People who live with type 1 diabetes (T1D) depend on insulin, which means they are exposed to its main side effect: the risk of hypoglycemia (blood sugar that is too low). Hypoglycemic episodes can be moderate (blood sugar under 4 mmol/L, with or without symptoms), serious (blood sugar under 3 mmol/L) or severe (inability to treat it alone, loss of consciousness).

In order to reach their target blood sugar levels, people with T1D have to adjust their insulin doses, but hypoglycemic episodes and fear associated with the risk of hypoglycemia are major hurdles to adequate insulin dose adjustments, which in turn increases the risk of hypoglycemia. 

Continuous glucose monitoring (CGM) systems are increasingly used and help to identify and better prevent hypoglycemic episodes. With a CGM, patients with T1D can monitor their blood sugar variability not only throughout the day, but also from one day to the next at a particular time. For example, waking up one day with low blood sugar and with high blood sugar the next indicates a significant fasting blood sugar variability.

A university medical centre in France (CHU de Montpellier) used a CGM to monitor the blood sugar levels of three people with T1D for 100 days. Their goal was to identify which factors increased the risk of hypoglycemia. The risk was measured according to time spent with blood sugar levels under three thresholds that carry a greater risk of severe hypoglycemia: 3.9 mmol/L, 3.45 mmol/L and 3.0 mmol/L.

Total daily dose of insulin, age and weight don’t increase the risk of hypoglycemia.

The study found that factors such as total daily dose of insulin, age and weight are not correlated with the risk of hypoglycemia. 

Two hypoglycemia risk factors: mean blood sugar level and blood sugar variability.

The study revealed that the time spent in hypoglycemia increased proportionately to the level of blood sugar variability and to how close the mean blood sugar is to normal ranges.

A mean blood sugar level lower than 6.9 mmol/L is the main factor associated with a higher amount of time spent under 3.9 mmol/L.

Time spent under 3.45 and 3.0 mmol/L is more impacted by blood sugar variability. The more significant the variability, the more time is spent under 3.45 mmol/L. The variability is generally measured based on the coefficient of variability (%CV) found in certain CGM reports (Dexcom, Medtronic). The %CV isn’t yet available in FreeStyle Libre reports, but should be available in the next improved version.

The study also found that regardless of mean blood sugar level, the number of hypoglycemic episodes is higher when the %CV is higher than 36%. This suggests that the %CV should be maintained under 34% to limit the risk of hypoglycemia as much as possible.  

While it’s important to consider blood sugar variability when adjusting insulin doses, the best thing to do before making any adjustment is to find out what is causing this variability and to decrease it (insulin taken after meals, missed insulin doses, lipodystrophies, carb counting errors, physical activity, excessive alcohol intake, not changing infusion sets often enough when using an insulin pump, etc.).  

Measuring the severity and frequency of hypoglycemic episodes in order to better identify the causes and find ways to minimize the risk is one of the main goals of the BETTER registry.

Reference:

• Monnier, L., Wojtusciszyn, A., Molinari, N., Colette, C., Renard, E., Owens, D. (2020). Respective Contributions of Glycemic Variability and Mean Daily Glucose as Predictors of Hypoglycemia in Type 1 Diabetes: Are They Equivalent? Diabetes Care. https://doi.org/10.2337/dc19-1549.