Introduction: Acrylamide has been shown to induce oxidative stress and β-cell toxicity in animal studies; however, population-based evidence remains limited and inconsistent. Therefore, this study aimed to evaluate the associations between acrylamide (AA) hemoglobin biomarkers and the risk of prediabetes and diabetes in the US population. Methods: Data were obtained from the 2013-2016 National Health and Nutrition Examination Survey (NHANES). Participants were classified into diabetes, prediabetes, and healthy control groups by their glycometabolic status. The associations between prediabetes and diabetes with AA biomarkers, specifically hemoglobin adducts of acrylamide (HbAA), glycidamide (HbGA), the Hb- GA/HbAA ratio, and their combined levels (HbAA + HbGA), were investigated using multivariate logistic regression and restricted cubic spline models. Results: The fully adjusted logistic regression analyses indicated that participants in the highest HbGA quartile had a significantly elevated risk of prediabetes (odd ratio [OR] = 2.47, 95% confidence interval [CI]: 1.52-4.02, P = 0.007; Ptrend = 0.005) and diabetes (OR = 2.46, 95% CI: 1.27-4.73, P = 0.019; Ptrend = 0.043). The HbGA/HbAA ratio showed a positive correlation with prediabetes (OR = 2.10, 95% CI: 1.05-4.20, P = 0.042; Ptrend = 0.024) and diabetes (OR = 5.58, 95% CI: 2.10-14.79, P = 0.008; Ptrend < 0.001). In contrast, HbAA levels were not significantly associated with either prediabetes (OR = 1.49, 95% CI: 0.86-2.61, P = 0.116; Ptrend = 0.088) or diabetes (OR = 0.92, 95% CI: 0.47-1.81, P = 0.744; Ptrend = 0.351). Discussion: The divergent patterns observed for HbAA and the HbGA/HbAA ratio may reflect a shift from exogenous exposure to intrinsic metabolic capacity across different stages of disease progression. Conclusion: Higher HbGA levels and elevated HbGA/HbAA ratios were associated with an increased prevalence of prediabetes and diabetes. Further research is needed to clarify the causal role of acrylamide exposure in abnormal glucose metabolism.
Diabetic foot ulcers (DFUs) are a serious diabetic complication leading to high rates of morbidity, amputation risks, and economic burdens on the treatment facilities. The present review continues our exploration of the novel paradigm of combining micronutrients with nanoparticles to address diabetes-related DFUs effectively. We performed a detailed examination of published studies to discuss our views on the ever-increasing utilization of essential micronutrients like zinc, selenium, and vitamins A, C, D, and E to modulate oxidative stress levels, stimulate the secretion of vascular endothelial growth factors, and aid in tissue repair mechanisms. This detailed scrutiny was carried out in parallel to analyze various nanoparticle-based systems to specifically address their bioavailability, stability, deliverability, and efficiency in carrying out wound repair in DFUs. Both micronutrients and nanoparticles have shown substantial activity to increase antioxidant mechanisms, boost the immunomodulatory system, and accelerate tissue repair mechanisms in DFUs. Both methods utilize advanced delivery mechanisms to precisely deliver drugs to the affected areas reliably. Novel delivery methods with micronutrients in DFUs showed a therapeutic integration approach to quicken the healing time to DFUs in faster re-epithelialization, decrease microbial counts, increase extracellular matrix remodeling, and improve healing rates in clinical settings. There is a need for further clinical development to stabilize formulations of combining micronutrients with delivering nanoparticles to serve clinical needs effectively in DFUs. There is a great potential influence in applying this novel multipurpose approach to treat DFUs effectively to increase healing rates and minimize risks of complications in diabetic clients.
INTRODUCTION:The seven isoforms of the NADPH oxidase (NOX) family-NOX1-5, DUOX1, and DUOX2-are multidomain enzymes that require distinct regulatory subunits for activation. These enzymes are major sources of reactive oxygen species (ROS), particularly the superoxide anion (O2·-), which exerts both cytotoxic and signalling effects. NADPH acts as a critical electron donor, maintaining cellular redox homeostasis and supporting anabolic metabolism. Dysregulated NOX activity has been linked to metabolic reprogramming in cancer and oxidative stress-induced complications in diabetes mellitus. METHODS:A focused systematic literature analysis was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases (up to March 2025). Studies exploring NOX isoform regulation, ROS generation, NADPH-driven redox metabolism, and NOX-related signalling in cancer and diabetes were critically reviewed. RESULTS:Aberrant activation of the NOX1, NOX2, and NOX4 isoforms is strongly associated with oncogenic PI3K/Akt and MAPK signalling cascades, promoting metabolic reprogramming and antioxidant dependency in tumour cells. In diabetes, chronic hyperglycemia induces persistent NOX activation, leading to excessive ROS production and contributing to microvascular complications such as retinopathy, nephropathy, and neuropathy. DISCUSSION:NOX enzymes act as redox integrators that couple metabolic state to cellular signalling. Their dysregulation drives divergent yet overlapping pathogenic outcomes in cancer and diabetes. Selective NOX inhibition may normalize redox tone, restore metabolic flexibility, and enhance therapeutic responses. Understanding NOX isoform-specific regulation offers opportunities for biomarker development and combination therapy design. CONCLUSION:NOX1, NOX2, and NOX4 are key regulators of oxidative metabolism in cancer and diabetes. Targeting these isoforms represents a promising translational approach to modulate redox imbalance, suppress tumour progression, and mitigate diabetic microvascular complications.
Diabetes mellitus affects both the peripheral and central nervous systems, giving rise to a spectrum of neurological complications that extend far beyond the traditional focus on diabetic peripheral neuropathy (DPN). Chronic hyperglycemia disrupts cellular homeostasis through increased formation of advanced glycation end-products, activation of inflammatory pathways, mitochondrial dysfunction, oxidative stress, and impaired neurovascular regulation. These disturbances converge to drive axonal degeneration, demyelination, synaptic injury, and progressive cognitive decline. Emerging evidence also highlights a critical role for gut dysbiosis and intestinal barrier dysfunction, which facilitate microbial translocation and systemic inflammation, ultimately disrupting the blood-brain barrier and amplifying neuroimmune injury. This narrative review synthesizes current mechanistic, clinical, and translational insights into how metabolic, inflammatory, vascular, and microbial pathways interact to produce diabetes-associated neurodegeneration. We summarize key molecular drivers-including mitochondrial ROS overproduction, microglial and astrocytic activation, endothelial dysfunction, and insulin resistance-while also describing their contributions to DPN, autonomic neuropathy, and diabetes-related cognitive impairment. We further integrate evidence from emerging therapeutic domains, including mitochondrial stabilizers, anti-inflammatory strategies, gut-microbiome modulation, and neurovascular-targeted interventions. Despite advances in understanding, disease-modifying therapies remain limited, and diagnostic tools for early detection are underutilized. Bridging these gaps will require longitudinal human studies, improved biomarkers, and integrative therapeutic approaches that target multiple convergent pathways. A deeper understanding of cross-talk among metabolic, immune, vascular, and microbial systems may enable earlier intervention and more effective strategies to mitigate the neurological burden of diabetes.
Background: Diabetes mellitus is among the most critical health issues all over the world, marked by persistent hyperglycemia, oxidative stress, inflammation, and the lack of insulin activity. The synthetic antidiabetic drugs that are on the market have a very short lifespan of use because of the side effects and failure to control metabolic dysregulation. The multi-targeted therapeutic advantages of phytochemicals present in medicinal plants are limited by low aqueous solubility, chemical instability, rapid metabolism, and low oral bioavailability. To address these restrictions, nano-phytotherapeutics have become a viable option to improve pharmacokinetics, increase tissue-specific delivery, and enable controlled release of bioactive compounds. Objective: The aim is to provide an overview of the therapeutic potential of three antidiabetic medicinal plants, Syzygium cumini, Pterocarpus santalinus, and Momordica cymbalaria, considering their major phytoconstituents and their mode of action. These three plants were selected because of their phytochemical diversity and complementary therapeutic potential, as well as their experimentally demonstrated antidiabetic activities and growing relevance in nanotechnology-based delivery systems. Anthocyanins, ellagic acid, pterostilbene, and cucurbitacins are some of the bioactive compounds with potent antihyperglycemic, antioxidant, and anti-inflammatory effects, making them promising candidates for nano-enabled formulations. Method: Compared to traditional plant extracts, a comparative study of polymeric nanoparticles, lipid-based nanocarriers, nanoemulsions, and green-synthesized metal nanoparticles has shown significant improvements in solubility, stability, bioavailability, and glycemic control. The present review provides a comprehensive, plant-specific, and carrier-oriented overview of current research, with particular emphasis on formulation relevance, mechanistic foundations, and translational limitations. Results: Although promising preclinical findings have been reported, several barriers to clinical translation remain unresolved, including the lack of long-term toxicological data, inconsistencies in phytochemical composition and preparation methods, and regulatory challenges specific to nano-herbal therapeutics. Furthermore, most existing studies are predominantly limited to in vitro and animal models, with a substantial lack of well-designed clinical studies and direct human validation. Conclusion: Stimuli-responsive nano-herbal therapeutics should be the focus of future research on rationally designed polyherbal nanoformulations, nanocarriers, AI-assisted optimization of formulation, and comprehensive pharmacokinetic and safety evaluations. These advancements may accelerate the development of long-term diabetes treatment with biocompatible nano-phytotherapeutics.
In the originally published article titled "Modern-Day Therapeutics and Ongoing Clinical Trials against Type 2 Diabetes Mellitus: A Narrative Review", published in "Current Diabetes Reviews", Vol: 21, 2025 [1], certain phrases and expressions were unclear, which may have affected readability. These have now been revised to improve clarity and ensure that the intended meaning is accurately conveyed. The corrections do not affect the results, interpretations, or conclusions of the article. We apologize for any inconvenience caused and appreciate the opportunity to rectify this matter. The original article can be found online at https://www.eurekaselect.com/article/140414 Original: 4.1.3. GLP-1 Receptor Agonist According to the latest press release, DD01 is therapeutic against hepatic steatosis and lowers body weight in T2DM patients diagnosed with or without fatty liver ailment. Corrected: 4.1.3. GLP-1 Receptor Agonist According to the latest press release, DD01 is therapeutic against hepatic steatosis and lowers body weight in T2DM patients diagnosed with or without fatty liver disorder.
INTRODUCTION:Adolescents and young adults living with type 1 diabetes mellitus (T1DM) deal with distinctive challenges that go beyond clinical management. This review synthesizes qualitative evidence to examine how biographical disruption, embodiment, and illness narratives shape the lived experience of this population. METHODS:Through a structured search across PubMed, Scopus, and Web of Science, 15 qualitative studies, published over the past decade, were identified. Thematic synthesis was conducted in seven domains: psychological burden, identity, adaptation, social experience, barriers, technology, and recommendations. RESULTS:Emotional turbulence, anxiety, distress, and fear of hypoglycemia were common amongst adolescents with T1DM. Identity was often a major concern over biomedical risks, showing some gender differences in illness experience. Daily life involved vigilance, and attempts to regain normalcy were common in this population. In social matters, stigma, surveillance, and peer disconnection were prominent, but these concerns were ameliorated by family and friend support. Automated insulin delivery (AID) may cause reduction of burden but increased autonomy, though access was unequal due to economic, educational, and clinical barriers. DISCUSSION:Findings emphasized how T1DM portrays disruption in biography, embodiment, and identity in adolescence and young adults, consistent with Charmaz's framework of chronic illness. The absence of multidisciplinary approaches limits the detection of psychosocial needs and still frequently contributes to undesirable results. Culture, gender, and structural inequities shapes how young people experience, manage, and make sense of their condition. CONCLUSION:T1DM in youth is a lived reality that reshapes identity, autonomy, and social belonging. Handling biographical disruption requires culturally sensitive, developmentally adapted, and relationally grounded interventions. Future research needs to expand representation and adopt longitudinal studies of adaptation.
Diabetes Mellitus (DM) increases the risk of Mild Cognitive Impairment (MCI) and dementia, severely impacting patients' quality of life and long-term future prospects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i), a class of oral hypoglycemic drugs, have recently been shown to have neuroprotective effects. Studies show that SGLT-2i ameliorates cognitive dysfunction in diabetic animal models through various mechanisms such as insulin pathways in the brain, cerebrovascular dysfuntion, neuroinflammation and oxidative stress, inhibition of Alzheimer's disease pathology, and neurotrophic factor expression. Clinical studies also show that SGLT-2i improves cognitive performance in diabetic patients, significantly reducing the risk of dementia and MCI. Despite the promising role of SGLT-2i in preventing and treating DM-related cognitive impairment, further studies and more robust clinical evidence are needed for its clinical application.
Metabolic Syndrome (MetS) is a global health concern characterized by a cluster of interrelated metabolic abnormalities, including insulin resistance, central obesity, dyslipidemia, hypertension, and chronic low-grade inflammation. These factors significantly increase the risk of developing Type 2 Diabetes Mellitus (T2DM), Cardiovascular Disease (CVD), and other complications. In recent years, plant-derived natural products and herbal medicines have garnered increasing attention for their potential to modulate the underlying mechanisms of Metabolic Syndrome (MetS) safely and cost-effectively. This review explores the therapeutic role and molecular mechanisms of several key botanicals, including berberine, Cinnamomum cassia (Cinnamon), Zingiber officinale (ginger), Trigonella foenum-graecum (Fenugreek), Nigella sativa (black seed), Curcuma longa (Curcumin), Artemisia dracunculus (Russian tarragon), Momordica charantia (bitter melon), and Vaccinium angustifolium (lowbush blueberry). These agents exert multifaceted effects, including the activation of AMPK, enhancement of insulin receptor signaling, increased GLUT4 translocation, anti-inflammatory and antioxidant activities, and modulation of lipid metabolism and gut microbiota. While preclinical data strongly support their efficacy, human clinical trials have shown mixed results due to factors such as inconsistent formulations, poor bioavailability, and individual variability. Despite these challenges, the evidence suggests that plant-based therapies may serve as effective adjuncts to conventional treatment, particularly in the early or preventive stages of MetS. The review highlights the importance of standardized formulations, enhanced delivery systems, and well-controlled clinical trials to validate their efficacy and integrate them into evidence-based therapeutic protocols. These findings support the growing role of natural products in the holistic management of metabolic syndrome.
BACKGROUND:Although low-Glycemic-Index (low-GI) diets are proposed to improve glucose balance and lipid metabolism, findings from Randomized Controlled Trials (RCTs) remain inconsistent. OBJECTIVE:To comprehensively evaluate the overall effects of low-GI diets on glycemic and lipid profiles across diverse populations and to identify potential differences in outcomes among subgroups. METHODS:This systematic review and meta-analysis, conducted following PRISMA guidelines, searched PubMed, Embase, Cochrane Library, and Web of Science through April 2025. Weighted Mean Difference (WMD) with 95% Confidence Interval (CI) was calculated. Subgroup and sensitivity analyses explored heterogeneity and robustness. RESULTS:Twenty-five RCTs involving 1,973 participants (12-75 years) were included. Low-GI diets significantly reduced fasting blood glucose (FBG; -0.19 mmol/L, p = 0.04), glycated hemoglobin (HbA1c; -0.22%, p < 0.01), and low-density lipoprotein cholesterol (LDL-C; -0.15 mmol/L, p < 0.01) compared with control diets. Although not statistically significant, low-GI diets tended to increase High-Density Lipoprotein Cholesterol (HDL-C) and reduce Fasting Insulin (FI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), Triglycerides (TG), and Total Cholesterol (TC). Subgroup analyses revealed stronger benefits in Type 2 Diabetes Mellitus (T2DM), individuals with baseline FBG ≥ 6.1 mmol/L, trials with intervention duration ≥ 12 weeks, and people in the Asia-Pacific region. Sensitivity analyses provided confirmation of the reliability of these outcomes. CONCLUSIONS:Low-GI diets improve glycemic control and modestly lower LDL-C, particularly in metabolically high-risk populations and with sustained intervention. These results highlight low-- GI diets as a practical nutritional strategy for metabolic health, while suggesting that baseline glucose status, intervention length, and population characteristics influence their effectiveness.
Type 2 Diabetes (T2D) is a complex metabolic disorder associated with insulin resistance (IR), chronic low-grade inflammation, and dysregulated glucose metabolism. Increasing evidence suggests that gut microbiota imbalances, or dysbiosis, may play a key role in its development and progression. This review aims to critically evaluate the existing literature on the role of gut microbiome-targeted interventions, specifically prebiotics and probiotics, in the prevention and management of T2D. The review highlights that prebiotics have shown modest benefits in improving insulin sensitivity and lowering fasting blood glucose (FBG), particularly in individuals with early metabolic dysfunction. Probiotic interventions using strains like Lactobacillus and Bifidobacterium have demonstrated variable outcomes, with some studies reporting improvements in glycaemic control and inflammatory markers. Proposed mechanisms include increased production of short-chain fatty acids (SCFAs), improved gut barrier integrity, and modulation of bile acids. However, findings remain inconsistent because studies differ in design, population characteristics, intervention type, and outcome measures. Taken together, the evidence suggests that microbiome- based therapies show early potential for influencing pathways involved in the development and management of type 2 diabetes, although current effects are modest. Larger and longer-term trials are needed to confirm efficacy, clarify mechanisms, and determine which individuals are most likely to respond to probiotic or prebiotic interventions.
Diabetic foot ulcers are severe complications of diabetes mellitus; they are characterized by chronic inflammation, poor wound healing, and high risks of infection leading to extended hospitalizations and amputation. Although progress has been made in the conventional care of wounds, current therapies still fall short in yielding optimal healing outcomes. In recent years, bioactive natural products and phytochemicals have emerged as promising therapeutic agents due to their diverse pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, and pro-angiogenic effects. Key active phytochemicals such as curcumin, quercetin, resveratrol, and berberine have been investigated for their potential to enhance wound closure, modulate immune function, and promote tissue regeneration. A literature review was conducted through a systematic search of electronic databases, including PubMed/MEDLINE, Scopus, Web of Science, ScienceDirect, and Google Scholar, using keywords such as "diabetic foot ulcers," "phytochemicals," "natural products," "wound healing," and "drug delivery systems." Many phytochemicals have been reported for their efficacy in DFU models, modulating oxidative stress, stimulating fibroblast proliferation, enhancing collagen synthesis, and inhibiting the growth of microbial biofilms. Advanced drug delivery platforms have been developed to improve the solubility, stability, and targeted delivery of these compounds to the site of injury, utilizing hydrogels, nanoparticles, and polymer-based scaffolds. Preclinical and some clinical studies support the therapeutic potential of these agents; however, translational challenges persist due to issues with formulation, standardization, and the need for large-scale clinical validation. Phytochemical-based interventions are, therefore, a promising complementary approach for treating DFUs. The integration of these natural agents into conventional wound care regimens can improve healing outcomes and reduce complications. Future studies should focus on well-designed clinical trials, detailed mechanistic studies, and standardized and scalable delivery systems to support the clinical translation of phytochemical therapies in DFU management.
In the previously published version of this article [1], the study limitations section was missing. To ensure completeness and clarity, this section has now been added. We apologize for any inconvenience caused and appreciate the opportunity to rectify this matter. The original article can be found online at https://www.eurekaselect.com/article/148532 The publisher apologizes for any inconvenience caused. Details of the error and its correction are provided here. CORRECTED VERSION STUDY LIMITATIONS This study has several limitations, including the fact that predictors were measured based on medical records in a multicenter setting, and the possible time-varying effects of the predictors could not be reported. Another limitation was that patients with T2DM were enrolled in three multicenters in Bali Province, Indonesia. Therefore, the results may not be generalized to other Asian populations because of different genetic backgrounds and healthcare systems.
In the previously published version of this article [1], the "Standards of Reporting" heading was missing. To ensure completeness and clarity, this heading has now been included. We apologize for any inconvenience caused and appreciate the opportunity to rectify this matter. The original article can be found online at https://www.eurekaselect.com/article/148228 Original CONSENT FOR PUBLICATION Not applicable. FUNDING This research was funded by Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF Grant: 0193-00001720/2024-11) and Conselho Nacional de Desenvolvimento Científico e Tecnológico and Empresa Brasileira de Serviços Hospitalares (CNPq/Ebserh Grant: 408020/2021-0). Corrected CONSENT FOR PUBLICATION Not applicable. STANDARDS OF REPORTING PRISMA guidelines were followed. FUNDING This research was funded by Fundação de Apoio à Pesquisa do Distrito Federal (FAPDF Grant: 0193-00001720/2024-11) and Conselho Nacional de Desenvolvimento Científico e Tecnológico and Empresa Brasileira de Serviços Hospitalares (CNPq/Ebserh Grant: 408020/2021-0).
Recent advancements in drug delivery technologies, bioactive molecules, and biomaterial design have transformed the therapeutic landscape of diabetic wound management. Diabetic wounds remain a major clinical challenge due to persistent inflammation, impaired angiogenesis, and reduced tissue regeneration, primarily caused by chronic hyperglycemia and oxidative stress. Emerging nanotechnology-based systems, such as polymeric, metallic, and lipid nanoparticles, enable site-specific drug delivery with enhanced stability, biocompatibility, and sustained release, thereby improving therapeutic efficacy. Complementary nanocarrier platforms like liposomes, niosomes, hydrogels, and nanohydrogels provide a moist microenvironment essential for cell proliferation and tissue remodeling while ensuring controlled drug release for faster wound closure. Advanced strategies, including dendrimers, transferosomes, microneedle arrays, and 3D-printed scaffolds, offer personalized, minimally invasive, and adaptive therapeutic solutions. Nanoemulsions and nanocapsules facilitate effective encapsulation and transport of hydrophobic drugs, broadening their clinical applicability. Incorporating bioactive growth factors such as VEGF, PDGF, chemokines, and stem cell-derived exosomes into these systems further enhances angiogenesis, modulates inflammation, and accelerates granulation tissue formation. Meanwhile, biopolymers like collagen, chitosan, hyaluronic acid, and silk sericin serve as natural scaffolds that support cell adhesion, migration, and epithelialization. Collectively, these emerging technologies signify a paradigm shift toward integrated, patient-specific, and regenerative approaches for diabetic wound healing, addressing the limitations of conventional therapies through the synergy of nanotechnology and bioengineering.
INTRODUCTION:Foot ulcers are a common and serious complication in patients with diabetes mellitus. Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) may serve as a reservoir for autoinfection. This study aimed to investigate the association between S. aureus isolates obtained from nasal passages and foot infections in diabetic patients. METHODS:Nasal and foot wound swabs were collected from 84 diabetic patients. Bacterial identification and antibiotic susceptibility testing were performed using the VITEK 2 system. Methicillin resistance was determined using Oxacillin Salt Agar Screen, PBP2a assays, and mecA gene detection. Genetic correlation between nasal and wound isolates was assessed by pulsed-field gel electrophoresis (PFGE). RESULTS:S. aureus was the most prevalent isolate, accounting for 33.1% of samples. Methicillin resistance was detected in 55.1% of foot wound isolates and 73.3% of nasal isolates. The mecA gene was identified in 95.3% of both S. aureus and coagulase-negative Staphylococci. PFGE analysis showed 100% genetic homology between paired nasal and wound isolates. DISCUSSION:The data confirmed that S. aureus is the predominant bacterium in diabetic foot lesions. Our findings also suggest that these infections in diabetic patients are likely of endogenous origin. CONCLUSION:Diabetic foot patients carrying S. aureus in the nares are at high risk of self-contamination. These findings highlight the need for routine nasal screening and decolonization strategies to reduce infection risk in this vulnerable population.
INTRODUCTION:Distal symmetric polyneuropathy (DSPN) is a debilitating diabetic complication that impairs Quality of Life (QoL). This study evaluated the effects of Alpha Lipoic Acid (ALA) plus B vitamins on QoL and metabolic parameters in diabetic patients with symptomatic DSPN. METHODS:In this randomized, double-blind, placebo-controlled trial, 80 patients were allocated to receive either oral ALA plus B vitamins, i.e., Bionerv® (n =40) (intervention group) or placebo (n = 40) for 12 weeks. QoL, Body Mass Index (BMI), and Blood Pressure (BP) were assessed at baseline, 6 weeks, and 12 weeks. QoL was measured using the Revised Diabetes Quality of Life Questionnaire (Rv-DQoL), where higher scores indicate poorer QoL. Metabolic parameters (glycated haemoglobin (HbA1c), fasting blood sugar (FBS), fasting lipid profile (FLP) were assessed at baseline and 12 weeks. RESULTS:In the intervention group, the mean Rv-DQoL score decreased significantly in withingroup analysis from 29.50 ± 5.25 at baseline to 24.37 ± 3.43 at week 12 [F(2,156)=55.16; p-value <0.001]. However, between-group differences were not significant (p-value =0.151). Blood pressure also declined significantly within the intervention group (p-value <0.05), but no significant differences were observed between the placebo and intervention groups (p-value >0.05). Metabolic parameters (HbA1c, FBS, FLP, BMI) showed no significant changes between intervention and control groups (p-value >0.05). DISCUSSION:Twelve-week treatment with ALA plus B vitamins resulted in improvements in QoL and BP among DSPN patients. However, these changes did not reach statistical significance compared with placebo, and no alterations in metabolic parameters were observed. The short duration and small sample size may have limited the detectability of effects. CONCLUSION:Twelve weeks of treatment with ALA and B vitamins resulted in an improvement in QoL and BP among DSPN patients. However, these changes did not reach statistical significance compared with placebo, and no alterations in metabolic parameters were observed.
Type 2 diabetes mellitus (T2DM) is a common global disease affecting more than 588 million people. This number is projected to reach 852 million by 2050, imposing a significant socioeconomic burden. Type 2 diabetes results from insulin resistance (IR) in peripheral tissues and dysfunction of pancreatic beta cells. These two mechanisms and their proper functioning in the body are influenced by genetic and environmental factors. Transcription factors (TFs) play pivotal roles in these processes by regulating the expression of genes governing glucose and lipid metabolism. This study reviews the current knowledge on key transcription factors involved in the pathophysiology of type 2 diabetes. In the liver, FOXO1 enhances gluconeogenesis through upregulation of PEPCK and G6Pase expression under IR conditions, whereas SREBP1c and ChREBP enhance de novo lipogenesis and exacerbate hepatic steatosis and systemic IR. In adipose tissue, PPARγ coordinates adipocyte differentiation and insulin sensitivity, but phosphorylation at Ser273 impairs adiponectin expression. NF-κB stimulates chronic inflammation and links metabolic stress to insulin resistance. In skeletal muscle, MEF2 isoforms coordinate mitochondrial biogenesis and oxidative metabolism with PGC-1α, which are impaired in T2DM. Disruption of these transcription factors results in metabolic dysfunction. This highlights their potential as therapeutic targets. Therapeutic options such as FOXO1 inhibitors or PPARγ agonists are promising, although challenges such as off-target effects remain. Understanding the mechanisms by which transcription factors contribute to the pathophysiology of T2DM provides insights into novel strategies to reduce the progression and complications of T2DM.
This narrative review aims to elucidate the significance of the synergistic effects of linagliptin and resveratrol and also explores their individual mechanisms of action in diabetic complications such as nephropathy. A systematic literature analysis examined the synergistic potential of resveratrol and linagliptin in diabetic nephropathy. A critical review of their antioxidant, anti-inflammatory, and anti-fibrotic mechanisms was conducted. Various studies revealed that linagliptin improves renal outcomes through both incretin-dependent and independent pathways, reducing oxidative stress, inflammation, and AGE-RAGE axis activation. It also exhibits the capacity to reduce albuminuria and renal fibrosis in diabetic animal models. Resveratrol similarly demonstrates substantial renoprotective benefits through activation of the AMPK/Nrf2 pathway, mitigating oxidative stress and downregulating inflammatory markers such as tumor necrosis factor-alpha and interleukin-1 beta. The synergistic use of linagliptin and resveratrol may provide greater benefits than their individual effects, including improved glycaemic control, reduced renal oxidative stress, and decreased inflammatory and fibrotic markers, thereby offering superior protection against diabetic nephropathy.
