Kaiser Wani

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.

ABCA1 C69T gene polymorphism and risk of type 2 diabetes mellitus in a Saudi population

Type 2 diabetes mellitus (T2DM) is a disease induced by complex interactions between environmental factors and certain genetic factors. Genetic variants in the Adenosine Binding Cassette Transporter Proteins 1 (ABCA1) have been associated with abnormalities of serum lipid levels of high-density lipoprotein (HDL-C). Decreased serum levels of HDL-C have often been observed in T2DM cases, and this condition has been considered to be involved in the mechanism of insulin resistance (IR). Therefore, we investigated possible association between ABCA1 C69T gene polymorphism and T2DM in a Saudi population. This study was carried out with 380 healthy control subjects and 376 T2DM patients. Genotyping of ABCA1 C69T polymorphism was carried out by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism technique. We observed that the frequency of the T allele of the ABCA1 C69T gene was significantly higher in healthy subjects compared to T2DM patients (0.28 vs 0.45; p<0.0001; OR (95% CI) = 0.4624 (0.3732–0.5729), and therefore the T allele may be a protective factor against T2DM in the Saudi population.

Association of vitamin B12 with pro-inflammatory cytokines and biochemical markers related to cardiometabolic risk in Saudi subjects

Background: This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population. Methods: A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m2 and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m2) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer. Results: Vitamin B12 was negatively associated with TNF-α (r = −0.14, p < 0.05), insulin (r = −0.230, p < 0.01) and HOMA-IR (r = −0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = −0.160, p < 0.01), insulin (r = −0.248, p < 0.01), HOMA-IR (r = −0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = −0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r2 = −0.17, p < 0.05) and in children (r2 = −0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r2 = −0.78, p < 0.05). Conclusions: Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population.

Circulating betatrophin in healthy control and type 2 diabetic subjects and its association with metabolic parameters

AIMS Betatrophin, a newly identified liver and adipose tissue-derived hormone, has been suggested as an inducer of β-cell proliferation in mice. However, the physiological role of betatrophin remains poorly understood in humans. Hence, the aim of this study was to investigate circulating betatrophin concentrations in normal and type 2 diabetes mellitus (T2DM) Saudi subjects and its association with various metabolic parameters. METHODS In this cross-sectional study, 200 Saudi adults (81 healthy non-T2DM controls, age: 41.43±8.35 [mean±SD]; BMI: 31.58±5.49 and 119 T2DM subjects, age: 48.78±11.76years; BMI: 30.25±4.83kg/m(2)) were studied. Anthropometric and fasting serum biochemical data were collected. Circulating betatrophin was measured using an enzyme-linked immunosorbent assay (ELISA) based kit. RESULTS We observed significantly higher levels of betatrophin in T2DM subjects compared to healthy controls (882.19±329.06 vs 657.14±261.04pg/ml, p<0.001). Furthermore, in T2DM subjects, betatrophin level was positively associated with blood pressure and serum fasting glucose (p<0.05). CONCLUSIONS Our results suggest that circulating betatrophin is significantly elevated in subjects with T2DM compared to healthy controls. Increase in the level of betatrophin in T2DM subjects might be a compensatory mechanism for enhanced insulin demand in T2DM condition.

Vitamin D Receptor Gene Polymorphisms Modify Cardiometabolic Response to Vitamin D Supplementation in T2DM Patients

There is conflicting evidence on the favorable effects of vitamin D supplementation on metabolic profile in Type 2 diabetes mellitus (T2DM) patients and this might be due to genetic variations in vitamin D receptors (VDRs). Thus, we studied the metabolic effects of a 12-month vitamin D supplementation in T2DM patients according to VDR polymorphisms. A total of 204 T2DM subjects received 2000 IU vitamin D3 daily for 12 months. Serum 25(OH)D and metabolic profiles were measured at baseline and after 12 months. VDR polymorphisms (Taq-I, Bsm-I, Apa-I and Fok-I) were identified using TaqMan genotyping assays. Vitamin D supplementation significantly increased HOMA β-cell function (p = 0.003) as well as significantly decreased triglycerides, total and LDL-cholesterol (p < 0.001). The lowest increment in 25(OH)D levels was detected in patients with Fok-I CC genotypes (p < 0.0001). With vitamin D supplementation, Taq-I GG genotype carriers showed significant improvements in triglycerides, LDL- and total cholesterol, insulin, HbA1c and HOMA-IR (p < 0.005, 0.01, < 0.001, < 0.005, 0.03 and 0.01, respectively). Similarly, Bsm-I TT genotype carriers showed significant improvements in triglycerides (p = 0.01), insulin and HOMA-IR (p-values < 0.05). In conclusion, improvements in metabolic profile due to vitamin D supplementation is influenced by VDR polymorphisms, specifically for carriers of Taq-I GG and Bsm-I TT genotypes.

Association of single nucleotide polymorphisms in microRNAs with susceptibility to hepatitis B virus infection and HBV‐related liver complications: A study in a Saudi Arabian population

The aim of this study was to evaluate the association of 10 SNPs in different microRNAs (miRNAs) with susceptibility to hepatitis B virus (HBV) infection, HBV clearance, persistence of chronic HBV infection, and progression to liver cirrhosis and hepatocellular carcinoma (HCC). Patients were categorized into the following groups: inactive HBV carrier, active HBV carrier, HBV‐cleared subject and cirrhosis+HCC. Samples were analysed for 10 SNPs in microRNAs using either PCR‐based genotyping or the TaqMan assay. We found that rs1358379 was associated with susceptibility to HBV infection, HBV clearance, persistent chronic HBV infection and liver cirrhosis+HCC. In addition, we found that rs2292832 and rs11614913 were associated with risk of HBV infection, viral clearance and cirrhosis+HCC, whereas rs2910164 was associated with proneness to HBV infection, and ability to clear the virus. There was evidence of associations between rs6505162 and HBV clearance and the development of liver disease, whereas a single association was found between rs2289030 and HBV clearance. Similarly, rs7372209 and rs4919510 were specifically associated with the development of HBV‐induced liver complications. SNPs in miRNAs affect the susceptibility, clearance and progression of HBV infection in Saudi Arabian patients. We found, using Gene Ontology or pathway analyses, that these genes may contribute to the pathophysiology of HBV infection and related liver complications. However, differences in the association of examined SNPs with various clinical stages indicate variations in the respective functional roles of these polymorphisms and their miRNAs, and thus, further investigation to fully explore their therapeutic potential is warranted.

Serum Uric Acid to Creatinine Ratio and Risk of Metabolic Syndrome in Saudi Type 2 Diabetic Patients

This study aimed to investigate whether uric acid to creatinine (UA/Cr) ratio is associated with higher risk of metabolic syndrome (MetS) and its components. 332 adult Saudi type 2 diabetes mellitus (T2DM) patients were divided into UA/Cr tertiles. Risk for full MetS was significantly highest in individuals that constitutes the uppermost serum UA/Cr tertile [Odds ratio (OR): 1.80, 95% confidence interval (CI): 1.0–3.3; p < 0.001) after adjustment for age, gender and BMI. Similarly, risk for individual components of MetS like central obesity, hypertriglyceridemia, low HDL-cholesterol and hypertension was significantly highest in this tertile with OR’s of 2.61 (1.2–5.6), 1.42 (0.7–2.3), 1.45 (0.7–2.8) and 1.16 (0.6–2.2) respectively (all p-values < 0.001) after adjustment for age, gender, BMI and other components of MetS. Furthermore, serum UA/Cr levels increased with increasing number of MetS components (mean values of 4.44, 4.49, 4.64, 4.89 and 4.91 respectively for 1,2,3,4 and 5 MetS components, p-values < 0.001 after adjusting for age, gender and BMI). Our data suggest that serum UA/Cr in T2DM patients is strongly associated with full MetS as well as its individual components. These findings are of considerable clinical importance as serum UA/Cr may be used as a marker in the pathogenesis of MetS.

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.

Sex-specific expression of apolipoprotein levels following replenishment of vitamin D

Numerous studies have been done to establish the relationship between vitamin D and lipids, yet a definitive causal link is not found. This interventional study aims to evaluate and compare levels of apolipoproteins among vitamin D deficient subjects at baseline and after they achieved full vitamin D status correction.120 Saudi adults with vitamin D deficiency [25(OH)D < 50nmol/l] were recruited and given 50,000IU cholecalciferol weekly for first 2 months, then twice a month for next 2 months, followed by daily 1000IU until month 6. Blood samples were taken at baseline and after 6 months. Serum 25(OH)D, lipid profile and apolipoproteins (A1, A2, B, C1, C2, C3, E and H) were analyzed using commercially available kits. Overall, serum 25(OH)D increased significantly(63.3 ± 16.5nmol/l at end of study vs. 32.5 ± 10.8 at baseline; p < 0.0001). In parallel, a significant increase in apolipoproteins C1, C2, C3 and E (all p-values < 0.01) and a significant decrease in apolipoprotein B (p = 0.02) was observed. Following, stratification according to sex, apolipoproteins C2 and C3 significantly increased only in males (p-values < 0.01) while apolipoprotein C1 significantly increased only in females (p < 0.01). In addition, apolipoprotein B significantly decreased only in females (p = 0.002). These results suggests role of vitamin D in modulation of circulating levels of lipoproteins. The sexual dimorphism observed in circulating levels of measured apolipoproteins following vitamin D correction may explain, in part, known sexual disparity in the events of cardiometabolic health.

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.