The effects of glucose-containing dialysate during dialysis in maintenance haemodialysis patients with type 2 diabetes

The effects of glucose-containing dialysate during dialysis in maintenance haemodialysis patients with type 2 diabetes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The effects of glucose-containing dialysate during dialysis in maintenance haemodialysis patients with type 2 diabetes Li He, Hui Chen, Lin Chen, Yingjun Zhang, Mingming Liu, Li Liu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4134845/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background ：Type 2 diabetes mellitus (T2DM) is the leading cause of end-stage renal disease (ESRD), and approximately 26%～47% of haemodialysis patients have diabetes. At present, most haemodialysis treatments use glucose-free dialysate. Howerver, the use of glucose-free dialysate resulted in an increased incidence of asymptomatic hypoglycemia during dialysis treatment.The aim of this study was to investigate the effect of glucose-containing dialysate during dialysis in Maintenance haemodialysis (MHD) patients combined with type 2 diabetes. Methods: A randomized controlled study was conducted to select 16 MHD patients with type 2 diabetes from March 2023 to April 2023. Patients were randomly divided into a glucose-containing dialysate group (n=8) and a glucose-free dialysate group (n=8). A Flash Continuous Glucose Monitoring System (CGMS) was used for blood glucose monitoring. The target time in range (TIR) of blood glucose levels, the frequency of dialysis hypoglycaemia and the changes in blood pressure and heart rate were compared between the two groups within 14 days. Results: In the glucose-containing dialysate group, the blood glucose TIR was greater than that in the glucose-free dialysate group within 14 days (50.50% vs. 30.75%, P < 0.05), on dialysis days (75.70% vs. 57.76%, P < 0.05) and on nondialysis days (74.67% vs. 57.76%, P < 0.05). Hypoglycaemia occurred less frequently in the glucose-containing dialysate group than in the glucose-free dialysate group during 4 hours of dialysis treatment (43 vs. 205). The frequency of hypoglycaemia in the glucose-containing dialysate group was significantly lower than that in the glucose-free dialysate group at the second hour of dialysis (P < 0.05). There was no significant difference in blood pressure or heart rate fluctuation between the two groups. Conclusion: Glucose-containing dialysate is beneficial for blood glucose management in MHD patients with type 2 diabetes, and the clinical application of glucose-containing dialysate in MHD patients with type 2 diabetes should be improved. hemodialysis glucose-containing dialysate type 2 diabetes hypoglycemia Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1 Introduction Diabetes is one of the most common chronic diseases, with 463 million adults currently living with diabetes worldwide, and this number is expected to reach 700 million by 2045 [ 1 ]. Type 2 diabetes mellitus (T2DM) is the leading cause of end-stage renal disease (ESRD), and approximately 26%ཞ47% of haemodialysis patients have diabetes[ 2 , 3 ]. Data from the China National Renal Data System (CNDRS) also show that diabetes became the leading cause of new haemodialysis in patients in 2022 (29.9%). The risk of cardiovascular disease (58%~87% vs. 7ཞ58.1%) and death (33%~33.7% vs. 2.3%~24%) in MHD patients with diabetes were greater than those in nondiabetic dialysis patients [ 4 – 7 ]. During the process of haemodialysis, patients with diabetes will have varying degrees of blood glucose fluctuations, among which hypoglycaemia is the most common occurrence, and this change will aggravate the occurrence of CVD [ 8 ]. At present, most haemodialysis treatments use glucose-free dialysate, mainly due to the ease of storage and low cost of glucose-free dialysate [ 9 ]. However, the use of glucose-free dialysate also increased the frequency of asymptomatic hypoglycaemia during dialysis treatment, which may be due to the decrease in the neurohumoural response caused by frequently recurring episodes of hypoglycaemia during dialysis [ 10 ]. Considering the possible problems associated with glucose-free dialysate, several studies have shown that glucose-containing dialysate provides better blood glucose control and less blood glucose fluctuations during haemodialysis treatment. Therefore, the overall adverse effects of MHD combined with type 2 diabetes should be reduced in the short and long term [ 8 , 11 , 12 ]. To reduce the frequency of hypoglycaemia during dialysis, European guidelines have recommended the use of glucose-containing dialysate for dialysis treatment in diabetic nephropathy patients [ 13 ]. The Flash Continuous Glucose Monitoring System (CGMS) is a wearable device that tracks glucose levels in tissue fluid through regular and frequent measurements throughout the day and night [ 6 , 14 ]. Current reports suggest that CGMS are well tolerated. In addition to collecting blood glucose data, wearing the device can also intervene in related behaviours in patients [ 15 ]. The guidelines recommend that people with type 1 and type 2 diabetes wear CGMS to improve their HbA1c levels and reduce the chance of hypoglycaemia [ 10 ]. Four patients who used glucose-free dialysate and wore CGMS for a total of 14 days were previously investigated to observe changes in their blood glucose levels. The results indicated that the mean blood glucose level (MBG) and area under the blood glucose curve (AUC) on dialysis days were lower than those on nondialysis days. At present, studies on the use of glucose-containing dialysate in haemodialysis mainly adopt before-after comparisons. Moreover, the included subjects lacked relevant studies on patients who underwent haemodialysis combined with type 2 diabetes. Therefore, the purpose of this study was to use a CGMS to monitor the effect of glucose-containing dialysate on blood glucose in MHD patients with type 2 diabetes. 2 Subject and Method 2.1 Study Population Patients who underwent regular dialysis at the haemodialysis centre of West China Hospital Sichuan University from February to April 2023 were selected. The inclusion criteria were as follows: (1) diagnosed with type 2 diabetes (ADA 2021 criteria [16]); (2) regular MHD for ≥ 3 months (3 times per week); and (3) aged ≥ 18 years. The exclusion criteria were as follows: (1) had malignant disease or overt infection/inflammation; (2) had been hospitalized for any reason within the past 3 months; and (3) refused to provide written consent. A total of 20 MHD patients with type 2 diabetes were included in this study. Random numbers were generated using SPSS 20.0, and the cells were divided into glucose-containing dialysate and glucose-free dialysate groups. Patients were assigned to the glucose-containing dialysate or glucose-free dialysate group at a 1:1 ratio. Allocation concealment was performed by sequentially numbing, opaque and concealing envelopes. They were opened when patients signed consent and were ready for cannulation and dialysis. This procedure ensured that neither the patients nor the nurses were aware of the group allocation. This study gained approval from the ethics committee of the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (Review (384), 2022). All the subjects signed written informed consent. This study has been registered and approved in the Chinese Clinical Trial Registry( https://www.chictr.org.cn ) , and the registration number is ChiCTR2300068343༈15/02/2023༉. 2.2 Method An AK96 (GAMBRO) Dialysis Machine (version 3.xx) was used with a high-throughput polysulfone hollow fibre membrane haemodialyzer, a membrane area of 1.5 m 2 , and an ultrafiltration coefficient of 48 ml/h/mmHg (OCI-HD150). Blood flow was 220–280 ml/min, and the dialysate flow rate was 500 ml/min. The anticoagulants used were heparin or low-molecular-weight heparin (LMWH). The dialysate components included Na + (138.0 mmol/L), K + (2.0 mmol/L), Ca 2+ (1.5 mmol/L), Mg 2+ (0.5 mmol/L), Cl − (109.5 mmol/L), acetate (3.0 mmol/L), and bicarbonate (32.0 mmol/L). Except for 5.55 mmol/L glucose, the other components were the same in the glucose-containing dialysate and the glucose-free dialysate. All patients were monitored using the Flash Continuous Glucose Monitoring System (CGMS) (Specifications and Models: FreeStyle Libre H). The sensor was placed subcutaneously on the nonarteriovenous fistula (AVF) or tunneled cuffed CVC (TCC) catheterized side of the upper arm and remained fixed for the next 14 days. The patients’ CGMS knowledge was assessed before use, and relevant precautions were explained. The monitor recorded and stored the blood glucose values of the patients every 15 minutes, and the blood glucose values were recorded continuously for 14 days. Patients in the glucose-containing dialysate group were treated with 5.55 mmol/L glucose-containing dialysate (the rest of the dialysate components remained unchanged) for 14 days (6 times). Patients in the glucose-free dialysate group received standard haemodialysis therapy for 14 days (6 times) using glucose-free dialysate. After 14 days, the sensor is removed, and the data are downloaded and stored on a computer and represented in graphs and values. During the study period, patients' insulin use, hypoglycaemic medication, and dietary habits did not change. Patients were advised that their records should be kept when they eat during dialysis. The target blood glucose range was defined as 3.9 ~ 10 mmol/L within the target range, 3 ~ 3.9 mmol/L below the target range, and above the target range 10 ~ 13.9 mmol/L. 2.3 Clinical Outcomes We extracted the blood glucose values collected by CGMS within 14 days to compare the TIR blood glucose levels, the glucose coefficient of variation(CV), and the number of hypoglycemia during dialysis between the two groups. We also compared fasting plasma glucose and fasting C-peptide values between the two groups before and after 14 days. Finally, we compared the changes of blood pressure and pulse rate between the two groups during 4 hours of dialysis. 2.4 Statistical analysis SPSS 22.0 software was used to analyse the data. Normally distributed quantitative data are expressed as ‾x ± s, and nonnormally distributed data are expressed as M (P25, P75). Independent sample t tests and Mann‒Whitney U tests were used for comparisons between groups. Qualitative data are expressed as [n (%)], and comparisons between groups were made using the X 2 test or Fisher exact probability test. P < 0.05 was considered to indicate statistical significance. 3 Results 3.1 General information A total of 20 patients were included in this study; among them, 1 patient in each of the glucose-containing dialysate groups and one in the glucose-free dialysate group had premature sensor shedding, resulting in incomplete CGM readings. One patient in the glucose-containing dialysate group withdrew from the study, and one patient in the glucose-free dialysate group was hospitalized with heart failure and lost to follow-up(Figure 1 ). Finally, the data of 16 patients (8 patients in the glucose-containing dialysate group and 8 patients in the glucose-free dialysate group) were analysed. There was no significant difference in the baseline data between the two groups. (Table 1 ) Table 1 Demographic and clinical indicators (n = 16) All subjects (16) Glucose-containing Dialysate group (8) Glucose-free Dialysate group (8) Gender( Male/Female ) 14/2 7/1 7/1 Age (years) 60.12 ± 9.15 63.37 ± 11.04 56.87 ± 5.77 Duration of dialysis (month) 32(26, 49) 44(15,49) 28(26,40) Duration of diabetes (year) 17.37 ± 8.48 17.12 ± 8.89 17.62 ± 8.65 ESRD cause, n (%) Diabetic nephropathy 10(62.50%) 5(62.50%) 6(75%) Others 6(37.50%) 3(37.50%) 2(25%) Complication, n (%) hypertension 14(87.50%) 7(87.50%) 7(87.50%) cardiovascular disease 9(56.25%) 4(50%) 5(62.50%) diabetic retinopathy 9(56.25%) 5(62.50%) 4(50%) Access type (AVF/TCC) 12/4 7/1 5/3 Hb(g/L) 114.31 ± 12.04 117.00 ± 10.55 111.62 ± 13.51 ALB(g/L) 42.31 ± 2.94 42.76 ± 2.74 41.86 ± 3.26 Glycosylated serum protein(GSP, %) 22.22 ± 8.07 19.28 ± 4.06 25.15 ± 10.16 HbA1c(%) 7.05 ± 1.29 6.72 ± 0.76 7.35 ± 1.67 BMI 25.15 ± 2.53 24.17 ± 2.31 26.13 ± 2.49 Antihypertensive drugs (yes/no) 14/2 7/1 7/1 Diabetes-related medication Insulin(yes/no) 12/4 6/2 6/2 ORAL antidiabetic drug(yes/no) 8/10 3/5 5/3 Total daily energy intake (kal) 1507.75 ± 378.27 1574.93 ± 358.39 1440.58 ± 409.71 Total daily protein intake (g) 49.54 ± 16.43 49.58 ± 18.68 49.51 ± 15.15 Taking food in dialysis (N) 61 26 35 3.2 Changes in relevant indices before and after 14 days in the two groups Fasting blood glucose, fasting C-peptide and the glucose CV were not significantly different between the two groups before and after 14 days of study. The data extracted by the CGMS showed no significant difference in the coefficient of variation of blood glucose between the two groups. However, the blood glucose TIR (14 days, dialysis days and nondialysis days) in the glucose-containing dialysate group was significantly greater than that in the glucose-free dialysate group (P < 0.05). (Table 2 ) Table 2 Changes in blood sugar levels in the two groups after 14 days Glucose-containing Dialysate group Glucose-free Dialysate group P 14 days TIR 50.50 ± 12.99 30.75 ± 15.58 0.016 Dialysis day TIR 75.70 ± 10.89 57.76 ± 17.69 0.028 Nondialysis day TIR 74.67 ± 11.60 55.53 ± 22.36 0.049 14 days glucose CV 35.83 ± 5.19 36.28 ± 8.13 0.897 Dialysis day glucose CV 34.61 ± 5.96 38.70 ± 10.78 0.363 Nondialysis day glucose CV 35.47 ± 7.11 32.36 ± 7.83 0.419 fasting blood-glucose(mmol/L) 0 days 6.50 ± 1.89 9.07 ± 3.59 0.095 after 14 days 5.89 ± 1.10 8.10 ± 3.84 0.156 Fasting C-peptide(nmol/L) 0 days 2.58(2.39, 4.93) 4.13(1.32, 6.72) 0.2 after 14 days 8.90(2.92, 13.3) 4.43(2.99, 11.9) 0.525 Frequency of hypoglycaemia within 1 hour of dialysis 0(0,0) 0 (0,1) 0.382 Frequency of hypoglycaemia within 2 hour of dialysis 0(0,2) 7 (0,8) 0.032 Frequency of hypoglycaemia within 3 hour of dialysis 0(0,1) 5 (0,9) 0.130 Frequency of hypoglycaemia within 4 hour of dialysis 0(0,2) 3 (0,8) 0.234 All patients wore the sensor on the day of dialysis, and the dialysis duration ranged from 5 days after the second dialysis session to all dialysis days before the sensor was removed. The nondialysis days included all nondialysis days from the second day after the sensor was worn to the day before the sensor was removed, for a total of 7 days. The bold font indicates P < 0.05. 3.3 Changes in blood glucose during 4 hours of dialysis During the observation period of 80 dialysis treatments, only one patient in the glucose-free dialysate group experienced 2 symptomatic hypoglycaemic events. Patients in the glucose-containing dialysate group had fewer episodes of hypoglycaemia per hour than those in the glucose-free group, and the number of episodes of hypoglycaemia up to two hours of dialysis was statistically significant (P<0.05) (Table 2 ). Glucose measurements taken every 15 minutes during a 4-hour dialysis period in both groups showed a greater decrease in blood glucose in the glucose-free dialysate group. (Fig. 2) 3.4 Changes in blood pressure and pulse rate during 4 hours of dialysis Blood pressure and pulse rate did not significantly differ between the two groups during dialysis, and the blood pressure and pulse rate were basically maintained at normal levels. However, the systolic blood pressure in the glucose-free dialysate group showed a decreasing trend, and Fig. 2 shows that the decrease in systolic blood pressure in the glucose-free dialysate group was more obvious than that in the glucose-containing dialysate group. (Figure 3, Fig. 4, Fig. 5) 4 Discussion A study by Abeesh showed that patients had significantly greater blood glucose TIR during the glucose-containing dialysate phase than during the glucose-free dialysate phase (33% vs. 18.7%) [ 8 ]. Sangill's study indicated that there was no significant difference in blood glucose levels, but the variability was significantly reduced after the use of glucose-containing dialysate in MHD patients with diabetes [17]. The results of the above studies were similar to those of the present study, in which the 14-day blood glucose TIR (50.5% vs. 30.75%, P < 0.05) of patients in the glucose-containing dialysate group was greater than that in the glucose-free dialysate group. Moreover, the blood glucose TIRs of the two groups on dialysis day (75.7% vs. 57.76%) and nondialysis day (74.67% vs. 55.53%) were greater in the glucose-containing dialysate group. Therefore, the use of glucose-containing dialysate may be more beneficial for blood glucose management in MHD patients with type 2 diabetes. In addition to maintaining the blood glucose TIR on dialysis days, it also has a certain effect on maintaining the blood glucose TIR on nondialysis days. In this study, the blood glucose level in the glucose-free dialysate group decreased gradually from 7.25 mmol/L to 5.02 mmol/L during 4 hours of dialysis (blood glucose results obtained by the sensor every 15 minutes). The blood glucose concentration in the glucose-containing dialysate group decreased from 7.75 mmol/L to 6.23 mmol/L. The decrease in blood glucose in the glucose-containing dialysate group was smaller than that in the glucose-free dialysate group. Previous studies have shown that HD improves insulin resistance and thus enhances muscle glucose uptake. HD can also change the pH of the red blood cell cytoplasm, leading to accelerated anaerobic metabolism and increased glucose consumption [18]. All of the above mechanisms can explain the decrease in blood glucose in patients during dialysis. In addition, during dialysis, asymptomatic hypoglycaemia occurred less frequently in the glucose-containing dialysate group than in the glucose-free dialysate group, which was similar to the results of Abeesh’s study. In the 80 HD treatments in this study, few symptoms were associated with hypoglycaemic events according to the CGMS. One patient in the glucose-free dialysate group had one symptomatic hypoglycaemic event during each of the two dialysis sessions. The occurrence of asymptomatic hypoglycaemia during dialysis may be due to the disruption of the neurohumoural response caused by frequently recurring episodes of hypoglycaemia during HD [19]. Studies have shown that long-term maintenance of low blood glucose levels increases the uptake of glucose by brain cells, thereby reducing the brain's perception of low blood glucose, which may also explain the asymptomatic phenomenon of hypoglycaemic episodes [20]. However, studies have shown that in people with diabetes, chronic hypoglycaemia can lead to impaired cognitive function and an increased risk of death [21, 22]. Therefore, reducing the occurrence of hypoglycaemia in MHD patients with type 2 diabetes is more conducive to their long-term survival and health. Glucose-containing dialysate can effectively reduce the occurrence of asymptomatic hypoglycaemia in MHD patients with type 2 diabetes. Therefore, the clinical use of glucose-containing dialysate in MHD patients with type 2 diabetes is necessary. Sangill suggested that the addition of glucose to dialysate could increase extracellular osmotic pressure, resulting in reduced fluid loss in intracellular compartments and thus reducing the occurrence of dialysis-related hypotension [17, 23]. Their study showed that the use of glucose-containing dialysate led to a significant reduction in systolic and diastolic blood pressure in dialysis patients, but this effect was more significant in nondiabetic dialysis patients and was not observed in MHD patients with diabetes [17]. The mechanism may be that the insulin secretion of nondiabetic dialysis patients increases with increasing dialysate glucose concentration. At physiological concentrations, insulin secretion causes blood vessels to dilate, leading to a drop in blood pressure[24]. Li's study showed that although 5.55 mmol/L glucose-containing dialysate could reduce blood sodium levels, it had no effect on blood pressure during dialysis[ 11 ]. These findings are consistent with the results of the present study. This study showed that during the 4 hours of dialysis, the blood pressure and pulse rate of the two groups fluctuated within the normal range, but the differences were not significant. However, the systolic blood pressure in the glucose-free dialysate group showed a decreasing trend in this study. At present, the effect of glucose-containing dialysate on the blood pressure and pulse rate of MHD patients with diabetes is still unclear and needs further study. Limitation Our study has some limitations. First, this study include a small sample size and a shorter observation period of 14 days for both groups of patients. In addition, this study only observed the use of different dialysates during dialysis, and no uniform intervention was performed on the dietary intake and use of glucose-controlling drugs in all patients, which may be a confounding factor. Finally, there is a lack of observation and comparison of the results of other dialysis measures. Conclusion In conclusion, the use of glucose-containing fluids, as compared with glucose-free fluids, may be beneficial in targeting glucose levels in MHD patients with type 2 diabetes. Glucose-containing dialysate may also affect the occurrence of asymptomatic hypoglycemia during dialysis in patients. The effect of glucose-containing dialysate on MHD with type 2 diabetes needs to be further studied by increasing the sample size and prolonging the observation time. Declarations Author Contribution Li He and Hui Chen are co-first authors; they have contributed equally to this work, and their contributions are the same. Lin Chen and Li He contributed to the conception and design of this study; Hui Chen and Li He carried out the statistical analysis; Yingjun Zhang, Mingming Liu and Li Liu participated in the data collection; Li He and Hui Chen drafted the manuscript; and Lin Chen and Yingjun Zhang critically reviewed the manuscript and supervised the whole study process. All the authors read and approved the final manuscript. Acknowledgement The authors would like to thank all team members who participated in this study. Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. References Teo, Z.L., et al., Global Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis. Ophthalmology, 2021. 128 (11): p. 1580-1591. Kramer, A., et al., The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015: a summary. Clin Kidney J, 2018. 11 (1): p. 108-122. Lu, Y., et al., Changing trends in end-stage renal disease patients with diabetes. Swiss Med Wkly, 2017. 147 : p. w14458. Momose, M., et al., Prognostic significance of stress myocardial ECG-gated perfusion imaging in asymptomatic patients with diabetic chronic kidney disease on initiation of haemodialysis. Eur J Nucl Med Mol Imaging, 2009. 36 (8): p. 1315-21. Schiller, A., et al., Vitamin D deficiency--prognostic marker or mortality risk factor in end stage renal disease patients with diabetes mellitus treated with hemodialysis--a prospective multicenter study. PLoS One, 2015. 10 (5): p. e0126586. Joubert, M. and Y. Reznik, Personal continuous glucose monitoring (CGM) in diabetes management: review of the literature and implementation for practical use. Diabetes Res Clin Pract, 2012. 96 (3): p. 294-305. Haapio, M., et al., Survival of patients with type 1 diabetes receiving renal replacement therapy in 1980-2007. 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Cryer, Reduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans. Diabetes, 1991. 40 (2): p. 223-6. McCall, A.L., et al., Chronic hypoglycemia increases brain glucose transport. Am J Physiol, 1986. 251 (4 Pt 1): p. E442-7. Heller, S.R. and I.A. Macdonald, The measurement of cognitive function during acute hypoglycaemia: experimental limitations and their effect on the study of hypoglycaemia unawareness. Diabet Med, 1996. 13 (7): p. 607-15. Ricks, J., et al., Glycemic control and cardiovascular mortality in hemodialysis patients with diabetes: a 6-year cohort study. Diabetes, 2012. 61 (3): p. 708-15. Henrich, W.L., T.D. Woodard, and J.J. McPhaul, Jr., The chronic efficacy and safety of high sodium dialysate: double-blind, crossover study. Am J Kidney Dis, 1982. 2 (3): p. 349-53. Baron, A.D., Hemodynamic actions of insulin. Am J Physiol, 1994. 267 (2 Pt 1): p. E187-202. 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07:15:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4134845/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4134845/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55318999,"identity":"9d2dfef4-0ef9-404c-83ba-f28202e89659","added_by":"auto","created_at":"2024-04-25 15:58:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":20620,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of patient inclusion.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4134845/v1/a1c08180f5d72b2bcc375813.png"},{"id":55319002,"identity":"b0149e53-c3f7-4abe-abb0-bef08bbcb4b0","added_by":"auto","created_at":"2024-04-25 15:58:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":21992,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4134845/v1/b6f331c4c821234d0d4e828e.png"},{"id":55320231,"identity":"7128b978-2365-43cf-ba86-64d83ad905ab","added_by":"auto","created_at":"2024-04-25 16:06:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":22518,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4134845/v1/73cda2a9a008ebeab24e4f6d.png"},{"id":55319000,"identity":"d88ee98f-17cd-4120-9f40-ae56544e4f8d","added_by":"auto","created_at":"2024-04-25 15:58:39","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":22091,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-4134845/v1/4befcbd6216b0650bd0e4427.png"},{"id":55320232,"identity":"67d0c265-2217-427e-a090-c0c0dd6017ed","added_by":"auto","created_at":"2024-04-25 16:06:39","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":19528,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-4134845/v1/d406c113bcd9683b6326ea36.png"},{"id":56999576,"identity":"88b94fb5-2ca6-4c89-af72-0024473d1449","added_by":"auto","created_at":"2024-05-23 08:23:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":750504,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4134845/v1/55230c54-12a3-4bc0-9f21-d9dbdbb903af.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The effects of glucose-containing dialysate during dialysis in maintenance haemodialysis patients with type 2 diabetes","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eDiabetes is one of the most common chronic diseases, with 463\u0026nbsp;million adults currently living with diabetes worldwide, and this number is expected to reach 700\u0026nbsp;million by 2045 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Type 2 diabetes mellitus (T2DM) is the leading cause of end-stage renal disease (ESRD), and approximately 26%ཞ47% of haemodialysis patients have diabetes[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Data from the China National Renal Data System (CNDRS) also show that diabetes became the leading cause of new haemodialysis in patients in 2022 (29.9%). The risk of cardiovascular disease (58%~87% vs. 7ཞ58.1%) and death (33%~33.7% vs. 2.3%~24%) in MHD patients with diabetes were greater than those in nondiabetic dialysis patients [\u003cspan additionalcitationids=\"CR5 CR6\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. During the process of haemodialysis, patients with diabetes will have varying degrees of blood glucose fluctuations, among which hypoglycaemia is the most common occurrence, and this change will aggravate the occurrence of CVD [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAt present, most haemodialysis treatments use glucose-free dialysate, mainly due to the ease of storage and low cost of glucose-free dialysate [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, the use of glucose-free dialysate also increased the frequency of asymptomatic hypoglycaemia during dialysis treatment, which may be due to the decrease in the neurohumoural response caused by frequently recurring episodes of hypoglycaemia during dialysis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Considering the possible problems associated with glucose-free dialysate, several studies have shown that glucose-containing dialysate provides better blood glucose control and less blood glucose fluctuations during haemodialysis treatment. Therefore, the overall adverse effects of MHD combined with type 2 diabetes should be reduced in the short and long term [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. To reduce the frequency of hypoglycaemia during dialysis, European guidelines have recommended the use of glucose-containing dialysate for dialysis treatment in diabetic nephropathy patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe Flash Continuous Glucose Monitoring System (CGMS) is a wearable device that tracks glucose levels in tissue fluid through regular and frequent measurements throughout the day and night [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Current reports suggest that CGMS are well tolerated. In addition to collecting blood glucose data, wearing the device can also intervene in related behaviours in patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The guidelines recommend that people with type 1 and type 2 diabetes wear CGMS to improve their HbA1c levels and reduce the chance of hypoglycaemia [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Four patients who used glucose-free dialysate and wore CGMS for a total of 14 days were previously investigated to observe changes in their blood glucose levels. The results indicated that the mean blood glucose level (MBG) and area under the blood glucose curve (AUC) on dialysis days were lower than those on nondialysis days. At present, studies on the use of glucose-containing dialysate in haemodialysis mainly adopt before-after comparisons. Moreover, the included subjects lacked relevant studies on patients who underwent haemodialysis combined with type 2 diabetes. Therefore, the purpose of this study was to use a CGMS to monitor the effect of glucose-containing dialysate on blood glucose in MHD patients with type 2 diabetes.\u003c/p\u003e"},{"header":"2 Subject and Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Population\u003c/h2\u003e \u003cp\u003ePatients who underwent regular dialysis at the haemodialysis centre of West China Hospital Sichuan University from February to April 2023 were selected. The inclusion criteria were as follows: (1) diagnosed with type 2 diabetes (ADA 2021 criteria [16]); (2) regular MHD for \u0026ge;\u0026thinsp;3 months (3 times per week); and (3) aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years. The exclusion criteria were as follows: (1) had malignant disease or overt infection/inflammation; (2) had been hospitalized for any reason within the past 3 months; and (3) refused to provide written consent. A total of 20 MHD patients with type 2 diabetes were included in this study. Random numbers were generated using SPSS 20.0, and the cells were divided into glucose-containing dialysate and glucose-free dialysate groups. Patients were assigned to the glucose-containing dialysate or glucose-free dialysate group at a 1:1 ratio. Allocation concealment was performed by sequentially numbing, opaque and concealing envelopes. They were opened when patients signed consent and were ready for cannulation and dialysis. This procedure ensured that neither the patients nor the nurses were aware of the group allocation.\u003c/p\u003e \u003cp\u003e This study gained approval from the ethics committee of the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (Review (384), 2022). All the subjects signed written informed consent. This study has been registered and approved in the Chinese Clinical Trial Registry(\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.chictr.org.cn\u003c/span\u003e\u003cspan address=\"https://www.chictr.org.cn\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cem\u003e)\u003c/em\u003e, and the registration number is ChiCTR2300068343༈15/02/2023༉.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Method\u003c/h2\u003e \u003cp\u003eAn AK96 (GAMBRO) Dialysis Machine (version 3.xx) was used with a high-throughput polysulfone hollow fibre membrane haemodialyzer, a membrane area of 1.5 m\u003csup\u003e2\u003c/sup\u003e, and an ultrafiltration coefficient of 48 ml/h/mmHg (OCI-HD150). Blood flow was 220\u0026ndash;280 ml/min, and the dialysate flow rate was 500 ml/min. The anticoagulants used were heparin or low-molecular-weight heparin (LMWH). The dialysate components included Na\u003csup\u003e+\u003c/sup\u003e (138.0 mmol/L), K\u003csup\u003e+\u003c/sup\u003e (2.0 mmol/L), Ca\u003csup\u003e2+\u003c/sup\u003e (1.5 mmol/L), Mg\u003csup\u003e2+\u003c/sup\u003e (0.5 mmol/L), Cl\u003csup\u003e\u0026minus;\u003c/sup\u003e (109.5 mmol/L), acetate (3.0 mmol/L), and bicarbonate (32.0 mmol/L). Except for 5.55 mmol/L glucose, the other components were the same in the glucose-containing dialysate and the glucose-free dialysate.\u003c/p\u003e \u003cp\u003eAll patients were monitored using the Flash Continuous Glucose Monitoring System (CGMS) (Specifications and Models: FreeStyle Libre H). The sensor was placed subcutaneously on the nonarteriovenous fistula (AVF) or tunneled cuffed CVC (TCC) catheterized side of the upper arm and remained fixed for the next 14 days. The patients\u0026rsquo; CGMS knowledge was assessed before use, and relevant precautions were explained. The monitor recorded and stored the blood glucose values of the patients every 15 minutes, and the blood glucose values were recorded continuously for 14 days. Patients in the glucose-containing dialysate group were treated with 5.55 mmol/L glucose-containing dialysate (the rest of the dialysate components remained unchanged) for 14 days (6 times). Patients in the glucose-free dialysate group received standard haemodialysis therapy for 14 days (6 times) using glucose-free dialysate. After 14 days, the sensor is removed, and the data are downloaded and stored on a computer and represented in graphs and values. During the study period, patients' insulin use, hypoglycaemic medication, and dietary habits did not change. Patients were advised that their records should be kept when they eat during dialysis. The target blood glucose range was defined as 3.9\u0026thinsp;~\u0026thinsp;10 mmol/L within the target range, 3\u0026thinsp;~\u0026thinsp;3.9 mmol/L below the target range, and above the target range 10\u0026thinsp;~\u0026thinsp;13.9 mmol/L.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Clinical Outcomes\u003c/h2\u003e \u003cp\u003eWe extracted the blood glucose values collected by CGMS within 14 days to compare the TIR blood glucose levels, the glucose coefficient of variation(CV), and the number of hypoglycemia during dialysis between the two groups. We also compared fasting plasma glucose and fasting C-peptide values between the two groups before and after 14 days. Finally, we compared the changes of blood pressure and pulse rate between the two groups during 4 hours of dialysis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical analysis\u003c/h2\u003e \u003cp\u003eSPSS 22.0 software was used to analyse the data. Normally distributed quantitative data are expressed as \u0026oline;x\u0026thinsp;\u0026plusmn;\u0026thinsp;s, and nonnormally distributed data are expressed as M (P25, P75). Independent sample t tests and Mann‒Whitney U tests were used for comparisons between groups. Qualitative data are expressed as [n (%)], and comparisons between groups were made using the X\u003csup\u003e2\u003c/sup\u003e test or Fisher exact probability test. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to indicate statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 General information\u003c/h2\u003e \u003cp\u003eA total of 20 patients were included in this study; among them, 1 patient in each of the glucose-containing dialysate groups and one in the glucose-free dialysate group had premature sensor shedding, resulting in incomplete CGM readings. One patient in the glucose-containing dialysate group withdrew from the study, and one patient in the glucose-free dialysate group was hospitalized with heart failure and lost to follow-up(Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Finally, the data of 16 patients (8 patients in the glucose-containing dialysate group and 8 patients in the glucose-free dialysate group) were analysed. There was no significant difference in the baseline data between the two groups. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic and clinical indicators (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll subjects\u003c/p\u003e \u003cp\u003e(16)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGlucose-containing Dialysate group\u003c/p\u003e \u003cp\u003e(8)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGlucose-free Dialysate group\u003c/p\u003e \u003cp\u003e(8)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender(\u003c/b\u003eMale/Female\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7/1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.12\u0026thinsp;\u0026plusmn;\u0026thinsp;9.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63.37\u0026thinsp;\u0026plusmn;\u0026thinsp;11.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56.87\u0026thinsp;\u0026plusmn;\u0026thinsp;5.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of dialysis\u003c/b\u003e(month)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(26, 49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44(15,49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28(26,40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of diabetes\u003c/b\u003e (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.37\u0026thinsp;\u0026plusmn;\u0026thinsp;8.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.12\u0026thinsp;\u0026plusmn;\u0026thinsp;8.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.62\u0026thinsp;\u0026plusmn;\u0026thinsp;8.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eESRD cause, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetic nephropathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(62.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(62.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(75%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6(37.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3(37.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(25%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplication, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14(87.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(87.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(87.50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecardiovascular disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(56.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(62.50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ediabetic retinopathy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9(56.25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(62.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAccess type\u003c/b\u003e (AVF/TCC)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5/3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHb(g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114.31\u0026thinsp;\u0026plusmn;\u0026thinsp;12.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e117.00\u0026thinsp;\u0026plusmn;\u0026thinsp;10.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e111.62\u0026thinsp;\u0026plusmn;\u0026thinsp;13.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALB(g/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.76\u0026thinsp;\u0026plusmn;\u0026thinsp;2.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.86\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGlycosylated serum protein(GSP, %)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.22\u0026thinsp;\u0026plusmn;\u0026thinsp;8.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.28\u0026thinsp;\u0026plusmn;\u0026thinsp;4.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.15\u0026thinsp;\u0026plusmn;\u0026thinsp;10.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHbA1c(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.05\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.72\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.35\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.15\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.17\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.13\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntihypertensive drugs\u003c/b\u003e(yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7/1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiabetes-related medication\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInsulin(yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6/2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eORAL antidiabetic drug(yes/no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5/3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal daily energy intake\u003c/b\u003e(kal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1507.75\u0026thinsp;\u0026plusmn;\u0026thinsp;378.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1574.93\u0026thinsp;\u0026plusmn;\u0026thinsp;358.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1440.58\u0026thinsp;\u0026plusmn;\u0026thinsp;409.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTotal daily protein intake\u003c/b\u003e(g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.54\u0026thinsp;\u0026plusmn;\u0026thinsp;16.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49.58\u0026thinsp;\u0026plusmn;\u0026thinsp;18.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49.51\u0026thinsp;\u0026plusmn;\u0026thinsp;15.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTaking food in dialysis\u003c/b\u003e(N)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Changes in relevant indices before and after 14 days in the two groups\u003c/h2\u003e \u003cp\u003eFasting blood glucose, fasting C-peptide and the glucose CV were not significantly different between the two groups before and after 14 days of study. The data extracted by the CGMS showed no significant difference in the coefficient of variation of blood glucose between the two groups. However, the blood glucose TIR (14 days, dialysis days and nondialysis days) in the glucose-containing dialysate group was significantly greater than that in the glucose-free dialysate group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eChanges in blood sugar levels in the two groups after 14 days\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGlucose-containing Dialysate group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGlucose-free Dialysate group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14 days TIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.50\u0026thinsp;\u0026plusmn;\u0026thinsp;12.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.75\u0026thinsp;\u0026plusmn;\u0026thinsp;15.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDialysis day TIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.70\u0026thinsp;\u0026plusmn;\u0026thinsp;10.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.76\u0026thinsp;\u0026plusmn;\u0026thinsp;17.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.028\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNondialysis day TIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74.67\u0026thinsp;\u0026plusmn;\u0026thinsp;11.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.53\u0026thinsp;\u0026plusmn;\u0026thinsp;22.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.049\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14 days glucose CV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.83\u0026thinsp;\u0026plusmn;\u0026thinsp;5.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.28\u0026thinsp;\u0026plusmn;\u0026thinsp;8.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.897\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDialysis day glucose CV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34.61\u0026thinsp;\u0026plusmn;\u0026thinsp;5.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.70\u0026thinsp;\u0026plusmn;\u0026thinsp;10.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.363\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNondialysis day glucose CV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.47\u0026thinsp;\u0026plusmn;\u0026thinsp;7.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.36\u0026thinsp;\u0026plusmn;\u0026thinsp;7.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003efasting blood-glucose(mmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.50\u0026thinsp;\u0026plusmn;\u0026thinsp;1.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.07\u0026thinsp;\u0026plusmn;\u0026thinsp;3.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eafter 14 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.10\u0026thinsp;\u0026plusmn;\u0026thinsp;3.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFasting C-peptide(nmol/L)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.58(2.39, 4.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.13(1.32, 6.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eafter 14 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.90(2.92, 13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.43(2.99, 11.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.525\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequency of hypoglycaemia within 1 hour of dialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0,0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.382\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequency of hypoglycaemia within 2 hour of dialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (0,8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.032\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequency of hypoglycaemia within 3 hour of dialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0,1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (0,9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.130\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequency of hypoglycaemia within 4 hour of dialysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0,2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (0,8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.234\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAll patients wore the sensor on the day of dialysis, and the dialysis duration ranged from 5 days after the second dialysis session to all dialysis days before the sensor was removed. The nondialysis days included all nondialysis days from the second day after the sensor was worn to the day before the sensor was removed, for a total of 7 days. The bold font indicates P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Changes in blood glucose during 4 hours of dialysis\u003c/h2\u003e \u003cp\u003eDuring the observation period of 80 dialysis treatments, only one patient in the glucose-free dialysate group experienced 2 symptomatic hypoglycaemic events. Patients in the glucose-containing dialysate group had fewer episodes of hypoglycaemia per hour than those in the glucose-free group, and the number of episodes of hypoglycaemia up to two hours of dialysis was statistically significant (P\u0026lt;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Glucose measurements taken every 15 minutes during a 4-hour dialysis period in both groups showed a greater decrease in blood glucose in the glucose-free dialysate group. (Fig.\u0026nbsp;2)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Changes in blood pressure and pulse rate during 4 hours of dialysis\u003c/h2\u003e \u003cp\u003eBlood pressure and pulse rate did not significantly differ between the two groups during dialysis, and the blood pressure and pulse rate were basically maintained at normal levels. However, the systolic blood pressure in the glucose-free dialysate group showed a decreasing trend, and Fig.\u0026nbsp;2 shows that the decrease in systolic blood pressure in the glucose-free dialysate group was more obvious than that in the glucose-containing dialysate group. (Figure 3, Fig.\u0026nbsp;4, Fig.\u0026nbsp;5)\u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eA study by Abeesh showed that patients had significantly greater blood glucose TIR during the glucose-containing dialysate phase than during the glucose-free dialysate phase (33% vs. 18.7%) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Sangill's study indicated that there was no significant difference in blood glucose levels, but the variability was significantly reduced after the use of glucose-containing dialysate in MHD patients with diabetes [17]. The results of the above studies were similar to those of the present study, in which the 14-day blood glucose TIR (50.5% vs. 30.75%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) of patients in the glucose-containing dialysate group was greater than that in the glucose-free dialysate group. Moreover, the blood glucose TIRs of the two groups on dialysis day (75.7% vs. 57.76%) and nondialysis day (74.67% vs. 55.53%) were greater in the glucose-containing dialysate group. Therefore, the use of glucose-containing dialysate may be more beneficial for blood glucose management in MHD patients with type 2 diabetes. In addition to maintaining the blood glucose TIR on dialysis days, it also has a certain effect on maintaining the blood glucose TIR on nondialysis days.\u003c/p\u003e \u003cp\u003eIn this study, the blood glucose level in the glucose-free dialysate group decreased gradually from 7.25 mmol/L to 5.02 mmol/L during 4 hours of dialysis (blood glucose results obtained by the sensor every 15 minutes). The blood glucose concentration in the glucose-containing dialysate group decreased from 7.75 mmol/L to 6.23 mmol/L. The decrease in blood glucose in the glucose-containing dialysate group was smaller than that in the glucose-free dialysate group. Previous studies have shown that HD improves insulin resistance and thus enhances muscle glucose uptake. HD can also change the pH of the red blood cell cytoplasm, leading to accelerated anaerobic metabolism and increased glucose consumption [18]. All of the above mechanisms can explain the decrease in blood glucose in patients during dialysis. In addition, during dialysis, asymptomatic hypoglycaemia occurred less frequently in the glucose-containing dialysate group than in the glucose-free dialysate group, which was similar to the results of Abeesh\u0026rsquo;s study. In the 80 HD treatments in this study, few symptoms were associated with hypoglycaemic events according to the CGMS. One patient in the glucose-free dialysate group had one symptomatic hypoglycaemic event during each of the two dialysis sessions. The occurrence of asymptomatic hypoglycaemia during dialysis may be due to the disruption of the neurohumoural response caused by frequently recurring episodes of hypoglycaemia during HD [19]. Studies have shown that long-term maintenance of low blood glucose levels increases the uptake of glucose by brain cells, thereby reducing the brain's perception of low blood glucose, which may also explain the asymptomatic phenomenon of hypoglycaemic episodes [20]. However, studies have shown that in people with diabetes, chronic hypoglycaemia can lead to impaired cognitive function and an increased risk of death [21, 22]. Therefore, reducing the occurrence of hypoglycaemia in MHD patients with type 2 diabetes is more conducive to their long-term survival and health. Glucose-containing dialysate can effectively reduce the occurrence of asymptomatic hypoglycaemia in MHD patients with type 2 diabetes. Therefore, the clinical use of glucose-containing dialysate in MHD patients with type 2 diabetes is necessary.\u003c/p\u003e \u003cp\u003eSangill suggested that the addition of glucose to dialysate could increase extracellular osmotic pressure, resulting in reduced fluid loss in intracellular compartments and thus reducing the occurrence of dialysis-related hypotension [17, 23]. Their study showed that the use of glucose-containing dialysate led to a significant reduction in systolic and diastolic blood pressure in dialysis patients, but this effect was more significant in nondiabetic dialysis patients and was not observed in MHD patients with diabetes [17]. The mechanism may be that the insulin secretion of nondiabetic dialysis patients increases with increasing dialysate glucose concentration. At physiological concentrations, insulin secretion causes blood vessels to dilate, leading to a drop in blood pressure[24]. Li's study showed that although 5.55 mmol/L glucose-containing dialysate could reduce blood sodium levels, it had no effect on blood pressure during dialysis[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These findings are consistent with the results of the present study. This study showed that during the 4 hours of dialysis, the blood pressure and pulse rate of the two groups fluctuated within the normal range, but the differences were not significant. However, the systolic blood pressure in the glucose-free dialysate group showed a decreasing trend in this study. At present, the effect of glucose-containing dialysate on the blood pressure and pulse rate of MHD patients with diabetes is still unclear and needs further study.\u003c/p\u003e"},{"header":"Limitation","content":"\u003cp\u003eOur study has some limitations. First, this study include a small sample size and a shorter observation period of 14 days for both groups of patients. In addition, this study only observed the use of different dialysates during dialysis, and no uniform intervention was performed on the dietary intake and use of glucose-controlling drugs in all patients, which may be a confounding factor. Finally, there is a lack of observation and comparison of the results of other dialysis measures.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, the use of glucose-containing fluids, as compared with glucose-free fluids, may be beneficial in targeting glucose levels in MHD patients with type 2 diabetes. Glucose-containing dialysate may also affect the occurrence of asymptomatic hypoglycemia during dialysis in patients. The effect of glucose-containing dialysate on MHD with type 2 diabetes needs to be further studied by increasing the sample size and prolonging the observation time.\u003c/p\u003e"},{"header":"Declarations ","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eLi He and Hui Chen are co-first authors; they have contributed equally to this work, and their contributions are the same. Lin Chen and Li He contributed to the conception and design of this study; Hui Chen and Li He carried out the statistical analysis; Yingjun Zhang, Mingming Liu and Li Liu participated in the data collection; Li He and Hui Chen drafted the manuscript; and Lin Chen and Yingjun Zhang critically reviewed the manuscript and supervised the whole study process. All the authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors would like to thank all team members who participated in this study.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eData \u0026nbsp; Availability \u0026nbsp;Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTeo, Z.L., et al., \u003cem\u003eGlobal Prevalence of Diabetic Retinopathy and Projection of Burden through 2045: Systematic Review and Meta-analysis.\u003c/em\u003e Ophthalmology, 2021. \u003cstrong\u003e128\u003c/strong\u003e(11): p. 1580-1591.\u003c/li\u003e\n\u003cli\u003eKramer, A., et al., \u003cem\u003eThe European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report 2015: a summary.\u003c/em\u003e Clin Kidney J, 2018. \u003cstrong\u003e11\u003c/strong\u003e(1): p. 108-122.\u003c/li\u003e\n\u003cli\u003eLu, Y., et al., \u003cem\u003eChanging trends in end-stage renal disease patients with diabetes.\u003c/em\u003e Swiss Med Wkly, 2017. \u003cstrong\u003e147\u003c/strong\u003e: p. w14458.\u003c/li\u003e\n\u003cli\u003eMomose, M., et al., \u003cem\u003ePrognostic significance of stress myocardial ECG-gated perfusion imaging in asymptomatic patients with diabetic chronic kidney disease on initiation of haemodialysis.\u003c/em\u003e Eur J Nucl Med Mol Imaging, 2009. \u003cstrong\u003e36\u003c/strong\u003e(8): p. 1315-21.\u003c/li\u003e\n\u003cli\u003eSchiller, A., et al., \u003cem\u003eVitamin D deficiency--prognostic marker or mortality risk factor in end stage renal disease patients with diabetes mellitus treated with hemodialysis--a prospective multicenter study.\u003c/em\u003e PLoS One, 2015. \u003cstrong\u003e10\u003c/strong\u003e(5): p. e0126586.\u003c/li\u003e\n\u003cli\u003eJoubert, M. and Y. 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S4-s6.\u003c/li\u003e\n\u003cli\u003eSangill, M. and E.B. Pedersen, \u003cem\u003eThe effect of glucose added to the dialysis fluid on blood pressure, blood glucose, and quality of life in hemodialysis patients: a placebo-controlled crossover study.\u003c/em\u003e Am J Kidney Dis, 2006. \u003cstrong\u003e47\u003c/strong\u003e(4): p. 636-43.\u003c/li\u003e\n\u003cli\u003eAbe, M. and K. Kalantar-Zadeh, \u003cem\u003eHaemodialysis-induced hypoglycaemia and glycaemic disarrays.\u003c/em\u003e Nat Rev Nephrol, 2015. \u003cstrong\u003e11\u003c/strong\u003e(5): p. 302-13.\u003c/li\u003e\n\u003cli\u003eHeller, S.R. and P.E. Cryer, \u003cem\u003eReduced neuroendocrine and symptomatic responses to subsequent hypoglycemia after 1 episode of hypoglycemia in nondiabetic humans.\u003c/em\u003e Diabetes, 1991. \u003cstrong\u003e40\u003c/strong\u003e(2): p. 223-6.\u003c/li\u003e\n\u003cli\u003eMcCall, A.L., et al., \u003cem\u003eChronic hypoglycemia increases brain glucose transport.\u003c/em\u003e Am J Physiol, 1986. \u003cstrong\u003e251\u003c/strong\u003e(4 Pt 1): p. E442-7.\u003c/li\u003e\n\u003cli\u003eHeller, S.R. and I.A. Macdonald, \u003cem\u003eThe measurement of cognitive function during acute hypoglycaemia: experimental limitations and their effect on the study of hypoglycaemia unawareness.\u003c/em\u003e Diabet Med, 1996. \u003cstrong\u003e13\u003c/strong\u003e(7): p. 607-15.\u003c/li\u003e\n\u003cli\u003eRicks, J., et al., \u003cem\u003eGlycemic control and cardiovascular mortality in hemodialysis patients with diabetes: a 6-year cohort study.\u003c/em\u003e Diabetes, 2012. \u003cstrong\u003e61\u003c/strong\u003e(3): p. 708-15.\u003c/li\u003e\n\u003cli\u003eHenrich, W.L., T.D. Woodard, and J.J. McPhaul, Jr., \u003cem\u003eThe chronic efficacy and safety of high sodium dialysate: double-blind, crossover study.\u003c/em\u003e Am J Kidney Dis, 1982. \u003cstrong\u003e2\u003c/strong\u003e(3): p. 349-53.\u003c/li\u003e\n\u003cli\u003eBaron, A.D., \u003cem\u003eHemodynamic actions of insulin.\u003c/em\u003e Am J Physiol, 1994. \u003cstrong\u003e267\u003c/strong\u003e(2 Pt 1): p. E187-202.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"hemodialysis, glucose-containing dialysate, type 2 diabetes, hypoglycemia","lastPublishedDoi":"10.21203/rs.3.rs-4134845/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4134845/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e：Type 2 diabetes mellitus (T2DM) is the leading cause of end-stage renal disease (ESRD), and approximately 26%～47% of haemodialysis patients have diabetes. At present, most haemodialysis treatments use glucose-free dialysate. Howerver, the use of glucose-free dialysate resulted in an increased incidence of asymptomatic hypoglycemia during dialysis treatment.The aim of this study was to investigate the effect of glucose-containing dialysate during dialysis in Maintenance haemodialysis (MHD) patients combined with type 2 diabetes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA randomized controlled study was conducted to select 16 MHD patients with type 2 diabetes from March 2023 to April 2023. Patients were randomly divided into a glucose-containing dialysate group (n=8) and a glucose-free dialysate group (n=8). A Flash Continuous Glucose Monitoring System (CGMS) was used for blood glucose monitoring. The target time in range (TIR) of blood glucose levels, the frequency of dialysis hypoglycaemia and the changes in blood pressure and heart rate were compared between the two groups within 14 days.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e In the glucose-containing dialysate group, the blood glucose TIR was greater than that in the glucose-free dialysate group within 14 days (50.50% vs. 30.75%, P \u0026lt; 0.05), on dialysis days (75.70% vs. 57.76%, P \u0026lt; 0.05) and on nondialysis days (74.67% vs. 57.76%, P \u0026lt; 0.05). Hypoglycaemia occurred less frequently in the glucose-containing dialysate group than in the glucose-free dialysate group during 4 hours of dialysis treatment (43 vs. 205). The frequency of hypoglycaemia in the glucose-containing dialysate group was significantly lower than that in the glucose-free dialysate group at the second hour of dialysis (P \u0026lt; 0.05). There was no significant difference in blood pressure or heart rate fluctuation between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e Glucose-containing dialysate is beneficial for blood glucose management in MHD patients with type 2 diabetes, and the clinical application of glucose-containing dialysate in MHD patients with type 2 diabetes should be improved.\u003c/p\u003e","manuscriptTitle":"The effects of glucose-containing dialysate during dialysis in maintenance haemodialysis patients with type 2 diabetes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-25 15:58:34","doi":"10.21203/rs.3.rs-4134845/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6868eb4e-e78d-453c-b63a-bfce58fe4f48","owner":[],"postedDate":"April 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-23T08:15:29+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-25 15:58:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4134845","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4134845","identity":"rs-4134845","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}