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Cerebral blood flow links insulin resistance and baroreflex sensitivity.

ABSTRACT: Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old) who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p < .05). Moreover, the relationship between insulin resistance and baroreflex sensitivity was statistically mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01). Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes.

SUBMITTER: Ryan JP

PROVIDER: S-EPMC3865223 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Cerebral blood flow links insulin resistance and baroreflex sensitivity.

Ryan John P JP Sheu Lei K LK Verstynen Timothy D TD Onyewuenyi Ikechukwu C IC Gianaros Peter J PJ

PloS one 20131216 12

Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulatio ...[more]

PMID: 24358272

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Project description:Recent studies in rabbits suggest that insulin resistance and reduced brain insulin contribute to impaired baroreflex control of heart rate (HR) during pregnancy; however, the mechanisms are unknown. The rat model is ideal to investigate these mechanisms because much is known about rat brain baroreflex neurocircuitry and insulin receptor locations. However, it is unclear in rats whether pregnancy impairs the HR baroreflex or whether insulin resistance is involved. Therefore, this study tested the hypothesis that in rats pregnancy decreases HR baroreflex sensitivity (BRS) and that this decrease is related to concurrent decreases in insulin sensitivity (IS). BRS was quantified before, during, and after pregnancy using complementary methods: 1) spontaneous BRS (sBRS) derived from sequence method analysis of telemetric, continuous arterial pressure recordings; and 2) maximal BRS of complete sigmoidal baroreflex relationships. IS was measured (hyperinsulinemic euglycemic clamp) to determine whether BRS and IS change in parallel. sBRS was reduced at midgestation [pregnancy day 10 (P10)], returned to nonpregnant (NP) levels on P18, and fell again at late gestation (P20) (sBRS in ms/mmHg: NP, 1.66 + or - 0.04; P10, 1.17 + or - 0.11; P18, 1.55 + or - 0.12; P20, 1.31 + or - 0.05; n = 5; P < 0.05). Similar triphasic patterns were observed for both maximal BRS [in beats x min(-1) x mmHg(-1): NP, 4.45 + or - 0.52 (n = 10); P11-12, 2.76 + or - 0.11 (n = 7); P17-18, 3.79 + or - 0.14 (n = 5); P19-20, 2.32 + or - 0.40 (n = 8); P < 0.0001] and previous and current measurements of IS (in mg glucose x kg(-1) x min(-1): NP, 32 + or - 2; P19-20, 15 + or - 1; P < 0.0005). Furthermore, during pregnancy, the standard deviation (SD) of MAP increased, and the SD of HR decreased, indirectly suggesting baroreflex impairment. sBRS increased transiently during parturition, and sBRS, maximal BRS, and IS normalized 3-4 days postpartum. In conclusion, pregnancy decreases HR BRS in rats. The parallel temporal changes in BRS and IS suggest a mechanistic link.

Project description:ImportanceCerebral microbleeds (CMBs) are collections of blood breakdown products that are a common incidental finding in magnetic resonance imaging of elderly individuals. Cerebral microbleeds are associated with cognitive deficits, but the mechanism is unclear. Studies show that individuals with CMBs related to symptomatic cerebral amyloid angiopathy have abnormal vascular reactivity and cerebral blood flow (CBF), but, to our knowledge, abnormalities in cerebral blood flow have not been reported for healthy individuals with incidental CMBs.ObjectiveTo evaluate the association of incidental CMBs with resting-state CBF, cerebral metabolism, cerebrovascular disease, β-amyloid (Aβ), and cognition.Design, setting, and participantsA cross-sectional study of 55 cognitively normal individuals with a mean (SD) age of 86.8 (2.7) years was conducted from May 1, 2010, to May 1, 2013, in an academic medical center in Pittsburgh; data analysis was performed between June 10, 2013, and April 9, 2015.Interventions3-Tesla magnetic resonance imaging was performed with susceptibility-weighted imaging or gradient-recalled echo to assess CMBs, arterial spin labeling for CBF, and T1- and T2-weighted imaging for atrophy, white matter hyperintensities, and infarcts. Positron emission tomography was conducted with fluorodeoxyglucose to measure cerebral metabolism and Pittsburgh compound B for fibrillar Aβ. Neuropsychological evaluation, including the Clinical Dementia Rating scale, was performed.Main outcomes and measuresMagnetic resonance images were rated for the presence and location of CMBs. Lobar CMBs were subclassified as cortical or subcortical. Measurements of CBF, metabolism, and Aβ were compared with the presence and number of CMBs with voxelwise and region-of-interest analyses.ResultsThe presence of cortical CMBs was associated with significantly reduced CBF in multiple regions on voxelwise and region-of-interest analyses (percentage difference in global CBF, -25.3%; P = .0003), with the largest reductions in the parietal cortex (-37.6%; P < .0001) and precuneus (-31.8%; P = .0006). Participants with any CMBs showed a nonsignificant trend toward reduced CBF. Participants with cortical CMBs had a significant association with greater prevalence of infarcts (24% vs 6%; P = .047) and demonstrated a trend to greater prevalence of deficits demonstrated on the Clinical Dementia Rating scale (45% vs 19%; P = .12). There was no difference in cortical amyloid (measured by Pittsburgh compound B positron emission tomography) between participants with and without CMBs (P = .60).Conclusions and relevanceIn cognitively normal elderly individuals, incidental CMBs in cortical locations are associated with widespread reductions in resting-state CBF. Chronic hypoperfusion may put these people at risk for neuronal injury and neurodegeneration. Our results suggest that resting-state CBF is a marker of CMB-related small-vessel disease.

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Cerebral blood flow links insulin resistance and baroreflex sensitivity.

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Cerebral blood flow links insulin resistance and baroreflex sensitivity.

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