|Year : 2023 | Volume
| Issue : 1 | Page : 13-16
Ambulatory glucose profile of type 2 diabetes patients with end-stage renal disease undergoing hemodialysis: A pilot study
Vedavati B Purandare1, Arjun L Kakrani2, Prashant S Bhalekar1, Ambika G Unnikrishnan1
1 Department of Diabetes and Endocrinology, Chellaram Diabetes Institute, Pune, Maharashtra, India
2 Department of Medicine, D. Y. Patil Medical College, Hospital and Research Centre, Pune, Maharashtra, India
|Date of Submission||30-Nov-2022|
|Date of Decision||16-Dec-2022|
|Date of Acceptance||16-Dec-2022|
|Date of Web Publication||18-Jan-2023|
Ambika G Unnikrishnan
Department of Diabetes and Endocrinology, Chellaram Diabetes Institute, Pune - 411 021, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Management of glucose levels in patients with diabetes mellitus and end-stage renal disease (ESRD) is challenging. There are various factors contributing to glycemic variability (GV), including altered metabolism of glucose and insulin in the ESRD stage. Continuous glucose monitoring (CGM) system measures glucose levels continuously and helps to study the glucose profile of patients undergoing hemodialysis (HD). This pilot study aimed to analyze the ambulatory glucose profile (AGP) of type 2 diabetes patients with ESRD undergoing HD and study the GV when patients were on HD (referred to as ON days) versus when patients were not on HD (referred as OFF days). Materials and Methods: We enrolled 10 patients with type 2 diabetes mellitus and ESRD undergoing maintenance HD in the study. Data regarding patient characteristics, including age, gender, duration of diabetes mellitus, HbA1c, and serum fructosamine, were collected. The AGP data obtained by the CGM sensor on the HD ON days was compared to AGP data on HD OFF days. Results: There was a significant linear correlation of CGM-derived average blood glucose with HbA1c value; however, the association was not significant with fructosamine level. The CGM-derived average glucose level was significantly lower during HD ON days compared to HD OFF days, difference being 29.9 mg/dl (−33.7, −26.0; P < 0.001), whereas GV was significantly higher during HD OFF days compared to ON days. Conclusion: The variation in the glucose levels was higher during the HD OFF days compared to HD ON days. Future AGP studies recruiting more number of patients on HD will help better understand the clinical impact of glucose profile and GV in ESRD patients.
Keywords: Ambulatory glucose profile, continuous glucose monitoring, end-stage renal disease, glycemic variability, hemodialysis
|How to cite this article:|
Purandare VB, Kakrani AL, Bhalekar PS, Unnikrishnan AG. Ambulatory glucose profile of type 2 diabetes patients with end-stage renal disease undergoing hemodialysis: A pilot study. Chron Diabetes Res Pract 2023;2:13-6
|How to cite this URL:|
Purandare VB, Kakrani AL, Bhalekar PS, Unnikrishnan AG. Ambulatory glucose profile of type 2 diabetes patients with end-stage renal disease undergoing hemodialysis: A pilot study. Chron Diabetes Res Pract [serial online] 2023 [cited 2023 Feb 5];2:13-6. Available from: https://cdrpj.org//text.asp?2023/2/1/13/368028
| Introduction|| |
Glucose management in patients with diabetes-related end-stage renal disease (ESRD) is challenging and glycemic variability (GV) is an important clinical problem., Continuous glucose monitoring (CGM) offers an effective method for understanding the glucose profile and GV in patients with diabetes mellitus. CGM enables the direct tracking of short-term (inter- and intraday) glucose variability, hyperglycemia, and hypoglycemia. There is increasing use of CGM, especially in those patients, in whom GV is seen or anticipated. In patients with diabetes and advanced kidney disease, there are various factors that contribute to GV. In patients with advanced kidney disease, intensive blood glucose control is not recommended as there is an increased risk of hypoglycemia due to diminished renal gluconeogenesis, impaired renal insulin degradation, and poor oral intake. Increased GV is particularly seen in patients on maintenance hemodialysis (HD). One of the several postulated reasons for hypoglycemia during HD is the loss of glucose across the dialyzer membrane. CGM, though not routinely recommended, could be a promising tool to assess and manage the GV in patients with diabetes on HD.
With this study, we aimed to document the glycemic patterns in patients with type 2 diabetes mellitus and ESRD undergoing HD. We also assessed the correlation between the CGM-derived glycemic parameter and laboratory value of HbA1c and serum fructosamine.
| Materials and Methods|| |
In this pilot study, 10 adult patients with type 2 diabetes mellitus and ESRD undergoing maintenance HD at Chellaram Hospital: Diabetes Care and Multispeciality, Pune, were included in the study. Patients with type 1 diabetes mellitus, severe hepatic dysfunction, critical and hospitalized patients, and patients with malignancy were excluded from the study. Written informed consent was obtained from all enrolled participants, and the study was approved by the institutional ethics committee. The study was conducted during January 2018 to March 2019.
Demographic and clinical characteristics of all enrolled participants were recorded at baseline, and the FreeStyle Libre Pro, a professional retrospective masked CGM device, was applied on the back of the upper arm for 14 days of CGM. The sensor continuously measured glucose in interstitial fluid through a small (5 mm long, 0.4 mm wide) filament that was inserted just under the skin. It recorded glucose levels every 15 min, capturing up to 1340 glucose results for up to 14 days. After 14 days, the Libre Pro reader was used to scan the sensor and download the 14-day data stored in the sensor.
The patients were on HD either twice a week or thrice a week. The day's patient underwent HD has been labeled as HD ON days, and the days when the patients were not on HD has been labeled as HD OFF days. Data regarding basic patient characteristics, including age, gender, duration of diabetes mellitus, HbA1c, and serum fructosamine, were also collected. The ambulatory glucose profile (AGP) data on the HD ON days was compared to AGP data on HD OFF days.
Statistical analysis was carried out using STATA 14.2 software (StataCorp LLC, 4905 Lakeway Drive, College Station, Texas 77845-4512, USA). As the number of participants in the study group was small, data were presented as median with interquartile Range (IQR), i.e., IQR. The median was favored over the mean in this data analysis as the median is not skewed by a small number in the data. Regression analysis was performed to see the linear correlation between the CGM-derived glycemic parameters, such as average blood glucose with HbA1c and serum fructosamine. The distribution of the parameters was compared by HD and no HD days using the Wilcoxon rank–sum test. A P < 0.05 was considered statistically significant.
| Results|| |
The baseline characteristics of the ten patients are summarized in [Table 1]. The median age of patients was 64 (60–71) years. Eight male and two female patients were recruited. The median duration of DM was 17 (10–23) years. All had diabetic retinopathy of various stages. The median HbA1c was 6.7%, and the median glucose management indicator was 7.2%.
Out of these 10 patients on HD, six patients had higher time below target (glucose level below 70 mg/dl) percentages of CGM readings on the HD ON days versus on HD OFF days and seven patients had higher time above target (glucose level above 180 mg/dl) on HD OFF days as compared to HD ON days.
Regression analysis of glycemic parameters showed a significant linear correlation between CGM-derived average blood glucose and HbA1c (r= 0.81; p=0.01) [Figure 1]a; however, it did not correlate with serum fructosamine (r=0.52; p=0.09) [Figure 1]b. Further, the serum fructosamine did not correlate with HbA1c also (P = 0.09).
|Figure 1: (a) Linear regression analysis to study correlation between average blood glucose and HbA1c. (b) Linear regression analysis to study correlation between average blood glucose and serum fructosamine|
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On trend analysis, variation in the glucose pattern significantly differs between HD ON days and HD OFF days [Figure 2]. On HD ON days' glucose levels were lower than HD OFF days. This difference was −29.9 mg/dl (−33.7, −26.0) with P < 0.001. Variation in the glucose levels was higher during the non-HD days compared to HD days. This variation was − 0.08 (−0.09, −0.07); P < 0.001 per hour on OFF HD days and HD ON days its − 0.04 (−0.07, −0.003); P = 0.03 per hour.
|Figure 2: Comparison of glycemic pattern on HD ON days versus HD OFF days. HD: Hemodialysis|
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Green line represents trend of average glucose levels of 10 patients on the HD ON days Blue line represents trend of average glucose levels of 10 patients on HD OFF days X axis represents time in hours from the start of CGM till CGM sensor stops (approximately 14 days); Y axis represents the glucose levels of CGM.
| Discussion|| |
From this pilot study, we observed that TBT was more frequent during HD ON days compared to HD OFF days, whereas TAT was higher during HD OFF days when compared to HD ON days. This suggests a tendency toward hypoglycemia on HD ON days and a tendency toward hyperglycemia on HD OFF days.
A pilot study published by our center showed high GV in patients on HD. The study was conducted on ten diabetes-related ESRD patients on HD. The CGM record showed asymptomatic hypoglycemia in these patients during HD. Glucose levels showed a fall during HD and then a rise to higher levels after the dialysis session.
In the DIALYDIAB pilot study, 15 patients on HD were recruited. Five-day CGM was done at baseline and after 2 weeks. The mean 24-h glucose, the mean amplitude of glucose excursions, and the standard deviation of mean glucose were significantly higher on the HD days compared to the dialysis-free days. On HD day, patients showed higher GV as compared to dialysis-free days.
A systematic review by Maurizio Gallieni et al. on CGM in HD patients with type 2 diabetes mellitus revealed a significant fluctuations in glucose levels during HD sessions. These studies reported a higher mean amplitude of glucose variations on the HD day. In these studies, CGM sensors of 2 days to 2 weeks were used. CGM data demonstrated higher GV in these patients on HD days.
In contrast to these study observations, in our study, higher GV was seen on HD OFF days as compared to HD ON days. This may be explained by the fact that in a tertiary care dialysis center with a focus on managing diabetes-related ESRD, patient's glucose levels are monitored during dialysis; they are offered a mid-dialysis snack to prevent severe hypoglycemia during HD followed by rebound hyperglycemia contributing to higher GV. However, this needs confirmation by a controlled trial.
Although, our study was limited by small sample size due to the cost of CGM device and other practical considerations in type 2 diabetes patients on hemodialysis, the data showed a significant linear correlation between the average blood glucose of CGM and HbA1c. Currently, HbA1c is not a gold standard glucose control measure in advanced kidney disease subjects due to various reasons. However, in our pilot study, HbA1c correlated significantly with the average blood glucose of AGP. Future studies recruiting more number of patients will give us better clarity regarding this. A study published by Presswala et al. published in October 2019 assessed the accuracy of HbA1c level using CGM in patients with advanced DKD. The results suggested that HbA1c can be an accurate measure of glycemic status among patients with DKD. This relationship appeared to hold true among patients with more advanced CKD. That data also showed a significant correlation between CGM-derived average glucose, A1c, and serum fructosamine.
| Conclusion|| |
To conclude, our pilot study of 10 patients on HD showed that on HD ON days, glucose levels were significantly lower as compared to those on HD OFF days. GV was higher during the HD OFF days compared to HD ON days. Future AGP studies recruiting more number of patients on HD will help better understand the clinical significance of glucose profile and GV in ESRD patients. This might help in better diabetes management in HD patients. Improvement of GV in patients on HD might help in decreasing morbidity and mortality in patients on HD and help improve quality of life. This might preserve their health for a prospective kidney transplant and also long-term health.
Study was approved by Institutional Ethics Committee of Chellaram Diabetes Institute, Pune, Letter number CDIEC/2017/073.
We acknowledge Dr. Shalbha Tiwari for her support and assistance in manuscript review and editing.
Financial support and sponsorship
The study was partially funded by Chellaram Foundation.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]