The additive effect of type 2 diabetes on fibrinogen, von Willebrand factor, tryptophan and threonine in people living with HIV

Chronic immune activation and ensuing inflammation that accompany HIV infection lead to adverse metabolic consequences and an increased risk of type 2 diabetes (T2D). We examined the additive effects of T2D on circulating biomarkers involved in inflammation, coagulation, and vascular function along with plasma amino acids in people living with HIV (PLWH). This cross-sectional study included PLWH with and without T2D (n=32 total). Analyses involved a multiplex platform for circulating biomarkers and gas chromatography-vacuum ultraviolet spectroscopy for plasma amino acids. In PLWH and T2D, both fibrinogen (2.0 +/- 0.6 vs 1.6 +/- 0.4 mu g/mL, p=0.02) and von Willebrand factor (vWF) (40.8 +/- 17.2 vs 26.7 +/- 13.8 mu g/mL, p=0.02) were increased and tryptophan (47 +/- 6 vs 53 +/- 8nmol/mL, p=0.03) and threonine (102 +/- 25 vs 125 +/- 33nmol/mL, p=0.03) were decreased. Fibrinogen, as a biomarker of inflammation, and vWF, as a biomarker of endothelial dysfunction, are augmented by the combined effects of HIV and T2D and may contribute to the pathogenesis of T2D in PLWH. Chronic immune activation and inflammation compromise the integrity of the intestinal mucosa, which increases mucus production. Tryptophan metabolism is altered by a loss of intestinal membrane integrity and threonine is consumed in the production of mucus. Metabolic competition arising from increased protein synthesis in the setting of chronic inflammation along with the associated loss in intestinal membrane integrity may be a primary mechanism in the pathogenesis of T2D in PLWH and requires further investigation.