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J Diabetes Metab. 2016 Apr;7(4). pii: 664. Epub 2016 Apr 28.

Impact of Major Depressive Disorder on Prediabetes by Impairing Insulin Sensitivity.

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  • 1Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, 1720 University Blvd, Birmingham AL, 35294, USA.
  • 2Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham AL, 35294, USA.
  • 3Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham AL, 35294, USA; Department of Nutrition Sciences, University of Alabama at Birmingham, and the Birmingham VA Medical Center, Birmingham AL, 35294, USA.


Reports regarding the associations between major depressive disorder (MDD) and diabetes remain heterogeneous. Our aim was to investigate whether glucose homeostasis and insulin sensitivity were impaired in the MDD patients and its mechanisms. A total of 30 patients with MDD and 30 matched controls were recruited. The oral glucose tolerance test and dual-energy X-ray absorptiometry scan were performed in each participant. Insulin signaling in postmortem brain tissues from other depressive patients and controls (obtained from Alabama brain bank) was examined. Insulin sensitivity was reduced substantially in the MDD patients, however, the fasting and 2-h glucose concentrations remained within the normal range through compensatory insulin secretion. Despite increased insulin secretion, 1-h glucose concentrations in the MDD patients were significantly elevated compared with the controls. MDD patients had greater visceral fat mass but lower adiponectin levels compared with the controls. Furthermore, phosphorylated-AKT levels in insulin signaling were decreased in postmortem brain tissues in patients with MDD. These results suggest that MDD patients are at a greater risk for diabetes due to decreased insulin sensitivity, reduced disposition index, and impaired glucose tolerance as manifested by elevated 1-h glucose concentrations following an oral glucose challenge. Mechanistic studies reveal that decreased insulin sensitivity is associated with increased visceral fat mass, lower adiponectin levels and impaired insulin action in postmortem brain tissues in the MDD patients. Our findings emphasize the importance of screening depressive patients to identify susceptible individuals for developing future diabetes with the hope of improving their health outcomes.


Atherosclerosis; Cardiovascular diseases; Glucose tolerance test; Insulin sensitivity; Phosphorylation; Prediabetes

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