Diabetology, Volume 6, Issue 5 (May 2025) – 8 articles

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, impulsivity and/or hyperactivity. In recent years, metabolic alterations, primarily obesity, insulin resistance, and diabetes, have emerged as frequent comorbidities in individuals with ADHD, suggesting a bidirectional relationship between neurodevelopmental and metabolic dysfunctions. Emerging evidence indicates that dysregulation of dopaminergic signaling, disturbances in the hypothalamic-pituitary-adrenal (HPA) axis, and chronic low-grade inflammation are central to both ADHD symptomatology and metabolic impairments. For instance, alterations in dopamine-related genes (e.g., DRD4, DAT1) not only affect cognitive and behavioral functions but also play a role in appetite regulation and glucose homeostasis. Epidemiological studies further demonstrate that individuals with ADHD exhibit poorer glycemic control and a higher prevalence of both type 1 and type 2 diabetes, while early-life metabolic challenges such as maternal diabetes may predispose offspring to ADHD. This review aims to comprehensively synthesize the epidemiological, genetic, and pathogenetic evidence linking ADHD to metabolic alterations. We discuss key pathophysiological pathways—including dopaminergic dysregulation, HPA axis disturbances, inflammation, and oxidative stress—and evaluate their contributions to the co-occurrence of ADHD and metabolic disorders. In addition, we explore the clinical implications and integrated treatment approaches that encompass lifestyle modifications, pharmacological therapies, and multidisciplinary care. Finally, we outline future research directions to develop personalized and holistic interventions. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major global health challenge, primarily driven by insulin resistance and beta-cell dysfunction. This study investigated the roles of p21-activated kinase 1 (PAK1) and calcium/calmodulin-dependent protein kinase II (CAMKII) in insulin secretion, aiming to elucidate their involvement in this process and their implications in T2DM pathophysiology. Methods: Using the Beta-TC-6 insulinoma cell line, we assessed colocalization and interaction of PAK1 and CAMKII under glucose stimulation through indirect immuno-fluorescence (IFI) and proximity ligation assays (PLA). To examine their expression dynamics in a physiological context, we performed immunohistochemistry (IHC) on pancreatic sections from wild-type (WT), prediabetic, and T2DM murine models. Additionally, bioinformatic analysis of publicly available RNA sequencing (RNA-Seq) data from human islets of healthy donors, prediabetic individuals, and T2DM patients provided translational validation. Results: High glucose conditions significantly increased PAK1-CAMKII colocalization, correlating with enhanced insulin secretion. Pharmacological inhibition of these kinases reduced insulin release, confirming their regulatory roles. Murine and human islet analyses showed a progressive increase in kinase expression from prediabetes to T2DM, highlighting their relevance in disease progression. Conclusions: The coordinated function of PAK1 and CaMKII in insulin secretion suggests their potential as biomarkers and therapeutic targets in T2DM. Further studies are warranted to explore their mechanistic roles and therapeutic applications in preserving beta-cell function. Full article

Background: Among individuals with type 2 diabetes (T2D), cardiovascular disease (CVD) is the leading cause of death, demanding prevention approaches. Exercise is a powerful option for non-pharmacological strategies to improve cardiovascular outcomes. This systematic review aims to evaluate the effects of aerobic, resistance, and combined training on CVD in individuals with T2D. Methods: From 2013 through the end of 2023, PubMed, Scopus, and Web of Science were systematically searched for articles. The studies included 15 articles lasting at least eight weeks and involving 1794 participants each. The cardiac events measured were blood pressure, lipid levels, heart rate variability (HRV), and inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6). Results: Aerobic training reduced systolic and diastolic blood pressure by 6 mmHg and 3 mmHg, respectively, while significantly enhancing lipid profiles, evidenced by an 8% reduction in LDL cholesterol and a 5% rise in HDL cholesterol. In addition, improvements in lean muscle mass, insulin sensitivity, and slight changes in inflammatory markers support the benefits of resistance training. The most pronounced effects emerged from combined training, which resulted in a 9 mmHg decrease in systolic blood pressure, a 6 mmHg decrease in diastolic pressure, a 10% reduction in LDL cholesterol, a 15% increase in HRV, and a 10% reduction in CRP and IL-6 levels. Conclusions: Combined training has more favorable effects on several key CVD risk factors than aerobic or resistance training alone. It can be regarded as the most effective exercise modality for decreasing CVD risk in adults with T2D. Full article

The literature describes an increased risk of eating disorders (EDs) in patients with Type 1 diabetes mellitus (T1DM) compared to the general population. This risk is mainly related to physical and psychosocial problems related to diabetes. EDs should be carefully assessed and treated in these patients since they are associated with poor glycemic control and significant repercussions of pathology. Background/Objectives: To study the presence of EDs in young Portuguese adults and adults with T1DM, and how gender; age group; method of insulin administration; carbohydrate counting; and body mass index [BMI] variables influence the risk of developing an ED. Methods: Data collection was carried out using an online questionnaire, which was disseminated through the media of several Portuguese diabetes associations. Results: The sample consisted of 47 participants, mostly female, with the age group between 26 and 35 years being most representative. A statistically significant association was found between the Eating Attitudes Test [EAT-26] scores and the BMI of the participants [p = 0.003]; other variables did not show statistically significant differences. Conclusions: To better understand the relationship between these two pathologies, further studies are needed, as well as the development of more screening instruments to assess the risk of EDs specific to T1DM, and preventive interventions and guidelines that can assist the various areas of health that support the population with T1DM. Full article

Background: Diabetes induces osteoporosis primarily by impairing osteoblast function. Intracellular zinc homeostasis, which is controlled by zinc transporters, plays a significant role in osteoblast differentiation. In the present study, we aimed to explore the role of zinc homeostasis in the pathogenesis of diabetic bone loss using a diabetic mouse model. Methods: Streptozotocin (STZ)-induced diabetic female mice were used for in vivo experiments. In vitro, the effects of zinc transporter knockdown using small interfering RNA was investigated in MC3T3E1 pre-osteoblastic cells. Results: STZ-induced diabetic mice exhibited severe bone loss and decreased expression of osteogenic genes, as well as a decrease in zinc content and the expression of several zinc transporters localized in the cellular membrane, including Zip6, Zip9, and Zip10 in the tibia. Moreover, the messenger RNA (mRNA) levels of Zip6, Zip9, and Zip10 were positively correlated with trabecular bone mineral density in the tibiae of diabetic mice. This in vitro study, using MC3T3E1 pre-osteoblastic cells, revealed that knockdown of Zip6 reduced the expression of osteogenic genes in pre-osteoblastic cells. Additionally, Zip6 knockdown downregulated protein levels of phosphorylated p38 mitogen-activated protein kinase (p38MAPK) in pre-osteoblastic cells, and this change was observed in the tibiae of diabetic mice. Conclusions: Our data suggest that the downregulation of zinc transporters localized in the cellular membrane, such as Zip6, may be involved in the impairment of osteoblastic differentiation through the inhibition of p38 MAPK signaling, leading to osteoporosis under diabetic conditions. Maintaining zinc homeostasis in bone tissues may be vital for preventing and treating diabetic bone loss, and zinc transporters may serve as novel therapeutic targets for diabetic osteoporosis. Full article

Background: Tuberculosis (TB) and diabetes mellitus (DM) comorbidity (TB-DM) presents a significant global health challenge, with diabetes increasing susceptibility to TB, worsening clinical outcomes, and impairing immune responses. Among these dysfunctions, macrophages—the primary immune cells responsible for pathogen recognition, phagocytosis, and bacterial clearance—exhibit profound alterations in TB-DM. However, the complex interplay between metabolic dysregulation, immune impairment, and macrophage dysfunction remains poorly defined. Objective: This scoping review systematically maps the literature on macrophage dysfunction in TB-DM, identifying key immunological impairments affecting phagocytosis, cytokine production, antigen presentation, macrophage polarisation, reactive oxygen species (ROS) and nitric oxide (NO) regulation, and chronic inflammation. Methods: A systematic search was conducted in PubMed, Web of Science, and Embase, covering studies from 2014 to 2024. Inclusion criteria focused on human studies investigating macrophage-specific mechanisms in TB-DM. Data extraction and synthesis were performed using Covidence, with findings grouped into key immunological themes. Results: A total of 44 studies were included, revealing significant impairments in macrophage function in TB-DM. Findings indicate reduced NO production, variable ROS dysregulation, altered M1/M2 polarisation, defective antigen presentation, and chronic inflammation. Elevated IL-10 and VEGF were associated with immune suppression and granuloma destabilisation, while eicosanoids (PGE2, LXA4) contributed to sustained inflammation. Conclusions: Macrophage dysfunction emerges as a central driver of immune failure in TB-DM, creating a self-perpetuating cycle of inflammation, immune exhaustion, and bacterial persistence. Understanding these mechanisms is essential for developing biomarker-driven diagnostics, host-directed therapies, targeted immunomodulation, and improving TB outcomes in diabetic populations. Future research should explore macrophage-targeted interventions to enhance immune function and mitigate TB-DM burden. Full article

Background/Objectives: The association between sexual dysfunctions and diabetes is largely known, but few studies investigated its prevalence in Type 1 Diabetes (T1D). The aim of this study was to evaluate the prevalence of sexual dysfunction in a group of men with T1D regardless of their age and to compare the prevalence in men treated with different intensive insulin regimens. Methods: The study population included 68 men affected by T1D, of whom 17 were on Multiple Daily Injections (MDI) and 51 were on Continuous Subcutaneous Insulin Infusion (41 on Advanced Hybrid Closed Loop System with catheters and 10 on patch pumps). All participants completed the International Index of Erectile Function (IIEF-15), which evaluates several domains of sexual function. Another questionnaire that evaluated general features, diabetes-specific features, and sexual-specific features was proposed to every participant. Results: The overall prevalence of erectile dysfunction was 48.5%, and the overall prevalence of a severe grade of erectile dysfunction was 26.5%. Correlations were demonstrated between the prevalence of erectile dysfunction and age and between the prevalence of erectile dysfunction and dyadic status. Age and dyadic status were also correlated with lower scores in several other domains of the IIEF-15 questionnaire. Conclusions: Men with Type 1 Diabetes present a high prevalence of erectile dysfunction, independent of glycometabolic control of the disease and insulin regimens; on the contrary, a great correlation is demonstrated with age and dyadic status. Full article

Background/Objectives: Glycemic control is essential for preventing both short- and long-term complications of type 2 diabetes (T2D), requiring strict adherence to pharmacological therapy. Medication adherence directly influences therapeutic effectiveness, making its assessment in clinical practice crucial. This study aimed to evaluate medication adherence in elderly patients with T2D and its association with glycemic control. Methods: A descriptive cross-sectional study was conducted in the Algarve, Portugal, involving 133 elderly patients (≥60 years) with T2D. Cardiometabolic parameters and medication adherence (global, intentional, and unintentional) were assessed. Statistical analyses were performed using IBM SPSS Statistics 28.0. Results: The study population had a mean age of 71.7 ± 5.7 years, with a predominance of male participants (57.9%) and a high prevalence of dyslipidemia and/or hypertension. Cardiometabolic control was generally poor, with only 26.3% achieving blood pressure targets (≤140/90 mmHg), 8.5% maintaining fasting glycemia within the recommended range (70–110 mg/dL), and 13.6% attaining glycated hemoglobin (HbA1c) values ≤ 7%. Despite this, medication adherence was notably high (97.7%), with no significant association with cardiometabolic control (p > 0.05). Unintentional non-adherence behaviors, such as forgetfulness and inconsistent medication schedules, were the most frequently reported. Conclusions: Although elderly patients with T2D demonstrated high medication adherence rates, their cardiometabolic control remained suboptimal. Unintentional non-adherence behaviors may contribute to poor glycemic control. However, medication adherence alone does not fully explain these outcomes, highlighting the need to assess adherence to other self-care behaviors, particularly dietary and physical activity patterns. Future interventions should integrate comprehensive lifestyle modifications alongside pharmacological management to enhance overall disease control. Full article