Endocrine disruptors are a category of substances, both of natural and synthetic origin, capable of interfering with hormonal systems at various levels. Their often persistent presence in the environment increases the risk of human exposure with potential adverse health effects. Some interferents appear to have the ability to alter glycemic homeostasis, leading to harmful consequences on glycemic metabolism and increasing the risk of developing diabetes mellitus. Such endocrine disruptors include heavy metals, pesticides, bisphenols, PBDEs, and phthalates. However, although some evidence suggests an association between exposure to these interferents and glycemic changes, the scientific evidence to date is conflicting. Moreover, the pathophysiological mechanism by which these substances can cause these alterations is not yet well understood. Therefore, more studies are needed to further the understanding of the association between exposure to endocrine disruptors and glycemic alterations to better delineate the underlying pathophysiological mechanisms.

KEY WORDS endocrine disruptors; diabetes; pesticides; heavy metals; bisphenol A.

Gestational diabetes mellitus (GDM), which is characterized by glucose intolerance first diagnosed during pregnancy, is one of the most common pregnancy complication. It is now affecting approximately 14% of pregnancies worldwide, and its prevalence continues to increase. Although GDM usually resolves after delivery, it may have several long-lasting health consequences, such as increased risk for type 2 diabetes mellitus and cardiovascular disease, on the mother as well as on the offspring.

An increasing body of evidences supports the notion that experiencing an adverse intrauterine environment, especially when due to maternal hyperglycemia, can affect cellular and organ systems during the early life of the offspring and interact with postnatal environmental and lifestyle factors to define metabolic disease risk.

The concept of lasting consequences of early-life environmental exposure for later disease risk is widely known as “fetal programming”, but the involved mechanisms are still not completely known.

Compelling evidences point to the epigenetic processes as an important mechanism underpinning lasting effects on the offspring.

The epigenetic processes, which include DNA methylation, the establishment of chromatin states by histones modifications and non-coding RNAs regulation, are able to modulate gene expression without DNA nucleotide sequence changes. These processes, physiologically involved in cell differentiation and the maintenance of the differentiated state, also play an important role in the complex interplay between genes and the environment. This interaction may result in the activation or deactivation of genes through induced epigenetic changes, thus facilitating adaptation to different environmental cues.

This review provides an overview of the critical role of epigenetic changes in fetal metabolic programming linked to GDM and their long-lasting health consequences.

KEY WORDS pregnancy; gestational diabetes; insulin secretion; long[1]term consequences; epigenetics; type 2 diabetes; diabetes risk.

AIM The aim of the study was to evaluate the quality of care indicators relating to 2019, the pre-pandemic year, from a gender perspective in people with type 1 diabetes (DM1).

DESIGN AND METHODS The data of patients with type 1 diabetes (DM1) seen in the year 2019, collected from the 282 diabetes services that participated in the retrospective observational study “Annals AMD”, were processed and the process, outcome intermediate, appropriateness, final outcome, and overall quality of care (Q score) were extracted.

RESULTS Data from 37,445 DM1 patients (16,971 women and 20,474 men) seen during 2019 were analyzed to allow comparison with previous editions of the AMD Annals. Women are older. There are no gen[1]der differences in monitoring process indicators. The mean HbA1c levels are 7.9% (63mmol/L) in women and 7.7% (60mmol/L) in men. The proportion of subjects with HbA1c≤ 7% (53 mmol/L) is higher among men (31.7%) than women (25.6%). The lipid profile does not show substantial gender differences. Mean blood pressure levels were higher in men than in women. 70.9% of women and 63.8% of men have systolic blood pressure values <= 130 mm Hg and 86.2% of women and 81.1% of men have diastolic blood pressure values <= 80 mmHg. II and III degree obesity was more frequent in females (BMI: 35.0-39.9: women: 3.1% and men: 1.9%; BMI>40: women: 0.9%, men: 0.4%). 12.2% of women and 10.3% of men have an eGFR <60 ml/m* 1.73m2. Micro/macroalbuminuria is present in 17.2% of women and 21.3% of men. Women are more treated with CSII: 21.1% F vs 14.8% M. The use of lipid-lowering drugs in women is lower than that of men in 2019 (F=34.4%, M=37.7%). 61% in both genders the Q Score is >25, a sign of an adequate overall quality of care.

CONCLUSIONS The data from the AMD annals analyzed according to gender for the year 2019 confirms the worse metabolic control of women with DM1, the lesser lipid-lowering treatment, the higher frequency of reduced eGFR, while in men blood pressure control is worse and the higher the frequency of microalbuminuria. Knowing these differences, and understanding their causes, is important for diabetes specialists to improve care for people with DM1.

KEY WORDS type 1 diabetes; gender differences; AMD Annals; quality of care.

OBJECTIVE OF THE STUDY To verify the evolution of the therapy’s quality in type 2 (DM2) diabetic patient In Italy, from a gender perspective.

DESIGN AND METHODS For the purpose of this analysis, data from the AMD Annals referring to patients with DM2, followed in italian diabetes centers in 2019, were used, comparing indicators of quality of care between male and female patients and compared to 2016 analysis.

RESULTS The data of 304,561 men and 227,169 women with DM2 followed by 282 diabetes centers in the year 2019 were evaluated. The prevalence of males and a general aging of the population are confirmed. The increase in survival mainly affects women, while the number of new diagnoses has grown in both sexes. Most process indicators improved, maintaining the advantage for males. Monitoring of glycated hemoglobin and blood pressure concerns almost all patients; the percentage of patients checked for lipid profile and renal function are lower. Foot screening activity remains stable and low and screening for retinopathy is reduced. The predictive indicators of cardiovascular (CV) risk remain against the female sex; in particular, women are more obese, have worse glycemic control, lipid profile and kidney function. The percentage of smokers is stable. The treatment of glycemia and dyslipidemia did not differ in the two sexes and the adoption of innovative drugs has significantly increased. The intensity of care for hypertension is higher in women. There was a general reduction in ACE-I/ARBS therapy in patients with microalbuminuria. It is confirmed that there is no under-treatment of women, despite their worse outcomes with regards to CV risk factors. Micro and macro[1]angiopathic complications confirm gender differences, but the quality of the data recording on final outcomes is still modest. More than 30% of patients are >75 years old, mostly women, and a significant percentage, in both sexes, use segretagogues/insulin.
Over the years, the overall quality of care has improved, in a similar way in both genders. More than 60% of patients have a Q score >25, with an increase of about 10 percentage points compared to 2016.

CONCLUSIONS The analysis of the 2019 data confirms a continuous improvement in the quality of diabetes care and adequate levels of overall assistance. The CV risk profile is still unfavorable for women. Elderly patients require specific adaptation and personalization of care.

KEY WORDS gender; DM2; AMD indicators.

AIM Aim of this survey is to explore the use of metformin in its standard and extended-release formulation in a community of Italian diabetes specialists.

METHODS We collected data about metformin prescription and use in our clinics administering a 13 questions web questionnaire to the members of the Italian Association of Medical Diabetologists (AMD). The questionnaire investigates the use of metformin and focuses on the use of prolonged-release metformin.

RESULTS 253 doctors participated in the survey. Most doctors prescribe metformin gradually until the effective dose is reached. Most participants (82.2%) recommend taking metformin with food. 70.4% of the participants believe that the use of metformin in pre-diabetes is justified even if the treatment is to be considered off-label and the same percentage believes that the drug induces negligible effects on the reduction of body weight.

Interestingly, as many as 77% of participants suggest discontinuing metformin before a contrast test, 80% prescribe extended-release metformin when standard metformin has triggered adverse effects. In their opinion, this formulation increases patient compliance and almost always resolves/ improves gastrointestinal symptoms. Interestingly, 50% of diabetologist recommend taking tables once a day; the others, suggest twice a day.

32.8% of the participants prescribe extended-release metformin for its easier use. Finally, the diabetologists prefer using metformin with other hypoglycemic agents at diabetes onset if the patient has marked hyperglycemia or an ongoing cardiovascular disease.

CONCLUSIONS The present survey shows that there is a difference in the use and prescription of metformin in its two formulations, standard and slow-release. Usually, slow-release metformin meets with greater prescribing approval due to the fewer side effects, the easier handling, and the greater patient satisfaction. However, it should be noted that metformin remains the drug of first choice in Italy.

KEY WORDS metformin extended-release; metformin immediate-release; diabetologists.

AMD Campania has promoted a nationwide online survey with the aim of assessing the sensitivity of diabetologists on issues such as over-insulinization and de-insulinization in type 2 diabetes patients.

For this purpose, we addressed 10 specific issues the participants were 155 with 67% aged over 50 years.

The regions responded uniformly. All participants (100%) are willing to review basal-bolus therapy in the light of new drugs for the treatment of type 2 diabetes.

Finally, 85% of participants believe that it is useful to have a flow chart that can make the therapeutic transition to de-insulinization easy, simple, and safe.

83% of the participants declared themselves in favor of the Note 100, a significant result underlining cultural acceptance of the prescriptive openness to other health figures, also given the skepticism with which the note itself was initially received.

KEY WORDS type 2 diabetes mellitus; de-insulinization; flow-chart.