Preoperative carbohydrate load to reduce perioperative glycemic variability and improve surgical outcomes:A scoping review

The detrimental effects of both diabetes mellitus(DM)and hyperglycemia in the perioperative period are well established and have driven extensive efforts to control blood glucose concentration(BGC)in a variety of clinical settings.It is now appreciated that acute BGC spikes,hypoglycemia,and high glycemic variability(GV)lead to more endothelial dysfunction and oxidative stress than uncomplicated,chronically elevated BGC.In the perioperative setting,fasting is the primary approach to reducing the risk for pulmonary aspiration;however,prolonged fasting drives the body into a catabolic state and therefore may increase GV.Elevated GV in the perioperative period is associated with an increased risk for postoperative complications,including morbidity and mortality.These challenges pose a conundrum for the management of patients typically instructed to fast for at least 8 h before surgery.Preliminary evidence suggests that the administration of an oral preoperative carbohydrate load(PCL)to stimulate endogenous insulin production and reduce GV in the perioperative period may attenuate BGC spikes and ultimately decrease postoperative morbidity,without significantly increasing the risk of pulmonary aspiration.The aim of this scoping review is to summarize the available evidence on the impact of PCL on perioperative GV and surgical outcomes,with an emphasis on evidence pertaining to patients with DM.The clinical relevance of GV will be summarized,the relationship between GV and postoperative course will be explored,and the impact of PCL on GV and surgical outcomes will be presented.A total of 13 articles,presented in three sections,were chosen for inclusion.This scoping review concludes that the benefits of a PCL outweigh the risks in most patients,even in those with well controlled type 2 DM.The administration of a PCL might effectively minimize metabolic derangements such as GV and ultimately result in reduced postoperative morbidity and mortality,but this remains to be proven.Future efforts to standardize the content and timing of a PCL are needed.Ultimately,a rigorous data-driven consensus opinion regarding PCL administration that identifies optimal carbohydrate content,volume,and timing of ingestion should be established.

Exenatide once weekly combined with metformin reduced glycemic variability in type 2 diabetes by using flash glucose monitoring system

BACKGROUND Multiple studies demonstrate that fluctuating blood glucose level produces greater damage compared with sustained hyperglycemia.Flash glucose monitoring system is an effective method in documenting blood glucose variability,contributing to better glucose management and reduced hypoglycemic event occurrence.AIM To investigate the improvement in glycemic variability(GV),blood glucose level,and metabolic indexes of patients with type 2 diabetes mellitus after combined treatment of exenatide once weekly(EXQW)and metformin.METHODS Twenty-five patients with type 2 diabetes mellitus suffering from poor blood glucose control under metformin treatment were recruited.The recruited patients were prescribed with oral metformin only(maintaining a dosage of metformin at≥1500 mg/day)for 2 wk(screening period),and then given EXQW(2 mg,subcutaneous injection)for 12 wk(experimental period).The flash glucose monitoring system was used to document blood glucose values during the screening period and the last 2 wk of the experimental period.RESULTS Four patients were excluded for various reasons,yielding a total of 21 patients,including 17 males and 4 females,with an average age of 48.8 years,who completed this study.The estimated glycated hemoglobin,mean blood glucose,fasting and postprandial blood glucose levels,and percentage of blood glucose above 7.8 mmol/L decreased compared to those at baseline(P=0.003,0.003,0.008,0.010,0.014,0.017,and 0.005,respectively),while the percentage of blood glucose between 3.9 and 7.8 mmol/L significantly increased(P=0.005).Parameters of GV including standard deviation of blood glucose,mean amplitude of glycemic excursions,mean of daily difference,area under the curve difference between percentiles 25 and 75,and area under the curve difference between percentiles 10 and 90 were significantly lower compared to that of baseline(P=0.017,0.006,0.000,0.024,0.036,respectively).The durations of blood glucose below 3.9 mmol/L during the day and nocturnal periods significantly increased after treatment(P=0.041 and 0.028,respectively),but there was no significant increase in severe hypoglycemia(<3.0 mmol/L)compared with that at baseline(P=0.207).In addition,some metabolic indicators improved after EXQW treatment.CONCLUSION EXQW combined with metformin can effectively improve blood glucose levels,reduce GV,and improve metabolic indicators.However,there is still a risk of nocturnal hypoglycemia,and careful attention should be paid to patients with EXQW treatment.

Glycemic variability in insulin treated type 2 diabetes with well-controlled hemoglobin Alc and its response to further treatment with acarbose

Background Glycemic variability, an HbAlc-independent risk factor, has more deleterious effects than sustained hyperglycemia in the development of diabetic complications. This study analyzed the characteristics of glycemic variability in type 2 diabetes mellitus （T2DM） with HbAlc 〈6.5% in duration of twice daily premixed insulin treatment and the effect of further treatment with acarbose. Methods Eighty-six T2DM patients who used premixed insulin analogue （insulin aspart 30） twice daily and had HbAlc 〈6.5% and 20 controlled subjects with normal glucose regulation （NGR） were monitored using the continuous glucose monitoring （CGM） system. The mean amplitude of glycemic excursions （MAGE）, mean of daily differences （MODD） were used for assessing intra-day, inter-day glycemic variability. Hypoglycemia was defined as glucose level 〈3.9 mmol/L for at least 15 minutes in CGM. According to reference values of MAGE, T2DM patients were classified into two groups： Iow-MAGE group with MAGE 〈3.4 mmol/L （L-MAGE） and high-MAGE group with MAGE 〉3.4 mmol/L （H-MAGE）. H-MAGE group received further treatment with acarbose for 2 weeks and was monitored a second time with CGM system. Results After first CGM, L-MAGE group had 41 cases, and H-MAGE group had 45 cases. The MAGE and MODD of T2DM group were all higher than those of subjects with NGR （P 〈0.01）. Twenty-four percent （n=11） in H-MAGE group had a total of 13 hypoglycemic events, 10 of the 13 events occurred at night, meanwhile 5% （n=-2） in L-MAGE group had a total of 2 hypoglycemic events, which also occurred at night （hypoglycemic events： 24% vs. 5%, X2=6.40, P 〈0.01）. MAGE value was correlated with hypoglycemia value and 2-hour postprandial plasma glucose value （r=-0.32 and 0.26, respectively, P 〈0.05）. After further acarbose therapy and secondly CGM, MAGE and MODD values in H-MAGE group were all significantly decreased （40%, P 〈0.01, and 15%, P 〈0.05, respectively）, but remained higher than in the subjects with NGR （P 〈0.05）; 2% （n=-l） had a total of 1 hypoglycemic event, incidence significantly decreased （2% vs. 24%, X2=9.61, P 〈0.01）. Conclusions CGM system can detect the glycemic variability and asymptomatic hypoglycemic events of T2DM with well-controlled HbAlc in duration of insulin treatment. Combination therapy of premixed insulin twice daily with acarbose can flat glycemic variability and decrease hypoglycemic events.

Comparison of glycemic variability and glycated hemoglobin as risk factors of coronary artery disease in patients with undiagnosed diabetes

Background The role of chronic hyperglycaemia as a coronary artery disease （CAD） risk factor is well-known, and the glycemic variability is still a matter of debate. The aim of this study was to investigate the association of admission glycemic excursion and hemoglobin Alc （HbA1c） with the presence and severity of CAD in patients with undiagnosed diabetes mellitus （DM）. Methods We studied 286 newly diagnosed DM patients without prior revascularization undergoing coronary angiography for suspected ischaemic chest pain. Patients were grouped into those with CAD and without CAD according to angiographic results. The severity of CAD was assessed using the Gensini score. Glycemic variability, indicated as the mean amplitude of glycemic excursions （MAGE）, was determined by a continuous glucose monitoring system. Serum levels of HbA1c and high-sensitive C-reactive protein （hs-CRP） as well as plasma concentrations of fasting glucose, lipids and creatinine were measured in all patients. Predictors of CAD were determined using multivariate Logistic regression model and receiver-operating characteristic （ROC） curves. Results The newly diagnosed DM patients with CAD were older, and more were male and current cigarette smokers compared with the patients without CAD. The CAD group had significantly higher levels of MAGE and HbA1c. Individuals with high levels of HbA1c （〉7%） or MAGE （〉3.4 mmol/L） had also significantly higher CAD prevalence. Logistic regression analysis revealed that high MAGE level and high HbA1c level were independent predictors for CAD. The area under the receiver-operating characteristic curve for MAGE （0.606, P=0.005） was superior to that for HbA1c （0.582, P=0.028）. Gensini score closely correlated with age, MAGE, HbA^c, hs-CRP, creatinine and total cholesterol. Multivariate analysis indicated that age （P 〈0.001）, MAGE （P 〈0.001）, HbA1c （P=0.022） and hs-CRP （P=0.005） were independent determinants for Gensini score. Conclusions Both admission glycemic excursion and chronic hyperglycaemia are associated with the severity of CAD in newly diagnosed DM patients. MAGE displays a significant value in predicting CAD in patients with undiagnosed diabetes even more than HbA1c.

Glycemic variability:Importance,relationship with physical activity,and the influence of exercise

Glycemic variability is a more sensitive assessment of glycemic health as opposed to traditional clinical mea-surements.It considers all blood glucose concentrations over a given period to better account for glucose oscil-lations that occur and provides clinicians with insight into how individuals regulate and/or maintain their glycemic health.The advancement of continuous glucose monitoring(CGM)allows for the measurement of free-living glucose concentrations while providing a more reliable assessment of treatment of dysregulated glycemic.CGM coupled with management of lifestyle behavioral factors,such as reduced sedentary behavior and increased physical activity and regular exercise,potentially offers a previously untapped method for promoting improved glycemic health through greater regulation of glucose concentrations.The aim of this review is to critically evaluate the evidence regarding the measurement of glycemic variability and summarize the current under-standing of the relationship between glycemic variability,sedentary behavior,physical activity,the influence of a single exercise session or repeated exercise sessions,and exercise training.This review considers information pertaining to the strengths and limitations for measuring glycemic variability and provides insight into future study designs aimed at evaluating the relationship between sedentary behavior and physical activity with,as well as the influence of exercise on,glycemic variability as a primary outcome.

Increased Preoperative Glucose Variability Is Associated with Adverse Perioperative Outcomes Following Orthopedic Surgery in Patients with Type 2 Diabetes Mellitus

The association between glucose variability(GV)and adverse perioperative outcomes in type 2 diabetes mellitus(T2DM)patients undergoing orthopedic surgery was investigated.A retrospective cohort study was performed by analyzing data on T2DM patients receiving continuous blood glucose(BG)monitoring and continuous subcutaneous insulin infusion treatment due to poorly controlled preoperative BG prior to orthopedic surgery.GV was assessed with coefficient of variation(CV).Postoperative and perioperative CV,hypoglycemia cases,and other perioperative outcomes(diabetes preparation time[DPT],length of stay[LOS],and perioperative and infective complication cases)were analyzed.Results showed that a total of 168 patients were grouped into preoperative CV tertiles:1st(n=56):0–0.2921,2nd(n=58):0.2922–0.3779,and 3rd(n=54):0.3780–0.5750.Fasting blood glucose(FBG),perioperative CV,rate of hypoglycemia cases(OR:5.53,95%CI:2.43–12.59)(all P<0.001)and DPT(P=0.024)were higher in the 3rd than in the 1st tertile.After adjustments of covariates,regression analysis indicated that the 3rd tertile was associated with increased perioperative CV(adjusted coefficient=0.515,P<0.001),DPT(adjusted coefficient=0.169,P=0.073),rate of hypoglycemia cases(OR:6.72,95%CI:2.69−16.82,P<0.001)and perioperative complication cases(OR:2.50,95%CI:0.90−7.01,P=0.080).In conclusion,preoperative GV is associated with increased perioperative GV and adverse perioperative outcomes including longer DPT and higher rates of hypoglycemia and perioperative complications.

The Relationship between Hypoglycaemic Episodes and Arrhythmias in Type 2 Diabetes Subjects after Acute Myocardial Infarction with ST-Segment Elevation—A Case Series

Background and Aims: Several studies have shown that hypoglycaemia, especially a severe episode is associated with an increased mortality rate in diabetes mellitus subjects with previous cardiovascular disease or acute coronary syndrome. One of the presumed mechanisms is the proarrhythmic effect of hypoglycaemia related to the prolongation of the action potential, or the catecholamine surge that follows an episode. The aim of this case series analysis was to investigate the relationship between hypoglycaemia and glucose variability with arrhythmic events in type 2 diabetes patients who suffered an acute myocardial infarction. Materials and Methods: We selected patients admitted consecutively to the cardiology department of Clinical Emergency Hospital in Bucharest for a period of three months with acute myocardial infarction and previously diagnosed type 2 diabetes. For each patient, a retrospective continuous glucose monitoring system (CGMS) or glucose sensor (Medtronic® Enlite, USA) and a dual electrocardiograph and blood pressure monitor for 24 hours were available. Also, patients had an oscillometric device (Arteriograph® TensioMed Ltd) for 24 hours or non-invasive monitoring of central blood pressure, pulse wave velocity and augmentation index. The data were analysed using Medtech®, TensioWin® and Carelink iPro® softwares. We used SPSS® version 20.0 (IBM) for the statistical analysis. The results are presented as median and interquartile range (IQR). Results and Discussion: Ten type 2 diabetes patients (4 males, 6 females) with anterior (4/10) and inferior acute myocardial infarction (6/10) were included. They were treated with insulin (3/10), sulphonylurea (Gliclazide) plus Metformin (4/10), Metformin monotherapy (2/10), or all three (1/10). The patients had a median age of 67.5 (3.25) years with a median disease duration of 8 (7.75) years. The median body mass index was 29.54 (5.65) kg/m2. The median HbA1c was 7.9% (3.15) % and C-peptide 3.3 (2.66) ng/ml. There were no significant differences regarding the number of atrial or ventricular premature beats, ventricular or atrial tachycardia or fibrillation, the duration of QT interval, systolic and diastolic blood pressure, aortic pressure, augmentation index, pulse wave velocity between subjects with hypoglycaemia and those without. There was a negative correlation between QTc and glucose values in patients with hypoglycaemia (Spearman coefficient correlation r = -0.232;p Conclusion: Mild hypoglycaemia in type 2 diabetes patients with systolic dysfunction after ST-elevated myocardial infarction did not increase the number of supraventricular premature beats and QTc duration. We suggest that non-severe hypoglycaemia does not increase the risk of arrhythmias in patients with type 2 diabetes.