Treatment Of Hyperglycemia Research Articles

Metformin and Amoxicillin/Clavulanate as Co-Administration for the Treatment of Hyperglycemia in Female Rats Caused by Alloxan.

Metformin and Amoxicillin/Clavulanate as Co-Administration for the Treatment of Hyperglycemia in Female Rats Caused by Alloxan.

Protective effects of Cuscuta chinensis Lam. extract against learning and memory dysfunction induced by streptozotocin and amyloid β25-35 in vivo model

Alzheimer’s disease (AD) is associated with hyperglycaemia and amyloid beta (Aβ) accumulation. In the present study, we investigated whether an aqueous extract of Cuscuta chinensis Lam. (CCWE) improved cognitive disorder in a hyperglycaemic and cognitive-impaired mouse model. Hyperglycaemia was induced by streptozotocin (STZ, 50 mg/kg) and a single intracerebroventricular injection of Aβ25-35 (25 nM) was performed. The Aβ25-35-injected hyperglycaemic mice were then administered CCWE (100 or 200 mg/kg/day) for 14-d. The protective effects of the CCWE were evaluated by behavioural tests and western blot analysis. The bioactive compounds in CCWE were isolated by UPLC-QTOF/MS analysis. The administration of CCWE improved the learning and memory function in STZ/Aβ25-35-injected mice. Moreover, CCWE positively regulated the amyloidogenic pathway-related proteins and insulin signalling-related proteins. The bioactive components in CCWE were also identified. These findings suggest the possibility of CCWE as a potential candidate for the dual-targeting treatment of hyperglycaemia and AD.

IMPACT OF PLANT METABOLITES IN GLUCOSE METABOLISM FOR REGULATION OF BLOOD GLUCOSE LEVEL IN DIABETES: AN EXCLUSIVE UPDATE

Objective: To explore the molecular targets of plant chemicals and their role in regulating hyperglycemia, providing insights into potential strategies for developing new treatment for this condition. Result and Discussion: Understanding the biochemical pathways involved in sugar regulation is crucial for developing treatments for conditions such as hyperglycemia. Phytochemicals derived from plants have shown promise in regulating blood sugar levels through various molecular targets. By targeting specific enzymes and pathways involved in glucose metabolism, these phytochemicals offer potential therapeutic benefits for managing hyperglycemia. Plant chemicals have demonstrated the ability to influence key enzymes and pathways in glucose metabolism. Phytochemicals have been found to modulate glycolysis, the Krebs cycle, and gluconeogenesis, offering the potential for regulating blood sugar levels. Additionally, these plant extracts have shown effects on processes such as cholesterol synthesis, glycogen synthesis and degradation, carbohydrate metabolism and absorption, as well as insulin production and release. The diverse impact of these medicinal plants on multiple physiological processes highlights their potential to address hyperglycemia through a multi-faceted approach. In this review, we will further explore the molecular targets and mechanisms of action of these plant chemicals, which can provide valuable insights for developing novel treatments for hyperglycemia.

Evaluation of the α-Amylase, α-Glucosidase, Tyrosinase Inhibitory and Photoprotective Activities of Organic Solvent and Aqueous Extracts of Retama monosperma Stem

Retama monosperma is a medicinal plant widely used in traditional medicine across the Mediterranean region to treat various conditions, including diabetes, rheumatism, hyperlipidemia, and hypertension. The present study aimed to investigate the enzyme (α-amylase, α-glucosidase, and tyrosinase) inhibitory activity as well as the photoprotective effect of the extracts of R. monosperma stem. Organic solvent (hexane, ethyl acetate, and ethanol) extracts of R. monosperma stem were obtained by Soxhlet extraction, while aqueous extract was obtained by maceration. The α-amylase and α-glucosidase inhibitory activities of the extracts were investigated in vitro using the spectrophotometric method. Furthermore, the efficacy of the extracts as dermo-protective and photoprotective agents were evaluated by tyrosinase inhibitory activity and by ultraviolet absorbance test. The results showed that the hexane extract exhibited the highest α-amylase inhibitory activity (IC50 = 273.91 ± 0.61 µg/mL), for the α-glucosidase inhibitory activity, the aqueous extract demonstrated the highest potency (IC50 = 2331.12 ± 2.69 µg/mL). The ethyl acetate extract showed the highest tyrosinase inhibitory activity (313.68 ± 0.88 µg QE/mg extract). Additionally, the 10 mg/mL aqueous extract displayed significant photoprotective activity, with high UVA (1.810 ± 0.031) and UVB (2.112 ± 0.008) absorbance values. The results of this study have highlighted the therapeutic potential of R. monosperma, and established a solid foundation for future research on natural therapies and the development of innovative drugs for the treatment of hyperglycemia and pigmentation disorders.

Acute hand dystonia and action myoclonus unveiling diabetic striatopathy: The critical role of hyperglycemia.

Diabetic striatopathy is a rare complication of diabetes mellitus characterised by movement disorders secondary to hyperglycemia. While most commonly associated with chorea and ballism, it may also present with other hyperkinetic manifestations, including, albeit rarely, isolated dystonia and myoclonus. We report a case of a patient with poorly controlled diabetes mellitus who developed acute hand dystonia and action myoclonus, highlighting the broader spectrum of hyperglycemia-induced movement disorders. A 64-year-old male with poorly controlled type 2 diabetes mellitus presented with acute dystonic posturing of the right hand and action myoclonus of the right forearm. On admission, his blood glucose was 648 mg/dL, with a glycated hemoglobin of 13.5%. Neurological examination revealed these motor abnormalities, while brain magnetic resonance imaging showed global cortical atrophy without acute lesions. Following the initiation of insulin therapy, abnormal movement disorders resolved within 6 h as blood glucose levels decreased to 253 mg/dL. This case highlights the importance of prompt recognition and treatment of hyperglycemia in patients with new-onset movement disorders. Diabetic striatopathy should be considered in the differential diagnosis, even in the absence of chorea or ballism, as glycemic control can lead to rapid symptom resolution. Although isolated dystonia and myoclonus in diabetic striatopathy are rare, their occurrence broadens the spectrum of hyperglycemia-induced movement disorders. Early diagnosis and management of hyperglycemia are essential for optimising patient outcomes. Further research is needed to characterise the spectrum and underlying mechanisms of diabetic striatopathy fully.

Management of Diabetes and Hyperglycemia in the Hospital: A Systematic Review of Clinical Practice Guidelines.

Inpatient hyperglycemia is common among adults, and management varies. To systematically identify guidelines on inpatient hyperglycemia management. MEDLINE, Guidelines International Network, and specialty society websites were searched from 1 January 2010 to 14 August 2024. Clinical practice guidelines pertaining to blood glucose management in hospitalized adults were included. Two authors screened articles and extracted data, and three assessed guideline quality. Recommendations on inpatient monitoring, treatment targets, medications, and care transitions were collected. Guidelines from 10 organizations met inclusion criteria, and 5 were assessed to be of high quality per the Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) instrument. All guidelines recommended monitoring blood glucose for patients with diabetes and nine for admission hyperglycemia. Eight guidelines recommended an upper blood glucose target of 180 mg/dL, five with a lower limit of 100 mg/dL and three of 140 mg/dL. Guidelines were in agreement on using capillary blood glucose monitoring, and three guidelines included discussion of continuous monitoring. Hyperglycemia treatment with basal-bolus insulin alone (n = 3) or with correction (n = 5) was most commonly recommended, while sliding scale insulin was advised against (n = 5). Guidance on use of oral diabetes medications was inconsistent. Five guidelines included discussion of transitioning to home medications. Recommendations for hypoglycemia management and diabetes management in older adults were largely limited to outpatient guidance. Non-English-language guidelines were excluded. While there is consensus on inpatient blood glucose monitoring and use of basal-bolus insulin, there is disagreement on treatment targets and use of home medications and little guidance on how to transition treatment at discharge.

Bioinformatics Combined With Biological Experiments to Identify the Pathogenetic Link of Type 2 Diabetes for Breast Cancer.

Type 2 diabetes mellitus (T2DM) constitutes a significant risk factor for breast cancer (BC), with affected women exhibiting a two- to three-fold increased likelihood of developing BC. Furthermore, women diagnosed with both BC and T2DM tend to experience poorer prognoses and exhibit greater resistance to various treatments compared to their non-diabetic counterparts. Consequently, elucidating the comorbidities associated with T2DM and BC is instrumental in enhancing the diagnostic and therapeutic strategies for BC. A series of bioinformatics methods including weighted gene co-expression network analysis (WGCNA), differentially expressed gene (DEG) analysis, machine learning, and single-cell sequencing analysis were used to identify the pathogenetic molecules of T2DM for BC. Biological experiments including CCK-8, colony formation, wound healing, transwell assay, immunohistochemistry, and immunofluorescence were performed to determine the molecule effect. By conducting WGCNA and DEG analysis on the profiles of T2DM (GSE25724 and GSE20966) and the TCGA cohort of BC, we identified a total of 27 common hub genes shared between T2DM and BC. These genes were significantly enriched in pathways related to cell differentiation, cellular developmental processes, focal adhesion, and the MAPK signaling pathway. Notably, among these 27 genes, CCNB2, XRCC2, and CENPI were associated with poor prognosis in BC. Moreover, single-cell RNA sequencing analysis revealed that CCNB2, XRCC2, and CENPI are enriched in cancer cells within BC tissues. Additionally, we observed that CCNB2, XRCC2, and CENPI were elevated in BC tissues provided by patients with a diabetes history and associated with KI67 expression. Hyperglycemia treatment elevated the expression levels of CCNB2, XRCC2, and CENPI in BC cells, which correlated with increased cell proliferation and mobility. Conversely, the knockdown of these genes partially mitigated the pro-proliferative and pro-migratory effects induced by hyperglycemia in BC cells. Our findings suggested that CCNB2, XRCC2, and CENPI may serve as key pathogenic mediators linking T2DM and BC. Targeting these molecules could potentially attenuate the adverse impacts of T2DM on BC progression.

Postprandial Hyperglycaemia Screening and Pregnancy Outcomes-Lessons From COVID -19.

During COVID-19, the diagnosis and treatment of GDM differed from conventional criteria. In Australia, during the alternative testing period, women with fasting glucose < 4.7 mmol/L were not diagnosed with GDM. To describe the maternal and neonatal outcomes of pregnant women with fasting blood glucose < 4.7 mmol/L for whom the diagnosis and treatment pathways differed before and during COVID-19. An Australian population-based data linkage study involving 3891 women with fasting blood glucose < 4.7 mmol/L between 24 and 32 weeks of gestation categorised into three groups: women diagnosed with GDM by postprandial hyperglycaemia (PPGDM; n = 226); normal glucose tolerance group (NGT; n = 3125) and women not tested for postprandial hyperglycaemia, mostly during COVID-19 (LFBG; n = 540). Perinatal outcomes were compared using generalised linear models. There were no differences between PPGDM and NGT groups in the risk of large for gestational age infants (RR 0.98, 95% CI: 0.63-1.52) although the mean birth weight (MD -103.43, 95% CI: -175.46 to -31.40)) was lower in the PPGDM group. The maternal and neonatal outcomes in the LFBG group were mostly comparable to the NGT group. In our study, the Australian COVID-19 GDM screening protocol, which includes initial fasting glucose testing, reduced the need for an OGTT in 67% of pregnant women. Diagnosis and treatment for postprandial hyperglycaemia in women with lower FBG should consider the benefits, as well as the financial, logistical and psychological costs involved.

Perceptions of the Feasibility and Benefit of Emergent Hyperglycemia Correction Concurrent with Stroke Reperfusion Treatment

Background: Hyperglycemia is common in acute ischemic stroke and is associated with worse outcomes and higher rates of symptomatic intracerebral hemorrhage following reperfusion therapy. Current stroke protocols prioritize time-sensitive reperfusion treatments, often overlooking hyperglycemia management during the emergent phase of care. Objective: This qualitative study explores emergency department registered nurses (EDRNs) and stroke coordinators' knowledge, perceptions, and barriers regarding hyperglycemia management in acute stroke patients undergoing reperfusion therapy. Methods: A phenomenological approach was used to conduct focus groups with 19 participants from 9 primary, 3 thrombectomy-capable, and 7 comprehensive stroke centers across six U.S. states. Thematic analysis identified key patterns related to hyperglycemia management and emergent stroke care. Results: Participants (n=19) identified several barriers to the emergent management of hyperglycemia in stroke patients, including staffing shortages, time constraints, and the absence of specific protocols. Despite the known impact of hyperglycemia on stroke outcomes, it was generally deprioritized in favor of achieving timely reperfusion treatment. The majority of participants reported that hyperglycemia management was not considered a priority in their institutions, particularly in the acute phase of stroke care. Suggestions to improve management included incorporating hyperglycemia treatment into order sets, improving staff education on its importance, and enhancing resource availability to support concurrent management alongside reperfusion therapies. Conclusion: EDRNs and stroke coordinators recognize the importance of glucose measurement but lack focus on hyperglycemia management due to systemic barriers and time-sensitive treatment priorities. Incorporating hyperglycemia management into acute stroke protocols could improve post-reperfusion outcomes and warrants further investigation.

Heterogeneous metabolic response of endothelial cells from different vascular beds to experimental hyperglycaemia and metformin.

Endothelial cells (ECs) are highly glycolytic, with mitochondria primarily serving a signalling function. Metabolic disruptions are early contributors to endothelial dysfunction, a primary feature of diabetic vascular complications, such as retinopathy, impaired wound healing and cerebral small vessel disease. The degree to which metabolism varies amongst such different vascular beds is unknown. Mitochondrial function was therefore characterised in human aortic, dermal, retinal and cerebral ECs in vitro, aiming to determine whether basal metabolism influences the response and susceptibility of vascular beds experimental hyperglycaemia (HG). Furthermore, the potential of metformin to maintain endothelial function independent of glycaemic control was assessed. Using a Seahorse analyser, metabolic function of human primary ECs from different vascular beds was compared under basal conditions, as well as HG and metformin treatment. ECs differed significantly in respiratory profile and glycolytic function. For example aortic ECs were preferentially aerobic, whereas dermal ECs were glycolytic. HG significantly lowered mitochondrial network area but elicited modest effects upon respiratory function at the same time as influencing glycolytic function in a manner that was possibly conditional upon basal utilisation. Metformin inhibited basal respiratory function at the same time as significantly enhancing glycolysis in retinal and brain ECs. These data suggest that EC responses to HG and metformin are influenced by the basal metabolic profile, highlighting the potential of targeting EC metabolism to preserve function in a diabetic condition. A nuanced approach is needed to address diabetic vascular complications and endothelial metabolic health in diabetes, both in the investigation of pathophysiology and in prospective therapeutics. KEY POINTS: Endothelial dysfunction is an early feature of diabetes-associated cardiovascular complications Endothelial cells (ECs) are highly glycolytic, with mitochondria serving a signalling function ECs are known to be heterogeneous in function, but how this is reflected in metabolism is not fully understood, in addition to how this influences their response to hyperglycaemia Using experimental hyperglycaemia (HG) in vitro, we demonstrate that ECs differed significantly in respiratory profile and glycolytic function. Their response to HG is possibly contingent upon this basal utilisation. These results suggest a nuanced approach is needed when investigating diabetic vascular complications, both in the investigation of pathophysiology and in prospective therapeutics.

Analysis of the Anti-diabetic properties of Lactuca Sativa (l.) Seeds from diverse Geographical regions

Lactuca sativa have been shown to have the potential to act as antidiabetic drugs, using diabetic rats as the subjects in the research that are currently being conducted. In the treatment of hyperglycemia and the prevention of metabolic problems associated with diabetes, these herbs have been shown to be effective. The utilization of Lactuca sativa for the treatment of diabetes has been employed for a considerable amount of time, and these findings lend credence to that approach. One possible reason for the reported antidiabetic effects could be that Lactucasativa can enhance the activity of pancreatic β-cells in the islets of Langerhans and increase their number. In order to ascertain the specific functions and areas of impact of these parts, as well as to evaluate the potential for synergistic effects between plant-derived products and synthetic medications, additional study is required to investigate the chemical components of the plant that are responsible for its hypoglycemic qualities. Different physicochemical properties, such as solid, semisolid, or liquid consistencies, can be included into topical formulations during the process of development. We are able to have a better understanding of the molecular pathways that are accountable for the affects that have been identified thanks to these investigations. The investigation of potential therapeutic targets follows the rapid identification and characterization of active molecules. Therefore, it will be less difficult to create a more potent and precise diabetes drug.

Murine gut microbial interactions exert antihyperglycemic effects.

The correlations between gut microbiota and host metabolism have been studied extensively, whereas little relevant work has been done to investigate the impact of gut microbial interactions on host metabolism. With the use of a bacteriocin-targeting strategy, we aimed to identify the gut microbes associated with glucose and lipid metabolism by adjusting the gut microbial composition of mice fed a high-fat diet. To fulfill this goal, a Listeria monocytogenes (Lmo)-derived bacteriocin Lmo2776 secretion module was constructed and integrated into the genome of Escherichia coli Nissle 1917 (EcN), yielding the Lmo2776-secreting strain EcN-2776. In high-fat diet-fed mice, EcN-2776 administration decreased blood glucose and increased serum triglyceride, and gene amplicon sequencing of 16S rRNA in these mice indicated that intestinal secretion of Lmo2776 led to adjustment of the gut microbial composition. Specifically, Lmo2776 restricted the growth of Ligilactobacillus murinus, thus alleviating its inhibitory impact towards Faecalibaculum rodentium. Further analyses indicated that F. rodentium administration decreased the fasting blood glucose of high-fat diet-fed mice, an effect that may be attributable to the intestinal consumption of glucose by F. rodentium. In this study, we identified the gut microbes associated with glucose metabolism, uncovered their interactions, and deciphered the impact of these gut microbial interactions on the host glucose metabolism. Our findings may pave the way for the treatment of hyperglycemia from the perspective of gut microbial interactions.

The Association between Vitamin B12 Deficiency and Metformin Therapy in Libyan Diabetic Patients

Metformin is the first line treatment of diabetic hyperglycaemia. However, numerous studies have shown that long-term use of metformin can result in a vitamin B12 deficiency. In this study, we sought to assess the prevalence of vitamin B12 deficiency in diabetic patients taking metformin on a long-term basis as well as the association between vitamin B12 deficiency and diabetic neuropathy. Across sectional study was conducted on 143 Libyan diabetic patients attending endocrinology outpatient diabetic centre in Benghazi, who are on metformin for at least 6 months, and eligible to the inclusion criteria. Data on metformin intake and confounding variables were collected from questionnaires. Serum vitamin B12 levels were estimated, and vitamin B12 deficiency was defined as serum B12 less than 196pg/ml. Data analysis was performed using the statistical package for social sciences (SPSS) version 28. The study involved 143 patients, with a majority being women (50.3%) and men (49.7%). The mean duration of diabetes was 10.52 ± 7.260 years. The mean daily dose of metformin was 1435.42 ± 377.766 mg for females and 1495.77 ± 392.678 mg for males. The mean duration of metformin intake was 7.93 ± 5.859 years for females and 7.34 ± 5.780 years for males. The mean serum vitamin B12 level was 469.78 ± 233.477 pg/mL, with males having non-significantly higher levels than females. 59.2% of male patients had vitamin B12 levels ≤420 pg/mL, while 51.4% of female patients had levels ≤420 pg/mL. Nevertheless, no patient had a vitamin B12 deficit. No significant correlation was observed between serum vitamin B12 levels with metformin dose, duration of action, or patient characteristics. Despite the high prevalence of peripheral neuropathy (36.4%), there was no significant difference in B12 levels between patients with and without neuropathy.

Current views on etiology, diagnosis, epidemiology and gene therapy of maturity onset diabetes in the young.

MODY, or maturity-onset diabetes of the young, is a group of monogenic diseases characterized by autosomal dominant inheritance of a non-insulin-dependent form of diabetes that classically manifests in adolescence or in young adults under 25 years of age. MODY is a rare cause of diabetes, accounting for 1% of all cases, and is often misdiagnosed as type 1 or type 2 diabetes. It is of great importance to accurately diagnose MODY, as this allows for the most appropriate treatment of patients and facilitates early diagnosis for them and their families. This disease has a high degree of phenotypic and genetic polymorphism. The most prevalent forms of the disease are attributed to mutations in three genes: GCK (MODY 2) and (HNF)1A/4A (MODY 3 and MODY 1). The remaining MODY subtypes, which are less prevalent, have been identified by next generation sequencing (NGS) in the last decade. Mutations in the GCK gene result in asymptomatic, stable fasting hyperglycemia, which does not require specific treatment. Mutations in the HNF1A and HNF4A genes result in pancreatic β-cell dysfunction, which in turn causes hyperglycemia. This often leads to diabetic angiopathy. The most commonly prescribed drugs for the treatment of hyperglycemia are sulfonylurea derivatives. Nevertheless, with advancing age, some patients may require insulin therapy due to the development of resistance to sulfonylurea drugs. The strategy of gene therapy for monogenic forms of MODY is still an experimental approach, and it is unlikely to be widely used in the clinic due to the peculiarities of MODY structure and the high genetic polymorphism and clinical variability even within the same form of the disease. Furthermore, there is a lack of clear gene-phenotypic correlations, and there is quite satisfactory curability in the majority of patients. This review presents the main clinical and genetic characteristics and mutation spectrum of common and rarer forms of MODY, with a detailed analysis of the field of application of AVV vectors in the correction of hyperglycemia and insulin resistance.

Imeglimin, unlike metformin, does not perturb differentiation of human induced pluripotent stem cells towards pancreatic β-like cells and rather enhances gain in β cell identity gene sets.

Metformin treatment for hyperglycemia in pregnancy (HIP) beneficially improves maternal glucose metabolism and reduces perinatal complications. However, metformin could impede pancreatic β cell development via impaired mitochondrial function. A new anti-diabetes drug imeglimin, developed based on metformin, improves mitochondrial function. Here we examine the effect of imeglimin on β cell differentiation using human induced pluripotent stem cell (iPSC)-derived pancreatic islet-like spheroid (SC-islet) models. Human iPSCs are differentiated into SC-islets by three-dimensional culture with and without imeglimin or metformin. Differentiation efficiencies of SC-islets were analyzed by flow cytometry, immunostaining, quantitative PCR, and insulin secretion assay. RNA sequencing and oxygen consumption rate were obtained for further characterization of SC-islets. SC-islets were cultured with proinflammatory cytokines, in part mimicking the uterus environment in HIP. Metformin perturbed SC-islet differentiation while imeglimin did not alter it. Furthermore, imeglimin enhanced the gene expressions of β cell lineage markers. Maintenance of mitochondrial function and optimization of TGF-β and Wnt signaling were considered potential mechanisms for augmented β cell maturation by imeglimin. In the presence of proinflammatory cytokines, imeglimin ameliorated β cell differentiation impaired by cytokines and metformin. Imeglimin does not perturb differentiation of SC-islet cells and rather enhances gain in β cell identity gene sets in contrast to metformin. This may lead to the improvement of in vitro β cell differentiation protocols.

Does the Consumption of Metformin Correlate With a Reduction in Mortality Among Patients With Type 2 Diabetes and COVID-19 in Morocco?

To assess whether metformin therapy for type 2 diabetes(T2DM) was associated with a reduced mortality rate in patients hospitalized for COVID-19 compared to other antihyperglycemic drugs. This retrospective study included patients with T2DM who tested positive for SARS-CoV-2 between 1 August 2020 and 1 August 2021. The patients were required to be aged over 18 years old and to be undergoing treatment for hyperglycemia, whether with metformin, other oral antidiabetic drugs, or insulin. A data exploitation sheet was completed for each patient. The Jamovi(https://www.jamovi.org/) software was applied to conduct the statistical analyses.Multivariate logistic regression was used to determine whether metformin use was associated with reduced mortality among patients with T2DM and COVID-19. We identified 115 COVID-19 patients with T2DM, of whom 41 were on metformin, 35 patients were on insulin, and 39 patients were on other oral antihyperglycemic agents; the average age of patients was 65.5±13.2 years, and 52.2% were male. The mortality rate was lower in the metformin user group (21.1%) compared to the non-user group (78.9%). The multivariate logistic regression model indicated that age (OR=1.06; 95% CI (1.02-1.10); p=0.002) and glycemia (OR=1.49; 95% CI (1.05-2.11); p=0.024) were significantly associated with mortality in patients with T2DM and COVID-19. Whereas, the use of metformin was identified as a protective factor (OR=0.34 95% CI (0.12-0.95); p=0.041). This study highlighted that metformin seems to be associated with significantly decreased mortality in adults with T2DM and COVID-19.

Renin-angiotensin-aldosterone system variations in type 2 diabetes mellitus patients with different complications and treatments: Implications for glucose metabolism.

The presence of hypertension and various acute or chronic complications may affect the renin-angiotensin-aldosterone system (RAAS) in patients with type 2 diabetes mellitus (T2DM), which plays a crucial role in the regulation of glucose metabolism. However, the quantitative distribution of the RAAS components in relation to the progression of T2DM and the treatment of hyperglycemia and hypertension, as well as their association with different stages of complications and glucose metabolism, has not been well studied. We enrolled a total of 151 patients with T2DM and essential hypertension, 40 patients with T2DM and normotension, and 46 healthy controls in the study. They were categorized into subgroups based on criteria for diabetic complications. Statistical analyses, including Spearman rank correlation and multiple linear regression, were conducted to assess the relationship between RAAS components and glucose metabolism indexes such as HbA1c, FBG, CP, HOMA-β, HOMA-IR, and UACR. The results revealed significant differences in AII, ALD, REN, and ARR levels across various complication subgroups. Notably, the concentrations of ALD and REN exhibited a consistent trend, while ARR showed an opposite trend to the REN concentration. More than 60% of hypertensive patients were treated with ACEI/ARBs and calcium channel blockers, while 29.8% of the patients were prescribed β-blockers, resulting in decreased REN and increased ARR levels. All T2DM patients received antidiabetic treatment, among which 95 (49.7%) took SGLT-2is, 40 (20.9%) took GLP-1RAs injection and 55(28.8%) took DPP-4is. The subsequent analysis revealed that SGLT-2is, GLP-1RAs, DPP-4is and other glucose-lowering agents had no statistically significant effect on the RAAS system (p > 0.05). The correlation matrix analysis indicated positive associations between ALD, REN, CP, and HOMA-IR. Furthermore, the REN levels were negatively correlated with UACR in the hypertensive group and positively correlated with HbA1c and FBG levels in the normotensive group. Multiple linear regression analysis demonstrated that ALD levels increased with higher levels of CP and HOMA-IR, independently of the RAAS system, anti-RAAS treatment and antidiabetic therapy. REN levels decreased with increasing UACR and β-blocker usage in the hypertensive group, while they increased with higher levels of HbA1c, FBG, and HOMA-IR in the normotensive group, independently of the RAAS system and antidiabetic therapy. The activation status of the RAAS system varied among T2DM patients with different complications, highlighting the need for clinical differentiation. ALD was positively associated with insulin resistance and glucose metabolism impairment, while REN exhibited negative correlations with urinary microalbumin and β-blocker usage, and positive correlations with hyperglycemia and insulin resistance. Blocking the RAAS system holds promise for improving insulin sensitivity and β-cell function, and potentially reversing abnormal glucose tolerance or ameliorating glucose metabolism disorders.

Synthesis, structural insights and bio-evaluation of N-phenoxyethylisatin hydrazones as potent α-glucosidase inhibitors.

Effective α-glucosidase inhibitors are vital for managing type 2 diabetes, emphasizing the need for novel and potent compounds. A series of novel N-phenoxyethylisatin hydrazones 1(a-l) have been synthesized and characterized by their spectral data, and in the case of 1l by its single crystal X-ray analysis. All the synthesized compounds were in vitro evaluated for their inhibition potential against the α-glucosidase enzyme. Interestingly, most of these compounds exhibited significant inhibitory activity against the α-glucosidase enzyme, with IC50 values ranging from 3.64 ± 0.13 to 94.89 ± 0.64 μM compared to the standard drug, acarbose (IC50 = 873.34 ± 1.67 μM). The compound 1e was found to be the most active compound of the series having an IC50 value of 3.64 ± 0.13 μM. Molecular docking studies revealed a binding score of -9.7 kcal mol-1 for 1e, slightly surpassing that of acarbose (-9.4 kcal mol-1). Unlike acarbose, which primarily relies on hydrogen bonding, the binding interactions of 1e are dominated by π-interactions. ADMET profiling confirmed favourable pharmacokinetics for these compounds, including good oral bioavailability, balanced hydrophilicity, and minimal predicted toxicity. These findings highlight the potential of these compounds as promising candidates for the development of more effective treatments for hyperglycemia.

Glypican-4 trajectory predicts the risk of gestational diabetes mellitus and the requirement for insulin therapy during pregnancy.

Gestational diabetes mellitus (GDM), characterized by the onset of glucose intolerance during pregnancy, results in a series of complications for maternal and fetal health. Oral glucose tolerance test (OGTT) for screening glucose metabolism is performed in mid-to-late pregnancy, which remains less time to optimize glycemic control. Glypican-4, an insulin-sensitive adipose hormone, exhibits correlations with metabolic indicators. This study aims to investigate the association between glypican-4 and the risk of developing GDM, as well as the effects on insulin therapy and postpartum glucose metabolism. Based on pregnancy 75-g OGTT results, 718 subjects were grouped into normal glucose tolerance (NGT, n = 345) and GDM (n = 373) groups. 373 GDM patients were divided into the diet (n = 237) and insulin (n = 136) groups according to the treatment of hyperglycemia in pregnancy. Based on postpartum 75-g OGTT results, 158 of the 373 GDM patients were further divided into theNGT after delivery (NGTd, n = 138) and abnormal glucose tolerance (AGT, n = 20) groups. Glypican-4 level was significantly higher in GDM than NGT subjects during pregnancy (P< 0.001). Glypican-4 was an independent predictor of GDM with the cut-offs were 0.40 ng/mL (5-12 weeks of gestation) and 0.79 ng/mL (13-23 weeks of gestation). Furthermore, glypican-4 level in the insulin group was higher than the diet group, which was a potential predictor of insulin therapy. Glypican-4 during pregnancy is associated with GDM risk, with higher levels indicating increased risk. Glypican-4 was also related to insulin therapy in GDM.

Targeting central pathway of Glucose-Dependent Insulinotropic Polypeptide, Glucagon and Glucagon-like Peptide-1 for metabolic regulation in obesity and type 2 diabetes.

Obesity and type 2 diabetes are significant public health challenges that greatly impact global well-being. The development of effective therapeutic strategies has become more and more concentrated on the central nervous system and metabolic regulation. The primary pharmaceutical interventions for the treatment of obesity and uncontrolled hyperglycemia are now generally considered to be incretin-based anti-diabetic treatments, particularly glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor agonists. This is a result of their substantial influence on the central nervous system and the consequent effects on energy balance and glucose regulation. It is increasingly crucial to understand the neural pathways of these pharmaceuticals. The purpose of this review is to compile and present the most recent central pathways regarding glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and glucagon receptors, with a particular emphasis on central metabolic regulation.