The escalating prevalence of diabetes poses a significant health concern. Uncontrolled diabetes leads to a multitude of complications. A comprehensive management plan and continual adaptation of guidelines is needed. The American Diabetes Association (ADA) is a guiding force in this domain, providing diabetes care recommendations for clinicians, laboratorians, researchers, and policymakers since 1989. The latest ADA guidelines present both challenges and opportunities for laboratories. The increased emphasis on glycated hemoglobin (HbA1c) testing for early diagnosis and personalized monitoring is expected to increase testing volumes, potentially leading to a rise in point-of-care testing. Ensuring standardized testing procedures becomes paramount to maintaining consistent and reliable results across laboratories. Moreover, laboratories may need to expand their test menus to accommodate the growing demand for personalized medicine approaches and collaborate closely with healthcare providers to support informed decision-making. This commentary provides a focused analysis of the 2024 ADA guidelines for the laboratory assessment of diabetes.

Stress is a state of threatened or perceived as threatened homeostasis that can be induced by various external and internal stimuli such as psychosocial factors, inflammatory or injurious conditions, and infections. In order to restore body homeostasis, adrenal glands produce and secrete glucocorticoids (GCs) and catecholamines (CAs), which are the main stress hormones that support the survival and adaptation of the organisms to the new environment. In contrast to the rather beneficial impact of acute and short-lasting stress, chronic stress and related dysregulation of the stress system is implicated in the development of many non-communicable diseases, including cancer. Particularly, ever-increasing experimental and clinical evidence implicates the involvement of CAs and GCs as well as the overexpression of their receptors in the activation of the major pathways involved in tumour development, metastasis, and resistance to various therapies. More importantly, results of experimental and epidemiological studies revealed that overexposure to stress hormones during pre- and early postnatal life might induce life-long or even transgenerational dysregulation of the stress system and predispose it to the development of various tumours. Although the exact mechanisms involved in the latter process are not yet fully known, it has been demonstrated that GC-induced epigenetic modifications can change the expression of several key genes involved in the regulation of the stress system, tumour initiation, and epigenetic imprinting. When such alterations occur in stem/progenitor cells (SPCs), this might not only lead to long-term dysfunction of the stress system but might promote the generation of cancer stem cells (CSCs). This review article discusses a hypothesis that stress hormones-mediated epigenetic reprograming of various SPCs during sensitive developmental periods, might contribute to their dysfunction and increased sensitivity to malignant transformation, thereby promoting tumorigenesis.

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency leads to high morbidity and mortality, despite the availability of life-saving corticosteroid replacement therapy. Gene therapy represents a promising potential treatment for monogenic disorders such as congenital adrenal hyperplasia, overcoming the limitations of corticosteroid replacement approaches. Adeno-associated viral vectors are currently the leading vector for direct in vivo gene delivery. However, physiological properties of the adrenal gland limit the application of adeno-associated viral vector-based gene addition strategies. To achieve durable correction in the adrenal gland, gene editing must be employed to stably introduce a genetic modification into the CYP21A2 locus. The safety of this and other gene editing approaches could be greatly improved by using lipid nanoparticles for the delivery of editing machinery mRNA. While little data exists regarding adrenocortical lipid nanoparticle targeting, physiological features of this organ (such as high relative blood flow, fenestrated endothelium, and cholesterol uptake) indicate the promise of these delivery vectors for the treatment of monogenic diseases of the adrenal cortex. This review discusses the complexities of developing gene therapy for congenital adrenal hyperplasia and explores the viability of novel gene therapy strategies in this application.

Adult-onset testosterone deficiency (TD) in men is diagnosed by the finding of low serum testosterone levels and recognised, associated symptoms. The condition has high prevalence in men over 50 years of age, particularly those with type 2 diabetes (T2DM). Accumulating data show adult-onset TD is associated with increased mortality risk. We review the literature and consider the evidence suggesting testosterone therapy (TTh) reduces mortality, especially in men with T2DM. We previously reported that in the Burntwood Lichfield Atherstone Sutton Coldfield Tamworth (BLAST) study screened cohort of men with adult-onset TD and T2DM adult-onset TD was associated with increased mortality with TTh decreasing this higher mortality. The data hinted that the effect was greater in older men. We confirmed this observation with statistical analyses to study the effect of age on the association between adult-onset TD and mortality; Cox regression analysis demonstrated that the reduced risk (hazard ratio: 0.61, 95% CI: 0.38–0.96) following TTh was restricted to men above the median age of 65.89 years. Finally, we speculate on putative mechanisms that may mediate these associations. Heterogeneity in men with adult-onset TD is expected in view of its definition of low testosterone levels together with associated clinical phenotypes that are not always directly related. Many of these classifying phenotypes are associated with increased mortality. Thus, it is perhaps possible that mechanism(s) of all-cause mortality reduction following TTh is via the impact on these associated phenotypes such as the metabolic syndrome (MetS), hyperglycaemia, hypertension, dyslipidaemia, low haematocrit, sex hormone binding levels, erectile dysfunction, etc. We propose that further research studying the effect of TTh takes heterogeneity into account.

Hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome is a rare genetic disorder caused by haploinsufficiency of the GATA3 gene. A very limited number of cases have been reported in the literature to date. Diagnosis is challenging as the phenotypic expression has wide heterogeneity due to variable penetrance of the underlying genetic mutation. Although the condition is inherited in an autosomal dominant pattern, sporadic cases do occur. This report presents a case of a 22-year-old female diagnosed with HDR syndrome, featuring bilateral cataract and bicornuate uterus. The GATA3 mutation detected in the patient was not identified in the family, suggesting it to be arising de novo. The present case report describes the rare phenotypic findings of bilateral cataract and bicornuate uterus associated with HDR, thus expanding the clinical spectrum of the syndrome.

Diabetes and cancer are two chronic metabolic diseases with ever-increasing incidence rates worldwide. These disorders can often occur together, as diabetes presents an important risk factor for cancer and some cancers could in turn lead to diabetes. In this perspective article, many more commonalities between diabetes and cancer are highlighted, including the role of lifestyle and environmental factors in the pathogenesis, the presence of a rather long latency period before clinical diagnosis of invasive disease, as well as the ultimate progression to diabetic complications or malignant metastases. Moreover, both of these devastating disorders still lack curative treatment options, whereas several currently approved antidiabetic and anticancer drugs have been originally derived from different natural sources. However, while in the case of diabetes, the main therapeutic goal is to maintain the pancreatic islet mass by preserving β-cells survival, the major purpose of cancer therapy is to kill malignant cells and reduce the neoplastic mass of solid tumors. It is expected that both diabetes and cancer, two systemic diseases with epidemic proportions, would be managed more effectively through an integral approach, considering many different aspects related to their pathogenesis, including also lifestyle changes and dietary modifications.