Abdullah M. Alnaami

Metabolic syndrome biomarkers and early breast cancer in Saudi women: evidence for the presence of a systemic stress response and/or a pre-existing metabolic syndrome-related neoplasia risk?

BackgroundObesity has been linked to many adverse health consequences, including breast cancer. This study aims to determine adipocytokine and other biological changes in recently diagnosed breast cancer patients before therapy is started.MethodsA total of 109 female Saudi subjects [56 newly diagnosed, treatment-naïve, histologically-confirmed breast cancer cases and 53 age- and BMI-matched controls] were enrolled in this study. Anthropometric data were collected. Serum insulin, adipocytokines and plasminogen activator inhibitor-1 (PAI-1) concentrations were measured using a customized multiplex Luminex assay. Hypersensitive C-Reactive Protein (CRP), tumor necrosis factor-alpha (TNF-α), and angiotensin II (ANG II) were measured using ELISA.ResultsA few days in the diagnosis, breast cancer subjects had significantly higher systolic blood pressure (p = 0.03), glucose (p = 0.01), triglycerides (p = 0.001), leptin (p = 0.044), resistin (p = 0.04), ANG II (p = 0.02), TNF-α (p = 0.045), and CRP (p = 0.04) than the controls. On the other hand, HDL (p = 0.01) and adiponectin (p = 0.02) were significantly lower in cancer subjects than controls. A significant association was found between elevated triglycerides (TG) and breast cancer [OR (95% CI), 6.1(1.8, 15.6), p = 0.004], as well as elevated ANG II [OR (95% CI), 5.2(1.2, 14.3), p = 0.03]. On the other hand, aPAI and HDL correlated negatively with breast cancer [OR (95% CI), 0.076(0.01, 0.34), p = 0.001; 0.30(0.09, 0.95), p 0.04, respectively].ConclusionCirculating ANGII and triglycerides were positively associated with early breast cancer. In contrast, HDL-cholesterol correlated negatively with ANG II and aPAI in these patients. This suggests that patients with recently diagnosed breast cancer have biochemical changes consistent with an activated stress response and/or that patients with metabolic syndrome manifestations have a higher risk of developing this disease.

Vitamin D Deficiency and Cardiometabolic Risks: A Juxtaposition of Arab Adolescents and Adults

The recent exponential surge in vitamin D research reflects the global epidemic of vitamin D deficiency and its potential impact on several chronic diseases in both children and adults. Several subpopulations, including Arab adolescent boys and girls, remain understudied. This study aims to fill this gap. A total of 2225 apparently healthy Saudi adolescents (1187 boys and 1038 girls, aged 13-17 years old) and 830 adults (368 men and 462 women, aged 18-50 years old) were respectively recruited from different public schools and medical practices within Riyadh, Saudi Arabia. Anthropometrics were taken and fasting blood samples withdrawn to examine serum glucose and lipid profile by routine analysis and 25-hydroxyvitamin D by ELISA. Almost half of the girls (47.0%) had vitamin D deficiency as compared to only 19.4% of the boys (p<0.001), 36.8% of the adult women and 17.7% of the adult men (p<0.001). Furthermore, in boys there were more significant inverse associations between serum 25(OH)vitamin D levels and cardiometabolic indices than girls, while in contrast women had more significant associations than men. Vitamin D deficiency was significantly associated with diabetes mellitus type 2 (DMT2) [OR 3.47 (CI1.26-5.55); p<0.05] and pre-DM [OR 2.47 (CI 1.48-4.12); p<0.01] in boys. Furthermore, vitamin D insufficiency was significantly associated with abdominal obesity in boys [OR 2.75 (CI 1.1-7.1); p<0.05]. These associations for DMT2 and abdominal obesity were not observed in adult males, girls and adult women. Vitamin D deficiency/insufficiency and hyperglycemia is high among Arab adolescents. Vitamin D deficiency is mostly associated with cardiometabolic risk factors in adolescent Arab boys. This indicates a sex- and age-related disadvantage for boys with low vitamin D status and challenges the extra-skeletal protection of vitamin D correction in adolescent females.

Does visceral adiposity index signify early metabolic risk in children and adolescents?: Association with insulin resistance, adipokines, and subclinical inflammation

Background:Visceral adiposity index (VAI) is a novel gender-specific index based on waist circumference (WC), BMI, and lipid parameters. Although VAI does not actually estimate visceral adiposity, it accurately reflects visceral fat function and insulin resistance. This index has not been studied in children thus far. This study aims to fill this gap.Methods:In a cohort of Saudi children and adolescents, anthropometric measurements and metabolic/hormonal profile were obtained.Results:A total of 543 subjects, 292 of whom were boys, were included (mean age: 11.9 ± 3.3 y; BMI: 19.8 ± 5.6 kg/m2). In all subjects, VAI was inferior to BMI and WC regarding its correlations with adiponectin, leptin, insulin resistance (homeostasis model of assessment–insulin resistance (HOMA-IR)), C-reactive protein (CRP) level, and systolic blood pressure, but it exhibited a stronger association with glucose in boys (r = 0.23; P < 0.01). In stepwise multivariate analyses, only BMI was consistent as an independent predictor of adiponectin, leptin, HOMA-IR, and CRP. VAI was the only index independently associated with glucose.Conclusion:Although VAI is related to glucose in children, it seems to be inferior to BMI in terms of association with insulin resistance, adipokines, and subclinical inflammation. Until specific studies can be performed in children, VAI should be extrapolated with caution in this age range.

Maternal inheritance of circulating irisin in humans

The recently discovered myokine irisin has been implicated in several observational studies as a potential therapeutic target for obesity-related diseases. However, no information is available as to the heritability of this hormone. The present study aims to fill this gap. A total of 120 families (n=254; 121 adults and 133 children) were included in the study taken from the Riyadh Biomarkers Research Program cohort. Information gathered include anthropometrics, and glycaemic, lipid and adipocytokine profiles. Irisin was measured using ELISA. Examining heritability between mother and offspring, the most significant heritable traits in sons included irisin (P=1.6×10(-5)), systolic blood pressure (P=3.6×10(-4)), total cholesterol (P=3.5×10(-7)) and LDL (low-density lipoprotein)-cholesterol (P=1.2×10(-6)). Heritable traits between mother and daughter again included irisin (P<0.002), as well as anthropometric associations such as waist (P<0.01) and hip (P<0.005) circumference and blood pressure (P<0.002); biochemically, principal associations were observed with HDL (high-density lipoprotein)-cholesterol (P<0.04) and TNF-α (tumour necrosis factor-α) (P<0.002). HDL-cholesterol was the single most significant predictor for irisin levels in adults, explaining 17% of the variance, whereas in children AngII (angiotensin II) was the most significant predictor of irisin levels, explaining 19% of the variance (P=0.003). Circulating irisin appears to be maternally inherited and is predicted by HDL-cholesterol in adults and AngII in children, both factors influenced by energy expenditure and regulation. Taken together, these findings suggest a significant role of irisin in energy-generating processes.

Associations of Spexin and cardiometabolic parameters among women with and without gestational diabetes mellitus

Spexin (SPX) is a novel biomarker abundantly expressed in several animal and human tissues implicated in food intake and glucose control, respectively. As new roles for SPX are emerging, the present study explored for the first time, the associations of SPX to several cardiometabolic indices and inflammatory markers in pregnant women, a demographic not yet investigated with respect to SPX. A total of 117 Saudi women subdivided to those with gestational diabetes mellitus (GDM) (N = 63) and those without (N = 54) were included in this cross-sectional study. Anthropometry, glycemic, lipid, vitamin D, adipocytokines and inflammatory markers were measured consecutively at baseline and after the 2nd and 3rd trimesters. Age- and BMI adjusted comparisons revealed that levels of SPX were not significantly different in pregnant women with and without GDM. In all subjects, circulating levels of SPX showed modest associations with glucose (R = 0.18; p = .08) and HOMA β (R = −0.19; p = .09) as well as significant positive associations with total cholesterol (R = 0.25; p = .02), LDL-cholesterol (R = 0.25; p = .02), 25(OH)D (R = 0.22; p = .04), albumin (R = 0.30; p < .01) and IL1β (R = 0.41; p < .01). Stepwise regression analysis also suggested that IL1β, leptin and albumin were the significant predictors of SPX. In summary, SPX levels modestly affect glucose and insulin sensitivity in pregnant women but is not associated with GDM and obesity. The significant association of SPX to ILβ warrants further investigation as to the role of SPX in immune modulation.

Vitamin D Deficiency Prevalence and Predictors in Early Pregnancy among Arab Women

Data regarding the prevalence and predictors of vitamin D deficiency during early pregnancy are limited. This study aims to fill this gap. A total of 578 Saudi women in their 1st trimester of pregnancy were recruited between January 2014 and December 2015 from three tertiary care antenatal clinics in Riyadh, Saudi Arabia. Information collected includes socio-economic, anthropometric, and biochemical data, including serum vitamin D (25(OH)D) levels, intake of calcium and vitamin D, physical activity, and sun exposure indices. Pregnant women with 25(OH)D levels <50 nmol/L were considered vitamin D deficient. The majority of participants (n = 468 (81%)) were vitamin D deficient. High levels of indoor activity, whole body clothing, multiparity, total cholesterol/HDL ratio(>3.5), low HDL-cholesterol, and living in West Riyadh were significant independent predictors for vitamin D deficiency, with odds ratios (ORs) (95% confidence interval) of 25.4 (5.5–117.3), 17.8 (2.3–138.5), 4.0 (1.7–9.5), 3.3 (1.4–7.9), 2.8 (1.2–6.4), and 2.0 (1.1–3.5), respectively. Factors like increased physical activity, sun exposure at noon, sunrise or sunset, high educational status, and residence in North Riyadh were protective against vitamin D deficiency with ORs 0.2 (0.1–0.5); 0.2 (0.1–0.6); 0.3 (0.1–0.9); and 0.4 (0.2–0.8), respectively. All ORs were adjusted for age, BMI, sun exposure, parity, summer season, vitamin D intake, multivitamin intake, physical activity, education, employment, living in the north, and coverage with clothing. In conclusion, the prevalence of vitamin D deficiency among Saudi women during early pregnancy was high (81%). Timely detection and appropriate supplementation with adequate amounts of vitamin D should reduce the risks of vitamin D deficiency and its complications during pregnancy.

Comparisons in childhood obesity and cardiometabolic risk factors among urban Saudi Arab adolescents in 2008 and 2013.

BACKGROUND We aimed to compare the prevalence of childhood obesity and other cardiometabolic risk factors from two independent cohorts (2008 and 2013) in Riyadh, Saudi Arabia. METHODS A total of 4549 adolescents aged 12-18 years [2454 boys, 2095 girls], taken from two independent cohorts, 5 years apart (2008 and 2013), were included. Anthropometrics were measured, and fasting blood samples were taken to ascertain glucose and lipid profile. RESULTS The overall prevalence of obesity was significantly higher in 2013 [15.3 (95% confidence interval 13.7-16.9)] than 2008 [12.6 (11.3-13.9)] (P = 0.012). Stratified by sex, the prevalence of obesity among boys was significantly higher in 2013 than 2008 [2008 = 12.0 (10.3-13.7) versus 2013 = 17.4 (15.1-19.7); P < 0.001]. The age groups 13 and 15 years had a significantly higher mean triglycerides in 2013 than 2008 (P-values 0.003 and <0.001, respectively) and lower mean HDL-cholesterol also in the 13 years old age group (P < 0.001). CONCLUSIONS The prevalence of childhood obesity in Saudi Arabia has increased in particular age groups (13-15 years) during a 5-year span. Special attention is warranted in these vulnerable age groups, particularly in boys, as cardiometabolic risk factors appear to worsen.

Effects of Different Dietary and Lifestyle Modification Therapies on Metabolic Syndrome in Prediabetic Arab Patients: A 12-Month Longitudinal Study

This three-arm, randomized, controlled study aimed to determine the differences in the effects of general advice (GA) on lifestyle change, intensive lifestyle modification programme (ILMP) and GA + metformin (GA + Met) in reducing the prevalence of full metabolic syndrome (MetS) in subjects with prediabetes; 294 Saudis with prediabetes (fasting glucose 5.6–6.9 mmol/L) were initially randomized, 263 completed 6 months and 237 completed 12 months. They were allocated into three groups: GA group which received a standard lifestyle change education; ILMP which followed a rigorous lifestyle modification support on diet and physical activity; and a GA + Met group. Anthropometric and biochemical estimations were measured. Full MetS (primary endpoint) and its components (secondary endpoint) were screened at baseline, 6 and 12 months. Full MetS in the ILMP group decreased by 26% (p < 0.001); in GA + Met group by 22.4% (p = 0.01) and in GA group by 8.2% (p = 0.28). The number of MetS components decreased significantly in the ILMP and GA + Met groups (mean change 0.81, p < 0.001 and 0.35, p = 0.05, respectively). Between-group comparison revealed a clinically significant decrease in MetS components in favor of the ILMP group (−0.58 (−0.88–0.28), p < 0.001). This study highlights the clinical potency of ILMP versus other diabetes prevention options in reducing MetS in Saudi adults with elevated fasting glucose.