Fasting Glucose Variation Predicts Microvascular Risk

Fasting glucose level variation may reveal more information than just sugar level and how well it is managed, including microvascular risk. 

Microvascular disease, or small blood vessel disease, is an unfortunate condition seen in patients with diabetes. This disease then results in further complications in the eyes, kidneys, and heart. Previous studies from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Veteran Affairs Diabetes Trials (VADT) have provided data that can be observed to give more insight into fasting glucose results. A closer look into the relationship between fasting glucose levels and small blood vessel disease risk can be explored by analyzing both studies’ data.  

This study took specific data from the ACCORD trial and VADT to analyze all the patient outcomes with varying fasting glucose levels for the severity of eye and kidney issues. To do so, the authors of the study observed documented severe eye or kidney issues and the fasting glucose levels measured in those patients. The measured primary outcome was the timed dependent variable of the severe eye or kidney damage from previous studies. The secondary effects are all the additional, if any, complications the patients experienced.  

The authors used the Wilcoxon test for the continuous data and Cox proportional hazard model for further statistical analysis to place the data as appropriate time-dependent variables properly. This allowed it to be determined if the fasting blood glucose variations had any relationship leading to the primary outcomes. Data included were signs of visual disturbances or loss, cataract removal, eye laser correction, serum creatine measurements, and urine albumin from both studies. 

ACCORD and VADT have provided hazard ratios for the coefficient of variation (CV), and average real variability (ARV) that support fasting glucose variation increases the risk of small vessel disease. It statistically indicated the risk of small vessel disease from both eye and kidney damage (63% risk), kidney damage (55% risk), and eye damage (42% risk). Kidney damage measured as a hazard ratio is significant (HR: 1.29 for ARV and 1.38 for CV). It shows more events occurring with each one increase of standard deviation in fasting glucose variation.  

Results from this meta-analysis were promising to indicate that fasting glucose variation could be a marker for the risk of small vessel disease in patients with diabetes. Though the findings were very promising, the limitation was that this meta-analysis only allowed data from patients with advanced cases of diabetes. This study gives more room for further investigation to see if fasting glucose variation is an independent factor for small vessel disease.  

Practice Pearls: 

• Fasting glucose variations seem to have a relationship with small vessel disease, but need further exploration to confirm this as a reliable biomarker. 
• Patients who experience severe eye or kidney damage have had poor glucose control with their therapy, as indicated by their visit-to-visit fasting glucose being so different. 
• Biomarkers are essential guides in preventing or diagnosing a disease before it becomes too severe for further medical interventions. 

Jin J Zhou, Ph.D., Juraj Koska, MD Ph.D., MD, VADT Investigators, Fasting Glucose Variation Predicts Microvascular Risk in ACCORD and VADT, The Journal of Clinical Endocrinology & Metabolism, December 25, 2020 

Eric Cheung, PharmD Candidate, USF Taneja College of Pharmacy