Variation of HbA1c affects cognition and white matter microstructure in healthy, young adults
Jonathan Repple, Greta Karliczek, Susanne Meinert, Katharina Foerster, Dominik Grotegerd, Janik Goltermann, Volker Arolt, Bernhard Baune, Udo Dannlowski, Nils Opel
doi: https://doi.org/10.1101/507186

Abstract
The metabolic serum marker HbA1c has been associated with both impaired cognitive performance and altered white matter integrity in patients suffering from diabetes mellitus. However, it remains unclear if higher levels of HbA1c might also affect brain
structure and function in healthy subjects. With the present study we therefore aimed to investigate the relationship between HbA1c levels and cognitive performance as well as white matter microstructure in healthy, young adults. To address this question,
associations between HbA1c and cognitive measures (NIH Cognition Toolbox) as well as DTI-derived imaging measures of white matter microstructure were investigated in a publicly available sample of healthy, young adults as part of the Humane Connectome
Project (n= 1206, mean age= 28.8 years, 45.5 % male). We found that HbA1c levels (range 4.1-6.3%) were significantly inversely correlated with measures of cognitive performance. Higher HbA1c levels were associated with significant and wide-spread
reductions in fractional anisotropy (FA) controlling for age, sex, body-mass index and education. FA reductions were furthermore found to covary with measures of cognitive performance. The same pattern of results could be observed in analyses restricted
to participants with HBA1c levels below 5.7%. The present study demonstrates that low-grade HbA1c variation below diagnostic threshold for diabetes is related to both cognitive performance and white matter integrity in healthy, young adults. These
findings highlight the detrimental impact of metabolic risk factors on brain physiology and underscore the importance of intensified preventive measures independent of the currently applied diagnostic HbA1c cut-off scores.

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"blood glucose, HbA1c, LDL/HDL ratio and heart rate were significantly decreased by phlebotomy"

Effects of phlebotomy-induced reduction of body iron stores on
metabolic syndrome: Results from a randomized clinical trial
Khosrow S Houschyar, Rainer Ludtke, Gustav J Dobos, Ulrich Kalus,
Martina Brocker-Preuss, Thomas Rampp, Benno Brinkhaus and Andreas
Michalsen
BMC Medicine 2012, 10:54 doi:10.1186/1741-7015-10-54
Published: 30 May 2012

Abstract (provisional)
Background
Metabolic syndrome (METS) is an increasingly prevalent but poorly
understood clinical entity characterized by insulin resistance,
glucose intolerance, dyslipidemia, hypertension and obesity. Increased oxidative stress catalyzed by accumulation of iron in excess of
physiologic requirements has been implicated in the pathogenesis of
METS but cause-and-effect relationships remain uncertain. The
hypothesis that phlebotomy-induced reduction of body iron stores would
alter clinical manifestations of METS was tested by a randomized
trial.
Methods
In a randomized-controlled single-blinded clinical trial 64 patients
with METS were randomly assigned to iron reduction by phlebotomy
(n=33) or to a waiting-list control group (n=31). Iron reduction
patients had 300ml of blood removed at entry and between 250-500ml
removed after 4 weeks depending on entry ferritin levels. Primary
outcomes were change of systolic blood pressure and of insulin
sensitivity as measured by HOMA-Index after 6 weeks. Secondary
outcomes included HbA1c, plasma-glucose, blood lipids and heart rate.
Results
Systolic blood pressure decreased from 148.5+/-12.3 mmHg to
130.5+/-11.8 mm Hg in the phlebotomy group and from 144.7+/-14.4 mmHg
to 143.8+/-11.9 mmHg in the control group (difference -16.6 mmHg;95%- CI:-20.7;-12.5;p<0.001). No significant effect on the HOMA-Index was
observed. Among secondary outcomes, blood glucose, HbA1c, LDL/HDL
ratio and heart rate were significantly decreased by phlebotomy.
Changes in blood pressure and HOMA-Index were correlated with
reduction of ferritin.
Conclusions
In patients with METS, phlebotomy with consecutive reduction of body
iron stores lowered blood pressure and resulted in improvements of
markers of cardiovascular risk and glycemic control. Blood donation
may have beneficial effects for donating subjects with METS.

Trial registration: ClinicalTrials.gov: NCT01328210
Please see related article: http://www.biomedcentral.com/1741-7015/10/53

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