Miriam E Tucker

September 29, 2015

STOCKHOLM — People with type 1 diabetes who have impaired awareness of hypoglycemia perform less well on neuropsychological tests than do those who are able to sense symptoms of low blood sugar, a new study finds.

The results were presented September 16, 2015, at the European Association for the Study of Diabetes (EASD) 2015 Meeting by Marit Rokne Bjørgaas, MD, PhD, of the Norwegian University of Science and Technology (NTNU) and St Olav's University Hospital, Trondheim, Norway.

Impaired awareness of hypoglycemia — a complication that develops in some patients after a long duration of type 1 diabetes and is often accompanied by autonomic neuropathy — increases the risk for severe hypoglycemia, which can lead to neuronal loss or injury, Dr Bjørgaas explained in her introduction.

In her cross-sectional study, 33 patients with type 1 diabetes and impaired hypoglycemic awareness performed less well on a neuropsychological test battery compared with type 1 diabetes patients with intact awareness and healthy controls. In particular, impairments were seen in tests measuring hippocampal function.

"We did not assess premorbid intelligence or cognition, so causality can't be inferred. But we hypothesize that the cognitive impairment may have been caused by recurrent episodes of severe hypoglycemia," Dr Bjørgaas said.

Asked to comment, session moderator Brian Frier, MD, honorary professor of diabetes at the University of Edinburgh, Scotland, told Medscape Medical News, "I think it's a very important question that has to be addressed. It's a very nice study and they've done it very carefully."

However, he cautioned, "These people would probably be perfectly normal in most ways. When you put them under a testing situation in a laboratory, then you find abnormalities. It doesn't mean most of these people with impaired awareness are going around with severe cognitive impairment."

Nonetheless, he continued, "I think this is a group of patients who need to be followed to see if, particularly in the long term on a longitudinal level, recurrent exposure to severe hypoglycemia causes cognitive impairment and cognitive decline. That's very important clinically."

Dr Frier told Medscape Medical News that the current preferred term in the field is "impaired hypoglycemic awareness" rather than "hypoglycemic unawareness," because patients often retain partial ability to sense symptoms.

Impairments Seen in Tests of Hippocampal Function

The 33 patients were deemed to have impaired hypoglycemic awareness based on a score of 4 or higher on the 7-point Gold Score, in which 1 is "always" aware and 7 "never" aware of hypoglycemia onset.

They were matched by gender, age, and diabetes duration with 35 type 1 diabetes patients who had "normal" awareness, defined as a Gold score of 1 or 2. Another 37 age- and gender-matched people without diabetes served as controls.

All underwent a web-based cognitive test battery. These included hippocampal-dependent tests of verbal memory (immediate and delayed recall), "objects in grid" (assessing spatial memory and immediate recall), and pattern separation (image recall).

Tests of prefrontal-parietal function included the "digit span backward" (assessing working memory), coding (executive functions and processing speed), and the "Tower of London" test (planning abilities).

The testing was postponed if the subject had symptomatic hypoglycemia the night before or on the morning of the test, and those with type 1 diabetes were given snacks just prior to the assessment tests to minimize the risk of hypoglycemia.

Slightly more than half of the subjects were female. They had a mean age of 47 years, and those with type 1 diabetes had a duration of about 30 years, with a mean HbA1c of about 8%. A quarter of the group with impaired hypoglycemic awareness used insulin pumps, compared with 30% of those with normal awareness.

More than a third (39%) of the group with impaired awareness had experienced at least one severe hypoglycemic episode — defined as having convulsions, loss of consciousness, or need for assistance — in the preceding year, compared with 20% of the group with normal hypoglycemic awareness. Few of either group had experienced three or more such episodes, 12% vs 3%. All study subjects had similar educational levels.

Those with impaired awareness of hypoglycemia had significantly worse results in pattern separation (P = .007), verbal memory delayed-recall test (P = 0.018), and objects-in-grid immediate recall (P = 0.043).

Which Came First?

Dr Frier noted, as Dr Bjørgaas herself had, that not having information about the IQ levels of these patients prior to developing the impairments in hypoglycemic awareness is a study flaw, since it's possible that people who are cognitively impaired to begin with may be less able to manage their diabetes well.

He also pointed out, "The problem with all the cognitive tests is there's a big overlap between domains. She's testing a number of different domains, but there's a big overlap."

Still, he said the study is an important step and the topic should be pursued further. "What it says is that when you test them, they're less good at some tests, which may be the effects of recurrent hypoglycemia over many years. The real key is what's going to happen to these people in the future."

In the meantime, Dr Frier doesn't advise routine cognitive function testing for everyone with hypoglycemic unawareness, but "there are occasional anecdotal cases where patients will say they're impaired. You should test those. Patients will tell you."

The study was funded by NTNU, St Olav's Hospital, Nord-Trøndelag Regional Health Authorities, the Norwegian Diabetes Association, the Norwegian Extra Foundation for Health and Rehabilitation, and the Johan Selmer Kvanes Legacy for Diabetes Research. Dr Bjørgaas and Dr Frier have no relevant financial relationships.

European Association for the Study of Diabetes 2015 Meeting; Stockholm, Sweden. Abstract 124, presented September 16, 2015.


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