Search Results (115)

Diabetes mellitus is a chronic metabolic disease that has a significant impact on public health and is becoming more and more common worldwide. Although effective, conventional therapies are often limited by high cost, adverse effects, and issues with patient compliance. As a result, there is growing interest in complementary and alternative therapies. Medicinal plants have played an essential role in diabetes treatment, especially in regions such as Romania, where biodiversity is high and traditional knowledge is well preserved. The pathophysiology, risk factors, and worldwide burden of diabetes are examined in this review, with an emphasis on the traditional use of medicinal plants for glycemic control. A total of 47 plant species were identified based on ethnopharmacological records and recent biomedical research, including both native flora and widely cultivated species. The bioactive compounds identified, such as flavonoids, triterpenic saponins, polyphenols, and alkaloids, have hypoglycemic effects through diverse mechanisms, including β-cell regeneration, insulin-mimetic action, inhibition of α-glucosidase and α-amylase, and oxidative stress reduction. A systematic literature search was conducted, including in vitro, in vivo, and clinical studies relevant to antidiabetic activity. Among the species reviewed, Urtica dioica, Silybum marianum, and Momordica charantia exhibited the most promising antidiabetic activity based on both preclinical and clinical evidence. Despite promising preclinical results, clinical evidence remains limited, and variability in phytochemical content poses challenges to reproducibility. This review highlights the potential of Romanian medicinal flora as a source of adjunctive therapies in diabetes care and underscores the need for standardization and clinical validation. Full article

Diabetes mellitus (DM), a chronic metabolic disease, poses a significant challenge to global health. Although type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and other types of diabetes mellitus differ in pathological mechanisms, they converge in that hyperglycemia is a universal clinical hallmark. Currently, the antidiabetic medications employed in clinical practice for blood glucose management require long-term administration and are associated with various side effects that can adversely impact human health. Plant heteropolysaccharides have emerged as promising candidates for anti-diabetic therapy, owing to their abundant natural sources, absence of toxicities, and confirmed hypoglycemic activities. This review aims to summarize the anti-diabetic mechanisms of plant heteropolysaccharides by dissecting the key biological pathways associated with clinical intervention in DM, including the modulation of insulin secretion, a reduction in insulin resistance, and an alteration in the composition of the gut microbiota. For these reasons, these findings provide a theoretical framework for the clinical application of plant heteropolysaccharides and indicate that they are expected to become natural agents used in treating DM. Full article

Diabetes mellitus (DM) is frequent in kidney transplant recipients (KTRs), reducing graft and patient survival. In recent years, hypoglycemic agents have been approved for chronic kidney disease (CKD) patients, such as sodium glucose co-transporter type 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP1RAs), and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs), such as finerenone. Several studies demonstrated the ability of these drugs to reduce cardiovascular (CV) events and kidney disease progression in diabetic CKD patients. In this review, we will describe their use in KTRs with type 2 DM or post-transplant diabetes mellitus (PTDM), focusing on the potential positive effects. In particular, we will report literature data from observational studies, meta-analyses, and clinical trials. Based on their mechanism of actions, these drugs may balance the negative effects of immunosuppressive therapy on metabolic balance, reducing the risk of PTDM and CV events, that remain the first cause of death in KTRs. Generally, SGLT2is and GLP1RAs appear to be safe and efficacious in KTRs, and no interaction with immunosuppressive drugs or an increased risk of rejection has been reported. Regarding finerenone, no literature data are available and only one clinical trial is ongoing. In conclusion, although the 2022 KDIGO guidelines recommend caution in KTRs, the last meeting in Vienna on PTDM encourages their use in this population. Full article

Objectives: The anticancer effects of PI3Kα inhibitors (PI3Ki) are constrained by their hyperglycemic side effects, while the efficacy of conventional hypoglycemic agents, such as insulin, metformin, and SGLT-2 inhibitors, in mitigating PI3Ki-induced hyperglycemia remains suboptimal. Dorzagliatin, a novel glucokinase activator, has been approved in China for the management of hyperglycemia, offering a promising alternative. This study aims to investigate the pharmacokinetic properties and potential mechanisms of drug interactions of dorzagliatin in the regulation of PI3K-induced hyperglycemia. Methods: Plasma concentrations of WX390, BYL719, and Dorz in mice were measured using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Pharmacokinetic (PK) parameters and PK/PD models were derived by using Phoenix WinNonlin 8.3.5 software. Blood glucose levels at various time points and tumor volume changes over a four-week period were assessed to explore the interactions when PI3Ki were combined with dorzagliatin. Results: The results indicated that, compared to the Dorz group, the combination groups (Dorz + BYL719, Dorz + WX390) exhibited increases in ${\mathrm{A}\mathrm{U}\mathrm{C}}_{0\to t}$ of dorzagliatin by 41.65% and 20.25%, and in C_max by 33.48% and 13.32%, respectively. In contrast, co-administration of these PI3Ki with dorzagliatin resulted in minimal increase in their plasma exposure. The combination therapy group (Dorz+BYL719) exhibited superior antitumor efficacy compared to the BYL719 group. Conclusions: Our findings indicate that the drug–drug interactions (DDIs) between dorzagliatin and multiple PI3Ki (including WX390 and BYL719) may partially account for the enhanced antitumor efficacy observed in the combination therapy group compared to PI3Ki monotherapy. This interaction may be explained by the inhibition of P-glycoprotein (P-gp) and the pharmacological mechanism of dorzagliatin regarding the activation of insulin regulation. Full article

Certain pharmacological properties of the methanolic extract of Justicia secunda Vahl leaves (Acanthaceae) were evaluated in Streptozotocin (STZ)-treated albino mice to confirm whether it could be considered an alternative candidate for the treatment of diabetes. Using qualitative phytochemistry, alkaloids, flavonoids, and tannins were detected. In an in vitro DPPH antioxidant activity test, high extract concentrations inhibited the radical by 90% during the first minutes of the reaction. The extract presented a slight genoprotective effect on mouse peripheral blood during the last days of the micronucleus test. Oral administration of the extract at a high dose every two days for 6 weeks caused a hypoglycemic effect in STZ-treated mice, protection against weight loss, and decreased blood triglyceride levels from week 3 of treatment. These effects could be mediated by the antioxidant activity of the detected metabolites and, perhaps, by an inhibitory effect on intestinal α-glucosidase. This renders J. secunda a good candidate for the long-term alternative treatment of diabetes without abandoning allopathic therapy. Full article

Background: Obesity is a growing global health concern associated with numerous comorbidities and high medication burden. This study aimed to evaluate the impact of low- and very-low-calorie diets (LCD/VLCD), combined with intensive lifestyle changes, on comorbidities and medication use in hospitalized patients with class II and III obesity. Methods: A retrospective cohort study was conducted using medical records of patients hospitalized for 3–6 months at a specialized obesity hospital in Brazil. Prescription data for antihypertensive, hypoglycemic, and lipid-lowering drugs were compared at admission, 3, and 6 months. Descriptive statistics, chi-squared tests, and t-tests were used to compare medication use and weight change over time. Results: Among 246 patients, the proportion of those using antihypertensives decreased from 74.4% at admission to 44.7% at 6 months (p < 0.02), with significant reductions also observed at 3 months (p < 0.001). Hypoglycemic prescriptions also declined at 3 months (p = 0.01), but not significantly at 6 months. Lipid-lowering medication use showed no significant changes. Average weight loss was 11% at 3 months and 21.3% at 6 months. Conclusions: Hospitalization with LCD/VLCD and lifestyle therapy was associated with a short-term reduction in medication burden, especially antihypertensives, supporting the potential of inpatient multidisciplinary strategies for severe obesity management. Full article

Objectives: This study compared the efficacy of continuous insulin infusion therapy (CIT) versus standard bolus insulin therapy in maintaining optimal perioperative glycemic control in patients with type 2 diabetes mellitus (T2DM) undergoing coronary artery bypass grafting (CABG), focusing on postoperative outcomes. Methods: In this single-center, open comparative study, 214 T2DM patients were selected from 1372 CABG cases (2016–2018) and divided into CIT (n = 28) and bolus therapy (n = 186) groups. Both groups were matched for sex, age, smoking status, body mass index, functional class of angina or heart failure, surgical characteristics and preoperative HbA1c. The target glucose range was 7.8–10 mmol/L (140–180 mg/dL), consistent with current guidelines. Glycemic control was assessed through frequent postoperative measurements, with particular attention to glucose variability and hypoglycemic events. Results: The CIT group demonstrated superior glycemic control, with significantly lower median glucose levels at 7, 8, 10, 12, and 13 h post-CABG (p < 0.05). Glycemic variability was reduced by 32% in the CIT group (p = 0.012), and the incidence of hypoglycemia (<3.9 mmol/L) was 3.6% versus 8.1% in the bolus group. While overall complication rates were similar, the CIT group had 0 cases of stroke, myocardial infarction, or wound infections versus 2.7%, 3.2%, and 5.9%, respectively, in the bolus group. Logistic regression confirmed that each 1 mmol/L increase in first-day glucose levels independently predicted both significant (OR 1.20, 95% CI 1.06–1.36) and serious complications (OR 1.16, 95% CI 1.03–1.30). Conclusions: CIT provided more stable postoperative glycemic control with reduced variability and hypoglycemia risk in T2DM patients after CABG. Although underpowered to detect differences in rare complications, our findings suggest CIT may improve outcomes. These results warrant validation in larger randomized trials. Full article

Diabetic retinopathy (DR) is a significant microvascular consequence of diabetes mellitus (DM), resulting in visual impairment and blindness. Controlling hyperglycemia is essential for avoiding and alleviating diabetic retinopathy. Nutrients and natural compounds possessing hypoglycemic characteristics present promising supplementary approaches to conventional therapies. This review assesses the influence of nutrients and natural substances on glycemic regulation and their possible effects on diabetic retinopathy. Goal: To investigate and consolidate knowledge about nutrients and natural compounds exhibiting hypoglycemic properties and their processes in the prevention and management of diabetic retinopathy. Approaches: Extensive reviews were conducted on pertinent studies from databases including PubMed, Scopus, and Web of Science. Selection criteria encompassed papers that examined natural substances, nutrients, or dietary supplements exhibiting effects on blood glucose levels and pathways associated to diabetic retinopathy. Principal findings were encapsulated according to their mechanisms, efficacy, and safety. Outcomes: Numerous foods, including omega-3 fatty acids, vitamin D, and polyphenols (e.g., curcumin, resveratrol), have hypoglycemic properties by improving insulin sensitivity and diminishing oxidative stress. Natural substances like berberine, quercetin, and flavonoids demonstrate analogous effects, influencing pathways associated with inflammation, advanced glycation end products (AGEs), and angiogenesis, which are critical factors in the evolution of diabetic retinopathy (DR). The synergistic benefits of integrating natural medicines with conventional antidiabetic medications may enhance glycemic control and reduce retinal damage. The safety profiles of these therapies are predominantly positive; nonetheless, clinical trials are still constrained in both breadth and scale. Conclusions: Nutrients and natural compounds are promising supplementary approaches for glycemic regulation and the therapy of diabetic retinopathy. Additional research, encompassing extensive clinical studies, is required to substantiate their efficacy, determine optimal dose, and verify long-term safety. The use of these natural substances into clinical practice may improve comprehensive management of diabetes and associated consequences. Full article

Background: Astrocytes play a key role in the inflammatory process accompanying various neurological diseases. Extracellular ATP accompanies inflammatory processes in the brain, but its effect on lipid mediators (oxylipins) in astrocytes remains elusive. Metformin is a hypoglycemic drug with an anti-inflammatory effect that has been actively investigated in the context of therapy for neuroinflammation, but its mechanisms of action are not fully elucidated. Therefore, we aimed to characterize the effects of ATP on inflammatory markers and oxylipin profiles; determine the dependence of these effects on the adaptation of astrocytes to high glucose levels; and evaluate the possibility of modulating ATP effects using metformin. Methods: We estimated the ATP-mediated response of primary rat astrocytes cultured at normal (NG, 5 mM) and high (HG, 22.5 mM) glucose concentrations for 48 h before stimulation. Cell responses were assessed by monitoring changes in the expression of inflammatory markers (TNFα, IL-6, IL-10, IL-1β, iNOS, and COX-2) and the synthesis of oxylipins (41 compounds), assayed with ultra-high-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). Intracellular pathways were assessed by analyzing the phosphorylation of p38; ERK MAPK; transcription factors STAT3 and NF-κB; and the enzymes mediating oxylipin synthesis, COX-1 and cPLA2. Results: The stimulation of cells with ATP does not affect the expression of pro-inflammatory markers, increases the activities of p38 and ERK MAPKs, and activates oxylipin synthesis, shifting the profiles toward an increase in anti-inflammatory compounds (PGD2, PGA2, 12-HHT, and 18-HEPE). The ATP effects are reduced in HG astrocytes. Metformin potentiated ATP-induced oxylipin synthesis (11-HETE, PGD2, 12-HHT, 15-HETE, 13-HDoHE, and 15-HETrE), which was predominantly evident in NG cells. Conclusions: Our data provide new evidence showing that ATP induces the release of anti-inflammatory oxylipins, and metformin enhances these effects. These results should be considered in the development of anti-inflammatory therapeutic approaches aimed at modulating astrocyte function in various pathologies. Full article

Diabetes mellitus (DM) is a major risk factor for cardiovascular disease, including heart failure (HF). A high proportion of DM patients eventually require cardiac surgery. While the traditional approach to DM therapy focuses on tight glucose control with insulin and oral hypoglycemic agents, novel antidiabetic drugs have emerged over the past two decades that offer not only improved glycemic control but also cardiovascular and renal protection, such as benefits in HF management. The aim of this review is to examine and evaluate the perioperative risk and benefits of novel antidiabetic agents in HF treatment for both DM and non-DM patients undergoing cardiac surgery. We specifically studied glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium–glucose cotransporter 2 inhibitors (SGLT2is). Although studies on novel antidiabetic therapy in cardiac surgeries were limited, the results showed all three agents to be safe for use in the perioperative period, with SLGT2i demonstrating the most benefits in HF management for those with or without DM and kidney impairment undergoing cardiac surgery. Future research on larger study populations and using a more rigorous study design is necessary in bridging current knowledge to improve patient outcomes. Full article

Type 2 diabetes (T2D) and metabolic (dysfunction)-associated steatotic liver disease (MASLD) affect a growing number of individuals worldwide. T2D and MASLD often coexist and substantially elevate the risk of adverse hepatic and cardiovascular clinical outcomes. Several common pathogenetic mechanisms are responsible for T2D and MASLD onset and progression, including insulin resistance, oxidative stress, and low-grade inflammation, among others. The latter can also be induced by gut microbiota and its derived metabolites. Natural bioactive compounds (NBCs) have been reported for their therapeutic potential in both T2D and MASLD. A large amount of evidence obtained from clinical trials suggests that compounds like berberine, curcumin, soluble fibers, and omega-3 fatty acids exhibit significant hypoglycemic, hypolipidemic, and hepatoprotective activity in humans and may be employed as adjunct therapy in T2D and MASLD management. In this review, the role of the most studied NBCs in the management of T2D and MASLD is discussed, emphasizing recent clinical evidence supporting these compounds’ efficacy and safety. Also, prebiotics that act against metabolic dysfunction by modulating gut microbiota are evaluated. Full article

Quinones, one of the oldest organic compounds, are of increasing interest due to their abundant presence in a wide range of natural sources and their remarkable biological activity. These compounds occur naturally in green leafy vegetables, fruits, herbs, animal and marine sources, and fermented products, and have demonstrated promising potential for use in health interventions, particularly in the prevention and management of type 2 diabetes (T2DM). This review aims to investigate the potential of quinones as a health intervention for T2DM from the multidimensional perspective of their sources, types, structure–activity relationship, glucose-lowering mechanism, toxicity reduction, and bioavailability enhancement. Emerging research highlights the hypoglycemic activities of quinones, mainly driven by their redox properties, which lead to covalent binding, and their structural substituent specificity, which leads to their non-covalent binding to biocomplexes. Quinones can improve insulin resistance and regulate glucose homeostasis by modulating mitochondrial function, inflammation, lipid profile, gastrointestinal absorption, and by acting as insulin mimetics. Meanwhile, increasing attention is being given to research focused on mitigating the toxicity of quinones during administration and enhancing their bioavailability. This review offers a critical foundation for the development of quinone-based health therapies and functional foods aimed at diabetes management. Full article

Diabetes mellitus is a metabolic disorder associated with oxidative stress, inflammation, and coagulation disturbances, which contribute to microvascular and macrovascular complications. We evaluated the therapeutic effects of lavender oil (Lavandula angustifolia) in a streptozotocin (STZ)-induced rat model of type 1 diabetes mellitus (T1DM) with experimentally induced thrombosis. Sixty male Wistar rats were divided into control, thrombosis, diabetes, thrombosis–diabetes, and lavender oil pretreatment groups (100 and 200 mg/kg body weight [bw]). Lavender oil exhibited dose-dependent benefits, with the 200 mg/kg bw dose leading to significant reductions in proinflammatory cytokines (e.g., tumor necrosis factor α (TNF-α); regulated upon activation, normal T cell expressed and secreted (RANTES); and monocyte chemoattractant protein-1 (MCP-1)) and oxidative stress, along with improved glycemic control, the partial restoration of C-peptide levels, and the attenuation of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9) activity (p < 0.0001). Histopathological and coagulation analyses confirmed its organ-protective and antithrombotic effects, including reduced tissue damage, vascular inflammation, and thrombus formation, and prolonged bleeding and clotting times. Our findings suggest that lavender oil exhibits dose-dependent antioxidant, anti-inflammatory, hypoglycemic, and organ-protective effects, indicating its potential as a complementary therapy for managing inflammation in T1DM with or without thrombosis. Full article

Diabetes mellitus (DM) is a chronic non-communicable disease with an increasing prevalence in Latin America and worldwide, impacting various social and economic areas. It causes numerous complications for those affected. Current treatments for diabetes include oral hypoglycemic drugs, which can lead to adverse effects and health complications. Other natural alternatives for DM treatment have been studied as adjunct therapies that could reduce or eliminate the need for antidiabetic medications. Several natural supplements may offer an alternative way to improve the quality of life for patients with DM, and they may have other nutraceutical applications. Due to their phenolic compound content, some leguminous substances have been proposed as these alternatives. Phenolic compounds, with their high antioxidant activity, have shown promising potential in insulin synthesis, secretion, and the functionality of the endocrine pancreas. This review provides valuable information on various leguminous plants with anti-diabetic properties, including antioxidant, hypoglycemic, anti-fat-induced damage, and anti-apoptotic properties in vitro and in vivo, attributed to the high content of phenolic compounds in their seeds. Natural products with antidiabetic and pharmacological treatment potential improve diabetes management by offering more effective and complementary alternatives. To integrate these herbal remedies into modern medicine, further research on phenolic compound type, doses, efficacy, and safety in the human population is needed. Full article

Background: This study addresses hypoglycemia in adults with inherited metabolic disorders (IMDs), highlighting the importance of intermittently scanned continuous glucose monitoring (isCGM). Despite the elevated risk of hypoglycemia in an important group of these diseases, the use of isCGM remains uncommon and there is limited evidence supporting its effectiveness. Methods: A longitudinal quasi-experimental study was performed in 18 adults with IMDs, evaluating the use of isCGM for 2 months. Time in hypoglycemia (TBR), hyperglycemia (TAR), and time in range (TIR) were monitored, in addition to symptomatic and asymptomatic hypoglycemic events. Follow-up visits were performed at 7 days, 14 days, and 2 months. Results: TBR < 70 mg/dL was significantly reduced from 1.5% at baseline to 0% at 2 months. A decrease in the number and duration of hypoglycemic events was also observed. In some IMD subgroups, isCGM enabled detection of asymptomatic hypoglycemia and adjustment to dietary management, improving glycemic control. Conclusions: isCGM is effective in detecting and reducing hypoglycemia in adults with IMDs, optimizing nutritional therapy, and improving the quality of life of patients and their families. Full article