Resting-State Brain Functional Connectivity Is Altered in Type 2 Diabetes

  1. Wouter S. Hoogenboom1,9
  1. 1Research Division, Joslin Diabetes Center, Boston, Massachusetts
  2. 2Department of Psychiatry, Harvard Medical School, Boston, Massachusetts
  3. 3Winthrop University Hospital, Mineola, New York
  4. 4Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, Massachusetts
  5. 5Brain Imaging Center, McLean Hospital, Belmont, Massachusetts
  6. 6Department of Medicine, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts
  7. 7Department of Medicine, Harvard Medical School, Boston, Massachusetts
  8. 8Departments of Psychiatry, Psychiatry and Behavioral Science Imaging, Brigham and Women’s Hospital, Boston, Massachusetts
  9. 9Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Boston, Massachusetts
  10. 10Clinical Neuroscience Division, Laboratory of Neuroscience, VA Boston Healthcare System, Harvard Medical School, Brockton, Massachusetts
  1. Corresponding author: Gail Musen, gail.musen{at}


Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). Populations at risk for AD show altered brain activity in the default mode network (DMN) before cognitive dysfunction. We evaluated this brain pattern in T2DM patients. We compared T2DM patients (n = 10, age = 56 ± 2.2 years, fasting plasma glucose [FPG] = 8.4 ± 1.3 mmol/L, HbA1c = 7.5 ± 0.54%) with nondiabetic age-matched control subjects (n = 11, age = 54 ± 1.8 years, FPG = 4.8 ± 0.2 mmol/L) using resting-state functional magnetic resonance imaging to evaluate functional connectivity strength among DMN regions. We also evaluated hippocampal volume, cognition, and insulin sensitivity by homeostasis model assessment of insulin resistance (HOMA-IR). Control subjects showed stronger correlations versus T2DM patients in the DMN between the seed (posterior cingulate) and bilateral middle temporal gyrus (β = 0.67 vs. 0.43), the right inferior and left medial frontal gyri (β = 0.75 vs. 0.54), and the left thalamus (β = 0.59 vs. 0.37), respectively, with no group differences in cognition or hippocampal size. In T2DM patients, HOMA-IR was inversely correlated with functional connectivity in the right inferior frontal gyrus and precuneus. T2DM patients showed reduced functional connectivity in the DMN compared with control subjects, which was associated with insulin resistance in selected brain regions, but there were no group effects of brain structure or cognition.

  • Received November 29, 2011.
  • Accepted March 24, 2012.

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