Vitamin D and Its Metabolites Deficiency in Acute Coronary Syndrome Patients Undergoing Coronary Angiography: A Case-Control Study.

BACKGROUND: Vitamin D deficiency is considered an emerging health problem that affects at least one billion patients worldwide. Calcitriol 1,25(OH)2D3 has several systemic effects, including anti-inflammatory, anti-thrombotic and anti-atherosclerotic impacts that explain its cardioprotective effects. The precise association between vitamin D and its metabolites and the value of supplements in acute coronary syndrome (ACS) is still controversial. This study aims to search the association between vitamin D2, D3, and metabolites and ACS in patients undergoing coronary angiography. MATERIALS AND METHODS: This was a case-control study on 73 consecutive adult patients with ACS undergoing coronary angiography compared to 50 controls without coronary artery disease and matched for age and sex from June 2019 till July 2019. Echocardiography and coronary angiography were done for all cases. Plasma vitamin D and its metabolites were measured at admission for all participants along with chemistry profiles. RESULTS: Vitamin D and its metabolites were statistically significantly lower in ACS patients than the controls. Multivariate regression analysis revealed that low levels of 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) significantly predicted ACS occurrence; the other significant predictors were high systolic blood pressure (BP), high total cholesterol, and low high-density lipoprotein-cholesterol. Interestingly, vitamin D2 and D3 did not significantly predict ACS (p>0.05). We did not find a statistically significant association between the number of affected coronary vessels and vitamin D metabolites. Moreover, there was no statistically significant correlation between vitamin D and its metabolites and left ventricular ejection fraction measured by echocardiography. CONCLUSION: There was a strong association between vitamin D and all its metabolites with ACS. Significantly, low 25(OH)D and 1,25(OH)2D predicted ACS, but vitamin D2 and D3 did not. Large randomized controlled trials are needed to verify the beneficial values of vitamin D supplementation in ACS patients.

MicroRNAs and Risk Factors for Diabetic Nephropathy in Egyptian Children and Adolescents with Type 1 Diabetes.

PURPOSE: Currently available markers for early detection of diabetic nephropathy (DN), the leading cause of end stage renal disease, have some limitations. There is insufficient evidence from previous studies about the role of several circulating microRNAs (miRNAs) in the early development of DN. This study aimed to describe the expression of miRNA-377, miRNA-93, miRNA-25, miRNA-216a, and miRNA-21 in a sample of type 1 diabetic children and adolescents to explore their association with DN and some indices of kidney injury. PATIENTS AND METHODS: Seventy type 1 diabetic patients, with 5 years' duration of diabetes or more, were recruited from Children's Hospital, Faculty of Medicine, Cairo University. Quantitative real-time reverse-transcription PCR (qRT-PCR) was used to measure the expression of the above mentioned miRNAs in serum and to assess its association with DN, and the studied risk factors. RESULTS: There was a significantly higher percentage of up-regulation of miRNA-377 and miRNA-93 (P=0.03, 0.02, respectively) in addition to significant down-regulation of miRNA-25 (P=0.01) in patients with DN than in patients without DN. In patients with DN, expression of miR-216a was significantly negatively correlated with creatinine (r=-0.4, P=0.04) and positively correlated with eGFR using creatinine (r=0.5, P=0.03). In the same group, expression of miR-21 was positively correlated with urinary cystatin C (r=0.6, P=0.01) and was negatively correlated with e-GFR using cystatin c (r=-0.6, P=0.01). miRNA-93 was associated with increased risk (odds ratio=15, 95% CI=12.03-24.63, P=0.01), while miRNA-25 was associated with decreased risk for albuminuria (odds ratio=0.15, 95% CI=0.08-0.55, P=0.03). CONCLUSION: miRNA-377, miRNA-93, miRNA-216a, and miRNA-21 may be implicated in the pathogenesis of DN, while miRNA-25 may have a reno-protective role. More studies are needed to document the value of these miRNAs as diagnostic biomarkers as well as therapeutic targets in DN.

Is subclinical atherosclerosis associated with visceral fat and fatty liver in adolescents with type 1 diabetes?

INTRODUCTION: There is a 3-fold higher prevalence of cardiovascular complications in patients with type 1 diabetes. The aim was to assess the relationship between subclinical atherosclerosis and visceral fat and fatty liver in diabetic adolescents. MATERIAL AND METHODS: The study was performed on 110 adolescents with type 1 diabetes (T1D) attending the Pediatric Diabetes Clinic of the University Hospital, Ismailia, Egypt. Their mean age was 14.2 ±0.7 years with a mean duration of diabetes 6 ±0.3 years. They were divided into group 1 which consisted of 55 adolescents with T1D and normal carotid intima media thickness (cIMT) and the second group which included 55 adolescents with T1D and subclinical atherosclerosis. All adolescents were normotensive, normo-albuminuric and had no retinopathy. Visceral fat thickness was measured as the distance between the anterior wall of the aorta and the posterior surface of the rectus abdominis muscle. Hepatic steatosis was diagnosed based on enlarged liver size and evidence of diffuse hyper-echogenicity of liver relative to kidneys. RESULTS: The mean visceral fat was significantly higher in adolescents with increased cIMT (4.8 ±1.6) than in the normal thickness group (3.9 ±1.4). Liver size was also significantly larger in the former group (13.73 ±2.26 versus 12.63 ±2.20) (p = 0.022). After adjusting for other variables, logistic regression demonstrated that glycated hemoglobin (HbA1c) and fatty liver are independent factors affecting cIMT, OR = 1.426 (p < 0.05) and OR = 4.71 (p < 0.05). CONCLUSIONS: In the present study, fatty liver and HbA1c were associated with subclinical atherosclerosis in lean adolescents with T1D.

Inflammatory Biomarkers of Cardiometabolic Risk in Obese Egyptian Type 2 Diabetics.

Inflammatory biomarkers provide a minimally invasive means for early detection and specific treatment of metabolic syndrome and related disorders. The objective of this work was to search for inflammatory biomarkers of cardiometabolic risk in obese type 2 diabetics. The study was performed on 165 persons attending the medical outpatient clinic of Ismailia General Hospital. Their mean age was (50.69 ± 10.15) years. They were divided into three groups. The control group was composed of 55 non-obese, non-diabetic healthy volunteers, 32 males and 23 females. Two study groups were included in this study: group 2 was composed of 55 obese, non-diabetic subjects, 25 males and 30 females matched for age and gender. All patients including the control were subjected to clinical history taking, a clinical examination for the measurement of body mass index (BMI). Investigations were carried out for fasting blood glucose, fasting serum insulin, insulin resistance (IR), the lipid profile, lipoprotein band lipoprotein phospholipase A2, and non-high-density lipoprotein cholesterol (non-HDL-C). Urea, albumin and creatinine analysis and liver function tests were performed, and a complete blood count (CBC) was taken. Hemoglobin A1C (HbA1C), serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested. There were statistically significant differences among the studied groups in terms of total cholesterol, non-HDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), lipoprotein-associated phospholipase A2 and apolipoprotein B. The inflammatory biomarkers hs-CRP, IL-6 and TNF-α were significantly statistically increased in the study groups by (1.62 ± 0.99, 2.32 ± 1.11), (1.73 ± 1.14, 2.53 ± 1.34), and (1.87 ± 1.09, 2.17 ± 0.89) respectively, where p < 0.01. Significant positive correlation was found between Homeostatic Model Assessment (HOMA)-IR, hs-CRP and IL-6. There was a significant positive correlation between non-HDL and hs-CRP, IL-6 and TNF-α and triglycerides and hs-CRP. In conclusion, in this study, CRP, IL-6, and TNF-α were significantly elevated in obese Egyptian type 2 diabetics and were positively correlated with insulin resistance, non-HDL and triglycerides. These inflammatory biomarkers could help in the premature identification of obese type 2 diabetic patients at high cardiometabolic risk. Additionally, these biomarkers are critical for providing prognostics and the validity of future potential anti-inflammatory therapeutic modalities.

Oral delivery of insulin from enteric-coated capsules containing sodium salicylate: effect on relative hypoglycemia of diabetic beagle dogs.

The hypoglycemic effect of Eudragit S100 enteric-coated capsules containing sodium salicylate as an absorption promoter formulated with insulin in various ways: as physical mixture, by wet granulation or in suppository bases (polyethylene glycol 4000 or Witepsol W35) was studied in hyperglycemic beagle dogs. The capsules containing insulin formulated with sodium salicylate (50 mg) and prepared by either physical mixing or wet granulation using 10% polyvinyl pyrollidone gave almost the same results producing a maximum reduction in plasma glucose level (C(max)) of 81.53+/-8.21 and 79.59+/-5.75%, T(max) of 6 and 5 h, area under the curve (AUC) of 69.37+/-48.64 and 57.98+/-23.15% reduction hour (% red. h) and resulting in relative hypoglycemia (RH) of 8.73+/-6.12 and 7.29+/-2.91%, respectively. Formulation of insulin with sodium salicylate in PEG 4000 produced a lower AUC of 37.30+/-10.36% red. h and RH of 4.69+/-1.3%. While, formulation in Witepsol W35 (0.5, 1.0 and 2.0 g) that was sieved to produce particle size of 180-315 microm and filled in enteric-coated capsules showed that formulating insulin and sodium salicylate in 1 g base is the best formulation. It produced 25% reduction in plasma glucose levels of the hyperglycemic beagle dogs at T(max) of 4 h and the largest AUC of 100.10+/-25.72% red. h, resulting in the highest RH of 12.59+/-3.23%. In conclusion, 25-30% reduction in plasma glucose levels and RH of about 12.5% relative to subcutaneous injection of regular soluble insulin can be achieved by formulating insulin in Witepsol W35 (1 g) with sodium salicylate (50 mg) as an absorption promoter, reducing the resulting mass into particle size 180-315 microm, packing into hard gelatin capsules and coating with Eudragit S100.