Abstract. Med. J. Cairo Univ., Vol. 78, No. 1, March: 35-41,

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1 Med. J. Cairo Univ., Vol. 78, No. 1, March: 35-41, 21 Retrospective Epidemiological Study, with Focus on Acute and Chronic Managements, of Patients Attending the Pediatric Outpatient Clinic of National Institute of Diabetes and Endocrinology, Cairo, Egypt MOHAMAD H. EL-HEFNAWY, Ph.D. 1 ; ATEF A. BASSYOUNI, M.D. 2 ; BELAL OMAR, M.D. 2 ; HASSAN EL-BANNA, M.D. 2 ; IBRAHIM A. EMARA, Ph.D. 3 and HELMY EL-GAZZAR, M.D. 4 The Departments of Pediatrics 1, Internal Medicine 2, Biochemistry 3, National Institute of Diabetes & Endocrinology (NIDE) and Clinical Pathology 4, Hearing & Speech Institute. Abstract Diabetes mellitus is the most common endocrine metabolic disorder of childhood. It is widely spread all over Egypt as its prevalence was found to be 1.9 per 1 among school aged children. The aim of this work was to do a retrospective epidemiological study of the records of diabetic children attending the outpatient pediatric clinic in NIDE. The files of 851 diabetic children were examined retrospectively without any reference to the personal data. Out of them, the files of 2 diabetic patients were also studied for determination of chronic management results represented by the type of insulin regimen used and estimation of the daily insulin dose per kg. We also assessed the outcome management of acute ketoacidosis from the files of 2 patients admitted to the ICU & inpatient departments. All the resulted data had been subjected to SPSS statistical program. The results showed that there is no statistical differences between male, (n=424) to female, (n=427) distribution. The results of this retrospective study showed that the mean age of onset of diabetes in children attending the outpatient pediatric clinic of National Institute of Diabetes was (mean=8.37 ± 1.96y). The present study showed also that there was a decrease of age of onset of diabetes among diabetic children as the age of onset between 5-<1 years were the highest percentage (46%). As regards the insulin regimen used by the diabetic children, 17.5% used conventional insulin therapy, 11% used modified insulin therapy as they used regular insulin before lunch and 71.5% used basal-bolus insulin regimen. The mean percentage of insulin unites per Kg. was 1. ±.38U/kg./day. The mean BMI was=24.54±6.42, while the BMI distribution was: 56% were with normal weight=<25, 27% were overweight=25: <3, 14% were obese=3: <4 and only 3% were with severe obesity where BMI=>4. The results showed also that 34.8% of the diabetic patients were doing continues home blood glucose monitoring with glucose sensors, 25.8% were doing the monitoring only with visual strips, while 39.4% of the diabetic children were not doing home monitoring at all. The study of control of diabetes showed that the Glycated HbA1c was <7% in 31%, 7-8% in 22%, >8-9% in 14% and >9% in 33%. As regards the diabetic patients with ketoacidosis, 39% of them were diagnosed as the first presentation of diabetes. The duration required, for ketoacidosis, to be resolved was <6 hr. in 44%, 6-12 hr. in 38.6%, >12-24 hr. in 12.6% and >24% in only 3.8%. The results showed, also, that only 4.3% of DKA-cases were with PH <7., 8.7% were with PH=7: 7.1, 7.7% were with PH >7.1: 7.2, 32.4% were with PH >7.2: 7.3 and 7.2% only were with PH >7.3. The above results showed also that 13.% of ketotic cases were with severe acidosis, 7.7% were with moderate acidosis and 32.4% were with mild acidosis. The discussion of these results documented that it will be essential to follow the international guidelines of management of type 1 diabetes and it was recommended to do proper diagnosis of different types of diabetes among diabetic children and to study the prevalence and incidence of diabetes among Egyptian children as the prevalence and incidence still uncertain till now. Key Words: Retrospective epidemiological Chronic management Diabetes and endocrinology. Introduction DIABETES mellitus is the most common endocrine metabolic disorder of childhood. It is widely spread all over Egypt as its prevalence was found to be 1.9 per 1 among school aged children [1]. The total number of people with diabetes is projected to rise from 171 million in 2 to 366 million in 23. The urban population in developing countries is projected to double between 2 and 23. For Egypt, the total projected number of people with diabetes is 6.7 million [2]. An increasing incidence rate of childhood-onset type 1 diabetes has been described in several countries, particularly among the youngest children and the Nordic countries have consistently been shown to have the highest incidence rates. Among the interesting findings was a significant regional variation within the country, but there was no indication of an increase in the incidence in any 35

2 36 Retrospective Epidemiological Study of NIDE Patients age-group during the current study period. Recently, there were big variations in age, sex distribution and residency together with other environmental factors. Geographical variations in type 1 diabetes can be interpreted as evidence of environmental and genetic factors in the etiology of the disease [3]. Aim of the work: The aim of this work was to do a retrospective epidemiological study of the old records of diabetic children attending the outpatient pediatric clinic in NIDE. The files of 2 diabetic patients were also studied for determination of chronic management results represented by the type of insulin regimen used and estimation of the daily insulin dose per kg. We also assessed the outcome management of acute ketoacidosis from the files of 2 patients admitted to the ICU and inpatient departments. Material and Methods The files of 851 diabetic children that were attending the outpatient pediatric clinic of National Institute of Diabetes and Endocrinology were examined retrospectively without any reference to the personal data. Approval had been taken from the research ethics committee of General Organization of teaching Hospitals and Institutes. Out of them, the files of 2 diabetic patients were also studied for determination of chronic management results represented by the type of insulin regimen used and estimation of the daily insulin dose per kg. We also assessed the outcome management of acute ketoacidosis from the files of 2 patients admitted to the ICU and inpatient departments. All the resulted data had been subjected to SPSS statistical program. Laboratory investigations were done for all the diabetic patients for the proper diagnosis of type of diabetes as: CBC, liver enzymes, s. Creatinine, lipid profile, including total cholesterol LDL-cholesterol, HDLcholesterol and triglycerides, fasting c-peptide, that was assayed in serum by two-site sandwich immunoassay using the ACS: 18 Automated Chemiluminescence systems according to the method of Hardy, et al. [4] and Glycated HbA1c that was done according to the method using an immunoturbidometric assay on Dimension RxLmax (Dade Behring) [5]. Estimation of c-peptide levels in blood had been done for all patients with estimation of the presence of auto-antibodies for proper diagnosis of type of diabetes. Beta cell function was considered positive if fasting c-peptide level was 1 ng/ml. Insulin Auto Antibodies (IAA), Islet Cell Auto antibodies (ICA) and anti-glutamic Acid Decarboxylase (Anti-GAD) were measured by ELISA kits (DRG diagnostic, Mountainside, NJ, USA) [6,7,8] respectively. Blood gases and electrolytes by using Ion Selective Electrode, (ISE), BG85 (CIBA-CORNING). Results This retrospective study examined 851 files of pediatric clinic that were done for diabetic patients from year 25 to 27. The results showed that there is no statistical differences between male, (number=424) to female, (number=427) distribution as shown in Table & Histogram (1). But there was a female predominance. Table & Histogram (1): Sex distribution among diabetic children. Sex distribution Number % Significance Male N.S. Female Male Female The results showed that: 44.7% of diabetic children were from Cairo, 35.7% from Giza, 15.5% from delta while only 4.7% were from Upper Egypt. This geographical distribution is not a representative to that in Egypt because almost most of attending cases to the outpatient pediatric clinic of National Diabetes Institute were coming from the near areas except in complicated cases that were referred from far areas. This distribution was represented in Table & Histogram number (2). Table & Histogram (3), showed the positive family history of diabetes. There was positive diabetes family history in 6.7% as regarding father, 5.8% as regarding mother, 4.% as regarding siblings, while the positive family history of diabetes for grandmother or grandfather was %, (all of them were diagnosed as type 2 diabetes, while for mother, father or siblings, most of them were diagnosed as type 1 diabetes).

3 Mohamad H. El-Hefnawy, et al. 37 Table & Histogram (2): Geographical distribution of diabetic children attending outpatient pediatric clinic in National Diabetes Institute. Geographical distribution Number % Cairo Giza Delta Upper Egypt Table & Histogram (4): Showed that 8.6% of diabetic children were on breast feeding, % were on artificial cows milk and 2. 1 % only were on artificial milk formula. Feeding during lactation Number % Breast feeding Artificial cows milk Artificial milk formula Cairo Giza Delta Upper Egypt Family history of diabetes Diabetic father Diabetic mother Diabetic siblings Diabetic grandfathers or/and grandmothers Number % Cairo Giza Delta Upper Egypt Table & Histogram (3): The positive family history of diabetes among diabetic children attending outpatient pediatric clinic in National Institute of Diabetes Father Mother Siblings Others Father Mother Siblings Others Table & Histogram (4), showed that 8.6% of diabetic children were on breast feeding, 13.1% were on artificial cows milk and 2. 1 % only were on artificial milk formula. The results of this retrospective study showed that the mean age of onset of diabetes in children attending the outpatient pediatric clinic of National Institute of Diabetes was (mean=8.37 ± 1.96). Table (5), showed the distribution of age of onset of diabetes in these children. Table & Histogram (5): The distribution of age of onset of diabetes in children attending outpatient pediatric clinic of National Institute of Diabetes. Age of onset of diabetes Number % >5 years : < 1 years years Age of onset <5 y Age of onset Age of onset =5-1 y =1-15 y Age of onset <5 y Age of onset=5-1 y Age of onset=1-15 y Breast feeding Artificial cows milk Artificial milk formula The results showed, also, that age distribution of diabetic children attending the outpatient clinic of National Institute of Diabetes were as shown in Table & Histogram (6).

4 38 Retrospective Epidemiological Study of NIDE Patients Table & Histogram (6): Age distribution of children attending the outpatient pediatric clinic in National Institute of Diabetes. Age of diabetic children Number % <5 years : <1 years years >5 years 5-<1 years >1 years >5 years 5-<1 years >1 years The mean of BMI of the diabetic children was =24.54±6.42, while the BMI distribution was obvious in Table & Histogram (7). Table & Histogram (7): BMI distribution among diabetic children attending National Institute of Diabetes. used basal-bolus insulin regimen, as had been shown in Histogram (1). Histogram (11), sowed that only 4.3% of DKAcases were with Ph <7., 8.7% were with Ph=7: 7.1, 7.7% were with Ph 7.1: 7.2, 32.4% were with Ph=7.2: 7.3 and 7.2% were with Ph >7.3. The above results showed that 13.% of ketotic cases were with severe acidosis, 7.7% were with moderate acidosis and 32.4% were with mild acidosis. The mean percentage of insulin unites per Kg. was 1.±.38U/kg. 18% 8% 8% 38% 38% <.5.5:<1 1:< :<2 Histogram (8): Percentage of insulin unites per Kg used by diabetic children. >2 BMI Number % < : < : <4 14 > % 39% Recent cases Old cases BMI <25 BMI 25-3 BMI >3-4 BMI >4 Histogram (9): Percentage of recent cases of diabetic patients admitted with diabetic ketosis. 71.5% 17.5% 11% Histogram (9), showed that the recent cases presented with diabetic ketoacidosis were about 39% of the total ketotic cases admitted at that time. The duration required for ketosis to be resolved was <6 hr. in 44%, 6-12 hr. in 38.6%, >12-24 hr. in 12.6% and >24% in only 3.8%. As regards the insulin regimen used by the diabetic children were, 17.5% used conventional insulin therapy, 11% used modified insulin therapy as they used regular insulin before lunch and 71.5% Convensional insulin therapy Modified insulin therapy Basal-bolus insulin therapy Histogram (1): Comparison between different types of insulin therapy used by diabetic children.

5 Mohamad H. El-Hefnawy, et al. 39 % 7.2% 32.4% % % % 1.6 PH <7 >7:7.1 >7.1:7.2 >7.2:7.3 >7.3 Histogram (11): Estimation of different levels of PH at admission of diabetic patients with diabetic ketosis. <6 hr >6:12 hr >12:24 hr >24:36 hr >36:48 hr 2.3 <6 hr >6:12 hr >12: >24: >36: 24 hr 36 hr 48 hr Histogram (12): Estimation of number of hours required for resolution of ketosis in diabetic children. Discussion The results of this study showed that there was no statistical difference between male to female distribution with female predominance. The same results were recorded by Ghali et al. [9] and Arab et al. [1]. While Salem et al. [1], demonstrated a male predominance and this male predominance was very strange and this may be due to the small number of the study and it was restricted only to a small area in Egypt. The geographical distribution of the patients attending the outpatient clinic of NIDE is not representative to the distribution of diabetes in Egypt as the NIDE is located in Cairo and Giza is the nearest governorate to Cairo, but upper Egypt is far from Cairo and only the complicated cases were referred to NIDE. This study revealed that the diabetic children that had positive family history of diabetes from father were 6.7%, mother 5.8%, siblings 4.% and grandfathers & grandmothers 31.3%. This result goes with the international results which documented that for the offspring of diabetic fathers, the cumulative incidence of type 1 diabetes by age 2 years is 6%, or 2 times that for general population [11,12,13]. For the offspring of diabetic mothers, the corresponding cumulative incidence is approximately 2%, which is only seven times that in the general population [14,15]. The risk for offspring of mothers with type 1 diabetes was lower than that for offspring of fathers with type 1 diabetes regardless of the parents age at diagnosis, which may be due to that the exposure to a diabetic environment in utero may have a protective effect on the offspring, perhaps by increasing immunologic tolerance to the antigen involved in the autoimmune destruction of the pancreatic beta cells [16]. The high percentage of positive diabetic history in grandfathers or grandmothers is not of value as all of them were type 2 diabetes. The present study showed that there was a decrease of age of onset of diabetes among diabetic children as the age of onset between 5-<1 years were the highest percentage (46%) [17,18,19]. Concern about early exposure to cow s milk protein as a trigger of beta cell autoimmunity and the subsequent development of type 1 diabetes in susceptible individuals receives a lot of attention. The epidemiologic evidence suggesting this hypothesis came from a case-control study that found a decreased frequency/duration of breastfeeding in cases. The effect could be due to a lack of a protective effect of breast feeding or to exposure to an initiator of autoimmunity in cow s milk. Subsequent studies have been inconsistent in replicating this finding and the overall small magnitude of the effect can plausibly be attributed to recall bias [2]. Pliminary results of follow-up studies that monitor the appearance of autoimmunity to beta-cells in high risk infants and small children have not found any association with early exposure to cow s milk [21]. The results of this study proved that there was no role of cow s milk in the pathophysiology of type 1 diabetes in children as the above results. The age distribution of diabetic children attending the pediatric clinic at that time could not be representative to age distribution of diabetes among Egyptian children as at that time there were an official regulations that limit the age of children to 12 years only. The mean of BMI of the diabetic children was=24.54±6.42kg/m 2, while the BMI distribution was 56% were <25, 27% were 25: <3, 14% were 3: <4 and only 3% were 4. These results showed that most of diabetic children were not obese and the small percentage of obesity could be due to use of insulin with tendency to do strict control of diabetes. While the prevalence of

6 4 Retrospective Epidemiological Study of NIDE Patients obesity was higher during study of diabetes as a whole, type 1 & type 2, in 22 [1]. Diabetic kitoacidosis (DKA) is often the initial manifestation of type 1 diabetes in children and occur at any time during the course of the disease, with precipitating factors being acute infection, misguided advice to stop insulin therapy because of anorexia related to acute infection, or deliberate omission of insulin [22]. The results of this study showed that only 4.3% of DKA-cases were with PH <7., 8.7% were with PH=7: 7.1, 7.7% were with PH >7.1: 7.2, 32.4% were with PH >7.2: 7.3 and 7.2% only were with PH > 7.3. The above results showed also that 13.% of ketotic cases were with severe acidosis, 7.7% were with moderate acidosis and 32.4% were with mild acidosis. In a recent European survey, 42% of patients presented with DKA [23], among whom 33% had mild DKA (ph <7.3) and 9% severe DKA (ph <7. 1). As DKA is an emergency, that requires meticulous care, a physician should be present continuously during the first 6-8h. If this is not possible in a conventional ward, the child should be admitted to an intensive-care unit. This is mandatory in very young children and in children who are in coma or have severe ketoacidosis. Blood glucose and ph must be normalized slowly, over several days if necessary, to avoid an abrupt drop in blood osmolarity that might precipitate cerebral edema. The treatment should then be modified according to the child s progress, which must be carefully monitored [24]. Conclusions and recommendations: From the study of the files of the diabetic children attending the outpatient pediatric clinic of NIDE, it could be concluded that there was no statistical difference between male to female children with female predominance. Most of the diabetic children were from Cairo and Giza as these tow governorates are the nearest ones to the NIDE. The offspring of type 1 diabetic father are more liable to diabetes than offspring of diabetic mother and this goes with the international results. It was concluded also that the artificial cow s milk lactation could not be a precipitating cause for type 1 diabetes in children. Lastly, it could be recommended that it will be essential to diagnose different types of diabetes among diabetic children and to study the prevalence and incidence of diabetes among Egyptian children as the prevalence and incidence still uncertain till now. References 1- SALEM M., EL-SHEIKH N., EL-KHOLY M., et al.: Epidemiological study of IDDM among East Cairo school children. J. Egypt Publ. Health Assoc., 2: 65, WILD S., et al.: Global prevalence of diabetes estimates for the year 2 and projections for 23. Diabetes Care, 27: , JONER, GEIR M.D., Ph.D. 1 ; STENE, LARS C. M.S., Ph.D. 1,2 ; SOVIK, ODDMUND M.D.: Prospective Registration of Type 1 Diabetes in Children Aged, [Epidemiology/Health Services/Psychosocial Research] Diabetes Care, Volume 27 (7), July, pp , HARDY RW., COHN M. and KONRAD R.J.: Automated chemiluminescent assay for c-peptide. J. Clin. Lab. Anal., 14 (1): 17-9, GREY V. and AEBI C.: Immunoturbidimetric method for determination of hemoglobin A1 c. Clin. Chem., 42 (12): 246-7, ZANCHETA R., RUSSO V., PRESOTTO F., et al.: Detection of insulin autoantibodies using an Elisa technique in first-relatives of IDDM patients and in autoimmune patients. Diabetes Res., 6 (4): , SCHERBAUM W.A., SEISSLER J., HEDDERICH U., et al.: Determination of islet cell antibodies using an Elisa system with a preparation of rat insulinoma (RIN A2) cells. Diabetes Res., 1 (2): 97-12, WILD T., SCHERBAUM, GLEICHMANN H., LANDT M., et al.: Comparison of a new anti-glutamic acid decarboxylase (GAD) enzyme-linked immunosorbant assay (ELISA) with radioimmunoassay methods: A multicenter study. Horm. Metab. Res., 29 (8): 43-6, GHALY I., SALAH N., ANWAR O., et al.: Evaluation of control achieved by specialized clinic for diabetic children. J. Arab. Child, 2 (4): 33-11, ARAB M., EL KAFRAWY N., RIFAIE M.R., et al.: Epidemiology of diabetes complications in Egypt. The Egyptian J. of Diabetes, Vol. 7 No. 2 July, 5-65, WAGENER D.K., SACKS J.M., LAPONE R.E., et al.: The Pittsburge srudy of insulin-dependent diabetes mellitus. Risk for diabetes among relatives of IDDM. Diabetes, 31: 136, ALLEN C., PALTA M. and D. ALESSIO D.J.: Risk of diabetes in siblings and other relatives of IDDM subjects. Diabetes, 4: 831, WARRAM J.H., KROLEWSKI A.S., GOTTLIEB M.S., et al.: Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. N. Engl. J. Med., 311: , LAPORTE R.E., FISHBEIN H.A., DARSH A.L., et al.: The Pittesburge insulin-dependent diabetes mellitus (ID- DM) registery: The incidence of insulin-dependent diabetes mellitus in Allegheny Country, Pennsylvania. Diabetes, 3: , WRRAM J.H., KROLEWSKI A.S. and KHAN C.R.: Determinants of IDDM and perinatal mortality in children of diabetic mothers. Diabetes, 37: , WARRAM J.H., MARTIN B.C. and KROLEWSKI A.S.: Risk of IDDM in children of diabetic mothers decreases

7 Mohamad H. El-Hefnawy, et al. 41 with increasing maternal age at pregnancy. Diabetes, 4: , KARVONEN M., PITKANEIMI J. and TUOMILEHTO J.: The onset of age of type 1 diabetes in Finnish children has become younger: The Finnish Childhood Diabetes Registry Group. Diabetes Care, 22: , CHRISTAU B., KORMANN H., CHRISTY M., et al.: Incidence of insulin-dependent diabetes mellitus (-29 years at onset) in Denmark. Acta. Med. Scand Suppl., 624: 54-6, MOLBAK A.G., CHRISTAU BB., MARNER B., et al.: Incidence of insulin-dependent diabetes mellitus in age groups over 3 years in Denmark. Diabet. Med., 11: , NORRIS J.M. and SCOTT F.W.: A meta-analysis of infant diet and insulin-dependent diabetes mellitus: Do biases play a role? Epidemiology, 7: 87-92, NORRIS J.M., BEATY B., KLINGENSMITH G., et al.: Lack of association between early exposure to cows milk protein and beta-cell autoimmunity: Diabetes autoimmunity study in the young (DAISY). JAMA, 276: , SMITH C.P., FITH D., BENNETT S., et al.: Ketoacidosis occurring in newly diagnosed and established diabetic children. Acta. Paediatr, 87: , LEVY-MARCHAL C., PATTERN C.C. and GREEN A.: Eurodiab ACE Study Group. Geographical variation of presentation at diagnosis of type 1 diabetes in children: the EURODIAB Study. Diabetologia, 44 (Suppl. 3): b75- b8, KITABCHI A.E., UMPIERREZ G.E., MURPHY M.B., et al.: Management of hyperglycemic crises in patients with diabetes. Diabetes Care, 24: , 21.