Effects Of Glucose Variability Research Articles

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

Glucose variability (GV), which describes fluctuations in blood glucose levels within the day, is a phenomenon that is increasingly becoming the target of scientific attention when it comes to increased risk of coronary heart disease. Effects of GV may contribute to the development of metabolic syndrome and type 2 diabetes. Hyperglycemia can lead to oxidative stress resulting in molecular damage due to accumulation of reactive oxygen species (ROS). To discover more about the immediate effects of GV, continuous vs. bolus intravenous glucose administration was applied to 10 healthy men aged 21-30 years over a time frame of 48 h. Whole blood and plasma were analyzed for DNA damage using a comet assay with 3 different treatments (lysis buffer, H2O2, and the lesion-specific enzyme formamidopyrimidine DNA glycosylase (FPG)) as well as for the oxidative stress markers protein carbonyls (PC), unconjugated bilirubin (UCB), and ferric reducing antioxidant power (FRAP). A significant time effect was found in the three DNA damage treatments as well as in PC and UCB possibly due to circadian changes on oxidative stress, but no intervention group effect was observed for any of the markers. In conclusion, bolus vs. continuous glucose administration had no significant acute effect on DNA damage and markers of oxidative stress in healthy men.

Effects of glucose variability on hematopoietic stem/progenitor cells in patients with type 1 diabetes.

Diabetes reduces the levels of hematopoietic stem/progenitor cells (HSPCs), which can contribute to organ and tissue homeostasis. Among patients with diabetes, lower HSPC levels predict the development or worsening of micro- and macro-angiopathy. High glucose variability is also associated with diabetic complications and we have previously shown that acute hypoglycaemia can stimulate stem/progenitor cells. Thus, we evaluated the relationship between glucose variability or time in hypoglycaemia and HSPCs in patients with type 1 diabetes (T1D). Patients with T1D were compared to healthy subjects. HSPCs (CD34+, CD133+, CD34+CD133+, CD34 + CD45dim) were quantified by flow cytometry. Using flash glucose monitoring system for 90days, we calculated several measures of glucose variability and time in hypoglycaemia. Forty-four patients with T1D and 44 healthy subjects were enrolled. Compared to healthy controls, T1D patients had significantly lower levels of HSPCs and duration of diabetes was inversely correlated with HSPC levels. Significant direct correlations were found between HSPC levels and the coefficient of variation of glucose levels or time in hypoglycaemia, which were stronger in patients with short-term than in those with long-standing diabetes. This study confirms the pauperization of HSPCs in T1D patients and demonstrates a potential HSPC-stimulatory effect of hypoglycaemia, which mitigates with long-lasting diabetes. These data are consistent with a model whereby disease chronicity progressively blunts the release of HSPCs in response to adrenergic triggers, like hypoglycaemic events.

Effects of Glucose and Blood Pressure Variability on Oxidative Stress in Type 2 Diabetes with Hypertension

Aims: This study was performed to evaluate the effects of glucose variability (GV) and blood pressure variability (BV) on oxidative stress in type 2 diabetes patients with hypertension. Methods: Fifty-seven inpatients with type 2 diabetes (studied from May 2015 to august 2017) underwent continuous glucose monitoring (CGM) and ambulatory BP monitoring (ABPM) in a cross-sectional study. The plasma total oxidant capacity against N,N-diethylparaphenylendiamine was measured as a marker of oxidative stress using the d-ROMs test. The GV, mean glucose level (MGL), mean amplitude of glycemic excursions (MAGE), and area under the postprandial plasma glucose curve (AUCPP) were measured by CGM. The BV, mean blood pressure (MBP), max blood pressure (MaxBP), minimum blood pressure (MinBP), and standard deviation of blood pressure (BPSD) during the systole (S) and diastole (D) were measured by ABPM over daytime (day), nighttime (night), and 24-hour (24) periods. Results: The 57 participants were 65.3±12.9 years old, with a disease duration of 14.7±12.4 years and HbA1c of 8.5±1.2 %. In univariate analysis, MAGE (r=0.446,p<0.001), night DBPSD (r=0.323,p=0.014), and eGFR (r=0.287, p=0.030) were significantly correlated with the d-ROMs. In the stepwise multiple regression analysis, MAGE (β=0.344, t=3.075, p=0.003), night DBPSD (β=0.230, t=2.034, p=0.047), eGFR (β=-0.234, t=-2.137, p=0.037), and smoking (β=0.315, t=2.873, p=0.006) were identified as independent factors contributing to the d-ROMs (multiple R2 = 0.363). Conclusions: Daily glucose variability and nighttime systolic blood pressure variability are associated with oxidative stress in type 2 diabetes with hypertension. Disclosure M. Ohara: None. H. Nagaike: None. T. Yamamoto: None. T. Hayashi: None. T. Fukui: None. T. Hirano: Speaker's Bureau; Self; Novo Nordisk Inc., AstraZeneca.