NMR based clinical metabolomics study revealed aberrant proline biosynthesis and mitochondrial dysfunction in patients of mild cognitive impairment

The prevalence of type-2 diabetes mellitus (T2DM) is tremendously increasing in older population because of several reasons and studies have shown that such old-age T2DM patients have 50-65% higher risk of developing cognitive impairment and its progression towards mild cognitive impairment (MCI). The studies claim that in the majority of MCI patients, the diabetes selectively involves the brain and the condition is now considered as a neuroendocrine disorder, even referred to as type 3 diabetes (T3D). Impaired glucose metabolism and mitochondrial dysfunction in neurodegenerative diseases, particularly in MCI, is compelling. Therefore, clinical interest is emerging to understand the role of mitochondria in T2DM and T3D which may provide important insights into pathogenesis of such chronic diseases and may indeed provide a target for improved patient care. The present study, therefore, aims to compare the serum metabolic profiles of MCI patients with age and sex matched T2DM patients with respect to normal control (NC) subjects. The results revealed that abnormal glutamate-to-glutamine cycling and proline metabolism in MCI patients. Compared to T2DM patients, the elevated circulatory proline levels in MCI patients hinted towards abnormal mitochondrial functioning underlying cognitive impairment.