Wide swings in blood sugar predict poor diabetes management
Keeping your average blood sugar in a healthy range isn’t enough
Continuous glucose monitoring (CGM) uses a small device painlessly affixed on an upper arm. The unit measures glucose levels in the fluid between muscle cells every 5-15 minutes and periodically transmits that information to a cell phone and/or computer. The widespread availability of CGM will revolutionize diabetes research and management.
One of the early studies that used continuous glucose monitoring confirmed that glucose concentrations in interstitial fluid correlated closely with those of blood in finger capillaries for 24 healthy participants. Thus, continuous glucose monitoring data validly represented blood glucose concentrations. The study reported other interesting results with major clinical implications. Average peak glucose and total interstitial glucose after standardized meals (all with 50 grams of carbohydrates and varying amounts of protein and fat) varied widely. The highest average interstitial glucose occurred after meals with readily absorbed foods: rice pudding with sugar and cinnamon (133 mg/dL) and toast, honey, jam, curd cheese, orange juice (137 mg/dL). The lowest average interstitial glucose occurred after meals with more slowly absorbed foods: kidney beans, whole-meal bread, salami, cheese (99 mg/dL) and grilled salmon, broccoli, carrots, wild rice, cream (122 mg/dL). Meals with higher proportions of fiber, protein, and fat (as shown in the photo) also induced smaller rises in post-meal blood glucose.
High average levels of blood sugar (hyperglycemia) predict increased risk of diabetes complications, such as kidney disease. But do large fluctuations of blood glucose levels also increase risk of other diabetes complications? Researchers recruited 27 type 2 diabetic patients and 22 healthy controls for an experiment in which blood glucose levels were maintained at constant levels or oscillated over a 48-hour period. The outcomes of interest included changes in blood vessel flexibility (more flexibility is better—within bounds) and two measures of oxidative stress (nitrotyrosine and free 8-iso FPGF2alpha concentrations). As expected, a higher constant level of blood glucose led to lower blood vessel flexibility and increases in both measures of oxidative stress for both healthy and diabetic participants from 6-24 hours after a blood glucose level was established. Compared to constant blood glucose levels, oscillating blood glucose levels led to significantly greater declines in blood vessel flexibility and increases in both measures of oxidative stress. Thus, maintaining average blood glucose levels below a healthy limit (for example, 100 mg/mL) isn’t enough. Reducing blood glucose level fluctuations also matters.
Glycaemia researcher Antonio Ceriello found increasing evidence that greater glycemic variability predicts greater risk of diabetic complications, including cardiovascular and microvascular complications. Ceriello found that both short-term (using a CGM over a day or two) and long-term (HbA1c measured in blood samples over several months often between doctor office visits) provide valuable information about glucose variability. The widespread availability of inexpensive continuous interstitial glucose monitoring devices has prompted researchers to develop ways to characterize glucose variability. Different measures appear to provide somewhat different information about risk of diabetes-related complications. In the future, clinicians will use measures of glucose variability from continuous glucose monitoring to help both diabetics and non-diabetics better manage their blood sugar.
While HbA1c integrates blood glucose levels over a period of 2-3 months, they reveal little about short-term variability. Yet, recent research suggests that short-term (over hours or days) variability may be a better measure of blood glucose control. A recent review found that higher blood glucose variability predicted higher risk of macrovascular (such as coronary artery malfunction) and microvascular (such as retinal damage) complications than did HbA1c levels in diabetic persons. Higher blood glucose variability also predicted higher incidence of mortality. Alas, science has yet to establish consensus methods to measure short-term variability. The recent wide-spread availability of continuous glucose monitoring will provide data that researchers can use to develop ways to characterize glucose variability that predict human health.
A new review by Antonio Ceriello and colleagues acknowledges that, for decades, HbA1c has been considered as the gold standard of diabetes management. Keeping HbA1c levels below a certain number (for example, 6.9 percent), reflects successful diabetes management. More recently, researchers identified blunting the post-meal spike in blood sugar one hour after a meal, thereby preventing hyperglycemia, as a diabetes management goal. Avoiding periods low blood glucose (hypoglycemia) appears to be just as important as avoiding periods of high blood sugar (hyperglycemia). Currently, developing measures of glycemic variability that predict risk of diabetes complications, such a retinal problems, compromised kidney function and peripheral neuropathy, occupies the attention of researchers and attracts the attention of clinicians. Both the time spent in the desired range for HbA1c and the degree of variation of interstitial glucose appear to be keys to effective diabetes management. For example, recent research showed that diabetic patients who used CGM reduced their HbA1c levels and their time spent in hypoglycemia. Plus, new drugs, such as GLP-1 agonists, show promise for reducing HbA1c, glucose variability, hyperglycemia, and hypoglycemia. A new day in diabetes care is coming.