Assessing interstitial fluid dynamics in type 2 diabetes mellitus and prediabetes cases through diffusion tensor imaging analysis along the perivascular space

Front Aging Neurosci. 2024 Mar 7:16:1362457. doi: 10.3389/fnagi.2024.1362457. eCollection 2024.

Abstract

Background and purpose: Glymphatic system in type 2 diabetes mellitus (T2DM) but not in the prodrome, prediabetes (Pre-DM) was investigated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Association between glymphatic system and insulin resistance of prominent characteristic in T2DM and Pre-DM between is yet elucidated. Therefore, this study delves into the interstitial fluid dynamics using the DTI-ALPS in both Pre-DM and T2DM and association with insulin resistance.

Materials and methods: In our cross-sectional study, we assessed 70 elderly individuals from the Bunkyo Health Study, which included 22 with Pre-DM, 18 with T2DM, and 33 healthy controls with normal glucose metabolism (NGM). We utilized the general linear model (GLM) to evaluate the ALPS index based on DTI-ALPS across these groups, considering variables like sex, age, intracranial volume, years of education, anamnesis of hypertension and hyperlipidemia, and the total Fazekas scale. Furthermore, we have explored the relationship between the ALPS index and insulin resistance, as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) using GLM and the same set of covariates.

Results: In the T2DM group, the ALPS index demonstrated a reduction compared with the NGM group [family-wise error (FWE)-corrected p < 0.001; Cohen's d = -1.32]. Similarly, the Pre-DM group had a lower ALPS index than the NGM group (FWE-corrected p < 0.001; Cohen's d = -1.04). However, there was no significant disparity between the T2DM and Pre-DM groups (FWE-corrected p = 1.00; Cohen's d = -0.63). A negative correlation was observed between the ALPS index and HOMA-IR in the combined T2DM and Pre-DM groups (partial correlation coefficient r = -0.35, p < 0.005).

Conclusion: The ALPS index significantly decreased in both the pre-DM and T2DM groups and showed a correlated with insulin resistance. This indicated that changes in interstitial fluid dynamics are associated with insulin resistance.

Keywords: diffusion-magnetic resonance imaging; glymphatic system; insulin resistance; prediabetes; type 2 diabetes mellitus.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was partially supported by the Juntendo Research Branding Project; the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI; Grant numbers 23H02865 and 23K14927); a Grant-in-Aid for Special Research in Subsidies for ordinary expenses of private schools from the Promotion and Mutual Aid Corporation for Private Schools of Japan; and the Brain/MINDS Beyond program of the Japan Agency for Medical Research and Development (AMED) under Grant Numbers JP18dm0307004 and JP19dm0307101 and AMED under Grant Number JP21wm0425006.