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Prospectively determined impact of type 1 diabetes on brain volume during development.

Perantie DC, Koller JM, Weaver PM, Lugar HM, Black KJ, White NH, Hershey T - Diabetes (2011)

Bottom Line: The T1DM and nondiabetic control (NDC) sibling groups did not differ in whole brain or voxel-wise change over the 2-year follow-up.However, within the T1DM group, participants with more hyperglycemia had a greater decrease in whole brain gray matter compared with those with less hyperglycemia (P < 0.05).Participants who experienced severe hypoglycemia had greater decreases in occipital/parietal white matter volume compared with those with no severe hypoglycemia (P < 0.05) and compared with the NDC sibling group (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA.

ABSTRACT

Objective: The impact of type 1 diabetes mellitus (T1DM) on the developing central nervous system is not well understood. Cross-sectional, retrospective studies suggest that exposure to glycemic extremes during development is harmful to brain structure in youth with T1DM. However, these studies cannot identify brain regions that change differentially over time depending on the degree of exposure to glycemic extremes.

Research design and methods: We performed a longitudinal, prospective structural neuroimaging study of youth with T1DM (n = 75; mean age = 12.5 years) and their nondiabetic siblings (n = 25; mean age = 12.5 years). Each participant was scanned twice, separated by 2 years. Blood glucose control measurements (HbA(1c), glucose meter results, and reports of severe hypoglycemia) were acquired during the 2-year follow-up. Sophisticated image registration algorithms were performed, followed by whole brain and voxel-wise statistical analyses of the change in gray and white matter volume, controlling for age, sex, and age of diabetes onset.

Results: The T1DM and nondiabetic control (NDC) sibling groups did not differ in whole brain or voxel-wise change over the 2-year follow-up. However, within the T1DM group, participants with more hyperglycemia had a greater decrease in whole brain gray matter compared with those with less hyperglycemia (P < 0.05). Participants who experienced severe hypoglycemia had greater decreases in occipital/parietal white matter volume compared with those with no severe hypoglycemia (P < 0.05) and compared with the NDC sibling group (P < 0.05).

Conclusions: These results demonstrate that within diabetes, exposure to hyperglycemia and severe hypoglycemia may result in subtle deviation from normal developmental trajectories of the brain.

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A: Mean ± SEM percent change in whole brain gray matter across hyperglycemia subgroups and NDCs. *Different from other HbA1c groups (P < 0.05) and marginally different from NDC (P = 0.06). B: Occipital/parietal white matter across severe hypoglycemia subgroups and NDCs. *Different from other groups (P < 0.05). C: Statistical image showing occipital/parietal region where T1DM with any hypoglycemia differ from T1DM with no hypoglycemia. Hypo, hypoglycemia. (A high-quality digital representation of this figure is available in the online issue.)
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Figure 2: A: Mean ± SEM percent change in whole brain gray matter across hyperglycemia subgroups and NDCs. *Different from other HbA1c groups (P < 0.05) and marginally different from NDC (P = 0.06). B: Occipital/parietal white matter across severe hypoglycemia subgroups and NDCs. *Different from other groups (P < 0.05). C: Statistical image showing occipital/parietal region where T1DM with any hypoglycemia differ from T1DM with no hypoglycemia. Hypo, hypoglycemia. (A high-quality digital representation of this figure is available in the online issue.)

Mentions: Hierarchical linear regression revealed that higher 2-year mean HbA1c was associated with greater decreases in whole brain gray matter after controlling for age, sex, and age of onset [F change(1,62) = 6.1, P = 0.017]. To compare with NDC, we performed general linear modeling analyses using HbA1c subgroups and the NDC group. This analysis revealed a main effect of time [F(1,94) = 10.2, P = 0.002], and an interaction between time and group [F(3,94) = 3.3, P = 0.025] (Table 3). Pairwise comparisons showed that the high-HbA1c group had a significantly greater percent decrease in whole brain gray matter over time than the low-HbA1c (P = 0.04) and medium-HbA1c subgroups (P = 0.002), but not compared with the NDC group (P = 0.06) (Fig. 2A). Change in whole brain white matter was not associated with mean HbA1c [F change(1,62) = 0.45, P = 0.51].


Prospectively determined impact of type 1 diabetes on brain volume during development.

Perantie DC, Koller JM, Weaver PM, Lugar HM, Black KJ, White NH, Hershey T - Diabetes (2011)

A: Mean ± SEM percent change in whole brain gray matter across hyperglycemia subgroups and NDCs. *Different from other HbA1c groups (P < 0.05) and marginally different from NDC (P = 0.06). B: Occipital/parietal white matter across severe hypoglycemia subgroups and NDCs. *Different from other groups (P < 0.05). C: Statistical image showing occipital/parietal region where T1DM with any hypoglycemia differ from T1DM with no hypoglycemia. Hypo, hypoglycemia. (A high-quality digital representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3198062&req=5

Figure 2: A: Mean ± SEM percent change in whole brain gray matter across hyperglycemia subgroups and NDCs. *Different from other HbA1c groups (P < 0.05) and marginally different from NDC (P = 0.06). B: Occipital/parietal white matter across severe hypoglycemia subgroups and NDCs. *Different from other groups (P < 0.05). C: Statistical image showing occipital/parietal region where T1DM with any hypoglycemia differ from T1DM with no hypoglycemia. Hypo, hypoglycemia. (A high-quality digital representation of this figure is available in the online issue.)
Mentions: Hierarchical linear regression revealed that higher 2-year mean HbA1c was associated with greater decreases in whole brain gray matter after controlling for age, sex, and age of onset [F change(1,62) = 6.1, P = 0.017]. To compare with NDC, we performed general linear modeling analyses using HbA1c subgroups and the NDC group. This analysis revealed a main effect of time [F(1,94) = 10.2, P = 0.002], and an interaction between time and group [F(3,94) = 3.3, P = 0.025] (Table 3). Pairwise comparisons showed that the high-HbA1c group had a significantly greater percent decrease in whole brain gray matter over time than the low-HbA1c (P = 0.04) and medium-HbA1c subgroups (P = 0.002), but not compared with the NDC group (P = 0.06) (Fig. 2A). Change in whole brain white matter was not associated with mean HbA1c [F change(1,62) = 0.45, P = 0.51].

Bottom Line: The T1DM and nondiabetic control (NDC) sibling groups did not differ in whole brain or voxel-wise change over the 2-year follow-up.However, within the T1DM group, participants with more hyperglycemia had a greater decrease in whole brain gray matter compared with those with less hyperglycemia (P < 0.05).Participants who experienced severe hypoglycemia had greater decreases in occipital/parietal white matter volume compared with those with no severe hypoglycemia (P < 0.05) and compared with the NDC sibling group (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA.

ABSTRACT

Objective: The impact of type 1 diabetes mellitus (T1DM) on the developing central nervous system is not well understood. Cross-sectional, retrospective studies suggest that exposure to glycemic extremes during development is harmful to brain structure in youth with T1DM. However, these studies cannot identify brain regions that change differentially over time depending on the degree of exposure to glycemic extremes.

Research design and methods: We performed a longitudinal, prospective structural neuroimaging study of youth with T1DM (n = 75; mean age = 12.5 years) and their nondiabetic siblings (n = 25; mean age = 12.5 years). Each participant was scanned twice, separated by 2 years. Blood glucose control measurements (HbA(1c), glucose meter results, and reports of severe hypoglycemia) were acquired during the 2-year follow-up. Sophisticated image registration algorithms were performed, followed by whole brain and voxel-wise statistical analyses of the change in gray and white matter volume, controlling for age, sex, and age of diabetes onset.

Results: The T1DM and nondiabetic control (NDC) sibling groups did not differ in whole brain or voxel-wise change over the 2-year follow-up. However, within the T1DM group, participants with more hyperglycemia had a greater decrease in whole brain gray matter compared with those with less hyperglycemia (P < 0.05). Participants who experienced severe hypoglycemia had greater decreases in occipital/parietal white matter volume compared with those with no severe hypoglycemia (P < 0.05) and compared with the NDC sibling group (P < 0.05).

Conclusions: These results demonstrate that within diabetes, exposure to hyperglycemia and severe hypoglycemia may result in subtle deviation from normal developmental trajectories of the brain.

Show MeSH
Related in: MedlinePlus