EFFECTS OF AGGRESSIVE APPROACH TO THE MULTIPLE RISK FACTORS FOR DIABETIC NEPHROPATHY ON PROTEINURIA REDUCTION IN DIABETES TYPE 2 PATIENTS

Dietary interventions with protein and salt restriction, good glucose control, smoking cessation, aggressive blood pressure control, good control of cholesterol and triglycerides, use of ACE inhibitors and ARBs can delay the progression of diabetic nephropathy. Th e aim of this study was to present the eff ects of aggressive treatment of the multiple risk factors for diabetic nephropathy on proteinuria in patients with type  diabetes. In this study we included  patients with diabetes type  and insuffi cient regulation of glycaemia. Th e patients were followed for three months period. Glycated haemoglobin (HbAc), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), blood pressure, cholesterol and triglycerides and proteinuria were followed prior and after the study. Prior the study patients were treated with premix insulin divided in two daily doses + metformin after the lunch and they had insuffi cient regulation of glycaemia. During the study patients were treated with one daily dose of basal insulin, three doses of metformin ( mg), one daily dose of atorvastatin ( mg) and one daily dose of ramipril ( to  mg). Doses of insulin were titrated separately for each patients (,-, IU/kg). Patients were advised to start with lifestyle modifi cation, increased physical activity and dietary interventions with protein and salt restriction, energy restricted diet and smoking cessation. A total of  patients (male  and female ) with diabetes type  were studied. Th e mean age of the subjects was ±, years. Th e mean diabetes duration was ,±, years. Th e mean body mass index decreased from ,±, kg/m to , ±, kg/m after the study. Mean HbAc decreased from , ± ,  to , ± ,  (p<,). Mean fasting glycemia decreased from ,±, mmol/dm to ,±, mmol/dm (p < ,). Mean postmeal glycemia decreased from , ± , mmol/dm to , ± , mmol/dm (p<,). Th e mean cholesterol level decreased from , ±, mmol/dm to , ± EFFECTS OF AGGRESSIVE APPROACH TO THE MULTIPLE RISK FACTORS FOR DIABETIC NEPHROPATHY ON PROTEINURIA REDUCTION IN DIABETES TYPE 2 PATIENTS Belma Aščić – Buturović1*, Mirsad Kacila2, Mehmed Kulić2 1 Clinic of Endocrinology, Diabetes Mellitus and Metabolic Diseases, University of Sarajevo Clinics Centre, Bolnička ,   Sarajevo, Bosnia and Herzegovina 2 Center for Heart Diseases, University of Sarajevo Clinics Centre, Bolnička ,   Sarajevo, Bosnia and Herzegovina * Corresponding author


Introduction
Diabetes mellitus is leading cause for diabetic nephropathy and it is strong risk factor for end stage of renal disease.Th e prognosis of diabetic patients with nephropathy is very bad due to cardiovascular disease which is leading course for mortality in this population.Diabetic nephropathy is manifested by proteinuria.Prevalence of proteinuria is the same in both types of diabetes.Improved glycemic control, aggressive control of hypertension and dyslipidemia can reduce the incidence of end stage renal disease in both types of diabetes (). - of type  and  - of type  patients with long lasting diabetes, develop nephropathy, indicated by proteinuria ().The results of recent prospective studies present that good glycemic control can reduce microalbuminuria in patients in the early stage of diabetes.ACE inhibitors and angiotensin II receptor blockers in clinical trials reduced microalbuminuria in diabetic patients in the absence of hypertension ().Long term clinical studies which included patients with type  and  diabetes have documented the benefi cial effects of glucose control, blood pressure and serum cholesterol control in improving of urinary protein level ().The United Kingdom Diabetes Study showed that the treatment for establishing good glycemic control was less important then the achieving good control, with HbAc less than  and preprandial glucose in the range of , mmol/dm  to , mmol/ dm  .Tight glycemic control can reduced the incidence for diabetic nephropathy for  ().Hypertension and microalbuminuria is presented in almost  of persons at the time of diagnosis of type  diabetes, therefore detection and treatment of proteinuria is very important for prevention of diabetic nephropathy and end stage of renal disease ().
Th e aim of this study was to present the eff ects of aggressive treatment of the multiple risk factors for diabetic nephropathy (dietary interventions with protein and salt restriction, good glycemic control, smoking cessation, aggressive blood pressure control, good control of cholesterol and triglycerides, use of ACE inhibitors) on proteinuria in patients with type  diabetes.

Material and Methods
A total of  (male  and female ) patients with diabetes type  were studied.Th e patients were followed for six months period.Glycosilated haemoglobin (HbAc), body mass index (BMI), fasting plasma glucosae (FPG), postprandial plasma glucose (PPG), blood pressure, cholesterol and triglycerides and proteinuria were followed prior and after the study.Th e mean age of the subjects was ±, years.Th e mean diabetes duration was ,±, years.The mean body mass index decreased from ,±, kg/m  to , ±, kg/m  after the study.Prior the study patients were treated with premix insulin devided in two daily doses + metformin after the lunch and they had insuffi cient regulation of glycaemia.During the study patients were treated with one daily dose of basal insulin, three doses of metformin ( mg), one daily dose of atorvastatin ( mg) and one daily dose of ramipril ( to  mg).Doses of insulin were titrated separately for each patient (,-, IU/kg).Patients were advised to start with lifestyle modification, increased physical activity and dietary interventions with protein and salt restriction, energy restricted diet and smoking cessation.Doses of insulin were titrated separately for each patients (,-, IU/kg).

Results
After six months of treatment with one daily dose of basal insulin, three doses of metformin ( mg), one daily dose of atorvastatin ( mg) and one daily dose of ramipril ( to  mg) significant decrease was observed in fasting glucose, postmeal glucose level, glycosilated haemoglobin, blood preassure and proteinuria level.Weight reduction, holesterol, and tryglicerides level were recorded after the study.A total of  patients (male  and female ) with diabetes type  were studied.Th e mean age of the sub-, mmol/dm  (p<,).Th e mean triglicerides level decreased from , ± , mmol/dm  to , ± , mmol/dm  (p<,).Th e signifi cant decrease of proteinuria was recorded, prior the study the mean albuminuria was , ± , g/dm  and after the study was , ± , g/dm  (p<,).Mean blood pressure prior the study was ±,/, ± , mm Hg (p<,), after the study was  ±

Discussion
Type  diabetes is ever-growing health problem in the world.It is expected that around  millions people will be affected by the year .Development of macrovascular and microvascular complications in patients with diabetes mellitus type  is proportionally to the level of morbidity and mortality in this population.
Prevention and delay of late complications of diabetes is important for this population.Good treatment of the risk factors such as glycaemia, hypertension and dyslipidemia, with life style modifi cation could prevent micro and macrovascular complications in this population.
In the United States there are about . patients with end stage renal disease.Diabetes mellitus is risk factor for renal disease and  of end ,/ ,±, mmHg.Eff ective control of glycaemia, blood pressure, cholesterol and triglycerides, use of ACE inhibitors, dietary interventions with protein and salt restriction, smoking cessation, can delay the progression of nephropathy in type  diabetes.KEY WORDS: diabetes type , diabetic nephropathy, proteinuria reduction BELMA AŠČIĆ  BUTUROVIĆ ET AL.: EFFECTS OF AGGRESSIVE APPROACH TO THE MULTIPLE RISK FACTORS FOR DIABETIC NEPHROPATHY ON PROTEINURIA REDUCTION IN DIABETES TYPE 2 PATIENTS jects was ±, years.Th e mean diabetes duration was ,±, years.Th e mean body mass index decreased from ,±, kg/m  to , ±, kg/m  after the study.Mean HbAc decreased from , ± ,  to , ± , (p<,), Table ., Figure .Mean fasting glycemia decreased from ,±, mmol/dm  to ,±, mmol/ dm  ( p < ,), Table ., Figure .Mean postmeal glycemia decreased from , ± , mmol/dm  to , ± , mmol/dm  (p<,), Table., Figure .Th e mean cholesterol level decreased from , ±, mmol/dm  to , ± , mmol/dm  (p<,), Table ., Figure .Th e mean triglicerides level decreased from , ± , mmol/dm  to , ± , mmol/dm  (p<,), Table ., Figure .Th e signifi cant decrease of proteinuria was recorded, prior the study the mean albuminuria was , ± , g/dm  and after the study was , ± , g/dm  (p<,), Table ., Figure .Mean blood pressure prior the study was ±,/, ± , mm Hg (p<,), after the study was  ± ,/ ,±, mmHg, Table  Figure , .

TABLE 1 .
Group of patients treated with one daily dose of basal insulin analog + metformin Positive result should be confi rmed().In our study we improved control of glycaemia, hypertension, albuminuria, and dyslipidemia by using of basal insulin analogue and metformin, ACE inhibitors, atorvastatin, dietary interventions with protein and salt restriction, smoking cessation.Long term prospective studies have documented the benefi cial eff ects of targeting these risk factors for prevention of diabetic nephropathy.ConclusionEff ective control of glycaemia, blood pressure, cholesterol and triglycerides, use of ACE inhibitors, dietary interventions with protein and salt restriction, smoking cessation, can delay the progression of nephropathy in type  diabetes.