Sickle cell disease (SCD) is a group of genetic conditions that result from the inheritance of abnormal genes, thereby resulting in the production of abnormal hemoglobin in red blood cells (Akinyanju, 2015). The most common and most severe form of SCD, sickle cell anemia (SCA), refers to homozygosity for the sickle hemoglobin (Hb), known as HbSS (Piel et al., 2017). Hemoglobin polymerization leads to abnormally rigid and adhesive red blood cells (RBCs) that obstruct blood vessels, leading to tissue damage from poor perfusion in HbSS, hence provoking inflammation, as they stimulate and damage surrounding tissues and cells (Serjeant, 1997) (Platt, 2000). Keikhaei et al. showed that pro-inflammatory cytokines, especially lL-8 and IL-17 were increased in SCD patients in the steady state when compared to those in controls (apparently normal individuals) and increased in the crisis state when compared to the steady state (Keikhaei et al., 2013). This suggests that there is a background inflammation in the steady state which escalates during crisis.

The body mass index (BMI) is broadly used to categorize a person as underweight, normal weight, overweight, or obese based on tissue mass (muscle, fat, and bone) and height (Malcolm, 2015). Historically, it is well documented that children with SCD were underweight, particularly those with HbSS due to a characteristic basal hypercatabolic metabolism (Thomas et al., 2000; Barden et al., 2000).

Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid oxidation (Díez and Iglesias, 2003). Adiponectin is secreted from adipose tissue (and also from the placenta during pregnancy) into the blood. It is a specific protein with presumptive antiatherogenic, insulin-sensitizing, and anti-inflammatory characteristics (Chen et al., 2006; (Hotta et al., 2000; (Bełtowski et al., 2008). Adiponectin is considered important in the etiopathogenesis of many vascular and inflammatory disorders due to its anti-inflammatory actions (Zhu et al., 2008; (Cui et al., 2011). It also inhibits the synthesis of pro-inflammatory cytokines such as IL-6, IL-18, and TNF-α synthesis by blocking NF-κB activation (Yamaguchi et al., 2005; Chandrasekar et al., 2008; Ouchi and Walsh, 2017).

Exploring the role of adiponectin in sickle cell anemia hence becomes important, given that sickle cell anemia has a background chronic inflammatory state and adiponectin may be an important therapeutic target in its management.

There was a total of 84 subjects recruited for this study which included 25 homozygous sickle cell (HbSS) subjects in the steady state, nine homozygous sickle cell (HbSS) patients whose crisis were resolving, 25 heterozygous sickle cell (HbAS) subjects, and 25 hemoglobin phenotype AA subjects. The HbSS subjects in the steady state were 14 nonpregnant females and 11 males; HbSS in crisis resolution included eight females and one male; HbAS included 16 males and 9 females, while HbAA included 14 males and 11 females. Their age range was between 10 and 48 years with the median age of the homozygous sickle cell subjects in the steady state being 25.50 years; the median age for the homozygous sickle cell subjects in crisis resolution was 27.00 years and that for the heterozygous sickle cell subjects was 23.00 years and the HbAA controls was 24.00 years (Table 1). Table 1 also shows the mean BMI (kg/m) in the various hemoglobin phenotype groups. A significant difference was observed in the mean BMI between the different hemoglobin phenotype groups. However, there was no significant difference in the mean BMI between the homozygous sickle cell anemia patients in the steady and crisis resolution states and between the sickle cell anemia in crisis resolution and the control group (p > 0.05).

Table 2 shows the median levels of adiponectin in the different hemoglobin phenotype groups. There was no significant difference in the median serum levels of adiponectin in the different hemoglobin phenotype groups and between sickle cell anemia patients in the steady state and crisis resolution state.

Table 3 shows that disease severity in SCA patients in the steady state had no correlation with serum adiponectin (p = 0.87). Figure 1 shows the relationship between serum levels of adiponectin and sickle cell disease severity for subjects in the steady state.

We have shown from this study that the mean serum adiponectin levels were not significantly different amongst the subjects from the different hemoglobin phenotypes, which is in contrast to the findings by Makis et al., who reported elevated adiponectin levels in steady state sickle cell anemia patients when compared with control subjects. This seems to suggest that in our data set of sickle cell anemia patients in the steady state, adiponectin does not constitute part of the endocrinopathy that affects these patients. Genetic variation could be the likely explanation of this difference between our data set and that of Makis et al. (2012).

The finding from this study reveals that the BMI is significantly decreased in sickle cell anemia in the steady state when compared with that of the control group (HbAA) is corroborated by Odetunde et al. (2016). Poor growth and nutrition are common in children with sickle cell anemia (SCA), which was demonstrated by Oredugba et al. in which the nutritional status in children with SCA negatively affected the anthropometric status, disease severity, and body composition of the patients (Oredugba, 2002). Some have hypothesized that underweight in SCA is caused by a hypermetabolic state, which increases energy demand that may lead to an undernourished state if not offset by increased nutrient consumption (Hibbert et al., 2006). Increased expenditure of energy at rest is a major metabolic change associated with HbSS. Barden et al. reported that energy expenditure at rest is approximately 15–20% higher in adolescents with HbSS than HbAA (Barden et al., 2000). This study showed no significant disparity in the BMI of subjects in the steady state when compared to those in crisis resolution, which is in agreement with the study by Iwalokun et al. (2011). This may be because the crisis duration may not be long enough to significantly alter the patients weight.

Although Makis et al. found a positive correlation between adiponectin and inflammatory markers, we found no correlation between adiponectin and disease severity. This may be because our disease severity scoring system is a composite of many parameters and therefore is more robust in predicting actual disease severity.

Our finding agrees with the report by Hall et al. (2018) which showed no association between BMI of sickle cell anemia subjects and disease severity. Also, no correlation was found between age and disease severity, which contrasts with the study by Adegoke and Kuti (2013), who found a positive correlation between age and disease severity.

Our data suggest that adiponectin does not seem to constitute part of sickle cell endocrinopathy in steady state sickle cell anemia patients at Nnewi, Southeast Nigeria. Also from the study, we found that the subjects with sickle cell anemia in crisis resolution and steady states had lower BMI values than HbAA and HbAS subjects. We therefore recommend that the nutritional needs of patients living with sickle cell anemia should be given more attention to improve the general well-being of the patients.