Microvascular function mediates link between adiposity, cognitive decline in diabetics

Impaired endothelium-independent vascular smooth muscle reactivity negotiates the relationship between poor cognitive performance and high visceral adiposity in elderly adults with type 2 diabetes (T2D), according to a new Singapore study.

“The mechanism(s) linking central adiposity and cognitive deficits in older adults with T2D is not well elucidated. Blunted endothelium-independent vasodilation mediated the association between increased visceral adiposity and reduced cognition that may represent a distinctive feature in T2D,” said researchers. “Therefore, strategies to decrease visceral fat and preserve VSMC function may mitigate cognitive impairment.”

In 907 elderly T2D patients (mean age, 64±6 years; 50 percent male), the mean cognitive performance scores, measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Mini-Mental State Examination (MMSE), were 99.8±7.1 and 28.2±2.2, respectively. [Microcirculation 2020;doi:10.1111/micc.12609]

Visceral fat area (VFA) was generally high in the cohort, with a mean value of 129.2±37.2 cm². The median absolute differences in skin microcirculation perfusion before and after endothelium-dependent (EDV) and -independent (EIV) vasodilation were 49.2 and 25.5 PU, respectively.

Separate linear regression models found that VFA was significantly correlated with the total RBANS score. The same was true for the RBANS domains of delayed and immediate memory. VFA was also significantly associated with MMSE, but not with language, attention or visuospatial/constructional performance.

Notably, adjusting for EIV attenuated the relationship VFA and RBANS score.

Researchers found that EIV had a partially mediating effect on the link between VFA and the total RBANS score. It exerted similar effects on the relationship between VFA and immediate memory, delayed memory and MMSE score. No mediating effect was recorded for language, attention and visuospatial/constructional abilities.

In comparison, EDV did not correlate independently with neither RBANS nor MMSE, and demonstrated no mediatory effect on the link between VFA and any cognitive function variable.

“This is the first study to demonstrate a potential mediatory role of impaired EIV in the relationship between visceral adiposity and diminished cognition, specifically immediate and delayed memory abilities,” the researchers said, suggesting that microvascular function may be a key player in the cognitive declines attributable to adiposity in diabetics.

“The association may be driven by augmented production of reactive oxygen species by adipocytes, leading to increased oxidative stress,” they explained. “This process, in turn, causes deranged expression and secretion of inflammatory adipokines such as leptin.”

Consistent and high levels of leptin on obesity have been shown to play a role in vascular smooth muscle dysfunction by weakening vascular relaxation. [Am J Physiol Regul Integr Comp Physiol 2016;310:R960-967]

The present findings may also indicate that strategies to reduce visceral fat and preserve vascular smooth muscle cell function may help counter cognitive decline in this population, the researchers added.