Hyperglycemia In Diabetic Patients Research Articles

Insulin Adjustments for Hospitalized COVID-19 Patients on a Fixed Dexamethasone Protocol

Introduction: COVID-19, in combination with steroid treatment, is known to propagate hyperglycemia in diabetic patients. The purpose of this study was to establish a new insulin protocol for diabetic patients with COVID-19 on the dexamethasone protocol for better glycemic control. Research Design and Methods: This was a retrospective cohort study conducted at NYU Langone Long Island Hospital from 1 July 2020 to 1 July 2021. Eligible cases had to meet the following inclusion criteria: age of 18 years or greater, history of or new-onset diabetes, diagnosis of COVID-19 and receiving the 10 day dexamethasone treatment, length of stay of at least 3 days with a minimum of 48 h of glucose monitoring, and requiring basal and prandial insulin with correction during hospital stay. Data were collected using the hospital’s electronic record system. The total basal, prandial, and daily doses of insulin on the day at which glycemic control was achieved, or if glycemic control was not achieved by the discharge date, then on the completion date of the dexamethasone treatment, were collected and assessed. Results: A total of 145 patient cases were analyzed. About 46% of patients achieved glycemic control. The average insulin dose required was 0.67 (0.61–0.74) unit/kg. The mean total dose of insulin was 59 units. The mean total basal dose was 21 units. The mean total prandial dose was 38 units. The average prandial doses were higher than the basal doses for all participants. Conclusions: Diabetic patients with COVID-19 on dexamethasone should be initiated on at least 0.6–0.7 u/kg of insulin to achieve glycemic control.

The mechanism of Chebulae Fructus Immaturus promote diabetic wound healing based on network pharmacology and experimental verification

Ethnopharmacological relevanceDiabetic ulcers (DUs) are commonly seen in the lower limbs, especially the feet. Long-term hyperglycaemia in diabetic patients may cause peripheral microvascular damage, which affects local blood flow reconstruction when the skin is ruptured. This results in delayed or even non-healing of skin wounds. Chebulae Fructus Immaturus (CFI) is a traditional Chinese medicine. According to traditional Chinese medicine theory, CFI belongs to the lung channel and large intestine channel. Clinical data confirm a significant clinical effect of CFI in the treatment of skin diseases. CFI can be safely used to treat wounds due to its natural active ingredients. Aim of the studyThis study utilised HPLC-ESI-QTOF-MS/MS combined with network pharmacology to investigate the mechanism of Chebulae Fructus Immaturus extract (CFIE) in the treatment of DU. Moreover, the efficacy of CFIE on DU was verified in vitro and in vivo by constructing cell models and mouse models. Materials and methodsThe main ingredients of CFIE were identified by HPLC-ESI-QTOF-MS/MS. The targets of these ingredients were predicted by database analysis and intersected with the DU targets. Gene ontology (GO) was used for functional enrichment of differential genes, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for enrichment of signalling pathways related to the differential genes. The network pharmacology findings were validated in vivo and in vitro, and the affinity of key targets and active components was assessed using molecular docking. ResultsTwenty-nine compounds of CFIE were identified by HPLC-ESI-QTOF-MS/MS, and their potential targets were predicted. Among these, 41 targets were associated with DU. KEGG enrichment analysis showed that the PI3K/AKT and HIF-1α signalling pathways were significantly enriched, which may be related to the promotion of wound angiogenesis. In vitro cell experiments showed that CFIE promoted the proliferation, migration and angiogenesis of HUVECs, and also affected the expression of pathway-related proteins. In vivo experiments showed that CFIE increased the expression of pathway-related proteins in wound tissue and promoted the formation of blood vessels. ConclusionsIn summary, this study systematically demonstrated the possible therapeutic effects and mechanisms of CFIE on DU through network pharmacology analysis and experimental verification. The results revealed that CFIE can accelerate the angiogenesis of diabetic wounds through the PI3K/AKT and HIF-1α signalling pathways, ultimately promoting the healing of diabetic wounds.

Revolutionizing fracture fixation in diabetic and non-diabetic rats: High mobility group box 1-based coating for enhanced osseointegration.

Chronic inflammation and hyperglycemia in diabetic patients increase the risk of implant failure and impaired fracture healing. We previously developed and characterized a titanium (Ti) coating strategy using an imidazolium-based ionic liquid (IonL) with a fully reduced, non-oxidizable High Mobility Group Box 1 (HMGB1) isoform (Ti-IonL-HMGB1) to immunomodulate tissue healing. In this study, we used an open reduction fracture fixation (ORIF) model in non-diabetic (ND) and diabetic (D) rats to further investigate the effectiveness of this Ti-IonL-HMGB1 coating on orthopedic applications. Ninety male Lewis rats (12-15weeks) were divided into D (n=45) and ND (n=45) groups that were distributed into three subgroups based on the type of local treatment received: Ti (uncoated Ti), Ti-IonL, and Ti-IonL-HMGB1 implants. Fracture healing and osseointegration were evaluated using microtomographic, histological, and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), Runt-related transcription factor 2 (RUNX2), and HMGB1 markers at 2, 10, and 21days post-ORIF. Scanning Electron Microscopy verified the coating stability after placement. Microtomographic and histological analysis demonstrated increased fracture healing and osseointegration for ND rats in all treatment groups at 10days, with impaired healing for D rats. Immunohistochemical analysis exhibited elevated PCNA+ and RUNX2+ cells for D animals treated with Ti-IonL-HMGB1 at 21days compared to all other groups. The immunohistochemical marker HMGB1 was elevated at all time points for D animals in comparison to ND animals, yet was lowered for D tissues near the Ti-IonL-HMGB1 treated implant. Improved osseous healing was demonstrated in D animals with Ti-IonL-HMGB1 treatment by 21days, compared to D animals with other treatments. To the best of our knowledge, this is the first study analyzing Ti-IonL-HMGB1 implantation in an injury site through ORIF procedures in ND and D rats. This surface approach has potential for improving implanted biomaterials in diabetic environments.

Comparative solubilization of Gliclazide in solutions of two anionic micelles with asymmetrical hydrophobic chain length: An experimental and theoretical analysis

Gliclazide (GCL) is used widely for reducing hyperglycemia in diabetic patients. It has poor solubility which leads to low oral bioavailability because of significant first-pass metabolism. In this work, we have employed two anionic micellar solutions of different hydrophobic chain lengths to solubilize GCL. They are sodiumtetradecyl sulfate (STS) and sodiumdodecyl sulfate (SDS). Our results reveal that longer hydrophobic chain was better suited for solubilizing GCL. The drug-surfactant interactions were assessed through FT-IR, conductivity, UV-Spectrophotometry, dynamic light scattering and antioxidant study. The results were compared with computational studies. There was negative free energy of micellization and positive entropy of micellization GCL + STS and GCL + SDS systems predicting spontaneity of the processes as calculated from the conductivity experiments. From the UV spectral studies, using Benesi-Hildebrand (B-H) equation, the binding constants demonstrated higher value for GCL + STS (0.286 M−1) compared to GCL + SDS (0.0231 M−1). The antioxidant properties of the above two combinations show that STS (93.14 %) has higher radical scavenging activity (RSA %) compared to SDS (77.45 %). Protein binding studies too indicated higher binding constant for STS than SDS with the drug. The docking model also supported the above findings. The longer hydrophobic chain length facilitated the solubilization of GCL with improved properties. This study offers a novel drug formulation for widely used drug GCL.

Discovery of triazole tethered thymol/carvacrol-coumarin hybrids as new class of α-glucosidase inhibitors with potent in vivo antihyperglycemic activities

Keeping in view the inhibitory potential of monoterpenes thymol and carvacrol as well as coumarin nucleus against α-glucosidase, novel series of thymol/carvacrol-coumarin hybrids was designed, synthesized and evaluated for α-glucosidase inhibitory potential. Among the series of hybrid molecules, AS14 with IC50 value of 4.32 ± 0.11 μM was selective α-glucosidase inhibitor over α-amylase (IC50 = 37.36 ± 0.84 μM). AS14 was non-toxic toward mouse normal fibroblast cells (L929: IC50 > 100 μM). Molecular docking and dynamic simulation studies confirmed desired interactions of AS14 with α-glucosidase responsible for the inhibition of its catalysis capabilities. Acute oral toxicity study confirmed AS14 as safer molecule for in vivo pharmacological investigations with LD50 value of 300 mg/kg. AS14 also showed acute hypoglycaemic effects [reduction in blood glucose levels at 1 hr of administration in maltose loading test (at 10 and 20 mg/kg by 62.65 % and 70.12 %) and sucrose loading test (at 10 and 20 mg/kg by 59.65 % and 60.23 %), respectively] as well as long term (28 days) fasting blood glucose reduction (At day 28: 10 mg/kg = 54.69 % and 20 mg/kg = 62.23 % reduction in fasting blood glucose levels) capabilities in streptozotocin induced diabetic rats. Overall study represents, AS14 as potential α-glucosidase inhibitor with adequate efficacy and safety profile and act as an effective hit lead for the further development of potent and safer α-glucosidase inhibitors for the management of postprandial hyperglycemia in diabetic patients.

Eremophila purpurascens: Anti-oxidant, Anti-hyperglycemic, and Hepatoprotective Potential of Its Polyphenolic Rich Leaf Extract and Its LC-ESI-MS/MS Chemical Characterization and Standardization.

The genus Eremophila, despite comprising more than 250 species, has scarce literature studies that could be traced concerning the chemical profile and bioactivity of Eremophila purpurascens. The current study targets the investigation of the in vitro and in vivo anti-oxidant, anti-hyperglycemic, and hepatoprotective potential of the polyphenol-rich leaf extract of E. purpurascens (EP). EP showed promising total anti-oxidant capacity with IC50 values of 106 and 114 μg/mL in 2,2'-azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) and diphenyl-1-picrylhydrazyl (DPPH) assays, respectively, with total anti-oxidant capacities of 331, 245, and 1767 μmol/g in ABTS, DPPH, and ferric reducing anti-oxidant power assays, respectively. In HepG2 cells, pre-treated with CCl4, a dose of 100 μg/mL EP ameliorated the reduced superoxide dismutase and glutathione levels and total anti-oxidant capacity with values of 312.5 U/mL, 15.47 mg/dL, and 1.03 nmol/mL, respectively. In vitro anti-diabetic evaluation using 3T3-L1 adipocyte culture showed that at a dose of 30 μg/mL, the EP extract elicited a 6.3% decrease in the concentration of glucose (22.4 mmol/L), showing significant amelioration with regard to pioglitazone and insulin. EP also demonstrated elevated serum insulin by 77.78% with a marked reduction in fasting blood glucose level by 64.55% relative to the streptozotocin diabetic rats in vivo. EP also relieved the liver stress markers both in vitro in CCl4 and in vivo in tamoxifen (TAM) models. EP markedly decreased TAM toxicity, as demonstrated by the decline in the liver stress markers, ALT and AST, by 36.1 and 51.1%, respectively. It also relieved the oxidative stress triggered by TAM, as revealed by the reduction in the levels of TBARs and TNF-α by 21.4 and 40%, respectively. Liquid chromatography electrospray ionization mass spectrometry of EP revealed a total of twelve peaks belonging to phenylpropanoids, lignans, and phenolics, where verbascoside and pinoresinol-4-O-β-d-glucoside represented the most abundant secondary metabolites. The docking experiment showed that tri-O-galloyl-hexoside had the best fitting within the NADPH oxidase active sites with binding energy (ΔG = -81.12 kcal/mol). Thus, the plant can be of beneficial value in the control of hyperglycemia in diabetic patients, besides its prophylactic potential against hepatic complications.

Diabetes Mellitus: A Leading Cause of Death Worldwide

Diabetes mellitus, or commonly known as diabetes, is a metabolic disorder characterized by chronic hyperglycemia which results in insulin resistance, impaired insulin synthesis, or sometimes both. Diabetes affects roughly 400 million people worldwide and the majority being those who are from middle to low income countries. With 1.5 million diabetes related deaths worldwide each year, this literature review aims to give information about the 2 types of diabetes and also highlighting the appropriate preventative measures. Type 1 diabetes refers to the lack of insulin production and type 2 diabetes refers to lower production of insulin and increased insulin resistance; both will result in hyperglycemia in diabetic patients. Furthermore, this literature review also aims to explore and describe the pathogenesis and treatments of the 2 types of diabetes.

Pancreatic biomarkers: role in diabetes mellitus

Diabetes mellitus refers to a group of diseases that cause high blood sugar levels. The most common type is type 2 diabetes, which is caused by insulin resistance and inadequate insulin production. However, diabetes can also result from conditions affecting the exocrine pancreas. Both type 1 and type 2 diabetes patients may experience changes in their pancreatic exocrine function, leading to reduced levels of fecal elastase-1 in many cases. This review article focuses on the role of specific pancreatic biomarkers in diabetes mellitus, including cholecystokinin, trypsin, chymotrypsin, carboxypeptidase, amylase, lipase, secretin, elastase-1, and retinol-binding protein 4 about recent advances and discoveries, significant gaps in the literature, current debates, and potential directions for future research related to these biomarkers about diabetes mellitus. This review article discusses various biomarkers related to pancreatic exocrine and endocrine function and their implications in diabetes. It suggests that gut cholecystokinin may play a role in lowering glucose synthesis through a neural network and resistance to it could contribute to hyperglycemia in diabetic patients. It also discusses the use of various markers such as serum trypsin concentration, amylase and lipase levels, pancreatic elastase levels, and fasting secretin levels to assess pancreatic exocrine function. Additionally, the article explores the role of carboxypeptidase E in the endocrine and neurological systems and its association with disorders. Moreover, it also highlights the involvement of retinol-binding protein 4 in the development of type 2 diabetes and insulin resistance.

Inhibitory Potential of Different Bilberry (Vaccinium myrtillus L.) Extracts on Human Salivary α-Amylase.

Recently, consumer preferences for bilberries have increased markedly. This fact is probably related to their natural constituents, such as phenolic compounds including anthocyanins and tannins, as well as the vitamins and minerals they contain. Phenolic compounds are known for their numerous beneficial effects on human health. Moreover, bilberry fruits have been shown to inhibit the activity of carbohydrate hydrolyzing enzymes, which can significantly decrease the postprandial increase in blood glucose levels. Thus, the aim of the present study is to investigate the inhibitory effect of Vaccinium myrtillus L. extracts on key enzyme α-amylase, linked to type 2 diabetes. No data have been published on the inhibitory properties of Vaccinium myrtillus L. fruits growing wild in Bulgaria against carbohydrate enzymes. Bilberry extracts were analyzed for total polyphenols, total anthocyanin content, antioxidant activity and their inhibitory properties against α-amylase. The contents of flavonols, anthocyanins and stilbenes were determined by HPLC analysis. The identified flavonols in the analyzed bilberry extracts were mainly represented by quercetin derivatives as rutinoside. The predominant anthocyanins for both aqueous and organic solvents were delphinidin-3-galactoside and malvidin-3-glucoside. The results revealed that bilberry extracts are effective inhibitors of α-amylase, with IC50 values from 20.8 to 194.8 μg GAE/mL. All the samples proved to have antioxidant activity measured by three different in vitro assays (FRAP, CUPRAC and DPPH). The inhibitory properties of V. myrtillus L. extracts may provide a new direction in the development and research of new pharmaceuticals for the suppression of postprandial hyperglycemia in diabetic patients.

The effect of vitamin D deficiency on glycemic control in patients with type 2 diabetes mellitus

Multiple factors are involved in the development of type 2 diabetes mellitus (T2DM), but an imbalance between free radical formation and antioxidant removal is the main cause of diabetic complications. Micronutrients with antioxidant properties may have a role in the development of diabetes mellitus (DM) and its complications. Vitamin D has recently been found to have membrane antioxidant effect and a relationship to the development of T2DM, as it can modify its risk. Whether vitamin D deficiency has an effect on hyperglycemia in diabetic patients or not need further study. Our aim was to examine the effect of vitamin D deficiency on glycemic control in T2DM. We examined the vitamin D levels of 100 patients with T2DM and correlated them with fasting blood sugar and glycated hemoglobin A1c (HbA1c) levels. High levels of fasting blood sugar and HbA1c levels were significantly associated with vitamin D deficiency. Vitamin D deficiency negatively affects glycemic control in patients with T2DM.

A proteoglycan isolated from Ganoderma lucidum attenuates diabetic kidney disease by inhibiting oxidative stress-induced renal fibrosis both in vitro and in vivo.

Ganoderma lucidum (G. lucidum) was regarded as "miraculous herb" by the Chinese and recorded detailly in the "Shen Nong Ben Cao Jing" as a tonic to improve health and prolong life. A proteoglycan (namely, FYGL) was extracted from Ganoderma lucidum, which was a water-soluble hyperbranched proteoglycan, and was found to be able to protect pancreatic tissue against oxidative stress damage. Diabetic kidney disease (DKD) is a complication of diabetes, but the effective treatment is still lack. Chronic hyperglycemia in diabetic patients induce the accumulation of ROS, which injure the renal tissue and lead to the renal dysfunction. In this work, the efficacy and target mechanics of FYGL on diabetic renal function were investigated. In the present study, the mechanism of the reno-protection of FYGL was analyzed on diabetic db/db mice and rat glomerular mesangial cells (HBZY-1) induced by high glucose (HG) with palmitate (PA) (HG/PA). In vitro, the levels of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) were evaluated by commercial kits. the expressions of NOX1 and NOX4, phosphorylation of MAPK and NF-κB, and pro-fibrotic proteins were measured by Western blot. In vivo, diabetic db/db mice were gavaged with FYGL for 8 weeks, body weight and fasting blood glucose (FBG) were tested weekly. On 8th week, the serum, urine and renal tissue were collected for glucose tolerance test (OGTT), redox indicator (SOD, CAT, GSH and MDA), lipid metabolism (TC, TG, LDL and HDL), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), 8-oxo-deoxyguanosine (8-OHdG), and the changes of histopathology and expression of collagen IV and AGEs. The results in vitro showed that FYGL significantly inhibited the HG/PA-induced HBZY-1cells proliferation, ROS generation, MDA production, promoted SOD activity, and suppressed NOX1, NOX4, MAPK, NF-κB, and pro-fibrotic proteins expression. In addition, FYGL markedly alleviated blood glucose, antioxidant activity and lipid metabolism, improved renal functions, and relieved renal histopathological abnormalities, especially renal fibrosis. The antioxidant activity of FYGL can reduce ROS caused by diabetes and protect renal from oxidative stress-induced dysfunction, thereby improving renal function. This study shows that FYGL has the potential to treat diabetic kidney disease.

The effect of 6% hydroxyethyl starch 130/0.4 preloading on the blood glucose levels in diabetic patients undergoing orthopedic surgery with spinal anesthesia: a randomized pilot study.

Perioperative hyperglycemia can occur in surgical patients and may increase postoperative morbidity and mortality, especially in patients with diabetes. Therefore, we conducted the present study to evaluate whether the administration of 6% hydroxyethyl starch (HES)-130/0.4 increases blood glucose levels in patients with diabetes. Forty patients undergoing lower limb surgery under spinal anesthesia were randomly allocated into two groups according to the fluids administered 20 min before spinal anesthesia (Group L, lactated Ringer's solution; Group H, 6% HES-130/0.4). Patient characteristics, intraoperative variables, blood glucose levels, mean blood pressure (MBP), and heart rate (HR) were recorded at five time-points (0, 20, 60, 120, and 240 min). A total of 39 patients were analyzed (Group L, n = 20; Group H, n = 19). The amount of intraoperative fluid was significantly higher in Group L than in Group H (718.2 ml vs. 530.0 ml, P = 0.010). There were no significant differences in the changes in blood glucose levels, HR, or MBP between the two groups (P = 0.737, P = 0.896, and P = 0.141, respectively). Serial changes in mean blood glucose levels from baseline also showed no significant differences between the groups (P = 0.764). There were no significant changes in blood glucose levels when lactated Ringer's solution or 6% HES-130 was used. When compared to the lactated Ringer's solution, no evidence that 6% HES-130/0.4 produces hyperglycemia in diabetic patients could be found. Further evaluation of larger populations is needed.

The Relationship between Hba1c Levels and Body Mass Index with Severity of Diabetic Neuropathy at Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia

Introduction: Diabetic neuropathy is the most common microvascular complication in diabetes mellitus patients. Diabetic neuropathy is known to be associated with conditions of hyperglycemia and obesity that occur in diabetic patients. Hyperglycemia in diabetic patients can be monitored through HbA1c levels. This study aimed to assess the relationship between HbA1C values and body mass index with the severity of diabetic neuropathy based on nerve conduction velocity examination.
 Methods: A study with a cross-sectional design with a total of 25 subjects with diabetes mellitus. The severity of diabetic neuropathy was determined based on Baba's diabetic neuropathy classification (BDC), degrees 0 to 4. In all study subjects, plasma HbA1c levels were examined, and body mass index was assessed. The relationship between categorical variables was tested with the chi-square test, and the relationship between numerical and categorical variables with a one-way ANOVA test, the value was considered statistically significant if the p-value <0.05.
 Results: The 25 subjects with diabetes found a mean age of 54.88 (±SD 8.918) years, with a gender distribution of 46.4% for women and 42.9% for men. The average HbA1c level was 8.9560 (± 2.21850), and the highest body mass index was obese (50%). There was a significant relationship between HbA1c levels and the severity of diabetic neuropathy based on electrophysiological examination (p<0.05), but there was no significant relationship between the value of body mass index and the severity of diabetic neuropathy.
 Conclusion: Increased HbA1c levels are associated with increased severity of peripheral neuropathy in patients with diabetes mellitus.

The alteration of advanced glycation end products and its potential role on bone loss under microgravity

Bone loss occurs in astronauts during long-term space flight, and hardly recover to the normal level after back to the earth. This is because the mechanism of microgravity-induced osteoporosis is still unclear. Advanced glycation end products (AGEs) are formed between reducing sugars and long-lived proteins and are verified to be the pathogenic mechanism for diabetic and aging osteoporosis. These non-enzymatic glycation products are considered to have adverse effects on bone metabolism and bone quality which consist of bone microstructure and bone organic matrix. However, whether AGEs accumulation happened under microgravity is not clear yet. AGEs accumulation can be induced by hyperglycemia in diabetic patients and senior people. Hyperglycemia was also found to occur in astronauts during spaceflight or under simulated microgravity, however, whether it also can cause bone matrix AGEs accumulation remains unrevealed, and whether AGEs involve in the disuse osteoporosis is as well not clear yet. Therefore, in this study, we explored the AGEs changes and genesis, together with its potential relationship with disuse osteoporosis under simulated microgravity by using a rat tail-suspended model. Sixteen 8-week-old female Sprague-Dawley rats were randomly distributed into control (CON) and tail-suspension (TS) groups. After 21-days of an experiment, fluorescent total AGEs and pentosidine in bone matrix were separately detected by fluorescence microscope and High Performance Liquid Chromatography (HPLC); soluble AGEs and glucose-related biomarkers in serum were detected by ELISA; bone microstructure was evaluated by Micro-CT, and mRNA expression of bone metabolism biomarkers (OCN, ALP, RANKL/OPG) in bone was determined by QPCR. Results showed that after tail-suspension AGEs fluorescent intensity and PEN content increased in trabecular bone while no significant changes in cortical bone; serum glucose increased and was positively correlated with bone matrix AGEs; trabecular bone microstructure was deteriorated, ALP and OCN mRNA expression decreased while RANKL/OPG mRNA expression increased, and all of them showed correlations with bone matrix AGEs. The results suggested under simulated microgravity, bone matrix AGEs accumulation may be attributed to the elevated serum glucose, and preferred to occur in trabecular bone first. AGEs accumulation in bone matrix accompanied negative effects on trabecular bone microstructure and bone metabolism activities under simulated microgravity, suggesting AGEs accumulation may be a culprit in disused bone loss.

"Ficus johannis Boiss. leaves ethanolic extract ameliorate streptozotocin-induced diabetes in rats by upregulating the expressions of GCK, GLUT4, and IGF and downregulating G6P".

The leaves of Ficus johannis Boiss (F. johannis), commonly known as Fig tree, Anjir, and Teen, are used by the folk medicinal practitioners in Iran for controlling hyperglycemia in diabetic patients. This study investigated the pharmacological basis for antidiabetic effect of the ethanolic extract of F. johannis leaves using in vitro and in vivo experimental models. Qualitative screening of phytochemicals, estimation of total phenolic and flavonoid contents, and in vitro antioxidant and α-amylase inhibition assays were performed. Moreover, the High-performance liquid chromatography (HPLC) quantification, acute toxicity, glucose tolerance, and in vivo antidiabetic effect along with the evaluation of gene expressions involved in diabetes mellitus were carried out. Significant quantities of phenolic (71.208 ± 2.89 mgg-1 GAE) and flavonoid (26.38 ± 3.53 mgg-1 QE) were present. Inhibitory concentration (IC50) of the plant extract exhibited an excellent in vitro antioxidant (IC50 = 33.81µg/mL) and α-amylase (IC50 = 12.18µg/mL) inhibitory potential. The HPLC analysis confirmed the gallic acid (257.79 mgg-1) as main constituent of the extract followed by kaempferol (22.86 mgg-1), myricetin (0.16 mgg-1), and quercetin (3.22 mgg-1). Ethanolic extract displayed glucose tolerance in normo-glycemic rats. Streptozotocin-induced hyperglycemia declined dose dependently in the extract treated rats with improvement in lipid profile and liver and renal function biomarkers. The F. johannis-treated groups showed an increase in mRNA expressions of glucose transporter 4 (GLUT-4), glucokinase, insulin growth like factor 1 and peroxisomal proliferator activating receptor gamma in pancreas. However, the Glucose-6-phosphatase was downregulated. Present study suggests that the ethanolic extract of F. johannis leaves demonstrates a good anti-diabetic profile by improving insulin sensitivity, GLUT-4 translocation, and carbohydrate metabolism while inhibiting lipogenesis.

Phenolic profile, α-amylase inhibition and molecular docking scrutiny of the trunk bark of Pinus pinea growing in Tunisia

The phenolic profile of ethyl acetate and methanol extracts from the trunk bark of Pinus pinea growing in Tunisia was determined using Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-HRMS) method and their anti-α-amylase potential and the mode of inhibition were determined in a kinetic study. Methanol extract was found to be richer in phenolics. Eighteen constituents were identified in ethyl acetate extract with trans-taxifolin (7.57 g/kg), as the main compound. Eighteen compounds were detected in methanol extract with ellagic acid (88.06 g/kg), as the major constituent. Ethyl acetate and methanol extracts inhibited α-amylase with half-maximal inhibitory concentration (IC50) values of 9.16 and 8.33 μg/mL, respectively. The ethyl acetate and methanol extracts exerted a non-competitive and a competitive inhibition on α-amylase enzyme, respectively. This activity was supported by molecular docking analysis of some major compounds of both extracts. All these compounds showed a low binding energy and they could bind with the key residues including ASP-206 and GLU-230 of the α-amylase enzyme and these ligands were also surrounded by other active site residues. These findings suggest that P. pinea extracts could serve as safe and efficient α-amylase inhibitors to treat postprandial hyperglycemia in diabetic patients.

Fenugreek (Trigonella foenum-graecum): Nutraceutical values, phytochemical, ethnomedicinal and pharmacological overview

• Current review deals with the traditional knowledge of active components in fenugreek ( Trigonella foenum-graecum ). • Fenugreek is highly potent medicinal herb which can be used in the modern medicine system. • Review provides several health & therapeutic benefits as well as nutraceutical properties of fenugreek. Trigonella foenum-graecum Linne, commonly known as fenugreek, is a herb with medicinal and nutraceutical values which has been used from ancient times in the Indian medicine system. According to the literature analysis, the presence of various bioactive compounds such as alkaloids, flavonoids, saponins, fibers, fatty acids, etc. contributes to the therapeutic potential of the herb. In context to its therapeutic competency, fenugreek has anti-biotic, anti-oxidant, anti-carcinogen properties and controls hyperglycemia in diabetic patients. The present review is an attempt to highlight the nutraceutical, health and therapeutic benefits of fenugreek.

Infarct size, inflammatory burden and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) with pleiotropic beneficial effects. Nowadays, the inflammation response in the setting of acute myocardial infarction (AMI) has been proposed as a potential pharmacological intervention target. In this setting, we tested the hypothesis that the SGLT2-I displays anti-inflammatory effect along with glucose-lowering properties. We investigated the relationship between stress hyperglycemia, inflammation burden and infarct size in a cohort of type 2 diabetic AMI patients treated with SGLT2-I versus other oral anti-diabetic (OAD) agents alone. Methods In this multicenter international registry, all diabetic patients with AMI treated with percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the admission anti-diabetic therapy, patients were divided into those receiving SGLT2-I versus other OAD agents alone. Patients on insulin therapy alone or combined with OAD agents were excluded from the study. The following inflammatory markers were evaluated at different time points: total white blood cell, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR), C-reactive protein. Infarct size was assessed by peak troponin levels and echocardiographic parameters. Results The final study population consisted of 583 patients hospitalized for AMI (both STEMI and NSTEMI) classified as SGLT2-I users (n=98) versus other OAD agents alone (n=485). Admission hyperglycemia was more prevalent among the other OAD agents group. Reduced infarct size was detected in patients treated with SGLT2-I compared to those treated with other OAD agents alone. Both at admission, and after 24 hours, inflammatory indices were significantly higher in patients treated with other OAD agents alone, with a significant increase in neutrophils levels at 24 hours, compared to the SGLT2-I group. In multivariate analysis, SGLT2-I emerged as a significant predictor of reduced inflammatory response (OR 0.45, 95% CI 0.27–0.75, p=0.002), together with peak troponin values, independently of age, admission creatinine values and admission glycemia. Conclusions Type 2 Diabetic patients hospitalized for AMI and receiving SGLT2-I exhibited modest inflammatory response and myocardial damage/infarct size compared to other OAD agents alone, independently of glucose-metabolic control. Our findings pave the way for new pathophysiological and therapeutic insights regarding the cardioprotective effect of SGLT2-I in the setting of coronary artery disease. Funding Acknowledgement Type of funding sources: None.

Do Dipeptidyl Peptidase-4 Inhibitors Increase the Risk of Heart Failure in Patients with Type 2 Diabetes?

Dipeptidyl peptidase-4 inhibitors (DDP-4Is) or gliptins have been extensively studied in recent years. These studies have shown the safety and efficacy of gliptins in managing hyperglycemia in diabetic patients. However, there is an ongoing debate on whether DDP-4Is are associated with a higher risk for developing heart failure. It is expected that long-term data from patients who are currently prescribed DDP-4Is will provide a clearer understanding of their potential benefits. This should also help guide the development of future guidelines. The focus of this perspective is on associations between the "use of DPP-4Is" and "increased risk of heart failure". Thus, we examine several key publications and reviews on clinical trials on this class of oral antidiabetic medications. For this communication, the pertinent literature has been critically analyzed to provide an evidence-based overview of the evolving concept of DPP-4Is-induced risk of heart failure.

Hyperglycemia in Severe and Critical COVID-19 Patients: Risk Factors and Outcomes.

Background: Hyperglycemia is commonly seen in critically ill patients. This disorder was also seen in coronavirus disease 2019 (COVID-19) patients and was associated with a worse prognosis. The current study determined the prevalence, risk factors, and prognostic implications of hyperglycemia in COVID-19 patients.Method: This was a retrospective observational study performed in an intensive care unit for COVID-19 patients. Electronic data of COVID-19 patients admitted to the intensive care unit from August 2nd to October 15th, 2021, were collected. Patients were divided into non-hyperglycemia, hyperglycemia in diabetic patients, and hyperglycemia in non-diabetic patients. Primary outcomes were 28-day and in-hospital mortalities. Multinomial logistic regression and multivariable Cox regression models were used to determine the risk factors for hyperglycemia and mortality, respectively.Results: Hyperglycemia was documented in 65.6% of patients: diabetic patients (44.8%) and new-onset hyperglycemia (20.8%). In-hospital and 28-day mortality rates were 30.2% and 26.1%, respectively. Respiratory failure, corticosteroid therapy, and a higher level of procalcitonin were risk factors for hyperglycemia in diabetic patients, whereas cardiovascular diseases, respiratory failure, and higher aspartate aminotransferase/glutamate aminotransferase ratio were risk factors for hyperglycemia in non-diabetic patients. The risk of the 28-day mortality rate was highest in the new-onset hyperglycemia (hazard ratio [HR] 3.535, 95% confidence interval [CI] 1.338-9.338, p=0.011), which was higher than hyperglycemia in type 2 diabetes mellitus patients (HR 1.408, 95% CI 0.513-3.862, p=0.506).Conclusion: Hyperglycemia was common in COVID-19 patients in the intensive care unit. Hyperglycemia reflected the disease severity but was also secondary to therapeutic intervention. New-onset hyperglycemia was associated with poorer outcomes than that in diabetic patients.