PEDIATRICOBESITY ORIGINALRESEARCH
Cardiometabolic risk factors and insulin resistance in obese children and adolescents: relation to puberty B. Tobisch1, L. Blatniczky1 and L. Barkai2,3 1
St. John’s and North-Buda United Hospitals of Budapest Municipality, Budapest, Hungary; 2Postgraduate Institute of Pediatrics, Medical and Health Science Center, University of Debrecen, Miskolc, Hungary; 3Department of Theoretical Health Sciences, Faculty of Health Care, University of Miskolc, Miskolc, Hungary Received 20 March 2013; revised 30 August 2013; accepted 12 September 2013
What is already known about this subject
What this study adds
• The prevalence of obesity with concomitant increasing risk for having cardiometabolic diseases is rising in the childhood population. • Insulin resistance has a key role in metabolic changes in these children. • Insulin levels elevate as puberty commences in every individual.
• Children with increased risk for cardiometabolic diseases show significant differences in insulin levels even before the onset of puberty compared with those without risks. • The pattern of appearance of dyslipidaemia also varies in children with risk factors even in the pre-pubertal group from those without risk. • Children with metabolic syndrome display considerably pronounced changes in their metabolic parameters before the onset of puberty, which become more pronounced as puberty passes.
Summary Background: Insulin resistance (IR) has a key role in the metabolic changes in obese children. In commencing puberty, the insulin levels elevate. It is not clear, however, how insulin levels develop if the metabolic syndrome appears.
Objectives: Metabolic changes were assessed in obese children before, during and after puberty to analyse the relationship between IR and puberty in subjects with and without metabolic syndrome. Methods: Three hundred thirty-four obese children (5–19 years) attended the study. The criteria of the International Diabetes Federation were used to assess the presence of cardiometabolic risks (CMRs). Subjects with increased CMR were compared with those without risk (nCMR). Pubertal staging, lipid levels, plasma glucose and insulin levels during oral glucose tolerance test were determined in each participant. IR was expressed by homeostasis model assessment (HOMA-IR) and the ratio of glucose and insulin areas under the curve (AUC-IR). Results: Significantly higher AUC-IR were found in pre-pubertal CMR children compared with nCMR subjects (11.84 ± 1.03 vs. 8.00 ± 0.69; P < 0.01), but no difference was discovered during and after puberty. HOMA-IR differs between CMR and nCMR only in post-puberty (6.03 ± 1.26 vs. 2.54 ± 0.23; P < 0.01). CMR children have dyslipidaemia before the onset of puberty. Conclusions: CMR is associated with increased postprandial IR in pre-pubertal and increased fasting IR in post-pubertal obese children. Dyslipidaemia appeared already in pre-puberty in CMR children. Keywords: Insulin resistance, metabolic syndrome, obesity, puberty.
Address for correspondence: Dr L Barkai, Department of Theoretical Health Sciences, Faculty of Health Care, University of Miskolc, 3508 Miskolc, Mész u.1., Hungary. E-mail: [email protected] © 2013 The Authors Pediatric Obesity © 2013 International Association for the Study of Obesity. Pediatric Obesity 10, 37–44
ORIGINALRESEARCH
doi:10.1111/j.2047-6310.2013.00202.x
ORIGINALRESEARCH
38 |
B. Tobisch et al.
Introduction Childhood obesity, and its associated metabolic complications as concomitant cardiometabolic comorbidity, is rapidly emerging as one of the greatest global challenges of the 21st century. About 110 million children are now classified as overweight or obese (1). Obesity has a prevalence of 15–16% among subjects aged 6–17 years in the United States as well as in Europe. Another 10–15% of children and adolescents appear to be at risk of obesity (2). Children with obesity pass through to adulthood with greatly increased cardiometabolic risks (CMRs) (3,4). Overweight or obesity is not only a risk factor for the metabolic syndrome, but also the most important risk factor for the development of type 2 diabetes mellitus (T2DM) in youth. Indeed, the increasing prevalence of overweight closely parallels the rise in the number of cases of T2DM (5,6). However, about 85% of patients who have T2DM are also obese (7). The insulin resistance (IR) and its complications in children unfortunately and usually progresses in their pubertal transition to adulthood, and affected children tend to die earlier through cardiovascular (CV) events than their own parents (8). Therefore detecting subjects at risk (with metabolic syndrome) among a large number of obese children appears to be a critical step. The criteria of the metabolic syndrome are well described in adult literature, whereas largely because of the normal physiological changes that occur in children and adolescents with respect to growth and puberty, it is difficult to find a standard definition of the syndrome in the paediatric age group (9). To estimate the elevated CMRs, that is to say the metabolic syndrome, different affiliations worked out score systems: one of those is the modified criteria of the Adult Treatment Panel III (ATP III) (10) or another one is the International Diabetes Federation (IDF) scores (11). Both have been adapted to children as well (11–13) However, whatever definition of the syndrome is used, the prevalence of the metabolic syndrome in the paediatric age group has increased worldwide. IR is the principal metabolic abnormality that is common to the development of the metabolic syndrome in both children and adults (9). Its central role in the process is a well-known, clarified phenomenon (3,8,9). During puberty, an increase in insulin levels can be detected both in boys and girls (4,14,15). It is not clear, however, what happens with insulin levels and insulin sensitivity in obese children having increased CMRs. It is also not clear whether fasting or postprandial IR occurs earlier during pubertal development in obese children, and what is the difference between subjects with and without CMR.
Therefore, the aim of this study was to assess CMR factors in obese children and adolescents, and to analyse and compare their insulin levels and IR before, during and after puberty in children having higher risk for cardiometabolic diseases compared with those without risk factors. Children who proved to have significant CV risk factors are given dietary education and lifestyle advices, and referred to diabetes/obesity outpatient clinics for regular follow-up.
Methods Participants Three hundred thirty-four obese children and adolescents (aged 5–19 years) having a waist circumference higher than 90 percentile in their peer group, according to the IDF criteria, were recruited to participate in this study (11). These subjects were selected from two urban outpatient obesity centres of Hungary. The same protocol was used by the same investigators. Data were collected between January 2006 and December 2011. All the participants gave informed consent to participate in the study, which was approved by the regional ethics committee.
Procedures Anthropometric assessments included height, weight, waist circumference, systolic and diastolic blood pressure (BP) measurements, and pubertal staging assessment for each participant. Body mass index (BMI) was calculated by dividing weight (kg) by height squared (m2). The waist circumference was measured with a non-stretchable tape at the narrowest point between the costal margin and the iliac crest (16). Percentiles for waist circumference described by Fernandez et al. were used as reference values (16). Children with a waist circumference higher than or equal to 90 percentile of their peer group were involved in the study. BP was measured using an automatic BP monitor (Omron 0197 Digital Automatic Blood Pressure Monitor, Kyoto, Japan), with the subject in seated position on the left upper arm. Pubertal development was assessed according to Tanner criteria (breast and pubic hair stages for girls; genitalia and pubic hair stages for boys), and subjects were assigned to one of three categories on the basis of pubertal stages: pre-pubertal (T1), pubertal (T2–4) and post-pubertal (T5). CMR was assessed using the IDF’s criteria for the metabolic syndrome in children and adolescents (11). Increased CMR (metabolic syndrome)
© 2013 The Authors Pediatric Obesity © 2013 International Association for the Study of Obesity. Pediatric Obesity 10, 37–44
was defined if an individual had a waist circumference higher than 90 percentile plus two or more findings from the following: elevated fasting plasma glucose (FPG; ≥5.6 mmol L−1), elevated triglyceride (TG; ≥1.7 mmol L−1), decreased high-density lipoprotein (HDL) cholesterol (
Cardiometabolic risk factors and insulin resistance in obese children and adolescents: relation to puberty B. Tobisch1, L. Blatniczky1 and L. Barkai2,3 1
St. John’s and North-Buda United Hospitals of Budapest Municipality, Budapest, Hungary; 2Postgraduate Institute of Pediatrics, Medical and Health Science Center, University of Debrecen, Miskolc, Hungary; 3Department of Theoretical Health Sciences, Faculty of Health Care, University of Miskolc, Miskolc, Hungary Received 20 March 2013; revised 30 August 2013; accepted 12 September 2013
What is already known about this subject
What this study adds
• The prevalence of obesity with concomitant increasing risk for having cardiometabolic diseases is rising in the childhood population. • Insulin resistance has a key role in metabolic changes in these children. • Insulin levels elevate as puberty commences in every individual.
• Children with increased risk for cardiometabolic diseases show significant differences in insulin levels even before the onset of puberty compared with those without risks. • The pattern of appearance of dyslipidaemia also varies in children with risk factors even in the pre-pubertal group from those without risk. • Children with metabolic syndrome display considerably pronounced changes in their metabolic parameters before the onset of puberty, which become more pronounced as puberty passes.
Summary Background: Insulin resistance (IR) has a key role in the metabolic changes in obese children. In commencing puberty, the insulin levels elevate. It is not clear, however, how insulin levels develop if the metabolic syndrome appears.
Objectives: Metabolic changes were assessed in obese children before, during and after puberty to analyse the relationship between IR and puberty in subjects with and without metabolic syndrome. Methods: Three hundred thirty-four obese children (5–19 years) attended the study. The criteria of the International Diabetes Federation were used to assess the presence of cardiometabolic risks (CMRs). Subjects with increased CMR were compared with those without risk (nCMR). Pubertal staging, lipid levels, plasma glucose and insulin levels during oral glucose tolerance test were determined in each participant. IR was expressed by homeostasis model assessment (HOMA-IR) and the ratio of glucose and insulin areas under the curve (AUC-IR). Results: Significantly higher AUC-IR were found in pre-pubertal CMR children compared with nCMR subjects (11.84 ± 1.03 vs. 8.00 ± 0.69; P < 0.01), but no difference was discovered during and after puberty. HOMA-IR differs between CMR and nCMR only in post-puberty (6.03 ± 1.26 vs. 2.54 ± 0.23; P < 0.01). CMR children have dyslipidaemia before the onset of puberty. Conclusions: CMR is associated with increased postprandial IR in pre-pubertal and increased fasting IR in post-pubertal obese children. Dyslipidaemia appeared already in pre-puberty in CMR children. Keywords: Insulin resistance, metabolic syndrome, obesity, puberty.
Address for correspondence: Dr L Barkai, Department of Theoretical Health Sciences, Faculty of Health Care, University of Miskolc, 3508 Miskolc, Mész u.1., Hungary. E-mail: [email protected] © 2013 The Authors Pediatric Obesity © 2013 International Association for the Study of Obesity. Pediatric Obesity 10, 37–44
ORIGINALRESEARCH
doi:10.1111/j.2047-6310.2013.00202.x
ORIGINALRESEARCH
38 |
B. Tobisch et al.
Introduction Childhood obesity, and its associated metabolic complications as concomitant cardiometabolic comorbidity, is rapidly emerging as one of the greatest global challenges of the 21st century. About 110 million children are now classified as overweight or obese (1). Obesity has a prevalence of 15–16% among subjects aged 6–17 years in the United States as well as in Europe. Another 10–15% of children and adolescents appear to be at risk of obesity (2). Children with obesity pass through to adulthood with greatly increased cardiometabolic risks (CMRs) (3,4). Overweight or obesity is not only a risk factor for the metabolic syndrome, but also the most important risk factor for the development of type 2 diabetes mellitus (T2DM) in youth. Indeed, the increasing prevalence of overweight closely parallels the rise in the number of cases of T2DM (5,6). However, about 85% of patients who have T2DM are also obese (7). The insulin resistance (IR) and its complications in children unfortunately and usually progresses in their pubertal transition to adulthood, and affected children tend to die earlier through cardiovascular (CV) events than their own parents (8). Therefore detecting subjects at risk (with metabolic syndrome) among a large number of obese children appears to be a critical step. The criteria of the metabolic syndrome are well described in adult literature, whereas largely because of the normal physiological changes that occur in children and adolescents with respect to growth and puberty, it is difficult to find a standard definition of the syndrome in the paediatric age group (9). To estimate the elevated CMRs, that is to say the metabolic syndrome, different affiliations worked out score systems: one of those is the modified criteria of the Adult Treatment Panel III (ATP III) (10) or another one is the International Diabetes Federation (IDF) scores (11). Both have been adapted to children as well (11–13) However, whatever definition of the syndrome is used, the prevalence of the metabolic syndrome in the paediatric age group has increased worldwide. IR is the principal metabolic abnormality that is common to the development of the metabolic syndrome in both children and adults (9). Its central role in the process is a well-known, clarified phenomenon (3,8,9). During puberty, an increase in insulin levels can be detected both in boys and girls (4,14,15). It is not clear, however, what happens with insulin levels and insulin sensitivity in obese children having increased CMRs. It is also not clear whether fasting or postprandial IR occurs earlier during pubertal development in obese children, and what is the difference between subjects with and without CMR.
Therefore, the aim of this study was to assess CMR factors in obese children and adolescents, and to analyse and compare their insulin levels and IR before, during and after puberty in children having higher risk for cardiometabolic diseases compared with those without risk factors. Children who proved to have significant CV risk factors are given dietary education and lifestyle advices, and referred to diabetes/obesity outpatient clinics for regular follow-up.
Methods Participants Three hundred thirty-four obese children and adolescents (aged 5–19 years) having a waist circumference higher than 90 percentile in their peer group, according to the IDF criteria, were recruited to participate in this study (11). These subjects were selected from two urban outpatient obesity centres of Hungary. The same protocol was used by the same investigators. Data were collected between January 2006 and December 2011. All the participants gave informed consent to participate in the study, which was approved by the regional ethics committee.
Procedures Anthropometric assessments included height, weight, waist circumference, systolic and diastolic blood pressure (BP) measurements, and pubertal staging assessment for each participant. Body mass index (BMI) was calculated by dividing weight (kg) by height squared (m2). The waist circumference was measured with a non-stretchable tape at the narrowest point between the costal margin and the iliac crest (16). Percentiles for waist circumference described by Fernandez et al. were used as reference values (16). Children with a waist circumference higher than or equal to 90 percentile of their peer group were involved in the study. BP was measured using an automatic BP monitor (Omron 0197 Digital Automatic Blood Pressure Monitor, Kyoto, Japan), with the subject in seated position on the left upper arm. Pubertal development was assessed according to Tanner criteria (breast and pubic hair stages for girls; genitalia and pubic hair stages for boys), and subjects were assigned to one of three categories on the basis of pubertal stages: pre-pubertal (T1), pubertal (T2–4) and post-pubertal (T5). CMR was assessed using the IDF’s criteria for the metabolic syndrome in children and adolescents (11). Increased CMR (metabolic syndrome)
© 2013 The Authors Pediatric Obesity © 2013 International Association for the Study of Obesity. Pediatric Obesity 10, 37–44
was defined if an individual had a waist circumference higher than 90 percentile plus two or more findings from the following: elevated fasting plasma glucose (FPG; ≥5.6 mmol L−1), elevated triglyceride (TG; ≥1.7 mmol L−1), decreased high-density lipoprotein (HDL) cholesterol (
