Background: Diabetes mellitus and vitamin D deficiency (VDD) are widespread global health concerns with overlapping metabolic risks. Emerging evidence suggests a bidirectional relationship: VDD exacerbates insulin resistance, whereas diabetes mellitus disrupts vitamin D metabolism. Methods: This meta-analysis was registered prospectively (PROSPERO CRD42025639951). We conducted a comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library from their inception to January 2025 for observational studies examining the bidirectional associations between VDD and diabetes mellitus. Studies were eligible if they (1) employed cohort or case-control designs, (2) defined VDD as serum 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL, and (3) diagnosed diabetes mellitus according to the American Diabetes Association (ADA) criteria. Two reviewers independently extracted data and assessed study quality using the Newcastle-Ottawa scale. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models (STATA 15.1 and RevMan 5.4). Results: Among 53 studies (n = 552,032), individuals with VDD had a 53% increased risk of developing type 2 diabetes mellitus (T2DM) (OR = 1.53, 95% CI: 1.38–1.70). Conversely, individuals with type 1 diabetes mellitus (T1DM) and T2DM had a 2.02-fold and 2.62-fold increased risk of VDD, respectively. Subgroup analyses demonstrated stronger associations in Asian populations (T1DM: OR = 2.21; Europe: OR = 1.65; P < 0.05 for regional difference) and among normal-weight T2DM patients (OR = 7.68, compared to obese: OR = 5.21). Discussion: This meta-analysis reveals a bidirectional link between VDD and diabetes mellitus, emphasizing subtype- and phenotype-specific risk profiles. Clinically, routine monitoring of serum 25(OH)D levels is recommended for diabetic patients, particularly in high-risk subgroups such as individuals with T1DM or lean T2DM phenotypes, and suggests targeted vitamin D supplementation for high-risk groups. On a public health scale, fortifying staple foods with vitamin D in regions with high deficiency rates, such as Asia, could alleviate the dual burden of VDD and diabetes mellitus.

Aim: This analysis examined the prevalence and incidence of type 2 diabetes mellitus (T2DM) and co-morbid lung disease in the UK Biobank population. Methods: Non-communicable inflammatory lung diseases, body mass index (BMI), age, glycated haemoglobin (HbA1c), sex, smoking status, diabetes status, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) data were obtained. Participants were categorised by BMI: lean (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥ 30 kg/m2). Fisher’s exact test identified lung disease prevalence and incidence. Kruskal-Wallis assessed lung function variance and its correlation with HbA1c. Cox regression analysed the impact of confounders on time to lung disease events. Results: Overweight and obesity increased the prevalence and incidence of chronic obstructive pulmonary disease, asthma, and bronchitis, but this was not evident in cases of bronchiectasis in those without T2DM (P < 0.05–0.0001). Conversely, T2DM increased lung disease risk across all BMIs (P < 0.0001) and reduced FEV1 and FVC even after HbA1c normalisation (P < 0.0001). FEV1 and FEV1/FVC were negatively correlated with HbA1c. Age, diabetes, being a woman, smoking, reduced FEV1 and FEV1/FVC ratio, but not BMI, were factors in lung disease development in T2DM. Conclusions: Inflammatory lung conditions are more common in T2DM patients, regardless of BMI. The pattern of lung decline suggests restrictive impairment, despite a high risk of obstructive disorders. This data adds to the evidence that the lungs are a target organ of diabetes damage.

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.