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Insulin resistance (IR), marked by reduced cellular responsiveness to insulin, and obesity, defined by the excessive accumulation of adipose tissue, are two intertwined conditions that significantly contribute to the global burden of cardiometabolic diseases. Adipose tissue, beyond merely storing triglycerides, acts as an active producer of biomolecules. In obesity, as adipose tissue undergoes hypertrophy, it becomes dysfunctional, altering the release of adipocyte-derived factors, known as adipokines. This dysfunction promotes low-grade chronic inflammation, exacerbates IR, and creates a hyperglycemic, proatherogenic, and prothrombotic environment. However, the fundamental cause of these phenomena remains unclear. This narrative review points to hypoxia as a critical trigger for the molecular changes associated with fat accumulation, particularly within visceral adipose tissue (VAT). The activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor that regulates homeostatic responses to low oxygen levels, initiates a series of molecular events in VAT, leading to the aberrant release of adipokines, many of which are still unexplored, and potentially affecting peripheral insulin sensitivity. Recent discoveries have highlighted the role of hypoxia and miRNA-128 in regulating the insulin receptor in visceral adipocytes, contributing to their dysfunctional behavior, including impaired glucose uptake. Understanding the complex interplay between adipose tissue hypoxia, dysfunction, inflammation, and IR in obesity is essential for developing innovative, targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Gynecomastia in adolescence is a benign condition that mostly disappears spontaneously within approximately two years from onset. When it is associated with hypogonadism, it may suggest a disorder of sexual differentiation. We report the case of a young man (18 years old) with gynecomastia associated with azoospermia, small testes, hyperestrogenism and hypergonadotropic hypogonadism. A karyotype 46,XX was found, and searching for SRY (sex-determining region Y) by fluorescence in situ hybridization (FISH) highlighted the presence of the gene on the terminal region of the short arm, with breakpoints likely in Xp22.3 and Yp11.3. Implications of testosterone replacement therapy with respect to sex differentiation disorder and to physical performance are discussed. [ABSTRACT FROM AUTHOR]

In recent years, there has been a dramatic increase in the number of pregnancies complicated by gestational diabetes mellitus (GDM). GDM occurs when maternal insulin resistance develops and/or progresses during gestation, and it is not compensated by a rise in maternal insulin secretion. If not properly managed, this condition can cause serious short-term and long-term problems for both mother and child. Lifestyle changes are the first line of treatment for GDM, but if ineffective, insulin injections are the recommended pharmacological treatment choice. Some guidance authorities and scientific societies have proposed the use of metformin as an alternative pharmacological option for treating GDM, but there is not yet a unanimous consensus on this. Although the use of metformin appears to be safe for the mother, concerns remain about its long-term metabolic effects on the child that is exposed in utero to the drug, given that metformin, contrary to insulin, crosses the placenta. This review article describes the existing lines of evidence about the use of metformin in pregnancies complicated by GDM, in order to clarify its potential benefits and limits, and to help clinicians make decisions about who could benefit most from this drug treatment. [ABSTRACT FROM AUTHOR]

Background: Obesity constitutes a chronic, low-grade inflammatory status that predisposes people to the development of insulin resistance and cardiometabolic complications. Hypoxia, a main pathological feature of visceral fat in obese individuals, has been shown to affect the secretome of murine 3T3-L1 adipose cells, causing the upregulation of prothymosin-alpha (ProT-α), which is a protein with immunomodulatory functions that was originally found in the thymus. The aim of this case–control observational study was to measure the circulating levels of ProT-α in obese and lean individuals and determine whether such levels are correlated with inflammatory and metabolic parameters. Methods: Sixty-one obese patients (BMI ≥ 30 Kg/m2) and fifty-one age-matched, lean controls (BMI 18.5–24.9 Kg/m2) were recruited in the Endocrinology Unit ("Mater-Domini") of the University Hospital of Catanzaro, Italy. The exclusion criteria included affliction with acute and systemic inflammatory states (i.e., leukocytosis), recent infectious diseases or vaccinations, obesity complications (i.e., type 2 diabetes mellitus and cardiovascular diseases), hepatic or renal failure, pregnancy and lactation, cancer, use of drugs or alcohol, and smoking. Apart from routine biochemical determinations, serum samples were screened for the presence of ProT-α using an ELISA method and for the presence of a panel of inflammatory cytokines and growth factors via a multiparametric chemiluminescence micro-array. Results: Between the age-matched groups, no statistically significant differences were shown in relation to fasting glucose, HbA1c, liver function tests, lipid profiles, circulating interleukins (IL)-1α, -1β, -2, -4, -8, and -10, MCP-1, TNF-α, VEGF and EGF. Instead, significantly higher median levels were observed in obese patients vs. lean controls with respect to fasting insulin levels (p < 0.001), a classic insulin resistance marker, and IL-6 (p = 0.004). In addition, ProT-α levels were significantly and considerably higher in obese patients compared to lean controls (median ProT-α, 600.0 vs. 411.5 pg/mL, p = 0.004) and showed a moderate to strong positive relationship with fasting insulin levels and selected cytokines (i.e., TNF-α and IL-8). Conclusions: An increase in circulating levels of ProT-α is linked with obesity and can be detected before any clinical cardiometabolic complications develop. ProT-α may represent a novel and sensitive biomarker for inflammation and insulin resistance in obese individuals. [ABSTRACT FROM AUTHOR]