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To compare the antihypertensive effectiveness of sour tea (ST; Hibiscus sabdariffa) with black tea (BT) infusion in diabetic patients, this double-blind randomized controlled trial was carried out. Sixty diabetic patients with mild hypertension, without taking antihypertensive or antihyperlipidaemic medicines, were recruited in the study. The patients were randomly allocated to the ST and BT groups and instructed to drink ST and BT infusions two times a day for 1 month. Their blood pressure (BP) was measured on days 0, 15 and 30 of the study. The mean of systolic BP (SBP) in the ST group decreased from 134.4±11.8 mm Hg at the beginning of the study to 112.7±5.7 mm Hg after 1 month (P-value <0.001), whereas this measure changed from 118.6±14.9 to 127.3±8.7 mm Hg (P-value=0.002) in the BT group during the same period. The intervention had no statistically significant effect on the mean of diastolic BP (DBP) in either the ST or BT group. The mean pulse pressure (PP) of the patients in the ST group decreased from 52.2±12.2 to 34.5±9.3 mm Hg (P-value <0.001) during the study, whereas in the BT group, it increased from 41.9±11.7 to 47.3±9.6 mm Hg (P-value=0.01). In conclusion, consuming ST infusion had positive effects on BP in type II diabetic patients with mild hypertension. This study supports the results of similar studies in which antihypertensive effects have been shown for ST.Journal of Human Hypertension (2009) 23, 48–54; doi:10.1038/jhh.2008.100; published online 7 August 2008 [ABSTRACT FROM AUTHOR]

Inflammation contributes to the pathogenesis of type 2 diabetes (T2DM). This study sought to document how the systemic biomarkers of inflammation varied based on food choices among patients with T2DM. This cross-sectional study enrolled ambulatory patients with T2DM. Demographic and clinical information was collected. Five drops of fingerstick blood were collected using an absorbent paper device (HemaSpot HFR). C-reactive protein (CRP), serum amyloid A protein (SAA), and fibrinogen were measured using a Luminex assay. Patient-generated 7-day food diaries were analyzed using a validated food processor software. Data were analyzed by Pearson's correlation tests, linear regression and logistic regression with the significance level set at 0.05. Among the 71 participants, 43 (60.6%) were females. The average age and duration of T2DM were 64.1 ± 10.3 and 15.8 ± 9.1 years, respectively. In a simple linear regression run with selected micronutrients, iron [F (1, 53) = 5.319, p < 0.05, adj. R2 = 0.074] significantly predicted plasma CRP. This significance was lost with multiple linear regressions including age, gender, BMI, T2DM duration, T2DM complications, glycohemoglobin A1c (HbA1c) and other micronutrients. The average intake of most micronutrients by the participants was below the recommended daily intake. A higher intake of iron-rich foods was associated with higher levels of systemic inflammation in a simple linear regression model, but the association was not present after adjusting for patient factors like age, gender, BMI and T2DM-related variables. This relationship needs to be explored further given the key role of inflammation in the pathogenesis of T2DM and its associated complications. [ABSTRACT FROM AUTHOR]

Background and Aims: The purpose of this meta‐analysis was to investigate the effect of vitamin D supplementation on hemoglobin A1C (HbA1C), fasting blood sugar (FBS), low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), systolic blood pressure (SBP), and the total vitamin D level in patients with Type 2 diabetes (T2DM). Methods: A systematic search was conducted in databases such as PubMed (Medline), Scopus, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov using relevant keywords from January 1990 to January 2024. After screening and extracting data, a qualitative evaluation of articles was performed using the Cochrane risk‐of‐bias tool for randomized trials (RoB 2). Results: The findings revealed that vitamin D supplementation significantly decreased the mean HbA1C (SMD: −0.15; 95% CI: −0.29, −0.20; Isquare: 79.76%; p value < 0.001) and mean FBS (SMD: −0.28; 95% CI: −0.40, −0.15; Isquare: 70.13%; p value < 0.001), lowered SBP (SMD: −0.06; 95% CI: −0.16, −0.05; Isquare: 39.63%; p value = 0.23), and reduced LDL (SMD: −0.11; 95% CI: −0.28, −0.05; Isquare: 73.66%; p value < 0.001). Furthermore, vitamin D supplementation increased the average HDL (SMD: 0.13; 95% CI: 0.04, 0.29; Isquare: 79.33%; p value < 0.001) and vitamin D levels (SMD: 1.78; 95% CI: 1.53, 2.04; Isquare: 91.92%; p value < 0.001) in patients with T2DM. Subgroup analyses showed that weight gain, BMI, and duration of the disease could reduce the effect of vitamin D supplementation on diabetes control in affected patients. Conclusion: The results also indicated that taking vitamin D supplements in the amount of 50,000 IU had a significant effect on reducing the indicators related to diabetes control. Based on the combined evidence, the findings of this meta‐analysis suggest that vitamin D supplementation can significantly improve glycemic control and reduce the risk of complications associated with T2DM, especially cardiovascular diseases (CVDs). [ABSTRACT FROM AUTHOR]

An extremely dangerous side effect of type I and type II diabetes is diabetic nephropathy (DN). From the early microproteinuria to end-stage renal failure, it progresses. About one in three diabetics in the US suffer from diabetic nephropathy. Chronic hyperglycemia is the primary cause of diabetic ketoacidosis. Hyperglycemia (HG) has the potential to cause humoral mediators and cytokines to be produced by both resident and non-resident renal cells. These substances may interfere with cell growth, alter renal cell and tissue phenotype and function, interact with proteins, produce advanced glycation end products (AGEs), damage tubules and glomeruli, and ultimately cause kidney disease. Poor blood glucose management is thus a significant risk factor for the onset of DN. An alternate course of treatment for DN may use extracts from herbal remedies. Medicinal plants' bioactive components stop DN from progressing. Attention has to be paid to the role that traditional herbs and medications play in the treatment of diabetic nephropathy, particularly in India where several fruits and herbs are believed to provide health benefits. Natural compounds influence the KEAP1/Nrf2/ARE and NFB pathways in addition to having antioxidant and anti-inflammatory properties. The efficacy of entire herbs, plants, or seeds, together with their active components, in treating diabetic nephropathy was investigated in preclinical research. Natural compounds are biologically active substances that come from natural sources and are beneficial for treating specific illnesses. Numerous natural substances, such as glycosides, polysaccharides, terpenoids, alkaloids, flavonoids, and polyphenols, have been shown to enhance DN. The exorbitant expenses associated with contemporary medications suggest that other approaches are necessary for improved DN treatment. Future research on herbal remedies may provide a natural key to open a pharmacy for diabetologists. [ABSTRACT FROM AUTHOR]

Obesity disrupts glucose metabolism, leading to insulin resistance (IR) and cardiometabolic diseases. Consumption of cow's milk and other dairy products may influence glucose metabolism. Within the complex matrix of cow's milk, various carbohydrates, lipids, and peptides act as bioactive molecules to alter human metabolism. Here, we summarize data from human studies and rodent experiments illustrating how these bioactive molecules regulate insulin and glucose homeostasis, supplemented with in vitro studies of the mechanisms behind their effects. Bioactive carbohydrates, including lactose, galactose, and oligosaccharides, generally reduce hyperglycemia, possibly by preventing gut microbiota dysbiosis. Milk-derived lipids of the milk fat globular membrane improve activation of insulin signaling pathways in animal trials but seem to have little impact on glycemia in human studies. However, other lipids produced by ruminants, including polar lipids, odd-chain, trans-, and branched-chain fatty acids, produce neutral or contradictory effects on glucose metabolism. Bioactive peptides derived from whey and casein may exert their effects both directly through their insulinotropic effects or renin-angiotensin-aldosterone system inhibition and indirectly by the regulation of incretin hormones. Overall, the results bolster many observational studies in humans and suggest that cow's milk intake reduces the risk of, and can perhaps be used in treating, metabolic disorders. However, the mechanisms of action for most bioactive compounds in milk are still largely undiscovered. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present meta-analysis of randomized controlled trials, probiotic fermented milk supplementation appeared to be beneficial in lowering the levels of fasting plasma glucose, HbA1c, total cholesterol, and C-reactive protein. While these findings are encouraging, they should be interpreted cautiously, as considerable limitations of the included trials and analyses precluded solid conclusions. Modulating gut microbiota composition through probiotic administration has been proposed as a novel therapy for type 2 diabetes mellitus (T2DM), and fermented milk is arguably the most common and ideal probiotic carrier. The present meta-analysis was performed to assess the effects of probiotic fermented milk supplementation on glucose and lipid metabolism parameters and inflammatory markers in patients with T2DM using published data from randomized controlled trials (RCTs). The PubMed, Web of Science, and Cochrane Library databases were searched for relevant RCTs. A random-effects model was used to generate the weighted mean difference (WMD) and 95% confidence interval (95% CI). Probiotic fermented milk supplementation reduced the levels of fasting plasma glucose (MD = −17.01, 95% CI −26.43, −7.58 mg/dL; n = 7), hemoglobin A1c (MD = −0.47, 95% CI −0.74, −0.21%; n = 7), total cholesterol (MD = −5.15, 95% CI −9.52, −0.78 mg/dL; n = 7), and C-reactive protein (MD = −0.25, 95% CI −0.43, −0.08; n = 3) but did not significantly affect the levels of HOMA-IR (MD = −0.89, 95% CI −2.55, 0.78; n = 3), triglyceride (MD = −4.69, 95% CI −14.67, 5.30 mg/dL; n = 6), low-density lipoprotein cholesterol (MD = −4.25, 95% CI −8.63, 0.13 mg/dL; n = 7), high-density lipoprotein cholesterol (MD = 1.20, 95% CI −0.96, 3.36 mg/dL; n = 7), and tumor necrosis factor-alpha (MD: −0.58, 95% CI −1.47, 0.32 pg/mL; n = 2). In summary, the present findings provide a crude indication of the potential benefits of probiotic fermented milk supplementation in improving glucose and lipid metabolism and inflammation in patients with T2DM. However, more robust evidence is needed to determine the clinical significance of probiotic fermented milk in the management of T2DM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problem. Numerous studies have indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, and has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, antihyperglycemic, anti-apoptotic, and antihyperlipidemic, among other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM. [ABSTRACT FROM AUTHOR]

Background: There has been a significant rise in the number of individuals diagnosed with type 2 diabetes mellitus (T2DM), with the condition reaching epidemic proportions globally. This study examined the dietary pattern of a sample of Saudi Arabian adults with T2DM compared to control non-diabetics. Methods: Data from 414 participants, 207 control and 207 T2DM was analyzed. Anthropometric measurements, foods intake such as vegetables, fruits, whole grains, fried foods, sweetened juice, sweets, and pastries consumption as well as physical activity were obtained by an interview-survey. Results: The consumption of vegetables, green and leafy vegetables, starchy vegetables, fruits, proteins, and milk was significantly higher in the diabetics (p< 0.0001 for all and p<0.01 for starchy vegetables). Of the case group, 79.7% of them consumed whole-wheat bread while 54.6% of them consumed low fat milk (p<0.0001). There was a significant decrease in the percentage of cases who consumed discretionary foods and sweetened juices and soft drinks (24.1%), avoided sweets (75.8%) and pastries (37.1%), (p<0.0001). There were also significant increases in the percentages of participants who use healthy fat (as olive oil) in the case group (78.7%) (p<0.001). There was a significant increase in the percentage of diabetics who followed a diet to lose weight (15%) (p<0.05). The majority of the two study groups were physically inactive (control 95.2% & case 94.2%). Conclusions: The results of this study provide insight on that diabetics generally follow a healthy diet, yet their engagement in physical activity may not be optimal. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean Diet (MedDiet) is the dietary pattern par excellence for managing and preventing metabolic diseases, such as Type 2 Diabetes (T2DM). The MedDiet incorporates spices and aromatic herbs, which are abundant sources of bioactive compounds. The aim of this study was to analyze the effect of all aromatic herbs and spices included in the MedDiet, such as black cumin, clove, parsley, saffron, thyme, ginger, black pepper, rosemary, turmeric, basil, oregano, and cinnamon, on the glycemic profile in T2DM subjects. Methods: PubMed, Web of Science, and Scopus databases were searched for interventional studies investigating the effect of these aromatic herbs and spices on the glycemic profile in T2DM subjects. Results: This systematic review retrieved 6958 studies, of which 77 were included in the qualitative synthesis and 45 were included in the meta-analysis. Our results showed that cinnamon, turmeric, ginger, black cumin, and saffron significantly improved the fasting glucose levels in T2DM subjects. The most significant decreases in fasting glucose were achieved after supplementation with black cumin, followed by cinnamon and ginger, which achieved a decrease of between 27 and 17 mg/dL. Conclusions: Only ginger and black cumin reported a significant improvement in glycated hemoglobin, and only cinnamon and ginger showed a significant decrease in insulin. [ABSTRACT FROM AUTHOR]

This systematic review extensively investigated the role of the genetic and transcriptomic factors in late complications of type 2 diabetes mellitus (T2DM) and the current approaches targeting oxidative-stress-related pathways with antioxidant therapies. To cover our broad research area, we have conducted two systematic searches, the first focusing on genetic and transcriptomic factors affecting oxidative stress and the second one focusing on the antioxidant therapies in late complications of T2DM. The final review included 33 genetic and transcriptomic studies and 23 interventional randomized clinical trials. The conducted systematic review highlights the important role of oxidative stress in the development of late complications in T2DM patients. However, the current level of evidence does not support the use of genetic and transcriptomic factors as predictive and prognostic biomarkers for the development of T2DM late complications. Further studies are needed to elucidate the potential of targeting oxidative-stress-related pathways for novel preventative and therapeutic approaches. Additionally, antioxidants both in dietary and supplement form have been shown to improve different metabolic and biochemical parameters in T2DM patients with developed late complications. In recent years, studies have improved in methodological quality despite still mainly focusing on microvascular late complications of T2DM. Furthermore, the observed interventional studies suggest non-homogeneity in the duration of observation. As many studies do not provide post-intervention follow-up testing, it is difficult to assess the long-term health benefits of antioxidant supplementation. [ABSTRACT FROM AUTHOR]

Postprandial insulin secretion has been associated with metabolic disorders such as hyperlipidemia and type 2 diabetes. Therefore, we aimed to explore the relationship between dietary insulin indices and dietary pattern with the risk of Metabolic Syndrome (MetS). The participants of the present cross-sectional study were included among the individuals who participated in the Hoveyzeh Cohort Study (HCS). A total of 3905 Iranian adults, aged 35–70 years, are included in the current analysis. The Food Frequency Questionnaire (FFQ) is used to calculate the dietary Insulin Index (DII), Insulin Load (DIL), and dietary pattern. Dietary pattern was derived using Reduced-Rank Regression (RRR) based on intake of protein (g/day), fiber (g/day), fat (g/day), magnesium (mg/day), and dietary insulin index were considered as response variables. The Generalized Linear Model was used to obtain the odds ratio (OR) and 95% confidence interval (CI) for MetS based on gender, while considering quartiles of DIL, DII scores, and dietary pattern, adjusted for potential confounders. The mean ± SD of age and BMI of the participants in the top quartile of DIL were 45.72 ± 8.05 years and 28.25 ± 5.02 kg/m2, respectively. The mean ± SD of DII was 40.53 ± 4.06 and the mean ± SD of DIL was 117,986.1 ± 30,714.06. A significant positive association was observed between DIL and MetS in women after adjusting for confounding factors (OR: 1.51; 95% CI 1.16; 1.96). No significant association was seen between DIL, DII, and MetS among men. A derived dietary pattern characterized by high intakes of fruits, sugar, sweet deserts, Whole Grains, and dairy was associated with an increased risk of MetS in adjusted model2 among women (OR: 1.41; 95% CI 1.13; 1.75) and men in the same model (OR: 2.09; 95% CI 1.35; 3.21).However, the final model was significant just for men (OR: 2.08; 95% CI 1.35; 3.21) and not for women (OR: 1.24; 95% CI 0.96; 1.60). Our findings showed that adherence to a diet with a high insulin load can increase the risk of MetS in women. In addition, a derived dietary pattern by RRR indicated that a diet rich in fruits, sugar, sweet deserts, whole Grains, and dairy is related to increased risk of MetS in both men and women. [ABSTRACT FROM AUTHOR]

Background: Abnormalities in glucose and lipid metabolism contribute to the progression and exacerbation of type 2 diabetes mellitus (T2DM). Fish oil and probiotics are dietary supplements that have the potential to improve glucose and lipid metabolism. However, their efficacy remains unclear in T2DM patients. Methods: PubMed, Embase, and the Cochrane Library were retrieved to collect randomized controlled trials (RCTs) on the efficacy of fish oil or probiotic supplementation in T2DM patients from the database inception to December 13, 2023. Primary outcome indicators encompassed glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR) and blood lipid profile (triglyceride (TG) and total cholesterol (TC). Secondary outcome indicators included inflammatory markers such as tumor necrosis factor -α (TNF-α) and adipocytokine (including leptin and adiponectin). The R software was used for statistical analysis, and GraphPad Prism was used for figure rendering. Results: A total of 60 RCTs involving 3845 T2DM patients were included in the analysis. The results showed that the probiotics (Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium, etc.) were more effective in reducing HOMA-IR than fish oil (Surca = 0.935). Bifidobacterium demonstrated the highest efficacy in reducing HbA1c levels (Surca = 0.963). Regarding lipid metabolism, fish oil was superior to probiotics in lowering TG and TC levels (Surca values of 0.978 and 0.902, respectively). Furthermore, fish oil outperformed probiotics in reducing TNF-α (Surca = 0.839) and leptin (Surca = 0.712), and increasing adiponectin levels (Surca = 0.742). Node-splitting analysis showed good consistency (P > 0.05 for direct, indirect, and network comparison across various interventions). Conclusions: In T2DM patients, fish oil was more effective than probiotics in regulating lipid metabolism. Probiotics outperformed fish oil in regulating glucose metabolism particularly; specifically, Bifidobacterium showed higher efficacy in reducing blood glucose. [ABSTRACT FROM AUTHOR]

Backgrounds: Although the significance of diet in preventing or managing diabetes complications is highlighted in current literature, there is insufficient evidence regarding the correlation between nutrient patterns and these complications. The objective of this case-control study is to investigate this relationship by analyzing the dietary intake of nutrients in participants with and without type 2 diabetes (T2D). Methods: A case-control study was conducted at the Tabriz Center of Metabolism and Endocrinology to investigate the relationship between nutrient patterns and type 2 diabetes (T2D). The study enrolled 225 newly diagnosed cases of T2D and 225 controls. The dietary intake of nutrients was assessed using a validated semi-quantitative food frequency questionnaire (FFQ). Principal component analysis using Varimax rotation was used to obtain nutrient patterns. Logistic regression analysis was performed to estimate the risk of T2D. Results: The participants' mean (SD) age and BMI were 39.8 (8.8) years and 27.8 (3.6) kg/m2, respectively. The results identified three major nutrient patterns. The first nutrient pattern was characterized by high consumption of sucrose, animal protein, vitamin E, vitamin B1, vitamin B12, calcium, phosphorus, zinc, and potassium. The second nutrient pattern included fiber, plant protein, vitamin D, Riboflavin, Vitamin B5, copper, and Magnesium. The third nutrient pattern was characterized by fiber, plant protein, vitamin A, riboflavin, vitamin C, calcium, and potassium. Individuals in the highest tertile of nutrient pattern 3 (NP3) had a lower risk of T2D compared to those in the lowest tertile after adjusting for confounders. The odds ratio was 0.52 with a 95% confidence interval of 0.30–0.89 and a P_trend of 0.039. Conclusion: This study found that conforming to a nutrient pattern consisting of plant protein, vitamin C, vitamin A, vitamin B2, potassium, and calcium is linked to a lower likelihood of developing T2D.The initial results suggest that following a nutrient pattern that includes these nutrients may reduce the risk of T2D. However, further research is required to confirm the relationship between nutrient patterns and T2D. [ABSTRACT FROM AUTHOR]

Meat is a major part of human diets for centuries, a source of protein and essential nutrients, but concerns have been raised about the potential negative health impacts associated with high meat consumption. This review paper aims to provide an overview of the current scientific evidence on the effects of meat consumption on consumer health. The review covers the evidence on the relationship between meat consumption and various health outcomes, including cardiovascular disease, cancer, type 2 diabetes, and obesity. The review discusses the potential for promoting healthy meat consumption patterns and recommendations for consumers and policy-makers to reduce meat consumption and promote healthier dietary choices. Overall, the review highlights the complex relationship between meat consumption and consumer health, and the need for further research to better understand this relationship and inform public health policy and dietary guidelines. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM), one of the most serious non-communicable diseases, has long-term negative effects on the healthcare system due to its microvascular and macrovascular manifestations, which can be fatal if left untreated. Nutraceuticals, on the other hand, are alternative therapy choices of orally consumed natural food ingredients applicable in the management of several diseases, including diabetes mellitus. Through their antioxidant capabilities and bioactive components, nutraceuticals have been clinically demonstrated to be effective in preventing a number of ailments, including cancer, diabetes, heart disease, and kidney problems. Flavonoids, which are categorized as phytochemicals, are present in several of these nutraceuticals. Cocoa, one of the flavanols engaged in the treatment of diabetes mellitus, provides an additional non-pharmaceutical intervention in the management of diabetes mellitus, which, in part, is because of its high antioxidant capacity. Additionally, flavonoids improve insulin resistance and sensitivity, dyslipidemia, endothelial function, and blood pressure, as well as lower oxidative stress and inflammatory processes. As a result, they may be able to stop the progression of long-term vascular consequences of diabetes, such as cardiovascular disease, neuropathy, nephropathy, and retinopathy. Therefore, the effects of nutraceuticals (as an alternative treatment) on diabetic-related micro- and macrovascular problems are the main focus of this review. [ABSTRACT FROM AUTHOR]

Objective: Recently, the association between sexual dysfunction (SD) and diabetes has been proven in various studies. The study aimed to determine the frequency of SD and identify risk factors related to SD in men with Type 2 diabetes mellitus (T2DM). Materials and Methods: The cross-sectional study was conducted on 114 men with T2DM who had referred to the Yazd Diabetes Center from 2019-2020. All of them filled out a standard questionnaire with a specified validity and reliability. The analysis was performed using ANOVA and Chi-square by SPSS, version 22 software. Results: The mean age of participants was 52.48 (±5.33). The SD frequency was 73.7%. The mean SD score was 17.89 (±12). There was a significant relationship between the total SD and neuropathy (P: 0.0001), retinopathy (P: 0.0001), nephropathy (P: 0.023), type of treatment (P: 0.0001), age (P: 0.0001) and addiction (P: 0.031). There was no significant relationship between the total SD score and hyperlipidemia (P: 0.371), hypertension (P: 0.683), Hb1Ac (P: 0.816), duration of diabetes (P: 0.101) and smoking (P: 0.29). Conclusion: Due to the high frequency of sexual dysfunction in men with T2DM, it is recommended that SD be considered as an important complication in these patients so that by identifying indicators related to this complication in patients with diabetes, sexual health clinics take the necessary measures to solve sexual problems in these patients. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease's development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM. Methods: This systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes' certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373. Results: Four thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA1c) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA1c, with standard-treatment (STA-TRE) as reference (MD − 0.17, 95%CI − 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD − 11.72, 95%CI − 17.82 to − 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence. Conclusions: The high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients. [ABSTRACT FROM AUTHOR]

Obesity and overweight represent a growing health problem worldwide. Genes regulating the intake and metabolism of different nutrients can positively or negatively influence the efficacy of nutritional interventions against obesity and its complications. The aim of this study was to assess changes in anthropometric and clinical parameters and the adherence to a Mediterranean diet (MedDiet) over time in relation to nutrigenetic variants in overweight or obese subjects affected by Type 2 Diabetes (T2D) or dysglycemia, who were included in a nutritional program. A total of 23 subjects were included in this study. Clinical parameters, physical activity levels, and the adherence to a MedDiet were evaluated at baseline, at 6 (T6), and at 12 months (T12) during and after a diet/lifestyle intervention. In a single blood sample from each subject, rs1984112 (A>G) and rs1761667 (G>A) in CD36; rs7950226 (G>A) in BMAL1; and rs1801260 (A>G), rs4864548 (A>G), and rs3736544 (G>A) in CLOCK were genotyped with Real-Time PCR. Significant associations were observed between CD36 rs1761667 and weight (p = 0.025), hip circumference (p = 0.042), triglycerides (p = 0.047), and HbA1c (p = 0.012) at baseline. Moreover, the genotype AA in CD36 rs1761667 was significantly associated with a lower BMI when compared to G carriers at baseline, at T6, and also at T12. In addition, subjects with the AA genotype at CD36 rs1984112 had significantly lower levels of HbA1c (p = 0.027) than the GG and AG genotypes at baseline. These results show that variants in CD36 can have an impact on anthropometric and clinical parameters in overweight or obese subjects affected by T2D or dysglycemia, and that it might influence the success of the diet/lifestyle intervention. [ABSTRACT FROM AUTHOR]

Background: Evidence from preclinical studies has found a correlation between the development of type 2 diabetes (T2D) and vitamin D deficiency. However, evidence from randomized controlled trials (RCTs) revealed inconclusive results on vitamin D supplementation. We explored the effect of vitamin D on inflammation and dyslipidemia in T2D. Methods: We comprehensively searched for RCTs evaluating the effect of vitamin D in T2D on PubMed. Data were analyzed using Review Manager 5.3 and reports, such as standardized mean difference (SMD) and 95% confidence intervals (CI) at a 5% significant level using a random effect model. Results: This study revealed a significant reduction in tumor necrosis factor-alpha (TNF-α) SMD = (−0.51, 95%CI (−0.93, −0.09); p = 0.02), high sensitivity C-reactive protein (hs-CRP) SMD = (−1.06, 95%CI (−1.67, −0.45); p < 0.05) in vitamin D compared to placebo. Additionally, interleukin-6 (IL-6) exhibited a marginal effect SMD = (−0.52, 95%CI (−1.05, 0.01), p = 0.05). Furthermore, a significant reduction in the level of triglycerides SMD = (−0.65, 95%CI (−1.11, −0.18), p < 0.05) was observed, concomitant to a significantly increased high-density lipoprotein (HDL) level SMD = (0.53, 95%CI (0.08, 0.98), p = 0.02). However, no statistically significant changes were observed in total cholesterols SMD = (−0.16, 95%CI (−0.57, 0.24), p = 0.43) and low-density lipoprotein (LDL) SMD = (−0.06, 95%CI (−0.37, 0.24), p = 0.67). Conclusions: These findings suggest that vitamin D supplementation may be beneficial in ameliorating inflammation and dyslipidemia in T2D patients. [ABSTRACT FROM AUTHOR]

Fermented foods refer to beverages or foods made by carefully regulated microbial growth and the enzymatic conversion of dietary components. Fermented foods have recently become more popular. Studies on fermented foods suggest the types of bacteria and bioactive peptides involved in this process, revealing linkages that may have impacts on human health. By identifying the bacteria and bioactive peptides involved in this process, studies on fermented foods suggest relationships that may have impressions on human health. Fermented foods have been associated with obesity, cardiovascular disease, and type 2 diabetes. In this article, fermented dairy products, vegetables and fruits, legumes, meats, and grains are included. Two elements in particular are emphasized when discussing the fermentation of all of these foods: bioactive chemicals generated during fermentation and microorganisms involved during fermentation. Organic acids, bioactive peptides, conjugated linoleic acid, biogenic amines, isoflavones, phytoestrogens, and nattokinase are a few of the bioactive compounds included in this review. Also, certain bacteria such as Lactobacillus, Bifidobacterium, Streptococcus, and Bacillus species, which are utilized in the fermentation process are mentioned. The effects of both substances including anti-fungal and antioxidant properties; the modulation of intestinal microbiota; anti-inflammatory, antidiabetes, anti-obesity, anticancer, and antihypertension properties; and the protection of cognitive function are explained in this review. [ABSTRACT FROM AUTHOR]

Background: The prevalence of type 2 diabetes is a global health challenge that requires continuous care. Non-pharmaceutical interventions in controlling and treating type 2 diabetes can be less costly and have fewer complications. Accordingly, this study identifies non-pharmaceutical interventions in controlling and treating type 2 diabetes through systematic review. Methods: This study is a systematic review of the papers published in non-pharmaceutical interventions to control and treat type 2 diabetes. The authors have used the standard guideline of systematic review (PRISMA). A total of 41 papers were selected from 529 full-text articles published between 2014 and 2020. The search included the electronic data banks, including Medline, Science Direct, Embase, Scopus, Cochrane Library, and the Google Scholar search engine. Results: Non-pharmaceutical interventions were classified into four categories: Lifestyle, treatment devices, traditional treatment, and education. The results showed that lifestyle modification is the most effective non-pharmaceutical intervention for treating type 2 diabetes. Conclusion: Study findings show that applying non-pharmaceutical interventions effectively controls and prevents type-2 diabetes complications. Education is a part that needs to be given more attention. [ABSTRACT FROM AUTHOR]

Albeit the reasonableness of vitamin D supplementation in lessening unmistakable diabetes stays muddled, vitamin D has arisen as a huge indicator of progress in type 2 diabetes. We played out a thorough meta-examination that included hybrid investigations and controlled preliminaries randomly chosen to account for this uncertainty. Our findings add to the ongoing discussion surrounding this issue and provide useful information regarding the possibility that vitamin D plays a role in the treatment of type 2 diabetes. In this systematic review, we wanted to provide a comprehensive overview of the most recent data on the effects of vitamin D on people with type 2 diabetes. We searched multiple databases in accordance with PRISMA guidelines and found 40 relevant studies published between 2015 and 2022. may make the disease more likely to happen to you. However, other considerations, such as one's lifestyle, diet, and genetic predisposition to type 2 diabetes, are essential. Conversely, our meta-investigation of randomized clinical preliminaries found that vitamin D supplementation didn't fundamentally lessen the gamble of creating type 2 diabetes. According to these findings, supplementing vitamin D levels may not be sufficient to stop disease progression. The individual and the underlying pathophysiology of the disease may determine how Diabetes type 2 can be fought with vitamin D. Basically the survey takes a better reaching evaluation of the nowadays information on the types of diabetes with the connection. More exploration is expected to all the more likely comprehend the components in question and to investigate extra preventive methodologies and mediations for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Impaired iron metabolism has been increasingly observed in many diseases, but a deeper, mechanistic understanding of the cellular impact of altered iron metabolism is still lacking. In addition, deficits in neuronal energy metabolism due to reduced glucose import were described for Alzheimer's disease (AD) and its comorbidities like obesity, depression, cardiovascular disease, and type 2 diabetes mellitus. The aim of this review is to present the molecular link between both observations. Insufficient cellular glucose uptake triggers increased ferritin expression, leading to depletion of the cellular free iron pool and stabilization of the hypoxia-induced factor (HIF) 1α. This transcription factor induces the expression of the glucose transporters (Glut) 1 and 3 and shifts the cellular metabolism towards glycolysis. If this first line of defense is not adequate for sufficient glucose supply, further reduction of the intracellular iron pool affects the enzymes of the mitochondrial electron transport chain and activates the AMP-activated kinase (AMPK). This enzyme triggers the translocation of Glut4 to the plasma membrane as well as the autophagic recycling of cell components in order to mobilize energy resources. Moreover, AMPK activates the autophagic process of ferritinophagy, which provides free iron urgently needed as a cofactor for the synthesis of heme- and iron–sulfur proteins. Excessive activation of this pathway ends in ferroptosis, a special iron-dependent form of cell death, while hampered AMPK activation steadily reduces the iron pools, leading to hypoferremia with iron sequestration in the spleen and liver. Long-lasting iron depletion affects erythropoiesis and results in anemia of chronic disease, a common condition in patients with AD and its comorbidities. Instead of iron supplementation, drugs, diet, or phytochemicals that improve energy supply and cellular glucose uptake should be administered to counteract hypoferremia and anemia of chronic disease. [ABSTRACT FROM AUTHOR]

Celery (Apium graveolens) was shown to have beneficial effects on cardiometabolic factors in animal models. As the progression of type 2 diabetes mellitus (T2DM) adversely affects cardiometabolic factors, we aimed to assess the effects of celery powder on glycemic and anthropometric indices, lipid profile, liver function, oxidative stress, and blood pressure of individuals with T2DM. In a pilot randomized, double‐blinded, placebo‐controlled clinical trial, 50 eligible adults with T2DM were randomly divided into two groups of intervention and control to consume either 750 mg of celery powder (obtained from fresh celery) or placebo along with a low‐calorie diet for 12 weeks, respectively. Dietary intake, physical activity, and cardiometabolic factors were assessed before and at the end of the study. Thirty‐six patients finished the study (18 in each group). Consumption of celery powder significantly reduced body fat percentage (p =.021). Between‐group analysis for changes in cardiometabolic factors did not show significant differences. Although malondialdehyde was reduced in the intervention group and increased in the control group, between‐group changes were not significant. Although the insulin‐level change was statistically insignificant, a clinical improvement was observed in the intervention group. A 750‐mg daily supplementation of celery powder for 12 weeks did not improve the cardiometabolic factors of patients with T2DM. Further studies are suggested. [ABSTRACT FROM AUTHOR]

Propolis, a natural resinous mixture rich in polyphenols, produced by bees from a variety of plant sources, has shown significant therapeutic effects and may prevent the development of certain chronic diseases like type 2 diabetes mellitus (T2DM). The objective of this study was to evaluate the effect of supplementation with standardized poplar propolis extract powder (PPEP) on insulin homeostasis in non-diabetic insulin-resistant volunteers with obesity. In this randomized, controlled, crossover trial, nine non-diabetic insulin-resistant volunteers with obesity, aged 49 ± 7 years, were subjected to two periods of supplementation (placebo and PPEP) for 3 months. Blood samples and anthropomorphic data were collected at baseline and at the end of each phase of the intervention. PPEP supplementation improved insulin sensitivity by significantly decreasing the percentage of insulin-resistant subjects and the insulin sensitivity Matsuda index (ISI-M). According to this study, supplementation with standardized PPEP for 3 months in non-diabetic insulin-resistant volunteers with obesity led to an improvement in insulin homeostasis by its effect on insulin resistance and secretion. This study suggests that poplar propolis has a preventive effect on the physiopathological mechanisms of T2DM and, therefore, that it can help to prevent the development of the disease. [ABSTRACT FROM AUTHOR]

Aims: This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and its related bioactive compounds on glycemic and metabolic parameters in patients with type 2 diabetes (T2DM), prediabetes, and metabolic syndrome (MetS) together with a sub-group analysis of different CL preparation forms. Methods: An umbrella review (UR) and updated systematic reviews and meta-analyses (SRMAs) were conducted to evaluate the effects of CL compared with a placebo/standard treatment in adult T2DM, prediabetes, and MetS. The MEDLINE, Embase, The Cochrane Central Register of Control Trials, and Scopus databases were searched from inception to September 2022. The primary efficacy outcomes were hemoglobin A1C (HbA1C) and fasting blood glucose (FBG). The corrected covered area (CCA) was used to assess overlap. Mean differences were pooled across individual RCTs using a random-effects model. Subgroup and sensitivity analyses were performed for various CL preparation forms. Results: Fourteen SRMAs of 61 individual RCTs were included in the UR. The updated SRMA included 28 studies. The CCA was 11.54%, indicating high overlap across SRMAs. The updated SRMA revealed significant reduction in FBG and HbA1C with CL supplementation, obtaining a mean difference (95% confidence interval [CI]) of –8.129 (–12.175, –4.084) mg/dL and –0.134 (–0.304, –0.037) %, respectively. FBG and HbA1C levels decreased with all CL preparation forms as did other metabolic parameters levels. The results of the sensitivity and subgroup analyses were consistent with those of the main analysis. Conclusion: CL supplementation can significantly reduce FBG and HbA1C levels and other metabolic parameters in T2DM and mitigate related conditions, including prediabetes and MetS. Trial registration: PROSPERO (CRD42016042131). [ABSTRACT FROM AUTHOR]

Objective: Gene-diet interaction plays a key role in the inter-individual differences in lipid abnormalities as a major risk factor for cardiovascular diseases (CVDs). Thus, we explored the interaction between CETP TaqB1 polymorphism with dietary acid load (DAL) on lipid profile among type 2 diabetes mellitus (T2DM). Method: This cross-sectional study conducted on 220 Iranian patients with T2DM. Dietary acid load (PRAL and NEAP) was calculated via a validated food-frequency questionnaire (FFQ). The polymerase chain reaction (PCR) used for genotyping Taq1B polymorphism. Biochemical markers were measured by standard protocol. The interaction between CETP Taq1B polymorphism and DAL (PRAL and NEAP) on lipid profile was performed by a generalized linear regression model (GLM). Results: The overall prevalence of rs708272 genotypes was 8.6%, 72.7% and 18.6% for B1B1, B1B2 and B2B2 genotype respectively. This study showed that people with the B1B1 genotype had greater LDL, TC, LDL/HDL, and TG when they consumed diets that scored higher on the NEAP and PRAL indexes than those with the B1B2 and B2B2 genotypes. Besides, carriers of the B1B1 allele who were in the highest tertile of NEAP, had lower HDL (P Interaction < 0.05). Conclusions: In summary, the lipid profile might be improved in B1B1 homozygotes by less adherence to DAL indexes, however, the findings should be validated in high-quality interventional studies. [ABSTRACT FROM AUTHOR]

Background: Carnitine is necessary for allowing the long-chain fatty acids to pass the inner mitochondrial membrane to induce β -oxidation. Lack of carnitine and abnormalities of mitochondria play an important role in forming fatty deposition in the liver, and hence, developing steatohepatitis. Carnitine and acylcarnitine identified in human erythrocytes and intra-erythrocyte acetylcarnitine have a significant relationship with the plasma levels. Methods: The present study was conducted to investigate the possible effects of L-carnitine on liver function, folate and vitamin B12 levels in patients with type 2 diabetes mellitus (T2DM). In this study, 70 patients with T2DM were randomly assigned to either a L-carnitine (CG) and a placebo group (PG). For 12 weeks, the first group received 1000 mg/d oral Lcarnitine, whereas the second group received 1000 mg/day wheat starch as placebo. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), folate, Vitamin B12, complete blood count (CBC) including blood cells and indicators related to anemia were assessed at baseline. Results: 64 patients managed to complete the study (32 in each group). The results indicated that consumption of L-carnitine compared with placebo had no significant effect on liver enzymes, folate, vitamin B12, and CBC with differential. Conclusions: Daily intake of 1000 mg L-carnitine for 12 weeks had no effect on liver function and anemia indicators including CBC, folate, and vitamins B12. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) affects a large part of the adult population and impairs its quality of life. Because of this, natural compounds with antioxidant, anti-inflammatory and hypoglycemic properties have been used as adjuvants. Among these compounds, resveratrol (RV) stands out, a polyphenol that has been studied in several clinical trials, the results of which are controversial. We conducted a randomized clinical trial on 97 older adults with T2D to evaluate the effect of RV on oxidative stress markers and sirtuin 1, using doses of 1000 mg/day (EG1000, n = 37) and 500 mg/day (EG500, n = 32) compared with a placebo (PG, n = 28). Biochemical markers, oxidative stress and sirtuin 1 levels were measured at baseline and after six months. We observed a statistically significant increase (p < 0.05) in total antioxidant capacity, antioxidant gap, the percentage of subjects without oxidant stress and sirtuin 1 levels in EG1000. In the PG, we observed a significant increase (p < 0.05) in lipoperoxides, isoprostanes and C-reactive protein levels. An increase in the oxidative stress score and in the percentage of subjects with mild and moderate oxidative stress was observed too. Our findings suggest that 1000 mg/day of RV exerts a more efficient antioxidant effect than 500 mg/day. [ABSTRACT FROM AUTHOR]

Diet frequency may potentially influence metabolic health. However, general population-based evidence on the association between meal frequency and type 2 diabetes mellitus (T2DM) remains limited and inconclusive. Thus, this study aimed to investigate the association between meal frequency and T2DM in resource limited area. A total of 29,405 qualified participants were enrolled from the Henan rural cohort study. Data on meal frequency were collected through a validated face-to-face questionnaire survey. Logistic regression models were utilized to explore the association between meal frequency and T2DM. Compared with 21 times per week meal frequency group, the adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) were 0.75 (0.58, 0.95) and 0.70 (0.54, 0.90) for 16–20 times/week group and 14–15 times/week group, respectively. For the analysis of the three meals, significant associations were only found between dinner frequency and T2DM. Compared with seven times per week dinner group, the ORs (95%CIs) were 0.66 (0.42, 0.99) and 0.51 (0.29, 0.82) for the group with three to six times/week and zero to two times/week. Reduced meal frequency, especially dinner frequency, was associated with lower prevalence of T2DM, which suggests that an appropriate reduction in meal frequency per week may have a role in decreasing the risk of T2DM. [ABSTRACT FROM AUTHOR]

Most medical investigations have found a reduced blood level of miR-146a in type 2 diabetes (T2D) patients, suggesting an important role for miR-146a (microRNA-146a) in the etiology of diabetes mellitus (DM) and its consequences. Furthermore, injection of miR-146a mimic has been confirmed to alleviate diabetes mellitus in diabetic animal models. In this line, deregulation of miR-146a expression has been linked to the progression of nephropathy, neuropathy, wound healing, olfactory dysfunction, cardiovascular disorders, and retinopathy in diabetic patients. In this review, besides a comprehensive review of the function of miR-146a in DM, we discussed new findings on type 1 (T1MD) and type 2 (T2DM) diabetes mellitus, highlighting the discrepancies between clinical and preclinical investigations and elucidating the biological pathways regulated through miR-146a in DM-affected tissues. [ABSTRACT FROM AUTHOR]

Metabolic diseases have become a serious threat to human health worldwide. It is crucial to look for effective drugs from natural products to treat metabolic diseases. Curcumin, a natural polyphenolic compound, is mainly obtained from the rhizomes of the genus Curcuma. In recent years, clinical trials using curcumin for the treatment of metabolic diseases have been increasing. In this review, we provide a timely and comprehensive summary of the clinical progress of curcumin in the treatment of three metabolic diseases, namely type 2 diabetes mellitus (T2DM), obesity and non-alcoholic fatty liver disease (NAFLD). The therapeutic effects and underlying mechanisms of curcumin on these three diseases are presented categorically. Accumulating clinical evidence demonstrates that curcumin has good therapeutic potential and a low number of side effects for the three metabolic diseases. It can lower blood glucose and lipid levels, improve insulin resistance and reduce inflammation and oxidative stress. Overall, curcumin may be an effective drug for the treatment of T2DM, obesity and NAFLD. However, more high-quality clinical trials are still required in the future to verify its efficacy and determine its molecular mechanisms and targets. [ABSTRACT FROM AUTHOR]

Over the years, there has been heightened interest in the health benefits of n-3 polyunsaturated fatty acids (PUFA) in reducing chronic diseases such as, cardiovascular disease (CVD), cancer, type 2 diabetes, and acute macular degeneration (AMD). Due to inconsistent findings in the evidence, a review to critically examine the plethora of evidence from randomized controlled trials (RCTs) in n-3 PUFA research was undertaken. The aim of this review is to study the highest level of evidence and to identify gaps in n-3 PUFA research. RCTs were originally designed for pharmaceutical research and later adopted for nutrition and food-related research. RCTs with active diseases assume that n-3 PUFA will have "drug" like effects, and this high expectation may have led to the inconsistent evidence in the literature. The inconsistency in the literature may be related to varying doses of n-3 PUFA, sources of n-3 PUFA (food vs. supplement; plant vs. marine), type of n-3 PUFA (mixture vs. purified), trial duration, population characteristics, sample size, and genetic variation. For future research, there is a need to distinguish between primary and secondary prevention, and to focus RCTs on primary prevention of chronic diseases by n-3 PUFA which is lacking in the literature. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of a number of endocrine disorders; this, in turn, suggests a potential role for the vitamin-like substance coenzyme Q10 (CoQ10) in the pathogenesis and treatment of these disorders, on the basis of its key roles in mitochondrial function, and as an antioxidant. In this article we have therefore reviewed the role of CoQ10 deficiency and supplementation in disorders of the thyroid, pancreas, gonads, pituitary and adrenals, with a particular focus on hyperthyroidism, type II diabetes, male infertility and polycystic ovary syndrome. [ABSTRACT FROM AUTHOR]

Reference genes are obligatory for accurate normalization of mRNA transcript levels across samples and experimental conditions in Real Time-polymerase chain reaction (qRT-PCR) based quantitative gene expression assays. Selection of stably expressed reference genes is therefore crucial for ensuring reproducibility of such assays. However, there is a complete dearth of data on stability of commonly used reference genes in Peripheral Blood Mononuclear Cells (PBMCs) from Type 2 diabetes mellitus (T2DM) patients. We have evaluated the gene expression stability of 4 widely used reference genes (Beta-actin, ACTB; Peptidylprolyl Isomerase B, PPIB; Tyrosine 3 Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Zeta, YWHAZ; and Glyceraldehyde-3-Phosphate Dehydrogenase, GAPDH); in PBMCs from 39 T2DM patients and 47 normoglycemic (NGT) subjects. ACTB and YWHAZ were found to be the most stable genes in PBMCs from T2DM patients and therefore, can be recommended as suitable reference genes in similar contexts. GAPDH and PPIB expressions were not stable in PBMCs from T2DM patients. On using ACTB and YWHAZ as reference genes for measuring relative expression of GAPDH and PPIB in these subjects, relative GAPDH expression was found to be significantly lower in female T2DM patients, compared to female NGT subjects [GAPDH relative normalization unit (RNU): female T2DM (n = 19), median (Q1, Q3): 9.0 (8.1, 9.9); female NGT (n = 18): median (Q1, Q3): 10.1 (9.1, 11.0); P = 0.034]. Dysregulation of GAPDH in PBMCs from female T2DM patients could be associated with sex-specific differences in pathogenesis and outcomes of T2DM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with still growing incidence among adults and young people worldwide. Patients with T2DM are more susceptible to developing coronary artery disease (CAD) than non-diabetic individuals. The currently used diagnostic methods do not ensure the detection of CAD at an early stage. Thus, extensive research on non-invasive, blood-based biomarkers is necessary to avoid life-threatening events. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that are stable in human body fluids and easily detectable. A number of reports have highlighted that the aberrant expression of miRNAs may impair the diversity of signaling pathways underlying the pathophysiology of atherosclerosis, which is a key player linking T2DM with CAD. The preclinical evidence suggests the atheroprotective and atherogenic influence of miRNAs on every step of T2DM-induced atherogenesis, including endothelial dysfunction, endothelial to mesenchymal transition, macrophage activation, vascular smooth muscle cells proliferation/migration, platelet hyperactivity, and calcification. Among the 122 analyzed miRNAs, 14 top miRNAs appear to be the most consistently dysregulated in T2DM and CAD, whereas 10 miRNAs are altered in T2DM, CAD, and T2DM-CAD patients. This up-to-date overview aims to discuss the role of miRNAs in the development of diabetic CAD, emphasizing their potential clinical usefulness as novel, non-invasive biomarkers and therapeutic targets for T2DM individuals with a predisposition to undergo CAD. [ABSTRACT FROM AUTHOR]

Background: Flaxseed and its components have an anti-diabetic effect. Glycemic control is improved by flaxseeds and flax lignin. High levels of soluble fiber and other bioactive components of flaxseeds help in maintaining normal plasma glucose levels and have a protective effect against diabetes risk. Aim: This study aimed to find out the effect of addition of flaxseed (FXS) or flaxseed oil (FXO) to bakery products on blood glucose, body mass index, and serum lipids in type 2 diabetic patients. Design: An experimental design was conducted to achieve aim of this study. Setting: the study was carried out diabetes unite (diabetes clinic) at Armed Forces hospital, Beni-Suef city, Egypt. Subjects: Randomized cross-sectional study of cases 90 geriatric patients who have diabetic mellitus types 2 in the previous mentioned setting. Tools: I- Complete history taken; it was used to assess demographic characteristics and height of patients with type 2 diabetes mellitus-II- Full clinical examination to assess patients' fasting and postprandial blood, body mass index, cholesterol, low and high density lipoproteins (LDL & HDL), serum and creatinine level in urine. Results: revealed that, there was a statistically significant improvement in studied subjects' clinical examination in studied group 1 and group 2 after flaxseed intervention. there is a statistically significant improvement in studied subjects' clinical examination in studied group 1 and group 2 than control subjects after flaxseed intervention except HDL, HbA1C and BMI among group2. Conclusion: There was a positive effect for flaxseeds on DM type 2 outcomes among geriatric diabetic patients. Recommendations: Increasing public awareness regarding the benefits of using flaxseeds in improving diabetes mellitus outcomes after consulting a doctor to use the appropriate dose. [ABSTRACT FROM AUTHOR]

Perivascular adipose tissue (PVAT)-derived extracellular vesicles (EVs) with small exosome(s) (PVAT-dEVexos) from the descending aorta are capable of entering capillaries and systemic circulation. These PVAT-dEVexos are delivered to the central nervous system (CNS) in preclinical, obese, insulin and leptin resistant, diabetic, db/db mouse models and humans with T2DM. Once within the CNS, these exosomes are capable of traversing the blood–brain barrier and the blood-cerebrospinal fluid barrier resulting in activation of the neuroglia microglia cell(s) (aMGCs) and the formation of reactive astrocytes (rACs). The chronic peripheral inflammation in the PVAT via crown-like structures consists of activated macrophages and mast cells, which harbor peripheral adipokines, cytokines, and chemokines (pCC) in addition to the EV exosomes. These pCC are transported to the systemic circulation where they may act synergistically with the PVAT-dEVexos to amplify the activation of neuroglia and result in chronic neuroinflammation. Once activated, the MGCs and ACs will contribute to even greater neuroinflammation via central nervous cytokines/chemokines (cnsCC). Activated neuroglia results in an increase of cnsCC and the creation of a vicious cycle of ongoing chronic neuroinflammation and increased redox stress. The increase in reactive oxygen species (ROS) involves the reactive species interactome that not only include reactive oxygen but also reactive nitrogen and sulfur species wherein a vicious cycle of ROS begetting inflammation and inflammation begetting ROS develops. Thus, the CNS perceives peripheral systemic inflammation from the obese PVAT depots as an injury and a response to injury wound healing mechanism develops with activation of neuroglia, cellular remodeling, neurodegeneration, and impaired cognition. [ABSTRACT FROM AUTHOR]

MicroRNA regulates multiple pathways in inflammatory response, adipogenesis, and glucose and lipid metabolism, which are involved in metabolic syndrome (MetS). Thus, this systematic review aimed at synthesizing the evidence on the relationships between circulating microRNA and risk factors for MetS. The systematic review was registered in the PROSPERO database (CRD42020168100) and included 24 case-control studies evaluating microRNA expression in serum/plasma of individuals ≥5 years old. Most of the studies focused on 13 microRNAs with higher frequency and there were robust connections between miR-146a and miR-122 with risk factors for MetS, based on average weighted degree. In addition, there was an association of miR-222 with adiposity, lipid metabolism, glycemic metabolism, and chronic inflammation and an association of miR-126, miR-221, and miR-423 with adiposity, lipid, and glycemic metabolism. A major part of circulating microRNA was upregulated in individuals with risk factors for MetS, showing correlations with glycemic and lipid markers and body adiposity. Circulating microRNA showed distinct expression profiles according to the clinical condition of individuals, being particularly linked with increased body fat. However, the exploration of factors associated with variations in microRNA expression was limited by the variety of microRNAs investigated by risk factor in diverse studies identified in this systematic review. [ABSTRACT FROM AUTHOR]

Aims: To compare the effects of replacing regular dietary oils intake with sesame (SO), canola (CO), and sesame–canola (SCO) oils (a novel blend), on cardiometabolic markers in adults with type 2 diabetes mellitus (T2DM), in a triple-blind, three-way, randomized, crossover clinical trial. Methods: Participants were assigned to receive SO, CO, and SCO in three 9-week phases (4 weeks apart). Cardiometabolic makers (serum lipids, Apolipoprotein, cardiovascular risk scores, kidney markers, and blood pressure) were considered at the beginning and the end of intervention phases. Results: Ninety-two, ninety-five, and ninety-five participants completed the SO, SCO, and CO periods, respectively. After CO consumption, serum Apo A-1 concentrations were significantly higher compared with the SCO period in the whole population (p < 0.05). A considerable reduction in visceral adiposity index values was seen in the CO compared with the SO period in males (p < 0.05). Serum high-density lipoprotein concentration was also significantly higher after the SO intake compared with SCO in females (p < 0.05). The between-period analysis showed a substantial reduction in diastolic blood pressure in the SCO period compared with the CO and SO periods and lower systolic blood pressure after SCO versus CO intake in males (p < 0.05). Conclusions: Canola oil might protect CVD through improving Apo A-1 levels in patients with T2DM (particularly in females) and visceral adiposity index in male patients. However, the blend oil might beneficially affect blood pressure in men. Future sex-specific studies might warrant the current findings. Registry of clinical trials: This trial was registered in the Iranian Registry of Clinical Trials (IRCT, registration ID: IRCT2016091312571N6). [ABSTRACT FROM AUTHOR]

Obesity remains a global health problem. Chronic low-grade inflammation in this pathology has been related to comorbidities such as cognitive alterations that, in the long term, can lead to neurodegenerative diseases. Neuroinflammation or gliosis in patients with obesity and type 2 diabetes mellitus has been related to the effect of adipokines, high lipid levels and glucose, which increase the production of free radicals. Cerebral gliosis can be a risk factor for developing neurodegenerative diseases, and antioxidants could be an alternative for the prevention and treatment of neural comorbidities in obese patients. Aim: Identify the immunological and oxidative stress mechanisms that produce gliosis in patients with obesity and propose antioxidants as an alternative to reducing neuroinflammation. Method: Advanced searches were performed in scientific databases: PubMed, ProQuest, EBSCO, and the Science Citation index for research on the physiopathology of gliosis in obese patients and for the possible role of antioxidants in its management. Conclusion: Patients with obesity can develop neuroinflammation, conditioned by various adipokines, excess lipids and glucose, which results in an increase in free radicals that must be neutralized with antioxidants to reduce gliosis and the risk of long-term neurodegeneration. [ABSTRACT FROM AUTHOR]

Background: Several clinical trials have suggested that resveratrol has hypoglycemic properties; however, there are other studies in which such an effect has not been observed. Methods: We carried out a systematic search in several databases; seventeen studies were selected for the systematic review and fifteen were included in the meta-analysis. Results: Resveratrol decreases glucose levels in subjects aged 45–59 years at doses <250 mg/day (−8.64 mg/dL, p < 0.00001), 250–500 mg/day (−22.24 mg/dL, p = 0.0003), and 500–1000 mg/day (−28.40 mg/dL, p = 0.0008), while in subjects older than 60 years, it only decreases with doses of 250–500 mg/day. Likewise, HbA1c improved in subjects aged 45–59 years with doses of 250–500 mg (−0.60%, p < 0.00001), but not in subjects older than 60 years. Insulin levels improved in subjects aged 45–59 years with doses < 250 mg/day (−0.80 mIU/L, p = 0.0003) and doses of 250–500 mg/day (−5.0 mIU/L, p = 0.0003), although in subjects older than 60 years, they only improved with doses of 250–500 mg/day (−1.79 mIU/L, p = 0.01). On the other hand, HOMA-IR only improved in subjects older than 60 years with doses of 250–500 mg/day (−0.40, p = 0.01). Conclusions: Resveratrol has a statistically significant dose–response effect on glucose concentrations, HbA1c, and insulin levels; however, there is not enough scientific evidence to propose a therapeutic dose. [ABSTRACT FROM AUTHOR]

Background. There are few reports on the relationship between dietary patterns and cardiovascular disease (CVD) risk in patients with type 2 diabetes (T2D). This study aimed to explore relationships between dietary patterns and CVD risk in the T2D population using multiple statistical analysis methods. Methods. A total of 2,984 patients with T2D from the Xinjiang Multi-Ethnic Cohort, 555 of whom were suffering from CVD, were enrolled in this study. Participants' dietary intake was measured by the semiquantitative food frequency questionnaire (FFQ). Three statistical methods were used to construct dietary patterns, including principal component analysis (PCA) method, reduced-rank regressions (RRR) method, and partial least-squares regression (PLS) method. Then, the association between dietary patterns and CVD risk in T2D patients was analyzed by logistic regression. After excluding participants with CVD, the associations between dietary patterns and 10-year CVD risk scores were subsequently evaluated to reduce reverse causality. Results. In this study, four dietary patterns were identified by three methods. Adjustment for confounding factors, subjects with the highest scores on the "high-protein and high-carbohydrate" patterns derived from PCA, RRR, and PLS had higher odds of CVD than those with the lowest scores (OR: 2.89, 95% CI: 2.11–3.96, P t r e n d < 0.001 ; OR: 2.96, 95% CI: 2.17–4.03, P t r e n d < 0.001 ; OR: 2.01, 95% CI: 1.50–2.70, P t r e n d < 0.001 , respectively). However, the dietary pattern of PCA-prudent was not significantly related to the odds of having CVD in T2D patients (adjusted ORQ4vsQ1: 0.93, 95% CI: 0.70–1.24, P t r e n d = 0.474). Interestingly, we also found significant associations between "high-protein and high-carbohydrate" patterns and the elevated predicted 10-year CVD risk in T2D patients (all P t r e n d < 0.05). Conclusion. The positive correlation between "high-protein and high-carbohydrate" patterns and CVD risk in T2D patients was robust across all three data-driven approaches. These findings may have public health significance, encouraging an emphasis on food choices in the usual diet and promoting nutritional interventions for patients with T2D to prevent CVD. [ABSTRACT FROM AUTHOR]

Cocoa consumption as a diet has been shown to improve cardiometabolic biomarkers for T2D, but results were inconsistent. A comprehensive search from PubMed, Web of Science, Embase, and The Cochrane Library to identify the randomised controlled trials investigating the impacts of cocoa products consumption on cardiometabolic biomarkers in T2D was performed up to December 2020. Twelve trials involving 9 long-term and 3 short-term studies were included. The cocoa products significantly decreased low density lipoprotein-cholesterol (WMD: −9.955 mg/dL, 95% CI: −17.408, −2.501, p = 0.009), triglyceride (WMD: −15.364 mg/dL, 95% CI: −23.383, −7.346, p < 0.001), blood glucose (WMD: −9.105 mg/dL, 95% CI: −15.022, −3.189, p = 0.003), and C-reactive protein (WMD: −0.978 mg/L, 95% CI: −1.687, −0.269, p = 0.007) in long-term. The results indicated the beneficial long-term effects of cocoa products intake on cardiometabolic biomarkers for T2D, especially on blood glucose, lipid metabolism (LDL-C and TG), and inflammation (CRP). [ABSTRACT FROM AUTHOR]

This investigation with aimed the effect of APOA2–265 T > C polymorphism and dietary acid load (DAL) as either potential renal acid load (PRAL) and net endogenous acid production (NEAP) intake interaction on metabolic markers in type 2 diabetes mellitus (T2DM). In present cross-sectional study, 737 patients with T2DM (290 men and 447 women) were enlisted from diabetes centers in Tehran. The dietary intakes of all participants during the last year was acquired by a validated semi-quantitative food frequency (FFQ) questionnaire. Polymerase chain reaction (PCR) was used for genotyping the APOA2–265 T > C. Biochemical indises containing leptin, ghrelin, total cholesterol (Bailey et al., J Clin Invest 97:1147–1453, 1996), low-density lipoprotein cholestrol (LDL-C), high-density lipoprotein cholestrol (HDL-C), triglyceride (TG), superoxide dismutase (SOD), high sensitivy C-reactive protein (hs-CRP), total antioxidant capacity (TAC), pentraxin-3 (PTX3), prostaglandin F2α (PGF2α) and interleukin 18 (IL18) were measured by standard method. Atherogenic indices (AIP, AC, CR-I, CR-II) were calculated. The gene-diet interactions were evaluated using an GLM. The frequency overall prevalence of rs5082 genotypes was 63.82 and 36.17% for T-allele and C-allele respectively. TG, Ghrelin, and hs-CRP concentrations were significantly higher among carriers with C allele than TT homozygotes. However, TC/CC genotypes have lower PTX3 than TT homozygotes (P < 0.05). C-allele carriers had highest mean of BMI (PNEAP=0.04, PPRAL = 0.006), WC (PNEAP=0.04, PPRAL = 0.04), TC (PNEAP=0.03, PPRAL = 0.01), ghrelin (PNEAP=0.01, PPRAL = 0.04), and leptin (PNEAP=0.04, PPRAL = 0.03) when placed in top tertiles of NEAP and PRAL.BMI, WC, TC, ghrelin, and leptin levels may be modified in C carriers by decreasing DAL, though, further investigations are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Health promotion campaigns have advocated for individuals to 'eat a rainbow' of fruits and vegetables (FV). However, the literature has only focused on individual color pigments or individual health outcomes. This umbrella review synthesized the evidence on the health effects of a variety of color-associated bioactive pigments found in FV (carotenoids, flavonoids, betalains and chlorophylls), compared to placebo or low intakes. A systematic search of PubMed, EMBASE, CINAHL and CENTRAL was conducted on 20 October 2021, without date limits. Meta-analyzed outcomes were evaluated for certainty via the GRADE system. Risk of bias was assessed using the Centre for Evidence-Based Medicine critical appraisal tools. A total of 86 studies were included, 449 meta-analyzed health outcomes, and data from over 37 million participants were identified. A total of 42% of health outcomes were improved by color-associated pigments (91% GRADE rating very low to low). Unique health effects were identified: n = 6 red, n = 10 orange, n = 3 yellow, n = 6 pale yellow, n = 3 white, n = 8 purple/blue and n = 1 green. Health outcomes associated with multiple color pigments were body weight, lipid profile, inflammation, cardiovascular disease, mortality, type 2 diabetes and cancer. Findings show that color-associated FV variety may confer additional benefits to population health beyond total FV intake. [ABSTRACT FROM AUTHOR]

Background: It has been reported that more than half of those with type 2 diabetes used at least one complementary and alternative approach. Among the most preferred of these approaches, herbal products/food supplements are widely used in the management of diabetes in many countries. Aim: This study aims to examine the use of herbal products/food supplements in diabetes management of individuals with type 2 diabetes in Turkey. Method and Material: This study was a cross-sectional and descriptive type. The research is conducted in Diabetes Monitoring and Education Clinics of three hospitals located in a city center in Turkey. The sample of the study consisted of 118 individuals with type 2 diabetes. The data were collected using the Introductory Information Form and the Data Form questioning the use of herbal products/food supplements. Results: It was determined that 28.8% of the participants used herbal products for glycemic control. The herbal products that are most frequently used by these users are cinnamon (29.4%), lemon and yoghurt (23.5%), and olive leaves (20.5%). A statistically significant difference was found between the use of herbal products with respect to the gender and education (p <0.05) of the users. Conclusion: It was determined that one of the three diabetic individuals with type 2 diabetes included in the study used herbal products while no food supplement use was observed. It was determined that women prefer herbal products more than men and high school along with university graduates prefer them more than primary school graduates. Most of these users also did not inform health professionals that they used herbal products. [ABSTRACT FROM AUTHOR]

Sleep disorders are linked to obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). The evidence suggests that dietary carbohydrate content may be related to sleep duration. We designed a study to investigate the association between a low-carbohydrate diet (LCD) with long sleep duration (> 8 h) and short sleep duration (< 5 h). This cross-sectional analysis was conducted on data obtained from the recruitment phase of Yazd Health Study (YaHS) and the Taghzieh Mardom-e-YaZd (TAMYZ). The dietary intake was assessed using a validated food frequency questionnaire. The LCD score was calculated for each subject based on summing up assigned scores to deciles of percentages of energy from macronutrients. Sleep duration was assessed using a nocturnal sleep questionnaire. The association between LCD and sleep duration was evaluated using logistic regressions in crude and adjusted models. A total of 5929 subjects were entered into the analysis. Most of the participants were aged 20–29 years (24.8%), male (52.2%) and never smokers (87.7%). After adjusting for level of physical activity, age, sex, total energy, smoking status and body mass index in model III, a significant direct association was observed between LCD score with long sleep duration (OR 1.15; 95% CI1–1.32, P = 0.049) and short sleep duration (OR 1.29; 95% CI 1.02–1.62, P = 0.028). Higher LCD score is associated with higher chance of long sleep duration and short sleep duration. Regarding the nature of our study, cohort and clinical trial studies in future are required to reach a causal association and a definitive conclusion. [ABSTRACT FROM AUTHOR]

We performed a meta‐analysis on randomized controlled trials (RCTs) to evaluate the efficacy of Zingiberaceae on cardiovascular risk factors in type 2 diabetes mellitus (T2DM). PubMed, Web of Science, Embase, The Cochrane Library, and Scopus were searched systematically until October 18, 2021. Thirty‐four RCTs with 2154 patients met our inclusion. Pooled analysis indicated that Zingiberaceae can significantly improve body weight (BW) (WMD = −1.012, 95% CI: −1.673, −0.351, p =.003), fasting blood glucose (FBG) (WMD = −14.292, 95% CI: −18.588, −9.995, p <.001), glycosylated hemoglobin 1c (HbA1c) (WMD = −0.432, 95% CI: −0.607, −0.257, p <.001), serum insulin (WMD = −2.036, 95% CI: −2.857, −1.216, p <.001), homeostasis model assessment insulin resistance (HOMA‐IR) (WMD = −0.886, 95% CI: −1.375, −0.398, p <.001), high density lipoprotein‐cholesterol (HDL‐C) (WMD = 0.850, 95% CI: 0.018, 1.682, p =.045), triglyceride (TG) (WMD = −17.636, 95% CI: −27.121, −8.151, p <.001), diastolic blood pressure (DBP) (WMD = −0.642, 95% CI: −1.148, −0.137, p =.013), C‐reactive protein (CRP) (WMD = −0.623, 95% CI: −1.061, −0.186, p =.005), tumor necrosis factor‐α (TNF‐α) (WMD = −3.020, 95% CI: −4.327, −1.712, p <.001), and interleukin 6 (IL‐6) (WMD = −1.147, 95% CI: −1.887, −0.406, p =.002). The supplementation of Zingiberaceae may be an effective adjunctive therapy in management of T2DM and prevention cardiovascular complications by decreasing BW, improving blood glucose control, insulin resistance, lipid profiles (HDL‐C and TG), blood pressure (DBP), and reducing inflammation (CRP, TNF‐α, and IL‐6). Practical applications: Approximately half of the deaths of individuals with diabetes mellitus (DM) are attributable to cardiovascular disease (CVD), and individuals with T2DM have a two‐fold increased risk of cardiovascular mortality than healthy individuals. Currently, T2DM is mainly treated with hypoglycemic medication such as sulfonylureas, thiazolidinediones, meglitinides, and biguanides. Nevertheless, most of them with long‐term usage could cause side effects, including hypoglycemia and gastrointestinal troubles. Several species of the Zingiberaceae family are used in traditional herbal medicines, which have been widely used in traditional and complementary medicine. Proving the potential benefits of Zingiberaceae on T2DM and its cardiovascular complications has positive clinical implications for the use of this practical herb. [ABSTRACT FROM AUTHOR]

Introduction: Many Ayurvedic medicines have the potential for managing type 2 diabetes mellitus (T2DM), with previous systematic reviews demonstrating effectiveness and safety for specific Ayurvedic medicines. However, many of the reviews need updating and none provide a comprehensive summary of all the Ayurvedic medicines evaluated for managing T2DM. Objective: The objective of this systematic review was to evaluate and synthesize evidence on the effectiveness and safety of Ayurvedic medicines for managing T2DM. Inclusion criteria: Published and unpublished RCTs assessing the effectiveness and safety of Ayurvedic medicines for managing T2DM in adults. Methods: The JBI systematic review methodology was followed. A comprehensive search of sources (including 18 electronic databases) from inception to 16 January 2021 was made. No language restrictions were applied. Data synthesis was conducted using narrative synthesis and random effects meta-analyses, where appropriate. Pooled results are reported as mean differences (MD) with 95% confidence intervals (CI). Results: Out of 32,519 records identified from the searches, 219 articles were included in the systematic review representing 199 RCTs (21,191 participants) of 98 Ayurvedic medicines. Overall, in the studies reviewed the methodology was not adequately reported, resulting in poorer methodological quality scoring. Glycated hemoglobin (HbA1c) was reduced using Aegle marmelos (L.) Corrêa (MD -1.6%; 95% CI −3 to −0.3), Boswellia serrata Roxb. (−0.5; −0.7 to −0.4), Gynostemma pentaphyllum (Thunb.) Makino (−1; −1.5 to −0.6), Momordica charantia L. (−0.3; −0.4 to −0.1), Nigella sativa L. (−0.4; −0.6 to −0.1), Plantago ovata Forssk. (−0.9; −1.4 to −0.3), Tinospora cordifolia (Willd.) Hook.f. and Thomson (−0.5; −0.6 to −0.5), Trigonella foenum-graecum L. (−0.6; −0.9 to −0.4), and Urtica dioica L. (−1.3; −2.4 to −0.2) compared to control. Similarly, fasting blood glucose (FBG) was reduced by 4–56 mg/dl for a range of Ayurvedic medicines. Very few studies assessed health-related quality of life (HRQoL). Adverse events were not reported in many studies, and if reported, these were mostly none to mild and predominately related to the gastrointestinal tract. Conclusion: The current evidence suggests the benefit of a range of Ayurvedic medicines in improving glycemic control in T2DM patients. Given the limitations of the available evidence and to strengthen the evidence base, high-quality RCTs should be conducted and reported. [ABSTRACT FROM AUTHOR]