DIABETIC NEPHROPATHY AND HYPERTENSION: STUDIES ON ELECTROLYTE HOMEOSTASIS AND DYSLIPIDEMIA

Diabetes mellitus is a chronic metabolic disorder that can lead to serious cardiovascular, renal, neurologic and retinal complications. Diabetic nephropathy has become the leading cause of end-stage renal disease globally. Hypertension usually clusters with the other components of the cardiometabolic syndrome such as smoking, central obesity, physical inactivity, longer duration of diabetes, increased age, insulin resistance, poor glycemic control, microalbuminuria, dyslipidemia. These studies are sometimes contradictory although the role of sodium, potassium, calcium and magnesium in the blood pressure regulation particularly during diabetes mellitus is well established. Na+ -K+-ATPase transport is thought to be linked to several complications of diabetes mellitus. Glycosylation the non-enzymatic linkage of glucose with proteins has also been found to facilitate the atherogenecity in diabetic patients. In addition to baseline age and GFR, the long-term averaged risk factors that were predictive of kidney disease in diabetes include hypertension, obesity, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol etc. The endothelial dysfunction associated with diabetes has been attributed to a lack of bioavailable nitric oxide. Nitric oxide-dependent vasodilation has been shown to be an important factor in the maintenance and regulation of vascular tone in the renal microcirculation. The relationship of elevated serum sialic acid with serum lipids and also with mean daily insulin dose in diabetic patients has been established in previous studies. Elevated serum sialic acid is also associated with several risk factors for diabetic vascular disease such as diabetes duration, HbA1c, obesity, plasma triglyceride, and cholesterol concentrations.\ud \ud In the light of above mentioned facts, the present study was carried out to describe diabetic nephropathy with reference to the influential role of electrolyte homeostasis, glycemic control, dyslipidemia, endothelial dysfunction, acute phase response and other demographic features to this disorder, which has been the foremost basis of morbidity and mortality world wide and rapidly progressing in Pakistan according to the life style and socio-economic conditions of our society.\ud \ud Patients admitted in diabetic wards of various hospitals of Karachi were selected and divided into five groups as follows: Group I: Non-diabetic, normotensive control subjects. Group II: Diabetic, normotensive patients. Group III: Diabetic, hypertensive patients. Group IV: Diabetic, Hypertensive patients with nephropathy. Group V: Non-diabetic, Hypertensive patients.\ud \ud The diagnosis of diabetes was made according to the World Health Organization's (WHO) criteria. The study protocol was approved by the regulations of institutional ethical committee for the use of human subjects in research. An informed consent was obtained from each patient/attendant by explaining the study in brief. The patients' blood pressure was measured by standard mercury sphygmomanometer. Their fasting blood samples were drawn and analyzed for the estimations of intra erythrocyte and serum electrolytes, Na+-K+-ATPase activity, blood glucose, HbA1c, serum triglyceride, cholesterol, LDL-cholesterol, HDL-cholesterol, urea, creatinine, GFR, urinary albumin excretion, nitric oxide and serum sialic acid levels. Main findings are as follows:\ud \ud Group II patients showed a significant rise in intra erythrocyte sodium, serum potassium and calcium levels where as intra erythrocyte potassium, Na+-K+-ATPase, serum sodium and magnesium levels were significantly decreased as compared to control subjects. Group III showed a significant increase intra erythrocyte sodium levels but intra erythrocyte potassium, Na+-K+-ATPase, serum sodium, calcium and magnesium levels were significantly decreased as compared to control subjects. Group IV patients 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 subjects. Group V patients showed a significant reduction in Na+-K+-ATPase and serum sodium levels as compared to control subjects.\ud \ud All the groups showed significant rise in fasting blood glucose levels as compared to control subjects except Group V. Where as HbA1c levels were found significantly high in all the patients as compared to control subjects.\ud \ud Group II patients showed significant rise in serum cholesterol and LDL levels and decrease in serum HDL levels. The Group III, IV and V patients showed a significant rise in serum triglyceride, cholesterol and LDL levels where as decrease in HDL levels as compared to control subjects.\ud \ud A significant reduction was observed in GFR levels in all the patients as compared to control subjects. Group III patients showed a significant rise in serum creatinine and osmolality levels. Group IV patients showed a significant increase in serum urea, creatinine and osmolality levels as compared to control subjects. Persistent albuminuria was also observed in Group IV patients.\ud \ud Significantly decreased production of serum nitric oxide with increased concentration of serum sialic acid was observed in Group III, IV and V patients as compared to control subjects.\ud \ud Our findings have implications that the rate of decline of renal function bears a clear relationship with hypertension, derangements of electrolyte homeostasis, poor glycemic control, abnormal lipid metabolism, renal insufficiencies, endothelial dysfunction and production of acute phase response in tissues affected from the microvascular complications of diabetes for example hypertension and nephropathy. These parameters should be taken into account during screening procedures regarding identification of diabetic patients to get them rid of progressive renal impairment leading to end stage renal disease (ESRD)