A high glycemic burden drives functional and metabolic alterations of human monocytes in patients with type 1 diabetes

Dataset

Description

Diabetes mellitus is associated with serious long-term complications, including increased cardiovascular risk and a higher occurrence of infections. These diabetes-related complications are suggestive of altered responses of the innate immune system. Recent studies have shown that energy metabolism of monocytes is a crucial determinant of their functionality. Here we investigate whether metabolism and function of monocytes are changed in patients with diabetes and aim to identify diabetes-associated factors driving these alterations. Patients with type 1 diabetes (T1D) and healthy age-, sex- and BMI-matched nondiabetic controls were recruited and detailed characteristics related to disease status including diabetes duration and glycemic burden (HbA1c levels) were collected. Monocytes were isolated from peripheral blood to determine immune functionality, metabolic responses and to perform transcriptome analyses. Upon ex vivo stimulation with TLR-4 agonist LPS or TLR-2 agonist P3C, monocytes of patients with T1D secreted lower levels of various cytokines (TNFα, IL-1β and IL-1Ra) and had lower glycolytic rates in comparison to monocytes isolated from matched controls. Stratification based on HbA1c levels revealed that a lower cytokine secretion was coupled to a higher glycolytic rate of monocytes in patients with a higher glycemic burden. Gene expression signatures of circulating monocytes displayed an enhanced inflammatory expression pattern that was associated with this high glycemic burden. A high glycemic burden in patients with T1D promotes expression of inflammatory genes of monocytes in vivo and is coupled to an impaired relationship between metabolism and inflammatory function upon activation ex vivo.
Date made available9 Oct 2020
PublisherWageningen University

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