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New insights on risk factors for severe hypoglycemia in people with type 2 diabetes

Results of NIDDK-supported research have improved understanding of factors that can help predict vulnerability to severe hypoglycemia in African American and white individuals with type 2 diabetes. Although untreated diabetes results in blood glucose levels that are too high, accidental over-treatment can lead to blood glucose levels that are too low, a condition known as hypoglycemia. If glucose levels fall far enough, severe hypoglycemia can cause seizures, loss of consciousness, and even death. More mild instances of hypoglycemia can be disorienting, and may raise the odds of accidental injury. Hypoglycemia can occur not only when a person accidentally takes too much of a diabetes medication such as insulin or sulfonylurea, but also when a prescribed dose is accompanied by either more physical exercise or fewer calories consumed than usual, or when an unrelated illness such as an infection temporarily alters a person’s metabolism. Importantly, while people with diabetes can live many years without a serious hypoglycemic episode, some people seem to be more susceptible to the problem.

To find ways to assess the risk of severe hypoglycemic episodes in people with diabetes, researchers examined outcomes from a well characterized cohort of 1,206 African American and white women and men with diabetes who had participated in a prior study. The participants, who averaged 64 years of age at the beginning of the study, were followed for a median of about 15 years—that is, half of the study participants were followed for that long or longer, and half for that long or less. During the study, 185 participants were treated at least once for severe hypoglycemia in emergency rooms, via an ambulance call, and/or by hospitalization. The study confirmed some prior research that showed, for example, that risk of severe hypoglycemia increases with age, with poor cognitive function, and with poor kidney function, and is higher in African Americans than in whites.

In addition, the study found some intriguing new risk factors. Not only is cognitive dysfunction a risk, but physical disability, assessed by the inability to perform activities of daily living, was found to be a new risk for hypoglycemia. Another demographic risk factor identified by this study is the use of Medicaid insurance, which may reflect socioeconomic disparities. Interestingly, researchers found that people with greater fluctuations in blood glucose control—indicated by low blood levels of a compound called 1,5-anhydroglucitol (1,5-AG)—were at elevated risk for an episode of severe hypoglycemia. This means 1,5-AG may be a valuable new laboratory test of hypoglycemia risk, since A1c levels reflect a person’s average blood glucose levels over several weeks, but indicate nothing about how much blood glucose has fluctuated around that average during that time period. Taken together, these results may help health care providers predict which people with type 2 diabetes may benefit from additional monitoring to prevent episodes of severe hypoglycemia.


Lee AK, Lee CJ, Huang ES,…Selvin E.  Risk factors for severe hypoglycemia in black and white adults with diabetes:  The Atherosclerosis Risk in Communities (ARIC) StudyDiabetes Care 40:1661-1667, doi: 10.2337/dc17-0819, 2017.
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