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Real-time CGM improves hypoglycemic awareness

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November 28, 2017

Michael R. Rickels
Michael R. Rickels

Adults with long-standing type 1 diabetes may increase awareness of hypoglycemia and reduce severity of hypoglycemic events by using real-time continuous glucose monitoring, but the endogenous glucose counterregulation is only modestly improved, study data show.

“In long-standing type 1 diabetes, patients can develop reduced symptom awareness of hypoglycemia that can contribute to experiencing severe hypoglycemia episodes where assistance from another person is required and can result in seizures and coma,” Michael R. Rickels, MD, MS, associate professor of medicine in the division of endocrinology, diabetes and metabolism at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, told Endocrine Today. “This study was undertaken to determine if real-time knowledge of glucose levels, available continuously from a CGM, can specifically help the patients who are having the most problematic hypoglycemia to experience less low blood glucose and recover symptom awareness and physiologic defenses against the development of low blood glucose.”

Rickels and colleagues evaluated data on 11 adults with type 1 diabetes for more than 10 years (mean duration, 31 years; mean HbA1c, 7.2%; mean daily insulin requirement, 0.5 U/kg-1; 8 using insulin pump) and 12 adults without diabetes to determine whether real-time CGM can be used as a strategy for hypoglycemia avoidance and improved endogenous glucose counterregulation. Hypoglycemic and euglycemic clamps were used to measure the endogenous glucose production response before and 6 and 18 months after CGM initiation.

Hypoglycemia awareness (P < .01) and severity (P < .001) improved in participants with type 1 diabetes during the intervention period; a trend was also observed for a reduction in glycemic lability (P = .1).

During the hypoglycemic clamp, hyperinsulinemia was comparable in controls and participants with type 1 diabetes before and 6 and 18 months after implementation of real-time CGM.

Physiologic response in participants with diabetes did not change from before to 6 months after CGM initiation; however, endogenous glucose production improved by 18 months (P < .05 compared with pre-CGM measurement, but remained lower than among controls (P .01 for all comparisons.

“These findings are significant because in the absence of physiologic defenses against the development of low blood glucose, near-constant use of CGM may be required to minimize the burden of problematic hypoglycemia in patients with long-standing type 1 diabetes,” Rickels said. “Such patients would benefit from more consistent and universal health insurance coverage for this potentially lifesaving intervention.” – by Amber Cox

For more information:

Michael R. Rickels, MD, MS, can be reached at

Disclosures: The authors report no relevant financial disclosures.

itj+ Perspective

David C. Klonoff

In type 1 diabetes the glucose counterregulation response to hypoglycemia is mainly mediated by epinephrine release. This response leads to both endogenous glucose production by the liver and symptoms of hypoglycemia. This study by Rickels and colleagues assessed whether the use of real-time continuous glucose monitoring can decrease the severity of mild and severe hypoglycemia in patients with type 1 diabetes with hypoglycemia-associated autonomic failure, and if so, identify the physiologic mechanism for the improved glucose levels.

The investigators found improvements in hypoglycemia awareness and hypoglycemia severity. There was only a slight improvement, however, in the endogenous glucose-production response to study-induced hypoglycemia that is required to automatically prevent or correct low blood glucose levels.

The significance of this study is that, while it is known that CGM presents both real-time absolute glycemic levels as well as the rate of change trend information to allow actions to prevent hypoglycemia, the presence of an improvement in the defective automatic counterregulatory response has not been identified with this tool. This study demonstrated — in the presence of severe hypoglycemia — increased symptoms of hypoglycemia with the use of real-time CGM — presumably due to release of some amount of epinephrine — but no increase in an automatic endogenous glucose production response from counterregulatory hormones. Thus, CGM users with hypoglycemia-associated autonomic failure will need to continue to monitor and treat themselves with an expectation of decreased hypoglycemia, but should not expect an improvement in their body’s ability to automatically respond to hypoglycemia with an effective counterregulatory hormone response.

David C. Klonoff, MD, FACP, FRCP

Clinical Professor of Medicine,
University of California, San Francisco
Medical Director,
Diabetes Research Institute,
Mills-Peninsula Medical Center

Disclosure: Klonoff reports he is a consultant for Ascensia, Eoflow, Lifecare and Novo Nordisk.