Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (−5%, P < 0.05), whereas both LC+Ex (−16%, P < 0.001) and LC (−12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: −32%, LC: −45%, and LC+Ex: −44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (−76%, P = 0.035) and a tendency for a reduction in LC (−70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (−27%, P = 0.001) and LC+Ex (−35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.

What is the central question of this study? Does passive heat stress of +2°C oesophageal temperature change concentrations of circulating arterial endothelial- and platelet-derived microparticles in healthy adults? What is the main finding and its importance? Concentrations of circulating endothelial- and platelet-derived microparticles were markedly decreased in heat stress. Reductions in circulating microparticles might indicate favourable vascular changes associated with non-pathological hyperthermia. Interest in circulating endothelial- and platelet-derived microparticles (EMPs and PMPs, respectively) has increased because of their potential pathogenic role in vascular disease and as biomarkers for vascular health. Hyperthermia is commonly associated with a pro-inflammatory stress but might also provide vascular protection when the temperature elevation is non-pathological. Circulating microparticles might contribute to the cellular adjustments and resultant vascular impacts of hyperthermia. Here, we determined whether circulating concentrations of arterial EMPs and PMPs are altered by passive heat stress (+2°C oesophageal temperature). Ten healthy young men (age 23 ± 3 years) completed the study. Hyperthermia was achieved by circulating ∼49°C water through a water-perfused suit that covered the entire body except the hands, feet and head. Arterial (radial) blood samples were obtained immediately before heating (normothermia) and in hyperthermia. The mean ± SD oesophageal temperature in normothermia was 37.2 ± 0.1°C and in hyperthermia 39.1 ± 0.1°C. Concentrations of circulating EMPs and PMPs were markedly decreased in hyperthermia. Activation-derived EMPs were reduced by ∼30% (mean ± SD; from 61 ± 8 to 43 ± 7 microparticles μl ; P < 0.05) and apoptosis-derived EMPs by ∼45% (from 46 ± 7 to 23 ± 3 microparticles μl ; P < 0.05). Likewise, circulating PMPs were reduced by ∼75% in response to hyperthermia (from 256 ± 43 to 62 ± 14 microparticles μl ). These beneficial reductions in circulating EMPs and PMPs in response to a 2°C increase in core temperature might partly underlie the reported vascular improvements following therapeutic bouts of physiological hyperthermia.

Background Circulating microparticles have emerged as biomarkers and effectors of vascular disease. Elevated rates of cardiovascular disease are seen in HIV ‐1–seropositive individuals. The aims of this study were to determine: (1) if circulating microparticles are elevated in antiretroviral therapy–treated HIV ‐1–seropositive adults; and (2) the effects of microparticles isolated from antiretroviral therapy –treated HIV ‐1–seropositive adults on endothelial cell function, in vitro. Methods and Results Circulating levels of endothelial‐, platelet‐, monocyte‐, and leukocyte‐derived microparticles were determined by flow cytometry in plasma from 15 healthy and 15 antiretroviral therapy–treated, virologically suppressed HIV ‐1–seropositive men. Human umbilical vein endothelial cells were treated with microparticles from individual subjects for 24 hours; thereafter, endothelial cell inflammation, oxidative stress, senescence, and apoptosis were assessed. Circulating concentrations of endothelial‐, platelet‐, monocyte‐, and leukocyte‐derived microparticles were significantly higher (≈35%–225%) in the HIV ‐1–seropositive compared with healthy men. Microparticles from HIV ‐1–seropositive men induced significantly greater endothelial cell release of interleukin‐6 and interleukin‐8 (≈20% and ≈35%, respectively) and nuclear factor‐κB expression while suppressing anti‐inflammatory microRNAs (miR‐146a and miR‐181b). Intracellular reactive oxygen species production and expression of reactive oxygen species –related heat shock protein 70 were both higher in cells treated with microparticles from the HIV ‐1–seropositive men. In addition, the percentage of senescent cells was significantly higher and sirtuin 1 expression lower in cells treated with HIV ‐1–related microparticles. Finally, caspase‐3 was significantly elevated by microparticles from HIV ‐1–seropositive men. Conclusions Circulating concentrations of endothelial‐, platelet‐, monocyte‐, and leukocyte‐derived microparticles were higher in antiretroviral therapy–treated HIV ‐1–seropositive men and adversely affect endothelial cells promoting cellular inflammation, oxidative stress, senescence, and apoptosis. Circulating microparticles may contribute to the vascular risk associated with HIV ‐1 infection.