Associations Between C-Reactive Protein, Insulin Sensitivity, and Resting Metabolic Rate in Adults: A Mediator Analysis

Abstract

Objective: Long-term positive energy balance promotes the development of obesity, a main risk factor for type 2 diabetes mellitus (T2DM). While an association between increased resting metabolic rate (RMR) and insulin sensitivity (IS) was shown previously, the underlying mechanisms remain unclear. Aim of the mediator analysis was to investigate the role of inflammation within the association between RMR and IS. Methods: Anthropometric, clinical, and lifestyle data were collected according to standard operating procedures. RMR was measured using indirect calorimetry. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as an IS parameter and C-reactive protein (CRP) was measured to represent the inflammatory status. Statistical analyses were performed using SPSS. Results: The analysis included 782 adults (517 females) with a mean age of 32.4 ± 12.0 years and a mean body mass index (BMI) of 24.6 ± 5.2 kg/m². Regression analysis indicated a significant evidence for associations between RMR and HOMA-IR (ß = 39.3 ± 7.3 kcal/d; p ≤ 0.001) and CRP and HOMA-IR (ß = 0.5 ± 0.1; p ≤ 0.001) after adjustment for fat-free mass, sex, age, and study site. Results of the mediator analysis did not support the hypothesis that CRP is a mediator for the association between RMR and HOMA-IR. These results did not change after participant stratification according to sex or BMI. Conclusion: A significant evidence for an association between RMR and IS was shown in a large cohort. However, the inflammatory status, determined via CRP levels, was not a mediator within this association.

Keywords: C-reactive protein; energy expenditure; homeostasis model assessment for insulin resistance; inflammation; insulin sensitivity; resting metabolic rate.

Figure 1

Association between RMR and (A) FFM or (B) BMI according to sex. Black dots represent data for males and open circles represent data for females. RMR, resting metabolic rate; FFM, fat-free mass; BMI, body mass index; R², proportion of variance supposed by regression.

Figure 2

Overview of the mediator analysis. Results are adjusted for FFM, sex, age, study site. *Significant p-values do not change after including CRP into the model. RMR, resting metabolic rate; CRP, C-reactive protein; HOMA-IR, homeostasis model assessment for insulin resistance.