Gender differences in the association of insulin resistance and high-sensitivity c-reactive protein in obese adolescents

Abstract

BackgroundLow-grade vascular inflammation is believed to initiate early atherosclerotic process by inducing insulin resistance (IR), with significant gender differences in adults. We evaluated the relationship between surrogate measures of inflammation and IR in obese adolescents.MethodsThe association among markers of inflammation [high-sensitivity c-reactive protein (hs-CRP)] and IR, cardiometabolic risk factors and body composition was retrospectively examined in 199 obese adolescents [(111 F/88 M), aged 15.5 ± 1.2 years]. Insulin resistance was assessed using homeostatic model assessment for insulin resistance (HOMA-IR).ResultsMales had higher body mass index SD-score (BMI-SDS), fat mass (FM), glucose, insulin, HOMA-IR, HbA1c, hs-CRP, triglycerides: HDL-C (TG:HDL-C) ratio than females (p < 0.05), whereas females had higher c-peptide: insulin ratio than males (p < 0.05). Also, 50.8% of subjects were identified with metabolic syndrome with similar gender distribution (M: 57.9% vs. F: 45.1%, p = 0.32). Hs-CRP was correlated with HOMA-IR in the cohort, even when controlling for FM (r = 0.26; p < 0.0001). However, hs-CRP and HOMA-IR displayed a significant correlation only in females (r = 0.37; p < 0.0001) when adjusting for FM and pubertal status. Also, c-peptide: insulin ratio was inversely correlated with hs-CRP (r = −0.32; p < 0.001) and HOMA-IR (r = −0.62; p < 0.0001) and partially mediated the relationship between these biomarkers only among females (β = 0.36, p < 0.001 to β = 0.18, p < 0.05; Sobel Test: p < 0.01).ConclusionsA positive association between hs-CRP and HOMA-IR was observed only in adolescent girls which was influenced by altered hepatic insulin clearance. This implies that obese adolescent girls may be at greatest risk of developing early atherosclerosis and diabetes.

Importance of anthropometry in assessing insulin resistance as a pre-alarming sign before the onset of metabolic syndrome: a study among apparently healthy subjects

“…Females tend to deposit more fat peripherally when compared to central deposition in males. And, these findings were supported by the earlier reports of Alemzadeh and Kichler [30]. Therefore, female subjects have a high tendency to develop IR-related metabolic abnormalities which suggests that lower total lean body mass and greater fat mass may play a strong role in pathogenesis of IR and related obesity among females.…”

Preadipocytes of obese humans display gender-specific bioenergetic responses to glucose and insulin

“…Nevertheless, our data indicate that improvement of mitochondrial function and the higher oxidative to glycolytic ratio of preadipocytes from obese women could be beneficial. Improved glucose homeostasis and insulin sensitivity is more frequently observed in obese women as compared to age- and BMI-matched men [47], [48], [49], [50], [51], [52]. Our cohort showed trends towards higher insulin sensitivity in women (Appendix A, Table S1).…”

Long Term High Fat Diet Treatment: An Appropriate Approach to Study the Sex-Specificity of the Autonomic and Cardiovascular Responses to Obesity in Mice

“…This sexual dimorphism in the metabolic and inflammatory responses to short term HFD treatments response may likely contribute to the mild cardiovascular alterations reported in obese female rodents. In opposition to female rodents, young adult women are not protected from obesity-associated metabolic and inflammatory disorders, and appear more prone to obesity-related CVD than men (Thorand et al, 2007 ; Alemzadeh and Kichler, 2014 ; Pradhan, 2014 ; Garcia et al, 2016 ), which suggests that current murine models of diet-induced obesity are inappropriate and create the need for new animal models better mimicking the human pathology. Therefore, the present study also aimed at developing a mouse model closely mimicking the human scenario, which would allow testing the hypothesis that sex differences in cardiovascular responses to body weight gain disappear in mice matched for changes in body weight, and in metabolic and inflammatory indices.…”