White Matter Lesions Linked to Rising Plasma Glucose

Daniel M. Keller, PhD

November 24, 2015

SANTIAGO, Chile — Higher fasting plasma glucose (FPG) levels are associated with a higher burden of brain white matter hyperintensities (WMH), particularly in the frontal lobes.

The association is especially strong in individuals with type 2 diabetes (T2D), a new study shows.

Lead author Nicolas Cherbuin, PhD, and colleagues in the Centre for Research on Ageing, Health and Wellbeing of the Australian National University in Canberra used data from the Personality and Total Health (PATH) Through Life Project, a large, longitudinal, population-based study investigating the time course and determinants of cognitive aging and mental health.

The study findings were presented here at the XXII World Congress of Neurology (WCN).

The PATH Through Life Project aims to follow approximately 7500 randomly selected adults in the greater Australian capital area over 20 years.

From an older age cohort (60 to 64 years; n = 2551), 401 community-living individuals were available for analysis. All were free of neurologic disorders, stroke, and gross brain abnormalities and had a Mini-Mental State Examination (MMSE) score of 27 or greater.

Using linear regression analysis, the researchers tested the association between FPG and WMH volumes, controlling for covariates of age, sex, intracranial volume, education, smoking, hypertension, body mass index (BMI), diabetes, and interactions of diabetes and sex.

Plasma glucose was measured after an overnight fast and was categorized as normal, defined as less than 5.6 mmol/L (<100.8 mg/dL), impaired (5.6 to 7 mmol/L [100.8 to 126 mg/dL]), or T2D (≥7 mmol/L [≥126 mg/dL] or self-report of T2D).

Patient groups with normal FPG (n = 276), impaired FPG (n = 86), or T2D (n = 39) were similar in age (approximately 63 years), education (14 years), and MMSE scores (29.26 to 29.45). BMI was higher in the impaired FPG and T2D groups than in the normal FPG group. There was also more hypertension in the T2D group.

WMH Mostly in Frontal and Temporal Lobes

Dr Cherbuin reported that among the entire cohort, higher FPG was associated with a higher burden of WMH in the right hemisphere (P = .02) but not in the left hemisphere. The effect was most prominent in the frontal and temporal lobes.

These findings were largely attributable to participants with impaired FPG or T2D, and the effect was most pronounced for participants with T2D.

Table. WMH Volumes per FPG Level

Location Normal FPG (n = 276) Impaired FPG (n = 86) T2D (n = 39)
Left hemisphere WMH (mm3) 2343.68 ± 2311.72 2331.07 ± 2528.34 2800.62 ± 2152.87
Right hemisphere WMH (mm3) 2379.59 ± 2645.19 2414.98 ± 2609.72 3199.79 ± 4031.47

Values are expressed as mean ± standard deviation.

 

Previous studies have shown that T2D is associated with brain atrophy, cognitive deficits, and increased risk for dementia. Elevated plasma glucose levels still within the normal range increase the risk for T2D.

Studies showed that in apparently healthy individuals, atrophy of the amygdala and hippocampus increased as FPG within the normal range increased. Striatum volumes decreased several years later in line with higher FPG or occult T2D. Functionally, poorer performance of fine motor skills is evident with higher FPG.

Session chairman Samuel Wiebe, MD, professor of neurology at the University of Calgary, Alberta, Canada, commented to Medscape Medical News that the present study intrigued him because it addresses the fact that the definition of normal glucose "maybe doesn't apply to everything…. You start having abnormalities in the brain even at levels that are within the normal range. This is important because, should we be defining normal glucose levels for different purposes?"

Higher levels of glucose even within the normal range may affect facets that are just beginning to be understood, such as white matter changes. "That's just one aspect. There could be other areas," he said. "So I think that that's an intriguing finding that deserves further study."

Dr Wiebe said the greater effect of elevated glucose seen in the frontal lobes may be related to some degree to their sheer size or to blood flow. "I think that the truth is that it is a spectrum. It begins to have an impact at a range of values that are lower than the cutoff" for traditional interventions, he said.

He feels it would be interesting to follow up this study with assessments that go beyond WMH volume measurements, such as tractography or connectivity studies that look at brain function.

There was no commercial funding for the study. Dr Cherbuin and Dr Wiebe have disclosed no relevant financial relationships.

XXII World Congress of Neurology (WCN). Abstract 434. Presented November, 2, 2015.

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