NDT Advance Access originally published online on September 22, 2004
Nephrology Dialysis Transplantation 2004 19(11):2693-2696; doi:10.1093/ndt/gfh455
Nephrol Dial Transplant Vol. 19 No. 11 © ERA-EDTA 2004; all rights reserved
Editorial Comment
Type 2 diabetes mellitus in children and adolescents—the 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 21–25, D-04317 Leipzig, Germany
Correspondence and offprint requests to: Professor Wieland Kiess, MD, Hospital for Children and Adolescents, Oststrasse 21–25, 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 [
1–7].
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 [
8–14]. 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
4–12 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,
19–21], 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 [
19–21]. 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,
24–29].
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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,
11–15,
29–30].
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
[
17–19].
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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
[
10–12,
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 10–14-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,
27–29].
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 [27–30]. 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 [13,14,25–27]. 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
[
9–11]. 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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References
|
|---|
- Pinhas-Hamiel O, Dolan LM, Daniels SR. Increased incidence of non-insulin-dependent diabetes mellitus among adolescents. J Pediatr 1996; 128: 608–615[CrossRef][ISI][Medline]
- Kapellen T, Raile K, Blüher M, Galler A, Paschke R, Kiess W. Type-2-Diabetes bei Kindern und Jugendlichen – ein weltweites Problem. Diabetes Stoffwechsel 2001; 10: 165–169
- American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care 2000; 23: 381–389[ISI][Medline]
- Brosnan CA, Upchruch S, Schreiner B. Type 2 diabetes in children and adolescents: an emerging disease. J Pediatr Hlth Care 2001; 15: 187–193[Medline]
- Ortega-Rodriguez E, Levy-marchal C, Tubiana N, Czernbichow P, Polak M. Emergence of type 2 diabetes in an hospital based cohort of children with diabetes mellitus. Diabetes Metab 2001; 27: 574–578[Medline]
- Kiess W, Gausche R, Keller A, Burmeisetr J, Willgerodt H, Keller E. Computer-guided, population based screening system for growth disorders (CrescNet) and on-line generation of normative data for growth and development. Horm Res 2001; 56 [Suppl 1]: 59–66
- Sinha R, Fisch G, Teague B et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002; 346: 802–810[Abstract/Free Full Text]
- Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. Br Med J 2000; 320: 1240–1243[Abstract/Free Full Text]
- Kiess W, Galler A, Reich A, Muller G, Kapellen T, Deutscher J, Raile K, Kratzsch J. Clinical aspects of obesity in childhood and adolescence. Obes Rev 2001; 2: 29–36[Medline]
- Deckelbaum RJ, Williams CL. Childhood obesity: the health issue. Obes Res 2001; 9 [Suppl 4]: 239S–243S
- Strauss RS, Pollack HA. Epidemic increase in childhood overweight, 1986–1998. J Am Med Assoc 2001; 286: 2845–2848[Abstract/Free Full Text]
- Palmert MR, Gordon CM, Kartashov AI, Legro RS, Emans SJ, Dunaif A. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endeocrinol Metab 2002; 87: 1017–1023
- Rowell HA, Evans BJ, Quarry-Horn JL, Kerrigan JR. Type 2 diabetes mellitus in adolescents. Adolesc Med 2002; 13: 1–12[Medline]
- Beck J, Brandt EN Jr, Blackett P, Copeland K. Prevention and early detection of type 2 diabetes in children and adolescents. J Okla State Med Assoc 2001; 94: 355–361[Medline]
- Gower BA. Syndromexin children: influence of ethnicity and visceral fat. Am J Hum Biol 1999; 11: 249–257[CrossRef][ISI][Medline]
- Dean HJ. Dancing with many different ghosts. Treatment of youth with type 2 diabetes. Diabetes Care 2002; 25: 237–238[Free Full Text]
- Johnson KH, Bazargan M, Cherpitel CJ. Alcohol, tobacco, and drug use and the onset of type 2 diabetes among inner-city minority patients. Am Board Fam Pract 2001; 14: 430–436
- Nicklas TA, Baranowski T, Cullen KW, Berenson G. Eating patterns, dietary quality and obesity. J Am Coll Nutr 2001; 20: 599–608[Abstract/Free Full Text]
- Dötsch J, Dittrich U, Rascher W, Kiess W. Macht Fernsehen dick? – Beziehung zwischen Adipositas bei Kindern und Jugendlichen und Konsum alter und neuer Medien. der kinderarzt 1997; 28: 1351–1356
- Daniels SR. Cardiovascular disease risk factors and atherosclerosis in children and adolescents. Curr Atheroscl Rep 2001; 3: 479–485
- Flynn JT. What's new in pediatric hypertension? Curr Hypertens Rep 2001; 3: 503–510[Medline]
- Drinkard B, McDuffie J, McCann S, Uwaifo GI, Nicholson J, Yanovski JA. Relationships between walk/run performance and cardiorespiratory fitness in adolescents who are overweight. Phys Ther 2001; 81: 1889–1896[Abstract/Free Full Text]
- Berenson GS. Bogalusa Heart study: a long-term community study of a rural biracial (black/white) population. Am J Med Sci 2001; 322: 267–274[CrossRef][Medline]
- Freedman DS, Khan LK, Dietz WH, Srinivasan SR, Berenson GS. Relationship of childhood obesity to corornary heart disease risk factors in adulthood: the Bogalusa Heart Study. Pediatrics 2001; 108: 712–718[Abstract/Free Full Text]
- Sahota P, Rudolf MC, Dixey R, Hill AJ, Barth JH, Cade J. Randomised controlled trial of primary school based intervention to reduce risk factors for obesity. Br Med J 2001; 323: 1029–1032[Abstract/Free Full Text]
- Andersen RE, Crespo CJ, Bartlett SJ. Relationship of physical activity and television watching with body weight and level of fatness among children: results from the third National health and Nutrition Examination Survey. J Am Med Assoc 1998; 279: 938–942[Abstract/Free Full Text]
- Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New Engl J Med 2002; 346: 393–493[Abstract/Free Full Text]
- Kay JP, Alemzadeh R, Langley G, D’Angelo L, Smith P, Holshouser D. Beneficial effects of metformin in normoglycemic morbidly obese adolescents. Metabolism 2001; 50: 1457–1461[CrossRef][ISI][Medline]
- Jones KL, Arslanian S, Peterova VA, Park JS, Tomlinson MJ. Effect of metformin in pediatric patients with type 2 diabetes. Diabetes Care 2002; 25: 89–94[Abstract/Free Full Text]
- Kiess W, Böttner A, Raile K et al. Type 2 diabetes mellitus in children and adolescents – a review from a European perspective. Horm Res 2003; 59 [Suppl 1]: 77–84
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Introduction
Definition and epidemiology