Meta-analysis of MTHFR C677T polymorphism and type 2 diabetes mellitus in MENA region.

BACKGROUND AND AIMS: The association of the C677T polymorphism of the Methylenetetrahydrofolate Reductase (MTHFR) gene with susceptibility to type 2 diabetes mellitus (T2DM) has been widely debated. Therefore, our aim is to conclusively resolve this controversy in the Middle East and North Africa region population through a meta-analysis. MATERIEL AND METHODS: We identified relevant articles by searching literature databases, such as PubMed, Web of Science, and Science Direct, to retrieve studies that examined the association between the MTHFR C677T polymorphism and the risk of developing T2DM. Using meta-analysis, we calculated the odds ratio (OR) and confidence interval (CI) values of these studies to assess the susceptibility to T2DM related to the C677T polymorphism of MTHFR gene. RESULTS: In this meta-analysis, we included a total of 13 publications comprising 2072 T2DM patients and 2164 control subjects. The results of the meta-analysis suggested that there is a significant association between the C677T polymorphism and T2DM risk in overall comparisons for allele contrasts (T vs C): OR = 1.25, 95% CI = 1.04-1.50, p = 0.015 and homozygous (TT vs CC): OR = 1.44, 95% CI = 1.01-2.05, p = 0.038). Subgroup analysis revealed that the C677T polymorphism is associated with a risk of T2DM in Asian populations, while there is no significant association between this polymorphism and T2DM in Caucasian and African populations. Furthermore, there was no evidence of publication bias. CONCLUSION: Our study's results suggest that the allele contrast of the C677T polymorphism of the MTHFR gene is associated with an increased risk of T2DM in the overall population, particularly among Asians.

Prevalence and risk factors of chronic complications among patients with type 2 diabetes mellitus in Morocco: a cross-sectional study.

Introduction: microvascular and macrovascular complications of type 2 diabetes mellitus (T2DM) are one of the major causes of morbidity and mortality worldwide among patients with T2DM. This study aims to estimate the prevalence of these chronic complications and identify the associated risk factors among Moroccan patients with T2DM. Methods: this cross-sectional study was conducted on 505 T2DM patients followed by the healthcare Centers of the Casablanca-Settat region from January 2017 to July 2018. The socio-demographic, anthropometric, biochemical, and clinical data were recorded using a structured survey. For statistical analysis, SPSS version 20 is used. Univariate and multivariate logistic regression analyses are used to determine the risk factors associated with chronic complications of T2DM. Results: among the 505 Moroccan patients with T2DM, 84.98% were women. The average age of the patients was 57.27±10.74 years. Diabetic eye disease was the most frequent complication (29.5%) followed by cardiovascular diseases (CVDs) (22.4%), kidney disease in diabetes (9.8%), diabetes foot (2.8%), and neuropathy (1.8%). Logistic regression analysis showed that the CVDs was associated with hypertension (OR: 2.41; 95% CI: 1.11-5.22; p=0.026), hypolipidemia treatment (OR: 2.20; 95% CI: 1.06-4.59; p=0.034), insulin use (OR= 0.39; 95%CI: 0.15-0.96, p=0.043) and LDL-C (OR: 1.01; 95% CI: 1-1.02; p=0.035) in T2DM patients. However, the major risk factors for the development of kidney disease in T2DM patients were a lack of regular physical activity (OR: 3.77; 95% CI: 1.22-11.67; p=0.021), hypolipidemia treatment (OR: 8.31; 95% CI: 1.86-36.97; p=0.005), and high serum creatinine (OR: 1.33; 95% CI: 1.16-1.53; p≤0.001). In addition, LDL-C levels were found to be a significant risk factor for diabetes eye disease (OR: 1.01; 95% CI: 1.00-1.03; p=0.008). Conclusion: this study shows that the increased duration of diabetes, insulin use, lack of regular physical exercise, hypertension, hypolipidemia treatment, high serum creatinine, and LDL-C were significant risk factors for chronic complications of T2DM in Moroccan patients.

Relationship between insertion/deletion (I/D) polymorphism of angiotensin converting enzyme (ACE) gene and susceptibility to type 2 diabetes mellitus in the Middle East and North Africa Region: A meta-analysis.

BACKGROUND AND AIMS: The association between insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene and the risk of type 2 diabetes mellitus (T2DM) remains controversial. This study aimed to assess the effect of the ACE I/D gene polymorphism on T2DM in the Middle East and North Africa region (MENA region). MATERIAL AND METHODS: Our data was extracted from PubMed, Science Direct, and the Web of Science. The predefined inclusion criteria included only the human case-control studies of English Peer-reviewed papers containing the data on genotype distributions of ACE I/D polymorphism and the T2DM risk. Review articles, meeting abstracts, editorials, animal studies, and studies not providing genotype distribution data or without sufficient data were excluded from this work. Results of this meta-analysis were expressed using odds ratios (OR) and 95% confidence intervals (CI). Indeed, the potential sources of heterogeneity and bias were examined by the Egger regression. RESULTS: Of 2755 identified articles, 10 studies were selected, including 2710 patients with T2DM and 2504 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and the D allele of ACE I/D gene polymorphism (OR = 1.97; 95% CI = 1.33-2.93, p = 0.0007), recessive (OR = 2.16; 95% CI = 1.27-3.67; p = 0.004), dominant (OR = 2.45; 95% CI = 1.54-3.91; p = 0.0001), homozygote (OR = 3.35; 95% CI = 1.78-6.29; p = 0.0001) and heterozygote comparisons (OR = 1.76; 95% CI = 1.07-2.88; p = 0.024). CONCLUSION: Our result suggests that this polymorphism may contribute to the development of T2DM in the MENA Region. This result needs to be confirmed by future well-designed studies with larger sample sizes in diverse populations and ethnicities.

Prevalence of dyslipidemia and the relationship between HbA1C and lipid profile in Moroccan patients with T2DM: a cross-sectional study.

Introduction: the increased prevalence of dyslipidemia in patients with type 2 diabetes mellitus (T2DM) results from uncontrolled hyperglycemia and consistently contributes to an elevated risk of cardiovascular complications. This study sought to estimate the prevalence of dyslipidemia and to investigate the relationship between glycated hemoglobin (HbA1C) and serum lipid levels in Moroccan patients with T2DM. Methods: a total of 505 patients with T2DM were included in this cross-sectional study, 77.4% with chronic complications and 22.6% without. The collected data were examined using statistical package for the social sciences (SPSS) version 20.0 software and appropriate statistical methods. Results: the data analysis showed that the mean and SD of age were 57.27±10.74 years. Among 505 patients with T2DM, the prevalence of hypercholesterolemia, hypertriglyceridemia, increased low-density lipoprotein cholesterol (LDL-C), and decreased HDL-C was 41.4%, 35.9%, 27.1%, and 17%, respectively. In addition, the data analysis showed that levels of total cholesterol (TC) (p≤0.001), triglycerides (p≤0.001), Low-density lipoprotein cholesterol (LDL-C) (p≤0.001), TC/HDL-C ratio (p=0.006), and LDL-C/HDL-C ratio (p=0.006) were significantly higher in T2DM patients with complications as compared to those without complications. The patients with HbA1C > 7.0% had significantly higher values of fasting blood glucose (FBG) (p≤0.001), total cholesterol (p≤0.001), triglycerides (p≤0.001), and TC/HDL-C ratio (p=0.025) as compared to the patients with HbA1C ≤ 7.0%. The HbA1C demonstrated a significant negative correlation with age (r=-0.139), and positive correlation with FBG (r=0.673), total cholesterol (r=0.189) and triglycerides (r=0.243). Conclusion: our results showed that HbA1C is the most important biomarker of long-term glycemic control and can also be a good indicator of the lipid profile.

Physicochemical Evaluation of Edible Cyanobacterium Arthrospira platensis Collected from the South Atlantic Coast of Morocco: A Promising Source of Dietary Supplements.

The cyanobacterium Arthrospira platensis (A. platensis)-a genus of nonheterocystous filamentous cyanobacteria-is used in industrial applications and as a food supply. The current research work aims to study the physicochemical characteristics of A. platensis indigenous to the Moroccan Atlantic coast at Laayoune (Foum El Oued lagoon). The contents of proteins, carbohydrates, vitamins, lipids, minerals, heavy metals, energy value, humidity, ash, pigments, and tannins in A. platensis were investigated using protocols as described in the earlier literature. The values of protein, carbohydrate, and lipid contents in A. platensis were 58.9 ± 0.07, 14.67, and 45.54% respectively. The values of vitamins B2 and B3 dosed in A. platensis were 1.31 ± 0.19 and 30.8 ± 0.001 mg/kg, respectively. The values of heavy metals including lead and chromium were 70 ± 4.5 and 5 ± 0.5 PPB (parts-per-billion), respectively; however, no trace concerning cadmium was detected. The values of energy value, humidity, and ash content were 346.48 ± 0.21, 11.6 ± 0.17%, and 9.1 ± 0.21% kcal/100 g, respectively. The results of pigment content showed the presence of chlorophyll b, chlorophyll a, and carotenoids of 37.506 ± 3.38, 26.066 ± 3.08, and 9.52 ± 0.22 mg/g, respectively. The results obtained revealed that A. platensis indigenous to the Moroccan Atlantic coast at Laayoune was found to be very rich in proteins, carbohydrates, vitamins, minerals, ash, and pigments and lower in heavy metals and saturated fats when compared with species investigated in the literature. Thus, A. platensis indigenous to the Moroccan Atlantic coast at Laayoune fulfills the requirements for being used as dietary supplements.

Phytochemistry, Antioxidant Activity, Antiproliferative Effect, and Acute Toxicity Testing of Two Moroccan Aristolochia Species.

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochia baetica (A. baetica) and Aristolochia paucinervis (A. paucinervis) have been largely used in Moroccan folk medicine. The objective of the study was to investigate the phytochemical composition, the antioxidant activity, the antiproliferative effect, and the acute toxicity of the methanolic extract of A. baetica and A. paucinervis roots. MATERIALS AND METHODS: Phytochemical composition of the methanolic extract of A. baetica and A. paucinervis roots were studied using qualitative and quantitative methods, the antioxidant activity was evaluated using DPPH assay, the antiproliferative effects against human cancer cell lines (T-24, HT-29, and Hep G-2) was assessed using WST1 assay, and the acute toxicity was carried out orally by gavage of single dose 2000 mg/kg to mice for 14 days. RESULTS: The two studied plants have different classes of secondary metabolites. The concentrations of the total polyphenolic content of A. baetica and A. paucinervis root extracts were estimated at 360 ± 20 mg GAE/g and 280 ± 27 mg GAE/g, respectively. The total flavonoids content of A. baetica and A. paucinervis extracts were estimated at 35 ± 8 mg QE/g and 235 ± 7 mg QE/g, respectively. A. baetica and A. paucinervis extracts exhibited promising DPPH activity with IC50 values of 150 ± 8 µg/ml and 160 ± 10 µg/ml, respectively. The extracts exerted also antiproliferative effects on all tested cancer cell lines (T-24, HT-29, and Hep G-2) with IC50 values ranging from 6 ± 1 µg/ml to 380 ± 7 µg/ml. Regarding the results of acute toxicity study, no signs of toxicities nor mortalities were observed on the oral treated mice with 2000 mg/kg of the two investigated exacts. CONCLUSION: The methanolic extracts of A. baetica and A. paucinervis possess several phytochemicals that exhibited promising free radical scavenging activity and antiproliferative effects.

Ethnopharmacological Survey of Herbal Remedies Used for the Treatment of Cancer in the Greater Casablanca-Morocco.

Medicinal plants played an important role in traditional medicine for the treatment of diseases since antiquities. The aim of the study is to carry out an ethnobotanical survey on medicinal plants used traditionally in cancer treatment in the region of Greater Casablanca-Morocco, and to enhance the traditional herbal medicine knowledge. 110 traditional healers in the study area were interviewed face to face to response a survey questionnaire including the names of plants used in cancer treatment, used parts, methods of preparation, and route of administration. Indices of Fidelity Level (FL), Use Value (UV), and Relative Frequency of Citation (RFC) were calculated to identify the most effective plants used for cancer treatment. Eight species were specified including Aristolochia baetica, Aristolochia paucinervis, Bryonia dioica, Aquilaria malaccensis, Marrubium vulgare, Lavandula maroccana, Ephedra alata, and Euphorbia resinifera belonging to 7 families. Aristolochiaceae, Aquilariaceae, and Cucurbitaceae were the most useful families in cancer treatment with high significant indices of UV, FL, and RFC with values of 1, 100%, and 1, respectively. Roots and leaves were the most commonly used plant parts. Decoction and powder mixed with honey were the frequently used method for remedies preparation. The present study showed that the people living in Morocco's economic capital are still highly dependent on traditional herbal medicine for the treatment of cancer. Therefore, it seems that herbal medicine still plays a crucial role in the primary healthcare system for the local population. During this survey, it was reported that even some plant families are highly toxic for humans like Aristolochiaceae that are frequently used in cancer treatment in the study area. As many people still rely on natural traditional medicine considering (it is safe with no side effects), so combined effort between all social categories including scientists and traditional healers should be established for involving the scientific validity of the used plants in the treatment of diseases.

Phytochemical Analysis and Toxicity Study of Aristolochia paucinervis Rhizomes Decoction Used in Moroccan Alternative Medicine: Histopathological and Biochemical Profiles.

ETHNOPHARMACOLOGICAL RELEVANCE: Aristolochia paucinervis (A. paucinervis) (Aristolochiaceae) is a plant frequently used in Moroccan alternative medicine. The aim of the current study is to investigate the phytochemical composition of rhizomes decoction of A. paucinervis (RDA) and to evaluate its acute and subacute toxicity following the OECD guidelines. MATERIALS AND METHODS: The qualitative phytochemical analysis of A. paucinervis was performed using standard qualitative phytochemical procedures. The acute toxicity of rhizomes decoction of the studied plant was evaluated in mice at single doses of 1, 2, and 4 g/kg of body weight for 14 days. In subacute toxicity study, the decoction was orally administered to mice at three different doses (0.5, 1, and 1.5 g/kg/day) for 28 days. Histopathological and biochemical parameters were investigated. RESULTS: The preliminary phytochemical screening showed the presence of flavonoids, saponins, alkaloids, and polyphenols and the absence of anthraquinones, sterols, and terpenes. There was no mortality and no significant changes occurred in animals treated with 1 and 2 g/kg in the acute toxicity model. The signs of toxicity and morbidity were remarkable with the highest tested dose (4g/kg). LD50 (dose required to kill 50% of the test population) was determined as 4 g/kg. Repeated oral administration of 1 and 1.5 g/kg/day of RDA for 28 days induced significant disturbance of serum parameters (AST, ALT, LDH, urea, creatinine). Kidney and liver extracted from mice fed with 1 and 1.5 g/kg/day showed significant histopathological injuries as tubular necrosis, inflammatory infiltrate, tubular degeneration, necrosis, and hepatic cholestasis. Meanwhile, neither histopathological nor biochemical alterations were observed in mice treated with 0.5 g/kg/day of body weight in comparison to the control group. CONCLUSION: RDA showed toxicity in mice at a dose of 1 g/kg/day under subacute toxicity conditions. RDA is safe at a single dose inferior to 4 g/kg of body weight. The plant extract prepared by decoction showed more poisonous effect than the extract prepared by maceration at room temperature.

Phytochemical Screening and Toxicological Study of Aristolochia baetica Linn Roots: Histopathological and Biochemical Evidence.

Aristolochia baetica (A. baetica) is a wild species of Aristolochiaceae family; its roots are used by Moroccan people against cancer for many years ago. The objective of the study was to investigate the phytochemical screening, acute and subacute toxicity of A. baetica roots growing in the north of Morocco. Qualitative and quantitative analyses of A. baetica roots were performed using standard methods; the acute toxicity of the root extract of the studied plant was assessed in mice by gavage of single doses of 1, 2, and 4 g/kg body weight for 14 days; by the time the subacute toxicity was done using repeated doses 1, 1.5, and 2 g/kg/day for 28 days. Histological changes and biochemical parameters as markers of kidney and liver function were evaluated. The results of phytochemical screening showed the presence of polyphenols, tannins, alkaloids, flavonoids, saponins, and the absence of anthraquinones, sterols, and terpenes. The results of acute toxicity showed the absence of mortality and signs of toxicity in groups treated with 1 and 2 g/kg; however, the clinical signs of toxicity were important and the rate of mortality was estimated at 16 % in the group treated with 4 g/kg. The results of subacute toxicity showed several changes of serum parameters registered in groups treated with 1.5 and 2 g/kg/day, respectively. The results showed also the absence of histological injuries in groups treated with 1 and 1.5 g/kg/day; meanwhile, the histological alterations were remarkable in treated group with the highest dose administered of 2 g/kg/day. The outcome of this work showed that the roots' extract of the studied plant was toxic in mice with repeated doses, but no toxic effect was observed with a single dose under 4g/kg.