Association of SNP rs9939609 in FTO gene with metabolic syndrome in type 2 diabetic subjects, rectruited from a tertiary care unit of Karachi, Pakistan

To determine the association of SNP in FTO gene, rs9939609, with Metabolic Syndrome [MS] in type 2 diabetic subjects at a tertiary care unit of Karachi, Pakistan. We genotyped FTO rs9939609 SNP in 296 patients with type 2 diabetes from the Out Patient Department [OPD] of Baqai Institute of Diabetology and Endocrinology [BIDE]. MS was defined on the basis of International Diabetes Federation [IDF] and National Cholesterol Education program [NCEP]criterion. Association between the rs9939609 SNP and MS was tested through chi-square and Z-tests by using odds ratio [OR] with 95% confidence intervals. The frequency of MS as defined by IDF criterion was significantly higher in female subjects as compared to male subjects [p= 0.006]. Carriers of ? 1 copy of the rs9939609 A allele were significantly more likely to had MS [69.6%] than non-carriers [30.4%], corresponding to a carrier odds ratio [OR] of 0.52 [95% confidence interval [CI] [0.29-0.93], with a similar trend for the ATP III-defined MS."A" allele carriers under dominant model, carry all the criterion of MS more significantly as compared to non-carriers. The FTO rs9939609 SNP was associated with an increased risk for Metabolic Syndrome in type 2 diabetic populations at a tertiary care unit of Karachi, Pakistan

Angiotensin converting enzyme [ACE] gene expression in experimentally induced liver cirrhosis in rats

Angiotensin converting enzyme [ACE] is a key player of Renin Angiotensin System [RAS], involved in conversion of active product, angiotensin-II. Alterations in RAS have been implicated in the pathophysiology of various diseases involving heart, kidney, lung and liver. This study is designed to investigate the association of ACE gene expression in induction of liver cirrhosis in rats. Total 12 male albino Wistar rats were selected and divided in two groups. Control group received 0.9% NaCl, where as Test group received thioacidamide [TAA], dissolved in 0.9%NaCl, injected intraperitoneally at a dosage of 200mg/Kg of body weight, twice a week for 12 weeks. The rats were decapitated and blood sample was collected at the end of experimental period and used for liver functions, enzyme activity, antioxidant enzymes and lipid peroxidation estimations. Genomic DNA was isolated from excised tissue determine the ACE genotypes using specific primers. The ACE gene expression in liver tissue was assessed using the quantitative RTPCR method. The activity of ALT, total and direct bilirubin, SOD and CAT levels were significantly high [p<0.05] and level of MDA was significantly low [p<0.05] in TAA treated rats as compared to control rats. The ACE gene expression after 12 weeks TAA treatment in cirrhotic rats was significantly increased [p<0.05] in comparison to controls. This study describes the importance of RAS in the development of hepatic fibrosis and the benefits of modulation of this system ACE gene expression. The finding of major up-regulation of ACE in the experimental rat liver provides further insight into the complexities of the RAS and its regulation in liver injury. The development of specific modulators of ACE activity and function, in future, will help determine the role of ACE and its genetic variants in the pathophysiology of liver disease

Relationship between serum nitric oxide and sialic acid in coexisted diabetes, hypertension and nephropathy

This study was designed to study the relationship between serum nitric oxide and sialic acid in patients of diabetic nephropathy. Total 210 diabetic patients including 115 males and 95 females, suffering from diabetes and nephropathy [DN] were selected followed by informed consent and approval from institutional ethical committee. Equal number of age and sex matched normal healthy subjects were selected without any known history of hyperglycemia, hypertension and renal insufficiency as controls. Fasting blood samples from patients and controls were collected and analyzed for serum nitric oxide, sialic acid, fasting blood glucose [FBG], serum urea, creatinine, HbA1c and golmerular filtration rate [GFR]. The raised levels [p<0.05] of systolic and diastolic blood pressures, BMI, FBG, HbA1c, serum urea, creatinine and sialic acid were noted in DN patients as compared to controls. Significantly lower levels of GFR and serum nitric oxide [p<0.05] were observed in DN patients as compared to controls. Strong negative correlation was found between serum sialic acid and nitric oxide levels in patients diabetic nephropathy [p<0.05]. The relationship between the levels of serum nitric oxide and sialic acid may be considered as a strong biochemical indicator for micro and macro vascular complications of diabetes such as hypertension and nephropathy. These parameters should be taken into account during screening procedures regarding identifications of the diabetic patients to get them rid of progressive renal impairment to ESRD

Glycemic control, dyslipidemia and endothelial dysfunction in coexisted diabetes, hypertension and nephropathy

Diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic and retinal complications. Diabetes clustered with hypertension and nephropathy has become the leading cause of end-stage renal disease globally. This study describes diabetes, hypertension and nephropathy with reference to glycemic control, dyslipidemia and endothelial dysfunction indicating the foremost basis of morbidity and mortality world wide and rapidly progressing in Pakistan. Study subjects selected and divided in four groups [60 each] followed by institutional ethical approval and informed consent. Group 1: non-diabetic, normotensive control subjects; Group 2: diabetic, normotensive patients; Group 3: diabetic, hypertensive patients and Group 4: diabetic, hypertensive patients with nephropathy. Their fasting blood samples analyzed for the estimations of blood glucose, HbA1c, serum triglyceride, cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine, nitric oxide and sialic acid levels. Results showed that all the groups showed significant rise in fasting blood glucose. Similarly HbA1c levels were also significantly high in all the patients as compared to controls. Group 2 showed significantly high serum cholesterol and LDL levels and low HDL levels. Group 3 and 4 showed significantly high serum triglyceride, cholesterol and LDL levels where as low HDL levels as compared to controls. Group 3 showed significantly high serum creatinine. Group 4 showed a significantly high serum urea and creatinine as compared to controls. Persistent albuminuria was characteristic in Group 4 patients. Significantly low production of serum nitric oxide with high concentration of serum sialic acid was observed in Group 3 and 4 as compared to controls. Results indicate a clear relationship of declining renal function with poor glycemic control, abnormal lipid metabolism, endothelial dysfunction and initiation of acute phase response in tissues affected from the microvascular complications of diabetes like hypertension and nephropathy. It must be taken into account while screening diabetic patients to get them rid of progressive renal impairment leading to end stage renal disease

Electrolytes and Na+-K+-Atpase: potential risk factors for the development of diabetic nephropathy

Diabetic nephropathy is the leading cause of death that affects more than 40% of diabetic patients. Its metabolic derangements are frequently accompanied with electrolyte imbalances. This study was aimed to evaluate the electrolyte homeostasis during the progression of diabetic nephropathy in various stages of developing nephropathy. Patients admitted in diabetic wards of various hospitals of Karachi were selected and divided into 4 groups with 50 individuals each. Group I [healthy normotensive, non-diabetics with normal renal functions as control]. Group II [diabetic patients with normal blood pressure and renal functions]. Group III [diabetic hypertensive patients without renal disease]. Group IV [diabetic nephropathy patients with nephropathy]. Their fasting blood samples were drawn and analyzed for the estimations of intra erythrocyte and serum electrolytes and Na+-K+-ATPase activity. Group II patients showed a significant increase in intra erythrocyte sodium, serum potassium and calcium levels where as intra erythrocyte potassium, Na+-K+-ATPase, serum sodium and magnesium were significantly decreased as compared to control. Group III showed a significant rise in intra erythrocyte sodium levels but intra erythrocyte potassium, Na+-K+-ATPase, serum sodium, calcium and magnesium were significantly lowered as compared to control. Group IV revealed a significant increase in intra erythrocyte sodium and significant decrease in intra erythrocyte potassium, Na+-K+-ATPase, serum sodium, calcium and magnesium levels as compared to control. The results suggest the progressive trends in electrolyte abnormalities in diabetes mellitus leading to end stage renal disease along with the abnormality of their chief transport mechanism. It points towards the potentiality of electrolytes disturbances as indicators for the progression of diabetic nephropathy and also beneficial in prognosis and treatment of the disease

Clinical correlation between frequent risk factors of diabetic nephropathy and serum sialic acid

It has been recently established that serum sialic acid is a potent cardiovascular and renal risk factor in the general population and elevated in diabetic type 2 patients. This study was designed to assess the coexistence of frequently documented risk factors of diabetic nephropathy with serum sialic acid. A total of 100 diabetic patients [50 with and 50 without nephropathy] aged 47.56 +/- 10.68 [mean +/- SD] years attending several diabetic clinics in the private sector in Karachi were included after informed consent was obtained. Systolic and diastolic blood pressures were recorded by standard mercury sphygmomanometer. Fasting blood samples were collected for estimations of blood glucose, HbA1c, serum urea, creatinine and sialic acid levels. Serum sialic acid, glucose, HbA1c, urea and creatinine levels were increased significantly [P<0.01] in patients with diabetic nephropathy compared to diabetic patients without nephropathy. Regression and correlation analysis showed a significant positive correlation between serum sialic acid and fasting blood glucose, HbA1c, serum urea and creatinine levels. Body Mass Index and blood pressure were also significantly higher in diabetic patients with diabetic nephropathy compared to those without nephropathy. Fifty four percent of diabetic nephropathy patients were smokers compared with 41% of patients in the control group [diabetic patients without nephropathy]. It is concluded that elevated serum sialic acid level is strongly associated with the presence of nephropathy, a microvascular complications of diabetes. As there is a significant unvaried link between serum sialic acid and diabetic nephropathy, consideration of sialic acid as potent disease marker for diabetic nephropathy is justified

Ionic and allied variations in normotensive and hypertensive diabetic patients

To investigate the disturbances of serum and red cell electrolytes in association with membrane Na[+]-K[+]- ATPase activity as well as the status of serum Urea, Creatinine and osmolality in normotensive diabetic and hypertensive diabetic patients. Thirty normotensive and thirty hypertensive patients [age and sex matched] were selected along with thirty control subjects. Erythrocytes were isolated from freshly drawn blood samples, washed and used for the estimation of sodium and potassium concentrations using flame photometer [Corning 410]. Erythrocyte membranes were prepared for the estimation of Na[+]-K+-ATPase activity in terms of inorganic phosphate released/mg protein/hour. Serum glucose, creatinine and urea were determined by well-documented ortho toulidine, Jaffe's and diacetyl monoxime methods respectively. Osmomat 030 was used to estimate the plasma osmolality. The intra-erythrocyte sodium, serum glucose, urea, creatinine and osmolality were increased significantly in hypertensive diabetic patients as compared to normotensive diabetic patients whereas Na+-K+-ATPase activity, serum sodium, potassium, magnesium and calcium were decreased significantly in hypertensive diabetic patients as compared to normotensive diabetic patients. Results confirmed that there is a significant difference between normotensive and hypertensive diabetic patients with respect to their electrolyte metabolism and associated pathways. These results will notably help the physicians to treat diabetic patients with associated morbidity like hypertension

Electrolytes and sodium transport mechanism in diabetes mellitus

The metabolic derangements and disturbances and their consequences in diabetes mellitus are well known more or less in details too. However, knowledge on the diabetic disorders in membrane functions and transport mechanisms is limited which is an essential factor in progression of the disease. Serum electrolytes were measured by flame photometer [Corning 410] and spectrophotometer [Spectro SC] in 60 diabetic patients with stable glycemic control [aged 38 +/- 2.5 years] and in 60 age-matched normal subjects with no known history of hyperglycemia as control. Erythrocytes were isolated from samples, washed and used for the estimation of sodium and potassium concentrations using flame photometer. Erythrocyte membranes were prepared for the estimation of Na+K+ATPase activity in terms of inorganic phosphate released/mg protein/hour. Na+K+ATPase activity, Intra-erythrocyte potassium and serum magnesium levels were significantly low in diabetic patients than in the controls. Serum and intra-erythrocyte sodium and serum potassium levels were increased significantly in patients as compared to control subjects. A significant effect of sex and interaction was observed on serum sodium, potassium and magnesium. A significant effect of sex, disease and interaction on red cell sodium, potassium and Na+K+ATPase activity was observed in male and female subjects. Na+K+ATPase dysfunction and changes in intra-erythrocyte and serum sodium, potassium and magnesium induced by diabetes may be implicated in the pathogenesis of neuropathy, nephropathy and vascular diseases in humans. It is suggested that male diabetic patients are at high risk of diabetic complications than females

Acute amphotericin-B induced nephrotoxicity in albino rats

Nephrotoxicity is one of the major problems encountered during treatment with amphotericin B which is a potent broad spectrum antifungal drug used in systemic and deep fungal infections. The present study was undertaken to investigate the acute effect on the morphology of renal parenchyma when drug is administered in nephrotoxic doses in albino rats. A total of 20 albino rats of either sex were taken and divided into two groups. Group A as control and Group B received a single dose [10 mg/Kg] of intraperitoneal amphotericin B. The animals were sacrificed and their kidneys were subjected to detailed histological examination. The morphological features observed in the kidney of these two groups were analyzed and compared. The animals receiving 10 mg/Kg amphotericin B as a single dose showed flattering of the tubular epithelial cells with loss of proximal tubular brush borders and accumulation of lymphocytes in the cortical interstitium as compared to control group. The number of the proximal tubules as well as the tubular cell nuclear count was also decreased significally. It is suggested that, amphotericin B induced damage to renal cortical tissues is due to free radical injury which later caused direct cytotoxicity to renal epithelium