Diabetology

Background/Objectives: Hormonal fluctuations during the menstrual cycle can affect glycemic control in women with type 1 diabetes (T1D), especially during the luteal phase, when increased insulin resistance may lead to prolonged hyperglycemia. Advanced Hybrid Closed-Loop (AHCL) systems could help manage these hormone-driven fluctuations. This study aimed to assess glycemic control across menstrual phases and explore the role of AHCL systems in counteracting the related glucose variability. Methods: A retrospective study was conducted including women with T1D and regular menstrual cycles (study group) and women on estroprogestin therapy (control group). Each group was subdivided by insulin delivery method (AHCL vs. non-AHCL). Glycemic metrics and insulin requirements were compared between the follicular and luteal phases, and between groups. Results: The study included 94 women (62 in the study group, 32 in the control group). In the study group, glycemic control worsened during the luteal phase, with increased average glucose, glycemic variability, and time above range > 250 mg/dL (+0.93%, p = 0.03) and reduced time in range 70–180 mg/dL. These changes were more pronounced among AHCL users, who also showed a significant increase in bolus insulin. No phase-related differences were observed in the control group or among non-AHCL users. Significantly higher insulin needs during the follicular phase were found in the study group compared with the controls. Conclusions: This study confirmed a worsening in glycemic control in women affected by T1D during the luteal phase of the menstrual cycle, suggesting a need for more tailored management. The clear efficacy of AHCL systems in counteracting hormone-related glycemic fluctuations has not been proved, highlighting the need for further research in larger, more homogeneous cohorts. Full article

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs) have transformed disease management, particularly in diabetes and obesity. However, recent shortages have disrupted patient care. This review explores the current evidence regarding their direct impact on patient populations and reviews the mitigation strategies recommended by relevant health organizations. Materials and Methods: We systematically searched PubMed, Scopus, and Web of Science for studies published from the earliest available data to 10 January 2025, using these terms: “GLP-1 AND shortage”, “liraglutide AND shortage”, “dulaglutide AND shortage”, “semaglutide AND shortage”, “exenatide AND shortage”, and “tirzepatide AND shortage”. Eligible studies needed to report measurable outcomes like prescription counts, specific laboratory findings, or the proportion of a study population achieving a defined outcome related to the shortage. Only English-language clinical research was considered, while other manuscripts were not included. The risk of bias was assessed using the Critical Appraisal Skills Programme checklist. Study characteristics and findings were summarized in tables. Results: Out of 295 identified manuscripts, 85 works were retained for further screening. Consequently, 8 studies met the inclusion criteria, covering 1036 participants with type 2 diabetes and 573 treated for obesity. In addition, two studies reported prescription prevalence, and one examined prescription counts. Key findings included reduced prescription rates and shifts in treatment practices. No studies assessed impacts on cardiovascular, renal outcomes, or mortality. Discussion and Conclusions: Evidence on the health effects of these shortages is limited. Existing studies highlight disruptions in diabetes and obesity care, but broader impacts remain unclear. Preventing future shortages requires coordinated efforts among all stakeholders. Therefore, we advocate for ethical planning, sustainable production, and fair distribution strategies to mitigate long-term consequences. Full article

Background/Objectives: The increasing prevalence of diabetes underscores the urgent need for non-invasive, rapid, and cost-effective diagnostic alternatives. This study presents a breath-based multiclass diabetes classification system leveraging only three gas sensors (CO, alcohol, and acetone) to analyze exhaled breath composition. Methods: Breath samples were collected from 58 participants (22 healthy, 7 prediabetic, and 29 diabetic), with blood glucose levels serving as the reference metric. To enhance classification performance, we introduced a novel biomarker, the alcohol-to-acetone ratio, through a feature engineering approach. Class imbalance was addressed using the Synthetic Minority Over-Sampling Technique (SMOTE), ensuring a balanced dataset for model training. A nested cross-validation framework with 3 outer and 3 inner folds was implemented. Multiple machine learning classifiers were evaluated, with Random Forest and Gradient Boosting emerging as the top-performing models. Results: An ensemble combining both yielded the highest overall performance, achieving an average accuracy of 98.86%, precision of 99.07%, recall of 98.81% and F1 score of 98.87%. These findings highlight the potential of gas sensor-based breath analysis as a highly accurate, scalable, and non-invasive method for diabetes screening. Conclusions: The proposed system offers a promising alternative to blood-based diagnostic approaches, paving the way for real-world applications in point-of-care diagnostics and continuous health monitoring. Full article

Background/Objectives: Insulin resistance is a key factor in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD), but accurately measuring it in patients with type 2 diabetes (T2D) remains challenging. This study examines the relationship between a recently proposed insulin resistance index and the presence of liver steatosis and fibrosis in individuals with T2D. Methods: This cross-sectional study utilized data from the 2017–2020 National Health and Nutrition Examination Survey. Patients with T2D who did not have chronic viral hepatitis or significant alcohol intake were included. The insulin sensitivity (IS) index was calculated using a formula incorporating body mass index, urine albumin-to-creatinine ratio, triglycerides, and gamma-glutamyl transferase. Liver stiffness and steatosis were assessed through transient elastography. MASLD was defined as a controlled attenuation parameter (CAP) of ≥274 decibels/meter (dB/m), while significant liver fibrosis was defined as a liver stiffness measurement (LSM) of ≥8 kPa. Multivariable logistic regression models, adjusted for potential confounders, were used to evaluate the association between IS and these liver outcomes. Results: A total of 1084 patients with T2D were analyzed. The prevalence of MASLD and significant liver fibrosis was 74.1% (95% CI 68.7–78.9) and 25.4% (95% CI 21.2–30.2), respectively. After adjusting for age, sex, waist circumference, and race/ethnicity, lower IS scores (indicating higher insulin resistance) were independently associated with increased odds of both MASLD (quartile 1 vs. quartile 4: OR 2.66, 95% CI 1.23–5.71) and significant liver fibrosis (quartile 1 vs. quartile 4: OR 3.30, 95% CI 1.45–7.51). These findings remained consistent across subgroups stratified by age, sex, and obesity status. Conclusions: This novel IS model, derived from commonly available clinical and biochemical markers, is independently associated with liver steatosis and fibrosis. Its application may help identify patients with more advanced MASLD, facilitating early intervention and risk stratification. Full article

The Glycemia Risk Index (GRI) aims to summarize the overall quality of a patient’s glycemic control in a single number, and it is calculated from the hypo- and hyperglycemia times from continuous glucose monitoring, weighted by coefficients. Despite its recent appearance in 2022, this new parameter has strong international support, with almost half a hundred indexed articles already incorporating this metric into their studies. The following is a breakdown of the main papers that have used GRI, divided according to the type of treatment used, the population studied, the type of diabetes, its association with other parameters, and its relationship with chronic complications and the quality of life of people living with diabetes. Full article

Cellular senescence, a phenomenon characterized by the accumulation of dysfunctional, metabolically active cells, is increasingly recognized to be a key player in aging-related metabolic disorders. It is accelerated by hyperglycemia through various molecular pathways, positioning it as a critical mechanism in the pathophysiology of type 2 diabetes mellitus (T2D) and a potential therapeutic target. Emerging evidence from animal and clinical studies suggests that the usage of senolytic drugs, which selectively deplete senescent cells, can improve blood glucose regulation and mitigate diabetic complications. However, despite the conceptual feasibility of this approach, several challenges remain in their translation to the clinic: the molecular mechanisms underlying the pathogenicity of cellular senescence in vivo remain incompletely understood, and organ-specific effects of senolytic administration are yet to be fully elucidated to ensure their safety and efficacy in clinical applications. This review explores the characteristics of cellular senescence and the senescence-associated secretory phenotype (SASP) in key tissues involved in glucose homeostasis, including the pancreas, liver, adipose tissue, and skeletal muscle and the potential applications of targeting cellular senescence as a therapeutic strategy for T2D management. Full article

Introduction: Managing glycemic fluctuations in critically ill elderly patients with type 2 diabetes mellitus (T2DM) poses significant challenges. This case report presents a unique scenario in which increased intravenous glucose (Glc) infusion, together with insulin therapy, improved glycemic control and reduced insulin requirements during a septic episode. This finding adds to the scientific literature by suggesting that adequate Glc administration may enhance insulin sensitivity in critically ill T2DM patients. Case report: An 84-year-old female patient with T2DM, hypertension, and chronic renal failure was admitted to the intensive care unit with fever, nausea, loss of appetite, and profound weakness. Laboratory findings revealed severe hyperglycemia, electrolyte imbalances, and markedly elevated inflammatory markers, leading to the diagnosis of decompensated T2DM that was complicated by sepsis. The initial treatment consisted of continuous intravenous (IV) insulin, crystalloid infusions, and broad-spectrum antibiotics. Despite insulin therapy and the absence of nutritional intake, the patient experienced extreme fluctuations in their blood glucose levels, ranging from hyperglycemia to hypoglycemia. Due to persistent glycemic instability, IV Glc infusion was initiated alongside continuous insulin therapy. Paradoxically, increasing Glc infusion administration rate led to a reduction in the required insulin doses and stabilization of blood glucose levels below 10 mmol·L⁻¹. The patient’s C-peptide levels were initially elevated but subsequently decreased following Glc administration as well, suggesting a reduction in endogenous insulin secretion and therefore higher insulin sensitivity. The patient’s clinical condition improved, allowing for the transition to a subcutaneous insulin regime and the initiation of oral feeding. She was later transferred to a general medical ward and discharged without further complications. Conclusions: This case highlights the complex interplay between Glc and insulin in critically ill elderly patients with T2DM during sepsis. The main takeaway is that carefully managed Glc infusion, in conjunction with flexible insulin therapy, can enhance insulin sensitivity and stabilize blood glucose levels without causing further hyperglycemia. Frequent glycemia monitoring and adaptable glycemic management strategies are essential in the ICU to address rapid glycemic fluctuations in this patient population. Full article

Background/Objectives: This study investigated factors affecting glycated hemoglobin (HbA1c) levels according to sleep duration in adults with diabetes. HbA1c is an important indicator for the diagnosis and management of diabetes, and lowering this value is important for reducing the risk of complications. Recent studies have shown that sleep duration and quality play important roles in controlling blood sugar levels in patients with diabetes. Therefore, we aimed to analyze the factors affecting HbA1c levels according to sleep duration in adult patients with diabetes and propose a personalized diabetes management strategy. Methods: This was a secondary analysis of data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted between 2022 and 2023. The study included 1363 adults aged ≥30 years who were diagnosed with diabetes by a doctor. The participants were categorized into three groups based on their sleep duration: <7 h, 7–9 h, and ≥9 h. Results: The significant factors affecting HbA1c levels varied according to sleep duration. Age, drinking, and stress were significant for those who slept for <7 h. For those sleeping 7–9 h, energy intake, protein intake, fat intake, and education level were significant. Health checkups and drinking were significant for those who slept for >9 h. Conclusions: This study suggests that sleep duration is an important variable in diabetes management and should be considered in personalized diabetes management strategies. Future studies should explore various factors related to sleep patterns in greater depth. Full article

Aims and Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder frequently associated with increased inflammation and dysregulated innate immune responses. Thus, patients with T2DM are predisposed to bacterial infections. However, the underlying mechanism is poorly understood. The NAD+-dependent deacetylase Sirtuin1 (SIRT1) plays an important role in regulating cellular metabolism, including T2DM and aging. Furthermore, we have recently demonstrated that SIRT1 critically regulates inflammatory pathways and autophagy during infection. Thus, we aimed to investigate SIRT1 expression and its correlation with autophagy in peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic patients. Methods: Clinical characteristics of the study subjects were obtained. SIRT1 and autophagic markers such as p62 and LC3-I/II were determined using Western blot analysis followed by densitometric analysis. Results: We found that SIRT1 levels were decreased in PBMCs of diabetic patients in an age-dependent manner. Importantly, reduced SIRT1 expression correlated with reduced LC3-II/I ratios, indicating reduced autophagy. Reduced SIRT1 also corresponded to decreased autophagic adaptor protein Sequestome-1/p62. Conclusions: In summary, our results suggest a potential role of SIRT1 in regulating autophagy in PBMCs from T2DM patients. Full article

Background/Objectives: The outcomes of diabetes therapy depend largely on how well patients can implement medical advice in their lives. The main aim of the DiabPeerS study was to evaluate a peer support instant messaging service (IMS) approach to diabetes self-management education and support (DSMES) for people with type 2 diabetes mellitus (T2DM). Methods: Participants with T2DM took part in a randomized controlled trial. Both the intervention group (IG) and the control group (CG) received standard therapy, but the IG additionally participated in the peer support IMS intervention. The duration of the intervention was 7 months, succeeded by a follow-up 7 months later. Eleven biochemical, six behavioral, and six psychosocial parameters were measured at four times. Results: The targeted sample size could not be reached, and 68 participants took part. The following results have been found for the main hypotheses: No influence on HbA1c was detected (IG: −0.27, CG: +0.06, p > 0.05). Diabetes self-management behaviors were unaffected (IG_diet: +0.02, CG_diet: +0.46, p > 0.05; IG_exercise: −0.72, CG_exercise: +0.44, p > 0.05; IG_bloodsugar: −0.21, CG_bloodsugar: +0.65, p > 0.05; IG_footcare: +0.37, CG_footcare: +1.13, p > 0.05). Quality of life increased during the intervention in both the IG (KSK: +8.92, PSK: +7.41, p < 0.001) and the CG (KSK: +8.73, PSK: +7.48, p < 0.001). Medication adherence increased in the IG (+3.31, p < 0.01), although these participants were still classified as non-adherent. Conclusions: A peer support IMS intervention is a promising approach, but we recommend combining the online setting with an initial face-to-face situation. Full article

The global prevalence of obesity and type 2 diabetes has increased considerably in recent decades, primarily due to behavioral changes associated with societal progress, such as increased consumption of high-calorie foods and sedentary lifestyles. Obesity is a disease of the energy homeostasis system, not merely a passive accumulation of fat. The hypothalamus serves as the regulatory center for energy balance, and together with peripheral organs, such as liver, pancreas, muscle and adipose tissue, controls food intake, energy expenditure, and whole-body metabolism. Adenosine, a product of ATP catabolism, exerts its effects through various G-protein-coupled receptors: A1R, A2AR, A2BR, and A3R. It plays a key role in regulating peripheral metabolism, including glucose homeostasis, insulin sensitivity, fat beta-oxidation, and lipolysis in adipose tissue. Beyond its roles in the CNS, adenosine receptors are also crucial in metabolic tissues, where they regulate glucose and lipid homeostasis and contribute to overall metabolic function. Several studies have been analyzing the role of adenosine system, specifically the adenosine receptors in the regulation of whole-body metabolism, and the importance of adenosine receptors in context of metabolic diseases and obesity. In this review, we provide an overview of the adenosine signaling system, highlighting its role in metabolic regulation as well as the pathophysiological mechanisms underlying obesity and type 2 diabetes. Full article

In the United States, at least one in three adults has prediabetes, a condition categorized by blood glucose levels higher than normal but not high enough to be classified as type 2 diabetes. The Centers for Disease Control and Prevention (CDC) recommends a modest weight loss of 5–7%, a reduction in A1C by 0.2%, and at least 150 min of physical activity per week to prevent or delay the onset of type 2 diabetes in individuals with prediabetes. Eat Smart, Move More, Prevent Diabetes (ESMMPD) is a CDC-recognized lifestyle-change program for individuals with prediabetes or at high risk of developing type 2 diabetes. ESMMPD consists of 26 lessons delivered over the course of a year by trained Lifestyle Coaches using Zoom^TM. Participants are taught strategies to implement health-promoting behaviors related to healthy eating, physical activity, and mindfulness into their daily lives. The core components of the program are planning, tracking, and living mindfully. The aim of this article is to provide insights into the development, delivery, and core components of the ESMMPD program for public health practitioners. Full article

Thyroid disorders (TDs) and diabetes mellitus (DM) represent significant metabolic pathologies with an important global burden. Diabetes, characterized by chronic hyperglycemia, induces widespread dysregulation of lipid, protein, and carbohydrate metabolism. The thyroid gland, a central regulator of endocrine homeostasis, modulates metabolic processes through the secretion of thyroid hormones (THs). A complex bidirectional relationship exists between type 2 diabetes mellitus (T2DM) and thyroid dysfunction, wherein each condition may exacerbate the pathophysiological consequences of the other. At the core of this interplay lies insulin resistance (IR), a fundamental mechanism underlying their coexistence and mutual aggravation. A thorough investigation into the underlying mechanisms of thyroid function could reveal new insights into the development and progression of T2DM. Grasping the clinical correlation between these widespread endocrine disorders is crucial for customizing treatments for individuals confronting both conditions. This narrative review seeks to offer an understanding of the epidemiological, pathophysiological, and clinical dimensions of the relationship between TD and T2DM. Considering the substantial clinical ramifications of concurrent T2DM and TD, it is imperative to institute suitable screening and management approaches for both endocrine disorders to guarantee optimal care for patients. Full article

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