Influence of blood glucose fluctuations on chemotherapy efficacy and safety in type 2 diabetes mellitus patients complicated with lung carcinoma

BACKGROUND Patients with type 2 diabetes mellitus(T2DM)have large fluctuations in blood glucose(BG),abnormal metabolic function and low immunity to varying degrees,which increases the risk of malignant tumor diseases and affects the efficacy of tumor chemotherapy.Controlling hyperglycemia may have important therapeutic implications for cancer patients.AIM To clarify the influence of BG fluctuations on chemotherapy efficacy and safety in T2DM patients complicated with lung carcinoma(LC).METHODS The clinical data of 60 T2DM+LC patients who presented to the First Affiliated Hospital of Ningbo University between January 2019 and January 2021 were retrospectively analyzed.All patients underwent chemotherapy and were grouped as a control group(CG;normal BG fluctuation with a mean fluctuation<3.9 mmol/L)and an observation group(OG;high BG fluctuation with a mean fluctuation≥3.9 mmol/L)based on their BG fluctuations,with 30 cases each.BGrelated indices,tumor markers,serum inflammatory cytokines and adverse reactions were comparatively analyzed.Pearson correlation analysis was performed to analyze the correlation between BG fluctuations and tumor markers.RESULTS The fasting blood glucose and 2-hour postprandial blood glucose levels in the OG were notably elevated compared with those in the CG,together with markedly higher mean amplitude of glycemic excursions(MAGE),mean of daily differences,largest amplitude of glycemic excursions and standard deviation of blood glucose(P<0.05).In addition,the OG exhibited evidently higher levels of carbohydrate antigen 19-9,carbohydrate antigen 125,carcinoembryonic antigen,neuron-specific enolase,cytokeratin 19,tumor necrosis factor-α,interleukin-6,and highsensitivity C-reactive protein than the CG(P<0.05).Pearson analysis revealed a positive association of MAGE with serum tumor markers.The incidence of adverse reactions was significantly higher in the OG than in the CG(P<0.05).CONCLUSION The greater the BG fluctuation in LC patients after chemotherapy,the more unfavorable the therapeutic effect of chemotherapy;the higher the level of tumor markers and inflammatory cytokines,the more adverse reactions the patient experiences.

Ginsenoside Rb1 relieves glucose fluctuationinduced oxidative stress and apoptosis in Schwann cells

Cultured Schwann cells were treated with 5.6 mM and 50 mM glucose alternating every 8 hours to simulate intermittent high glucose. The present study analyzed the neuroprotective effects of 1, 10 and 100 μM ginsenoside Rbl on oxidative damage and apoptosis in Schwann cells induced by intermittent high glucose. Flow cytometry demonstrated that ginsenoside Rbl reduced intermittent high glucose-mediated reactive oxygen species production. Enzyme linked immunosorbent assay showed that 8-hydroxy-2-deoxy guanosine levels in Schwann cells decreased following ginsenoside Rbl treatment. Quantitative real-time reverse transcription-PCR and western blot assay results revealed that ginsenoside Rbl inhibited intermittent high glucose-upregulated Bax expression, but antagonized intermittent high glucose-downregulated Bcl-2 expression in Schwann cells. These effects were most pronounced with 100 μM ginsenoside Rbl. These results indicate that ginsenoside Rbl inhibits intermittent high glucose-induced oxidative stress and apoptosis in Schwann cells.

Influence of High Blood Glucose Fluctuation on Endothelial Function of Type 2 Diabetes Mellitus Rats and Effects of Panax Quinquefolius Saponin of Stem and Leaf

Objective： To observe the influence of high blood glucose fluctuation on the endothelial function of type 2 diabetes mellitus （T2DM） rats and the effects of Panax Quinquefolius Saponin （PQS） of stem and leaf. Methods： The T2DM model was induced by intraperitoneal injection of a small dose of streptozotocin （STZ, 35 mg/kg） plus high fat and high caloric laboratory chow. Then, diabetic rats were divided into steady high blood glucose （SHG） group and fluctuant high blood glucose （FHG） group according to fasting blood glucose coefficient of variation （FBG-CV）, and then, the FHG group rats were divided into 4 groups according to the level of FBG-CV and fasting blood glucose： PQS 30 mg/（kg·d） group, PQS 60 mg/（kg·d） group, metformin hydrochloride control （MHC） group, and FHG control group, 10 in each group. Meanwhile, 10 rats without any treatment were used as normal control （NOR） group. Eight weeks later, the aortic arteries histology, plasma hepatocyte growth factor （HGF）, and serum nitric oxide （NO）, endothelin-1 （ET-1）, tumor necrosis factor α （TNF-α）, and soluble intercellular adhesion molecule 1 （slCAM-1） were measured. Results： In comparison with the NOR group, the level of plasma HGF and serum NO, ET-1 and TNF-α, and slCAM-1 in SHG and FHG control groups were all significantly increased （P〈0.01）; in comparison with the SHG group, plasma HGF and serum NO, ET-1, TNF-α, and slCAM-1 in FHG group were all significantly increased further （P〈0.01 or P〈0.05）; meanwhile, in comparison with the FHG control group, the level of plasma HGF and serum NO, ET-1, TNF- α, and slCAM-1 in PQS and MHC groups were all decreased significantly （P〈0.01）. However, comparison of the aortic arteries histology among groups showed no significant differences either before or after treatment. Conclusion： Blood glucose fluctuation could facilitate the development of vascular endothelial dysfunction in T2DM rats, while PQS could improve the endothelial function of T2DM rats with high blood glucose fluctuation, which may be related to its effects of relieving vessel stress, decreasing vasoconstrictor ET-1 production, preventing compensated increase of NO, and reducing inflammatory reaction.

Continuous Glucose Monitoring in the Patients with Diabetic Nephropathy

The aim of this study was to compare the difference of blood glucose(BG) fluctuation in the patients of type-2 diabetes mellitus(DM-2) with and without clinical diagnosed diabetic nephropathy(DN) by the continuous glucose monitoring system(CGMS).Thirty DM-2 patients with clinical diagnosed DN and fifteen DM-2 patients without complication underwent continuous glucose monitoring for 3 days(72 h) by CGMS.The difference of daily glucose fluctuation in both groups was compared by the parameter of CGMS.The 24-h mean blood glucose (MBG),minimal BG(MIN-BG),area under curve of BG over 7.8(AUC7.8),percentage of time of BG over 7.8 (PT7.8),area under curve of BG over 11.1(AUC11.1),percentage of time of BG over 11.1(PT11.1),as well as mean of daily difference(MODD) were significantly increased in the group of DN,compared with those in the group of DM-2 without complication(all statistic probability P<0.05).No statistical significance of mean amplitude of glycaemic excursion(MAGE) was found.In the group of DN,MBG,standard deviation of blood glucose(SDBG),large amplitude of glycaemic excursion(LAGE),AUC7.8,PT7.8,AUC11.1,PT11.1,MAGE and MODD were(10.7±1.9) mmol/L,(2.5±1.3) mmol/L,(9.2±3.9) mmol/L,3.2±1.7,(81±18)%,1.2±1.0,(42±24)%, (5.8±2.5) mmol/L and(2.6±1.5) mmol/L,respectively.The study showed that the BG level of the patients with DN fluctuated throughout the day.MBG of the patients with DN was higher than that of the patients of DM-2 without complications,with the characteristics of long-lasting high BG period,dramatic instability during the day and especially high postprandial blood glucose.CGMS is a useful tool for physicians to know the details of the change of BG in the patients with DN.

Effect of the change of ghrelin and its receptor on accelerating diabetic encephalopathy by blood glucose fluctuation in GK rats

Objective To explore the the effect of the changes of ghrelin and its receptor(GHSR1a)on accelerating diabetic encephalopathy by blood glucose fluctuation in GK rats.Methods Eight male wistar rats were set as normal control group(NC).16 male GK rats were randomly divided into sustained hyperglycemia group(MS)and blood glucose fluctuation group(MF).MF group