Background: Patients with KATP channel related diabetes (KATP-DM) experience improved glycemic control with sulfonylurea therapy, but the degree of improvement in their spectrum of neurological dysfunction remains unclear. We hypothesized that patients with KATP-DM have differences in brain white matter and associated neurodevelopmental impairments when compared to those with type 1 diabetes or sibling controls.
Methods: Subjects (8-20 years old) from the Monogenic Diabetes Registry at the University of Chicago included those with KATP-DM (n=8), type 1 or other non-KATP diabetes (n=7), and sibling controls (n=6). All participants had brain MRI with diffusion tensor imagining (DTI) on a 3T Philips Achieva Quasar scanner. Fractional anisotropy (FA) was used as an indirect measurement of myelin in the brain. Subjects also participated in validated neurodevelopmental assessments.
Results: Nonparametric Kruskal-Willis testing of analyzable DTI data [4 KATP-DM, 5 T1DM, 3 siblings] revealed that FA values of the corpus callosum were not statistically different (p=0.58). However, DTI of the white matter tracks in the right hippocampus approached a significant difference among the three groups (p=0.07). Third ventricular volumes among all three groups [9 KATP-DM, 7 T1DM, 5 siblings] were significantly different (p=0.05). Significant differences between groups as determined by one-way ANOVA were found in Perceptual IQ (F (2,14)=4.862, p=.025); visual motor integration (F (2,14)=5.579, p=.017); and graphomotor coordination (F (2,14)=5.399, p=.018).
Conclusion: In this first study using quantitative MRI methods in patients with KATP-DM, DTI revealed no overall difference but possible regional variation in FA, while ventricular volume and neurodevelopmental function were different among this cohort. Larger studies are needed to assess the potential differences in brain white matter as well as the benefits of early sulfonylurea therapy on neurologic development.
M.B. Lemelman: None. J. Wren-Jarvis: None. M.N. Scott: None. R. Martin: None. D. Carmody: Research Support; Self; Novo Nordisk Inc.. K. Wroblewski: None. S. Keedy: None. S.W. Greeley: Research Support; Self; Novo Nordisk Inc..