Pattern of dyslipidaemia and impact of increasing age and duration of type 2 diabetes mellitus on dyslipidaemia, insulin levels and insulin resistance.

OBJECTIVE: To study the pattern of dyslipidaemia in Type 2 Diabetes Mellitus patients and to determine the correlation of increasing age and duration of the disease with dyslipidaemia, insulin level and insulin resistance in diabetic patients. METHODS: The cross-sectional case-control study was conducted at Combined Military Hospital, Rawalpindi, and Centre for Research in Experimental and Applied Medicine, Army Medical College, Rawalpindi, Pakistan from June 2011 to June 2012, and comprised patients of type 2 diabetes mellitus and healthy controls. Serum levels of total cholesterol, triglycerides, low density lipoprotein, high-density lipoprotein and insulin in both the cases and the controls. Insulin resistance was calculated by Homeostatic Model of Assessment of insulin resistance. Correlation between increasing age and duration of the disease was determined using biochemical parameters. SPSS 17 was used for statistical analysis. RESULTS: Of the 112 subjects in the study, 72(64%) were patients and 40(36%) were healthy controls. Among the cases, hypertriglyceridaemia was the commonest in 44(61%) followed by low-density-lipoprotein-hypercholesterolaemia 36(50%). Among the controls, 20(50%) subjects had low-density-lipoprotein-hypercholesterolaemia, followed by hypertriglyceridaemia in 17(42.5%). Duration of the disease was not found to be correlated with dyslipidaemia or insulin resistance (p>0.05). There was strong negative correlation of duration of the disease with serum insulin levels (p=0.03). Age showed no significant correlation with dyslipidaemia, serum insulin levels or insulin resistance on regression analysis (p>0.05 each). CONCLUSIONS: In type diabetes mellitus, hypertriglyceridaemia was the commonest dyslipidaemia whereas hypercholesterolaemia was a risk factor in healthy individuals. Besides, the duration of disease was inversely correlated with serum insulin levels and positively correlated with dyslipidaemia.

Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM.

Effect of ascorbic acid and alpha tocopherol supplementation on acute restraint stress induced changes in testosterone, corticosterone and nor epinephrine levels in male Sprague Dawley rats.

BACKGROUND: Stress of various origins suppresses male reproductive functions through releasing stress hormones. Antioxidant like ascorbic acid (AA) and alpha tocopherol (AT) have been thought to protect the body against stress induced damage. Whether, these antioxidants confer protection against the stress induced increased levels of corticosterone and nor-epinephrine, and decreased testosterone secretion have been investigated in this study. METHODS: This quasi experimental study was carried out at the Department of Physiology, Army Medical College Rawalpindi in collaboration with National Institute of Health, Islamabad during March to September 2009. Eighty male Sprague Dawley rats were divided into five groups with sixteen rats in each group. Group-I served as the control without stress while group-II was exposed to restraint stress for 6 hours, group-III was administered AA, group-IVAT and group-V was supplemented with both the antioxidants along with standard diet for one month. All antioxidant supplemented groups were exposed to restraint stress for 6 hours. Immediately after the stress episode, blood sample was obtained for the assay of serum testosterone, serum corticosterone by EIA and plasma nor-epinephrine levels by ELISA. Data were analyzed on SPSS-13 and p-value less than 0.05 was considered significant. RESULTS: Acute restraint stress resulted in a statistically significant rise in corticosterone and nor-epinephrine levels and fall in serum testosterone levels. AA supplementation for one month revealed insignificant changes in stress induced hormonal parameters. AT alone and in combination with ascorbic acid prevented the fall in testosterone level as well as rise in corticosterone, however nor-epinephrine levels remained unchanged. CONCLUSION: Supplementation with AT alone or in combination with AA prevent reduction in testosterone and rise in corticosterone levels while keeping the nor-epinephrine levels unchanged after acute restraint stress in Sprague Dawley rats.

Steroidogenesis in amlodipine treated purified Leydig cells.

Drugs have been shown to adversely affect male fertility and recently anti-hypertensive drugs were added to the list. The anti-fertility effects of amlodipine, a calcium channel blocker, are well-illustrated in in vivo experiments but lack an in vitro proof. The present study was designed to experimentally elucidate the effects of amlodipine on Leydig cell steroidogenesis and intracellular calcium in vitro. Leydig cells of Sprague-Dawley rats were isolated and purified by Percoll. Cells were incubated for 3h with/without amlodipine in the presence/absence of LH, dbcAMP, Pregnenolone and 25-Hydroxycholesterol. Cytosolic calcium was measured in purified Leydig cells by fluorometric technique. The results showed significantly reduced (P<0.05) steroidogenesis and intracellular calcium in amlodipine exposed rats. The site of amlodipine induced steroidogenic inhibition seems to be prior to the formation of Pregnenolone at the level of StAR protein.

Effects of simvastatin on lipid profile and nerve conduction velocity in obese Sprague Dawley rats.

BACKGROUND: The incidence of obesity is increasing worldwide. The lipid derangements and decrease in nerve conduction velocity are important complications for which a number of treatment options are being considered. In this study, Simvastatin, a hydroxyl methyl glutaryl coenzyme A reductase inhibitor is studied for its effects on these complications of obesity. METHODS: The study was a randomised control trial conducted at Islamic International Medical College, Rawalpindi in collaboration with Railway General Hospital, Rawalpindi, and National Institute of Health, Islamabad. Ninety adult male Sprague Dawley rats were divided into three groups with thirty rats in each group. One group of rats was taken as control with normal diet while other two groups were given High Fat Diet (HFD) for the whole study period, i.e., 10 weeks. One of the HFD group was given Simvastatin along with high fat diet for four weeks. Lipid profile was done by enzymatic colorimetric method. Conduction velocity of sciatic nerve was determined with the help of PowerLab data acquisition system. RESULTS: The two groups with HFD showed more than 25% increase in weight at the end of study as compared to control group. HFD group showed significantly higher lipid profile and decreased sciatic nerve conduction velocity when compared with control. The group that was given Simvastatin showed significant improvement in lipid profile and increased sciatic nerve conduction velocity after 4 weeks when compared with the group that was given HFD without any intervention. CONCLUSIONS: Simvastatin is effective for improving the lipid profile and sciatic nerve conduction velocity in HFD induced obesity.

Effects of amlodipine on serum testosterone, testicular weight and gonado-somatic index in adult rats.

BACKGROUND: Calcium ions are vital in many biological processes including hormonal secretion, mitosis, reproduction, fertility and regulation of gene expression. Thus, calcium antagonists who are frequently prescribed for the cure of cardiovascular diseases may affect any of these physiological processes. METHODS: This quasi experimental study was done at Army Medical College, Rawalpindi from October 2007 to March 2008. Thirty male Sprague Dawley rats, purchased from National Institute of Health, Islamabad were divided into group A (vehicle treated controls) and group B (amlodipine treated). After receiving drug treatment for 50 days, all the rats were sacrificed. Serum was stored to measure testosterone by enzyme immunoassay technique. The testes were removed for measuring absolute testicular weight and gonado-somatic index. RESULTS: Serum testosterone, absolute testicular weight and gonado-somatic index were found to be significantly reduced in amlodipine treated rats. CONCLUSION: These results suggest that long-term treatment with amlodipine might be associated with significant testicular regression and reduction in serum testosterone. Furthermore, since dihydopyridine antagonists are widely used in hypertension, our data may have some clinical implication in the management of infertility associated with hypertension.