Hypoglycemia a Risk at All Levels of Diabetic Control

Nancy A. Melville

August 08, 2013

As many as 10% of patients with type 2 diabetes report experiencing severe hypoglycemia, and the risk is high across all levels of glycemic control, according to new research published online July 30 in Diabetes Care.

As a common side effect of intensive glucose-lowering therapy, hypoglycemia is logically more of a concern when patients are brought to normal glycemia levels, but this survey showed patients at the highest risk for hypoglycemia also included those with very poor glycemic control (ie, patients with high HbA1c levels).

The conventional wisdom that patients with the lowest HbA1c levels are at highest risk for hypoglycemia was therefore not supported by these findings, said lead author Kasia J. Lipska, MD, MHS, from Yale School of Medicine, New Haven, Connecticut.

"Any clinician will tell you that there are plenty of patients with diabetes who experience hypoglycemia, even when their diabetes is not well-controlled, but it was a surprise to see that it was so common across the various levels of glycemic control," she told Medscape Medical News.

U-Shaped Curve for Hypoglycemia and HbA1c

Dr. Lipska and her colleagues evaluated the responses of 9094 patients, aged 30 to 77 years, from Kaiser Permanente Northern California, who were being treated in a community setting with glucose-lowering therapy for type 2 diabetes and were surveyed in 2005–2006. The patients were asked about severe hypoglycemia requiring assistance in the prior year.

The study expands on prior research by examining the occurrence of hypoglycemia across multiple HbA1c categories and by using an outcome of self-reported severe hypoglycemia, the authors note.

Among the respondents, 985 (10.8%) patients self-reported experiencing severe hypoglycemia in the previous year, and 752 (76.3%) of those reporting hypoglycemia reported 1 to 3 events. In looking at all HbA1c levels, the rates of hypoglycemia ranged from 9.3% to 13.8%.

In comparison to patients with reference HbA1c levels of 7% to 7.9%, the adjusted relative risk (RR) for hypoglycemia among those with HbA1c levels under 6% was 1.25; with levels 6% to 6.9%, the RR was 1.01; for levels of 8% to 8.9%, the RR was 0.99; and for levels of 9% or higher, the RR was 1.16.

Variables including patient's age, duration of diabetes, and the type of diabetes medication did not significantly modify the HbA1c-hypoglycemia relationship.

"Although the absolute risk of hypoglycemia was higher in patients with longer duration of diabetes and in those who used insulin, the RR of hypoglycemia at the extremes of glycemic control (compared with the HbA1c reference) was similar regardless of age, diabetes duration, or category of diabetes medication," the authors write.

Findings Underline Complexities of Treatment

The findings underscore the difficulty of trying to control glucose levels in diabetes patients, Dr. Lipska explained. "It's really all about how hard you push and not necessarily where you end up," she said.

"What I mean by this is that any particular HbA1c level does not cause hypoglycemia — hypoglycemia occurs as a result of therapies we prescribe to lower glucose, [and] these therapies are then implemented in the daily lives of our patients.

"A patient with poor glycemic control may be prescribed multiple medications to lower HbA1c levels and still not achieve a desired glycemic target."

She speculated that one of the factors that may play a role in triggering hypoglycemia could be treatment with multiple medications.

"The use of multiple medications may result in higher hypoglycemia risk and in medication errors, intermittent compliance, mistimed or misdosed medications, or poor communication between clinician and patient," she explains.

"Perhaps it is also possible that the fear or treatment of hypoglycemia contributes to poor control, setting up a vicious cycle. We need to understand this better."

With the hypoglycemia concerns in mind, the American Diabetes Association and American Geriatrics Society each recommend individualized treatment approaches that carefully consider the known risks and benefits when setting glycemic targets, and Dr. Lipska said she also supports the approach.

"I think individualizing decisions and engaging patients in care are important to high-quality diabetes management," she said. "Hypoglycemia is common and unpleasant, and we know it's associated with poor outcomes."

Another recent study, published just last week, illustrates this, suggesting that episodes of severe hypoglycemia in patients with type 2 diabetes can double the risk for cardiovascular disease.

"Our study shows how commonly severe hypoglycemia is reported — we simply can't ignore it. We have to carefully weigh the risk of hypoglycemia against the benefits of treatment," Dr. Lipska concluded.

Diabetes Care . Published online July 30, 2013. Abstract

The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Lipska blogs for Medscape Medical News about diabetes meetings. She reports no other relevant financial relationships. Disclosures for the coauthors are listed in the article.

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