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Diabetes May Be a Risk Factor in All-Cause Mortality 

Feb 22, 2020
 
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Sandra Zaki, PharmD Candidate, Florida A&M University

Individuals with a high glucose variability are at risk of developing high-mortality conditions such as arteriosclerosis and sustained hyperglycemic episodes. 

All-cause mortality is an expression of the total deaths resulting from a given condition over a specific time. This study aims to find out if there is any correlation between GV and all-cause mortality in patients who have diabetes and are under hemodialysis. 

The study was conducted on individuals with diabetes mellitus. Participants had to be between 18 and 80 years of age, with more than three months of dialysis treatment. They also had to have stable Hemoglobin (Hb) levels. Patients with renal transplants and those with a history of cancer were excluded from the study group. Some base characteristics considered include age, sex, smoking habits, cerebrovascular disease. A GlucoDay biosensor device was used to monitor the blood glucose levels over 48 hours in 24-hour periods before and after hemodialysis. Hypoglycemia was defined as a blood glucose concentration of less than or equal to 3.9mmol/L. The ration between the SD and the mean glucose concentration expressed as percentiles were taken as the CV. 

The data collected from the patients were then statistically analyzed using a range of different tests. The differences present across the CV data groups obtained were tested using Student’s t-test, ANOVA, X2 test, Mann-Whitney U test, and fisher’s exact test. The independence of the CV was determined using Multiple Cox regression analysis. P values of >0.05 were considered statistically significant. 

The study group comprised of 1376 participants who all had diabetes mellitus and were under hemodialysis treatment. One hundred thirty-six of them were removed from the study group due to different limitations such as cancer (25), lack of consent to proceed with the study (74), and 37 whose follow up cases were lost. This left a final study group of 1240 participants who had been undergoing dialysis for an average of about 2.5 years. There were 4 CV quartiles; quartile 1 with <=31%, quartile 2 with 31%-40%; quartile 3 with 40%-52% and quartile 4 with >52%. The largest quartile had lower Hb and albumin and high hypoglycemia. Three hundred forty patients died from all causes over the 2.4-year follow-up, with the mortality risk highest in quartile 4: the largest quartile (HR 1.934, P<0.001). With the co-variates adjusted for, the Cox regression model still returned a statistically high positive correlation between the largest CV quartile and all-cause mortality (HR 1.887, P<0.001). Some of the physiological conditions of the patients also registered a positive correlation with all-cause mortality even at baseline. According to the data from the study, all-cause mortality increases as the CV of glucose rise.  

It is not known how a higher glucose variability is linked to an increased risk of mortality, but the study manages to show the correlation. Some of the working theories include increased oxidative stress due to glycemic fluctuation, which leads to the development of one or more mortal conditions such as sustained hyperglycemia and arteriosclerosis. Another approach is that glycemic variations result in high levels of inflammatory cytokines that cause dysfunction of the endothelium. These glycemic fluctuations also cause B-cells of the pancreas to become apoptotic. Death of these cells would result in catastrophic damage to the body due to unchecked glucose levels in the blood. Although very insightful, this study was limited in terms of study group selection; people with cancer were not included. The study group was also from the same dialysis center, and hence the results cannot be generalized. Further study is warranted to find out if any glucose-lowering medication has any effect on all-cause mortality in patients with diabetes on hemodialysis. 

Practice Pearls: 

  • Increasing glucose variability can result in increased risk for all-cause mortality.
  • Some conditions,such as low albumin, low Hb, and high hypoglycemia, are risk factors for all-cause mortality. 
  • Age, sex,and smoking increase the chances of all-cause mortality. 

 

Shi, S. Liu, H.-F. Yu, et al., Glycemic variability and all-cause mortality in patients with diabetes receiving hemodialysis: A prospective cohort study, Journal of Diabetes and Its Complications(2020), https://doi.org/10.1016/j.jdiacomp.2020.107549

 

Sandra Zaki, PharmD Candidate, Florida A&M University