Diabetology

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

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

Background: Insulin resistance (IR) is a metabolic disorder linked to type 2 diabetes and cardiovascular diseases. Visceral fat is a better predictor of IR than BMI and waist circumference due to its metabolic and inflammatory impact. Methods such as DEXA and bioimpedance (BIA) estimate body fat, while scales such as METS-IR, SPISE, and TyG assess IR risk. This study analyzes the utility of visceral and body fat measured by BIA compared to other indicators. Methods: A cross-sectional study was conducted on 8590 workers in the Balearic Islands, analyzing anthropometric, clinical, and analytical variables. Body fat and visceral fat were measured by bioimpedance, and insulin resistance was assessed using METS-IR, SPISE, and TyG. ROC curves were used to evaluate the predictive value of BMI, WC, and body fat. Results: The areas under the curve (AUCs) were highest for high METS-IR, particularly in women (>0.97), indicating excellent performance. TyG showed the lowest AUC, especially in men. Body and visceral fat showed the highest AUC for all IR scales. Youden’s indices were highest for high METS-IR, with good predictive capacity, while TyG showed low values, limiting its utility in predicting insulin resistance. Conclusions: Measuring body and visceral fat by BIA is superior to BMI or WC for estimating IR risk. Full article

Background/Objective: Prevention of foot ulceration is critical to reduce the amputation rate in individuals with diabetes mellitus (DM). We investigated the knowledge of diabetic foot care management and prevention of diabetic foot ulcer (DFU) among categories of healthcare practitioners (HCPs). Methods: This descriptive cross-sectional observational study was conducted at public healthcare facilities within the Charlotte Maxeke Johannesburg Academic Hospital Cluster in Gauteng, South Africa. Participants included podiatrists, physiotherapists, occupational therapists, dieticians, medical orthotists and prosthetists, nurses, and medical doctors. Data were collected using a self-administered questionnaire that assessed knowledge of DFU risk factors, foot examination, foot care, and appropriate footwear. Knowledge level was classified as extremely poor if less than 50% of participants from a category of HCPs answered appropriately, reasonable for 50–59%, average at 60–69%, above average from 70–79%, and excellent when ≥80%. The questionnaire was completed by 449 HCPs and analyzed using STATA version 15, with statistical significance set at a p-value less than 0.05. Results: A total of 449 HCPs participated, which comprised the following: 48.1% (216) therapeutic health practitioners (THPs), 37.4% (168) nurses, and 14.5% (65) medical doctors. Only 36% (162) of participants had prior education on DFU. The overall knowledge levels among participants were risk factors of DFU (80%), foot examination (80%), identification of limb-threatening conditions (82%), foot care (77%), and footwear (65%). Medical doctors had the highest median scores for risk factors (85) and foot examination (80), followed by nurses (80 for risk factors and 78 for foot examination). THPs had the lowest median scores for risk factors (78) and foot examinations (70). Differences in knowledge levels across HCPs were statistically significant (p < 0.05). Conclusions: THPs have insufficient knowledge of diabetic foot care and prevention of DFUs. Comprehensive training and targeted educational programs are needed to fill these gaps and improve patient care. Full article

Background: Diabetic foot osteomyelitis (DFO) constitutes a severe and prevalent complication of diabetes mellitus (DM). Individuals afflicted with DM exhibit an elevated risk for DFO development, attributable to a confluence of factors, including peripheral neuropathy, compromised circulation, and impaired immune function. Timely diagnosis and appropriate therapeutic intervention are paramount. In recent years, alongside the ablative approach, the feasibility of substituting compromised bone with a bone substitute has emerged. Methods: We retrospectively analyzed resorbable bone grafting procedures performed at our third-level center for the care of people with diabetes between 2019 and 2024. Forty-nine patients were included in this. The median follow-up period was 13 months (Q1 7, Q3 20). Results: At follow-up, 34 patients (69%) had achieved healing, with a median healing time of 2.3 months (Q1 1.5, Q3 5). Lesion location significantly influenced healing outcomes, with forefoot and midfoot lesions demonstrating an 86% healing rate compared to 50% for hindfoot lesions. Eleven patients (22%) experienced infectious relapse after a median of 1 month (Q1 0.7, Q3 2.9). An analysis of different bone substitutes did not reveal significant differences in terms of healing among the various products and between the presence or absence of a local antibiotic. Conclusions: Bone substitute implantation offers an additional conservative strategy for managing DFO. Healing rates are significantly higher for forefoot and midfoot lesions, suggesting that further research is needed to improve outcomes in hindfoot osteomyelitis. Selection of the most effective bone substitute requires further studies. Full article

Background: This study examined differences in body composition, dietary intake, and exercise habits between people with type 1 diabetes (T1DM) and those without diabetes (NDM). We also sought to clarify the clinical and lifestyle characteristics of overweight people with T1DM. Methods: This controlled cross-sectional study was conducted at a single center, and included 45 people with T1DM and 50 NDM individuals. Body composition, nutrient intake, and exercise habits were evaluated, and exercise habits were compared between people with a T1DM onset before 20 years of age and those with an onset at or after 20 years of age, in relation to the NDM group. Overweight was defined using a BMI of 25.0 kg/m² as the cutoff. Results: The T1DM group had significantly higher BMI and body fat than the NDM group, but no significant difference in muscle mass, and consumed a higher percentage of carbohydrates and a lower percentage of fat. The early-onset T1DM group had significantly lower exercise habits during their school years and in their current life than the NDM group. Individuals in the overweight T1DM group had a lower time in range on a continuous glucose monitor and a higher carbohydrate intake than those in the non-overweight T1DM group. Conclusions: The study suggested that the T1DM group had a significantly higher body fat percentage and carbohydrate intake, and significantly reduced exercise habits as students, compared to the NDM group. Full article

Although digital platforms have gained popularity in the delivery of diabetes interventions, few models have focused on type 1 diabetes (T1D), offer different support delivery mechanisms, and involve peer and health professional-led support. TRIFECTA is a six-month multi-modal digital support intervention that includes a 24/7 peer texting group, an “ask-the-expert” web-based portal, and professional-led virtual group-based interactive sessions. This study examined diabetes-specific quality of life (DSQoL) changes following TRIFECTA. DSQoL was measured using Type 1 Diabetes and Life, a self-report survey that allows for subscale analysis in different age groups. Among 60 adults with type 1 diabetes, improvements were observed for overall diabetes-specific quality of life, primarily driven by the 26–45 years cohort. Subscale analysis found DSQoL improved for emotional experiences and daily activities for adults 26–45 years old, and social isolation improved for adults 46–60 years old. Full article

Objectives: Excessive fetal growth is the most common fetal complication associated with gestational diabetes (GDM), resulting in adverse short- and long-term outcomes. Our main objective was to evaluate the influence of excessive fetal growth on Doppler ultrasonographic measurements of the Umbilical Artery (UA) among women with GDM during the third trimester of pregnancy. Methods: A retrospective study among 472 women with GDM was conducted. UA-PI was measured by Doppler ultrasonography three different times during the third trimester of pregnancy at 28, 32, and 36 weeks. Pregnancies were grouped according to the fetal weight centile or birthweight in two groups: large for gestational age (LGA) group (>90th percentile or ≥4000 g at birth) and adequate for gestational age (AGA) group (<90th percentile or <4000 g at birth, not including the intrauterine growth restrictions). Results: In the LGA group (n = 57, 12.1%), women had higher BMI (p = 0.0001) and fasting blood glucose than the AGA group (97.08 ± 40.69 vs. 86.29 ± 39.58 mg/dL; p = 0.0550). They required insulin therapy more frequently to achieve glycemic control (63.2% vs. 34%, p = 0.0001). In LGA, UA-PI decreased progressively from 28 to 36 weeks (p = 0.0048). The most pronounced reduction occurred at 32 weeks (p = 0.0076). Conclusions: All fetuses from mothers with GDM had a significant and progressive decline in UA-PI during the third trimester of pregnancy. LGA fetuses showed lower UA-PI values compared with AGA fetuses. Since maternal hyperglycemia increases the risk of fetal overweight and GDM may represent a fetal vascular disorder, it therefore seems possible that in LGA fetuses, maternal hyperglycemia could influence the fetal vasculature. Full article

Background: Diabetic kidney disease (DKD) represents a chronic microvascular complication with diabetes, affecting around one-third of diabetic individuals. Despite current therapies, progression to end-stage kidney disease remains a challenge. Abnormal hyperphosphorylation of the Tau protein is implicated in various age-related diseases. This study aimed to explore the link between renal Tau protein hyperphosphorylation and kidney damage in type 2 diabetes mellitus (T2DM). Methods: Sprague Dawley rats were administered lithium chloride (LiCl), an inhibitor of a glycogen synthase kinase-3 (GSK3) inhibitor known to reduce Tau hyperphosphorylation. LiCl was administered either daily or every other day at a dosage of 1 mmol/kg. The effects of LiCl on kidney function were assessed through proteinuria, the kidney-to-bodyweight ratio, inflammation, fibrosis, and TGF-β1 expression levels. Results: Diabetic rats exhibited increased proteinuria, renal hypertrophy, inflammation, fibrosis, and elevated TGF-β1 expression. Lithium chloride treatment reduced kidney hypertrophy, inflammation, and fibrosis, indicating that Tau hyperphosphorylation contributes to the pathogenesis of DKD. LiCl also regulated TGF-β1 expression, which was associated with improved renal outcomes. Conclusions: The inhibition of Tau hyperphosphorylation by lithium chloride offers a potential therapeutic strategy for mitigating kidney damage in diabetic kidney disease. This study proposes LiCl as a novel treatment approach to attenuate DKD progression. Full article

Type 2 diabetes (T2D) is a rapidly growing global health concern, projected to affect 1.3 billion people by 2050, necessitating a multidisciplinary approach. This review examines the epidemiological disparities in T2D, focusing on modifiable and nonmodifiable risk factors, socioeconomic determinants, and healthcare inequities. While genetic predisposition, age, and ethnicity contribute to T2D risk, socioeconomic status (SES) significantly mediates modifiable factors such as diet, physical activity, and access to healthcare. Lower SES is associated with poorer lifestyle choices, limited access to resources, and increased exposure to risk factors, exacerbating T2D prevalence among vulnerable populations. Geographic variations in T2D prevalence are evident, with racial and ethnic minorities and lower-income individuals being disproportionately affected in regions like the United States and Europe. The economic burden of T2D is substantial, with global healthcare expenditures reaching USD 966 billion in 2021 and projected to rise significantly, albeit with variations across different countries and health systems. Despite advancements in treatment, inequities in healthcare access persist, particularly in low- and middle-income countries, hindering optimal glycemic control and consequently contributing to preventable complications and poor health outcomes. This review highlights the critical need for targeted interventions and policy reforms to address the intersection of demographic, economic, and healthcare-related variables influencing T2D disparities. By bridging gaps in prevention, management, and treatment and accounting for the effect of SES on both modifiable and nonmodifiable risk factors, the global disease burden of T2D could be reduced and health equity could be improved. Full article