Associations of Bone Mineral Density with RANKL and Osteoprotegerin in Arab Postmenopausal Women: A Cross-Sectional Study.

Background and objective: There is limited information as to the association of several key bone markers with bone mineral density (BMD) in understudied ethnic groups. This study investigated the relationship between circulating levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL) with BMD in Arab postmenopausal women. Materials and methods: In this cross-sectional study, a total of 617 Saudi postmenopausal women from the Osteoporosis Registry of the Chair for Biomarkers of Chronic Diseases were included. Anthropometric data, BMD, and biochemical data were retrieved from the registry. Participants were stratified into three groups based on T-score; n = 169 with osteoporosis, n = 282 with osteopenia, and n = 166 normal. Analysis of bone markers including RANKL, OPG, osteocalcin, and N-terminal telopeptide (NTx) was completed using commercially available bioassays. Results: The results suggested that OPG was significantly and positively correlated with age in the osteoporosis group (r = 0.29, p < 0.05), while it was inversely correlated with BMD femoral neck left (r = −0.56, p < 0.001) and BMD femoral neck right (r = −0.37, p < 0.05) in the same group. Moreover, RANKL showed a significant inverse correlation with NTx in the osteopenia group (r = −0.37, p < 0.05). Furthermore, the RANKL/OPG ratio had a positive and significant correlation with BMI (r = 0.34, p < 0.05), BMD femoral neck left (r = 0.36, p < 0.05) and BMD femoral neck right (r = 0.35, p < 0.05) in the osteopenia group. By contrast, it showed a significant inverse correlation with waist to hip ratio in the osteoporosis group (r = −0.38, p < 0.05). Multiple regression analysis showed that OPG contributes to BMD variations in the osteopenia group (p = 0.03). Conclusions: In conclusion, changes in circulating levels of RANKL and OPG might be a protective mechanism contrary to the increased bone loss in postmenopausal women.

Vitamin D Receptor Gene Variants Susceptible to Osteoporosis in Arab Post-Menopausal Women.

Post-menopausal osteoporosis (PMO) is a multifactorial bone disorder in elderly women. Various vitamin D receptor (VDR) gene variants have been studied and associated with osteoporosis in other populations, but not in a homogenous Arab ethnic group. Herein, the current study explores the association between VDR polymorphisms and susceptibility to osteoporosis in Saudi postmenopausal women. In total, 600 Saudi postmenopausal women (N = 300 osteoporosis; N = 300 control) were genotyped for VDR gene variants (rs7975232, rs1544410, rs731236) using TaqMan® SNP genotyping assays. Bone mineral density (BMD) for the lumbar spine and femur was assessed using dual-energy X-ray absorptiometry (DEXA). The heterozygous frequency distributions AC of rs7975232, CT of rs1544410, and AG of rs731236 were significantly higher in the osteoporosis group than controls (p < 0.05). Heterozygous AC of rs7975232 (1.6; 95% CI 1.1-2.3; p < 0.023), CT of rs1544410 (1.6; 95% CI 1.1-2.4; p < 0.022), and AG of rs731236 (1.6; 95% CI 1.1-2.4; p < 0.024) were significantly associated with increased risk of osteoporosis, independent of age and BMI. In conclusion, VDR gene variants rs7975232, rs1544410, rs731236 had a significant effect on BMD and were associated with osteoporosis risk in Saudi postmenopausal women.

Vitamin D status of Arab Gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study.

OBJECTIVES: Vitamin D status in patients with COVID-19 is an on-going controversial issue. This study aims to determine differences in the serum 25(OH)D concentrations of Arab Gulf adult residents screened for SARS-CoV-2 and its association with risk of COVID-19 infection together with other comorbidities. METHODS: In this multi-center, case-control study, a total of 220 male and female adults presenting with none to mild symptoms were screened for COVID-19 (n = 138 RT-PCR-confirmed SARS-CoV-2 positive and 82 negative controls). Medical history was noted. Anthropometrics were measured and non-fasting blood samples were collected for the assessment of glucose, lipids, inflammatory markers and serum 25(OH)D concentrations. RESULTS: Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 positive group compared to the negative group after adjustment for age and BMI (52.8 nmol/l ± 11.0 versus 64.5 nmol/l ± 11.1; p = 0.009). Being elderly (> 60 years) [Odds ratio 6 (95% Confidence Interval, CI 2-18; p = 0.001) as well as having type 2 diabetes (T2D) [OR 6 (95% CI 3-14); p < 0.001)] and low HDL cholesterol (HDL-c) [OR 6 (95% CI 3-14); p < 0.001)] were significant risk factors for COVID-19 infection independent of age, sex and obesity. CONCLUSIONS: Among Arab Gulf residents screened for SARS-CoV-2, serum 25(OH) D levels were observed to be lower in those who tested positive than negative individuals, but it was the presence of old age, diabetes mellitus and low-HDL-c that were significantly associated with risk of COVID-19 infection. Large population-based randomized controlled trials should be conducted to assess the protective effects of vitamin D supplementation against COVID-19.

Lower vitamin D levels in Saudi pregnant women are associated with higher risk of developing GDM.

BACKGROUND: Gestational diabetes mellitus (GDM) has serious consequences such as increased risks of preeclampsia, macrosomia and cesarean delivery. Even though the mechanistic basis of GDM has not been completely understood, several risk factors have been identified and one of these is vitamin D. However, the link between vitamin D deficiency and development of GDM is yet to be proven with certainty. METHODS: This study aimed to investigate the link between the incidence of GDM and serum vitamin D level in pregnant women of Saudi Arabia. 515 Saudi women (ages 18-46) in their 24-28th week of pregnancy, visiting various hospitals of Riyadh, participated in this study. Serum vitamin D and various biochemical and anthropometric parameters were determined in the first trimester and the recruits were screened for GDM by OGTT according to IADPSG criteria in their 2nd trimester. The association between vitamin D deficiency and development of GDM was calculated based on odds ratio of the incidence of GDM among vitamin D deficient and normal women. RESULTS: In this study cohort of 515 pregnant women, in the first trimester vitamin D deficiency (< 50 nmol/l) was detected in 425 (82.5%). On their 2nd visit (2nd trimester), 116 (27.7%) were diagnosed with GDM out of 419 with OGTT, according to IADPSG criteria. GDM risk was significantly higher among vitamin D deficient than non-deficient women (Odds Ratio: 2.87; Confidence Interval: 1.32-6.25; P = 0.008) even after adjusting for season, sun exposure and vitamin D intake (OR: 2.9; CI: 1.07-7.89). Of the various anthropometric and biochemical parameters, the GDM women differed significantly from non-GDM women with respect to serum levels of triglycerides (in mmol/l) (1.3 ± 0.6; 1.5 ± 0.6, p = 0.018) and fasting glucose (in mmol/l) [4.7 (4.3-5.2); 5.1 (4.6-5.6), p < 0.01]. Also, fasting glucose level in the 2nd trimester correlated inversely to serum vitamin D level determined during the 1st trimester (r = - 0.121; p = 0.014). CONCLUSIONS: Results of our study reveal a significantly higher risk of development of GDM among pregnant women having deficient vitamin D status.

Vitamin D deficiency among subfertile women: case-control study.

OBJECTIVE: The objective of the study is to compare the dietary vitamin D and calcium intake among subfertile women (cases) versus pregnant women (controls) and to determine the vitamin D levels in the subfertile and pregnant women. The study design was an observational case-control study where a total of 181 (83 previously diagnosed subfertile cases from various causes and 98 pregnant controls) women of reproductive age. A validated questionnaire was used where it focused on key indicators evaluating vitamin D-related factors. Blood was withdrawn for the measurement of serum calcium, albumin and phosphate to exclude secondary causes that might affect vitamin D level. RESULTS: The prevalence of vitamin D deficiency was significantly higher in the subfertile group than controls (59.0% versus 40.4%; p < 0.01). Calcium supplements intake was significantly higher in controls than the subfertile group (64.6% versus 10.0%; p value < 0.001). Total dietary vitamin D intake (> 400 IU/day) was significantly higher in the controls than the subfertile group. CONCLUSION: Vitamin D deficiency is prevalent among subfertile women. Optimization of serum calcium and vitamin D levels is encouraged.

Giant prolactinomas: clinical manifestations and outcomes of 16 Arab cases.

BACKGROUND: The management of giant prolactinomas remains a major challenge, despite dopamine agonists being the first line of treatment, owing to its efficacy to normalize prolactin levels and reduce tumor volume. The aim of this study is to characterize the therapeutic aspects, manifestations and outcomes of 16 cases of giant prolactinomas admitted at a single tertiary center in Riyadh, Saudi Arabia. METHODS: Retrospective data collection involving 16 Saudi patients diagnosed with giant prolactinoma at the Pituitary Clinic in King Fahad Medical City, Riyadh, Saudi Arabia between January 2006 and July 2012. RESULTS: A total of 16 patients (ten males; six females) with age of diagnosis between 21 and 55 years (mean 34.9 years) were included in the analysis. The most common presenting features include headache, visual defects and sexual dysfunction. Baseline mean serum prolactin level were extremely high for both sexes which eventually decreased by as much as 97% after cabergoline treatment. Serum prolactin concentrations completely normalized in six patients and significantly decreased in five patients 3-5 times that of normal range. Tumor volume also decreased by an average of 86% for males and 87% for females. Two patients had no tumor size change with cabergoline and required surgery. CONCLUSION: Findings indicate that cabergoline provides dramatic clinical improvements with excellent safety profile. Cabergoline should therefore be considered as the primary therapy for giant prolactinomas.

Vitamin D deficiency and dyslipidemia in early pregnancy.

BACKGROUND: Vitamin D deficiency is a common nutritional issue and dietary supplementation in the general population, including pregnant women, is generally advised. Appropriately high levels of vitamin D are expected to play a role in containing the glycemic and atherogenic profiles observed in pregnancy. However, the relation between vitamin D status and the lipid metabolic profile in Saudi women, who are known to suffer from chronic vitamin D deficiency and high incidence of obesity and type II DM, during the course of pregnancy is not known. METHODS: In this study, we analyzed the relation between serum vitamin D level and various serum metabolic markers among Saudi women (n = 515) in their first trimester of pregnancy (11.2 ± 3.4 weeks). Coefficients of Pearson correlation and Spearman rank correlation were calculated for Gaussian and non-Gaussian variables, respectively. Serum vitamin D status was defined as (in nmol/L): deficient (<25), insufficient (25-50); sufficient (50-75) and desirable (>75). RESULTS: Results indicated that vitamin D status was sufficient in only 3.5% of the study participants and insufficient and deficient in 26.2% and 68.0% of participants, respectively. Serum vitamin D values in the overall study population correlated positively with serum levels of total cholesterol (R = 0.172; p < 0.01), triglycerides (R = 0.184; p < 0.01) and corrected calcium (R = 0.141; p < 0.05). In the subgroup of vitamin D deficient subjects (n = 350), log serum vitamin D values correlated with serum triglycerides (R = 0.23; p = 0.002) and cholesterol (R = 0.26; p = 0.001). CONCLUSIONS: The positive correlations between serum vitamin D and the atherogenic factors such as total cholesterol and triglycerides indicate a pro-atherogenic metabolic status in vitamin D deficient expectant mothers. This may represent an adaptation to the high metabolic demands of pregnancy.

A 6-month "self-monitoring" lifestyle modification with increased sunlight exposure modestly improves vitamin D status, lipid profile and glycemic status in overweight and obese Saudi adults with varying glycemic levels.

BACKGROUND: The over-all age-adjusted prevalence of diabetes mellitus type 2 (DMT2) in Saudi Arabia is unprecedented at 31%. Aggressive measures should be done to curb down increasing incidence. In this prospective 6-month study we aim to determine whether a self-monitoring, life-style modification program that includes increased sunlight exposure confer improvement in vitamin D status and health benefits among adult Saudi overweight and obese patients with varying glycemic status. METHODS: A total of 150 overweight and obese Saudi adults with varying glycemic status aged 30-60 years were included in this study. They were divided into 3 groups (Non-DMT2, Pre-diabetes and DMT2). Baseline anthropometrics and blood glucose were taken at baseline and after 6 months. Fasting blood sugar, lipid profile, calcium, albumin and phosphate were measured routinely. Serum 25(OH) vitamin D was measured using standard assays. Within the time period they were instructed to reduce total intake of fat, increased fiber intake and increase sun exposure. RESULTS: In all groups there was a significant improvement in vitamin D levels as well as serum triglycerides, LDL- and total cholesterol. However, a significant increase in serum glucose levels was noted in the non-DMT2 group, and a significant decrease in HDL-cholesterol in both non-DMT2 and pre-diabetes group. In the pre-diabetes group, 53.2% were able to normalize their fasting blood levels after 6 months, with 8.5% reaching the DMT2 stage and 38.3% remaining pre-diabetic. In all groups there was a significant increase in the prevalence of hypertension. CONCLUSION: Improving vitamin D status with modest lifestyle modifications over a short-period translates to improvement in lipid profile except HDL-cholesterol among overweight and obese Saudi adults, but not BMI and blood pressure. Findings of the present study merit further investigation as to whether full vitamin D status correction can delay or prevent onset of DMT2.

Lower vitamin D status is more common among Saudi adults with diabetes mellitus type 1 than in non-diabetics.

BACKGROUND: Vitamin D deficiency is an increasingly recognized comorbidity in patients with type 1 diabetes mellitus (DMT1), suggesting that vitamin D deficiency might play a role in DMT1. We aimed to determine and compare the vitamin D status of Saudi adults with and without DMT1. METHODS: A total of 60 Saudi adults with DMT1 from the Diabetes Clinics and 60 non-DM, healthy controls were included in the study. The mean age for those with DMT1 was 25.9 ± 16.1 years versus 36.7 ± 3.6 years among the controls. We measured serum 25-hydroxy vitamin D (25OHD), calcium, cholesterol, blood glucose, HDL, and triglycerides and compared the results between the DMT1 group and control subjects. RESULTS: Both the DMT1 and healthy groups had vitamin D deficiency. The mean levels of 25OHD were significantly lower in the DMT1 adults than in the controls (28.1 ± 1.4 nmol/L versus 33.4 ± 1.6 nmol/L). In the DMT1 adults, 66.7% were mildly, 31.7% moderately, and 3.3% severely vitamin D deficient as compared with 41.7% (mildly), 31.7% (moderately), and 5% (severely) in the control group. Overall, 100% of the DMT1 adults and 78% of the healthy children were vitamin D deficient. CONCLUSION: The prevalence of vitamin D deficiency among DMT1 adults was relatively high. Therefore, screening for vitamin D deficiency and supplementation for this population should be warranted.

Differences and associations of metabolic and vitamin D status among patients with and without sub-clinical hypothyroid dysfunction.

BACKGROUND: Sub-clinical hypothyroid dysfunction, a relatively understudied disorder in the Kingdom of Saudi Arabia (KSA), has significant clinical implications if not properly monitored. Also from KSA, more than 50% of the population suffer from hypovitaminosis D (<50 nmol/l). In this cross-sectional case-control study, we described the differences and associations in the metabolic patterns of adult Saudis with and without hypothyroid dysfunction in relation to their vitamin D status, PTH, calcium and lipid profile. METHODS: A total of 94 consenting adult Saudis [52 controls (without subclinical hypothyroidism), 42 cases (previously diagnosed subjects)] were included in this cross-sectional study. Anthropometrics were obtained and fasting blood samples were taken for ascertaining lipid and thyroid profile, as well as measuring PTH, 25(OH) vitamin D and calcium. RESULTS: Cases had a significantly higher body mass index than the controls (p < 0.001). Circulating triglycerides was also significantly higher in cases than the controls (p = 0.001). A significant positive association between HDL-cholesterol and PTH (R = 0.56; p = 0.001), as well as a negative and modestly significant negative association between LDL-cholesterol and PTH (R = - 20.0; p = 0.04) were observed. FT3 was inversely associated with circulating 25 (OH) vitamin D (R = -0.25; p = 0.01). CONCLUSIONS: Patients with hypothyroid dysfunction possess several cardiometabolic risk factors that include obesity and dyslipidemia. The association between PTH and cholesterol levels as well as the inverse association between vitamin D status and FT3 needs to be reassessed prospectively on a larger scale to confirm these findings.

Therapeutic Plasma Exchange in Refractory Atrial Fibrillation Secondary to a Thyroid Storm.

Thyrotoxic crisis (thyroid storm) is a severe form of hyperthyroidism. It has a wide range of symptoms, including cardiovascular manifestations that can be life-threatening and require prompt management. Cardiac manifestations of thyroid storm include hypertension, tachycardia, congestive heart failure, cardiac ischemia, and atrial fibrillation. Standard therapeutic approaches of thyroid storm are based on the use of thionamides, corticosteroids, and nonselective beta-blockers to inhibit thyroid hormone synthesis and release while also blocking thyroxin's peripheral effects. This approach is an effective measure in the management of these manifestations. However, when a patient fails to respond to conventional therapy, or there is end organ damage and surgery is not feasible, therapeutic plasma exchange (TPE) is a life-saving measure. Here, we report a case of a 27-year-old female who is known to have hyperthyroidism, but she was not compliant with her medication. She presented with symptoms of hyperthyroidism and was found to have a thyroid storm with refractory atrial fibrillation. Despite the effort to control her symptoms, she developed cardiac arrest, and after 15 minutes of cardiopulmonary resuscitation, she was revived. Amiodarone, beta-blockers, and cardioversion failed to improve the patient's status, and her condition deteriorated. So, we decided to use TPE, and she received three sessions in total. After the first session of TPE, her rhythm converted to sinus rhythm, and her heart rate was controlled to less than 100 beats per minute. She showed dramatic improvement clinically and biochemically. In conclusion, cardiac complications are potentially lethal complications of thyroid storm. Prompt restoration of a normal thyroid state can reverse these complications. When conventional therapy fails to ameliorate symptoms or organ deterioration is rapid and severe, TPE can be a safe and effective measure.

Dietary Calcium Intake and Osteoporosis Risk in Arab Adults.

Osteoporosis is a major public health concern in Saudi Arabia's aging population. There is particularly limited information on how diet affects bone loss in this ethnic group. The purpose of this study was to examine the association between dietary calcium (Ca) intake and osteoporosis risk in Saudi adults. A total of 1950 patients (416 males and 1534 females) with known risk factors for osteoporosis participated in this cross-sectional study. A short questionnaire (CaQ) was used to assess dietary Ca intakes in patients attending tertiary hospitals in Riyadh City. The prevalence of osteoporosis was 21.3% and was more common in females (93.5%). Patients with osteoporosis were older (p < 0.001) and had lower BMI (p < 0.001). Results showed that the overall mean Ca intake was only 445.1 mg/day (recommended dietary intake of 1300 mg/day). Tea intake (OR = 0.8 95%CI: 0.7-1.0; p = 0.02) and consumption of fish and eggs (OR = 0.9 95%CI: 0.8-1.0; p = 0.01) were significantly associated with a lower risk of osteoporosis. Furthermore, consumption of biscuits, cake and bread slices were significantly associated with higher incidence of osteoporosis (OR = 1.3 95%CI: 1.0-1.5; p = 0.02). In conclusion, extremely low dietary Ca intake was observed among Saudi adults already at risk of osteoporosis. A balanced diet including high amount of Ca, vitamin D and omega-3 fatty acids accompanied by limiting consumption of foods high in saturated fats and glycemic index may be helpful in reducing osteoporosis risk in the Saudi adult population.

Addressing the Continuum of Dysglycaemia and Vascular Complications in Prediabetes and Type 2 Diabetes: Need for Early and Intensive Treatment.

The onset of type 2 diabetes increases the risk of vascular complications and death. We know now that that this risk begins long before the diabetes diagnosis. Prediabetes and type 2 diabetes are not separate entities in practice and exist within a continuum of dysglycaemia and vascular risk that increases in severity over time. This excess risk requires early intervention with lifestyle therapy supported with pharmacologic antidiabetic therapy, intensified promptly where necessary throughout the duration of the diabetes continuum. Metformin is an evidence-based treatment for preventing prediabetes and improves cardiovascular outcomes in people with type 2 diabetes from diagnosis onwards. Newer agents (SGLT2 inhibitors and GLP-1 agonists) are appropriate for people presenting with type 2 diabetes and significant cardiovascular comorbidity. Additional therapies should be used without delay to achieve patients' individualised HbA1c goals and to minimise cardiovascular risk.

Association of bone mineralization markers with dietary nutrient intake in adolescents with and without biochemical osteomalacia.

Background: Dietary intake is widely known to play a crucial role in achieving peak bone mass among children and adolescents. Unfortunately, this information is lacking among Arab adolescents, an understudied demographic that has recently been observed to have a high prevalence of abnormal mineralization markers [low serum 25(OH)D, high serum alkaline phosphatase (ALP), low calcium (Ca) and/or inorganic phosphate (Pi)] suggestive of biochemical osteomalacia (OM, defined as any 2 of the 4 parameters). In order to fill this gap, we aimed to evaluate the associations of serum markers of biochemical OM with dietary intake of macronutrients, vitamins and trace minerals. Methods: Saudi adolescents (N = 2,938, 57.8% girls), aged 12-17 years from 60 different schools in Riyadh, Saudi Arabia were included. Dietary intake of nutrients was calculated following a semi-quantitative 24 h dietary recall over 3 weekdays and 1 weekend-day using a validated food frequency questionnaire. Compliance to reference daily intake (RDI) of macronutrients, vitamins and trace minerals were calculated. Fasting blood samples were collected and circulating levels of 25(OH)D, ALP, Ca, and Pi were analyzed. Results: A total of 1819 (1,083 girls and 736 boys) adolescents provided the dietary recall data. Biochemical OM was identified in 175 (9.6%) participants (13.5% in girls, 3.9% in boys, p < 0.01) while the rest served as controls (N = 1,644). All participants had serum 25(OH)D levels <50 nmoL/L. Most participants had very low dietary intakes of Ca (median ~ 290 mg) and vitamin D (median ~ 4 µg) which are far below the RDI of 1,300 mg/day and 20 µg/day, respectively. In contrast, excess dietary intakes of Pi, Na, K, and Fe were observed in all participants. In the biochemical OM group, thiamine and protein intake were significant predictors of serum 25(OH)D, explaining 4.3% of the variance perceived (r = 0.23, adjusted r2 = 4.3%, p = 0.01). Among controls, dietary vitamin C and vitamin D explained 0.6% of the total variation in serum 25(OH)D (r = 0.09, adjusted r2 = 0.6%, p = 0.004). Conclusion: Arab adolescents do not meet the RDI for dietary Ca and vitamin D, and none have sufficient vitamin D status (25(OH)D levels >50 nmol/L) but they exceed the RDI for dietary Pi. Interpreting these data in the light of the increased prevalence of rickets in Arab countries, food fortification to optimise vitamin D and Ca intake in Saudi adolescents should be considered.

General Public's Knowledge of Diabetes and Physical Activity in Saudi Arabia over Time: The Need to Refresh Awareness Campaigns.

Diabetes mellitus (DM) is a major health issue in Saudi Arabia. Prevention of DM and its complications requires an understanding of the disease and modifiable behaviors (e.g., physical activity-PA). The purpose of this study was to examine the trends in knowledge of the general population regarding DM to better understand the shortcomings in the current awareness programs. This article presents a cross-sectional series study where a survey was distributed to a total of 3493 participants over four years, from 2017 till 2020, to assess general knowledge about DM, including information about PA. The mean percentage of correct responses of DM general knowledge was 63.8 ± 19.0 in 2017, which decreased to 61.3 ± 18.7 in 2020 with a significant beta coefficient of -0.8 ± 0.2 (p < 0.001). Participants' awareness about PA remained constantly high for four years: the mean percentage of correct responses was 82.1 ± 23.6 in 2017 and 82.0 ± 23.1 in 2020, and the beta coefficient was -0.5 ± 0.3 (p = 0.147). Furthermore, stratification by demographics showed that the majority of the subgroups (age, sex, educational status, marital status, having relative with DM, nationality) reported a significant declining trend in general DM knowledge. In addition, some of the subgroups also showed a declining trend in PA awareness. Future prevention efforts should assess the community's DM knowledge regularly to tailor awareness efforts to the population segments that need heightened educational interventions.

Investigating the prevalence of pathogenic variants in Saudi Arabian patients with familial cancer using a multigene next generation sequencing panel.

Family history is an important factor in determining hereditary cancer risk for many cancer types. The emergence of next-generation sequencing (NGS) has expedited the discovery of many hereditary cancer susceptibility genes and the development of rapid, affordable testing kits. Here, a 30-gene targeted NGS panel for hereditary cancer risk assessment was tested and validated in a Saudi Arabian population. A total of 310 subjects were screened, including 57 non-cancer patients, 110 index patients with cancer and 143 of the cancer patients' family members, 16 of which also had cancer. Of the 310 subjects, 119 (38.4%) were carriers of pathogenic or likely pathogenic variants (PVs) affecting one or more of the following genes: TP53, ATM, CHEK2, CDH1, CDKN2A, BRCA1, BRCA2, PALB2, BRIP1, RAD51D, APC, MLH1, MSH2, MSH6, PMS2, PTEN, NBN/NBS1 and MUTYH. Among 126 patients and relatives with a history of cancer, 49 (38.9%) were carriers of PVs or likely PVs. Two variants in particular were significantly associated with the occurrence of a specific cancer in this population (APC c.3920T>A - colorectal cancer/Lynch syndrome (p = 0.026); TP53 c.868C>T; - multiple colon polyposis (p = 0.048)). Diverse variants in BRCA2, the majority of which have not previously been reported as pathogenic, were found at higher frequency in those with a history of cancer than in the general patient population. There was a higher background prevalence of genetic variants linked to familial cancers in this cohort than expected based on prevalence in other populations.

Fasting Ramadan in patients with T1DM - Saudi Arabia versus other countries during the COVID-19 pandemic.

BACKGROUND AND AIMS: To compare Saudi Arabia with other countries regarding patient attitudes towards fasting Ramadan and complications related to fasting during the COVID-19 pandemic. METHODS: Data collected from Saudi Arabia and 12 other mostly Muslim majority countries, via physician administered questionnaire within post Ramadan 2020. RESULTS: 1485 Type1 diabetes (T1DM) patients analyzed; 705 (47.5%) from Saudi Arabia vs. 780 (52.5%) from other countries. 1056 (71.1%) fasted Ramadan; 636 (90.2%) of Saudi patients vs. 420 (53.8%) of other countries. Experiencing Ramadan during the COVID-19 pandemic did not affect the Saudi T1DM patients' decision to fast while it significantly influenced their decision in other countries (1.4 vs 9.9%, P < 0.001). More Saudi patients needed to break the fast due to a diabetes related complication compared to other countries (67.4% vs. 46.8%, p=<0.001). The mean number of days fasted in Saudi and other countries was 24 ± 7 and 23 ± 8 days respectively. Hypoglycemic events were more common among Saudi patients during Ramadan compared to other countries 72% and 43.6% (p < 0.001) respectively. There was a significant difference in timing; the largest peak for Saudi Arabia patients was after dawn (35% vs 7%, p < 0.001), while it was pre-sunset for the other countries (23 vs 54%, p = 0.595). Day time-hyperglycemia was also more common among Saudi patients (48.6% vs. 39%, p < 0.001), however it was a less likely cause to break the fast (25.6% vs 38.3%, p < 0.001). CONCLUSION: Observing the fast of Ramadan is extremely common among Saudi T1DM patients compared to other Muslim countries and was not affected by the COVID-19 pandemic. However, it was associated with higher frequency of hypoglycemic and hyperglycemic episodes.

Ramadan fasting in people with diabetes and chronic kidney disease (CKD) during the COVID-19 pandemic: The DaR global survey.

BACKGROUND AND AIMS: The DaR Global survey was conducted to observe the impact of the COVID-19 pandemic on the intentions to fast and the outcomes of fasting in people with diabetes and chronic kidney disease (CKD). METHODS: Muslim people with diabetes and CKD were surveyed in 13 countries shortly after the end of Ramadan 2020, using a simple Survey Monkey questionnaire. RESULTS: This survey recruited 6736 people with diabetes, of which 707 (10.49%) had CKD. There were 118 (16.69%) people with type1 diabetes (T1D), and 589 (83.31%) were with type2 diabetes (T2D). 62 (65.24%) people with T1D and 448 (76.06%) people with T2D had fasted with CKD. Episodes of hypoglycaemia and hyperglycaemia were more frequent among people with T1D compared to T2D, 64.52% and 43.54% vs 25.22% and 22.32% respectively. Visits to the emergency department and hospitalization were more frequent among people with CKD, however no significant difference was found between people with T1D and T2D. CONCLUSION: The COVID-19 pandemic had only a minor effect on the intention to fast during Ramadan in people with diabetes and CKD. However, hypoglycaemia and hyperglycaemia were found to be more frequent, as well as emergency visits and hospital admissions among people with diabetic kidney disease. Prospective studies are needed in future to evaluate the risk indicators of hypoglycaemia and hyperglycaemia among fasting people with CKD, especially in the context of different stages of kidney disease.

Establishing the Prevalence of Osteomalacia in Arab Adolescents Using Biochemical Markers of Bone Health.

Nutrition-acquired osteomalacia is a bone mineralization disorder associated with dietary calcium and/or solar vitamin D deficiency, risk factors considered common in the Middle Eastern region. Establishing less invasive, cheap, and widely available diagnostic markers for this underdiagnosed entity is essential, in particular for screening in high-risk groups. This study assessed the prevalence of biochemical osteomalacia in Arab adolescents. In this cross-sectional study performed between September 2019 and March 2021, adolescents aged 12−17 years from 60 different secondary and preparatory year schools in Riyadh, Saudi Arabia were included. Anthropometrics and fasting blood samples were collected. Biochemical osteomalacia was defined as any two of the following four serum markers of hypomineralization, namely low 25 hydroxyvitamin D (25OHD < 30 nmol/L), high alkaline phosphatase (ALP), low calcium (Ca), and/or inorganic phosphorous (Pi). A total of 2938 Arab adolescents [1697 girls; mean age (years) 14.8 ± 1.8; 1241 boys; mean age 15.1 ± 1.6] were recruited. Vitamin D deficiency was noted in 56.2% (n = 953) of girls and 27.1% (n = 336) of boys (p < 0.001). The overall prevalence of biochemical osteomalacia was 10.0% (n = 295/2938) and was higher in girls than boys (14.7% vs. 3.6%, p < 0.001). The prevalence of low serum Ca and/or Pi was also higher in girls than in boys (24.2% vs. 12.5%, respectively, p < 0.001), as well as elevated ALP (5.1% vs. 1.5%, p < 0.001). Overall, girls were 4.6 times (95% CI 3.3−6.4) more likely to have biochemical osteomalacia than boys. Screening of apparently healthy Arab adolescents revealed a high prevalence of deranged mineralization markers suggestive of biochemical osteomalacia, which was significantly more common in girls than boys and was likely associated with Arab traditional clothing and diet. The proposed combination of typically altered mineralization markers for the diagnosis of osteomalacia is, at best, suggestive until further comparisons with established diagnostic tools (histological analysis of bone biopsies) are conducted.

Effects of a 12-Month Hybrid (In-Person + Virtual) Education Program in the Glycemic Status of Arab Youth.

This 12-month school-based intervention study investigated the effects of hybrid educational lifestyle modifications on glycemic control among Saudi youth with different glycemic statuses. A total of 2600 Arab adolescents aged 12−18 years were recruited from 60 randomly selected schools. Anthropometrics, blood glucose, and HbA1c were measured pre- and post-intervention. Participants were grouped according to baseline HbA1c into normal, prediabetes, and diabetes groups. All participants received lifestyle education at base line and at every 3-month interval to improve diet and exercise behavior. Diabetic and prediabetic participants received a tailored lifestyle intervention. Post-intervention, 643 participants were analyzed as follows: 20 participants from the diabetes group, 39 from prediabetes, and 584 from the normal group. A modest but significant improvement in the glycemic status of diabetic and prediabetic participants was observed, but not in the normal group. In the diabetes group, 11 (55%) participants achieved normal HbA1c levels, 5 had prediabetes levels, and only 4 remained within diabetes HbA1c levels. In the prediabetes group, 34 (87.2%) participants achieved normal HbA1c levels, while 2 (5.1%) participants remained prediabetic and 3 (7.7%) had diabetes HbA1c levels (p < 0.001). This hybrid lifestyle intervention program modestly reduces the risk of T2DM among youth with elevated HbA1c levels. The challenge of sustaining interest in adopting lifestyle changes for a longer duration should be addressed in further studies in this population.