Childhood type 1 diabetes mellitus and risk factor of interactions between dietary cow's milk intake and HLA-DR3/DR4 genotype.

Short-term breastfeeding and early exposure to dairy products into infant diets, may be critical factors for development of type 1 diabetes. In this study, we investigate whether cow's milk proteins are risk factors for type 1 diabetes in genetically susceptible individuals (HLA DR3/DR4) by using statistical analysis and in silico approach. In order to verify the potential risk of the early introduction of cow's milk, we conducted this study to validate the veracity of this hypothesis in our population. We included 121 subjects, 55 type 1 diabetics and 74 controls from the region of Tlemcen (Algeria). Thus, the in silico approach was performed to determine the molecular mimicry region between Bovine serum albumin and beta-lactoglobulin with self-Islet antigen 2 and glutamate decarboxylase 65 by determining their sequences and their 3D structures. The risk factors associated with type 1 diabetes in a genetically predisposed individual (HLA DR3/DR4) retained by the logistic model are: type 1 and type 2 diabetes inheritance, the early introduction of cow's milk before 6 months and breastfeeding less than 9 months. Besides, the epitopes of cow's milk proteins have the capacity to bind to predisposing HLA class II molecules (HLA DR3/DR4) and induce an immune reaction by the secretion of Interleukin 4 (Th2) and Interferon (Th1) which lead to the destruction of pancreatic beta cells. The early introduction of cow's milk proteins in susceptible individuals is considered as risk factors for the pathogenesis of T1DM. The in silico approach confirm that BSA and BLG share sequence and structure homology with IA2 and GAD65.Communicated by Ramaswamy H. Sarma.

Copper Isotopes and Copper to Zinc Ratio as Possible Biomarkers for Thyroid Cancer.

Thyroid cancer is the most common endocrine cancer. There is no systematic screening for such cancer, and the current challenge is to find potential biomarkers to facilitate an early diagnosis. Copper (Cu) and zinc (Zn) are essential micronutrients involved in the proper functioning of the thyroid gland, and changes in their concentrations have been observed in the development of cancer. Previous studies have highlighted the potential 65Cu/63Cu ratio (δ65Cu) to be a cancer biomarker. This study tests its sensitivity on plasma samples (n = 46) of Algerian patients with papillary thyroid carcinoma and a set of corresponding biopsies (n = 11). The δ65Cu ratio in blood and tumor samples was determined using multi collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), and their corresponding Cu and Zn plasma total concentrations using total reflection X-ray fluorescence (TXRF). Plasma concentrations of Cu were significantly higher (1346.1 ± 328.3 vs. 1060.5 ± 216.1 µg/L, p < 0.0001), and Zn significantly lower (942.1 ± 205.2 vs. 1027.9 ± 151.4 µg/L, p < 0.05) in thyroid cancer patients as compared to healthy controls (n = 50). Accordingly, the Cu/Zn ratio was significantly different between patients and controls (1.5 ± 0.4 vs. 1.0 ± 0.3, p < 0.0001). Furthermore, the δ65Cu plasma levels of patients were significantly lower than healthy controls (p < 0.0001), whereas thyroid tumor tissues presented high δ65Cu values. These results support the hypothesis that Cu isotopes and plasma trace elements may serve as suitable biomarkers of thyroid cancer diagnosis.

Se Status Prediction by Food Intake as Compared to Circulating Biomarkers in a West Algerian Population.

Algeria is the largest country in Africa, located close to the Mediterranean coastal area, where nutrients consumption varies widely. Local data on selenium composition of foods are not available. We postulated a close correlation between selenium status predictions from food consumption analysis with a quantitative analysis of circulating biomarkers of selenium status. Population characteristics were recorded from 158 participants and dietary selenium intake was calculated by 24-h recall. The average total plasma selenium was 92.4 ± 18.5 µg/L and the mean of selenium intake was 62.7 µg/day. The selenoprotein P concentration was 5.5 ± 2.0 mg/L and glutathione peroxidase 3 activity was 247.3 ± 41.5 U/L. A direct comparison of the dietary-derived selenium status to the circulating selenium biomarkers showed no significant interrelation. Based on absolute intakes of meat, potato and eggs, a model was deduced that outperforms the intake composition-based prediction from all food components significantly (DeLong's test, p = 0.029), yielding an area under the curve of 82%. Selenium status prediction from food intake remains a challenge. Imprecision of survey method or information on nutrient composition makes extrapolating selenium intake from food data providing incorrect insights into the nutritional status of a given population, and laboratory analyses are needed for reliable information.

Molecular mimicry between varicella, measles virus and Hsp60 in type 1 diabetes associated HLA-DR3/DR4 molecules.

BACKGROUND AND AIMS: Type 1 diabetes (T1D) is a multifactorial autoimmune disease that combines genetics and environmental factors. The aim of this study is to determine the environmental risk factors and to investigate how virals infections are risks factors for type 1 diabetics whom have HLA DR3/DR4 predisposition in our population. METHODS: This study includes 233 subjects, 145 diabetics and 88 controls from regions of the extreme western of Algeria. All the informations related to the disease were collected using predesigned questionnaire. Using in silico approach, we attempt to improve the understanding of this analytical result by molecular mimicry, which is associated with the breakdown of several autoimmune pathologies. RESULTS: The statistical study showed that history of varicella and measles infection and T1D related inheritance and type 2 diabetes are risk factors for T1D in the population of Tlemcen. We have determined the homologous antigenic regions between the glycoprotein "gE" of the varicella virus, the "hemagglutinin" of measles and the human protein "HSP60" at the level of their sequence and 3D structure. These cross-reactive epitopes bind to MHC class II molecules (HLA DR3/DR4) that predispose to T1D but not to MHC class II molecules (HLA DR2) that protect against T1D. This epitopes induce Th2 cells but only "hemagglutinin" and "Hsp60" can activate Th1 differentiation. This indicates their potential to destroy pancreatic cells ß. CONCLUSION: Our study can allow us to adapt biological markers to genetically predisposed T1D and to establish a preventive strategy for healthy genetic predisposed individuals in Tlemcen population.

Selenium overexposure induces insulin resistance: In silico study.

BACKGROUND AND AIMS: Several studies raise concerns about the possible association of high selenium exposure with insulin resistance and type 2 diabetes. This in silico study proposes a possible mechanism of insulin resistance in the case of overexposure to selenium. METHOD: A study was carried out using molecular modeling, where cysteines of the insulin-receptor are replaced by selenocysteines. Calculation of the interaction energy of the receptor was performed in both cases with Auto Dock Tools and Vina 4.2 software to predict whether the substitution of amino acid could lead to destabilization of the protein-ligand complex and therefore possibly insulin resistance. Finally, the docked complex was analyzed by using BIOVIA Discovery Studio Visualizer to show the type of interactions between the ligands and insulin-receptor, and to determine the distance of the ligands from the binding site on insulin-receptor. RESULTS: The results show that the substitution of cysteine by selenocysteine in the insulin receptor does not lead to stabilization of the complex receptor/insulin, but to its disruption.In addition, the types and the number of bonds between insulin and its receptor in the two cases are different, where 7 strong bonds between insulin and its receptor were found in the case of the cysteine complex compared to 6 weak bonds in the second case. CONCLUSION: Findings of this study suggest that misincorporation of selenocysteines in insulin receptor could lead to destabilization of the insulin-receptor complex and therefore may possibly cause an insulin resistance.

Dietary intake of magnesium in a type 1 diabetic pediatric population.

Several studies suggest the importance of adequate magnesium intake in the prevention of diabetes and/or its complications. The main objective of this study is to determine the daily dietary intake of magnesium in type 1 Algerian pediatric diabetics. The study involved a pediatric population of 201 individuals aged from 3 to 17 years, including 96 type 1 diabetics and 105 controls. The daily dietary intake of magnesium was determined by the 24-hour recall. The correlation between the intake of magnesium and glycemic control has been assessed in diabetics. The odds ratio was used to study the relationship between dietary magnesium intake and diabetes through multinomial logistic regression. The results indicate that there are 84% of diabetics with low magnesium intake compared to 61% of controls (P = 0.001). A negative but no significant correlation was found between magnesium intake, glycemia, and HbA1c. The multinomial logistic regression model showed that daily dietary magnesium intakes, lower than EFSA adequate intake, are associated with an OR of 5.50 (1.92-15.74; P = 0.002) in adjusted model for age, sex, and BMI. It is necessary to correct the low dietary intake of magnesium by changing the eating habits of the pediatric populations in western Algeria and more particularly type 1 diabetics.

Hematologic disorders during essential hypertension.

BACKGROUND: Besides the traditional risk factors, hematological changes may be involved in the development of arterial hypertension and in its pathogenesis. METHODS: The study, conducted on a sample of 545 subjects, 215 with hypertension and 330 witnesses, were evaluated for peripheral blood parameters in western Algeria; Logistic regression analysis was used to predict hypertension with hematological parameters. RESULTS: The characters studied related significantly; lower red blood cell levels have a three-and-a-half-fold risk of developing hypertension compared to those who have normal red blood cell counts (OR = 3.64, 95% CI = 1.37-9.65, p < 0.05). Subjects who have mean corpuscular volume rate below 80 fl are more exposed to hypertension (OR = 13.58, 95% CI = 4.68-39.41, p = 0.000). The mean corpuscular hemoglobin concentration reveals that subjects who have a lower than normal (<27 pg) are once less exposed to hypertension (OR = 0.04, 95% CI = 0.01-0.13, p = 0.000). Subjects who have lower platelet count than normal are twelve times more exposed to hypertension (OR = 12.13, 95% CI = 1.45-101.18, P = 0.021). Finally, the increase in sedimentation rate at one hour increases the risk of hypertension by 56.63 times compared to subjects with normal sedimentation rate (OR = 56.63, 95% CI = 3.37-597.33, P = 0.001). CONCLUSIONS: Hematological profile associated with essential hypertension retained Red blood cells ratio, mean corpuscular volume, mean corpuscular hemoglobin concentration, platelet ratio, and sedimentation rate at one hour.

Non-HDL cholesterol predictive factor of type 2 diabetes in the city of Tlemcen.

BACKGROUND: type 2 diabetes mellitus (T2DM) is associated with disorders of lipoprotein metabolism mixed dyslipidemia. The purpose of this study is to verify whether non high density lipoprotein cholesterol (non-HDL-C) can contribute to the development of T2DM in a population in the extreme western Algeria. METHODS: The study was conducted in Tlemcen region on a sample of 1852 subjects,1059 with T2DM and 793 controls, these were evaluated for biochemical parameters, measured using standard enzyme procedures (SFBC or IFCC recommendations) on the Beckman CX7® PLC (Beckman-Coulter®, NY, USA). All the information related to the disease were collected from the patients and recorded using predesigned questionnaire. RESULTS: The logistic model retained, the two levels of non-HDL-C: 130 mg/dl < non-HDL-C≤160 mg/dl (OR = 0,69; 95% CI = 0,49-0,97, P = 0,033) and non-HDL-C>190 mg/dl (OR = 2,22; 95% CI = 1,31-3,76, P = 0,003), inbreeding (OR = 1,71; 95% CI = 1,44-2,04, P = 0,000) and the two age groups 60-70 years (OR = 2,14; 95% CI = 1,47-3,1, P ≪ 0,001) and 70 years and over (OR = 2,26; 95% CI = 1,51-3,38, P ≪ 0,001). CONCLUSIONS: The logistic model shows that non-HDL-C contributes to the development of type 2 diabetes in our population.

Predictive value of non-HDL cholesterol for cardiovascular disease in a population in far western Algeria with type 2 diabetes.

BACKGROUND: Non high density lipoprotein cholesterol (non-HDL-C) is a risk factor for cardiovascular disease (CVD) in people with type 2 diabetes. The aim of our study is to estimate the relative multivariate risk of non-HDL-C in the occurrence of CVD in a population in the extreme western Algeria with type 2 diabetes mellitus (T2DM). METHODS: Our study was carried out in western Algeria on a population of 1111 subjects, 371 cardiopaths with T2DM and 740 controls. The biochemical balance was established using standard enzymatic procedures (SFBC or IFCC recommendations) on the Beckman CX7® PLC (Beckman-Coulter®, NY, USA). Information on the pathologies was collected by means of a questionnaire. RESULTS: The logistic model retained the two levels of non-HDL-C: 130 mg/dl < non-HDL-C≤160 mg/dl (OR = 0.11; 95% CI = 0.03-0,47, P = 0.003) and 160 mg/dl < non-HDL-C≤190 mg/dl (OR = 5.02; 95% CI = 1.1-22.87, P = 0.037) and smoking (OR = 19.27; 95% CI = 3.39-109.63, P = 0.001), inbreeding (OR = 3.65; 95% CI = 1.12-11,85, P = 0.031) and the two age groups 60-70 years (OR = 2.36; 95% CI = 1.32-4.2, P<<0.01) and 70 years and over (OR = 2.26; 95% CI = 1.19-4.29, P<<0.05). CONCLUSIONS: Non-HDL-C is a powerful risk factor for the occurrence of cardiovascular disease in type 2 diabetics in the extreme western Algeria.

Hematological profile associated with type 2 diabetes mellitus.

BACKGROUND: Hematological changes affecting blood cells and the coagulation factors are shown to be associated with diabetes mellitus. We investigated some of the hematological risk factors implicated in the development of type 2 diabetes mellitus. METHODS: The study conducted in western Algeria on a sample of 1852 subjects, 1059 with type 2 diabetes and 793 witnesses, were evaluated for peripheral blood parameters using hematology analyzer. All the informations related to the disease were collected from the patients and recorded using predesigned questionnaire. RESULTS: The logistic model retained, the mean corpuscular hemoglobin concentration reveals that subjects with concentration over the normal ratio (>36 g/dl) have an exposure risk six and half times higher than subjects with normal concentration (OR = 6.59; 95% CI = 2.51-17.31, P = 0.000). As regards to the platelets blood ratio, subjects with a ratio lower are five times more exposed to type 2 diabetes compared to subjects with a normal ratio (OR = 5.01; 95% CI = 1.78-14.13, P < 0.002). Our logistic model also retained basophils ratio (OR = 2.18; 95% CI = 1.35-3.53, P < 0.001) and sedimentation rate at one hour (OR = 7.83; 95% CI = 3.39-18.06, P = 0.000). CONCLUSIONS: Hematological profile associated with type 2 diabetes mellitus retained the mean corpuscular hemoglobin concentration over the normal ratio, lower platelets blood ratio, basophils ratio and sedimentation rate at one hour.

[Dosage of cadmium and lead in human blood by anodic stripping voltammetry]. / Dosage du cadmium et du plomb dans le sang humain par voltamétrie à redissolution anodique.

The objective is the determination of the conditions operating optimal to determine the concentration of the cadmium and the lead dissolved in the human blood. An electroanalytical method has been developed for the determination of lead and cadmium in whole blood by differential pulse anodic stripping voltammetry (DPASV) on a hanging mercury drop electrode (HMDE). The best conditions were found to be electrolyte support perchloric acid 0.02 M, the accumulation potential is -900 mV, and the accumulation time is 320 s. The obtained limits of detection are equal to 0.46 and 0.08 ng/mL respectively for the lead and the cadmium. The developed method was validated by the analysis of reference materials certified by total blood.

Whole blood selenium levels in healthy adults from the west of Algeria.

The purpose of this study was to assess whole blood selenium levels of 300 healthy adults living in four selected areas of the west of Algeria. Selenium was measured using differential pulse cathodic stripping voltammetry with a detection limit of 29.20 µg/L. The mean of whole blood selenium concentrations was 85.65 ± 21.60 µg/L ranging between 30.90 and 144.04 µg/L. This concentration did not vary significantly (P > 0.05) in relation to the gender of the subject, with concentrations of 87.75 ± 21.30 µg/L in men and 83.95 ± 21.60 µg/L in women group. Individuals older than 60 years had a whole blood selenium concentration significantly lower than the rest of the population. However, the measured selenium concentrations in the residential areas were not statistically different (P > 0.05). A total of 32 (10.70%) individuals exhibited whole blood selenium level below 60 µg/L. These results are similar to those of some European countries but are much lower than data observed in USA or seleniferous regions.