Insulin resistance damages brain white matter even with normal glucose

Insulin resistance (IR) exposes the brain along with the rest of the body to elevated insulin levels produced to overcome receptor resistance. Following earlier studies noted here including Dementia risk increased by higher blood sugar before diabetes, a new study just published in the journal Neurology offers yet more evidence that the higher levels of insulin damage brain white matter well before glucose and HgbA1c levels become elevated.To investigate the relationship between insulin resistance and brain white matter (WM, myelinated axonal tissue) damage the authors correlated diffusion tensor imaging of the brains of 127 subjects age 41–86 years with insulin resistance as determined by the homeostasis model assessment of IR (HOMA-IR). There was indeed a significant association:

"Participants were divided into 2 groups based on HOMA-IR values: “high HOMA-IR” (≥2.5, n = 27) and “low HOMA-IR” (<2.5, n = 100)...The high HOMA-IR group demonstrated decreased axial diffusivity broadly throughout the cerebral WM in areas such as the corpus callosum, corona radiata, cerebral peduncle, posterior thalamic radiation, and right superior longitudinal fasciculus, and WM underlying the frontal, parietal, and temporal lobes, as well as decreased fractional anisotropy in the body and genu of corpus callosum and parts of the superior and anterior corona radiata, compared with the low HOMA-IR group, independent of age, WM signal abnormality volume, and antihypertensive medication status. These regions additionally demonstrated linear associations between diffusion measures and HOMA-IR across all subjects, with higher HOMA-IR values being correlated with lower axial diffusivity."

In other words, regardless of age, higher insulin resistance predicted more abnormalities in the brain white matter. The authors conclude:

"In generally healthy adults, greater IR is associated with alterations in WM tissue integrity. These cross-sectional findings suggest that IR contributes to WM microstructural alterations in middle-aged and older adults. "

Clinical note: It is imperative for practitioners to assess for insulin resistance well before HgbA1c and glucose become elevated.