Purpose

Increasing neuroimaging studies of voxel-based morphometry (VBM) have revealed gray matter (GM) anomalies in patients with type 2 diabetes mellitus (T2DM)1. However, not all the studies reported entirely consistent findings, which may be due to small and heterogeneous samples of participants2-4, there has been increasing interest in using the meta-analysis approach to identify consistent results. So the aim of our study was to identify the alternations of global gray matter volumes (GMV) and consistent regional abnormalities in T2DM patients.

Method

A systematic search of relevant studies published in PubMed and Embase databases from January 2000 to March 2016 was conducted using a combination of keywords: (“voxel-based” OR “voxel-wise” OR “volumetric” OR “voxel based morphometry” OR “VBM” OR “morphometry” OR “gray matter”) AND (“diabetes” OR “diabetic” OR “diabetes mellitus” OR “type 2 diabetes mellitus” OR “T2DM”). Neuroimaging studies of both volumetric data and whole-brain VBM data were included. A quantitative meta-analysis of volumetric and whole-brain VBM studies in patients with T2DM compared with healthy controls (HCs) were performed by means of STATA package v.12.0 and anisotropic effect size version of signed differential mapping (AES-SDM) software package respectively.

Result

A total of 15 volumetric studies(1561 T2DM patients and 869 HCs) and 5 VBM studies (110 T2DM patients and 103 HCs) on GM investigations in T2DM patients vs. HCs were identified. The volumetric meta-analysis showed that there were significant differences (SMD=−0.56,95%CI=−0.81 to −0.31, P<0.01) of GMV between the two groups, suggesting that GMV of patients with T2DM was lower than HCs. The whole-brain VBM meta-analysis revealed that gray matter reductions in the left superior temporal gyrus, the right middle temporal gyrus, the right rolandic operculum, and the left fusiform gyrus in the T2DM patients compared with the HCs. No GMV increases were found. The results remained largely unchanged in the following jackknife sensitivity analyses. Meta-regression analysis showed that Mini-Mental State Examination (MMSE) scores have a positive relationship with the GMV in the right insula.

Discussion

We have revealed widespread GM atrophy, as well as regional atrophy, particularly in the right MTG. The MTG is implicated in neurodegeneration in T2DM such as regional neuronal loss, vascular abnormalities, micro-infarcts, hypometabolism, lower cerebral blood flow, and the like1,4. The MTG is part of the default mode network (DMN), which has been closely linked to cognition functions5. Based on these findings, we suggest that MTG atrophy may relate to cognitive dysfunction, and accelerate the transition from normal cognition to MCI in T2DM patients. The fusiform gyri are frequently identified a "visual-form area"6, our results show that The fusiform gyri is atropht inT2DM patients, which suggests that T2DM may have attention, memory and visual dysfunction. Another finding in our meta-analysis was that MMSE scores had a positive relationship with GMV in the right insula. The insula plays important integrative roles, it is also a core node of the salience network which is damaged in AD and MCI7-8

Conclusion

To our knowledge, this is the first whole-brain VBM meta-analysis showing the reduced volume of whole and regional gray matter in brain of T2DM patients, especially in the temporal lobe; the GM volumes of right insula had a positive relationship with MMSE scores, and those changes may be risk for the dementia. Further longitudinal search is need to confirm the gray matters changes and cognition dysfunction and their relationship to understand the pathophysiological mechanism underlying T2DM-induced cognitive impairment.

Acknowledgements

No acknowledgement found.

References

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