Reduction In Glucose Research Articles

Effects of Life Style Modifications (Dietary and Exercise) on Insulin Resistance in Egyptian Men with Impaired Glucose Tolerance

Insulin resistance (IR) is considered one of the most serious chronic conditions. Although IR usually starts silently (euglycemic state), it can seriously lead to impaired glucose tolerance and the development of diabetes mellitus (DM) with other debilitating complications. The current study was conducted for four months to test the application of healthy dietary modification and/or regular programmed exercise on 120 Egyptian male subjects with high blood glucose levels, high insulin levels, and high homeostatic model assessment of insulin resistance (HOMA-IR). They were assigned into 4 groups. The first group received no intervention (control). The second group received healthy dietary intervention. The third group received regular exercise program. The fourth group received both healthy dietary intervention and regular exercise program. Along with blood glucose and insulin levels; weight and triglycerides (TG) levels were also assessed. Compared to the control group, the results showed significant reduction (p˂0.05) in both fasting and postprandial blood glucose and insulin levels as represented by HOMA-IR along with significant reduction (p˂0.05) in the other metabolic parameters assessed during the study in both dietary intervention alone and exercise intervention alone groups. The reduction was more significant (p˂0.05) in the group that received both healthy dietary and regular exercise intervention. In conclusion; IR could be avoided if either healthy dietary modification and/or regular programmed exercise are adopted.

Efficacy and safety of the integration of traditional Chinese medicine and western medicine in the treatment of diabetes-associated cognitive decline: a systematic review and meta-analysis

Objective: In order to offer possible therapeutic treatment evidence for diabetes-associated cognitive decline (DACD), we thoroughly evaluated the effectiveness and safety of combining Traditional Chinese Medicine (TCM) and Western Medicine (WM) in the current study.Methods: The present study employed a comprehensive search strategy across multiple databases, namely, PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Scientific Journals Database (VIP), and Chinese Biomedical Literature Database (CBM), to identify relevant articles published until July 2023. Subsequently, a systematic review and meta-analysis of randomized controlled trials (RCTs) were conducted to assess the efficacy and safety of integrating TCM with WM for the treatment of DACD. The literature included in this study was assessed using the GRADE criteria and the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was conducted using RevMan 5.4 software.Results: A total of 20 RCTs involving 1,570 patients were ultimately included in this meta-analysis. The pooled results demonstrated that the integration of TCM and WM therapy significantly enhanced the overall effectiveness rate compared to WM therapy alone [OR = 4.94, 95% CI (3.56, 6.85), p < 0.00001]. Additionally, the combination therapy resulted in reductions in fasting blood glucose [MD = −0.30, 95% CI (−0.49, −0.10), p = 0.003], HbA1c [MD = −0.71, 95%CI (−1.03, −0.40), p < 0.00001], TNF-α levels [MD = −8.28, 95%CI (−13.12, −3.44), p = 0.0008], and TCM Syndrome Score [MD = −5.97, 95%CI (−9.06, −2.88), p = 0.0002]. Meanwhile, the combination therapy had a positive effect on MoCA Score [MD = 2.52, 95% CI (1.75, 3.30), p < 0.00001], and MMSE Score [MD = 2.31, 95% CI (1.33, 3.29), p < 0.00001]. In addition, the safety of the combination therapy was comparable to that of the WM alone [OR = 0.40, 95% CI (0.12, 1.31), p = 0.13].Conclusion: The integration of TCM and WM therapy outperformed WM alone in DACD treatment. Simultaneously, the combination therapy could improve the therapeutic effect on blood glucose, cognitive function, and inflammation to a certain extent with few adverse effects. However, given the constraints imposed by the quality limitations of the incorporated studies, as well as the potential presence of reporting bias, it is imperative that our findings be substantiated through rigorous, large-scale, randomized controlled trials of superior quality in the future.

Antidiabetic properties of Tarchonanthus camphoratus in fructose-induced diabetic Wistar rats

Tarchonantus camphoratus (TC) has been used traditionally to manage diabetes mellitus (DM) in Kenya but its efficacy has not been scientifically evaluated. This study aimed at evaluating the antidiabetic properties of TC crude leaf extract in diet-induced diabetic Wistar rats. DM was induced using high fructose (25% w/v) in drinking water for 12 weeks. Rats were divided into five groups (n=7): Groups I: normal control; II; diabetic untreated; III, IV & V; diabetic treated (21 days) with metformin (100 mg/kg.bw/day), 300 and 600 mg/kg.bw/day of TC extract respectively. Fasting body weights and blood glucose levels were monitored weekly. Oral glucose tolerance test, serum lipid profile, creatinine, urea, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total proteins (TP), C-reactive protein (CRP), albumin (ALB) and triglyceride (TG) mass in skeletal muscle were analysed at end of the study. Qualitative phytochemical analysis was done using standard procedures. Diabetic untreated rats had significantly higher body weights (p ˂0.05) compared to other groups. There was a significant reduction in fasting blood glucose in TC treatment groups compared to untreated controls. Increased glucose tolerance was observed in treated groups. TC extract significantly improved fructose-induced hypertriglyceridemia compared to DM groups. ALP, ALT, and CRP were significantly lowered while TP and ALB were elevated in the extract treated rats compared with untreated DM rats. DM group also exhibited significantly higher skeletal muscle TG mass when compared to normal control and diabetic treated groups. The phytochemical-rich TC leaf extract therefore possess potential alternative medicine for DM management.

The dual incretin co-agonist tirzepatide increases both insulin secretion and glucose effectiveness in model experiments in mice

Tirzepatide is a dual GIP and GLP-1 receptor co-agonist which is approved for glucose-lowering therapy in type 2 diabetes. Here, we explored its effects on beta cell function, insulin sensitivity and insulin-independent glucose elimination (glucose effectiveness) in normal mice. Anesthetized female C57/BL/6 J mice were injected intravenously with saline or glucose (0.125, 0.35 or 0.75 g/kg) with or without simultaneous administration of synthetic tirzepatide (3 nmol/kg). Samples were taken at 0, 1, 5, 10, 20 and 50 min. Glucose elimination rate was estimated by the percentage reduction in glucose from min 5 to min 20 (KG). The 50 min areas under the curve (AUC) for insulin and glucose were determined. Beta cell function was assessed as AUCinsulin divided by AUCglucose. Insulin sensitivity (SI) and glucose effectiveness (SG) were determined by minimal model analysis of the insulin and glucose data. Tirzepatide glucose-dependently reduced glucose levels and increased insulin levels. The slope for the regression of AUCinsulin versus AUCglucose was increased 7-fold by tirzepatide from 0.014 ± 0.004 with glucose only to 0.099 ± 0.016 (P < 0.001). SI was not affected by tirzepatide, whereas SG was increased by 78% (P < 0.001). The increase in SG contributed to an increase in KG by 74 ± 4% after glucose alone and by 67 ± 8% after glucose+ tirzepatide, whereas contribution by SI times AUCinsulin insulin (i.e., disposition index) was 26 ± 4% and 33 ± 8%, respectively. In conclusion, tirzepatide stimulates both insulin secretion and glucose effectiveness, with stimulation of glucose effectiveness being the prominent process to reduce glucose.

Once-weekly Insulin Icodec as Compared to Once-daily Basal Insulins: A Meta-analysis

BackgroundOnce-weekly basal insulin icodec has been tested in clinical trials for efficacy and safety over currently available glargine-100 and degludec in different clinical settings for type 2 diabetes. We performed this meta-analysis to evaluate its overall safety and efficacy as compared to glargine-100 and degludec (nonicodec), from all available randomized controlled trials. MethodsSeven trials comparing once-daily basal insulin analogs to once-weekly basal insulin icodec were included. Based on available information, outcomes in terms of HbA1c, fasting plasma glucose reduction, and increase in time in range (TIR) were compared. Side-effects were compared for overall hypoglycemia, severe hypoglycemia, and weight gain. The pooled effect size for continuously distributed data was measured as a reduction in “estimated differences in mean (with 95% CI).” For categorical data, the pooled effect size was measured as the Mantel-Haenszel risk ratio (with 95% CI). ResultsAnalyzing against the nonicodec comparators together, the “estimated mean changes” in HbA1c and fasting plasma glucose favoring icodec were −0.22% (−0.35, −0.10) and −1.59 mg% (−9.26, 6.08) respectively. The “estimated mean increment” in weight for icodec was 0.64 kg (0.61, 0.67). The “estimated mean percentage” increment in TIR for icodec was 4.24% (2.99, 5.49). The Mantel-Haenszel risk ratios for all hypoglycemic events and severe hypoglycemia for icodec were 1.24 (1.02, 1.50) (P = .03) and 0.81 (0.31, 2.08) (P is not significant), respectively, suggesting a 24% increased incidence of all hypoglycemia with icodec. ConclusionOnce-weekly basal insulin icodec as compared to once-daily basal insulin analogs had a slight increase in the risk of overall hypoglycemia and weight gain, without any difference in severe hypoglycemia, with similar glycemic control (in terms of fasting plasma glucose, HbA1c, and TIR).

Effect of Yoga and Walking on Glycemic Control for the Management of Type 2 Diabetes: A Systematic Review and Meta-analysis.

A daily habit of yogic practice or walking, along with an oral hypoglycemic agent (OHA) could be beneficial for better control of type 2 diabetes mellitus (T2DM). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to find out the efficiency of yoga or walking on glycemic control in T2DM. The present systematic review and meta-analysis were completed according to the PRISMA guidelines. The risk of bias in included studies was evaluated, by using the revised Cochrane risk-of-bias tool for randomized trials. Meta-analysis was implemented using RevMan software. Forest plots were used to illustrate the study findings and meta-analysis results. Sixteen studies were included in this systematic review, where 1820 participants were allocated to one of the following interventions: yoga, walking, and without any regular exercise (control group). Participants were between 17-75 years of age. Compared to the control group, the yoga group had a significant reduction in fasting blood glucose (FBG) by 31.98 mg/dL (95% CI = -47.93 to -16.03), postprandial blood glucose (PPBG) by 25.59 mg/dL (95% CI = -44.00 to -7.18], glycosylated hemoglobin (HbAlc) by 0.73% (95% CI = -1.24 to -0.22), fasting insulin by 7.19 μIU/mL (95% CI = -12.10 to -2.28), and homeostatic model assessment for insulin resistance (HOMA-IR) by 3.87 (95% CI = -8.40 to -0.66). Compared to the control group, the walking group had a significant reduction in FBG by 12.37 mg/dL (95% CI = -20.06 to -4.68) and HbA1c by 0.35% (95% CI = -0.70 to -0.01). Compared to the walking group, the yoga group had a significant reduction in FBG by 12.07 mg/dL (95% CI = -24.34 to - 0.20), HbA1c by 0.20% (95% CI = -0.37 to -0.04), fasting insulin by 10.06 μIU/mL (95% CI = -23.84 to 3.71) and HOMA-IR by 5.97 (95% CI = -16.92 to 4.99). Yoga or walking with OHA has positive effects on glycemic control. For the management of T2DM, yoga has relatively more significant effects on glycemic control than walking.Review registration number: PROSPERO registration number CRD42022310213.

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.

A Review on Antidiabetic Activity of Indian Medicinal Plant

Diabetes mellitus is one of the common metabolic disorders acquiring around 9.3% of adults worldwide in 2019.Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulin mimetic or insulin secretagogues activity) and activephytoconstituents having insulin mimetics activity. The treatment of diabetes is mainly based on the long-term use of pharmacological agents, often expensive and causing unpleasant side effects. There is an alarming increase in the number of pharmaceuticals taken in Europe. The aim of this paper is to concisely collect information concerning the few antidiabetic or hypoglycemic raw plant materials that are present in the consciousness of Indian and relatively easily accessible to them on the market and sometimes even grown on Indian plantations.The following raw materials are discussed in this mini-reviewBoerhaavia diffusa Linn. (Nyctaginaceae),Annona squamosa Linn. (Annonaceae),Bougainvillea spectabilis Linn. (Nyctaginaceae),Cassia kleinii Wight &amp; Arn. (Caesalpiniaceae),Coscinium fenestratum Colebr. (Menispermaceae),Ficus hispida Linn. (Moraceae),Murraya koenigii Linn. (Rutaceae),White Mulberry (Morus alba L.), Acacia arabica: (Babhul), Aegle marmelos: (Bengal Quince, Bel or Bilva), Allium cepa: (onion), Allium sativum: (garlic), Aloe vera and Aloe barbadensis, Azadirachta indica: (Neem), Eugenia jambolana: (Indian gooseberry, jamun), Mangifera indica: (Mango), Momordica charantia: (bitter gourd), Ocimum sanctum: (holy basil).

Anti-diabetic potential of Aconitum ferox roots

IntroductionAconitum ferox (A. ferox) is a traditional Chinese plant and recommended by the Chinese medicinal system as an anti-diabetic. According to the Chinese medicinal system, the tubers and roots of A. ferox (Family- Ranunculaceae) are commonly applied for various diseases, such as collapse, syncope, rheumatic fever, painful joints, gastroenteritis, diarrhea, diabetes, edema, bronchial asthma, various tumors, and some endocrinal problems. Till now there is no scientific studies have been published, therefore this plant has been chosen to investigate its anti-diabetic activity. Methods & methodologyWistar rats weighing 150–200 g of either sex were used in the study. Diabetes was induced by alloxan. Diabetes was confirmed after 48 h of a single intraperitoneal injection of alloxan (120 mg/kg) in Wistar rats. Extract of A. ferox (10 and 20 mg/kg) and Glimepiride (175 mg/kg, p.o) orally administered daily for 15 days. On the 15th day body weight was determined and blood was collected to the determine the biochemical parameters like blood glucose level, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides (TG), total cholesterol (TC) etc. ResultsThe results showed that extract of A. ferox at doses of 10 and 20 mg/kg showed a significant reduction in blood glucose, lipid profile and a significant improvement in body weight when compared to the diabetic control group due to the presence of various primary and secondary metabolites. ConclusionThese results suggest that the root extract of A. ferox possesses an antidiabetic effect on alloxan-induced diabetic rats and this justifies its use in traditional medicine and can be exploited in the management of diabetes but further research must be needed,

Fermentation of brown seaweeds Alaria esculenta and Saccharina latissima for new product development using Lactiplantbacillus plantarum, Saccharomyces cerevisiae and kombucha SCOBY

Two seaweed species were examined (Alaria esculenta and Saccharina latissima) as a fermentation feedstock for the development of a beverage. Three microbial groups were selected for experimentation; a single-species bacterium; Lactiplantibacillus plantarum, a single-species yeast; Saccharomyces cerevisiae and a multi-species culture; kombucha SCOBY (Symbiotic Culture of Bacteria and Yeast). Results showed SCOBY cultures were more successful in fermenting A. esculenta than S. latissima due to the lowered glucose content (4.069 ± 0.174 mg / mL and 12.224 ± 2.249 mg / mL, respectively). Likewise, L. plantarum played a major role in fermenting S. latissima, over A. esculenta, resulting in a lowered pH in the former but not the latter (6.44 ± 0.040 and 4.825 ± 0.045, respectively). S. cerevisiae does not appear to have been suitable as a fermentation medium for these two seaweed species under these conditions due to the lack of pH lowering, glucose reduction and acid production. All treatments showed an increased production of lactic acid, especially the SCOBY treated samples, which is an indicator of fermentation. There is potential for optimization of the seaweed fermentation process through strain selection, fermentation conditions optimization (temperature, time, pH) and seaweed biomass pretreatment. Glutamic acid, the amino acid responsible for umami flavour, was found in greater quantities in the S. cerevisiae treated seaweed, indicating that fermentation using S. cerevisiae cultures may improve the umami flavour profile of a seaweed fermented beverage product. In order to see if the seaweed species used had an impact on the SCOBY microbial makeup, the DNA profiles of the two SCOBYs used were analyzed. There were significant differences between the two SCOBYs. The A. esculenta SCOBY showed slightly rarer species of fungi and the species abundance of fungi was greater than that of S. latissima SCOBY. Furthermore, the number of fungal operational taxonomic units (OTUs) in A. esculenta SCOBY was higher than that in S. latissima SCOBY. This study shows the potential of using brown seaweed species as a fermentation substrate to develop a novel, fermented beverage.

Bitter gourd flavored Non-Alcoholic Wheat Beer (NAWB) exhibited antidiabetic properties by modulating carbohydrate metabolizing enzymes and upregulates insulin and GLUT-2 mRNA expressions in High Fat Diet/Streptozotocin (HFD/STZ) induced diabetic rats

To improve the control of Type 2 diabetes (T2D), this study investigated the potential benefits of an alcohol-free beer flavored with bitter gourd leaves, a plant with proven hypoglycemic properties. The high fat/streptozotocin (HFD/STZ) model was used to induce diabetes in Wistar rats as test subjects. The rats were divided into eight groups (n = 5) as follows: HP (STZ + 100% Hops); BG (STZ + 100% Bitter Gourd); 75:25BG (STZ + 75% Hops; 25%BG); 50:50BG (STZ + 50%Hops50%Bitter Gourd); 25:75BG (STZ + 25%Hops75%Bitter Gourd); Acarbose (STZ + Acarbose); DC (STZ-diabetic control group); NC (Normal Control group). Following a 14-day treatment, there was a significant (p < 0.05) reduction in blood sugar, serum glucose, α-amylase activity, α-glucosidase activity, and lipase activity. As the percentage of bitter gourd inclusion increased, the expression of GLUT-2 and insulin genes was upregulated. The beer sample with the lowest percentage inclusion of Hops (25:75BG) had the lowest glycemic index (GI). The study suggested that bitter gourd-flavored alcohol-free beer reduces blood glucose through muptiple pathways and could be a useful dietary intervention in the management of type 2 diabetes.Graphical

A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension.

Objective: This study aims to compare the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in hypertensive patients. Study Design: Prospective Observational. Setting: Hayatabad Medical Complex Peshawar. Period: December 2022 to May 2023. Material &amp; Methods: Approach was employed to investigate the metabolic impact of these antihypertensive medications. Involving a cohort of 660 hypertensive individuals. Data collection spanned over 12-week duration, with fasting glucose and lipid profiles assessed at baseline and 4, 8, and 12 weeks. Participants were categorized into hydrochlorothiazide and captopril groups, receiving standardized dosages of 25 mg/day and 50 mg/day, respectively. Fasting blood samples were analyzed for glucose and lipid parameters. Statistical analyses included paired t-tests and subgroup comparisons. Results: Both groups exhibited reductions in fasting glucose and lipid levels; however, these changes were not statistically significant within the 12-week timeframe. Comparison with national and international studies underscores population-specific variations in antihypertensive effects on metabolism. Conclusion: This study provides insights into the metabolic effects of hydrochlorothiazide and captopril among hypertensive patients. While immediate changes were not significant, the study contributes to the body of knowledge and calls for further research with extended follow-up and broader participant cohorts.

Evaluation of in vitro Antioxidant and Hypoglycemic Activities of Methanol Extract of Root of Cryptolepis buchanani in Streptozotocin-induced Diabetic Rats

Background: The present research aimed to assess the relationship between free radical scavenging activity and oral hypoglycemic potential of methanol extract of the root of Cryptolepis buchanani in Albino Wistar rats. Objective: The following research aimed to study and evaluate the antidiabetic efficacy of the natural plant extracts Cryptolepis buchanani. Methods: Phytochemical screening was done to analyze, and in vitro, the antioxidant activity of plant root extract has been evaluated using DPPH assay and Fe+3 Reducing Power Assay. Streptozotocin at a 60 mg/kg dose was used to induce diabetes in albino Wistar rats, which was then treated with methanol extracts (125 and 250 mg/kg, PO) to evaluate antidiabetic activity. Results: The results indicated that methanol extract of the root of Cryptolepis Buchanan had shown its promising antidiabetic potential at a dose of 250 mg/kg in experimental diabetic Wistar rats, which may be linked to its antioxidant property. Conclusion: This experimental study revealed that the extract could potentially alleviate the augmented oxidative state correlated with diabetes. The marked reduction in blood glucose levels proves the hypoglycemic activity of the plant.

Hypoglycaemic and anti-hyperglycaemic activity of aqueous extract of &lt;i&gt;Azanza garckeana&lt;/i&gt; leaves in normal and alloxan -induced diabetic rats

The aqueous extract of Azanza garckeana (AG) leaves was tested for hypoglycaemic and anti-hyperglycaemic activities. The extract was administered to Wistar rats orally at 100 and 150 mg/kg doses in oral glucose tolerance test (OGTT), glucose baseline conditions and diabetic conditions. OGTT was tested with the administration of the aqueous extract to normal rats and blood glucose levels were measured for each animal at 30, 60 and 120 minutes after glucose loading. For the hypoglycaemic activity, the extract was administered to normal rats and blood glucose levels were measured for each animal, at 30, 60 and 120 minutes. Alloxan induced diabetic rats were used to determine the anti-hyperglycaemic activity. The extract was administered for 14 days and blood glucose levels were measured for each animal at a weekly interval for 2 weeks. The OGTT study in normal rats showed that administration of the extract at 150 mg/kg reduced blood glucose levels within 30 to 60 minutes after glucose administration, as was also observed with the standard drug (glibenclamide). For the hypoglycaemic study, fasting blood glucose test in normal rats showed that aqueous extract of AG leaf at 150 mg/kg, produced significant (P &lt; 0.05) blood glucose reduction at 60 minutes after administration while glibenclamide revealed significant reduction throughout the time as compared with normal control. 150 mg/kg was the most effective dose during the anti-hyperglycaemic study as it had a significant reduction in blood glucose levels after the 7th day. However glibenclamide had a more significant reduction when compared with treated groups. In conclusion, these results clearly indicate that aqueous leaf extract of Azanza garckeana possess hypoglycaemic and anti-hyperglycaemic effects in normal and diabetic rats and thus support its traditional use to treat diabetes. Therefore, a detailed mechanism-based study and isolation of bioactive compounds responsible for the observed activities of Azanza garckeana is recommended.

Fasting mimicking diet inhibits tumor-associated macrophage survival and pro-tumor function in hypoxia: implications for combination therapy with anti-angiogenic agent

BackgroundRecent research shows that tumor-associated macrophages (TAMs) are the primary consumers of glucose in tumor tissue, surpassing that of tumor cells. Our previous studies revealed that inhibiting glucose uptake impairs the survival and tumor-promoting function of hypoxic TAMs, suggesting that glucose reduction by energy restriction (calorie restriction or short-term fasting) may has a significant impact on TAMs. The purpose of this study is to verify the effect of fasting-mimicking diet (FMD) on TAMs, and to determine whether FMD synergizes with anti-angiogenic drug apatinib via TAMs.MethodsThe effect of FMD on TAMs and its synergistic effects with apatinib were observed using an orthotopic mouse breast cancer model. An in vitro cell model, utilizing M2 macrophages derived from THP-1 cell line, was intended to assess the effects of low glucose on TAMs under hypoxic and normoxic conditions. Bioinformatics was used to screen for potential mechanisms of action, which were then validated both in vivo and in vitro.ResultsFMD significantly inhibit the pro-tumor function of TAMs in vivo and in vitro, with the inhibitory effect being more pronounced under hypoxic conditions. Additionally, the combination of FMD-mediated TAMs inhibition with apatinib results in synergistic anti-tumor activity. This effect is partially mediated by the downregulation of CCL8 expression and secretion by the mTOR-HIF-1α signaling pathway.ConclusionsThese results support further clinical combination studies of FMD and anti-angiogenic therapy as potential anti-tumor strategies.Graphical

The metabolomic signature of weight loss and remission in the Diabetes Remission Clinical Trial (DiRECT)

Aims/hypothesisHigh-throughput metabolomics technologies in a variety of study designs have demonstrated a consistent metabolomic signature of overweight and type 2 diabetes. However, the extent to which these metabolomic patterns can be reversed with weight loss and diabetes remission has been weakly investigated. We aimed to characterise the metabolomic consequences of a weight-loss intervention in individuals with type 2 diabetes.MethodsWe analysed 574 fasted serum samples collected within an existing RCT (the Diabetes Remission Clinical Trial [DiRECT]) (N=298). In the trial, participating primary care practices were randomly assigned (1:1) to provide either a weight management programme (intervention) or best-practice care by guidelines (control) treatment to individuals with type 2 diabetes. Here, metabolomics analysis was performed on samples collected at baseline and 12 months using both untargeted MS and targeted 1H-NMR spectroscopy. Multivariable regression models were fitted to evaluate the effect of the intervention on metabolite levels.ResultsDecreases in branched-chain amino acids, sugars and LDL triglycerides, and increases in sphingolipids, plasmalogens and metabolites related to fatty acid metabolism were associated with the intervention (Holm-corrected p<0.05). In individuals who lost more than 9 kg between baseline and 12 months, those who achieved diabetes remission saw greater reductions in glucose, fructose and mannose, compared with those who did not achieve remission.Conclusions/interpretationWe have characterised the metabolomic effects of an integrated weight management programme previously shown to deliver weight loss and diabetes remission. A large proportion of the metabolome appears to be modifiable. Patterns of change were largely and strikingly opposite to perturbances previously documented with the development of type 2 diabetes.Data availabilityThe data used for analysis are available on a research data repository (https://researchdata.gla.ac.uk/) with access given to researchers subject to appropriate data sharing agreements. Metabolite data preparation, data pre-processing, statistical analyses and figure generation were performed in R Studio v.1.0.143 using R v.4.0.2. The R code for this study has been made publicly available on GitHub at: https://github.com/lauracorbin/metabolomics_of_direct.Graphical

Comprehensive Evaluation of the Clinical Efficacy of an Anti-Diabetic Polyherbal Formulation

Background: There are several clinical studies examining the health advantages of several single medicinal herbs utilized in traditional blood glucose-lowering treatments. But very few or no studies on herbal formulations were made as Polyherbal for the same goal. As a result, it is now necessary to confirm that patients with hyperglycemia can benefit from such Polyherbal medicines as Dolabi. Methods: This prospective open-label, herbal coded test drug-controlled, randomized trial was conducted at the Munshiganj and Dhaka area in Bangladesh. We enrolled 108 male and 104 female patients of 30-70 years with primary and moderate hyperglycemia. They were recruited from the OPD of an Unani &amp; Ayurvedic hospital in Munshiganj and different Unani clinics in Dhaka, Bangladesh after fulfilling the inclusion criteria. Patients were randomly assigned to receive metformin hydrochloride 500 mg two times daily and 2 tablets of Dolabi two times daily by using a random numbers table with the help of an assistant. Blood samples, height, weight, blood pressure, and personal data were recorded—laboratory results were obtained at the study baseline, after 1.5 months and after 3 months of intervention. Results: In the case of the test drug, results showed a significant decrease in blood glucose level between the baseline and after 3 months, in males, it was from 9.83±1.17 to 7.72±1.06 mg/dL for fasting glucose, from 16.60±2.35 to 8.23±1.17 mg/dL for 2 hours PP glucose, from 9.33±1.17 to 7.45±2.03 percent for HbA1c and for Insulin it reduces from 183.10±27.59 to 168.10±29.59 pmol/ L. The control drug metformin hydrochloride also showed a significant decrease in blood glucose level between baseline and after 3 months, in the case of males it was from 9.99±2.52 to 6.97±1.76 mg/dL for fasting glucose, from 17.43±5.05 to 7.89±2.42 mg/dL for 2 hours PP glucose, from 10.43±2.36 to 6.87±1.18 percent for HbA1c and for Insulin it reduces from 198.75±30.61 to 183.75±30.61p mol/L. In the case of females the test drug showed a significant reduction in fasting glucose, 2 hours PP glucose, HbA1c and Insulin between the baseline and after 3 months, it was from 10.02±1.11 to 7.78±0.93 mg/dL, from 16.88±2.21 to 8.16±1.11 mg/dL, from 9.84±1.04 to 7.45±1.03 percent and from 199.47±30.90 to 173.47±30.90 mg/dL respectively. In the case of females, the control drug showed a significant reduction in fasting glucose, 2 hours PP glucose, HbA1c and Insulin between baseline and after 3 months, it was from 10.18±1.92 to 6.71±1.59 mg/dL, from 18.70±3.88 to 7.60±3.74 mg/dL, from 10.58±1.08 to 6.98±1.08 percent and from 200.00±31.83 to 188.00±31.83 mg/dL respectively. Conclusions: We can infer the following from the present study’s findings: The polyherbal formulation Dolabi is able to reduce the blood glucose level. It can be an effective drug for primary hyperglycemic patients.

Carnosine supplementation improves glucose control in adults with pre-diabetes and type 2 diabetes: A randomised controlled trial

Background and aimsType 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. Methods and resultsIn this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (−1.31 mmol/L; p = 0.02) and 120 min (−1.60 mmol/L, p = 0.02) and total glucose area under the curve (−3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. ConclusionThis study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation.

Bi-enzymatic chemo-mechanical feedback loop for continuous self-sustained actuation of conducting polymers

Artificial actuators have been extensively studied due to their wide range of applications from soft robotics to biomedicine. Herein we introduce an autonomous bi-enzymatic system where reversible motion is triggered by the spontaneous oxidation and reduction of glucose and oxygen, respectively. This chemo-mechanical actuation is completely autonomous and does not require any external trigger to induce self-sustained motion. The device takes advantage of the asymmetric uptake and release of ions on the anisotropic surface of a conducting polymer strip, occurring during the operation of the enzymes glucose oxidase and bilirubin oxidase immobilized on its surface. Both enzymes are connected via a redox polymer at each extremity of the strip, but at the opposite faces of the polymer film. The time-asymmetric consumption of both fuels by the enzymatic reactions produces a double break of symmetry of the film, leading to autonomous actuation. An additional break of symmetry, introduced by the irreversible overoxidation of one extremity of the polymer film, leads to a crawling-type motion of the free-standing polymer film. These reactions occur in a virtually unlimited continuous loop, causing long-term autonomous actuation of the device.

Physical exercise in kidney disease: A commonly undervalued treatment modality.

Physical inactivity has been identified as a risk factor for multiple disorders and a strong association exists between chronic kidney disease (CKD) and a sedentary lifestyle. Even though physical activity is crucial in the development and progression of disease, the general focus of the current medical practice is the pharmacological perspective of diseases with inadequate emphasis on lifestyle intervention. In this narrative review we explain the pathophysiological mechanisms underlying the beneficial effects of physical exercise on CKD in addition to discussing the clinical studies and trials centred on physical exercise in patients with CKD. Physical activity influences several pathophysiological mechanisms including inflammation, oxidative stress, vascular function, immune response and macromolecular metabolism. While exercise can initially induce stress responses like inflammation and oxidative stress, long-term physical activity leads to protective countermeasures and overall improved health. Trials in pre-dialysis CKD patients show that exercise can lead to reductions in body weight, inflammation markers and fasting plasma glucose. Furthermore, it improves patients' functional capacity, cardiorespiratory fitness and quality of life. The effects of exercise on kidney function have been inconsistent in these trials. In haemodialysis, peritoneal dialysis and kidney transplant patients exercise interventions improve cardiorespiratory fitness, walking capacity and quality of life. Combined training shows the best performance to increase peak oxygen uptake in haemodialysis patients. In kidney transplant recipients, exercise improves walking performance, quality of life and potentially arterial stiffness. However, exercise does not affect glucose metabolism, serum cholesterol and inflammation biomarkers. Long-term, adequately powered trials are needed to determine the long-term feasibility, and effects on quality of life and major clinical outcomes, including mortality and cardiovascular risk, in all CKD stages and particularly in kidney transplant patients, a scarcely investigated population. Physical exercise plays a crucial role in ameliorating inflammation, oxidative stress, vascular function, immune response and macromolecular metabolism, and contributes significantly to the quality of life for patients with CKD, irrespective of the treatment and stage. Its direct impact on kidney function remains uncertain. Further extensive, long-term trials to conclusively determine the effect of exercise on major clinical outcomes such as mortality and cardiovascular risk remain a research priority.