This study investigated the relationship between body mass index and hematologic parameters in Korean children and adolescents. Children with obesity have increased body fat mass, blood pressure, glucose, LDL-C, and blood cell counts, including WBC, RBC, and platelets. In particular, BMI SDS is positively and independently associated with hematologic parameters after adjusting for cofounding variables. To our knowledge, this is the largest population-based study of Korean children and adolescents.
It is well known that chronic inflammation around adipocytes plays an important role in obesity-related diseases (4). Because WBC count increases inflammatory status, it is reasonable to assume that WBCs are elevated in patients with obesity. One of the most plausible explanations is that adipose tissue produces IL- 6, a pro- inflammatory cytokine that plays a role in bone marrow granulopoiesis, WBC proliferation, and differentiation (24, 25). In our study, WBC increased by 0.275 (x103/mm3) in children with every 1-point increase in BMI SDS. The elevated WBC count, according to obesity degree, is consistent with previous results (26, 27). Meanwhile, relative elevation of WBC is associated with carotid atherosclerosis and impaired glucose tolerance (28). Tong et al. reported that patients with higher WBC counts had adverse metabolic profiles and elevated WBC counts, even when their levels were within normal range, and these elevations were associated with macrovascular and microvascular complications in T2DM (29). Furthermore, Anna et al. observed a significant decrease in WBC count after bariatric surgery and emphasized the importance of weight loss to reduce WBC count in morbid obesity (26).
Our findings are consistent with those of previous studies that found mean WBC count and MS prevalence increased with increasing degree of obesity in both boys and girls (13, 30). In Colombian children, WBC count was associated with truncal adiposity (12). Increased WBC count was associated with early glucose metabolism derangement and preclinical signs of liver, vascular, and cardiac damage in Italian children (31). Park et al. reported that higher WBC count was positively associated with increased risk of insulin resistance in Korean children and adolescents (32). Lee et al. suggested that elevated WBC count can be a surrogate marker for MS in Korean children and adolescents (13). Therefore, because it is inexpensive, WBC count has been suggested as an effective tool for identifying children with obesity at risk of potential complications (31, 32).
Red cell indices, including RBC count, Hb and Hct, were positively associated with BMI SDS in our study, which was consistent with previous studies. Mărginean et al. (33) reported significantly higher erythrocyte levels in children with obesity than controls, but there was no significant difference in Hb level. Additionally, several studies suggest that RBC is significantly correlated with MS (34, 35), and that Hb is significantly associated with high blood pressure (36). The mechanism of increased RBC cell indices in obesity is not known. Rather, there have been reports of more frequent iron deficiency anemia in subjects with obesity/overweight compared with normal weight subjects (37). This is believed to be largely related to an obesity-induced chronic inflammatory state and the influence of hepcidin. Bekri et al. (38) reported that hepcidin, which is a proinflammatory adipokine, reduces iron bioavailability by controlling the ferroportin-1 exporter, resulting in severe iron deficiency anemia in obesity. Although iron status, nutritional habits, and anemia incidence were not analyzed according to BMI subgroup, BMI SDS was independently associated with RBC indices.
Meanwhile, changes in RBC indices show gender differences. Kim et al. (39) reported that the total numbers of RBC increased significantly in male MS subjects but not in females. All RBC indices increased according to BMI SDS in our study, but the degree of increase differed between boys and girls: RBC count increased by 0.043 (x106/mm3) in boys and 0.019 (x106/mm3) in girls with every 1-point increase in BMI SDS. The increased RBC count in boys was more than twice as high as that in girls. Similar patterns were found in the analyses of Hb and Hct. Obesity is a chronic hypoxia state that causes adipose tissue dysfunction, inflammation, and insulin resistance(40). Chronic hypoxia can contribute to increased production of red and white blood cells. Additionally, ferritin, one of the inflammatory markers, increases in obesity (11), and might be linked to changes in RBC indices. Although adolescent girls typically have more body fat and less muscle than boys, they lose blood and iron periodically due to menstruation. Consequently, the increase in RBC according to increased BMI SDS might be relatively small in girls compared with boys.
Thrombocytosis is thought to reflect the presence of an inflammatory process, and platelet activation plays an important role in accelerating atherothrombosis (17). Lim et al. (41) reported that a higher platelet count was associated with increased prevalence and risk of metabolic syndrome in children and adolescents. In our study, platelet count increased by 8.372 (x103/mm3) with every 1-point increase in BMI SDS: by 8.715 (x103/mm3) in girls and 7.658 (x103/mm3) in boys. Platelet count increments also seem to be influenced by gender. Dorit et al. (16) reported that females with obesity had significantly elevated platelet counts compared with normal weight females, but no significant platelet count elevation was observed in males. Additionally, Charles et al. (42) reported a positive association between obesity and WBC or platelet counts among female officers, but not among male officers. In our study, BMI SDS was positively associated with hematologic parameters, but we also found evidence of sexual dimorphism, especially in red blood cell and platelet levels. Although it was a natural result, the adjusted mean RBC indices in boys was higher than in girls for all subgroups, as was that in RBC indices according to BMI SDS. In contrast, mean platelet count was higher in girls than in boys in all subgroups, with a larger increase in platelet count according to increased BMI SDS in girls. How gender differences affect blood cell composition and how they affect the risk of obesity complication is not well understood. Gender differences remain controversial, and further studies should be conducted.
This study has several limitations. First, this is a cross-sectional study, so it cannot identify causal relationships between obesity and hematologic parameters. Second, our study was conducted in children and adolescents between the ages of 10 and 18 years, so there were no data for children younger than 10 years. Third, pubertal status was not classified or analyzed; thus, the effect of puberty on hematologic changes was not considered. Fourth, we could not determine the mechanism of the relationships between BMI SDS and changes in hematologic indices. With regard to the links between BMI SDS and hematologic parameters, our results might not be appliable to general populations in specific environments, especially for contexts of severe obesity and malnutrition. Several studies showed that children with overweight or obesity have an elevated risk for iron deficiency anemia (43, 44). Nevertheless, this study showed that BMI SDS is an independent factor associated with hematological parameters in a relatively large number of children and adolescents. Our findings provide insights into estimating hematologic changes in children and adolescents with obesity and how to manage them.
In conclusion, this nationally representative population-based study showed that higher BMI is independently associated with high hematologic parameters including WBC, RBC, Hb, Hct, and platelet count in children and adolescents. Our results suggest that obesity is related to changes in the blood system, which might be a potential risk factor for obesity-related disease. When interpreting complete blood count in children and adolescents, it is important to consider its relevance to BMI and recognize that there are differences between boys and girls.