Effect of repeated bolus and continuous glucose infusion on a panel of circulating biomarkers in healthy volunteers

Abstract

Hypothesis Glycaemic variability (GV) refers to fluctuations in the blood glucose level and may contribute to complications in patients suffering from Diabetes. Several studies show negative effects of GV on the cardiovascular system, however there is still a lack of conclusive evidence. Using an explorative cardiovascular panel, it is possible to simultaneously measure the effects on proteins relevant for cardiovascular processes. The aim of this study was to investigate the effects of rapid glucose excursions on cardiovascular and metabolic parameters in healthy individuals. Methods An explorative single-blinded cross-over study was performed in ten healthy men. Subjects received 3 times 20 grams of glucose i.v. over 5 minutes or 60 grams of glucose continuously over 3 hours. Blood was taken for repeated measurements of the cardiovascular panel over the following 6 hours and again after 24 and 48 hours. Results We observed a significant elevation of 7 cardiovascular biomarkers (BMP6, SLAMF7, LOX-1, ADAMTS13, IL-1RA, IL-4RA, PTX3) at t = 360min after rapid glucose infusion compared to a continuous glucose infusion. Conclusions Intraday GV seems to have acute effects on cardiovascular proteins in healthy test persons. Rapid glucose administration compared to continuous administration showed significant changes in BMP6, SLAMF7, ADAMTS13, IL1RA, PTX3, IL-4RA and LOX-1. Clinical trial registration NCT04488848.

Effect of Hypoglycemia and Rebound Hyperglycemia on Proteomic Cardiovascular Risk Biomarkers

“…A SOMAscan assay was used to measure 54 of the 92 cardiovascular protein biomarkers previously described [ 19 ], which are the biomarkers available on the SOMAscan panel. These reflected biomarkers are involved in inflammation, cellular metabolic processes, cell adhesion, and immune response and complement activation.…”

“…Glucose variability has been suggested to be associated with increased cardiovascular risk [ 16 ], perhaps through increased oxidative stress [ 17 ], though a degree of controversy remains [ 18 ]. In a study of normal volunteers injected repeatedly with intravenous glucose to mimic intraday glucose variability (3 times 20 g of glucose intravenously over 5 min at intervals of one hour), acute effects on the cardiovascular risk protein markers bone morphogenetic protein 6 (BMP6); signaling lymphocyte activation molecular family 7 (SLAMF7); a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13); interleukin-1 receptor antagonist (IL1RA); pentraxin 3 (PTX3); interleukin 4 receptor alpha (IL-4RA); and lectin-like oxLDL (oxidized low-density lipoprotein) receptor 1 (LOX-1) were reported [ 19 ]. What is unclear is whether this is simply due to the increment in the blood glucose or whether it is the increment followed by the decrement that is responsible for the potential adverse cardiovascular risk marker profile and whether this response could be mimicked by a decrease in blood glucose alone.…”

“…What is unclear is whether this is simply due to the increment in the blood glucose or whether it is the increment followed by the decrement that is responsible for the potential adverse cardiovascular risk marker profile and whether this response could be mimicked by a decrease in blood glucose alone. The aim of this study was to measure the panel of cardiovascular risk proteins previously reported for glucose variability [ 19 ] in type 2 diabetes (T2D) and control subjects undergoing iatrogenic-induced mild prolonged hypoglycemia versus more acute severe hypoglycemia that was reversed immediately with a glucose rebound leading to marked and rapid hyperglycemia.…”

Effect of Repeated Bolus and Continuous Glucose Infusion on DNA Damage and Oxidative Stress Biomarkers in Healthy Male Volunteers

“…As described earlier by Feldbauer et al [22], 10 male volunteers with a mean age of 25 ± 3 (mean ± standard deviation) years (Min 21/Max 30) and a mean BMI of 25.6 ± 2.5 kg/m 2 (22.5/30.9) participated in the study. The mean waist circumference was 90 ± 8 cm (81/110), and the resting heart rate of the volunteers mean was 62 ± 11 bpm (53/88).…”

“…It was approved by the local joint research ethics committee of St. John of God Hospital Linz. This study investigated and described the effects of continuous vs. acute glucose administration on seven cardiovascular biomarkers (BMP6, SLAMF7, LOX-1, ADAMTS13, IL-1RA, IL-4RA, PTX3) [22]. The following inclusion criteria had to be fulfilled: male, non-smoker, between 18 and 40 years of age, HbA1c levels in normal ratio, and no history of type 2 diabetes.…”