In medicine, there is growing evidence that gender differences are important and lead to variations in the pathophysiology and treatment of many diseases with traits that appear to be particularly relevant in influencing the outcomes of many morbid forms. Today, the inclusion of gender in biomedical research, to improve the scientific quality and scientific relevance of knowledge, of technology is an increasingly present element precisely due to the practical implications that derive from it. Gender differences describe the biological variability between women and men, which is, in turn, related to differences in the information contained in sex chromosomes, the specific gene expression of autosomes linked to sex, the different number and quality of sex hormones, and their different effects on systems and organs, without neglecting the fact that each of the sexes has different target organs on which these hormones act. Additionally, both genders undergo metabolic changes throughout their lives, and this is especially true for women who show more dramatic changes due to their role in reproduction. Gender differences are not only the result of our genetic makeup but are also mixed with socio-cultural habits, behaviors, and lifestyles, differences between women and men, exposure to specific environmental influences, different food and lifestyle styles or stress, or different attitude in compliance with treatments and disease prevention campaigns. Gender differences also affect behavior throughout life, and physical changes can have implications for lifestyle, social roles, and mental health. Therefore, determinism and therapeutic outcome in chronic diseases are influenced by a complex combination of biological and environmental factors, not forgetting that there are many interactions of social and biological factors in women and men. This review will address the role of gender differences in the management of various forms of diabetes and its complications considering the different biological functions of hormones, the difference in body composition, physiological differences in glucose and fat metabolism, also considering the role of the microbiota. intestinal, as well as the description of gestational diabetes linked to possible pathophysiological events typical of reproduction.

Aim To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between CKD-mineral bone disorder biomarkers and vascular stiffness (Cardio Ankle Vascular Index, CAVI) in the course of type 2 diabetes (T2DM). Method we evaluated 174 T2DM patients (median age 56 y; M/F = 100/74) with diabetes duration less than 10 years and without decreased glomerular filtration rate (eGFR ≥60 ml/min/1.73 m ²) or macrovascular complications. Thirty-four age matched healthy subjects (M/F: 13/21; age: 53.5[50.0-57.7] y.o; eGFR 107.5[97.0-119.7]) ml/ml/min1.73m2) served as local reference control for CAVI (pathological: ≥8) and the novel CKD-MBD biomarkers. Results albumin-to-creatinine ratio (ACR) averaged 8.5 mg/g [5.6-17.2] with 12.6% of the patients showing pathologic values, indicative of incipient diabetic nephropathy (DN). Serum parathyroid hormone, Fibroblast Growth Factor 23 and Sclerostin were higher while 1,25-dihydroxyvitamin D and Klotho were lower than a control group. CAVI was normal (<8) in only 54% and correlated positively with age (p<.001), Hb1A1c (p=.036), systolic (p=.021) and diastolic blood pressure (DBP) (p=.001) and negatively with 25D (p=.046). In multivariate analysis, age, DBP, ACR, and s-Klotho were independent positive predictors of CAVI. Conclusion in the absence of overt cardiovascular disease and of chronic renal insufficiency, CAVI is frequently pathologic in T2DM. DBP, and ACR are modifiable risk factors of vascular stiffness in T2DM thus warranting optimal assessment.

Introduction Despite the development of several recommendations, glycemic control in a large proportion of patients with type 2 diabetes, including those treated with insulin, remains suboptimal. This study is aimed to identify a set of actions to promote the reduction of inappropriate clinical practices in type 2 diabetes failing basal insulin supported oral therapy (BOT). Methods A panel of diabetes specialists was assembled to identify a list of ten corrective actions, “things not to do,” for the management of type 2 diabetes: five concerning treatments, procedures and diagnostic tests and five about relationship, communication and information. The Choosing Wisely methodology and approach were the inspiration. Results A total of 73/73 (100%) panelists responded to the survey. Twenty-four actions were proposed. The final list of inappropriate actions deemed most important to improve the management of patients with type 2 diabetes failing BOT were: (1) do not use secretagogues—do not neglect the use of innovative glucose-lowering agents; (2) do not underestimate the risk of lack of hypoglycemia awareness; (3) do not underestimate the benefit of personalization of therapy; (4) do not delay insulin intensification; (5) do not delay modification of the therapeutic regimen. In the area of patient communication, the following actions were identified: (1) do not fail to train in the management of hypoglycemia; (2) do not underestimate whether the patient has understood the modification of therapy; (3) do not prescribe injection therapy without adequately instructing the patient to titrate it; (4) do not ignore the patient’s adherence; (5) do not stop listening to the patient and verify learning. Conclusion A set of corrective experience-based actions to enact in a timely manner, which can assist physicians in improving clinical outcomes and patients’ needs in terms of communications and interaction, is proposed. The list is intended to promote discussions among diabetes specialists to provide high-value diabetes care.

Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people with T2D free from overt vascular complications. In this cross-sectional study, arterial stiffness as measured using standard pulse wave velocity (PWV) was evaluated in 174 people with T2D without overt vascular disease. Then, we measured CHIT serum activity with an electrochemiluminescence assay in two subgroups of participants: 35 with the highest (high-PWV) and 40 with the lowest (low-PWV) PWV values. CHIT activity was no different between the low-PVW and high-PWV groups (12.7 [9.6–17.9] vs. 11.4 [8.8–15.0] nmol/mL/h, respectively). Compared with the low-PWV group, the high-PWV participants were older (p < 0.001); had a longer duration of diabetes (p = 0.03); higher ankle–brachial index ABI (p = 0.04), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.005), fasting blood glucose (p = 0.008), and HbA1c (p = 0.005); and lower eGFR (p = 0.03) and body mass index (BMI) (p = 0.01). No association was present with sex, duration of diabetes, age, BMI, peripheral blood pressure, laboratory parameters, and glucose-lowering medications or ongoing antihypertensive therapy. Although no association was found, this study provides novel data about the association of CHIT activity with CVD, focusing on a specific outcome (arterial stiffness) in a well-defined population of subjects with T2D without established CVD.

Diabetic gastroparesis (DGp) is a chronic complication of diabetes characterized by delayed gastric emptying with nausea, vomiting, early satiety, bloating, and poor glycemic control. Diagnosis requires objective testing, preferably a 4-h gastric emptying scan, along with assessment of symptom severity and quality of life for affected patients. Diabetic gastroparesis is the result of complex and overlapping mechanisms: autonomic (vagal) neuropathy, loss/dysfunction of interstitial cells of Cajal (ICC), enteric neuropathy, pyloric dysfunction (increased pyloric tone), and altered gut–brain signaling. Chronic hyperglycemia precipitates and worsens gastric dysmotility. Management remains multimodal: optimize glycemic control and nutrition, use evidence-based prokinetics and antiemetics, and consider targeted procedural/device therapies (G-POEM, gastric electrical stimulation) for refractory cases. The present is characterized by renewed drug development (ghrelin agonists such as relamorelin, with promising efficacy but a not-yet-well-established commercial pathway) and growing evidence for selective prokinetics already in use for other indications (prucalopride). Neuromodulation (Enterra GES) remains an option for selected refractory patients. Recent guidelines and studies define when and how to use these options, but no randomized head-to-head comparisons of the various therapeutic options are yet available, nor are long-term, real-world safety/efficacy registries for drugs and minimally invasive surgical procedures. There is still unsatisfactory evidence on how to safely manage GLP-1 receptor agonist therapy in diabetic patients predisposed to gastroparesis (balancing cardiorenal glycemic benefits versus gastrointestinal adverse effects), considering that these drugs can worsen gastric emptying and symptoms, requiring careful clinical judgment. This review aims to analyze and update clinicians on new evidence in the diagnosis and treatment of these conditions, starting from earlier recognition to achieving more rational treatment that balances the need for good glycemic control, control of gastrointestinal symptoms related to these complications, and an acceptable quality of life for the diabetic patient.