Brain Atrophy and Type 1 Diabetes

By Norman Latov, MD, PhD

Professor of Neurology, Weill Cornell Medicine

SYNOPSIS: In a long-term longitudinal study of people with type 1 diabetes, excessive brain atrophy and cognitive dysfunction were noted compared to healthy controls. The investigators calculated that type 1 diabetes resulted in six years of accelerated brain aging and brain atrophy that was separate and distinct from Alzheimer’s disease.

SOURCE: Habes M, Jacobson AM, Braffett BH, et al. Patterns of regional brain atrophy and brain aging in middle- and older-aged adults with type 1 diabetes. JAMA Netw Open 2023;6: e2316182.

Habes and colleagues compared differences in cognitive functions and neuroimaging markers of brain atrophy in patients with type 1 diabetes with healthy subjects as controls. The authors previously developed machine learning-derived indices for differentiating between age-related grey matter patterns of atrophy in cognitively normal adults and patterns of atrophy in patients with Alzheimer’s disease. Patients with diabetes were recruited from the Diabetes Control and Complications Trial (DCTT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study.

The study compared 416 EDIC subjects with type 1 diabetes, a median age of 60 years (range 44-74 years), and a median diabetes duration of 37 years (range 30-51 years), to 99 matched healthy controls. Cognitive function was evaluated using psychomotor and mental efficiency tests found to be particularly sensitive to diabetes, and tests of memory known to be sensitive to normal aging and mild cognitive impairment. The authors found that subjects with type 1 diabetes exhibited six additional years of brain aging (atrophy) compared to controls. Among EDIC participants, greater brain aging was statistically significantly associated with lower psychomotor and mental efficiency (P < 0.001). Psychomotor and mental efficiency scores were associated with volumes of the superior temporal gyrus, planum temporale, parietal operculum, thalamus proper area, and middle frontal gyrus and angular gyrus. There were no differences in markers of Alzheimer’s disease as determined by patterns of regional brain atrophy. Magnetic resonance imaging changes were not associated with measures of glycemia or with measures of diabetes-related complications, such as neuropathy, retinopathy, or kidney disease.

COMMENTARY

The study findings indicated that type 1 diabetes is associated with a pattern of brain atrophy and cognitive decline beginning in middle age that is consistent with accelerated aging of about six years in comparison to healthy subjects. As such, brain atrophy or accelerated aging can be added to the list of known diabetic complications. The pattern of brain atrophy was different than that associated with Alzheimer’s disease, indicating that the cognitive decline was not caused by Alzheimer’s disease, and that type 1 diabetes is not associated with a higher risk of developing Alzheimer’s disease.

Although the pattern of brain atrophy is similar to that associated with normal aging, given our lack of understanding of the processes underlying aging or the consequences of diabetes, it is not possible to know whether the same mechanisms are responsible for the brain atrophy in both. Accordingly, the term “diabetic brain atrophy” would be more appropriate than “accelerated aging” to describe the condition.

In other conditions associated with diabetes, such as neuropathy, retinopathy, or renal disease, suspected mechanisms include hyperglycemia, hypoglycemia, micro- or macro-vascular disease, inflammation, insulin resistance, oxidative stress, mitochondrial dysfunction, and coagulation or endothelial abnormalities.¹ These also are likely to be applicable to diabetic brain atrophy.

Given the multiple potential mechanisms or pathways that are affected by diabetes, it is unlikely that any one drug that targets a particular pathway would have significant benefit in preventing the atrophy. Presently, optimal treatment of diabetes aims at reducing the blood glucose levels to normal or near-normal levels while avoiding hypoglycemia, which can be difficult to achieve. However, promising research into the use of stem cell-derived islet cells to replenish the insulin-producing cells in the pancreas provides hope for a cure.²

REFERENCES

1. Husain KH, Sarhan SF, AlKhalifa H, et al. Dementia in diabetes: The role of hypoglycemia. Int J Mol Sci 2023;24:9846.
2. Drew L. How stem cells could fix type 1 diabetes. Nature. Published July 14, 2021. https://www.nature.com/articles/d41586-021-01842-x