Vitamin D supplementation in patients with diabetes mellitus type 2 on different therapeutic regimens: a one-year prospective study.

BACKGROUND: Little or no research has determined the effect of vitamin D3 supplementation in conjunction with pharmacological and non-pharmacological approaches in the diabetes mellitus type 2 (DMT2) patients. The objective of this study was to determine the effect of vitamin D3 supplementation in a cohort of Saudi DMT2 population on diet, insulin and/or different oral hypoglycemic agents and compare them with a non-DMT2 control cohort. METHODS: A total of 499 randomly selected Saudi subjects divided into 8 groups [Non-DMT2 Control = 151; Rosiglitazone alone = 49; Diet = 15; Insulin alone = 55; Insulin + Orals = 12; Metformin alone = 121; Oral agents combination = 37; Sulphonylurea alone = 59] were included in this 12-month interventional study. All DMT2 patients were given 2000 IU vitamin D3 daily, while the control group received none but were advised to increase sun exposure. Anthropometrics, glucose, lipid profile and 25-hydroxyvitamin D (25-OHVitD) were measured at baseline, 6 and 12 months. RESULTS: Circulating 25-OHVitD concentrations improved in all patient groups. The metformin group showed the highest change in circulating vitamin D levels both at 6 months (62.6%) and 12 months (50.6%) as compared to baseline (p < 0.001). No significant changes were observed in the BMI and glucose in any of the DMT2 groups. In contrast, the insulin + oral agents group showed more significant improvements in the metabolic profile, which included triglycerides and total cholesterol, as well as systolic blood pressure and HDL-cholesterol in males. Also, significant decreases in triglycerides were observed in the rosiglitazone and insulin + oral hypoglycemic agent groups both at 6 and 12 months of supplementation (both p-values <0.001). CONCLUSION: While in all DMT2 groups circulating levels of 25-OHVitD increased after supplementation, in DMT2 patients on insulin in combination with other drugs benefitted the most in improving cardiovascular risk. Metformin improves 25-hydroxyvitamin D levels but did not seem to confer other added cardiometabolic benefits.

Circulating leukocyte telomere length is highly heritable among families of Arab descent.

BACKGROUND: Telomere length, an indicator of ageing and longevity, has been correlated with several biomarkers of cardiometabolic disease in both Arab children and adults. It is not known, however, whether or not telomere length is a highly conserved inheritable trait in this homogeneous cohort, where age-related diseases are highly prevalent. As such, the aim of this study was to address the inheritability of telomere length in Saudi families and the impact of cardiometabolic disease biomarkers on telomere length. METHODS: A total of 119 randomly selected Saudi families (123 adults and 131 children) were included in this cross-sectional study. Anthropometrics were obtained and fasting blood samples were taken for routine analyses of fasting glucose and lipid profile. Leukocyte telomere length was determined using quantitative real time PCR. RESULTS: Telomere length was highly heritable as assessed by a parent-offspring regression [h2 = 0.64 (p = 0.0006)]. Telomere length was modestly associated with BMI (R(2) 0.07; p-value 0.0087), total cholesterol (R(2) 0.08; p-value 0.0033), and LDL-cholesterol (R(2) 0.15; p-value 3 x 10(-5)) after adjustments for gender, age and age within generation. CONCLUSION: The high heritability of telomere length in Arab families, and the associations of telomere length with various cardiometabolic parameters suggest heritable genetic fetal and/or epigenetic influences on the early predisposition of Arab children to age-related diseases and accelerated ageing.

Visceral obesity and inflammation markers in relation to serum prostate volume biomarkers among apparently healthy men.

BACKGROUND: Prostate disease incidence is expected to rise among developing nations secondary to increased prevalence of obesity and the elderly. Although many case-control studies have associated obesity to prostate cancer aggressiveness, few have correlated markers of prostate pathology to biomarkers of visceral obesity and insulin resistance, using an apparently healthy cohort. This study aims to fill this gap. MATERIALS AND METHODS: The 219 consenting adult Arab men, aged 30-70 years, were included in this cross-sectional study. Demographics were noted and anthropometrics measured. Fasting blood samples were extracted, and glycaemic and lipid profile were determined using routine laboratory methods. Serum adipocytokines and inflammatory markers were measured using multiplex assays. Total prostate-specific antigen (tPSA), free PSA (fPSA), parathyroid-related protein (PTHrP) and endoglin were measured using enzyme-linked immunosorbent assays. RESULTS: Serum triglycerides and waist-hip ratio (WHR) were significantly and positively associated with circulating (tPSA) levels in all subjects (P < 0·01). Systolic blood pressure (SBP), adiponectin, active plasminogen activator inhibitor-1 (aPAI-1) and insulin-like growth factor-1 (IGF-1) had significant inverse associations to tPSA. Stepwise linear regression revealed that adiponectin, IGF-1, WHR and PTHrP explained 30% of variance in tPSA levels (P < 0·0001), while SBP, resistin and BMI explained 18·7% of variance in endoglin (P = 0·001). CONCLUSIONS: The associations of adiponectin and WHR strengthen the link between insulin resistance and visceral adiposity to prostate volume markers among apparently healthy Arab men. Follow-up studies are needed to extend these preliminary findings so that early interventions can be provided to those at increased risk.

Publisher Correction: Sphingolipid serum profiling in vitamin D deficient and dyslipidemic obese dimorphic adults.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sphingolipid serum profiling in vitamin D deficient and dyslipidemic obese dimorphic adults.

Recent studies on Saudi Arabians indicate a prevalence of dyslipidemia and vitamin D deficiency (25(OH)D) in both normal weight and obese subjects. In the present study the sphingolipid pattern was investigated in 23 normolipidemic normal weight (NW), 46 vitamin D deficient dyslipidemic normal weight (-vitDNW) and 60 vitamin D deficient dyslipidemic obese (-vitDO) men and women by HPTLC-primuline profiling and LC-MS analyses. Results indicate higher levels of total ceramide (Cer) and dihydroceramide (dhCers C18-22) and lower levels of total sphingomyelins (SMs) and dihydrosphingomyelin (dhSM) not only in -vitDO subjects compared to NW, but also in -vitDNW individuals. A dependency on body mass index (BMI) was observed analyzing specific Cer acyl chains levels. Lower levels of C20 and 24 were observed in men and C24.2 in women, respectively. Furthermore, LC-MS analyses display dimorphic changes in NW, -vitDNW and -vitDO subjects. In conclusion, LC-MS data identify the independency of the axis high Cers, dhCers and SMs from obesity per se. Furthermore, it indicates that long chains Cers levels are specific target of weight gain and that circulating Cer and SM levels are linked to sexual dimorphism status and can contribute to predict obese related co-morbidities in men and women.

Intermediate and low abundant protein analysis of vitamin D deficient obese and non-obese subjects by MALDI-profiling.

Obesity is a pathological condition caused by genetic and environmental factors, including vitamin D deficiency, which increases the risk of developing cardiovascular disorders and diabetes. This case-control study was designed to verify whether serum profiles could be identified differentiating obese and non-obese Saudis characterized by vitamin D deficiency and pathological levels of triglycerides, high-density lipoprotein cholesterol and high total cholesterol levels. The serum protein profiles of 64 vitamin D deficient (serum 25(OH)D < 50nmol/L) individuals with metabolic syndrome and with (n = 31; BMI ≥ 30) or without (n = 33; BMI < 30) obesity were analyzed by a quantitative label-free mass spectrometry approach (MALDI-profiling), combined with different serum immunodepletion strategies (Human7 and Human14 immuno-chromatographies), to analyze the intermediate- and low-abundant protein components. The analysis of intermediate-abundant proteins (Human7) in obese vs. non-obese subjects identified 14 changed peaks (p < 0.05) in the m/z range 1500-35000. Furthermore, the Human14 depletion provided new profiles related to obesity (121 changed peaks). Among changed peaks, 11 were identified in the m/z range 1500-4000 Da by high-resolution tandem mass spectrometry, belonging to apolipoprotein CIII, apolipoprotein B100, alpha-1-antichymotrypsin and complement C3. Data herein show that distinct protein profiles identify specific peptides belonging to lipid metabolism and inflammation processes that are associated with obesity and vitamin D deficiency.

Effects of 12-month, 2000IU/day vitamin D supplementation on treatment naïve and vitamin D deficient Saudi type 2 diabetic patients.

OBJECTIVES: To determine whether 12-month, 2000IU/day vitamin D supplementation cardiometabolically improves treatment naïve type 2 diabetes mellitus (T2DM) Saudi patients with vitamin D deficiency.  METHODS: This 12-month interventional study was conducted at primary health centers in 5 different residential areas in Riyadh, Saudi Arabia between January 2013 and January 2014. Forty-five Saudi  T2DM  patients were enrolled. Baseline anthropometrics, glycemic, and lipid profiles were measured and repeated after 6 and 12 months. All subjects were provided with 2000IU vitamin D supplements for one year.   RESULTS: Vitamin D deficiency at baseline was 46.7%, 31.8% after 6 months, and 35.6% after 12 months, indicating an overall improvement in the vitamin D status in the entire cohort. Insulin and homeostatic model assessment-insulin resistance (HOMA-IR) after 12 months were significantly lower than a 6 months (p less than 0.05), but comparable to baseline values. Mean levels of triglycerides increased overtime from baseline (1.9±0.01 mmol/l) to 12 months (2.1±0.2 mmol). This modest increase in serum triglycerides was parallel to the insignificant decrease in circulating high-density lipoprotein -cholesterol levels.  CONCLUSION: Twelve-month vitamin D supplementation of 2000IU per day in a cohort of treatment naïve Saudi patients with T2DM resulted in improvement of several cardiometabolic parameters including systolic blood pressure, insulin, and HOMA-IR. Further studies that include a placebo group are suggested to reinforce findings.

Parent-offspring transmission of adipocytokine levels and their associations with metabolic traits.

Adipose tissue secreted cytokines (adipocytokines) have significant effects on the physiology and pathology of human metabolism relevant to diabetes and cardiovascular disease. We determined the relationship of the pattern of these circulating hormones with obesity-related phenotypes and whether such pattern is transmitted from parent to offspring. A combined total of 403 individuals from 156 consenting Saudi families divided into initial (119 families with 123 adults and 131 children) and replication (37 families with 58 adults and 91 children) cohorts were randomly selected from the RIYADH Cohort study. Anthropometrics were evaluated and metabolic measures such as fasting serum glucose, lipid profiles, insulin, leptin, adiponectin, resistin, tumor necrosis factor alpha (TNFα), activated plasminogen activator inhibitor 1 (aPAI1), high sensitivity C-reactive protein (hsCRP) and angiotensin II were also assessed. Parent-offspring regressions revealed that with the exception of hsCRP, all hormones measured showed evidence for significant inheritance. Principal component (PC) analysis of standardized hormone levels demonstrated surprising heritability of the three most common axes of variation. PC1, which explained 21% of the variation, was most strongly loaded on levels of leptin, TNFα, insulin, and aPAI1, and inversely with adiponectin. It was significantly associated with body mass index (BMI) and phenotypically stronger in children, and showed a heritability of ∼50%, after adjustment for age, gender and generational effects. We conclude that adipocytokines are highly heritable and their pattern of co-variation significantly influences BMI as early as the pre-teen years. Investigation at the genomic scale is required to determine the variants affecting the regulation of the hormones studied.

Severe hypovitaminosis D is widespread and more common in non-diabetics than diabetics in Saudi adults.

OBJECTIVE: To compare the incidence of hypovitaminosis D in subjects, with and without type 2 diabetes mellitus (T2DM), and determine its association to various risk factors. METHODS: Three hundred and forty-one (177 non-diabetic, and 164 T2DM) Saudi adults were included in this cross-sectional study conducted at the Biomarkers Research Program (BRP) of King Saud University, Riyadh, Kingdom of Saudi Arabia from March to August 2009. Anthropometrics and fasting blood samples were obtained. Fasting glucose (FG) and lipid profiles were determined. Serum 25-hydroxy vitamin D (25[OH]D) and parathyroid hormone (PTH) were quantified using enzyme-linked immunosorbent assay. Severe hypovitaminosis D was defined as serum 25(OH)D with levels <12.5 nmol/l. RESULTS: Age was the most significant predictor of 25(OH)D in both groups, explaining 25% (p=0.0005) and 16% of variances (p=0.0005). Waist-hip ratio, systolic blood pressure and body mass index were significant predictors of 25(OH)D among non-diabetics after age adjustment, explaining 21% of variance perceived (p=0.039). Serum PTH levels were higher in non-diabetic men and women. CONCLUSION: Severe hypovitaminosis D is prevalent in both non-diabetic and diabetic Saudis, but was more common in the young and middle-aged non-diabetics. The study further underscores the need for vitamin D fortification of the Saudi diet, and the promotion of vitamin D supplementation in both groups.