The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients.

PURPOSE: To investigate the allelic and genotypic frequencies of the two genetic variations, NC_000006.12: g.160275887C > T (rs662301) and NC_000006.12:g.160231826 T > C (rs315978), in the SLC22A2 gene among the Saudi population. The primary goal is to elucidate potential associations with these genetic variations and the response to metformin therapy over 6 months to enhance our knowledge of the genetic basis of Type 2 Diabetes Mellitus (T2DM) and its clinical management in the Saudi population. MATERIALS/METHODS: 76 newly diagnosed T2DM patients, aged 30 to 60, of both sexes and Saudi origin, were treated with metformin monotherapy. Blood samples were collected before and after 6 months of therapy,80 healthy individuals were included as controls. Genomic DNA was extracted. Genotyping of the SLC22A2 genetic variations was performed using TaqMan® SNP Genotyping Assays. Binary logistic regression was utilized to evaluate how certain clinical parameters influence T2DM concerning the presence of SLC22A2 gene variants. RESULTS: Among these patients, 73.3 % were responders, and 26.7 % were non-responders. For these variants, no statistically significant differences in genotype or allele frequencies were observed between responders and non-responders (p = 0.375 and p = 0.384 for rs662301; p = 0.473 and p = 0.481 for rs315978, respectively). For the SLC22A2 variant rs662301, the C/C genotype was significantly associated with increased T2DM risk with age and elevated HbA1c levels. Similarly, rs315978 revealed higher T2DM susceptibility and HbA1c elevation in C/C genotype carriers, specifically with advancing age compared to individuals with C/T and T/T genotypes. CONCLUSION: The study offers insights into the genetic landscape of T2DM in Saudi Arabia. Despite the absence of significant associations with treatment response, the study suggests potential age-specific associations, this highlights the complexity of the disease. This research underscores the necessity for expanded research, considering diverse populations and genetic factors, to develop personalized treatment approaches. This study serves as a foundation for future investigations into the Saudi population, recognizing the need for a larger sample size.

Exercise Habits During Ramadan Among Healthcare Professionals: A Cross-Sectional Observational Study From Jeddah, Saudi Arabia.

Background Fasting during Ramadan may affect several habits, including physical activity levels. Therefore, the present study was designed to assess changes in exercise habits among healthcare providers (HCPs) during Ramadan in Jeddah, Saudi Arabia. This study aimed to evaluate the factors associated with changes in exercise habits during Ramadan. Methodology This cross-sectional, observational study included HCPs working in Jeddah, Saudi Arabia. Data were collected using an electronic self-administered questionnaire between March and April 2020. McNemar's test was used to assess the difference between exercise habits during Ramadan and the rest of the year. Pearson's chi-square test was used to explore the factors affecting the rate and intensity of exercise during Ramadan. P-values less than 0.05 were considered statistically significant. Results A total of 89 HCPs were enrolled in the study. Of these, 64% (n = 57) were female, and 67.4% (n = 60) worked in governmental hospitals. Of these, 58.4% (n = 52) had moderate physical activity, and 41.6% (n = 37) had low exercise intensity during Ramadan. The percentage of low-intensity exercises increased to 52.8% (n = 47). Almost one-third of the HCPs who usually performed moderate or severe-intensity exercise decreased their intensity significantly to a low level. In addition, 10.8% (n = 4) of respondents upgraded their exercise intensity from low to moderate or severe levels during Ramadan. Meanwhile, Ramadan had no significant impact on the usual exercise rate. Conclusions The present study demonstrated the reduction in the intensity of exercise among HCPs during Ramadan without changing the usual exercise rate.

Evaluation of Osteoporosis Perception Among Saudi Arabian Premenopausal Women: A Cross-Sectional Survey Study Using the Osteoporosis Knowledge Assessment Tool (OKAT).

INTRODUCTION: Osteoporosis is a major clinical problem that affects the whole population, especially women. It is a condition that is becoming more prevalent with aging. The increase in bone fragility associated with the disease can lead to fractures, even from minor trauma. Our goal is to evaluate the extent of knowledge about osteoporosis and perceptions of it among premenopausal women in Saudi Arabia. METHOD: This descriptive cross-sectional study was conducted among premenopausal women during the months of June and July 2021. We distributed an online questionnaire on social networking sites and applications that Saudi women use on a daily basis. We used the Osteoporosis Knowledge Assessment Tool (OKAT) to evaluate the responses. RESULT: A total of 661 women took part in our study; 159 of them were excluded because they had either reached the menopausal period or had already been diagnosed with the disease. The overall perception of osteoporosis is noticeably poor, as only 55% of respondents had an acceptable level of knowledge. In addition, we found a statistically significant association between education level and knowledge level (p-value = 0.044). CONCLUSION: The findings revealed that more than half the participants scored "acceptable" in terms of their understanding of the disease, which indicates a serious awareness gap. This outcome demonstrates the necessity of increasing community awareness about osteoporosis to reduce potential harm and the financial burden of healthcare.

Are parents' willing to vaccinate their children against COVID-19? A qualitative study based on the Health Belief Model.

In response to the COVID-19 pandemic, several countries have started implementing voluntary or involuntary mass vaccination programs. Although vaccine acceptance is high among adults, uncertainty about whether to vaccinate children against COVID-19 remains a controversial theme. To date, few qualitative studies have explored parents' views on this topic. A qualitative descriptive study design was used to collect data and individual in-depth interviews were conducted with 50 parents in the Makkah region of Saudi Arabia. The Health Belief Model (HBM) was used as a guide in developing the interview guide. Each question was related to a construct of the HBM. The data were then analyzed using thematic content analysis and interpreted using NVivo software. Two major themes emerged: motivation to vaccinate children, which was influenced by perceived benefits, perceived severity, perceived suitability, collective responsibilities, confidence, and cues to action; and barriers to vaccination in children, which included complacency, rapid vaccine development, and uncertainty about the long-term side effects of the vaccine. The findings of this study revealed that the public is not sufficiently informed about the efficacy or side effects of the COVID-19 vaccine, increasing the awareness of which will help parents make informed decisions regarding vaccinating their children and potentially increase vaccine acceptance.

Currently, the debate about whether children should be vaccinated for COVID-19 is ongoing worldwide. This research explored the thoughts of Saudi Arabian parents in this regard through in-depth interviews. The viewpoints were grouped into two themes: motivators and barriers toward vaccination. The motivators included factors such as parents' beliefs that the vaccine would help protect their children and the aged against the severity of the disease, especially those with existing conditions such as obesity. They also felt that the vaccination would help develop the society's herd immunity against the virus and felt an obligation to have their children vaccinated. Barriers toward vaccination included factors such as concerns about the long-term side effects of the vaccine on children, and the belief that children's immune systems are strong enough to fight the virus and that the vaccine might negatively affect their immune systems. This study showed that parents need to be educated on the benefits and side effects of COVID-19 vaccination for children. The results of this study will help health authorities and the government to increase the uptake and acceptability of the COVID-19 vaccine for children.

Depression Among Patients With Type 2 Diabetes Mellitus at King Abdulaziz University Hospital (KAUH): A Cross-Sectional Study.

BACKGROUND:  Depression can increase the risk of diabetes-related complications, healthcare expenditures, and morbidity in patients with type 2 diabetes mellitus (T2DM). There have been increasing cases of diabetes in Saudi Arabia; however, research correlating depression with diabetes is lacking. The aim of this study was to find out how common depression is among T2DM patients at King Abdulaziz University Hospital (KAUH), Jeddah, and assess any additional risk factors for depression in these patients. METHODOLOGY:  A cross-sectional study using computer-assisted telephone interviews was conducted among patients with T2DM from June to August 2021. A total of 215 participants completed the survey. Symptoms and signs of depression were assessed using the Patient Health Questionnaire (PHQ-9). Univariate, bivariate, and multivariate statistical analyses were used to determine the prevalence and risk factors associated with depression. RESULTS: Depression was shown to be prevalent in 54% of type 2 diabetes patients, with the most common associated risk factors being not exercising (p=0.00) and having at least one diabetes-related complication (p=0.001). There was no evidence of a significant relationship between depression and gender or age, although females were, in general, more depressed than males. CONCLUSION: Diabetic patients have a significantly high prevalence of depression; therefore, it is vital to conduct regular screening for depression in patients diagnosed with T2DM.

Diabetes Mellitus and Related Admission Factors Among Hospitalized Patients in King Abdul-Aziz University Hospital in Jeddah, Saudi Arabia.

Background Diabetes mellitus (DM) is a rapidly increasing serious health problem that affects the population all over the world. The increasing prevalence of DM in Saudi Arabia is reflected in our hospital admissions as well. This study aimed to assess the proportion of DM (including type 1 and type 2 diabetes) among hospitalized patients and the reasons for admissions to the medical unit at King Abdul-Aziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Methods We conducted a hospital record-based cross-sectional study at KAUH from January to April 2021. The study included all adult patients admitted to the internal medicine wards and isolation unit but excluded patients in the coronary care unit and those with gestational diabetes. We reviewed the medical records to collect demographic data, causes of admission, laboratory results, and outcomes. Results Among the hospitalized patients, 49.9% had DM. The most common associated risk factors and causes of admission among patients with DM were hypertension (HTN; 73.2%) and dyslipidemia (43.1%). Other less common reasons for admission were heart failure (20.6%), coronavirus disease-2019 (COVID-19; 17.8%), chronic kidney disease (CKD; 14.5%), pneumonia (12.3%), and stroke (10%). Dyslipidemia, HTN, CKD, diabetic ketoacidosis, heart failure, and need for intensive care unit (ICU) admission were significantly higher in diabetic patients as compared to patients without diabetes. HTN, dyslipidemia, CKD, heart failure, stroke, acute abdomen, and malignancy were significantly higher in patients with type 2 diabetes. Among diabetic patients, those with non-Saudi nationality, low hemoglobin level, dyslipidemia, pneumonia, sepsis, and requiring ICU admission had a greater risk of death. Conclusions The high burden of DM on the secondary healthcare level in Saudi Arabia highlights the need for effective diabetes prevention and treatment strategies in primary care and hospital outpatient settings. Such measures would help reduce the hospitalization rate and ease the healthcare system's burden.

Understanding the Interrelationship between Education, Income, and Obesity among Adults in Saudi Arabia.

OBJECTIVE: To examine the association of sociodemographic variables with the odds of being obese among adults in Saudi Arabia, and to examine whether or not the association between the educational level and the odds of being obese among adults in Saudi Arabia is modified by the income level. METHODS: A total of 3,925 participants were recruited for this cross--sectional study. Sociodemographic and anthropometric data were collected using standardized procedures. Unadjusted and adjusted logistic regression models were examined, with a dichotomous obesity status variable as the outcome. Furthermore, an interaction term for income level with educational level was tested and appeared significant. Thus, additional regression models were run in order to examine the association between educational level and obesity status separately among the low- and higher-income groups. RESULTS: Compared to participants with a college degree or higher, illiterate participants and those with an elementary education had higher odds of obesity (OR: 2.76, 95% CI: 1.81-4.22, and OR: 2.68, 95% CI: 1.89-3.82, respectively). However, participants with a low income had lower odds than participants who had a higher income (OR: 0.84, 95% CI: 0.70-0.99). Examining the association between educational level and obesity while stratifying by income revealed that a negative association between education and obesity exists among both income groups. However, the magnitude of the ORs was higher among participants with higher income, suggesting a stronger association between education and obesity among wealthier individuals. CONCLUSION: Individuals in the highest income bracket with lower levels of education may have greater odds of obesity. Targeting them in intervention programs is warranted.

Prevalence and Associated Risk Factors of Gestational Diabetes Mellitus at a University Hospital in Saudi Arabia.

OBJECTIVES: We aimed to find out the prevalence and associated risk factors of GDM among females who attended antenatal clinic at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia (SA). METHODS: This retrospective study was carried out from 25th September 2016 till 20th December 2016, at the Endocrine Clinic, Faculty of Medicine, KAUH, Jeddah, SA. A total of 5000 women attended antenatal clinic and 637 women were referred to the endocrine clinic for GDM. The data of only 103 GDM was included in the study because only these patients' complete data was available. The electronic record of 93 pregnant age and BMI matched females, not having GDM were selected as a control group. RESULTS: The prevalence of GDM was 12.75% (637/5000). Parity was associated with GDM (X2=16.82, P=.001) and GDM was significantly higher in multigravida while no association of GDM was found with working status, place of living, hypertension, family history of DM and BMI. Logistic regression analysis revealed that grand multigravida female had the lower risk of GDM as compared to multi, primi and nulligravida while age, working status, place of living, hypertension, family history of DM and BMI were not found significant risk factors for GDM. In GDM group, according to nationality, 68(66%) women were Saudi while 35(34%) were expatriates' (Yemeni 11.2%, Egyptians 3.9%, Indians 3.9%, Pakistanis 2.9%, Sudanese 2.9%, Syrians 2.9% and others). CONCLUSIONS: The prevalence of GDM was 12.75% and it was not associated with working status, place of living, hypertension, family history of diabetes and BMI.

Detection of Secondary Metabolites as Biomarkers for the Early Diagnosis and Prevention of Type 2 Diabetes.

BACKGROUND: Type 2 diabetes, or T2D, is a metabolic disease that results in insulin resistance. In the present study, we hypothesize that metabolomic analysis in blood samples of T2D patients sharing the same ethnic background can recover new metabolic biomarkers and pathways that elucidate early diagnosis and predict the incidence of T2D. METHODS: The study included 34 T2D patients and 33 healthy volunteers recruited between the years 2012 and 2013; the secondary metabolites were extracted from blood samples and analyzed using HPLC. RESULTS: Principal coordinate analysis and hierarchical clustering patterns for the uncharacterized negatively and positively charged metabolites indicated that samples from healthy individuals and T2D patients were largely separated with only a few exceptions. The inspection of the top 10% secondary metabolites indicated an increase in fucose, tryptophan and choline levels in the T2D patients, while there was a reduction in carnitine, homoserine, allothreonine, serine and betaine as compared to healthy individuals. These metabolites participate mainly in three cross-talking pathways, namely "glucagon signaling", "glycine, serine and threonine" and "bile secretion". Reduced level of carnitine in T2D patients is known to participate in the impaired insulin-stimulated glucose utilization, while reduced betaine level in T2D patients is known as a common feature of this metabolic syndrome and can result in the reduced glycine production and the occurrence of insulin resistance. However, reduced levels of serine, homoserine and allothrionine, substrates for glycine production, indicate the depletion of glycine, thus possibly impair insulin sensitivity in T2D patients of the present study. CONCLUSION: We introduce serine, homoserine and allothrionine as new potential biomarkers of T2D.

Management of postprandial hyperglycaemia and weight gain in women with gestational diabetes mellitus using a novel telemonitoring system.

OBJECTIVES: The purpose of this study was to investigate the effect of remotely delivered telemedicine dietary advice on monitoring of blood glucose levels and weight gain of women with gestational diabetes mellitus (GDM). METHODS: Women with GDM were recruited and randomly allocated into two groups: a Tele-GDM group that received a telemonitoring device, and a control group that was followed-up traditionally. A telemonitoring service calculated the ratio of reaching or exceeding the pregnancy weight gain target (according to pre-pregnancy weight), following Institute of Medicine guidelines for healthy pregnancy weight gain. RESULTS: The sample comprised 27 women in the Tele-GDM group and 30 in the control group. At the end of pregnancy, the Tele-GDM group showed significantly lower 2-hour postprandial glucose levels than the control group. Most women in the Tele-GDM group reached their recommended range of weight gain at the end of pregnancy. Additionally, the Tele-GDM group showed significantly lower weight gain than the control group. CONCLUSIONS: Telemonitoring can facilitate close monitoring of women with GDM and motivate patients to adopt a healthy lifestyle.

Diabetes knowledge and its association with the weight status among residents of Jeddah City, Saudi Arabia.

OBJECTIVE: To examine the association of weight status with level of diabetes knowledge (symptoms and complications) among residents of Jeddah City, Saudi Arabia. METHODS: In a cross-sectional study, a questionnaire assessing sociodemographic and health characteristics and knowledge about diabetes and its symptoms and complications was utilized. Data of 3978 adults, 18 years of age or older, were collected from public mall sites in Jeddah city and surrounding areas. Participants were divided into three tertiles based on their knowledge scores. Weight and height were measured following standardized procedures, and body weight categories were defined based on body mass index (BMI). The association between weight status and tertiles of diabetes knowledge was examined using multinomial logistic regression analysis. RESULTS: Compared to normal-weight participants, participants who were underweight, overweight, or obese, did not differ with regards to knowledge about diabetes symptoms. Adjusted models showed that overweight and obese participants had lower odds of being in the lowest tertile of knowledge about diabetes complications compared to normal-weight participants (OR: 0.71, 95% CI: 0.58-0.86 and OR: 0.64, 95% CI: 0.51-0.79, respectively). With regards to general knowledge about diabetes, the knowledge of participants who were underweight did not differ when compared to normal-weight participants. Overweight and obese participants had lower odds of being in the lowest tertile of general knowledge about diabetes compared to normal-weight participants (OR: 0.78, 95% CI: 0.62-0.97 and OR: 0.60, 95% CI: 0.47-0.76, respectively). CONCLUSIONS: Overweight and obese individuals have better knowledge about diabetes compared to normal-weight individuals. Public health programs need to take into account the level of diabetes knowledge and tailor interventions to aid behavior and lifestyle change.

Obesity and morbid obesity associated with higher odds of hypoalbuminemia in adults without liver disease or renal failure.

BACKGROUND AND OBJECTIVE: Studies are needed in order to inform recommendations for interpreting albumin levels among obese individuals without known medical conditions associated with hypoalbuminemia. The objective of this study was to examine the association of obese and morbidly obese status with hypoalbuminemia, while adjusting for age, sex, diabetes, prediabetes, diabetic nephropathy, and nephrotic syndrome. PATIENTS AND METHODS: Retrospective data collection from adult patients presenting to the outpatient Endocrinology and Metabolism Clinic was performed between January 2015 and December 2015. An initial sample of 180 patients was selected. After excluding patients who were younger than 18 years, who had known cases of liver disease or renal failure, or who had missing data, a final sample of 122 subjects was identified. Serum albumin and objectively measured weight and height data were retrieved from hospital records. A board-certified endocrinologist reviewed patient records to identify the presence of renal and diabetic conditions. Descriptive statistics were used to examine sample characteristics. Multiple logistic regression analysis was used to examine the association of obesity and morbid obesity with hypoalbuminemia (serum albumin < 34 g/L) while adjusting for age, sex, diabetes, prediabetes, diabetic nephropathy, and nephrotic syndrome. RESULTS: Approximately 43% of the sample were categorized as obese and 13% were categorized as morbidly obese. The mean serum albumin level was 38.00 g/L (standard deviation [SD] = 4.26) among subjects who were neither overweight nor obese, 38.35 g/L (SD = 0.48) among overweight subjects, 34.57 g/L (SD = 4.71) among obese subjects, and 33.81 g/L (SD = 3.71) among morbidly obese subjects. Adjusting for age, sex, diabetes, prediabetes, nephrotic syndrome, and diabetic nephropathy, obese subjects had significantly higher odds of hypoalbuminemia (odds ratio [OR]: 4.10, 95% confidence interval [CI]: 1.50-11.27, P-value = 0.006), as did morbidly obese subjects (OR: 6.94, 95% CI: 1.91-25.23, P-value = 0.003). CONCLUSION: The findings suggest that obesity and morbid obesity can be considered as independent predictors of hypoalbuminemia. The findings can be used to inform future studies aiming to better understand the association of obesity and morbid obesity with hypoalbuminemia and to help inform guidelines for clinicians on how to correctly interpret and utilize serum albumin data for obese individuals.

Ethnicity and skin autofluorescence-based risk-engines for cardiovascular disease and diabetes mellitus.

Skin auto fluorescence (SAF) is used as a proxy for the accumulation of advanced glycation end products (AGEs) and has been proposed to stratify patients into cardiovascular disease (CVD) and diabetes mellitus (DM) risk groups. This study evaluates the effects of seven different ethnicities (Arab, Central-East African, Eastern Mediterranean, European, North African, South Asian and Southeast Asian) and gender on SAF as well as validating SAF assessment as a risk estimation tool for CVD and DM in an Arabian cohort. SAF data from self-reported healthy 2,780 individuals, collated from three independent studies, has been linear modelled using age and gender as a covariate. A cross-study harmonized effect size (Cohens'd) is provided for each ethnicity. Furthermore, new data has been collected from a clinically well-defined patient group of 235 individuals, to evaluate SAF as a clinical tool for DM and CVD-risk estimation in an Arab cohort. In an Arab population, SAF-based CVD and/or DM risk-estimation can be improved by referencing to ethnicity and gender-specific SAF values. Highest SAF values were observed for the North African population, followed by East Mediterranean, Arab, South Asian and European populations. The South Asian population had a slightly steeper slope in SAF values with age compared to other ethnic groups. All ethnic groups except Europeans showed a significant gender effect. When compared with a European group, effect size was highest for Eastern Mediterranean group and lowest for South Asian group. The Central-East African and Southeast Asian ethnicity matched closest to the Arab and Eastern Mediterranean ethnicities, respectively. Ethnic and gender-specific data improves performance in SAF-based CVD and DM risk estimation. The provided harmonized effect size allows a direct comparison of SAF in different ethnicities. For the first time, gender differences in SAF are described for North African and East Mediterranean populations.

Ginger Ingredients Alleviate Diabetic Prostatic Complications: Effect on Oxidative Stress and Fibrosis.

Prostatic complications are common in patients with diabetes. This study investigated the effect of different ginger ingredients: zingerone, geraniol, and 6-gingerol on the prostate in diabetic rats. Diabetes was induced in Wistar rats by streptozotocin intraperitoneal injection (50 mg/kg), and the rats were left for 10 weeks to develop prostatic complications. In diabetic treated groups, rats received daily oral zingerone, geraniol, and 6-gingerol in doses of 20, 200, and 75 mg/kg, respectively, in the last 8 weeks. Treatment with the compounds caused changes in the ventral prostate of diabetic animals as indicated by the columnar ductal epithelium and dense secretions. There was an amelioration of oxidative stress as evidenced by the lowering of prostate malondialdehyde and elevating prostate oxidized to reduced glutathione (GSH/GSSG) ratios by geraniol and 6-gingerol. None of the three ginger ingredients affected the hyperglycemia, reduction in body weight gain, and testosterone deficiency seen in diabetic animals. Interleukin-1ß and interleukin-6 levels remained unchanged. However, zingerone and geraniol ameliorated the fibrosis in diabetic prostate through suppressing the elevated prostate transforming growth factor beta 1 (TGFß1) and collagen IV. Therefore, ginger ingredients could be beneficial in alleviating diabetic prostatic complications through suppressing oxidative stress and tissue fibrosis.

Corrigendum: A new gender-specific model for skin autofluorescence risk stratification.

This corrects the article DOI: 10.1038/srep10198.

Review and Recommendations on Management of Adult Female Thalassemia Patients with Hypogonadism based on Literature Review and Experience of ICET-A Network Specialists.

BACKGROUND: Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications, mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and follow-up by specialists. The most common endocrine complication documented is hypogonadotropic hypogonadism which increases with age and associated comorbidities. It is thus important for physicians to have a clear understanding of the pathophysiology and management of this disorder. Also to be aware of the side effects, contraindications and monitoring of sex steroid therapy. In this paper, practical ICET-A recommendations for the management of hypogonadism in adult females with TM are addressed. METHODS: In March 2015, the Coordinator of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) conducted a two-step survey to assess the attitudes and practices of doctors in the ICET-A network taking care of adult female TM patients with hypogonadism. They were clinically characterized by the absence of pubertal development or discontinuation or regression of the maturation of secondary sex characteristics, and biochemically by persistent low FSH, LH and estradiol levels. Recently a supplementary survey on adult female hypogonadism in TM was undertaken within the ICET-A network. RESULTS: The completed questionnaires were returned by 16 of 27 specialists (59.2%) following 590 female TM patients over the age of 18 years; 315 patients (53.3%) had hypogonadism, and only 245 (74.6%) were on hormone replacement therapy (HRT). Contraceptive oral pills (COC) were the first treatment choice in 11 centers (68.7%). A wide range of COCs was used with different progestin contents. In general, the patients' compliance to treatment was reported as good in 81.2 % of centers. The frequency of required tests for follow-up HRT, in addition to the regular check-up for thalassemia, was variable in the participating centers. CONCLUSIONS: Doctors taking care of TM patients should have sound knowledge of the pathophysiology of hypogonadism in adult females with TM. They should know the potential effects of HRT including advantages and disadvantages of estrogen and progestins. Moreover, they should keep in consideration the emotional needs of these patients dreaming of attaining a full pubertal development.

Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective.

Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight &prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-ß (ER-ß) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone-induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-ß/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation.

A new gender-specific model for skin autofluorescence risk stratification.

Advanced glycation endproducts (AGEs) are believed to play a significant role in the pathophysiology of a variety of diseases including diabetes and cardiovascular diseases. Non-invasive skin autofluorescence (SAF) measurement serves as a proxy for tissue accumulation of AGEs. We assessed reference SAF and skin reflectance (SR) values in a Saudi population (n = 1,999) and evaluated the existing risk stratification scale. The mean SAF of the study cohort was 2.06 (SD = 0.57) arbitrary units (AU), which is considerably higher than the values reported for other populations. We show a previously unreported and significant difference in SAF values between men and women, with median (range) values of 1.77 AU (0.79-4.84 AU) and 2.20 AU (0.75-4.59 AU) respectively (p-value « 0.01). Age, presence of diabetes and BMI were the most influential variables in determining SAF values in men, whilst in female participants, SR was also highly correlated with SAF. Diabetes, hypertension and obesity all showed strong association with SAF, particularly when gender differences were taken into account. We propose an adjusted, gender-specific disease risk stratification scheme for Middle Eastern populations. SAF is a potentially valuable clinical screening tool for cardiovascular risk assessment but risk scores should take gender and ethnicity into consideration for accurate diagnosis.

Severe vitamin D deficiency: a significant predictor of early hypocalcemia after total thyroidectomy.

OBJECTIVE: To assess the role of preoperative serum 25 hydroxyvitamin D as predictor of hypocalcemia after total thyroidectomy. STUDY DESIGN: Retrospective cohort study. SETTING: University teaching hospital. SUBJECTS AND METHODS: All consecutively performed total and completion thyroidectomies from February 2007 to December 2013 were reviewed through a hospital database and patient charts. The relationship between postthyroidectomy laboratory hypocalcemia (serum calcium≤2 mmol/L), clinical hypocalcemia, and preoperative serum 25 hydroxyvitamin D level was evaluated. RESULTS: Two hundred thirteen patients were analyzed. The incidence of postoperative laboratory and clinical hypocalcemia was 19.7% and 17.8%, respectively. The incidence of laboratory and clinical hypocalcemia among severely deficient (<25 nmol/L), deficient (<50 nmol/L), insufficient (<75 nmol/L), and sufficient (≥75 nmol/L) serum 25 hydroxyvitamin D levels was 54% versus 33.9%, 10% versus 18%, 2.9% versus 11.6%, and 3.1% versus 0%, respectively. Multiple logistic regression analysis revealed preoperative severe vitamin D deficiency as a significant independent predictor of postoperative hypocalcemia (odds ratio [OR], 7.3; 95% confidence interval [CI], 2.3-22.9; P=.001). Parathyroid hormone level was also found to be an independent predictor of postoperative hypocalcemia (OR, 0.6; 95% CI, 0.5-0.8; P=.002). CONCLUSION: Postoperative clinical and laboratory hypocalcemia is significantly associated with low levels of serum 25 hydroxyvitamin D. Our findings identify severe vitamin D deficiency (<25 nmol/L) as an independent predictor of postoperative laboratory hypocalcemia. Early identification and management of patients at risk may reduce morbidity and costs.

Modulatory effect of silymarin on inflammatory mediators in experimentally induced benign prostatic hyperplasia: emphasis on PTEN, HIF-1α, and NF-κB.

The current study aimed to investigate the potential role of the anti-inflammatory effects of silymarin (SIL) in inhibiting experimentally induced benign prostatic hyperplasia (BPH) in rats. Rats were injected testosterone (3 mg/kg/day, subcutaneously (s.c.)) for 2 weeks. In the treatment group, SIL (50 mg/kg, per orally (p.o.)) was administered daily to rats concomitantly with testosterone. Rats were killed 72 h after the last testosterone injection. Then, prostate tissues were dissected out, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Rats treated with testosterone showed marked increase in prostate weight and prostate weight/body weight with histopathological picture of inflammation and hyperplasia as well as increased collagen deposition. Co-treatment with SIL significantly alleviated these pathological changes. Further, SIL attenuated testosterone-induced nuclear factor-kappa B (NF-κB), cyclooxygenase-II (COX-II), and inducible nitric oxide synthase (iNOS) upregulation, and blunted testosterone-mediated increase in nitric oxide level and messenger RNA (mRNA) expression of interleukin-6 (IL-6) and IL-8. Testosterone-induced downregulation of phosphatase and tensin homolog (PTEN) and upregulation of hypoxia-inducible factor 1α (HIF-1α) were alleviated by SIL. Our findings highlight the anti-inflammatory properties of SIL as a crucial mechanism of its preventive actions against experimental BPH. This can be attributed to, at least partly, attenuating the expression of NF-kB and the subsequent inflammatory cascade, ameliorating the expression of PTEN, and mitigating that of HIF-1α. These data warrant further investigations for the potential use of SIL in the management of BPH.