control without the risks associated with insulin therapy, such as hypoglycemia and weight gain. Moreover, it is a manageable, inexpensive, and generally well-tolerated drug for pregnant women. Despite its rationale for use, however, there is still disagreement over the benefits and risks associated with its prescription/administration. There is solid evidence that metformin is safe during the first trimester of pregnancy, with no risk of congenital malformations. During the remainder of pregnancy, metformin has been associated with a reduction in maternal weight gain and daily insulin requirements. In newborns, metformin appears to reduce hypoglycemia and macrosomia, although, in some situations, such as in pregestational type 2 diabetes, it may increase the risk of babies born SGA (small for gestational age). Furthermore, some studies hypothesise an increased risk of obesity and altered fat distribution in offspring in the long term in women using metformin during gestation. The purpose of this review is to gather and investigate evidence on the benefits and potential pitfalls of metformin use in pregnancy.

KEY WORDS diabetes in pregnancy; gestational diabetes; pre-gestational diabetes type 2; metformin; insulin; pregnancy.

The recent approval in Italy of the Law “Provisions Concerning the Establishment of a Diagnostic Program for Detecting Type 1 Diabetes and Celiac Disease in the Pediatric Population” opens up new scenarios for research and clinical care in the field of pediatric diabetes, which is a complex and growing pathology. The newly established National Observatory will be tasked with defining the screening protocols. Currently, among various ongoing lines of research, teplizumab treatment is available for patients in stage 2 of the disease, characterized by the presence of two or more autoantibodies and dysglycemia.

KEY WORDS type 1 diabetes mellitus; celiac disease; screening; pediatric age.