What Is Hypoglycemia Unawareness?

Q. How does one diagnose hypoglycemia unawareness?

A. The phenomenon of hypoglycemia unawareness (which is an impaired sympathoadrenal response) in persons with diabetes mellitus most often is determined by a patient’s history of very low blood glucose levels without immediate clinical symptoms or warning. This may be manifested by bizarre behavior, erratic motor vehicle driving or activities, loss of consciousness, seizures, or even death. The first symptom, often noticed by others, usually is confusion.¹ Clinicians, therefore, should question patients about symptoms in conjunction with low recorded glucose numbers, because this is a dangerous condition. When hypoglycemia unawareness occurs during sleep, patients may notice only elevated morning blood glucose levels (the Somogyi effect) due to enhanced counterregulatory effects to correct for the overnight low levels.

Q. What are the risk factors for hypoglycemia unawareness?

A. The most common risk factor for hypoglycemia unawareness is hypoglycemia-associated autonomic failure (HAAF), which is a generally reversible metabolic adaptation to frequent hypoglycemia.^1,2 HAAF often occurs due to overzealous treatment of hyperglycemia by patients and/or clinicians in an attempt to improve hemoglobin A_1c (HbA_1c) levels. This adaptation may develop rapidly and has been shown to occur after as few as three 2-hour periods of hypoglycemia within 30 hours.³

Generalized autonomic neuropathy, which may or may not be reversible, also may manifest similarly to HAAF but often is accompanied by other autonomic dysfunction symptoms (eg, gastroparesis, orthostatic hypotension, bladder dysfunction). Inaccurate glucose sampling or determination also may cause erroneous or inaccurate diagnosis (pseudohypoglycemia).

Q. What conditions may worsen hypoglycemia unawareness?

A. Hypoglycemia unawareness is more prevalent during sleep and with exercise.² Patients need to check glucose levels more carefully during these times in order to determine their risk. This may necessitate setting the alarm clock during the sleep interval, which is particularly important if the later morning glucose levels are inexplicably high.

Patients with type 1 diabetes or advanced type 2 diabetes not only may have attenuated hypoglycemia awareness, but also are at risk of having a diminished counterregulatory capacity to correct the hypoglycemia.²

Q. How does one manage hypoglycemia unawareness?

A. Like all persons with diabetes, persons with hypoglycemia unawareness should carry a medical alert ID, as well as glucose replacement and injectable glucagon. They should be instructed to always check glucose levels before operating a motor vehicle, maintaining a level greater than 100 mg/dL, and should follow the recommendations set forth by the U.S. National Highway Traffic Safety Administration.^4,5

The most important part of the long-term management of HAAF is to avoid hypoglycemia, allowing the natural compensatory mechanisms (such as the epinephrine and glucagon responses) to recover. This may take up to 2 weeks for initial responsiveness and 3 months for full recovery.¹ In the case of generalized autonomic dysfunction, the target glucose level and HbA_1c levels should be increased to a point at which patients are far less likely to become hypoglycemic.

In the event of high morning glucose levels that are rebound effects of overnight low levels, the treatment may be to decrease nocturnal insulin or to change the timing of long-acting basal insulin.

Q. How does one prevent hypoglycemia unawareness?

A. The first interventions to prevent hypoglycemia unawareness include patient education and dietary intervention.¹ Patients should carefully monitor blood glucose levels during exercise and soon after. Medication adjustments may include discontinuation of sulfonylureas or glinides and changing basal and/or mealtime insulins. Insulin pump therapy may be appropriate for some individuals. Many patients also benefit from continuous glucose monitoring, with alarms set to warn for low glucose levels and trends before confusion and other hypoglycemic events occur. n

Kim A. Carmichael, MD, is an associate professor of medicine in the Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research at Washington University School of Medicine in St Louis, Missouri. He discloses that he is on the speakers bureaus for Merck and Janssen, which may be relevant to the content of this article.

References:

1. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. J Clin Endocrinol Metab. 2013;98(5): 1845-1859.
2. Cryer PE. Mechanisms of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med. 2013;369(4):362-372.
3. Moheet A, Kumar A, Eberly LE, Kim J, Roberts R, Seaquist ER. Hypoglycemia-associated autonomic failure in healthy humans: comparison of two vs three periods of hypoglycemia on hypoglycemia-induced counterregulatory and symptom response 5 days later. J Clin Endocrinol Metab. 2014;99(2):664-670.
4. National Highway Traffic Safety Administration. Driver Fitness Medical Guidelines. Publication HS 811 210. http://www.nhtsa.gov/DOT/NHTSA/Traffic%20Injury%20Control/Articles/Associated%20Files/811210.pdf. Published September 2009. Accessed December 7, 2015.
5. Carmichael KA. What do doctors need to teach their patients with diabetes about driving their vehicles? Consultant. 2014;54(4):271-272.