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Type 2 diabetes appears linked to brain degeneration
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Severity and duration of type 2 diabetes could contribute to brain degeneration, but not small vessel ischemic disease, according to research published in Radiology.
Patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study at the University of Minnesota, Wake Forest Medical School, Columbia University and Case Western Reserve University were invited to participate in the Memory in Diabetes substudy. Researchers looked at data from 614 patients (mean age, 62 years) to examine the association between type 2 diabetes and brain structure.
“As diabetes becomes more common, better understanding of the disease and its management becomes even more important in order to minimize its effect on patient health,” R. Nick Bryan, MD, PhD, professor of radiology at the Perelman School of Medicine at the University of Pennsylvania, said in a press release.
R. Nick Bryan
Bryan and colleagues evaluated baseline severity of diabetes in patients by testing fasting plasma glucose levels, HbA1c levels and duration of the condition (mean, 9.9 years). Through MRI with fluid-attenuated inversion recovery, proton-density, T2-weighted and T1-weighted sequences, post-processed with an automated computer algorithm, researchers classified brain tissue as gray or white matter and as normal or ischemic. Linear regression models were used to determine the relationship between diabetes measure and MRI outcomes.
Longer duration of diabetes and higher FPG levels were associated with lower normal (beta level=–0.431 and –0.053, respectively; P<.01) and total gray matter volumes (beta level=–0.428 and –0.053, respectively; P<.01). An inverse correlation was seen between FPG and ischemic lesion volume (beta level=–0.006; P<.04). HbA1c was not associated with any MRI measure.
“Our results suggested that, for every 10 years of diabetes duration, the brain of a patient with diabetes looks approximately 2 years older than that of a non-diabetic person, in terms of gray matter volume.” Bryan said. “They did not seem to have more vascular disease due to the direct effect of diabetes.”
These findings could have implications for decline of cognitive function in patients with diabetes, the researchers wrote, raising the possibility that cognitive changes are more related to neurodegenerative disorders such as Alzheimer’s disease than vascular dementia.
Disclosure: The study is from the Action to Control Cardiovascular Risk in Diabetes project, funded through an interagency agreement between the National Institute on Aging and the National Heart, Lung, and Blood Institute.
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Tamara L. Wexler, MD, PhD
This study of brain images in adults with type 2 diabetes suggests that loss of gray matter volume may be another sequelae of poor glucose control over time; Bryan and colleagues found that long durations of diabetes and higher fasting plasma glucose levels (FPG) were associated with reduced brain (gray matter) volume in their subjects, though not with white matter lesions.
The specific cohort and outcome measures are important in considering generalizability of study results. The cohort was drawn from a substudy of the ACCORD trial, using baseline data from 614 subjects deemed to have high risk for cardiovascular disease. Exclusion criteria included serum creatinine >1.5 mg/dL (133 mmol/L). The cohort was 55-69 years, largely white (68%), hypertensive (81%), and with a slight majority of males (56%).
Diabetes severity was assessed by fasting plasma glucose level (FPG), HbA1c, and duration of disease (by recall). Brain volume was measured on MRI from four centers, using automated image analysis (and thus avoiding intra-reader variability).
After controlling for covariates including prior cardiovascular disease and hypertension, the authors found that subjects with >15 years diabetes had a statistically significant lower volume of total gray matter than subjects with diabetes <4 years.
Curiously, while FPG was inversely correlated with brain matter volume, HbA1c did not show a correlation. While FPG and HbA1c provide a sense of current diabetes control, they do not provide information regarding recent hypoglycemic (or hyperglycemic) excursions, nor glucose control over prior years. It is likely that control of diabetes figures prominently in any end-organ damage including brain volume (the average HbA1c of this cohort was 8.2).
The clinical significance of the findings remains to be determined. Of note, these results demonstrate differences in radiographic measures, and not direct measures of cognitive function.
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