Type 2 diabetes mellitus in children and adolescentsthe beginning of a renal catastrophe?
Wieland Kiess,
Antje Böttner,
Susann Blüher,
Klemens Raile,
Angela Galler and
Thomas Michael Kapellen
Hospital for Children and Adolescents, University of Leipzig, Oststrasse 2125, D-04317 Leipzig, Germany
Correspondence and offprint requests to: Professor Wieland Kiess, MD, Hospital for Children and Adolescents, Oststrasse 2125, D-04317 Leipzig, Germany. Email: kiw{at}medizin.uni-leipzig.de
Keywords: adolescents; body mass index; children; genetics; lifestyle; obesity; renal failure; type 2 diabetes mellitus
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Introduction
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Changes in food consumption and exercise are fueling a worldwide increase in obesity in children and adolescents. As a consequence of this dramatic development an increasing rate of type 2 diabetes mellitus has been recorded in children and adolescents around the world. Both genetic and environmental factors contribute to the pathogenesis of type 2 diabetes. Preventive programmes fighting obesity in children should be developed on a large scale. It is the prevention of obesity that will help to reverse the emerging epidemic of type 2 diabetes. Preventive programmes should focus on exercise training and reduction of sedatory behaviour such as television viewing, should encourage healthy nutrition and support general education programmes, since lower school education is clearly associated with higher obesity rates and hence susceptibility to acquire type 2 diabetes. Until recently it has been assumed that type 2 diabetes mellitus occurs only rarely at a young age. In the mid 1990s, investigators around the world began to observe an increasing incidence of type 2 diabetes. This observation followed a striking increase in both the prevalence and the degree of obesity in children [17]. This review summarizes the presently available data on type 2 diabetes in children and adolescents and points to the danger of diabetic kidney disease at a young age.
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Definition and epidemiology
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Overweight is the most common health problem facing children everywhere in the world [814]. The prevalence of overweight at a young age is increasing worldwide [16]. By 1998, in the United States, the prevalence of overweight among children aged 412 years had increased to 21.8% in Hispanics, 21.5% in African Americans and 12.3% in non-Hispanic whites [16]. Recently, Sinha et al. [7] reported that the prevalence of impaired glucose tolerance was 25% among 55 children and 21% among 112 adolescents with marked obesity. In their sample, type 2 diabetes was identified in 4% of the obese adolescents. In addition, screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome also yields a high number of affected individuals with impaired carbohydrate metabolism [17,18]. The first cases of type 2 diabetes have been found in white UK teenagers [2,7,1921], in Japanese youths [22], in Indian adolescents [23] and young adults and teenagers in Central Europe [4,7]. Obesity (body mass index more than +3 SDS or >99th percentile) was usually present in these patients [1921]. In all ethnic groups in the Unites States, the incidence of type 2 diabetes has increased substantially over the past several years [17,19]. In fact, in the United States, in some populations, type 2 diabetes is now the predominant form of diabetes in children and adolescents [2,5,6,15] and children as young as 8 years of age are now being diagnosed with the disease [19,2429].
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Pathogenesis: genetics and environmental factors
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Both genetic factors and environmental/exogenous factors play a role in the pathogenesis of type 2 diabetes [2,3,5,19,21,30]. Family history, ethnicity and the concordance in monozygotic twins all point to inheritance of the disease while the recent and striking increase in the number of individuals affected points to a pathogenetic role of exogenous factors (Table 1). It is interesting to note that adipose tissue that expands in the obese state synthesizes and secretes metabolites and signalling proteins (Table 2). These factors alter insulin secretion, insulin sensitivity and even cause insulin resistance. The adipose tissue thus seems to play an important role in the pathogenesis of type 2 diabetes. Hence, obesity is the key risk factor for type 2 diabetes at a young age. Pediatric obesity may be defined as body mass index >95th percentile for age and sex taken from large population-based surveys [9,1115,2930]. Changes in specific eating patterns as well as alterations of the level of physical activity at a young age may explain the increase in adiposity among children. Increases have, for example, occurred in respect to the number of meals eaten at restaurants, food availability, portion sizes, snacking and meal-skipping, as well as in regards to hours spent in front of the TV set [1719].
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Diagnosis and clinical presentation
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The criteria of the diagnosis of diabetes are those outlined by the World Health Organisation and the American Diabetes Association guidelines [3]. Frequently, an elevated blood glucose level and the typical symptoms of polyuria, polydipsia and unexplained weight loss lead to the diagnosis. Obese children with a family history of type 2 diabetes and particularly African American, native American and Hispanic children are at risk. Acanthosis nigricans and hyperandrogenism are seen regardless of the ethnic background of the patients and represent clinical indicators for the presence of type 2 diabetes [24]. The well-known complications of diabetes such as hyperlipidaemia and hypertension (see below) must also be addressed in children and adolescents, who until now have not normally been screened for these conditions [19]. It is important to note that even early in life, substantial co-morbidity is found in children with type 2 diabetes and obesity [1012,14]. Among the most common sequelae of childhood obesity are hypertension, dyslipidaemia and psychosocial problems. These disorders lead in their turn to additional co-morbidity such as cardiovascular disease in early adulthood [20]. It is therefore mandatory to carefully screen all obese children for hypertension and dyslipidaemia [25,27,30].
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Consequences in adult life
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The proportion of the population that is obese or overweight increases steadily with each decade of life until about the age of 60 years in Western societies [6,8,9,11]. Since many obese children stay obese in adulthood, the co-morbid conditions associated with obesity later in adult life represent a major health burden in industrialized societies. For example, in a study of 854 subjects, 8% of 1- or 2-year-olds without obese parents were obese in adulthood, while 79% of 1014-year-olds who were obese and had at least one obese parent remained obese in adulthood [9,10]. In addition, childhood obesity seems to actually increase the risk of subsequent morbidity whether or not obesity persists in adulthood [30]. Physical performance is directly related to cardiorespiratory fitness in adolescents and therefore could serve as a predictor of subsequent cardiovascular disease [26]. The Bogalusa Heart Study shows that fitness and absence of overweight at a young age can prevent the occurrence of atherosclerosis, coronary artery disease and hypertension [23,24]. On the other hand, positive effects of a reduction of fat mass on the improvement of metabolic risk factors in obese children have been shown [30].
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Treatment and prevention
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Because obesity is the number one risk factor for type 2 diabetes, it is imperative that effective treatment for obesity be developed. Therapeutic strategies include all of the following: psychological and family therapy interventions, lifestyle/behaviour modification and nutrition education. The role of regular exercise is emphasized [11,22,26,30]. Multidisciplinary outpatient treatments are considered to be the most effective [9,16]. Health insurance providers and policy makers should strongly support obesity prevention programmes as the most cost-effective therapy for type 2 diabetes. Exercise and physical activity have both an effect on body weight reduction as well as on insulin sensitivity [25,26]. Any comprehensive treatment protocol for type 2 diabetes should therefore include exercise programmes and physical training. Most importantly, lifestyle intervention programmes have turned out to be more effective than pharmacotherapy for the prevention of progression from impaired glucose tolerance to overt type 2 diabetes in obese adults [3,2729].
However, long-term treatment including pharmacotherapy may be necessary for the majority of very obese adolescents. This is the case because diet and exercise programmes alone and in combination with educational interventions have proven to fail under most circumstances [28]. At the present time, two of the medications used to treat obesity in adults, orlistat and sibutramine, are increasingly used in obese adolescents as well. The American Diabetes Association has concluded for the moment that metformin is safe and effective for treatment of type 2 diabetes in paediatric patients [2,5]. However, great care should be exerted when prescription of antiobesity medication is considered for children [15,28]. Most of these drugs have not yet been sufficiently studied with respect to long-term efficacy, safety and overall long-term effects in children and adolescents [11,12,14]. Even less is known about therapy in chil-dren with comorbid conditions which frequently accompany type 2 diabetes mellitus. There are no evidence-based guidelines for what therapy to use in obese children or when to employ it for hyperlipidaemia and hypertension.
The treatment of type 2 diabetes in the young age groups is particularly challenging because of the diverse linguistic, geographic, cultural, social, economic and political barriers. The latter influence the access to, acceptance of, and success of treatment [16]. As was pointed out recently, we need to improve our communication and cross-cultural skills in order to effectively treat type 2 diabetes. Sometimes, it might actually be necessary to wait a few more weeks or months before considering pills or insulin in a youth who is making progress (with respect to diet and exercise interventions) [15,16].
A population and community approach for prevention of obesity in childhood and hence type 2 diabetes in childhood and adolescence seems to be the most promising and reasonable treatment strategy available at the moment. However, primary prevention has proven to be difficult or impossible in most societies [2730]. Good nutrition and modest exercise for pregnant women as well as monitoring of intrauterine growth of the child are mandatory. After birth, rapid weight gain should be avoided and principles of good nutrition and physical activities should be taught at all ages [30]. Breast feeding should strongly be recommended. Children's food choice can be influenced by early intervention and guidance. In fact, teacher training, modification of school meals and physical education are effective in reducing risk factors for obesity [13,14,2527]. The cost-effectiveness of group and mixed family-based treatments for childhood obesity has been tested and proven. The effect of weight loss on comorbid conditions and most importantly on the development of type 2 diabetes has been proven [30].
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Perspectives
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Obesity is the most common chronic disorder in the industrialized societies. In some countries, the prevalence of obesity in childhood and adolescence has become higher than that of asthma and eczema [911]. Childhood obesity is associated with substantial co-morbidity and late sequelae [11,14,20,27]. While diagnostic strategies are straightforward, treatment remains frustrating both for the patient, the family and the multidisciplinary team caring for obese children. In our opinion, much more attention should be given to the development of preventive strategies early in life. Finally, and most importantly, public awareness of the ever increasing health burden and economic dimension of the childhood obesity epidemic is of upmost importance.
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Acknowledgments
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W.K. is supported in part by a grant from BMBF, IZKF Leipzig, Leipzig, Germany (grant B11 and B15), an unrestricted educational grant from Pfizer, USA, and the 6th Framework Programme, European Union. A. Böttner and K. Raile gratefully acknowledge grants from the German Diabetes Society (DDG) and Ely Lilly International Foundation (K.R.).
Conflict of interest statement. None declared.
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