METABOLIC CONTROL OF TYPE 1 DIABETES IN CHILDREN TREATED WITH INSULIN PUMP THERAPY

In this paper we present study of metabolic control in children suff ering from TYPE  Diabetes Mellitus (TDM) who use insulin pump (IP) therapy, and who were treated at Paediatric Clinic

Introduction TYPE  Diabetes Mellitus (TDM) is the most frequent endocrinologic disease in children.Chronic course of the disease, and life-long substitution insulin-therapy which must be coordinated with the food, physical activity and with the results of selfmonitoring blood glucose are the factors that make life of these children and their families very difficult.Bad metabolic control of TDM that is represented with glycosylated haemoglobin level (HbAc) higher than ,  leads to chronic micro vascular complications: nephropathy, retinopathy and neuropathy.Progression of chronic complication in the patients with long-lasted bad metabolic control of diabetes results in invalidity and lethal outcome ().The aim of the treatment of diabetes is achievement of long-lasting good metabolic control of the illness with HbAc level less than , .DCCT study documented that decrease of HbAc for ,  reduces incidence of chronic diabetes complication for -  ().Each kind of therapy that can provide attaining of this aim parallel with normal growth and development of the child is justified.Increasing use of insulin pumps (IP) in therapy of diabetes characterized last decade.This therapy is the most similar to physiologic way of insulin secretion in non-diabetic persons because it is -hours lasting subcutaneous delivery of insulin (basal delivery) with bolus dose delivery in the meal-time ().Numerous studies confi rmed that patients with IP therapy reach better metabolic control of their TDM with less hypoglycaemic episodes and stabile body weight (, ).Less number of injections for - times during IP therapy compared to intensive insulin therapy ( insulin doses daily), is very important for patient.Instead of prick with needle for every dose of insulin in IP therapy insulin is continuously delivered through thin, small plastic tube subcutaneously positioned which is replaced every - days.All these technical preferences of IP therapy enable more flexibility in time and quality of meals that significantly improves life quality of young patient and his family ().Although the price of IP therapy is signifi cantly higher than for intensive insulin therapy, long-lasting positive eff ects of this therapy in children excuse their use.(, ) IP therapy was introduced for the first time in Bosnia and Herzegovina at Paediatric Clinic of University of Sarajevo Clinics Centre for TDM patients in  year.Patients for IP therapy were selected according medical and non-medical indications that were established on the base of indications from leading Diabetes Associations and authors.Those indications were originally fitted to our needs (, ).Our indications for introducing IP therapy were: medical and others.Medical indications were: bad metabolic control of TDM (HbAc> ,), significantly elevated insulin autoantibody (>,), early age of TDM beginning (age<  years), duration of TDM (≥  years) and associated diseases.Other indications were: motivation for IP therapy, TDM in closest relative and bad life quality during previous treatment.Patients had to satisfy at least one indication from each group.Leading indications for IP introducing were significantly elevated insulin autoantibody, motivation for IP therapy and bad life quality.All patients satisfi ed at least  indications.

Aim of the Study
Th e aim of this study is to correlate the level of metabolic regulation represented with HbAc value in children and adolescents with TDM before and  months after introduction of IP therapy.Patients were treated at Paediatric Clinic in Sarajevo.

Material and Methods
All patients - years of age suffering from TDM and treated with IP therapy at Paediatric Clinic in Sarajevo were observed in this study.This study represents retrospective analysis of metabolic control of children suffering from TDM in who was introduced IP insulin therapy in the period from the st March  to the st September .We analysed: • patients according sex and age • duration of TDM • therapy before IP introduction • HbAc value just before IP therapy introduction • HbAc value  months after IP therapy introduction Data were collected from patients' histories.TDM was diagnosed and treated at Paediatric Clinic in Sarajevo.Data concerning insulin therapy were updated at least every three months at check-up time.All patients had insulin pumps produced by Medtronic Minimed and models were  and .HbAc estimation was performed just before introducing IP therapy, and than  months after start the IP therapy.Method for HbAc estimation was micro column, and this method is on the list of standardized methods according National Glycohemoglobin Standardization Program (NSGP) with referent value of HbAc < ,  for non-diabetic persons ().

Results
In this paper is analysed metabolic control of TDM in paediatric patients just before and  months after introducing IP therapy.In the period fromst March  tost S e p t e m b e r     I P t h e r a p y w a s i n t r oduced in  paediatric patients with TDM.
Age range and sex structure of observed patients are presented on Table  . presents mean value of HbAc before IP therapy introduction was ,  with standard deviation , , and  months after IP therapy introduction HbAc value was ,  with standard deviation , .Correlation between these values was highly signifi cant p = ,.

Discussion
IP therapy was introduced in  TDM children what is   of total number of TDM patients up to  years old in Canton Sarajevo ().Percent of patients with IP therapy comparing with the total number of treated TDM patients in some studies is between -  (, ).There were more boys (, ) with introduced IP therapy what is correspondent with higher incidence of TDM in boys () .IP therapy was introduced mostly in the patients of age range between - years what is coincident with the period of intensive activity and schooling and is Long-lasting good metabolic control attaining is the aim of complete management of this disease.Every therapy that will help to reduce HbAc level under ,  is desirable and justified.
Our study confi rmed IP therapy like mean for attaining better metabolic control of TDM in children and adolescents.DCCT study pointed out connection between HbAc level and incidence of appearing and progression of chronic micro vascular complications of diabetes, and its following study: EDIC study confirmed significance of each period of good metabolic control in the life of TDM patient ().Periods of good metabolic control of diabetes with HbAc level les then ,  are "memorized" and protect patient from appearance and progression of micro vascular complications ().Th at is why each reduction of HbAc value towards goal value is extraordinary important in children who must live whole life with their TDM.

Conclusion
IP therapy introduced in paediatric TDM patients treated at Paediatric Clinic in Sarajevo proved significantly ( p=,) better metabolic regulation of diabetes just after six months' long term treatment.Our results are comparable to other groups referring to eff ects of IP therapy in paediatric patients.

Table  .
. Analyzed is metabolic control in  boys age range - years and in  girls age range - years, mean age of all patients was ,±, years.Most TDM patients (, ) to who we introduced IP therapy were from age group - years, and less (, ) were younger than  years what is presented at Table .In the moment of IP therapy introduction same number of patients  (, ) had TDM duration less than fi ve years and from  to  years what is presented at Table .points out that before IP introduction classic insulin was used by ,  of T DM patients and insulin analogues used ,  of T DM patients.Most of observed patients  (, ) just before IP therapy introduction had HbAc value in the range between  and  .There were less patients (, ) with HbAc value higher than , , and ,  patients had HbAc values below ,  before IP therapy introduction what is presented at Table .

TABLE 1 .
Age range and sex structure of T1DM patients in moment of IP therapy introduction

TABLE 2 .
Sex structure and age groups of T1DM patients in moment of IP therapy introduction

TABLE 3 .
T1DM duration in moment of IP therapy introduction

TABLE 4 .
Th erapy T1DM patients before IP therapy introduction

TABLE 5 .
HbA1c values before and 6 months after IP therapy introduction

TABLE 6 .
Correlation in HbA1c values before and 6 months after IP therapy introduction also coincident with pubertal period of fast growth and development.Swan et al.indicate that the start of fastacting insulin analogue action is postponed in the period of puberty compared with pre pubertal patients(). in the fi rst year of IP therapy of paediatric patients, and reduction was highest in those children who had HbAc level over ,  before IP therapy().Our study points out that only ,  of all observed patients had HbAc level over ,  after  months long IP therapy, and there were no patient with HbAc level over , .Before start of IP therapy there were ,  of our patients with HbAc in the range between ,-, , and ,  of patients with HbAc value over , .Spanish authors' study reported about reduction level of HbAc from , ± ,  to , ± ,  even two months after start of IP therapy in children().