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Hyperglycemia, not insulin resistance, influences cognitive decline in type 1 diabetes
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Older adults with type 1 diabetes experience a pattern of cognitive decline that is similar to the decline observed in age-matched adults with type 2 diabetes, but such changes in those with type 1 diabetes are likely influenced more by hyperglycemia than insulin resistance, according to an analysis of three study cohorts.
“Two decades ago, patients with type 1 diabetes typically did not live beyond 55 years, an age before symptoms of late-onset dementia typically begin to arise,” Hillary Keenan MS, PhD, assistant professor of medicine at Harvard Medical School and associate director of epidemiology and biostatistics, rare disease, at Sanofi Genzyme, and colleagues wrote. “However, as longevity with type 1 diabetes increases, it is unknown whether these individuals have the same propensity for dementia or for accelerated aging pathologies as patients with type 2 diabetes. Therefore, evaluation of older individuals with type 1 diabetes for deficits in psychomotor efficiency, attention and executive function reported in young and middle-aged adults is warranted.”
Keenan and colleagues analyzed data from 82 adults with type 1 diabetes recruited from Joslin Diabetes Center’s Medalist study, a cohort of U.S. patients who have had type 1 diabetes for at least 50 years and who completed medical history questionnaires and underwent clinical and ophthalmic exams to evaluate disease complications (mean age, 67 years; 54.9% women; mean HbA1c, 7.1%). Researchers also analyzed data from 31 age-matched patients with type 2 diabetes (23 Joslin patients and 8 patients recruited online; mean age, 69 years; mean age at diagnosis, 50 years; 48.4% women; mean HbA1c, 8.1%) and 30 age-matched controls without diabetes recruited online (mean age, 64 years; 40% women). In the Medalist cohort, researchers additionally evaluated the association of complications with cognition.
All participants underwent cognitive assessment for general intelligence, executive function, working memory, long-term memory and psychomotor speed after exceeding a blood glucose of 4.4 mmol/L (snacks were given to some participants, with glucose readings taken every 15 minutes until level was reached). Tests completed included the Wechsler Abbreviated Scale of Intelligence, the Trail Making Number-Letter Switching subtest, the Letter-Number Sequence subtest, the Rey Auditory Verbal Learning Test and the Grooved Pegboard for both the dominant and nondominant hand.
Within the Medalist cohort, 34.6% had cardiovascular disease, 41.9% had proliferative diabetic retinopathy and 4.9% had diabetic nephropathy.
The mean Wechsler Abbreviated Scale of Intelligence scores were 120.3 for controls, 117.1 for patients with type 1 diabetes and 111.8 for those with type 2 diabetes. In initial analyses, people with type 1 and type 2 diabetes performed worse on measures of immediate and delayed recalls (P .002), psychomotor speed in both hands (P .01) and executive function (P = .05), according to the researchers.
“In unadjusted comparison, those with diabetes (type 1 and type 2) were similar on most facets,” the researchers wrote. “This remained true for immediate and delayed recall with adjustment for potential confounders of age and IQ among Medalists. Individuals with type 2 diabetes also performed worse than control subjects on these tests, with immediate recall reaching significance and delayed recall approaching significance.”
In analyzing complications data for the Medalists’ cohort, researchers observed the largest differences in cognitive function among those with and without CVD and those with and without diabetic retinopathy. In the Medalists’ cohort, typical hallmarks of insulin resistance were associated with cognitive deficits, including higher BMI (P = .02), higher prevalence of hypertension (P = .002) and statin use (P = .05). In Medalists, CVD was independently associated with executive function, even after adjustment for factors associated with insulin resistance (P = .03). HbA1c was also independently associated with executive function (P = .04), according to researchers.
“The underlying mechanism [in type 1 diabetes] is likely to be weighted more to hyperglycemia than insulin resistance, which is often the underlying culprit in type 2 diabetes,” the researchers wrote. “In Medalists, long-term hyperglycemia may have led to the accumulation of damage to both the parenchyma and vasculature of the brain.”
Keenan said most people with type 1 diabetes for at least 50 years show minimal signs of cognitive decline that, with effort, may be avoidable, and that further research will likely elucidate mechanisms and means to reduce this phenomenon.
“Additionally, the small deficits observed correlated with complications, predominantly cardiovascular disease, but some also with proliferative diabetic retinopathy and individuals with these pathologies may be a focus of increased screening,” Keenan said. “It is important to note that previous studies in the Medalists aged at least 50 years have shown moderate physical activity is associated with reduced prevalence of CVD.”
The researchers noted that efforts should be made to further study older adults with type 1 diabetes, including imaging studies to better understand neurodegenerative properties. – by Regina Schaffer
For more information:
Hillary Keenan MS, PhD, can be reached at Harvard Medical School, 25 Shattuck St, Boston, MA 02115; email: hillaryakeenan@gmail.com.
Disclosures: The Joslin Medalist study is supported by the NIDDK and the JDRF. The authors report no relevant financial disclosures.
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