(OR10-06-23) Hyperglycaemia in Obesity Is Associated With Impaired Ex Vivo T Cell Function: An Interim Analysis of the Nutrition and Immunity (NutrIMM) Study

Objectives: Obesity and its related metabolic complications are associated with immune dysfunction. Little is known regarding the independent contribution of adiposity, hyperglycemia, and dietary patterns in altering immune responses. The aim of this study was to assess the immunophenotype of helper T (Th) cells and T cell function in lean individuals (lean-NG) and individuals with obesity and normoglycemia (obese-NG), glucose intolerance (obese-GI), and type 2 diabetes (obese-T2D).

Methods: Participants were stratified to one of four groups: 1) lean-NG (n=31), 2) obese-NG, (n=17), 3) obese-GI, (n=21) and 4) obese-T2D (n=13). All participants consumed an isocaloric standardized North American type diet (35% fat, 48% carbohydrate, 17% protein) for 4 weeks to dissect out the contribution of diet to that of glycemia on the immune system. Fasting blood samples were collected before and after the intervention. Immunophenotypic characterization was performed in whole blood using flow cytometry to identify the proportion of the following cell populations relative to the T helper population (CD3+CD4+): Th1 (CCR10- CD183+CD185+CD194-CD196-), Th2 (CCR10-CD183-CD185-CD194+CD196-), and Th17 (CCR10-CD183-CD185-CD194+CD196+). Peripheral blood mononuclear cells were isolated and stimulated with phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) to assess T cell function by measuring ex vivo interleukin-2 (IL-2) production (a T cell proliferation marker).

Results: IL-2 production after PHA stimulation was higher in lean compared to Obese-GI and Obese-T2D, whereas after PWM stimulation, Obese-GI and Obese-T2D had lower production compared to Obese-NG. Post-intervention, Obese-T2D had a higher proportion of Th1 cells compared to both the lean and Obese-NG groups and a higher proportion of Th2 cells compared to the lean group only (all p< 0.05). At baseline, Obese-T2D had a higher proportion of Th17 cells compared to all other groups (p=0.002), which was no longer significant after the intervention.

Conclusions: Our interim analysis suggests that the function of T cells decline as hyperglycemia develops in obesity despite increased proportions of Th1 cells, which is in line with the reported increased risk of infection in this population.

Funding Sources: Supported by Canadian Institutes of Health Research