Abstract
An increase in the prevalence of pediatric type 2 diabetes mellitus (T2DM) has been reported by numerous studies in the United States during the past two decades. Available data from Europe are scarce, but also suggest the rising prevalence of this disease in overweight children. The aim of this study was to determine the prevalence of previously undiagnosed T2DM, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in a clinic cohort of otherwise healthy overweight and obese Caucasian children and adolescents living in Serbia. The study group consisted of 301 subjects (176 girls, 125 boys) aged 5.2–18.9 years, with body mass index >90th percentile. Oral glucose tolerance test was performed in all subjects. Previously undiagnosed T2DM was discovered in 0.3% (n=1) and impaired glucose regulation in 15.9% (n=48) of the subjects. Isolated IFG was detected in 4.3% (n=13), isolated IGT in 8.3% (n=25) and combined IFG and IGT in 3.3% (n=10) of the subjects. Disturbances of glucose metabolism were present in a substantial number of the subjects, which emphasizes the need for prevention and treatment of childhood obesity.
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Introduction
The epidemic of childhood obesity is accompanied by increased rates of associated comorbidities in the pediatric population.1 Type 2 diabetes mellitus (T2DM) is emerging in the young as one of the most alarming consequences of childhood obesity.2
The global prevalence of T2DM in children and adolescents is difficult to establish. Most of the epidemiological data regarding pediatric T2DM comes from the United Staets, with an estimated prevalence of 4% in obese children and adolescents, while more than 20% of obese youth have impaired glucose tolerance (IGT).3, 4
In Europe, there are no data on population-based incidence and prevalence of T2DM in children and adolescents, though the rising prevalence of T2DM has been observed in studies conducted in clinic cohorts of overweight and obese children, ranging from 0.1% in Italy to 1.9% in Hungary.2, 5 Prevalence of IGT reported by these studies varies from 4.5 to 17.3%, and while similar data are available for Germany, France and Finland, there are so far no data for most of Europe, including Serbia.2, 6, 7
Subjects and methods
We studied a group of 301 overweight and obese children as well as adolescents of Caucasian origin. There were 176 female and 125 male subjects, aged 5.2–18.9 years, with a mean age of 13.3±3.1 (mean±s.d.) years. The main inclusion criteria were diet-induced overweight or obesity (body mass index (BMI) >90th percentile). Patients with secondary obesity syndromes and other illnesses, including previously diagnosed T2DM, were excluded from this study. Informed consent was obtained from the parents of all participants or, when appropriate, from the patients, after the hospital ethics committee approval.
Pubertal development
Pubertal development was assessed according to Tanner stages8, 9 and categorized into three groups: prepubertal (Tanner stage I), pubertal (Tanner stages II and III) and late pubertal/postpubertal (Tanner stages IV and V).
Oral glucose tolerance test (OGTT) and laboratory measurements
After a 12-h overnight fast, oral glucose tolerance test (OGTT) was performed in all subjects according to established recommendations.10 Subjects were given glucose at a dose of 1.75 g per kg of body weight (maximum 75 g). Blood samples were drawn at baseline and after 60 and 120 min to measure glucose concentration. Glucose regulation was assessed according to the American Diabetes Association guidelines.11 Normal glucose regulation was defined as fasting glucose <5.6 mmol l−1 and 120 min glucose <7.8 mmol l−1. Impaired fasting glucose (IFG) was defined as a fasting glucose level of 5.6–6.9 mmol l−1 and IGT was defined as a 120-min glucose level of 7.8–11.0 mmol l−1. T2DM was defined as a fasting glucose level of ⩾7.0 mmol l−1 and/or 120-min glucose level of ⩾11.1 mmol l−1. The term impaired glucose regulation was used for all subjects with IFG, IGT or T2DM.
In addition, baseline, 60- and 120-min insulin concentrations were measured, as well as fasting levels of triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein cholesterol, uric acid and transaminases.
Calculations
BMI percentiles and standard deviation scores (BMI-SDS) were calculated in accordance with the WHO growth reference charts using AnthroPlus software.12, 13 Children were then categorized as being overweight (BMI >90th but ⩽97th percentile) or obese (BMI>97th percentile).
Waist circumference percentiles were calculated according to the reference values by Fernandez et al.,14 and blood pressure percentiles according to the current European guidelines.15
The degree of insulin resistance was determined by homeostatic model assessment-insulin resistance16 and calculated as the product of the fasting glucose and insulin concentrations (in mmol l−1 and mU l−1, respectively) divided by 22.5.
β-Cell function was assessed using the insulinogenic index, calculated as the ratio of the increase in the insulin level to the increase in the glucose level during the first 60 min of oral glucose tolerance test (OGTT). Although the insulinogenic index (IGI) is usually calculated during 30 min of oral glucose tolerance test (OGTT), the 60-min insulinogenic index (IGI) correlates well with the 30-min index and the early insulin response obtained using a hyperglycemic clamp technique.3, 17
Statistical analysis
The differences in the means of variables between groups were tested using both parametric and nonparametric tests depending on the distribution of the variables. No adjustment for multivariate analysis was carried out because of the observational character of the study and relatively low prevalence of impaired glucose regulation.
Probability values of <0.05 were considered to be significant, and values are expressed as frequencies or means±s.d. unless otherwise stated. SPSS version 10.1 (SPSS, Chicago, IL, USA) was used for analysis.
Results
Clinical data
By study design, all subjects had BMI >90th percentile, 282 (93.7%) children were obese (BMI >97th percentile) and 19 (6.3%) were overweight. The mean BMI of the study group was 32.4±5.9 kg m−2 (range: 19.0–53.7 kg m−2), and the mean BMI-SDS was 3.2±1.2 (range: 1.3–9.7).
In all, 71 (23.6%) of the children were prepubertal, 65 (21.6%) patients were in Tanner stages II or III and 165 (54.8%) were in Tanner stages IV or V.
Prevalence of IFG, IGT and T2DM
Impaired glucose regulation was present in a total of 49 (16.2%) patients. Isolated IFG was discovered in 13 (4.3%) subjects, isolated IGT in 25 (8.3%) and combined IFG and IGT (IFG&IGT) in 10 (3.3%) patients (Figure 1). Previously undiagnosed T2DM was discovered in one subject (0.3%).
Clinical and metabolic characteristics of children with impaired glucose regulation
Selected clinical and metabolic characteristics of the subjects with IFG, IGT and IFG&IGT compared with patients with normal glucose regulation are shown in Table 1. In order to maintain the validity of the results, the subject with T2DM has been excluded from further analysis.
Compared with patients with normal glucose regulation, subjects with impaired glucose regulation were more likely to be in later stages of pubertal development, and had higher triglyceride concentrations, higher 120-min insulin levels, higher degree of insulin resistance and β-cell dysfunction. Although the difference between genders was not statistically significant, higher prevalence of impaired glucose regulation was observed in female subjects (χ2, df=1, P=0.055). No differences were found for chronological age, BMI, BMI-SDS, waist circumference, blood pressure and basal levels of insulin, uric acid, liver function tests, high-density lipoprotein, low-density lipoprotein and total cholesterol.
Discussion
With the rising worldwide prevalence of childhood obesity, T2DM has emerged as a new threat to the pediatric population and future generations of adults.2, 18 Scarce available data on the prevalence of pediatric T2DM in Europe are mainly derived from multiple clinical studies, each with some recruitment bias.5
The results of the first report regarding T2DM in a clinic population of otherwise healthy overweight and obese youth living in Serbia indicate a low prevalence of previously undiagnosed T2DM in this population, but a substantial prevalence of other disturbances in glucose metabolism. These findings correlate well with the results of other European clinical studies, and, in the absence of population-based prevalence data, provide the only insight regarding pediatric T2DM in the region.2, 5, 7
Subjects with impaired glucose regulation had elevated triglycerides, higher 120-min insulin levels, higher degree of insulin resistance and β-cell dysfunction, which, together with similar findings reported in other pediatric studies, urges for further longitudinal research in the metabolic consequences of these prediabetic states in childhood.3, 7, 19
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Vukovic, R., Mitrovic, K., Milenkovic, T. et al. Type 2 diabetes mellitus and impaired glucose regulation in overweight and obese children and adolescents living in Serbia. Int J Obes 36, 1479–1481 (2012). https://doi.org/10.1038/ijo.2011.273
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DOI: https://doi.org/10.1038/ijo.2011.273
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