P37 Association between inflammation, speed of psychomotor reaction and risk of diabetes

Abstract

Introduction: The inflammatory JNK (c-Jun N-terminal Kinase) pathway plays a central role in the development of neuroinflammation and type 2 diabetes mellitus (T2DM). The systemic subclinical inflammation is an emblematic feature of T2DM and associated diseases. It is accompanied of activation of inflammatory machrophages which, in a generalized manner, infiltrate and damage a myriad of organs including, among others, CNS and pancreas. Those machrophages, derived from inflammatory monocytes, early overexpress the JNK pathway, even among nondiabetic individuals, especially with obesity. Even though is known that obesity and T2DM impair the CNS, these associations are complex. Prospective studies of high quality have shown that children with high intellectual quotient have a lower prevalence of obesity during adulthood, due to a healthier lifestyle, suggesting that the diabesity-CNS avenue could be bidirectional.

Objectives: To explore relationships between the monocyte expression of JNK, the speed of psychomotor reaction (measure correlated with intelligence) and the risk of T2DM.

Materials and methods: Design: 102 healthy adults Argentinian women (39.7 ± 13.0 years old), free of any medication, were recruited in a cross-sectional epidemiological study. Measures: the active (phosphorylated) form of JNK (JNK-p) was measured by intracellular ELISA in fresh monocytes obtained by plastic adherence from peripheral blood mononuclear cells purified with the Ficoll/Hypaque method. The speed of psychomotor response to multiple visual stimulus (Four Choice Reaction Time, FCRT) was measured with the test of Deary-Liewald, a software which quantifies in milliseconds their mean (FCRT-M) and standard deviation (FCRT-SD). The risk of T2DM was evaluated with the FINDRISC (FINnish Diabetes Risk SCore) questionnaire, and the insulin resistance with the HOMA-IR.

Results: In age-adjusted regression analyses, the monocyte expression of JNK-p and measures of psychomotor speed (FCRT-M y FCRT-SD) were positively associated with multiple risk factors for T2DM including FINDRISC (P = 0.032, 0.008 and 0.001, respectively), HOMA-IR (P <0.0001, 0.025 and 0.0003), BMI (P <0.0001 for all variables), waist circumference, WC (P = 0.04, 0.0007 and <0.0001), and total body fat (P = 0.02, and <0,0001 for both FCRT-M y FCRT-SD). The expression of JNK-p was positively associated, in age-adjusted analyses, with FCRT-M (P = 0.0045) and FCRT-SD (P = 0.0044), the higher inflammation, the higher retarded psychomotor response. In Bayesian mediation tests (tests of Sobel), FCRT-SD, the principal FCRT measure associated with T2DM risk, partially mediated all associations of JNK-p with variables of risk for T2DM such as the FINDRISC questionnaire (36.6%, P = 0.041), HOMA-IR (16.9%, P = 0.044), BMI (43%, P = 0.019), WC (51.4%, P = 0.018) and total body fat (43.3%, P <0.0001). FCRT-M partially mediated the associations of JNK-p with BMI (37.3%, P = 0.028), WC (42.9%, P = 0.012) and total body fat (37.9%, P = 0.030).

Conclusions: The monocyte expression of JNK-p (central inflammatory pathway) was associated with several risk factors for T2DM (FINDRISC questionnaire, BMI, HOMAIR, WC and total body fat), and that was partially mediated by FCRT (lesser psychomotor speed), especially FCRT-SD, results supported by multiple evidences. The higher psychomotor speed, the higher intelligence, a greater correlation with FCRT-SD than FCRT-M. An elevated intelligence during childhood has been associated with a lower
prevalence of obesity in adulthood, due to a healthier lifestyle. The JNK activation has been associated with a retarded psychomotor speed due to its neuroinflammatory action.