Increasing Prevalence of Type 2 Diabetes Mellitus in Thai Children and Adolescents Associated with Increasing Prevalence of Obesity

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1 Ο Freund Publishing House Ltd., London Journal of Pediatric Endocrinology & Metabolism, 16, 7177 (2003) Increasing Prevalence of Type 2 Diabetes Mellitus in Thai Children and Adolescents Associated with Increasing Prevalence of Obesity S. Likitmaskul, P. Kiattisathavee, K. Chaichanwatanakul, L. Punnakanta, K. Angsusingha and C. Tuchinda Division of Endocrinology and Metabolism, Department of Peditrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand ABSTRACT Type 2 diabetes mellitus (DM) is being diagnosed more frequently in children and adolescents. Thailand has a low incidence of childhood DM. This study reviewed patients with DM in the Division of Pediatric Endocrinology, Faculty of Medicine, Siriraj Hospital compared to our previous study. The results demonstrate that type 2 DM in Thai children and adolescents has increased from 5% during to 17.9% during Mean age was 11.6 years. Mean BMI was 27.8 kg/m 2. Fiftysix percent were diagnosed on routine examination. The period of increase in type 2 DM is associated with an increase of obesity prevalence from 5.8% in 1990 to 13.3% in This result emphasizes the importance of encouraging daily physical activity and healthy diet in our populations and also alerts our pediatricians and endocrinologists to the possibilities of type 2 DM in these age groups. KEY WORDS type 2 diabetes mellitus, body mass index, obesity, children, adolescents, Thailand Reprint address: Supawadee Likitmaskul, M.D. Division of Endocrinology and Metabolism Department of Pediatrics Faculty of Medicine, Siriraj Hospital Mahidol University Bangkok 10700, Thailand sislk@mahidol.ac.th INTRODUCTION Childhood and adolescent diabetes mellitus (DM) in Thailand is uncommon but not rare. During the past decade, epidemiology studies have reported a low incidence of 0.19/100,000/year during and /100,000/yearr during ' 3. However, according to our report 4, we found an increasing number of newly diagnosed cases in our center during winter and summer seasons. The classification of DM during was 93.3% type 1, 5% of type 2 and 1.7% other types 4. Interestingly, several studies have reported an increasing prevalence of type 2 DM in children and adolescents since 1990, especially in populations such as AfricanAmericans, Native Americans, Hispanics and Japanese 5 " 8. These results are concomitant with an increased prevalence of obesity 7 " 9. In Thailand, the national income has been increasing rapidly. The gross national product (GNP) has increased from 50,000 million baht in 1960, to 600,000 million baht in 1980, and to 4 million million baht in This has obviously brought about changes in our society. Owing to globalization, and imitation of youths' lifestyle around the world, especially in eating patterns and fashion, Thai society has changed from an agricultural lifestyle to an industrialized lifestyle with an increase in sedentary activities. A national nutritional assessment survey reported that the total fat content in dietary intake has increased from 8.9% of total daily calories in to 21.8% in and up to 26.3% in Meanwhile, only 5% of women and 13% of men aged between 15 and 24 years spend leisure time on outdoor activities; the rest watch television, listen to the radio, read and sleep 14. A national public health survey showed an increasing amount of overweight in all age groups; the number of overweight VOLUME 16, NO. 1,

2 72 S. LIKITMASKUL ET AL. children aged 612 years increased significantly from 5.8% in to 13.3% in These numbers varied in different types of schools, with some private schools in Bangkok (the capital city) having as many as 30% overweight pupils, as shown in Table 1. Surprisingly, even in the slum area of Bangkok, we also found 15% of children aged 615 years to be overweight in the last survey in (Table 1). These data alert us to this serious public health problem. The present study aimed to investigate whether this is a new trend in the causation of DM in Thai children and adolescents, and also to characterize the clinical manifestations of type 2 DM in Thai youth. PATIENTS AND METHODS We reviewed the medical records of patients with newly diagnosed DM aged 014 years presenting from January 1997 to December 1999 at the Endocrine Unit, Pediatric Department, Faculty of Medicine, Siriraj Hospital, Mahidol University. Patients were informed that the data were collected for an epidemiological study. The individual data at diagnosis included signs and symptoms of DM, age, weight, height, birth weight, family history of DM, hypertension and heart disease, and acanthosis nigricans. Initial laboratory investigations, including blood glucose, serum ketones, electrolytes, lipid profiles, antibodies to glutamic acid decarboxylase (GAD), insulin autoantibodies (IAA), glycosylated hemoglobin (HbAu) and insulin level, were also noted. Oral glucose tolerance tests (OGTT) were carried out in patients with type 2 DM. The types of DM were differentiated according to the report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus 18 and as recommended by Rosenbloom et α/. 8. The diagnostic criteria for type 2 DM included obesity (weight for height >95 percentile for age), hyperglycemia, negative GAD and IAA antibodies, and insulin therapy not required until December 2001, and either one sign of insulin resistance (acanthosis nigricans, hypertension, hyperlipidemia) or measurable fasting insulin level. For type 1 DM, the criteria for diagnosis included hyperglycemia with ketosis plus either positive antibodies or requirement for continuing insulin therapy. Clinical manifestations at diagnosis, and initial management of type 2 DM were also recorded. Weight for height was calculated as actual weight (kg) divided by ideal weight for height on the Thai national growth chart 19 multiplied by 100. Body mass index (BMI) was calculated by weight (kg) divided by [height (m)] 2. Student's ttest was used for data analysis. TABLE 1 Prevalence of overweight in children aged 515 years in Bangkok metropolitan area during the last 10 years in relaiion to different types of school Type of school (%) Universitycontrolled schools Private schools Government schools ] 3 3 Metropolitan schools Slum area Total no. of children 1,675 2,885 2, JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM

3 TYPE 2 DIABETES MELLITUS IN THAI CHILDREN 73 RESULTS There were a total of 39 patients diagnosed with DM during the study period. Twentyeight patients (71.8%) were diagnosed with type 1 DM. Seven patients (17.9%) were diagnosed with type 2 DM. Another four patients (10.3%) had other types of DM PraderWilli syndrome, systemic lupus erythematosus (SLE) and Lasparaginaseinduced diabetic ketoacidosis (DKA) during leukemia treatment (Table 2). Clinical manifestations and laboratory data of patients with type 2 and type 1 DM are shown in Table 3. Mean age at diagnosis of type 2 DM was close to the adolescent age (11.6 years old) compared to 7.8 years old in patients with type 1 DM (p = 0.001). In the type 2 group, the patients were obese; mean weight for height was 159.1% and mean BMI was 27.8 kg/m 2, compared to 107.6% (p = ) and 16.8 kg/m 2 (p <0.0001) in the type 1 group, respectively. Mean HbAi c was lower in the type 2 group at 9.5% compared to 11.9% (p = 0.08) in the type 1 group. Hypercholesterolemia and hypertriglyceridemia were frequent in both groups. GAD and IAA antibodies were not detected in the type 2 group. Acanthosis nigricans was found in 71.4% of patients with type 2 DM but not found in patients with type 1 DM. Fasting insulin levels were measured in patients with type 2 DM and the mean level was found to be 28.8 μυ/ml. DKA was found in 78% of patients with type 1 DM and 14.2% of patients with type 2 DM. Of the seven patients with type 2 DM, three were female and four were male. Six out of the seven had records of birth weight, and all birth weights were normal. One patient had no family history of DM, hypertension or heart disease. Only three patients (44%) presented with signs and symptoms of DM; two (28%) presented during acute illness (asthmatic attack and acute leukemia); the remaining two patients (28%) were detected during OGTTs as part of obesity evaluation. In the patient with leukemia, the patient had a history of weight loss and presented with DKA during L asparaginase induction for leukemia therapy. After stopping Lasparaginase, he was controlled with a diabetic diet for 3 months, after which an OGTT was carried out and found to be positive. He tested positive for both acanthosis nigricans and family history of DM. The management regimen in type 2 DM in children has been under discussion. Three patients were started with insulin injections, and discontinued by 2 weeks, after which two patients received oral antihyperglycemic drugs and one TABLE 2 Classification of childhood and adolescent diabetes mellitus (age 014 years) in the Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, during Jan 1997Dec 1999 compared to our previous study 4 Total number Type 1 DM Type 2 DM Other type of DM Cases/year Our Previous Study 4 Jan 1987Dec 1996 No. % (ßthalassemia major) 5.9 Present study Jan 1997Dec 1999 No. % :, 'V I i (PraderWilli syndrome [1], ; SLE [1], leukemia [2]) >ιλι 13.0 VOLUME 16. NO. 1,2003

4 74 S. LIK.ITMASK.UL ET AL. TABLE 3 Clinical and laboratory manifestations of type 1 and type 2 diabetes mellitus in Thai children aged 014 years Type 1 DM Type 2 DM ρ value Age at diagnosis (yr; range) 7.8 ±3.9 ( ) 11.6 ±2.1 ( ) Wt for Ht (%; range) ± 16(79146) ±21 (134194) BMI (kg/m 2 ; range) 16.8 ±2.5 (12.723) 27.8 ± 3.2 ( ) F:M 1.15:1 0.75:1 Family history of DM 57% Family history of DM or hypertension/heart disease 85% Acanthosis nigricans 0% 71.4% DKA at onset 78% 14.2% Fasting insulin (μυ/ml) 28.8 ±21 (1375) AntiGAD positive 53% 0% IAA positive 47% 0% HbA, c (%; range) 11.9 ±2.5 ( ) 9.5 ±3.6 ( ) 0.08 Cholesterol >170 mg% 68.1% 71% Triglycerides >130 mg% 33% 43% patient was diet controlled. Another four patients had initial therapy with oral antihyperglycemic agents two patients combined sulfonylurea and biguanide (metformin); two (who had no symptoms of DM and were detected during OGTT) had only biguanide (metformin). After 3 months, every patient received metformin and only two patients had this combined with sulfonylurea. No one required ongoing insulin therapy (Table 4). DISCUSSION The diagnostic criteria for type 2 DM in children are still not conclusive; clinical longterm follow up is important. However, our patients with type 2 DM were all obese, hyperglycemic, had negative antibodies, did not require ongoing insulin therapy, and had no DKA episode during follow up. They all had measurable fasting insulin levels, as shown in Table 3, and did not have any clinical characteristics of syndromes or causes for the WHO classification of 'DM of other type'. In the group diagnosed with type 1 DM, all continue to require insulin therapy until the present. The main differences between the two groups are with/without insulin therapy for blood glucose control, and negative/positive antibodies. In the type 2. DM group, HbAi c was improved by oral hypoglycemic drugs and weight control with a diet and exercise program during follow up, as shown in Table 4. Type 2 DM in children and adolescents has increased in the Thai population compared to our previous study 4, from 5% to 17.9%, as shown in Table 2. The majority of patients were in the early adolescent age group and in obese children. Acanthosis nigricans were found in 71.4% of patients. Only 44% had significant signs and symptoms of DM. Fiftysix percent were incidentally diagnosed on either routine physical JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM

5 TYPE 2 DIABETES MELLITUS IN THAI CHILDREN 75 TABLE 4 Management and follow up of individual patients with type 2 diabetes mellitus Patient # Initial management Insulin injection 3d 2 wk 1 wk Sulfonylurea Metformin (mg/d) Diet control ' Continued management After 3 mo. Metformin (mg/d) Sulfonylurea + + After 1 yr Metformin (mg/d) Sulfonylurea no med. After 2 yr Metformin (mg/d) Sulfonylurea no med. Follow up HbA, c (%) Initial After 3 mo. treatment After 1 yr treatment After 2 yr treatment BMI (kg/m 2 ) Initial After 3 mo. treatment After 1 yr treatment After 2 yr treatment _ 30.4 _ 28.2 examination or during acute illness. The period of increase was concomitant with an increase in the prevalence of obesity in the country. These results support the view that an emerging epidemic of type 2 DM in the young is taking place in the Thai population. Thailand has a significantly low incidence of childhood and adolescent DM, but has a relatively high prevalence of type 2 DM in adulthood, especially at older age Therefore, we can predict that the number of patients with type 2 DM in our country will be much higher in the near VOLUME 16, NO. 1,2003

6 76 S. LIKITMASKUL ET AL. future, and related to childhood obesity. This result should alert all physicians to making differential diagnosis of type 1 and type 2 DM in the young. We suggest that it is very important to pay attention to overweight in late childhood and adolescent age, whether or not there is any sign of insulin resistance; further investigations on ßcell function or close observation for evidence of type 2 DM should be done. These results should also alert public health officials to encourage daily physical activity, less sedentary behavior, and a high fiber, low fat, low calorie diet, for future prevention of the disease. Further research directed at an understanding of the basic biology of insulin action and production as well as genetic factors of specific ethnic groups may be helpful for the future management and prevention of type 2 DM. CONCLUSIONS These data demonstrate an increase of type 2 DM in Thai children and adolescents similar to that in other countries. This result should alert pediatricians and endocrinologists to consider this diagnosis in this group of patients. ACKNOWLEDGEMENTS These data were presented at the 26 th Annual Meeting of ISPAD, Los Angeles, CA, USA, The authors wish to thank the ISPAD 2000 organizing committee for their kind support and also Ms Amornrat Pipatsathiant and Ms Tassanee Yenlukroy for their helpful assistance. REFERENCES 1. Tuchinda C, Angsusingha K, Chaichanwatanakul K, Likitmaskul S, Vanasaeng S. The epidemiology of insulin dependent diabetes mellitus (IDDM): report from Thailand. J Med Assoc Thai 1992; 75: Panamonta O, Laopaiboon M, Tuchinda C. Incidence of childhood type 1 (insulin dependent diabetes mellitus) in northeastern Thailand. J Med Assoc Thai 2000; 83: Patarakijvanich N, Tuchinda C. Incidence of diabetes mellitus type 1 in children of southern Thailand. J Med Assoc Thai 2001; 84: Likitmaskul S, Angsusingha K, Morris S, Kiattisakthavee P, Chaichanwatanakul K, Tuchinda C. Type 1 diabetes in Thai children aged 014 year. J Med Assoc Thai 1999; 82: PinhasHamiel O, Dolan LM, Daniels SR, Standiford D, Khoury PR, Zeitler P. Increased incidence of non insulin dependent diabetes mellitus among adolescents. J Pediatr 1996; 128: Neufeld ND, Raffal LJ, Landon C, Chen YDI, Vadheim CM. Early presentation of type 2 diabetes in Mexican American youth. Diabetes Care 1998; 21: Kitagawa T, Owada M, Urakami T, Yamauchi K. Increase incidence of non insulin dependent diabetes mellitus among Japanese school children correlates with an increased intake of animal protein and fat. Clin Pediatr 1998; 37: Rosenbloom AL, Young RS, Joe JR, Winter WE. Emerging epidemic of type 2 diabetes in youth. Diabetes Care 1999; 22: Young TK, Dean HJ, Flett B, WoodSteimann P. Childhood obesity in a population at high risk for type 2 diabetes. J Pediatr 2000; 136: National Statistical Report Bangkok: National Statistical Office, Office of Prime Minister. 11. Nutrition Survey for Thailand, OctoberDecember. Bangkok: Interdepartmental Committee on Nutrition for National Defense (ICNND); December Third National Nutrition Survey Report. Bangkok: Department of Health, Ministry of Public Health, A Study of Nutrition and Lipid Profiles in Labour and Administrative Population. Bangkok: Department of Health, Ministry of Public Health, A Study of Lifestyle in Thai Youth (aged 1524 years old) Thai Health Status. Bangkok: Institute for Population and Social Research, Mahidol University, Chittchang U. Development of simple anthropometric tools for growth monitoring in primary school children. D.Sc. Thesis (Nutrition), Mahidol University, Ruangdarakanon N. Health status in school children aged 612 years. Department of Health Survey. Bangkok: Ministry of Public Health, 1996; KlanKlin S, Asaranuruk S. Nutrition and nutritional status of school aged children in slum area, Bangkok. J Health 1999;81: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000; 23: s4sl Chavalittamrong B, Tampradub S, Vanprapar N. Height and weight of Thai children: high socioeconomic group of some selected urban populations. J Med Assoc Thai 1989; Chaisiri K, Pongpaew P, Tungtrongchitr R, Phonrat B, Kulleap S, Kuhathong C, Suttiwong P, Intarakhao C. Prevalence of abnormal glucose tolerance in Khon Kaen province and validity of urine stick and fasting blood sugar as screening tools. J Med Assoc Thai 1997; 80: JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM

7 TYPE 2 DIABETES MELLITUS IN THAI CHILDREN 21. Suwanwalaikorn S, Nitiyanant W, Puavilai K. Prevalence of diabetes mellitus and impaired glucose tolerance in high risk Thai population, comparing old and new criteria for diagnosis. 11 th AsiaOceania Congress of Endocrinology, April 1998, Seoul, Korea (Abst). VOLUME 16, NO. 1,2003

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