Search results for: gestational diabetes mellitus

Authors: Sajjad Rezaei, Mahdieh Molanouri Shamsi, Azadeh Jamali

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Background and purpose: Surfactant protein D (SP-D) is a lung-specific protein that is detectable in human plasma. Effect of exercise training on SP-D levels as well as its relation to metabolic indices is not known. The present study then aimed to investigate the effects of 10 weeks of aerobic training on serum levels of SP-D and insulin resistance in women with type 2 diabetes. Materials and methods: Twenty-two overweight women with type 2 diabetes mellitus were recruited through deliberate sampling and randomly assigned to intervention and control groups (11 in each group). The intervention group underwent a progressive aerobic training program for 10 weeks, 3 days per week, 30-55 min/day at 50-75% heart rate reserve (HRR). Control group continued with its everyday routine. Blood samples were obtained before and after training for biochemical analysis. Within-group and between-group differences were analyzed with paired and independent t-tests in spss software, respectively, and the relation between variables was analyzed with Pearson’s correlation coefficient (all at P = 0.05). Results: Significant differences were observed between groups in leptin, glucose, waist circumference and VO2 max after training. SP-D was decreased and VO2 max was increased significantly in intervention group. However, no significant correlation was observed between SP-D and other variables. Conclusion: Since there was no corresponding decrease in insulin resistance with decreased levels of SP-D, it seems unlikely for SP-D to mediate the association between obesity and insulin resistance in type 2 diabetics.

Keywords: exercise training, SP-D, insulin resistance, type 2 diabetes

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Authors: Filip Franciszek Karuga, Szymon Turkiewicz, Marta Ditmer, Marcin Sochal, Piotr Białasiewicz, Agata Gabryelska

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Circadian rhythm, an internal coordinator of physiological processes is composed of a set of semi-autonomous clocks. Clocks are regulated through the expression of circadian clock genes which form feedback loops, creating an oscillator. The primary loop consists of activators: CLOCK, BMAL1 and repressors: CRY, PER. CLOCK can be substituted by the Neuronal PAS Domain Protein 2 (NPAS2). Orphan nuclear receptor (REV-ERB-α) is a component of the secondary major loop, modulating the expression of BMAL1. Circadian clocks might be disrupted by the obstructive sleep apnea (OSA), which has also been associated with type II diabetes mellitus (DM2). Interestingly, studies suggest that dysregulation of NPAS2 and REV-ERB-α might contribute to the pathophysiology of DM2 as well. The goal of our study was to examine the role of NPAS2 and REV-ERB-α in DM2 in OSA patients. After examination of the clinical data, all participants underwent polysomnography (PSG) to assess their apnea-hypopnea index (AHI). Based on the acquired data participants were assigned to one of 3 groups: OSA (AHI>30, no DM2; n=17 for NPAS2 and 34 for REV-ERB-α), DM2 (AHI>30 + DM2; n=7 for NPAS2 and 15 for REV-ERB-α) and control group (AHI<5, no DM2; n=16 for NPAS2 and 31 for REV-ERB-α). ELISA immunoassay was performed to assess the serum protein level of REV-ERB-α and NPAS2. The only statistically significant difference between groups was observed in NPAS2 protein level (p=0.037). Post-hoc analysis showed significant differences between the OSA and the control group (p=0.017). AHI and NPAS2 level was significantly correlated (r=-0.478, p=0.002) in all groups. A significant correlation was observed between the REV-ERB-α level and sleep efficiency (r=0.617, p=0.005) as well as sleep maintenance efficiency (r=0.645, p=0.003) in the OSA group. We conclude, that NPAS2 is associated with OSA severity and might contribute to metabolic sequelae of this disease. REV-ERB-α on the other hand can influence sleep continuity and efficiency.

Keywords: OSA, diabetes mellitus, endocrinology, chronobiology

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Authors: Zena F. Mushtaq, Iqbal M. Abbas

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Background: Diabetes mellitus during pregnancy is one of the major medical and social problems with increasing prevalence in last decades and may lead to more vulnerable to dental problems and increased risk for periodontal diseases. Objectives: To assess oral hygiene behaviors among pregnant women with diabetes who attended primary health care centers and find out the relationship between oral hygiene behaviors and studied variables. Methodology: A cross sectional design was conducted from 7 July to 30 September 2014 on non probability (convenient sample) of 150 pregnant women with diabetes was selected from twelve Primary Health Care Centers at Baghdad city. Questionnaire format is tool for data collection which had designed and consisted of three main parts including: socio demographic, reproductive characteristics and items of oral hygiene behaviors among pregnant women with diabetes. Reliability of the questionnaire was determined through internal consistency of correlation coefficient (R= 0.940) and validity of content was determined through reviewing it by (12) experts in different specialties and was determined through pilot study. Descriptive and inferential statistics were used to analyze collected data. Result: Result of study revealed that (35.3%) of study sample was (35-39) years old with mean and SD is (X & SD = 33.57 ± 5.54) years, and (34.7%) of the study sample was graduated from primary school and less, half of the study sample was government employment and self employed, (42.7%) of the study sample had moderate socioeconomic status, the highest percentage (70.0%) of the study sample was nonsmokers, The result indicates that oral hygiene behaviors have moderate mean score in all items. There are no statistical significant association between oral hygiene domain and studied variables. Conclusions: All items related to health behavior concerning oral hygiene is in moderate mean of score, which may expose pregnant women with diabetes to high risk of periodontal diseases. Recommendations: Dental care provider should perform a dental examination at least every three months for each pregnant woman with diabetes, explanation of the effect of DM on periodontal health, oral hygiene instruction, oral prophylaxis, professional cleaning and treatment of periodontal diseases(scaling and root planing) when needed.

Keywords: diabetes, health behavior, pregnant women, oral hygiene

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Authors: Mengistu G. Woldu, Hani Y. Zaki, Areeg Faggad, Badreldin E. Abdalla

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Background: Type 2 diabetes mellitus (T2DM) is a complex, degenerative, and multi-factorial disease, which is culpable for huge mortality and morbidity worldwide. Even though relatively significant numbers of studies are conducted on the genetics domain of this disease in the developed world, there is huge information gap in the sub-Saharan Africa region in general and in Eritrea in particular. Objective: The principal aim of this study was to investigate the association of common variants of the Insulin Receptor Substrate 1 (IRS1) and Transcription Factor 7-Like 2 (TCF7L2) genes with T2DM in the Eritrean population. Method: In this cross-sectional case control study 200 T2DM patients and 112 non-diabetes subjects were participated and genotyping of the IRS1 (rs13431179, rs16822615, 16822644rs, rs1801123) and TCF7L2 (rs7092484) tag SNPs were carries out using PCR-RFLP method of analysis. Haplotype analyses were carried out using Plink version 1.07, and Haploview 4.2 software. Linkage disequilibrium (LD), and Hardy-Weinberg equilibrium (HWE) analyses were performed using the Plink software. All descriptive statistical data analyses were carried out using SPSS (Version-20) software. Throughout the analysis p-value ≤0.05 was considered statistically significant. Result: Significant association was found between rs13431179 SNP of the IRS1 gene and T2DM under the recessive model of inheritance (OR=9.00, 95%CI=1.17-69.07, p=0.035), and marginally significant association found in the genotypic model (OR=7.50, 95%CI=0.94-60.06, p=0.058). The rs7092484 SNP of the TCF7L2 gene also showed markedly significant association with T2DM in the recessive (OR=3.61, 95%CI=1.70-7.67, p=0.001); and allelic (OR=1.80, 95%CI=1.23-2.62, p=0.002) models. Moreover, eight haplotypes of the IRS1 gene found to have significant association withT2DM (p=0.013 to 0.049). Assessments made on the interactions of genotypes of the rs13431179 and rs7092484 SNPs with various parameters demonstrated that high density lipoprotein (HDL), low density lipoprotein (LDL), waist circumference (WC), and systolic blood pressure (SBP) are the best T2DM onset predicting models. Furthermore, genotypes of the rs7092484 SNP showed significant association with various atherogenic indexes (Atherogenic index of plasma, LDL/HDL, and CHLO/HDL); and Eritreans carrying the GG or GA genotypes were predicted to be more susceptible to cardiovascular diseases onset. Conclusions: Results of this study suggest that IRS1 (rs13431179) and TCF7L2 (rs7092484) gene polymorphisms are associated with increased risk of T2DM in Eritreans.

Keywords: IRS1, SNP, TCF7L2, type 2 diabetes

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Authors: Dedy Pratama, Akhmadu Muradi, Hilman Ibrahim, Raden Suhartono, Alexander Jayadi Utama, Patrianef Darwis, S. Dwi Anita, Luluk Yunaini, Kemas Dahlan

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Introduction: Vascular endothelial growth factor (VEGF) gene shows association with various angiogenesis conditions including Diabetic Foot Ulcer (DFU) disease. In this study, we performed this study to examine VEGF gene polymorphism associated with DFU. Methods: Case-control study of polymorphism of VEGF gene +405 C>G and -460 T>C, of diabetes mellitus (DM) type 2 with Diabetic Foot Ulcer (DFU) in Cipto Mangunkusumo National Hospital (RSCM) Jakarta from June to December 2016. Results: There were 203 patients, 102 patients with DFU and 101 patients without DFU. Forty-nine point 8 percent of total samples is male and 50,2% female with mean age 56,06 years. Distribution of the wild-type genotype VEGF +405 C>G wild type CC was found in 6,9% of respondents, the number of mutant heterozygote CG was 69,5% and mutant homozygote GG was 19,7%. Cumulatively, there were 6,9% wild-type and 85,2% mutant and 3,9% of total blood samples could not be detected on PCR-RFLP. Distribution of VEGF allele +405 C>G C alleles were 43% and G alleles were 57%. Distribution of genotype from VEGF gene -460 T>C is wild type TT 42,9%, mutant heterozygote TC 37,9% and mutant homozygote CC 13,3%. Cumulatively, there were 42,9% wild-type and 51% mutant type. Distribution of VEGF -460 T>C were 62% T allele and 38% C allele. Conclusion: In this study we found the distribution of alleles from VEGF +405 C>G is C 43% and G 57% and from VEGF -460 T>C; T 62% and C 38%. We propose that G allele in VEGF +405 C>G can act as a protective allele and on the other hands T allele in VEGF -460 T>C could be acted as a risk factor for DFU in diabetic patients.

Keywords: diabetic foot ulcer, diabetes mellitus, polymorphism, VEGF

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Authors: Maria Dora Horvath, Norbert Buzas, Zsanett Tesch

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Diabetes management poses many unique challenges for children and their parents. The use of a diabetes management device should not be one of these challenges as the purpose of these devices is to make the management more convenient. The objective of our study was to examine how demographical, psychological and diabetes-related factors determine the choices parents make regarding their child’s diabetes management technologies and how they perceive advanced devices. We conducted the study using an online questionnaire with 318 parents (mostly mothers). The questions of the survey were about demographical, diabetes-related and psychological factors (diabetes management problems, diabetes management competence). In addition, we asked the parents opinions about advanced diabetes management devices. We expanded our data with semi-structured in-depth interviews. 61 % of the participants Self-Monitored Blood Glucose (SMBG), and 39 % used a Continuous Glucose Monitoring System (CGM). Considering insulin administration, 58 % used Multiple Daily Insulin Injections (MDII) and 42 % used Continuous Subcutaneous Insulin Infusion (CSII). Parents who used diverse combinations of diabetes management devices showed significant differences in age (parents’ and child’s), the monthly cost of diabetes, the duration of diabetes, the highest level of education and average monthly household income. CGM users perceived diabetes management problems significantly more severe than SMBG users and CSII users felt significantly more competent in diabetes management than MDII users. Avoiding CGM use due to lack of financial resources was determined by diagnosis duration. While avoiding its use by the cause of the child rejecting, it was determined by the child’s age and diabetes competence. Using MDII instead of CSII because of the child’s rejection was determined by the monthly cost of diabetes and child’s age. We conducted a complex empirical study in which we examined perceptions and experiences of advanced and less advanced diabetes management technologies comprehensively. Our study highlights the factors that fundamentally influence parents’ motivations and choices about diabetes management technologies. These results could contribute to developing diabetes management technologies more suitable for children living with type 1 diabetes and their parents.

Keywords: advanced diabetes management technologies, children living with type 1 diabetes, diabetes management, motivation, parents

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Authors: Nditsheni Ramakuela, Sonto Maputle, Base Khoza, Augustine Tugli

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Inadequate health literacy can cause difficulties in understanding and compliance to treatment plan. With diabetic condition, self-care activities include behaviours of following a diet plan, avoiding high fat foods, increased exercise, self-glucose monitoring, and foot care. Patients with poor health literacy have difficulty interpreting medication warning labels, following directions on a prescription label and identifying their medications. Difficulties in understanding and performing self-care and health-related activities may ultimately lead to poor health outcomes. The study explored and described factors affecting health literacy and self-care to diabetic regimen by female patients at selected hospital in Limpopo Province of South Africa. Qualitative and explorative research design was used. Female patients who were admitted and diagnosed with diabetes in female medical ward constituted the study population. Non-probability, purposive sampling was used to select 20 female patients diagnosed with diabetes, who were above 18 years and admitted during April–November 2014. An in-depth face-to-face, unstructured interview was used to collect data. Data were analysed using open coding method. Measures to ensure trustworthiness and ethical considerations were adhered to. Findings revealed factors affecting health literacy for diabetic self-care activities amongst patients were; patient, family, disease and facility related. Proposed recommendations were; to strengthen diabetes education and patient-provider partnership. This is important and must be transferred to strengthen self-care activities to fully benefit the patient.

Keywords: compliance, diabetes mellitus, diabetic regimen, health literacy, self activities

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Authors: Shilpa Varghese, Adarsh Eregowda

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Introduction: The normal development and maturation of the central nervous system is significantly influenced by thyroid hormones. Small for gestational age (SGA) babies have a distinct hormonal profile than kids born at an acceptable birth weight for gestational age, according to several studies (AGA). In SGA babies, thyroid size is larger when expressed as a percentage of body weight, indicating that low thyroid hormone levels throughout foetal life may be partially compensated for. Numerous investigations have found that compared to full-term and preterm AGA neonates, SGA babies exhibit considerably decreased thyroid plasma levels. According to our hypothesis, term and preterm SGA newborns have greater thyroid-stimulating hormone (TSH) concentrations than those that are normal for gestational age (AGA) and a higher incidence of thyroid dysfunction. Need for the study: Clinically diagnosed Assessment of term SGA babies confirming thyroid dysfunction unclear Requirement and importance of ft4 along with tsh and comparative values of ft4 in SGA babies as compared to AGA babies unclear. Inclusion criteria : SGA infants including preterm (<37 weeks of gestation) term (37-40 weeks) – comparing with preterm and term AGA infants. 3.76 7.66 0 2 4 6 8 10 12 AGA Babies SGA Babies Mean Mean TSH Comparison 2.73 1.52 0 0.5 1 1.5 2 2.5 3 3.5 4 AGA Babies SGA Babies Mean Mean FT4 Comparison Discussion : According to this study, neonates with SGA had considerably higher TSH levels than newborns with AGA. Our findings have been supported by results from earlier research. The TSH level range was established to 7.5 mU/L in the study by Bosch-Giménez et al, found greater TSH concentrations in SGA newborns. Thyroid hormone levels from newborns that are tiny for gestational age were found to be higher than AGA in our investigation. According to Franco et al., blood T4 concentrations are lower in both preterm and term SGA infants, while TSH concentrations are only noticeably greater in term SGA infants compared to AGA ones. According to our study analysis, the SGA group had considerably greater FT4 concentrations. Therefore, our findings are consistent with those of the two studies that SGA babies have a higher incidence of transient hypothyroidism and need close follow-up. Conclusions: A greater frequency of thyroid dysfunction and considerably higher TSH values within the normal range were seen in preterm and term SGA babies. The SGA babies who exhibit these characteristics should have ongoing endocrinologic testing and periodic TFTs.

Keywords: thyroid hormone, thyroid function tests, small for gestationl age, appropriate for gestational age

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Authors: Neelofar, Khursheed Alam, Jamal Ahmad

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Protein modification in diabetes mellitus may lead to early glycation products (EGPs) or amadori product as well as advanced glycation end products (AGEs). Early glycation involves the reaction of glucose with N-terminal and lysyl side chain amino groups to form Schiff’s base which undergoes rearrangements to form more stable early glycation product known as Amadori product. After Amadori, the reactions become more complicated leading to the formation of advanced glycation end products (AGEs) that interact with various AGE receptors, thereby playing an important role in the long-term complications of diabetes. Millard reaction or nonenzymatic glycation reaction accelerate in diabetes due to hyperglycation and alter serum protein’s structure, their normal functions that lead micro and macro vascular complications in diabetic patients. In this study, Human Serum Albumin (HSA) with a constant concentration was incubated with different concentrations of glucose at 370C for a week. At 4th day, Amadori product was formed that was confirmed by colorimetric method NBT assay and TBA assay which both are authenticate early glycation product. Conformational changes in native as well as all samples of Amadori albumin with different concentrations of glucose were investigated by various biophysical and biochemical techniques. Main biophysical techniques hyperchromacity, quenching of fluorescence intensity, FTIR, CD and SDS-PAGE were used. Further conformational changes were observed by biochemical assays mainly HMF formation, fructoseamine, reduction of fructoseamine with NaBH4, carbonyl content estimation, lysine and arginine residues estimation, ANS binding property and thiol group estimation. This study find structural and biochemical changes in Amadori modified HSA with normal to hyperchronic range of glucose with respect to native HSA. When glucose concentration was increased from normal to chronic range biochemical and structural changes also increased. Highest alteration in secondary and tertiary structure and conformation in glycated HSA was observed at the hyperchronic concentration (75mM) of glucose. Although it has been found that Amadori modified proteins is also involved in secondary complications of diabetes as AGEs but very few studies have been done to analyze the conformational changes in Amadori modified proteins due to early glycation. Most of the studies were found on the structural changes in Amadori protein at a particular glucose concentration but no study was found to compare the biophysical and biochemical changes in HSA due to early glycation with a range of glucose concentration at a constant incubation time. So this study provide the information about the biochemical and biophysical changes occur in Amadori modified albumin at a range of glucose normal to chronic in diabetes. Although many implicates currently in use i.e. glycaemic control, insulin treatment and other chemical therapies that can control many aspects of diabetes. However, even with intensive use of current antidiabetic agents more than 50 % of diabetic patient’s type 2 suffers poor glycaemic control and 18 % develop serious complications within six years of diagnosis. Experimental evidence related to diabetes suggests that preventing the nonenzymatic glycation of relevant proteins or blocking their biological effects might beneficially influence the evolution of vascular complications in diabetic patients or quantization of amadori adduct of HSA by authentic antibodies against HSA-EGPs can be used as marker for early detection of the initiation/progression of secondary complications of diabetes. So this research work may be helpful for the same.

Keywords: diabetes mellitus, glycation, albumin, amadori, biophysical and biochemical techniques

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Authors: Farah Amalina Mohamed Affandi, Redhwan Ahmad Al-Naggar, Seok Mui Wang, Thanikasalam Kathiresan

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Gestational choriocarcinoma is a condition in which there is an abnormal growth or a tumor inside the women’s uterus after conception. It is a type of gestational trophoblastic disease which is relatively rare and malignant. The current epidemiological data of this disease are inadequate. The purposes of this study are to examine the epidemiology of choriocarcinoma and their risk factors based on all available population-based and hospital-based data of the disease. In this study, we searched The MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases using the keywords ‘choriocarcinoma’, ‘gestational’, ‘gestational choriocarcinoma’ and ‘epidemiology’. We included only human studies published in English between 1995 and 2015 to ensure up to date evidence. Case studies, case reports, animal studies, letters to the editor, news, and review articles were excluded. Retrieved articles were screened in three phases. In the first phase, any articles that did not match the inclusion criteria based solely on titles were excluded. In the second phase, the abstracts of remaining articles were screened thoroughly; any articles that did not meet our inclusion criteria were excluded. In the final phase, full texts of the remaining articles were read and assessed to exclude articles that did not meet the inclusion criteria or any articles that fulfilled the exclusion criteria. Duplicates articles were also removed. Systematic reviews and meta-analysis were excluded. Extracted data were summarized in table and figures descriptively. The reference lists of included studies were thoroughly reviewed in search for other relevant studies. A total of ten studies met all the selection criteria. Nine were retrospective studies and one was cohort study. Total numbers of 4563 cases of choriocarcinoma were reviewed from several countries which are Korea, Japan, South Africa, USA, New Mexico, Finland, Turkey, China, Brazil and The Netherlands. Different studies included different range of age with their mean age of 28.5 to 30.0 years. All studies investigated on the disease’s incidence rate, only two studies examined on the risk factors or associations of the disease. Approximately 20% of the studies showed a reduction in the incidence of choriocarcinoma while the other 80% showed inconsistencies in rate. Associations of age, fertility age, occupations and socio-demographic with the status remains unclear. There is limited information on the epidemiological aspects of gestational choriocarcinoma. The observed results indicated there was a decrease in the incidence rate of gestational choriocarcinoma globally. These could be due to the reduction in the incidence of molar pregnancy and the efficacy of the treatment, mainly by chemotherapy.

Keywords: epidemiology, gestational choriocarcinoma, incidence, prevalence, risk factor

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Authors: Samira Rabiei, Faezeh Askari, Reza Rastmanesh

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Objective: To evaluate the effects of nutrition education and adherence to a healthy diet on glycemic and lipidemic control in patients with T2DM. Material and Methods: A randomized controlled trial was conducted on 494 patients with T2DM, aged 14-87 years from both sexes who were selected by convenience sampling from referees to Aliebneabitaleb hospital in Ghom. The participants were divided into two 247 person groups by stratified randomization. Both groups received a diet adjusted based on ideal body weight, and the intervention group was additionally educated about healthy food choices regarding diabetes. Information on medications, psychological factors, diet and physical activity was obtained from questionnaires. Blood samples were collected to measure FBS, 2 hPG, HbA1c, cholesterol, and triglyceride. After 2 months, weight and biochemical parameters were measured again. Independent T-test, Mann-Whitney, Chi-square, and Wilcoxon were used as appropriate. Logistic regression was used to determine the odds ratio of abnormal glycemic and lipidemic control according to the intervention. Results: The mean weight, FBS, 2 hPG, cholesterol and triglyceride after intervention were significantly lower than before that (p < 0.05). Discussion: Nutrition education plus a weigh reducer diet is more effective on glycemic and lipidemic control than a weight reducer diet, alone.

Keywords: type 2 diabetes mellitus, nutrition education, glycemic control, lipid profile

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Authors: Adriana Garcia-Gurrola, Carlos Adrian Peña Natividad, Ana Laura Martinez Martinez, Alberto Abraham Escobar Puentes, Estefania Ochoa Ruiz, Aracely Serrano Medina, Abraham Wall Medrano, Simon Yobanny Reyes Lopez

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Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by elevated blood glucose levels. Quercetin is a natural flavonoid with a hypoglycemic effect, but reported data are inconsistent due mainly to the structural instability and low solubility of quercetin. Nanoencapsulation is a distinct strategy to overcome the intrinsic limitations of quercetin. Therefore, this work aims to develop a quercetin nano-formulation based on biopolymeric starch nanoparticles to enhance the release and hypoglycemic effect of quercetin in T2DM induced mice model. Starch-quercetin nanoparticles were synthesized using high-intensity ultrasonication, and structural and colloidal properties were determined by FTIR and DLS. For in vivo studies, CD1 male mice (n=25) were divided into five groups (n=5). T2DM was induced using a high-fat and high-sugar diet for 32 weeks and streptozotocin injection. Group 1 consisted of healthy mice fed with a normal diet and water ad libitum; Group 2 were diabetic mice treated with saline solution; Group 3 were diabetic mice treated with glibenclamide; Group 4 were diabetic mice treated with empty nanoparticles; and Group 5 was diabetic mice treated with quercetin nanoparticles. Quercetin nanoparticles had a hydrodynamic size of 232 ± 88.45 nm, a PDI of 0.310 ± 0.04 and a zeta potential of -4 ± 0.85 mV. The encapsulation efficiency of nanoparticles was 58 ± 3.33 %. No significant differences (p = > 0.05) were observed in biochemical parameters (lipids, insulin, and peptide C). Groups 3 and 5 showed a similar hypoglycemic effect, but quercetin nanoparticles showed a longer-lasting effect. Histopathological studies reveal that T2DM mice groups showed degenerated and fatty liver tissue; however, a treated group with quercetin nanoparticles showed liver tissue like that of the healthy mice group. These results demonstrate that quercetin nano-formulations based on starch nanoparticles are effective alternatives with hypoglycemic effects.

Keywords: quercetin, diabetes mellitus tipo 2, in vivo study, nanoparticles

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Authors: Abdullah S. Alghamdi, Khaled Alghamdi, Richard O. Jenkins, Parvez I. Haris

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Background: Quantity and quality of sleep have been reported to be significant risk factors for obesity and development of metabolic disorders such as type 2 diabetes mellitus (T2DM). The relationship between diabetes and sleep quantity was reported to be U-shaped, which means increased or decreased sleeping hours can increase the risk of diabetes. The plasma glucagon levels were found to continuously decrease during night-time sleep in healthy individuals, independently of blood glucose and insulin levels. The disturbance of the circadian rhythm is also important and has been linked with an increased the chance of diabetes incidence. There is a lack of research on sleep patterns on Saudis with T2DM and how this is affected by Ramadan fasting. Aim: To assess the sleeping patterns of Saudis with T2DM (before, during, and after Ramadan), using two different techniques and relate this to their HbA1c levels. Method: This study recruited 82 Saudi with T2DM, who chose to fast during Ramadan, from the Endocrine and Diabetic Centre of Al Iman General Hospital, Riyadh, Saudi Arabia. Ethical approvals for the study were obtained from De Montfort University and Saudi Ministry of Health. Their sleeping patterns were assessed by a self-administered questionnaire (before, during, and after Ramadan). The assessment included the daily total sleeping hours (DTSH), and total night-time sleeping hours (TNTSH) of the participants. In addition, sleeping patterns of 36 patients, randomly selected from the 82 participants, were further tracked during and after Ramadan by using Fitbit Flex 2™ accelerometer. Blood samples were collected in each period for measuring HbA1c. Results: Questionnaire analysis revealed that the sleeping patterns significantly changed between the periods, with shorter hours during Ramadan (P < 0.001 for DTSH, and P < 0.001 for TNTSH). These findings were confirmed by the Fitbit data, which also indicated significant shorter sleeping hours for the DTSH, and the TNTSH during Ramadan (P < 0.001 and P < 0.001, respectively). Although there were no significant correlations between the questionnaire and Fitbit data, the TNTSH were shorter among the participants in all periods by both techniques. The mean HbA1c significantly varied between periods, with lowest level during Ramadan. Although the statistical tests did not show significant variances in the mean HbA1c between the groups of participants regarding their hours of sleeping, the lowest mean HbA1c was observed in the group of participants who slept for 6-8 hours and had longer night-time sleeping hours. Conclusion: A short sleep duration, and absence of night-time sleep were significantly observed among the majority of the study population during Ramadan, which could suppress the full benefits of Ramadan fasting for diabetic patients. This study showed that there is a good agreement between the findings of the questionnaire and the Fitbit device for evaluating sleeping patterns in a Saudi population. A larger study is needed in the future to investigate the impact of Ramadan fasting on sleep quality and quantity and its relationship with health and disease.

Keywords: Diabetes, Fasting, Fitbit, HbA1c, IPAQ, Ramadan, Sleep

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Authors: Nasiruddin Khan, Nasser M. Al-Daghri, Dara A. Al-Disi, Asim Al-Fadda, Mohamed Al-Seif, Gyanendra Tripathi, A. L. Harte, Philip G. Mcternan

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For the last few decades, the prevalence of type 2 diabetes mellitus (T2DM) in the Kingdom of Saudi Arabia (KSA) is increasing alarmingly high and is unprecedented at 31.6 %. Preventive measures should be taken to curb down the increasing incidence. In this prospective, 3-month study, we aimed to determine whether dietary modification program would confer favorable affects among overweight and obese adult Saudi women with or without T2DM. A total of 92 Saudi women [18 healthy controls, 24 overweight subjects and 50 overweight or obese patients with early onset T2DM were included in this prospective study. Baseline anthropometrics and fasting blood samples were taken at baseline and after 3 months. Fasting blood sugar and lipid profile were measured routinely. A 500 Kcal deficit energy diet less than their daily recommended dietary allowances were prescribed to all participants. After 3 months of follow-up visit, significant improvements were observed in both the overweight and DMT2 group as compared to baseline with decreased mean BMI [Overweight Group 28.54±1.49 versus 27.95±2.25, p<0.05; DMT2 group 35.24±7.67 versus 35.04±8.07, p<0.05] and hip circumference [Overweight group 109.67±5.01 versus 108.07±4.07, p<0.05; DMT2 group 112.3±13.43 versus 109.21±12.71, p<0.01]. Moreover, in the overweight group, baseline HDL-cholesterol was significantly associated with protein intake and inversely associated with carbohydrate intake in controls. In the DMT2 group, carbohydrate intake at baseline was significantly associated with BMI. A 3-month 500kcal/day deficit dietary modification alone is probably effective among adult overweight or obese Saudi females without or with T2DM. Longer prospective studies are to determine whether the dietary intervention alone can reduce progression of T2DM among high-risk adult Arabs.

Keywords: diet, lipid, obesity, T2DM

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Authors: K. J. Keerthi, Vasundhara Kamineni, A. Ravi Shanker, T. Rammurthy, A. Vijaya Lakshmi, Q. Hasan

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Pancreatic β-cells are the predominant insulin-producing cell types within the Islets of Langerhans and insulin is the primary hormone which regulates carbohydrate and fat metabolism. Apoptosis of β-cells or insufficient insulin production leads to Diabetes Mellitus (DM). Current therapy for diabetes includes either medical management or insulin replacement and regular monitoring. Replacement of β- cells is an attractive treatment option for both Type-1 and Type-2 DM in view of the recent paper which indicates that β-cells apoptosis is the common underlying cause for both the Types of DM. With the development of Edmonton protocol, pancreatic β-cells allo-transplantation became possible, but this is still not considered as standard of care due to subsequent requirement of lifelong immunosuppression and the scarcity of suitable healthy organs to retrieve pancreatic β-cell. Fetal pancreatic cells from abortuses were developed as a possible therapeutic option for Diabetes, however, this posed several ethical issues. Hence, in the present study Mesenchymal stem cells (MSCs) were differentiated into insulin producing cells which were isolated from Human Umbilical cord (HUC) tissue. MSCs have already made their mark in the growing field of regenerative medicine, and their therapeutic worth has already been validated for a number of conditions. HUC samples were collected with prior informed consent as approved by the Institutional ethical committee. HUC (n=26) were processed using a combination of both mechanical and enzymatic (collagenase-II, 100 U/ml, Gibco ) methods to obtain MSCs which were cultured in-vitro in L-DMEM (Low glucose Dulbecco's Modified Eagle's Medium, Sigma, 4.5 mM glucose/L), 10% FBS in 5% CO2 incubator at 37°C. After reaching 80-90% confluency, MSCs were characterized with Flowcytometry and Immunocytochemistry for specific cell surface antigens. Cells expressed CD90+, CD73+, CD105+, CD34-, CD45-, HLA-DR-/Low and Vimentin+. These cells were differentiated to β-cells by using H-DMEM (High glucose Dulbecco's Modified Eagle's Medium,25 mM glucose/L, Gibco), β-Mercaptoethanol (0.1mM, Hi-Media), basic Fibroblast growth factor (10 µg /L,Gibco), and Nicotinamide (10 mmol/L, Hi-Media). Pancreatic β-cells were confirmed by positive Dithizone staining and were found to be functionally active as they released 8 IU/ml insulin on glucose stimulation. Isolating MSCs from usually discarded, abundantly available HUC tissue, expanding and differentiating to β-cells may be the most feasible cell therapy option for the millions of people suffering from DM globally.

Keywords: diabetes mellitus, human umbilical cord, mesenchymal stem cells, differentiation

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Authors: Daniel Gredig, Annabelle Bartelsen-Raemy

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Social work services offered to people living with diabetes tend to be moulded by the prevailing understanding that social work is to support people living with diabetes in their adherence to medical prescription and/or life style changes. As diabetes has been conceived as a condition facing no stigma, discrimination of people living with diabetes has not been considered. However, there is growing evidence of stigma. To our knowledge, nevertheless, there have been no comprehensive, in-depth studies of stigma and its impact. Against this background and challenging the present layout of services for people living with diabetes, the present study aimed to establish whether: -people living with diabetes in Switzerland experience stigma, and if so, in what context and to what extent; -experiencing stigma impacts the quality of life of those affected. It was hypothesized that stigma would impact on their quality of life. It was further hypothesized that low self-esteem, psychological distress, depression, and a lack of social support would be mediating factors. For data collection an anonymous paper-and-pencil self-administered questionnaire was used which drew on a qualitative elicitation study. Data were analysed using descriptive statistics and structural equation modelling. To generate a large and diverse convenience sample the questionnaire was distributed to the readers of journal destined to diabetics living in Switzerland issued in German and French. The sample included 3347 people with type 1 and 2 diabetes, aged 16–96, living in diverse living conditions in the German- and French-speaking areas of Switzerland. Respondents reported experiences of discrimination in various contexts and stereotyping based on the belief that diabetics have a low work performance; are inefficient in the workplace; inferior; weak-willed in their ability to manage health-related issues; take advantage of their condition and are viewed as pitiful or sick people. Respondents who reported higher levels of perceived stigma reported higher levels of psychological distress (β = .37), more pronounced depressive symptoms (β=.33), and less social support (β = -.22). Higher psychological distress (β = -.29) and more pronounced depressive symptoms (β = -.28), in turn, predicted lower quality of life. These research findings challenge the prevailing understanding of social work services for people living with diabetes in Switzerland and beyond. They call for a less individualistic approach, the consideration of the social context service users are placed in their everyday life, and addressing stigma. So, social work could partner with people living with diabetes in order to fight against discrimination and stereotypes. This could include identifying and designing educational and public awareness strategies. In direct social work with people living with diabetes, this could include broaching experiences of stigma and modes of coping with. This study was carried out in collaboration with the Swiss Diabetes Association. The association accepted the challenging conclusions from this study. It connected to the results and is currently discussing the priorities and courses of action to be taken.

Keywords: diabetes, discrimination, quality of life, services, stigma

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Authors: Samereh Abdoli, Amit Vora, Anusha Vora

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Aim: To qualitatively investigate diabetes burnout in parents of children with Type 1 Diabetes (T1D) who shared their experiences through YouTube videos in order to inform future interventions and improve diabetes practice. Methods: A qualitative descriptive approach was used to explore YouTube videos. Of the 568 videos that were identified, only 9 videos met the inclusion criteria of the study. Results: After the videos were transcribed and analyzed using qualitative content analysis, it was revealed that parents shared common concerns and experiences and they translated into three main themes: I do not ever get a break, I am exhausted, I can’t burn out, and I just need a break Conclusion: All in all, the literature revealed that there are negative psychosocial outcomes associated with caring for a child with T1D, but there is a lack of information on diabetes burnout and how parents’ well-being are affected. Reports of self-neglect and sleep deprivation only confirm the need for intervention for parents of children with T1D. The hope with this study is that burnout can be recognized early on and appropriate interventions put in place to help parents cope with the stressors of caring for a child with a chronic disease.

Keywords: Diabetes burnout, type 1 diabetes, qualitative research, parents

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Authors: Pedro Batista, André Vinha, Filipe Castelo, Bárbara Costa, Ricardo Sousa, Raquel Ricardo, André Pinto

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Background: Septic arthritis is a diagnosis that must be considered in any patient presenting with acute joint swelling and fever. Among the several risk factors for septic arthritis, such as age, rheumatoid arthritis, recent surgery, or skin infection, diabetes mellitus can sometimes be the main risk factor. Staphylococcus aureus is the most common pathogen isolated in septic arthritis; however, it is uncommon in monomicrobial necrotizing fasciitis. Objectives: A case report of concomitant septic arthritis and necrotizing fasciitis in a patient with undiagnosed diabetes based on clinical history. Study Design & Methods: We report a case of a 58-year-old Portuguese previously healthy man who presented to the emergency department with fever and left knee swelling and pain for two days. The blood work revealed ketonemia of 6.7 mmol/L and glycemia of 496 mg/dL. The vital signs were significant for a temperature of 38.5 ºC and 123 bpm of heart rate. The left knee had edema and inflammatory signs. Computed tomography of the left knee showed diffuse edema of the subcutaneous cellular tissue and soft tissue air bubbles. A diagnosis of septic arthritis and necrotising fasciitis was made. He was taken to the operating room for surgical debridement. The samples collected intraoperatively were sent for microbiological analysis, revealing infection by multi-sensitive Staphylococcus aureus. Given this result, the empiric flucloxacillin (500 mg IV) and clindamycin (1000 mg IV) were maintained for 3 weeks. On the seventh day of hospitalization, there was a significant improvement in subcutaneous and musculoskeletal tissues. After two weeks of hospitalization, there was no purulent content and partial closure of the wounds was possible. After 3 weeks, he was switched to oral antibiotics (flucloxacillin 500 mg). A week later, a urinary infection by Pseudomonas aeruginosa was diagnosed and ciprofloxacin 500 mg was administered for 7 days without complications. After 30 days of hospital admission, the patient was discharged home and recovered. Results: The final diagnosis of concomitant septic arthritis and necrotizing fasciitis was made based on the imaging findings, surgical exploration and microbiological tests results. Conclusions: Early antibiotic administration and surgical debridement are key in the management of septic arthritis and necrotizing fasciitis. Furthermore, risk factors control (euglycemic blood glucose levels) must always be taken into account given the crucial role in the patient's recovery.

Keywords: septic arthritis, Necrotizing fasciitis, diabetes, Staphylococcus Aureus

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Authors: C. Mayuren, C. K. Paul Wang, K. Purushotham, C. Dinesh Kumar

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Diabetes Mellitus (DM) is one of the most common non-communicable diseases globally. Although significant advances have led to better understanding of the condition and the development of effective therapies and preventive strategies, the pathway to cure remains elusive and DM prevails as a serious medical challenge in the 21st century. Oxidative stress has been suggested to contribute to the progression and pathophysiological conditions of diabetes. Madecassoside (MA) a major pentacyclic triterpenoid, has been demonstrated to possess various biological activities. However, no attempt has been made to study the antioxidant activity in diabetic rats. Therefore, the present study is aimed to evaluate the antioxidant effect of MA on streptozotocin-nicotinamide induced type-2 diabetes in Sprague-Dawley rats. The study protocol was approved by the institutional ethical committee prior to the conduct of research. Adult male Sprague-Dawley rats weighing 250-300 g were used in the study. The animals were rendered diabetic with a single intraperitoneal dose of streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg). The diabetic animals after a stabilisation period of 14 days received various treatments (Madecassoside 50 mg/kg; Glimepiride 2.5 mg/kg) suspended in 0.5% carboxymethyl cellulose orally, for a period of 28 days. The animals fasted overnight after the last treatment were sacrificed and the pancreas, liver and kidneys were isolated. The weighted quantity of the samples of various treatments were homogenised in ice-cold condition and were subjected to lipid peroxidation, catalase and superoxide dismutase assay. The data’s obtained were subjected to statistical analysis. Diabetic rats showed significant increase in lipid peroxidation and decrease in enzymatic antioxidant levels. All the treated groups had significantly higher SOD, CAT and reduced LPO activity in the pancreas, liver and kidney. Results suggest madecassoside to have potential antioxidant effect against the diabetic model. However further investigations are necessary to study the mechanism at the cellular level.

Keywords: antioxidant, diabetes, madecassoside, nicotinamide, streptozotocin

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Authors: Zahid Hussain, Nayyab Sultan

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This study describes the preparation of zinc oxide nanoparticles and their anti-diabetic effect individually and with the combination of Momordica charantia plant extract. This plant is termed bitter melon, balsam pear, bitter gourd, or karela. Blood glucose levels in mice were monitored in their random state before and after the administration of zinc oxide nanoparticles and plant extract. The powdered form of nanoparticles and the selected plant were used as an oral treatment. Diabetes was induced in mice by using a chemical named as streptozotocin. It is an artificial diabetes-inducing chemical. In the case of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg); the maximum anti-diabetic effect observed was 70% ± 1.6 and 75% ± 1.3, respectively. In the case of the combination of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg), the maximum anti-diabetic effect observed was 86% ± 2.0. The results obtained were more effective as compared to standard drugs Amaryl (3mg/kg), having an effectiveness of 52% ± 2.4, and Glucophage (500mg/kg), having an effectiveness of 29% ± 2.1. Results indicate that zinc oxide nanoparticles and plant extract in combination are more helpful in treating diabetes as compared to their individual treatments. It is considered a natural treatment without any side effects rather than using standard drugs, which shows adverse side effects on health, and most probably detoxifies in liver and kidneys. More experimental work and extensive research procedures are still required in order to make them applicable to pharmaceutical industries.

Keywords: albino mice, amaryl, anti-diabetic effect, blood glucose level, Camellia sinensis, diabetes mellitus, Momordica charantia plant extract, streptozotocin, zinc oxide nanoparticles

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Authors: Reham Algheshairy, Khaled Tayeb, Christopher Smith, Rebecca Gregg, Haruna Musa

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Background: Diabetes is a medical condition that refers to the pancreas’ inability to secrete sufficient insulin levels, a hormone responsible for controlling glucose levels in the body. Any surplus glucose in the blood stream is excreted through the urinary system. Insulin resistance in blood cells can also cause this condition despite the fact that the pancreas is producing the required amount of insulin A number of researchers claim that the prevalence of diabetes in Saudi Arabia has reached epidemic proportions, although one study did observe one positive in the rise in the awareness of diabetes, possibly indicative of Saudi Arabia’s improving healthcare system. While a number of factors can cause diabetes, the ever-increasing incidence of the disease in Saudi Arabia has been blamed primarily on low levels of physical activity and high levels of obesity. Objectives: The project has two aims. The first aim of the project is to investigate the regulatory effects of consumption of Nigella seeds and Ajwah dates on blood glucose levels in diabetic patients with type 2 diabetes. The second aim of the project is to investigate whether these dietary factors may have potentially beneficial effects in controlling the complications that associated with type 2 diabetes. Methods: This use a random-cross intervention trail of 75 Saudi male and female with type 2 diabetes in Al-Noor hospital in Makkah ( KSA) aged between 18 and 70 years were divided into 3 groups. Group 1 will consume 2g of Nigella Sativa seeds daily along with a modified diet for 12 weeks, group 2 will be given Ajwah dates daily with a modified diet for 12 weeks and group 3 will follow a modified diet for 12 weeks. Anthropometric measurements were taken at baseline, along with bloods for HbA1c, fasting blood sugar and at the end of 12 weeks. Results: This study found significant decrease in blood level (FBG & 2PPBG) and HbA1c in the groups with diet and Nigella seeds) compared to Ajwa date. However, there is no significant change were found in HbA1c, FBG and 2hrpp regarding Ajwa group. Conclusion: This study illustrated a significant improvement in some markers of glycaemia following 2 g of Ns and diet for 12 weeks. The dose of 2g/day of consumed Nigella seeds was found to be more effective in controlling BGL and HbA1c than control and Ajwa groups. This suggests that Nigella seeds and following a diet may have a potential effect (a role in controlling outcomes for type 2 diabetes and controlling the disease). Further research is needed on a large scale to determine the optimum dose and duration of Nigella and Ajwa in order to achieve the desired results.

Keywords: type 2 diabetes, Nigella seeds, Ajwa dates, fasting blood glucose, control

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Authors: Shalini Adiga, Shashikant Chetty, Jisha, Shobha Kamath

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Background: Moderate impairment of learning and memory has been observed in both type 1 and 2 diabetes mellitus in humans and experimental animals. A Change in glucose utilization and oxidative stress that occur in diabetes are considered the main reasons for cognitive dysfunction. Objective: Costus igneus (CI) which is known to possess hypoglycemic activity was evaluated in this study for its effect on learning and memory in normal and diabetic rats. Methods: Wistar rats were divided into control, CI-alcoholic extract treated normal (250 and 500mg/kg), diabetic control and CI-treated diabetic groups. CI treatment was continued for 4 weeks. For induction of diabetes, a single dose of streptozotocin was injected (30 mg/kg i.p). Entrance latency and time spent in the dark room during acquisition and at 24 and 48h after an aversive shock in a passive avoidance model was used as an index of learning and memory. Glutathione and malondialdehyde levels in brain and blood glucose were measured. Data was analysed using ANOVA. Results: During the three trials in exploration test, the diabetic control rats exhibited no significant change in entrance latency or in the total time spent in the dark compartment. During retention testing, the entrance latency of the diabetic treated groups was two times less at 24h and three times less at 48h after aversive stimulus as compared to diabetic rats. The normal drug-treated rats showed similar behaviour as the saline control. Treatment with CI significantly reduced the raised blood sugar and MDA levels of diabetic rats. Conclusion: Costus igneus prevented the cognitive dysfunction in diabetic rats which can be attributed to its antioxidant and antihyperglycemic activities.

Keywords: Costus igneous, diabetes, learning and memory, cognitive dysfunction

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Authors: Gupta Renu, T. S. Roy

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Introduction: For the prospect of successful replacement therapies in treatment of Diabetes mallitus it is necessary to know events occurring during normal human pancreas development. Literature of human pancreas development are few in number as well as mainly related to first trimester because of ethical and technical difficulties. So the study was conducted on 12 fetuses from 12 gestational weeks (GW) to 5 months of infant to know normal development of exocrine and endocrine part of human pancreas. Material and Methods: Human fetalpancreases were screened by haematoxyline and eosin staining and done electron microscopy for suitable specimens to know ultrastructural detail of fetal pancreas. Results:It was observed arborized tubules, the cells budding out from these tubules differentiated into primitive acini and islets in 12thGW. At 14 weeks scanty granules were observed in the endocrine cells which coincided with the capillary invasion of the islets. The ducts and acini were surrounded by well-organized connective tissue. The acinihad elongated cells, small amount of cytoplasm and large open face euchromatic nuclei with single nucleolus. The mature form of islets of Langerhans was observed close to the acini and duct in 20 GW fetus. Connective tissue around the duct was well organized.No significant developmental change was observed early postnatal, infant. Conclusion: The development of both component exocrine as well as endocrine part of human fetal pancreas was studied by light and electron microscopy. Observations suggested that the fetal pancreas contained mainly ducts, few acini, many centroacinar cells, and large undifferentiated tissue.

Keywords: gestational weeks (GW), acini, islets of Langerhans, ducts

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Authors: Ozlem Karabulutlu, Kiymet Yesilcicek Calik, Nazli Akar

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Objectives: To examine fear of childbirth according to parity, gestational age, prenatal education, and obstetric history. Methods: The study was performed as a questionnaire design in a State Hospital in Kars, Turkey with 403 unselected pregnant who were recruited from the delivery unit. The data were collected via 3 questionnaires; the first with sociodemographic and obstetric features, the second with Wijma Delivery Expectance/Experience Questionnaire (W-DEQ) scale, and the third with the scale of Beck Anxiety Inventory (BAI). Results: The W-DEQ and BAI scores were higher in nulliparous than multiparous woman (W-DEQ 67.08±28.33, 59.87±26.91, P=0.039<0.05, BAI 18.97±9.5, 16.65±11.83, P=0.0009<0.05 respectively). Moreover, W-DEQ and BAI scores of pregnant whose gestational week was ≤37 / ≥41 and who didn’t receive training and had vaginal delivery was higher than those whose gestational week was 38-40 weeks and who received prenatal training and had cesarean delivery (W-DEQ 67.54±29.20, 56.44±22.59, 69.72±25.53 p<0.05, BAI 21.41±9.07; 15.77±11.20, 18.36±10.57 p<0.05 respectively). Both in nulliparous and multiparous, as W-DEQ score increases BAI score increases too (r=0.256; p=0.000<0.05). Conclusions: Severe fear of childbirth and anxiety was more common in nulliparous women, preterm and post-term pregnancy and who did not receive prenatal training and had vaginal delivery.

Keywords: Beck Anxiety Inventory (BAI), fear of birth, parity, pregnant women, Wijma Delivery Expectance/Experience Questionnaire (W-DEQ)

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Authors: Nicholas Abdilmasih, Habib Rezanejad

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This study investigates the gene expression induction efficiency of single versus multiple guide RNAs (gRNAs) targeting the NGN3 gene using the CRISPR activation system in HEK293 cells. Our study aimed to contribute to optimizing the use of gRNAs in gene therapy applications, particularly in treating diseases like diabetes, where precise gene regulation is essential. The experimental design involves culturing HEK293 cells, and once they reach approximately 70-80% confluence, cells were transfected with specific gRNAs targeting the NGN3 gene promoter. Specific gRNAs targeting the NGN3 promoter that was previously designed, incorporated into plasmid clone cassettes and introduced into HEK293 cells through co-transfection using pCAG-DDdCas9-VP192-EGFP transactivator. Post-transfection, cell viability, and fluorescence were monitored to assess transfection efficiency. RNA was extracted, converted to cDNA, and analyzed via qPCR to measure NGN3 expression levels. Results indicated that specific combinations of fewer gRNAs led to higher NGN3 activation compared to multiple gRNAs, challenging the assumption that more gRNAs result in synergistic gene activation. These findings suggest that optimized gRNA combinations can enhance gene therapy efficiency, potentially leading to more effective treatments for conditions like diabetes.

Keywords: CRISPR activation, Diabetes mellitus, gene therapy, guide RNA, Neurogenin3

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Authors: Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML

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Type 1 diabetes is caused by autoimmune destruction of insulin-secreting beta cells in the pancreas. T cells are known to play an important role in this immune-mediated destruction; however, there is no general consensus regarding alterations in cytokine production or T cell subsets in peripheral blood of patients with type 1 diabetes. Using polychromatic flow cytometry of peripheral blood mononuclear cells (PBMCs), we assessed production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 by memory CD4 T effector (Teff) cells in 69 patients with type 1 diabetes and 61 healthy donors. We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). In a separate cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. Consistent with the increased production of IL-21, we also found a 14.9% increase in circulating Tfh cells in the patients with type 1 diabetes (95% CI 2.9, 26.9; p = 0.016). Analysis of IL-21 production by PBMCs from a subset of 46 of the 62 donors immunophenotyped for Tfh showed that frequency of Tfh cells was associated with the frequency of IL-21+ cells (r2 = 0.174, p = 0.004). These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.

Keywords: T follicular helper cell, IL-21, IL-17, type 1 diabetes

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Authors: Issam M Hajjaji, Adel Tajoury, Salah R Benhamid

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The MENA region has the highest prevalence of diabetes in the world. Various risk scores were developed, not all appropriate locally. The objective of this study is to apply the FINDRISC Score to adult Libyan males to determine its significance, sensitivity, specificity and Positive Predictive Values as an initial screening tool for type 2 diabetes, and suggest a cut-off point. Methods: 600 subjects answered the questionnaire at their place of work, and their waist, weight, height & BP were measured. Thereafter, after excluding those with known diabetes, an Oral Glucose Tolerance Test was done. Results: 414 subjects aged 19-78 completed the questionnaire and tests. 35 (8.4%) had impaired glucose tolerance (IGT) and 13 (3.1%) had diabetes (DM). The AUC-ROC for IGT was 0.614 (95% CI: 0.527-0.701), for DM 0.810 (95% CI: 0.709-0.911) and for both 0.689 (95% CI: 0.609-0.769). The Positive Predictive Value for a cut-off score of 5 were 15.5%, 11.7% & 5.7% for both conditions combined, prediabetes & diabetes respectively. The equivalent values for a cut-off score of 8 were 16.1%, 9.0% & 7.7%. The Negative Predictive Values were uniformly above 90%. Conclusions & Recommendations: The FINDRISC Score had a low predictive value for dysglycaemia in this sample and performed at a level of significance for IGT that is similar to other MENA countries, but did better for DM. A larger sample that included women is suggested, with a view of adjusting the Score to suit the local population.

Keywords: diabetes, FINDRISK, Libya, prediabetes

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Authors: Omolola Soji-Omoniwa, Babasoji Omoniwa

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The hypolipidemic effect of leaf essential oil of Citrus sinensis in alloxan–induced diabetic rats was evaluated. Forty albino rats (150–200 g) were randomly selected into 4 groups of 10 rats each, representing Normal Control, Diabetic Control, Diabetic treated with 14.2 mg/kg body weight Metformin and Diabetic treated with 110 mg/kg body weight leaf essential oil of Citrus sinensis. Diabetes was induced in the animals by intraperitoneal administration of single dose alloxan monohydrate (150 mg/kg body weight). The leaf essential oil of Citrus sinensis was administered every other day to the Diabetic rats for a period of 15 days. The effects of leaf essential oil on High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Trigylcerides and Cholesterol were evaluated. A significant reduction (p <0.05) in LDL, Triglycerides and cholesterol levels and a significant increase (p<0 .05) in HDL was observed. Leaf essential oil of Citrus sinensis possesses hypolipidemic properties.

Keywords: Citrus sinensis, Diabetes mellitus, hypolipidemic, leaf essential oil

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Authors: Saeed Pourhassan, Nastaran Maghbouli

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1) Background It has been hypothesized that, in individuals with diabetes mellitus, the peripheral nerve is swollen due to sorbitol over-accumulation. Additionally growing evidence supported electro diagnostic study of diabetes induced neuropathy as a method having some challenges. 2) Objective To examine the performance of sonographic cross-sectional area (CSA) measurements in the diagnosis of diabetic polyneuropathy (DPN). 3) Data Sources Electronic databases, comprising PubMed and EMBASE and Google scholar, were searched for the appropriate studies before Jan 1, 2020. 4) Study Selection Eleven trials comparing different peripheral nerve CSA measurements between participants with and without DPN were included. 5) Data Extraction Study design, participants' demographic characteristics, diagnostic reference of DPN, and evaluated peripheral nerves and methods of CSA measurement. 6) Data Synthesis Among different peripheral nerves, Tibial nerve diagnostic odds ratios pooled from five studies (713 participants) were 4.46 (95% CI, 0.35–8.57) and the largest one with P<0.0001, I²:64%. Median nerve CSA at wrist and mid-arm took second and third place with ORs= 2.82 (1.50-4.15), 2.02(0.26-3.77) respectively. The sensitivities and specificities pooled from two studies for Sural nerve were 0.78 (95% CI, 0.68–0.89), and 0.68 (95% CI, 0.53–0.74). Included studies for other nerves were limited to one study. The largest sensitivity was for Sural nerve and the largest specificity was for Tibial nerve. 7) Conclusions The peripheral nerves CSA measured by ultrasound imaging is useful for the diagnosis of DPN and is most significantly different between patients and participants without DPN at the Tibial nerve. Because the Tibial nerve CSA in healthy participants, at various locations, rarely exceeds 24 mm2, this value can be considered as a cutoff point for diagnosing DPN.

Keywords: diabetes, diagnosis, polyneuropathy, ultrasound

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Authors: Rashini Maduka, C. R. Wijesinghe, A. R. Weerasinghe

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Drug-drug interactions (DDIs) can happen when two or more drugs are taken together. Today DDIs have become a serious health issue due to adverse drug effects. In vivo and in vitro methods for identifying DDIs are time-consuming and costly. Therefore, in-silico-based approaches are preferred in DDI identification. Most machine learning models for DDI prediction are used chemical and biological drug properties as features. However, some drug features are not available and costly to extract. Therefore, it is better to make automatic feature engineering. Furthermore, people who have diabetes already suffer from other diseases and take more than one medicine together. Then adverse drug effects may happen to diabetic patients and cause unpleasant reactions in the body. In this study, we present a model with a graph convolutional autoencoder and a graph decoder using a dataset from DrugBank version 5.1.3. The main objective of the model is to identify unknown interactions between antidiabetic drugs and the drugs taken by diabetic patients for other diseases. We considered automatic feature engineering and used Known DDIs only as the input for the model. Our model has achieved 0.86 in AUC and 0.86 in AP.

Keywords: drug-drug interaction prediction, graph embedding, graph convolutional networks, adverse drug effects

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