Severe hypoglycemia detrimental to long-term cognition in type 1 diabetes
medwireNews: Two studies, including a long-term DCCT analysis, highlight the importance of severe hypoglycemia in the risk for people with type 1 diabetes developing dementia.
The DCCT analysis, which is published in The Lancet Diabetes & Endocrinology, encompasses 32 years of follow-up of 1051 participants.
In a linked commentary, Brian Frier (University of Edinburgh, UK) notes that the role of hypoglycemia in cognitive decline did not emerge at the 18-year follow-up of this cohort, when only high glycated hemoglobin (HbA1c) was significantly associated with cognitive function.
This underlines “the inherent value of continuing longitudinal evaluation,” he writes.
By the 32-year follow-up, the participants were a median age of 59 years, and had a median diabetes duration of 37 years, and 68% had a history of hypertension. Over the course of the study, 482 participants had reported a total of 1608 episodes of severe hypoglycemia. Frier notes that this is likely an underestimate, given the DCCT’s narrow definition of hypoglycemia leading to seizure or coma.
Psychomotor and mental efficiency significantly declined from baseline to the 32-year follow-up, with average z-score decreasing by 1.36, having been only mildly reduced at the 18-year follow-up, and there were also slight reductions in immediate memory and delayed recall.
Higher HbA1c and blood pressure were significantly associated with psychomotor and mental efficiency, as was severe hypoglycemia, such that exposure to the three factors combined had an effect equivalent to that of aging 9.4 years.
Individually, each 1% HbA1c increase was equivalent to aging 3.3 years, each 5 mmHg rise in blood pressure was equivalent to 4.0 years of aging, and exposure to one or more severe hypoglycemia events had an effect equivalent to 4.6 years of aging.
Alan Jacobson (NYU Long Island School of Medicine, New York, USA) and study co-authors also found a dose–response relationship between the number of severe hypoglycemia events and psychomotor and mental efficiency, with the latter worsening across categories defined by exposure to no events, one to five events, and more than five events.
Frier notes that this cumulative effect is consistent with results from cross-sectional studies. And he points out that, of the three risk factors identified, “severe hypoglycaemia is probably the most difficult to eliminate since suboptimal glycaemic control and hypertension are more readily treatable.”
But he also cautions that it is not clear if the impact of these factors on cognition “would be perceptible clinically (if at all) and whether it would affect everyday activities, such as driving.”
On a similar theme, a study published in Neurology found that both severe hypoglycemia and severe hyperglycemia, identified in medical records using ICD-9 codes, were significantly associated with the risk for dementia in people with type 1 diabetes.
The 2821 individuals included in this study were identified in the Kaiser Permanente Northern California Diabetes Registry. During an average 6.9 years of follow-up, 5.4% of these people developed dementia, giving an age-adjusted rate of 14.3 per 1000 person–years.
The rate per 1000 person–years was approximately doubled in the 14.1% of the cohort with a history of at least one severe hypoglycemia event, at 26.5 versus 13.2 in those without exposure to severe hypoglycemia.
The corresponding rates per 1000 person–years were 79.6 versus 13.4 in the 11.9% with exposure to severe hyperglycemia versus those without, and 98.5 in the 3.1% of people with exposure to both events versus 12.8 in those with neither.
All associations between severe events and dementia risk remained significant after accounting for age, sex, race, HbA1c, depression, nephropathy, and stroke, report Rachel Whitmer (University of California Davis, USA) and co-researchers.
In his commentary, Frier writes: “As life expectancy for people with type 1 diabetes has steadily improved and many are now living much longer, the present observations have important clinical implications.”
He speculates that the aging brain might be particularly susceptible to the impact of severe hypoglycemia, especially in the context of co-existing cerebrovascular disease.
“In addition to the importance of maintaining metabolic and blood pressure control, the avoidance of severe hypoglycaemia is essential to preserve cognitive function later in life,” Frier concludes.
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