Challenging the Importance of Hypoglycemia in Type 2 Diabetes
A debate took place between two distinguished professors, Dr. Brian Frier and Dr. Phillip Cryer from the University of Edinburgh and Washington University in St. Louis, respectively, about the importance of hypoglycemia in type 2 diabetes (T2D)—is it truly serious or not? Their thoughts just may surprise you.
Dr. Brian Frier’s Position: Prevalence of Hypoglycemia in T2D is High
The debate began with Dr. Frier’s position that hypoglycemia is a serious issue in advanced type 2 diabetes. Dr. Frier discussed how hypoglycemia should be measured; he suggested the usage of more precise definitions for non-severe, severe and nocturnal hypoglycemic episodes and prospective recording is essential for an accurate assessment. A prospective study looks for outcomes of the development of disease during the time of the study, typically over a long period of time. Currently, retrospective, cross-sectional and online studies underestimate the frequency of hypoglycemia and defining severe hypoglycemia as a coma is a more robust measure but identifies fewer episodes.
He highlighted the serious limitations to data in hypo trials such as the studying of selected populations. According to Frier, the data showing the prevalence of data are usually derived from insurance claims databases or clinical trials, which study selected populations and exclude others such as:
- People at high risk of hypoglycemic events
- People over the age of 70 with multiple incidences or complications—very few systematic studies have been performed in this age group
- People with impaired hypoglycemia awareness
Also, trial lengths are too short to record events accurately and people behave differently when they are being closely supervised in clinical trials. This suggests rates of hypoglycemia are higher in the general populations compared to what clinical trials show.
When compared to type 1 diabetes (T1D), the incidences of hypoglycemia in type 2 diabetes becomes more frequent with increasing duration of insulin treatment. Dr. Frier referenced the Hypoglycemia Amongst insulin-Treated patients with diabetes (HAT) study to show hypoglycemia is a bigger problem among people with T2D on a global basis. The HAT study was a non-interventional retrospective and prospective study of self-reported hypoglycemic events and took place in 24 countries with over 27,000 people. Though the number of events was higher in people with T1D, the number of people with T2D (19,563) observed in the study more than doubled the amount of T1D patients (8,022). Therefore, the prevalence of hypoglycemia in type 2 diabetes is higher.
An analysis of 46 real-world studies of 532,000 people with type 2 diabetes, the prevalence of non-severe hypoglycemia was 52 percent with an average of 23 episodes per person-year; 21 percent for severe hypoglycemia, with an average of one episode per year.
In summary, Dr. Frier says hypoglycemia is a real and serious problem for the following reasons:
- It’s common in people with type 2 diabetes treated with insulin and to a lesser extent, sulfronylureas.
- Globally, it represents a much larger problem than in type 1 diabetes in absolute numbers.
- It’s associated with potentially serious morbidity and mortality, especially in older adults.
- Few systematic studies are completed for this age group.
- In Italy, 17 percent of hospital admissions were for severe hypoglycemia, 49 percent had dementia and the average A1c was less than 5.9 percent (40 mmol/mol).
Dr. Phillip Cryer: Clinically Important vs. Severe Hypoglycemia
Dr. Cryer’s take on this argument was less about if hypoglycemia was serious or not; in fact, he agreed with Dr. Frier that it is a serious issue to be addressed among people with type 2 diabetes. His position instead was on the terminology—that we should replace serious, clinically important hypoglycemia with severe hypoglycemia. He reviewed several publications to answer two questions:
- What is the frequency of measured “serious, clinically-important hypoglycemia” (<3.0 mmol/L54 mg/dL) compared to self-reported, unmeasured, clinical “severe hypoglycemia” in diabetes?
- What is the frequency of serious clinically-important diabetes in type 2 diabetes compared with type 1?
To answer these questions Dr. Cryer noted self-reported unmeasured, clinical severe hypoglycemia in people with T1D, but in contrast, many continuous glucose monitor (CGM) reports indicate that serious, clinically important hypoglycemia actually occurs every few days in T1D. For example, a person with T1D with an A1c of 6.7 and 7.6 experiences these incidences every 14-15 days and every two days, respectively. In type 2 diabetes, a person with an A1c of 7.6 and 6.6 experiences it every 12 days and 23 days, respectively.
This article is part of Beyond Type 2’s ADA 2019 coverage. For full ADA 2019 coverage, click here.
