Assessing the possible association between MTHFR (rs1801133) and GPx-1 (rs1050450) polymorphisms with the risk of type 2 diabetes, diabetic neuropathy, and diabetic retinopathy.

PURPOSE: Oxidative stress in chronic hyperglycemia could injure the tissues and onset of diabetes-related complications like retinopathy and neuropathy. This study investigates the association between methylenetetrahydrofolate reductase (MTHFR) and glutathione peroxidase (GPx) genetic variants with these complications. METHODS: In this case-control study, 400 individuals, including 100 healthy subjects and 300 patients with type 2 diabetes mellitus (T2DM) in three subgroups: with retinopathy(n = 100), with neuropathy(n = 100), and without complication (n = 100) from West Iran, were studied. MTHFR (rs1801133) and GPx-1 (rs1050450) variants were identified by the PCR-RFLP method. The plasma levels of GPx activity, glutathione, malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidative stress (TOS) were measured by chemical methods. RESULTS: Higher BMI, TOS and MDA levels were observed in patients with neuropathy compared to other patients and controls. Diabetic patients with neuropathy had lower levels of glutathione (7.8 ± 4.5; P < 0.001), GPx activity (39.5 ± 8.5; P < 0.001), and TAC (703.1 ± 129.1; P = 0.0001) in comparison with other groups. The patients without complication and retinopathic patients had higher plasma levels of glutathione (12.2 ± 2.4; p = 0.02) and TAC (793.4 ± 124.6; P < 0.001), respectively. MTHFR TT genotype significantly correlated with lower levels of TOS (3.5 ± 1.1; P < 0.001) and OSI (0.0050 ± 0.001; P < 0.001). Subjects with the GPx-1 TT genotype had higher levels of MDA (6.8 ± 2.5; P = 0.02) and lower levels of TOS (3.7 ± 1.6; P < 0.001), which is statistically significant. TT genotype of MTHFR was associated with 3.9 fold (95% CI 1.04-4.76; P = 0.0436) increased risk of neuropathy. Also, GPx-1 CT genotype increased the risk of retinopathy [OR = 2.7 (95% CI = 1.38-5.44; P = 0.0039)]. CONCLUSION: The MTHFR TT genotype increased the risk of neuropathy in diabetic patients significantly. The GPx-1 CT genotype is related to increased retinopathy risk among diabetic patients. Both MTHFR and Gpx-1 TT genotypes were associated with higher BMI levels.

H6PD Gene Polymorphisms (R453Q and D151A) and Polycystic Ovary Syndrome: A Case-Control Study in A Population of Iranian Kurdish Women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is known as the most common endocrine and metabolic disorder in the reproductive-age women. Due to the effects of PCOS on the physical and mental health, the investigation of the factors affecting the development of PCOS is crucial. Hexose-6-phosphate dehydrogenase (H6PD) is a microsomal enzyme that catalyzes the first two reactions of the oxidative chain of the pentose phosphate pathway. The present study examined the polymorphisms of the H6PD gene (R453Q and D151A) in PCOS patients of Iranian Kurdish women.
Materials and Methods: In this case-control study, a total, of 200 female volunteers in two equal groups participated in our study. The PCOS patients were selected based on the Rotterdam diagnostic criteria. The association of H6PD gene polymorphisms, D151A and R453Q, with the development of PCOS were investigated. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping. Statistical analysis was applied by the SPSS (version 16) software.
Results: Statistically significant lower frequencies of AA+AG genotype (37% vs. 55%, P=0.01) and A allele (22.5%
vs. 34%, P=0.01) of R453Q were observed in the patients compared to the controls. In the case of D151A, no significant
differences were observed in the frequency of genotypes and alleles between the two groups. CONCLUSION: The findings of this study suggest that variants of H6PD R453Q affect the risk of PCOS.

Comparing shear wave elastography and fine needle aspiration in the diagnosis of solid thyroid nodules.

This descriptive study was performed on individuals who were referred to Imam Reza Hospital for fine needle aspiration biopsy (FNAB) based on the results of gray scale ultrasound and the decision of the referring physician. In addition to determining the gray scale characteristics of the nodules, shear wave elastography (SWE) was also performed and the results were recorded. These were also taken from the patients FNAB results. Finally, the findings of SWE and FNAB methods were compared and analyzed using SPSS software version 16. Based on the results presented herein, a significant relationship was observed between the results of SWE and FNA in the diagnosis of malignancy in solid thyroid nodules. This agreement was found to be higher in men (K = 0.866) than women (K = 0.849). Taken together, our data suggest that shear wave elastography can replace FNA in the diagnosis of malignancy in solid thyroid nodules.

Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM, diabetic neuropathy, diabetic retinopathy, and obesity.

INTRODUCTION: Chronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1-Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications. METHODS: In a case-control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR-RFLP method, the Keap1 (rs11085735) variants were identified. RESULTS: Neuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype. CONCLUSIONS: Our study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.

Gestational Diabetes Mellitus (GDM), Hypothyroidism, and Gene Variants (Keap1 Rs11085735) in Patients with Preeclampsia.

Background: Preeclampsia is a multifactorial hypertensive disorder of pregnancy with multisystem involvement. Recent studies have demonstrated that preeclampsia is associated with increased placental oxidative stress at the cellular level. The nuclear factor erythroid-2-like 2 (Nrf2) / Kelch-like ECH-associated protein 1 (Keap1) signaling is an antioxidant pathway that plays an important role in protecting cells against oxidative stress. Here, we aimed to determine the possible association between the Keap1 variants and genetic susceptibility to preeclampsia. Methods: In a case-control study, 150 preeclampsia patients and 150 women with normal pregnancy from Northern Iran were selected to evaluate the genotypes of Keap1 (rs11085735) using the polymerase chain reaction (PCR)-restriction length polymorphism (RFLP) method. Results: A significant association between genotypes of Keap1 rs11085735 polymorphism with the renal function biomarkers and the risk of preeclampsia was not found. However, the aspartate aminotransferase (AST) level was higher in the presence of the Keap1 AA genotype compared to AC and CC genotypes. We found a significantly higher prevalence of gestational diabetes mellitus (GDM) in mild- and severe- preeclampsia and also hypothyroidism in severe preeclampsia compared to controls. Conclusion: We found an association between preeclampsia with GDM and hypothyroidism. Our findings suggest that the Keap1rs11085735 polymorphism may not be a risk factor for susceptibility to preeclampsia in our studied population; however, this polymorphism could affect the activity of AST.

The Effect of Leptin Receptor Gene Polymorphisms (R223Q and P1019P) in Susceptibility to Polycystic Ovarian Syndrome in Kurdish Women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the known endocrinopathy disorder in the reproductive phase of women's life. More than half of the women with PCOS suffer from obesity which impacts the ovarian functions by leptin levels. Here the R223Q and P1019P polymorphisms of leptin receptor (LEPR) gene were examined in PCOS patients of Kurdish women from west of Iran. MATERIALS AND METHODS: In this case-control study, one hundred women with PCOS and 100 healthy women bearing similar age range were selected based on Rotterdam diagnostic criteria. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to genotype polymorphisms LEPR (R223Q and P1019P), by respectively the BsaWI and NcoI restriction enzymes. Pearson's chi-square (χ2) test was used to analyze the variation in genetic distributions and unconditional logistic regression model was used to calculate the odds ratio (OR; 95% CI). RESULTS: Genotype frequencies of the R223Q and P1019P polymorphisms showed significant difference between the patients with PCOS compared to the controls. G allele (R223Q) reduced the risk of PCOS about 0.49-fold (P<0.001). While, T allele (P1019P) increased the risk of PCOS 2.69-fold (P<0.001). CONCLUSION: It can be concluded that the R223Q and P1019P polymorphisms showed a significant association with PCOS susceptibility risk. It seems that G allele (R223Q) with reducing OR had a protective effect on this syndrome, while T allele (P1019P) with increasing OR was a risk factor for PCOS.

Comment on "Association between Interleukin-32 and Interleukin-17A Single Nucleotide Polymorphisms and Serum Levels with Polycystic Ovary Syndrome".

No Abstract.

Targeting Glycoproteins as a therapeutic strategy for diabetes mellitus and its complications.

OBJECTIVES: Glycoproteins are organic compounds formed from proteins and carbohydrates, which are found in many parts of the living systems including the cell membranes. Furthermore, impaired metabolism of glycoprotein components plays the main role in the pathogenesis of diabetes mellitus. The aim of this study is to investigate the influence of glycoprotein levels in the treatment of diabetes mellitus. METHODS: All relevant papers in the English language were compiled by searching electronic databases, including Scopus, PubMed and Cochrane library. The keywords of glycoprotein, diabetes mellitus, glycan, glycosylation, and inhibitor were searched until January 2019. RESULTS: Glycoproteins are pivotal elements in the regulation of cell proliferation, growth, maturation and signaling pathways. Moreover, they are involved in drug binding, drug transportation, efflux of chemicals and stability of therapeutic proteins. These functions, structure, composition, linkages, biosynthesis, significance and biological effects are discussed as related to their use as a therapeutic strategy for the treatment of diabetes mellitus and its complications. CONCLUSIONS: The findings revealed several chemical and natural compounds have significant beneficial effects on glycoprotein metabolism. The comprehension of glycoprotein structure and functions are very essential and inevitable to enhance the knowledge of glycoengineering for glycoprotein-based therapeutics as may be required for the treatment of diabetes mellitus and its associated complications. Graphical abstract.

Nanoformulations of natural products for management of metabolic syndrome.

Metabolic syndrome is a common metabolic disorder which has become a public health challenge worldwide. There has been growing interest in medications including natural products as complementary or alternative choices for common chemical therapeutics regarding their limited side effects and ease of access. Nanosizing these compounds may help to increase their solubility, bioavailability, and promisingly enhance their efficacy. This study, for the first time, provides a comprehensive overview of the application of natural-products-based nanoformulations in the management of metabolic syndrome. Different phytochemicals including curcumin, berberine, Capsicum oleoresin, naringenin, emodin, gymnemic acid, resveratrol, quercetin, scutellarin, stevioside, silybin, baicalin, and others have been nanosized hitherto, and their nanosizing method and effect in treatment and alleviating metabolic syndrome have been reviewed and discussed in this study. It has been discovered that there are several pathways or molecular targets relevant to metabolic disorders which are affected by these compounds. Various natural-based nanoformulations have shown promising effect in treatment of metabolic syndrome, and therefore can be considered as future candidates instead of or in conjunction with pharmaceutical drugs if they pass clinical trials successfully.

Polyphenols for diabetes associated neuropathy: Pharmacological targets and clinical perspective.

OBJECTIVES: Diabetic neuropathy (DNP) is a widespread and debilitating complication with complex pathophysiology that is caused by neuronal dysfunction in diabetic patients. Conventional therapeutics for DNP are quite challenging due to their serious adverse effects. Hence, there is a need to investigate novel effective and safe options. The novelty of the present study was to provide available therapeutic approaches, emerging molecular mechanisms, signaling pathways and future directions of DNP as well as polyphenols' effect, which accordingly, give new insights for paving the way for novel treatments in DNP. EVIDENCE ACQUISITION: A comprehensive review was done in electronic databases including Medline, PubMed, Web of Science, Scopus, national database (Irandoc and SID), and related articles regarding metabolic pathways on the pathogenesis of DNP as well as the polyphenols' effect. The keywords "diabetic neuropathy" and "diabetes mellitus" in the title/abstract and "polyphenol" in the whole text were used. Data were collected from inception until May 2019. RESULTS: DNP complications is mostly related to a poor glycemic control and metabolic imbalances mainly inflammation and oxidative stress. Several signaling and molecular pathways play key roles in the pathogenesis and progression of DNP. Among natural entities, polyphenols are suggested as multi-target alternatives affecting most of these pathogenesis mechanisms in DNP. CONCLUSION: The findings revealed novel pathogenicity signaling pathways of DNP and affirmed the auspicious role of polyphenols to tackle these destructive pathways in order to prevent, manage, and treat various diseases. Graphical Abstract .

Pharmacological effects of gallic acid in health and diseases: A mechanistic review.

OBJECTIVES: Gallic acid is a natural phenolic compound found in several fruits and medicinal plants. It is reported to have several health-promoting effects. This review aims to summarize the pharmacological and biological activities of gallic acid in vitro and animal models to depict the pharmacological status of this compound for future studies. MATERIALS AND METHODS: All relevant papers in the English language were collected up to June 2018. The keywords of gallic acid, antioxidant, anticancer, antimicrobial, gastrointestinal-, cardiovascular-, metabolic-, neuropsychological-, and miscellaneous- diseases were searched in Google Scholar, PubMed, and Scopus. RESULTS: Several beneficial effects are reported for gallic acid, including antioxidant, anti-inflammatory, and antineoplastic properties. This compound has been reported to have therapeutic activities in gastrointestinal, neuropsychological, metabolic, and cardiovascular disorders. CONCLUSION: Current evidence confirms the pharmacological and therapeutic interventions of gallic acid in multiple health complications; however, available data are limited to just cellular and animal studies. Future investigations are essential to further define the safety and therapeutic efficacy of gallic acid in humans.

Natural flavonoids for the prevention of colon cancer: A comprehensive review of preclinical and clinical studies.

Flavonoids comprise a group of natural polyphenols consisting of more than 5,000 subtypes mostly existing in fruits and vegetables. Flavonoids consumption could potentially attenuate the incidence and recurrence risk of colorectal cancers through their antiperoxidative, antioxidant, and anti-inflammatory effects. In addition, these compounds regulate the mitochondrial function, balance the bacterial flora and promote the apoptosis process in cancerous cells. However, some previous data failed to show the effectiveness of flavonoids in reducing the risk of colorectal cancer. In this study, we have reviewed the efficacy of different flavonoids subtypes on the risk of colon cancer and molecular mechanisms involved in this process in both clinical and animal studies. In addition, we tried to elucidate the potential synergy between these compounds and current colorectal cancer treatments.

Comparison of Vitex agnus-castus Extracts with Placebo in Reducing Menopausal Symptoms: A Randomized Double-Blind Study.

BACKGROUND: Menopausal symptoms have remarkable negative effects on women's quality of life, justifying the need to assess various therapeutic options. This research aimed to determine the effectiveness of Vitex agnus-castus extracts in alleviating menopausal symptoms in comparison with that of placebo. METHODS: This study was a randomized controlled double-blind clinical trial with a study group of 52 women referred to a clinic in Kermanshah in 2017. The participants were randomly divided into two groups: Vitex group (26 subjects) and placebo group (26 subjects). Menopausal symptoms were assessed using the Greene Scale before and 8 weeks after the intervention. RESULTS: After the intervention, the mean scores for total menopausal disorder, anxiety, and vasomotor dysfunction were significantly lower in the Vitex group than in the placebo group (P<0.05). The mean scores of the variables of somatic complications, depression, and sexual dysfunction did not show significant differences between the Vitex and placebo groups (P>0.05). CONCLUSION: Administration of Vitex agnus-castus extracts as a phytoestrogenic medicine can alleviate menopausal symptoms in women.

Effect of resveratrol on metabolic syndrome components: A systematic review and meta-analysis.

We summarized 16 controlled studies and evaluated the correlation of resveratrol supplementation with metabolic parameters such as the body weight, waist circumference (WC), systolic blood pressure (sbp), HDL, total cholesterol, triglyceride and glucose levels. This meta-analysis was carried out to determine the association between the resveratrol intake with metabolic parameters in metabolic syndrome patients. PubMed, Scopus, Cochrane and Google Scholar were searched from inception to December 2018 using relevant keywords. All articles were independently reviewed by two authors using predetermined selection criteria. We have selected the studies that investigated the effects of resveratrol on metabolic parameters. Of 16 studies, 10 were performed on human subjects, and in 6 studies animal models were used. Standard mean difference (SMD) with 95% confidence interval were determined using Der Simonian and Laird random-effects modeling, when there was a significant heterogeneity between studies. Funnel plot and Egger's test were conducted to examine the risk of publication bias. Pooled effect sizes in human studies indicated a significant impact of resveratrol supplementation on glucose level [-1.73 (-2.99, -0.47); p = 0.007)] and WC [-1.73 (-2.79, -0.67); p = 0.001] compared with the control group. Also combining the results of studies on rat samples (n = 6), indicated significant effect of resveratrol on decreasing weight [-22.95 (-44.74, -1.17); p = 0.04], TGs [-6.76 (-11.10, -2.42); p = 0.001], sbp [-7.30 (-12.48, -2.13); p = 0.006], and it can influence significantly on increasing HDL level (4.75 (1.87, 7.63); p = 0.001). However, resveratrol was not significantly effective on total cholesterol in both samples. The results of subgroup analysis of human studies showed that resveratrol has significant effect on metabolic parameters (glucose level and WC) at the dosage of > 500 mg and with long-term interventions ≥ 10 weeks. Administration of resveratrol can meaningfully reduce the BW, WC, TGs, and glucose level, also it can increase HDL, but not total cholesterol.

Medicinal plants and their isolated phytochemicals for the management of chemotherapy-induced neuropathy: therapeutic targets and clinical perspective.

BACKGROUND: Chemotherapy, as one of the main approaches of cancer treatment, is accompanied with several adverse effects, including chemotherapy-induced peripheral neuropathy (CIPN). Since current methods to control the condition are not completely effective, new treatment options should be introduced. Medicinal plants can be suitable candidates to be assessed regarding their effects in CIPN. Current paper reviews the available preclinical and clinical studies on the efficacy of herbal medicines in CIPN. METHODS: Electronic databases including PubMed, Scopus, and Cochrane library were searched with the keywords "neuropathy" in the title/abstract and "plant", "extract", or "herb" in the whole text. Data were collected from inception until April 2018. RESULTS: Plants such as chamomile (Matricaria chamomilla L.), sage (Salvia officinalis L.), cinnamon (Cinnamomum cassia (L.) D. Don), and sweet flag (Acorus calamus L.) as well as phytochemicals like matrine, curcumin, and thioctic acid have demonstrated beneficial effects in animal models of CIPN via prevention of axonal degeneration, decrease in total calcium level, improvement of endogenous antioxidant defense mechanisms such as superoxide dismutase and reduced glutathione, and regulation of neural cell apoptosis, nuclear factor-ĸB, cyclooxygenase-2, and nitric oxide signaling. Also, five clinical trials have evaluated the effect of herbal products in patients with CIPN. CONCLUSIONS: There are currently limited clinical evidence on medicinal plants for CIPN which shows the necessity of future mechanistic studies, as well as well-designed clinical trial for further confirmation of the safety and efficacy of herbal medicines in CIPN. Graphical abstract Schematic mechanisms of medicinal plants to prevent chemotherapy-induced neuropathy: NO: nitric oxide, TNF: tumor necrosis factor, PG: prostaglandin, NF-ĸB: nuclear factor kappa B, LPO: lipid peroxidation, ROS: reactive oxygen species, COX: cyclooxygenase, IL: interleukin, ERK: extracellular signal-related kinase, X: inhibition, ↓: induction.

Targeting AMPK signaling pathway by natural products for treatment of diabetes mellitus and its complications.

Diabetes affects a large population of the world. Lifestyle, obesity, dietary habits, and genetic factors contribute to this metabolic disease. A target pathway to control diabetes is the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. AMPK is a heterotrimeric protein with α, ß, and γ subunits. In several studies, AMPK activation enhanced glucose uptake into cells and inhibited intracellular glucose production. Impairment of AMPK activity is present in diabetes, according to some studies. Drugs used in the treatment of diabetes, such as metformin, are also known to act through regulation of AMPK. Thus, drugs that activate and regulate AMPK are potential candidates for the treatment of diabetes. In addition, many patients encounter important adverse effects, like hypoglycemia, while using allopathic drugs. As a result, the investigation of plant-derived natural drugs that lack adverse side effects and treat diabetes is necessary. Natural products like berberine, quercetin, resveratrol, and so forth have shown significant potential in regulating and activating the AMPK pathway which can lead to manage diabetes mellitus and its complications.

Salivary Profile in Adult Type 2 Diabetes Mellitus Patients: A Case-control Study.

OBJECTIVE: To evaluate salivary factors in type 2 diabetes melliuts patients. METHODS: The case-control study was conducted from June to November 2016 at Kermanshah University of Medical Sciences, Kermanshah, Iran, and comprised patients with type 2 diabetes mellitus and healthy controls matched in terms of age and gender. Unstimulated saliva samples were collected in the morning after an overnight fast of 8-12 hours. The samples were centrifuged at 1500 rpm for 5 minutes, and every isolated transparent liquid was immediately frozen at a temperature of -45ºC in a tube. The test sample was later aspirated, and readings were taken. The data was analyzed using SPSS 16.. RESULTS: Of the 200 subjects, 100(50%) were diabetic patients and 100(50%) were healthy controls. The two groups were matched with regard to age, gender, diabetes duration, serum glucose, and glycated haemoglobin (p>0.05 each). In terms of laboratory variables, there were significant differences between the groups related to urea, phosphorus, pH, and glucose (p<0.05 each). Urea and glucose levels were higher in the patient group than the controls (p<0.05 each). Also, calcium and total protein levels were higher in male patients compared to female patients (p < 0.0 5 each) . CONCLUSIONS: Salivary pH, urea, calcium, phosphorus, glucose, and total protein levels could be bio chemical parameters for screening, diagnosis and monitoring of diabetes .

Association between CYP19A

Acne vulgaris (AV) is a common skin disease that causes physical and psychological problems for the affected individual. In addition to systemic changes in hormone levels, overproduction of local steroids, especially androgens are associated with AV. Cytochrome (CYP) 19 is involved in the synthesis of estrogens. The aim of the present study was to investigate the influence of CYP19A

Effect of diabetes mellitus type 2 on salivary glucose, immunoglobulin A, total protein, and amylase levels in adults: A systematic review and meta-analysis of case-control studies.

BACKGROUND: Saliva is a fluid with the complex compound which can be used as diagnostic markers for type 2 diabetes (T2D). This meta-analysis evaluated salivary glucose, immunoglobulin A (IgA), total protein, and amylase levels in adult T2D compared with the controls as well as the correlation of salivary glucose levels with serum glucose and hemoglobin A1C (HbA1c) levels in both groups. MATERIALS AND METHODS: Web of Science, Scopus, PubMed, and Cochrane Library databases were searched up to July 2017. A random-effects analysis was performed using the mean difference (MD) and 95% confidence intervals. The search terms were "T2D, IgA, amylase, total protein, or glucose" combination with "saliva." The studied variables were the sample size, the percentage of male, the mean age, the condition of saliva sampling, and the salivary levels of mentioned factors. RESULTS: A total of 25 studies were included in this meta-analysis with 1432 and 900 diabetic patients and healthy controls, respectively. MD of salivary glucose level in patients with T2D, compared with the healthy controls, in fasting and nonfasting conditions were 6.23 mg/dL (P = 0.0002) and 6.70 mg/dL (P < 0.00001), respectively. Furthermore, the fasting salivary total protein in the patients was significantly higher than the controls (MD = 167.96 mg/dL; P = 0.03). Non-fasting salivary amylase and secretory IgA levels were significantly lower in the patients (MD = -48.61 IU/mL; P < 0.00001) than in the controls (MD = -9.42 IU/mL; P = 0.0006), respectively. The pooled estimate showed a significant correlation between salivary and serum glucose in the patients (r = 0.765; P < 0.001) and the controls (r = 0.646; P < 0.001) and between salivary glucose and serum glycated hemoglobin in the patients (r = 0.721; P < 0.001). CONCLUSION: Measurement of these salivary factors can be helpful for diagnostic and monitoring purposes of T2D. In addition, salivary glucose as a diagnostic tool can evaluate serum glucose and HbA1c levels in the diabetic patients.

Anthocyanins in the Management of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review.

The term "metabolic syndrome" (MetS) refers to a combination of diabetes, high blood pressure, and obesity. The origin of MetS includes a combination of multiple factors, such as sedentary lifestyle, unhealthy diet choice, and genetic factors. MetS is highly prevalent and adversely affects the general population by elevating risk of cardiovascular complications, organ failure, and much other pathology associated with late-stage diabetes. Anthocyanins (ANTs) are health-promoting bioactive compounds belonging to the flavonoids subclass of polyphenols. Numerous studies have reported the potential therapeutic benefits on MetS syndrome and diabetes from fruits rich in ANTs. This review summarizes the role of several dietary ANTs on preventing and managing MetS as well as the pharmacological mechanisms and biopharmaceutical features of their action. We also discuss potential nanoformulation and encapsulation approaches that may enhance the bioefficacy of ANTs in MetS. Experiments have demonstrated that ANTs may attenuate the symptoms of MetS via improving insulin resistance, impaired glucose tolerance, dyslipidaemia, cholesterol levels, hypertension, blood glucose, protecting ß cells, and preventing free radical production. In brief, the intake of ANT-rich supplements should be considered due to their plausible ability for prevention and management of MetS. Additionally, randomized double-blind clinical trials are obligatory for evaluating the bioefficacy and pharmacological mechanisms of ANTs and their pharmaceutical formulations in patients with MetS.