A Quest for Potential Role of Vitamin D in Type II Diabetes Mellitus Induced Diabetic Kidney Disease.

Diabetes mellitus is a metabolic disorder characterized by high blood sugar levels. In recent years, T2DM has become a worldwide health issue due to an increase in incidence and prevalence. Diabetic kidney disease (DKD) is one of the devastating consequences of diabetes, especially owing to T2DM and the key clinical manifestation of DKD is weakened renal function and progressive proteinuria. DKD affects approximately 1/3rd of patients with diabetes mellitus, and T2DM is the predominant cause of end-stage kidney disease (ESKD). Several lines of studies have observed the association between vitamin D deficiency and the progression and etiology of type II diabetes mellitus. Emerging experimental evidence has shown that T2DM is associated with various kinds of kidney diseases. Recent evidence has also shown that an alteration in VDR (vitamin D receptor) signaling in podocytes leads to DKD. The present review aims to examine vitamin D metabolism and its correlation with T2DM. Furthermore, we discuss the potential role of vitamin D and VDR in diabetic kidney disease.

The dichloromethane fraction from Calotropis gigantea (L.) Dryand. stem bark extract prevents liver cancer in SDT rats with insulin-independent diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: Calotropis gigantea (L.) Dryand. (C. gigantea) is a traditional medicinal plant, recognized for its effectiveness in managing diabetes, along with its notable antioxidant, anti-inflammatory, and anticancer properties. Type II diabetes mellitus (T2DM) is characterized by chronic metabolic disorders associated with an elevated risk of hepatocellular carcinoma (HCC) due to hyperglycemia and impaired insulin response. The scientific validation of C. gigantea's ethnopharmacological efficacy offers advantages in alleviating cancer progression in T2DM complications, enriching existing knowledge and potentially aiding future clinical cancer treatments. AIM: This study aimed to investigate the preventive potential of the dichloromethane fraction of C. gigantea stem bark extract (CGDCM) against diethylnitrosamine (DEN)-induced HCC in T2DM rats, aiming to reduce cancer incidence associated with diabetes while validating C. gigantea's ethnopharmacological efficacy. MATERIALS AND METHODS: Spontaneously Diabetic Torii (SDT) rats were administered DEN to induce HCC (SDT-DEN-VEH), followed by treatment with CGDCM. Metformin was used as a positive control (SDT-DEN-MET). All the treatments were administered for 10 weeks after the initial DEN injection. Diabetes-related parameters, including serum levels of glucose, insulin, and glycosylated hemoglobin (HbA1c), as well as liver function enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase), were quantified. Serum inflammation biomarkers interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated. Liver tissue samples were analyzed for inflammation protein expression (IL-6, TNF-α, transforming growth factor-ß1 (TGF-ß1), and α-smooth muscle actin (α-SMA)). Histopathological evaluation was performed to assess hepatic necrosis, inflammation, and fibrosis. Liver cell proliferation was determined using immunohistochemistry for Ki-67 expression. RESULTS: Rats with SDT-DEN-induced HCC treated with CGDCM exhibited reduced serum glucose levels, elevated insulin levels, and decreased HbA1c levels. CGDCM treatment also reduced elevated hepatic IL-6, TNF-α, TGF-ß1, and α-SMA levels in SDT-DEN-VEH rats. Additionally, CGDCM treatment prevented hepatocyte damage, fibrosis, and cell proliferation. No adverse effects on normal organs were observed with CGDCM treatment, suggesting its safety for the treatment of HCC complications associated with diabetes. Additionally, the absence of adverse effects in SD rats treated with CGDCM at 2.5 mg/kg further supports the notion of its safe usage. CONCLUSIONS: These findings suggest that C. gigantea stem bark extract exerts preventive effects against the development of HCC complications in patients with T2DM, expanding the potential benefits of its ethnopharmacological advantages.

In Silico Investigation against Inhibitors of Alpha-Amylase Using Structure-based Screening, Molecular Docking, and Molecular Simulations Studies.

Type-II diabetes mellitus is a chronic disorder that results from fluctuations in the glucose level leading to hyperglycemia with severe adverse effects increasing worldwide. Alpha-Amylase is the key enzyme involved in the mechanism of glucose formation therefore Alpha-Amylase inhibitors have become a therapeutic target in the development of new leads as they have the potential to suppress glucose levels. Existing drugs targeting Alpha-Amylase highlight major drawbacks in terms of poor absorption rate that causes several gastrointestinal issues. So, this research is aimed to develop novel inhibitors interacting with Alpha-Amylase's active site using structural-based screening, binding pattern analysis, and molecular dynamic simulation. Hence, to search for a potential lead, we analyzed a total of 133 valiolamine derivatives and 535 desoxynojirimycin derivatives that exhibited drug-like properties screened through Lipinski filters. Virtual screening followed by binding interaction analysis we identified ten compounds that exhibited better binding energy scores compared to the standard drugs voglibose and miglitol, used in our study. The docking analysis, ADMET and metabolic site prediction estimated the best top two compounds with good drug profiles. Further, top compounds VG9 and VG15 were promoted to simulation study using the Biovia Discovery study to access the stability at a time interval of 100 ns. MD simulation results revealed that our compound VG9 possesses better conformational stability in the complex to the active site residues of Alpha-Amylase target protein than standard drug voglibose. Thus, our investigation revealed that compound VG9 also exhibits the best pharmacokinetic as well as binding affinity results and could act as a potential lead compound targeting Alpha-Amylase for Type II diabetes.

Understanding the structural dynamics of human islet amyloid polypeptide: Advancements in and applications of ion-mobility mass spectrometry.

Human islet amyloid polypeptide (hIAPP) forms amyloid deposits that contribute to ß-cell death in pancreatic islets and are considered a hallmark of Type II diabetes Mellitus (T2DM). Evidence suggests that the early oligomers of hIAPP formed during the aggregation process are the primary pathological agent in islet amyloid induced ß-cell death. The self-assembly mechanism of hIAPP, however, remains elusive, largely due to limitations in conventional biophysical techniques for probing the distribution or capturing detailed structures of the early, structurally dynamic oligomers. The advent of Ion-mobility Mass Spectrometry (IM-MS) has enabled the characterisation of hIAPP early oligomers in the gas phase, paving the way towards a deeper understanding of the oligomerisation mechanism and the correlation of structural information with the cytotoxicity of the oligomers. The sensitivity and the rapid structural characterisation provided by IM-MS also show promise in screening hIAPP inhibitors, categorising their modes of inhibition through "spectral fingerprints". This review delves into the application of IM-MS to the dissection of the complex steps of hIAPP oligomerisation, examining the inhibitory influence of metal ions, and exploring the characterisation of hetero-oligomerisation with different hIAPP variants. We highlight the potential of IM-MS as a tool for the high-throughput screening of hIAPP inhibitors, and for providing insights into their modes of action. Finally, we discuss advances afforded by recent advancements in tandem IM-MS and the combination of gas phase spectroscopy with IM-MS, which promise to deliver a more sensitive and higher-resolution structural portrait of hIAPP oligomers. Such information may help facilitate a new era of targeted therapeutic strategies for islet amyloidosis in T2DM.

Tongue image fusion and analysis of thermal and visible images in diabetes mellitus using machine learning techniques.

The study aimed to achieve the following objectives: (1) to perform the fusion of thermal and visible tongue images with various fusion rules of discrete wavelet transform (DWT) to classify diabetes and normal subjects; (2) to obtain the statistical features in the required region of interest from the tongue image before and after fusion; (3) to distinguish the healthy and diabetes using fused tongue images based on deep and machine learning algorithms. The study participants comprised of 80 normal subjects and age- and sex-matched 80 diabetes patients. The biochemical tests such as fasting glucose, postprandial, Hba1c are taken for all the participants. The visible and thermal tongue images are acquired using digital single lens reference camera and thermal infrared cameras, respectively. The digital and thermal tongue images are fused based on the wavelet transform method. Then Gray level co-occurrence matrix features are extracted individually from the visible, thermal, and fused tongue images. The machine learning classifiers and deep learning networks such as VGG16 and ResNet50 was used to classify the normal and diabetes mellitus. Image quality metrics are implemented to compare the classifiers' performance before and after fusion. Support vector machine outperformed the machine learning classifiers, well after fusion with an accuracy of 88.12% compared to before the fusion process (Thermal-84.37%; Visible-63.1%). VGG16 produced the classification accuracy of 94.37% after fusion and attained 90.62% and 85% before fusion of individual thermal and visible tongue images, respectively. Therefore, this study results indicates that fused tongue images might be used as a non-contact elemental tool for pre-screening type II diabetes mellitus.

Evaluating the impact of metabolic and cognitive stress on ghrelin and nesfatin-1 hormones in patients with diabetes and diabetic depression.

Nesfatin-1 and ghrelin, initially recognised as hormones involved in regulating energy, have emerged as crucial players with vital functions in various human body systems. In this study, we conducted a comparative assessment of nesfatin-1 and ghrelin responses in individuals experiencing metabolic stress due to diabetes, those with depressive diabetes characterised by both metabolic and mental stress, and healthy controls. We collected blood samples from a total of 90 participants, consisting of 30 people with type II diabetes mellitus (DM), 30 people with type II DM and major depressive disorders, and 30 healthy individuals. Diabetes was diagnosed based on glycated haemoglobin (HbA1c) levels, while depression was assessed using DSM-V criteria. Insulin resistance (HOMA-IR) was calculated, and serum ghrelin and nesfatin-1 levels were measured using ELISA kits. We observed statistically significant decreases in nesfatin-1 and ghrelin levels in the diabetic group (p < 0.0001). However, in the depressive diabetic group, nesfatin-1 levels increased significantly, while ghrelin levels decreased further. The nesfatin-1 to ghrelin ratio decreased in the diabetic group but increased significantly in the depressive diabetic group (p < 0.0001). Nesfatin-1 and ghrelin hormones exhibit parallel impacts in response to metabolic stress, but nesfatin-1 demonstrates contrasting actions compared to ghrelin when mental stress is added to metabolic stress. The findings of this study suggest that nesfatin-1 and ghrelin hormones may play active roles as protective, prognostic, and even etiological factors in various stress situations, particularly those involving mental stress, in addition to their known functions in regulating energy.

Incident Diabetes among Older Asian, Native Hawaiian and Pacific Islander Women with Breast Cancer.

BACKGROUND: The risk of diabetes among Asian, Native Hawaiian and Pacific Islander (ANHPI) women after breast cancer is unclear. This study estimated the risk of incident type II diabetes in older ANHPI and older Non-Hispanic White (NHW) women with breast cancer from the US National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Medicare linked claims. METHODS: A matched cohort of 7,122 older ANHPI and 21,365 older NHW women with breast cancer were identified from the SEER-Medicare between 2000 and 2017. To assess the risk of incident type II diabetes after breast cancer, hazard ratios (HRs) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazards model. RESULTS: During the mean 8 years of follow-up, 9.3% of older women with breast cancer developed incident type II diabetes. In comparison with NHW women, all older ANHPI women without known history of diabetes had an elevated risk of diabetes after breast cancer; with strong associations observed for Pacific Islander (HR = 3.09, 95%CI 1.43, 6.67), Vietnamese (HR = 2.12, 95%CI 1.33, 2.36), and Filipino (HR = 2.02, 95%CI 1.57, 2.59) women with breast cancer, adjusting for potential confounders. Among ANHPI women with breast cancer, more baseline comorbidities and obesity were risk factors for developing incident type II diabetes. CONCLUSION: ANHPI women diagnosed with breast cancer had an elevated risk of type II diabetes compared with older NHW women with breast cancer. Routine monitoring and management of diabetes are warranted in older ANHPI women with breast cancer.

Cutaneous hypersensitivity reaction to dulaglutide: A case report of an allergic reaction.

GLP-1 (glucagon-like peptide-1) receptor agonists are a class of anti-diabetic agents that act by inducing insulin secretion and inhibiting glucagon release in a glucose-dependent manner. They are particularly promising because of their long duration of action, reduced risk of hypoglycaemia and the added benefit of weight loss. Trulicity ® dulaglutide is a GLP-1 receptor agonist approved for type II diabetes and chronic weight management in obese adults. A few rare cases of hypersensitivity reactions have been reported in patients taking the GLP-1 receptor agonists dulaglutide and liraglutide. Here we present a new case of cutaneous hypersensitivity reactions in a man taking dulaglutide for type II diabetes. A 52-year-old man who had been taking dulaglutide for 5 weeks developed a rash on the abdomen when the dose was increased for 3 months. The patient experienced resolution of symptoms within days of stopping dulaglutide.

Spontaneous Expulsive Suprachoroidal Hemorrhage in a Middle-Aged Patient With Hypertension, Type II Diabetes, and Associated Retinopathy.

We report the clinical course of spontaneous expulsive suprachoroidal hemorrhage (SESCH) in a middle-aged man. A 50-year-old man with a history of uncontrolled hypertension and type II diabetes presented with massive preretinal hemorrhage in the posterior pole of the right eye (RE). Two weeks later, he presented with elevated intraocular pressure (IOP) and a nearly obliterated anterior chamber with coagulated blood behind the lens in the RE. We performed two rounds of surgery, including cataract surgery, vitrectomy, and sclerotomy. The choroidal detachment was clearly visible behind the posterior capsule during the cataract surgery. The surgical intervention successfully lowered the IOP and alleviated the pain. In rare cases of SESCH, maintaining awareness when patients show vulnerability in their choroidal vessels is of high importance.

Type II diabetes mellitus increases the risk of inflammatory bowel disease in a prospective cohort study.

BACKGROUND: Inflammatory bowel disease is a common digestive disorder and diabetes can lead to intestinal dysfunction. Patients with inflammatory bowel disease in combination with diabetes present a higher rate of hospitalization and consumption of medical resources, yet the association between type 2 diabetes and Inflammatory bowel disease remains unknown. METHODS: We studied 313,008 participants from the UK Biobank, including 5891 patients with type 2 diabetes at baseline. Multivariate Cox proportional risk models were constructed to examine the risks associated with type 2 diabetes and inflammatory bowel disease and its subtypes (Crohn's disease, ulcerative colitis). Potential confounders including sociodemographic, lifestyle, physical body indicators, psychological state, hypertension, and thyroid-related disorders were adjusted. Propensity score matching was also performed to analyze their sensitivity. RESULTS: Of a total of 313,008 participants included in the study, 5891 (1.88 %) were diagnosed with type 2 diabetes mellitus at baseline and 1829 (0.58 %) of the entire cohort developed inflammatory bowel disease during follow-up, with a median follow-up time of 13.72 years. Patients with type 2 diabetes had a higher cumulative risk of inflammatory bowel disease compared to the non-type 2 diabetes population (inflammatory bowel disease: 1.24% vs. 0.57%, p < 0.001; Crohn's disease: 0.46% vs. 0.15%, p < 0.001; ulcerative colitis: 0.73% vs. 0.35%, p < 0.001). Multivariate Cox regression analysis showed that type 2 diabetes was independently associated with inflammatory bowel disease (Hazard Ratio: 1.61 [95% Confidence Interval: 1.26-2.06], p < 0.001), Crohn's disease (Hazard Ratio: 2.10 [95% Confidence Interval: 1.39-3.17], p < 0.001) and ulcerative colitis (Hazard Ratio: 1.58 [95% Confidence Interval: 1.15-2.18], p = 0.005). In a propensity-matched analysis, type 2 diabetes still showed its ability to predict the risk of inflammatory bowel disease (Hazard Ratio: 2.09 [95% Confidence Interval: 1.55-2.83], p < 0.001), Crohn's disease (Hazard Ratio: 3.49 [95% Confidence Interval: 2.00 to 6.09], p < 0.001), and ulcerative colitis (Hazard Ratio: 1.76 [95% Confidence Interval: 1.20 to 2.56], p = 0.003) of robustness. CONCLUSION: In patients with type 2 diabetes mellitus, the risk of inflammatory bowel disease is higher, and the presence of gastrointestinal symptoms in patients with type 2 diabetes requires vigilance for the possibility of inflammatory bowel disease in clinical practice.

Molecular interactions between a diphenyl scaffold and PED/PEA15: Implications for type II diabetes therapeutics targeting PED/PEA15 - Phospholipase D1 interaction.

In a recent study, we have identified BPH03 as a promising scaffold for the development of compounds aimed at modulating the interaction between PED/PEA15 (Phosphoprotein Enriched in Diabetes/Phosphoprotein Enriched in Astrocytes 15) and PLD1 (phospholipase D1), with potential applications in type II diabetes therapy. PED/PEA15 is known to be overexpressed in certain forms of diabetes, where it binds to PLD1, thereby reducing insulin-stimulated glucose transport. The inhibition of this interaction reestablishes basal glucose transport, indicating PED as a potential target of ligands capable to recover glucose tolerance and insulin sensitivity. In this study, we employ computational methods to provide a detailed description of BPH03 interaction with PED, evidencing the presence of a hidden druggable pocket within its PLD1 binding surface. We also elucidate the conformational changes that occur during PED interaction with BPH03. Moreover, we report new NMR data supporting the in-silico findings and indicating that BPH03 disrupts the PED/PLD1 interface displacing PLD1 from its interaction with PED. Our study represents a significant advancement toward the development of potential therapeutics for the treatment of type II diabetes.

A comparative study of urinary levels of multiple metals and neurotransmitter correlations between GDM and T2DM populations.

OBJECTIVE: The pathogenesis of GDM and T2DM are closely related to various metals in vivo, and changes in the concentration of these metal exposures can lead to neuropathy through the DNA damage pathway caused by the accumulation of ROS. METHOD: Urine samples were analyzed for heavy metals and trace elements by ICP-MS, neurotransmitter metabolites by HPLC, 8-OH-dG by HPLC-MS and metabolomics by UPLC-MS. RESULT: Cd and Hg were risk factors for T2DM. There was a positive correlation between 8-OH-dG and neurotransmitter metabolites in both two populations. For GDM, the metabolite with the largest down-regulation effect was desloratadine and the largest up-regulation effect was D-glycine. That tyrosine and carbon metabolites were upregulated in the GDM population and downregulated in the T2DM population. CONCLUSION: The BMI, urinary Cd and Hg endo-exposure levels correlated with elevated blood glucose, and the latter may cause changes in the DNA damage marker 8-OH-dG in both study populations and trigger common responses to neurological alterations changes in the neurotransmitter. Tyrosine, carbonin metabolites, alanine, aspartate, and glutamate were signature metabolites that were altered in both study populations. These indicators and markers have clinical implications for monitoring and prevention of neurological injury in patients with GDM and T2DM.

The Impact of Three-Month Quercetin Intake on Quality of Life and Anxiety in Patients With Type II Diabetes Mellitus: An Early Data Analysis From a Randomized Controlled Trial.

BACKGROUND: Diabetes is a high-prevalence, major chronic metabolic disease demanding effective interventions. Quercetin, a phytochemical with potential health benefits, has garnered interest for its therapeutic properties. AIM: This study was designed to capture the early efficacy and clinical safety aspects following quercetin administration in patients with type II diabetes mellitus (T2DM). METHODS: The main study involved a randomized allocation procedure to assign non-insulin-treated patients attending the 4th Health Unit of Heraklion to intervention and control groups based on age and sex. The intervention group (n=50) received 500 mg of quercetin daily for 12 + (8 free intervals) + 12 weeks, alongside their usual treatment, while the control group (n=50) did not. After randomization, for the intermediary 12-week follow-up, data from 38 patients (intervention: 20; control: 18) were analyzed in this report. All subjects provided informed consent for the collection of anthropometric measurements, vital signs, daily habits data, and PiKo-6 spirometric readings. Additionally, participants responded to the Short Anxiety Screening Test (SAST) and the 36-Item Short Form Health Survey (SF-36) questionnaires. RESULTS: Thirty-eight participants were included (60% men and 40% women in the intervention group; 38.9% men and 61.1% women in the control group). In the treatment arm, Forced Expiratory Volume in the first second (FEV1) measured with PiKo-6 showed a Δ%- change for the intervention arm: +6.8%, control: -0.2% (p=0.059), systolic blood pressure; intervention: -7.4%, control: -3.7% (p=0.117), waist circumference; intervention: -1.5% control: -0.7% (p=0.455) and night-time sleep; intervention: +5.3%, control: +1.4% (p=0.926) were favourably influenced. The treatment group exhibited significant enhancements in both anxiety levels assessed by the anxiety symptoms scale (SAST-10, p=0.026) and quality of life evaluated by the SF-36 (p<0.001). CONCLUSIONS: Positive evidence is emerging for a pleiotropic effect of quercetin intake in patients with T2DM, specifically in terms of anxiety reduction and amelioration of life quality, in just 12 weeks of administration and without adverse effects, indicating clinical safety and underscoring its potential for integration in T2DM supportive care.

Linarin Ameliorates Restenosis After Vascular Injury in Type 2 Diabetes Mellitus via Regulating ADAM10-Mediated Notch Signaling Pathway.

Vascular lesions frequently arise as complication in patients diagnosed with diabetes mellitus (DM). Presently, percutaneous coronary intervention (PCI) and antithrombotic therapy serve as primary treatments. However, in-stent restenosis persists as a challenging clinical issue following PCI, lacking sustained and effective treatment. Linarin (LN) exhibits diverse pharmacological activities and is regarded as a potential drug for treating various diseases, including DM. But its specific role in restenosis after vascular injury in DM patients remains unclear. A rat model of diabetes-related restenosis was established to evaluate the role of LN on neointimal hyperplasia. Vascular smooth muscle cells (VSMCs) stimulated by high glucose (HG, 30 mM) underwent LN treatment. Additionally, an overexpression plasmid of A disintegrin and metalloproteinases (ADAM10) was constructed to transfect VSMCs. We employed CCK-8, Brdu, wound-healing scratch, and transwell migration assays to evaluate the proliferation and migration of VSMCs. Furthermore, western blot and immunofluorescence assays were utilized to investigate the expressions of ADAM10 and the downstream Notch signaling pathway in vivo and in vitro models. LN notably alleviated intimal hyperplasia after vascular injury in DM rats and reduced the protein expression of ADAM10, alongside its downstream Notch1 signaling pathway-related proteins (Notch1, NICD and Hes1) in rat carotid artery tissues. LN effectively suppressed the proliferation and migration of VSMCs induced by HG, downregulating the protein expression of ADAM10, Notch1, NICD and Hes1. Moreover, our findings indicated that ADAM10 overexpression significantly reversed LN's effects on proliferation, migration, and the expression of Notch1 signaling pathway-related proteins in HG-treated VSMCs. LN demonstrates potential therapeutic efficacy in addressing restenosis after diabetic-related vascular injury, with the ADAM10 mediated Notch signaling pathway playing a pivotal role.

Standardization parameters and synergism of source plant materials for the antidiabetic efficacy of the Rauvolfia-Citrus tea.

The introduction of glucagon-like peptide 1 (GLP-1)-based therapies has greatly improved the management of type 2 diabetes (T2D), as they ensure good blood glucose control and promote weight loss. Ingestion of standardized herbal remedies that promote the same endogenous metabolic processes affected by the GLP-1-based treatments could provide cheaper alternatives in low- and middle-income countries, where there is currently an increase in the incidence of T2D. The focus in this study was to determine quality control parameters and the prime factors for the Rauvolfia-Citrus tea (RC-tea), as used in Nigerian traditional medicine to treat T2D. We have previously shown that the RC-tea that is made by boiling leaves of Rauvolfia vomitoria Afzel. and fruits of Citrus aurantium L. causes normalization of blood glucose and reduction of ectopic lipid accumulation in genetic diabetic (BKS-db) mice and in humans with T2D. The standardized RC-tea was made by boiling 40 g dried R. vomitoria foliage and 200 g fresh C. aurantium fruits per litre. The resulting golden-brown extract is free of microbial contamination, has pH 5 and contains ca. 230 mg naringin (marker compound for C. aurantium) and 25 mg robinin (marker compound for R. vomitoria) per litre. In addition, the herbal extract has the characteristic HPLC-DAD fingerprint where the marker compounds, naringin and robinin have retention times of approximately 26.3 min and 26.9 min, respectively, when using the outlined column and gradient elution conditions. Comparative evaluations of the antidiabetic effects of the standardized RC-tea and boiling water-extracts made with C. aurantium fruits alone (CA), R. vomitoria foliage alone (RV) and a combination of CA and RV, (CA + RV) in BKS-db mice, indicate that components from R. vomitoria foliage drive the reductions in ectopic lipid accumulation, since CA-treated mice lacked this effect. However, the normalization of blood glucose arises from combination of components from the two source plant materials as administration of either CA or RV resulted in hypoglycaemia. Interestingly, treatment with the CA + RV mixture, generated by mixing individually produced CA and RV plant extracts, resulted in hyperglycaemia, possibly due to drug-drug interactions of the blood glucose-reducing components in either plant extract. Hence, our data show that the best antidiabetic outcome results from the traditional practice of boiling R. vomitoria foliage and C. aurantium fruits together.

Genistein and metformin regulate glycerol kinase and the enzymes of glycerol 3-phosphate shuttle in a differential manner in myocytes, hepatocytes and adipocytes.

Glycerol kinase (GK) and glycerol 3-phosphate dehydrogenase (GPDH) are critical in glucose homeostasis. The role of genistein and metformin on these enzymes and glucose production was investigated in C2C12, HepG2, and 3T3-L1 cells. Enzyme kinetics, Real-Time PCR and western blots were performed to determine enzyme activities and expressions of mRNAs and proteins. Glucose production and uptake were also measured in these cells. siRNAs were used to assess their impact on the enzymes and glucose production. Ki values for the compounds were determined using purified GK and GPDH. Genistein decreased GK activity by ∼45 %, while metformin reduced cGPDH and mGPDH activities by ∼32 % and âˆ¼43 %, respectively. Insignificant changes in expressions (mRNAs and proteins) of the enzymes were observed. The compounds showed dose-dependent alterations in glucose production and uptake in these cells. Genistein non-competitively inhibited His-GK activity (Ki 19.12 µM), while metformin non-competitively inhibited His-cGPDH (Ki 75.52 µM) and mGPDH (Ki 54.70 µM) activities. siRNAs transfection showed ∼50 % and âˆ¼35 % decrease in activities of GK and mGPDH and a decrease in glucose production (0.38-fold and 0.42-fold) in 3T3-L1 cells. Considering the differential effects of the compounds, this study may provide insights into the potential therapeutic strategies for type II diabetes mellitus.

Prevalence of metabolic syndrome and associated factors among patient with type 2 diabetes mellitus in Ethiopia, 2023: asystematic review and meta analysis.

BACKGROUND: Metabolic syndrome is a complex pathophysiologic state which characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidaemia. The Adult Treatment Panel III report (ATP III) of the National Cholesterol Education Programme identified the metabolic syndrome as a serious public health issue in the modern era. In Western and Asian nations, the frequency of metabolic syndrome is rising, especially in developing regions experiencing rapid socio-environmental changes, in Sub-Saharan Africa; metabolic syndrome may be present in more than 70% of people with type 2 diabetes mellitus. Therefore the objective of our study was to estimate the pooled prevalence of metabolic syndrome and associated factors among type II diabetes mellitus patient. METHOD: This systematic review and meta-analysis included original articles of cross sectional studies published in the English language. Searches were carried out in PubMed, Web of Science, Google Scholar, and grey literature Journals from 2013 to June 2023. A random-effects model was used to estimate the pooled prevalence of metabolic syndrome among type II Diabetes mellitus patient in Ethiopia. Heterogeneity was assessed using the I2 statistic. Subgroup analysis was also conducted based on study area. Egger's test was used to assess publication bias. Sensitivity analysis was also conducted. RESULTS: Out of 300 potential articles, 8 cross sectional studies were included in this systematic review and meta-analysis study. The pooled prevalence of metabolic syndrome among patient with type II diabetes mellitus in Ethiopia was found to be 64.49% (95% CI: 62.39, 66.59) and 52.38% (95% CI: 50.05, 54.73) by using NCEP/ATP III and IDF criteria, respectively. The weighted pooled prevalence of metabolic syndrome among type II diabetes mellitus patients by sub group analysis based on the study region was 63.79% (95% CI: 56.48, 71.11) and 52.23% (95%CI: 47.37, 57.22) by using NCEP/ATP III and IDF criteria, respectively. Being female and increased body mass index were factors associated with metabolic syndrome among type II diabetes mellitus patients. CONCLUSION: The prevalence of metabolic syndrome among type II patient is high. Therefore, policymakers, clinicians, and concerned stakeholders shall urge effective strategies in the control, prevention, and management of metabolic syndrome among type II diabetes mellitus.

Probing benzenesulfonamide-thiazolidinone hybrids as multitarget directed ligands for efficient control of type 2 diabetes mellitus through targeting the enzymes: α-glucosidase and carbonic anhydrase II.

Diabetes mellitus is a chronic metabolic disorder characterized by improper expression/function of a number of key enzymes that can be regarded as targets for anti-diabetic drug design. Herein, we report the design, synthesis, and biological assessment of two series of thiazolidinone-based sulfonamides 4a-l and 5a-c as multitarget directed ligands (MTDLs) with potential anti-diabetic activity through targeting the enzymes: α-glucosidase and human carbonic anhydrase (hCA) II. The synthesized sulfonamides were evaluated for their inhibitory activity against α-glucosidase where most of the compounds showed good to potent activities. Compounds 4d and 4e showed potent inhibitory activities (IC50 = 0.440 and 0.3456 µM), comparable with that of the positive control (acarbose; IC50 = 0.420 µM). All the synthesized derivatives were also tested for their inhibitory activities against hCA I, II, IX, and XII. They exhibited different levels of inhibition against these isoforms. Compound 4d outstood as the most potent one against hCA II with Ki equals to 7.0 nM, more potent than the reference standard (acetazolamide; Ki = 12.0 nM). In silico studies for the most active compounds within the active sites of α-glucosidase and hCA II revealed good binding modes that can explain their biological activities. MM-GBSA refinements and molecular dynamic simulations were performed on the top-ranking docking pose of the most potent compound 4d to confirm the formation of stable complex with both targets. Compound 4d was screened for its in vivo antihyperglycemic efficacy by using the oral glucose tolerance test. Compound 4d decreased blood glucose level to 217 mg/dl, better than the standard acarbose (234 mg/dl). Hence, this revealed its synergistic mode of action on post prandial hyperglycemia and hepatic gluconeogenesis. Thus, these benzenesulfonamide thiazolidinone hybrids could be considered as promising multi-target candidates for the treatment of type II diabetes mellitus.

A new era for food in health? The FDA announces a qualified health claim for yogurt intake and type 2 diabetes mellitus risk reduction.

INTRODUCTION: Over the last two decades research has grown regarding dairy intake and health. It has been reported by many that yogurt intake may be associated with reduced risk of type 2 diabetes mellitus (T2D). In this report, the United States Food and Drug Administration (FDA) decision to announce a qualified health claim for yogurt products regarding reduced risk of T2D in response to a Danone North America petition is discussed. METHODS: Relevant literature cited in the petition along with supporting evidence from PubMed and Google Scholar databases until April 1st, 2024 were used. Literature was found using relevant keywords. RESULTS: On March 1st, 2024, the United States Food and Drug Administration (FDA) announced the first ever qualified health claim, stating that eating yogurt regularly may reduce the risk of T2D according to limited scientific evidence. The enforcement discretion letter was critically reviewed and discussed regarding its future implications for people with T2M and public health. CONCLUSIONS: It is unclear how this FDA decision will affect public health and nutrition in the long-term. Limited scientific evidence suggests that at least 3 servings of yogurt per week may reduce the risk of T2D incidence for the general population. Yogurt will not cure or treat people with T2D.

Long-Term Adherence to the Mediterranean Diet Reduces 20-Year Diabetes Incidence: The ATTICA Cohort Study (2002-2022).

This study aimed to evaluate the association between adherence to the Mediterranean diet and the 20-year incidence of type II diabetes mellitus (T2DM) among adults from the ATTICA study. This study involved a prospective cohort of 3042 men and women recruited at baseline from the Attica region in Greece. Sociodemographic, anthropometric, lifestyle, and clinical characteristics were evaluated at baseline and follow-up examinations; adherence to the Mediterranean diet was assessed through the MedDietScore (range 0-55); four Mediterranean diet trajectories were identified (i.e., increasing, decreasing, and sustained high and sustained low adherence levels). For the present analysis, data from 2000 individuals with complete information were used (age 43 ± 13 years; 49% men). Over the 20-year period, 26.3% (95%CI 24.4%, 28.3%) of participants developed T2DM; men exhibited a 1.5-times higher incidence compared to women (p < 0.001). Individuals consistently close to the Mediterranean diet throughout the studied period had an improved glycemic and lipidemic profile (at baseline and at 10-y follow-up) (all p-values < 0.001) and showed a 21% reduction in their 20-year risk of developing T2DM compared to those who were consistently away (RR = 0.79, 95%CI 0.47, 0.86). A long-term adherence to the Mediterranean diet is protective against the onset of T2DM and, therefore, could be incorporated in public health actions for the prevention of the disease.