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Insulin Resistance’s Effects on Tissue Iron Stores and Cognitive Performance

BIO (brain iron overload) could be a potentially useful MRI biomarker for insulin resistance and obesity-associated cognitive dysfunction…. 

The researchers explored potential factors contributing to increased hepatic iron concentration (HIC) and brain iron overload (BIO), both of which were identified by MRI. They also evaluated the impact of HIC and BIO on cognitive performance in search of a pattern among obese and nonobese patients.

They conducted a preliminary MRI case-control study and prospectively recruited a group of 23 middle-aged obese patients without diabetes that averaged at an age of 50.4 ± 7.7 years and a BMI of 43.7 ± 4.4 kg/m2 and included 13 women and a group of 20 healthy nonobese volunteers that averaged at an age of 48.8 ± 9.5 years and a BMI of 24.3 ± 3.54 kg/m2 and included 10 women. The iron load was evaluated in white and gray matter and the liver by MRI, IR was measured using an oral glucose tolerance test and HOMA-IR, and cognitive performance was assessed using a battery of neuropsychological tests in all of these participants. In order to identify the independent associations of BIO and cognitive function, the researchers performed a multivariate regression analysis.

In the obese group, there were significant increases in iron load detected at the caudate nucleus (p <0.001), lenticular nucleus (p=0.004), hypothalamus (p=0.002), hippocampus (p <0.001), and liver (p <0.001) and a positive correlation between HIC and BIO at the caudate (r=0.517, p <0.001), hypothalamus (r=0.396, p=0.009), and hippocampus (r=0.347, p <0.023). There was an independent association between the area under the curve of insulin and BIO at the caudate (p=0.001), hippocampus (p=0.028), and HIC (p=0.025). There was another independent association between declined cognitive performance and BIO at the caudate (p=0.028), hypothalamus (p=0.006), and lenticular nucleus (p=0.012).

The researchers concluded that obesity and IR could be contributing factors to increased HIC and BIO. Patients with increased HIC and BIO were associated with declined cognitive performance when compared to healthy patients. Researchers believe that BIO could potentially be used as an MRI biomarker to indicate the presence of IR and obesity-associated cognitive dysfunction.

Practice Pearls:
  • Obesity and IR may contribute to increased HIC and BIO.
  • When compared to healthy patients, patients with increased HIC and BIO were associated with diminished cognitive performance.
  • BIO may have the potential to be an MRI biomarker indicating the presence of IR and obesity-associated cognitive dysfunction.

Blasco G, Puig J, Daunis-I-Estadella J, Molina X, Xifra G, Fernández-Aranda F, Pedraza S, Ricart W, Portero-Otín M, Fernández-Real JM. Brain Iron Overload, Insulin Resistance and Cognitive Performance in Obese Subjects: A Preliminary MRI Case-Control Study. Diabetes Care. 2014 Aug 14; pii: DC_140664 [Epub ahead of print].