The American Diabetes Association has updated its guidance for those treating and researching hypoglycemia , joining with the European Association for the Study of Diabetes to specify that a level of less than 3 mmol/L (54 mg/dL) should be considered “clinically important hypoglycemia.”
“A single glucose level should be agreed to that has serious clinical and health-economic consequences,” the ADA and EASD stated in the new guidelines . “This would enable the diabetes and regulatory communities to compare the effectiveness of interventions in reducing hypoglycemia, be they pharmacological, technological, or educational. It would also permit the use of meta-analysis as a statistical tool to increase power when comparing interventions.”
An international, multidisciplinary group – the International Hypoglycemia Study Group – was formed to create distinct definitions of the various levels of severity that hypoglycemia can have. The new guidelines contain three levels, which should be used by clinicians to determine what amounts of blood glucose are significant enough to be clinically reported.
“I commend the ADA and the EASD for the very thoughtful recommendations regarding clinically significant hypoglycemia and establishing criteria for reporting hypoglycemia in clinical trials,” said Helena W. Rodbard, MD , a Rockville, Md., endocrinologist and former president of the American Association of Clinical Endocrinologists, in an interview.
“Currently, there is no uniform agreement to what constitutes reportable hypoglycemia in clinical trials,” she said. “In some studies, it is defined as a blood glucose level of less than 70 mg/dL, whereas in others it is defined as a blood glucose level less than 54 mg/dL.”
The guidelines define first-level hypoglycemia as any glucose level of 3.9 mmol/L (70 mg/dL) or less. This is not considered low enough to be reported on a consistent basis in clinical studies; however, that determination must ultimately be made by the investigators, as the parameters for what is significant often vary from study to study.
The second level is the 3 mmol/L (54 mg/dL), which now is deemed to be a clinically significant level of hypoglycemia. Because it is “sufficiently low to indicate serious, clinically important hypoglycemia,” it should be reported as part of any clinical studies. Finally, the third level, less than 2.8 mmol/L (50 mg/dL), indicates severe hypoglycemia and is classified as any individual with “severe cognitive impairment requiring external assistance for recovery,” according to the guidelines ( Diabetes Care. 2016 Dec 1. doi: 10.2337/dc16-2215 ).
“We formed our multidisciplinary group 3 years ago with a goal to increase awareness of hypoglycemia as a major side effect of current treatment in diabetes by educational activities among the diabetes community – including patients, their families and professionals – to benefit patient care,” said Simon R. Heller, MD of the University of Sheffield (England), who was a coauthor of the guidelines. “We developed the idea that a reclassification of hypoglycemia would be useful and are delighted that both the American Diabetes Association and EASD have agreed.”
With a new standard of hypoglycemic values that are deemed clinically significant, the ADA and EASD hope that comparing different insulins, medications, technologies, and educational interventions will now become easier and more standardized, leading to better care worldwide.
Although there is general agreement as to where severe hypoglycemia really begins, the newly defined glucose levels are “a step in the right direction,” according to Dr. Rodbard.
The International Hypoglycaemia Study Group developed these guidelines through a grant from Novo Nordisk, awarded to the Six Degrees Academy of Toronto. Dr. Heller has received advisory or consultation fees from Lilly, Novo Nordisk, Takeda, Merck, Sharp & Dohme, and Becton Dickinson; has served as a speaker for AstraZeneca, Lilly, Novo Nordisk, Boehringer Ingelheim, and Takeda; and has received research support from Medtronic U.K. Dr. Rodbard did not report any financial disclosures.