Hypothesized pathways for the association of vitamin D status and insulin sensitivity with resting energy expenditure: a cross sectional mediation analysis in Australian adults of European ancestry

Abstract

Background: The role of vitamin D in human energy expenditure requires confirmation. We explored whether insulin sensitivity (IS)/insulin resistance (IR) mediated the association of vitamin D status (25OHD) on resting energy expenditure (REE).

Methods: REE, body composition (by DEXA) and clinical biochemistry of 155 Australian men and women were collated. A hypothesized mediation pathway through IS/IR on the direct association between 25OHD and REE was modeled, using three surrogate indices of IS/IR: McAuley's insulin sensitivity index (McA), Quantitative insulin sensitivity check index (QUICKI) and triglyceride to glucose ratio (TYG). The modeling was performed on PROCESS SPSS Macro (version 4.0) based on 5000 bootstrapped samples, with and without the adjustment for covariates.

Results: Unadjusted models indicated a sizeable negative mediation by all IS/IR indices but no significant direct effect of 25OHD on REE. On adjustment for covariates, a negative indirect mediation effect of McA [β coefficient (SE) -2.1(0.821); bootstrapped 95% CI:-3.934, -0.703; p < 0.05] and a similar negative mediation of TYG [-1.935 (0.780); bootstrapped 95% CI: (-3.679, -0.622; p < 0.05] was observed. These models also showed a positive direct effect of 25OHD on REE. In contrast, QUICKI made a smaller contribution to the total effect though in the same direction as the other two measures [-0.783 (0.534); bootstrapped 95% CI: (-1.939, 0.134; P > 0.05].

Conclusions: A sizeable, partial, negative mediation of IS/IR on the direct relationship between 25OHD and REE, dampened the total effect of vitamin D on REE. Validation of the proposed causal framework would clarify vitamin D's role in human energy metabolism.

Fig. 1. Model of mediation pathways of insulin sensitivity or insulin resistance on the association between vitamin D status and resting energy expenditure.

A1, A2, A3 are the indirect pathways from 25OHD to each IS/IR index, while the corresponding paths B1, B2 B3 links each IS/IR to REE. Ć is the direct pathway from 25OHD to REE. Total effect of a model is given by C = [Ć + (A x B)]. 25OHD, 25dihydroxycholecalciferol; McA McAuleys index; QUICKI Quantitative insulin insensitivity check index; TYG Triglyceride and glucose index; REE Resting energy expenditure.

Fig. 2. Simplified directed acyclical graph (DAG) of covariates influencing the causal pathway of vitamin D to REE.

The simplified DAG included covariates age, gender, FM fatmass, FFM fat free mass, WC waist circumference, and season. Green line shows causal path and pink line biasing path.