Oral phytate supplementation on the progression of mild cognitive impairment, brain iron deposition and diabetic retinopathy in patients with type 2 diabetes: a concept paper for a randomized double blind placebo controlled trial (the PHYND trial).

Type 2 diabetes mellitus has a worldwide prevalence of 10.5% in the adult population (20-79 years), and by 2045, the prevalence is expected to keep rising to one in eight adults living with diabetes. Mild cognitive impairment has a global prevalence of 19.7% in adults aged 50 years. Both conditions have shown a concerning increase in prevalence rates over the past 10 years, highlighting a growing public health challenge. Future forecasts indicate that the prevalence of dementia (no estimations done for individuals with mild cognitive impairment) is expected to nearly triple by 2050. Type 2 diabetes mellitus is a risk factor for the development of cognitive impairment, and such impairment increase the likelihood of poor glycemic/metabolic control. High phytate intake has been shown to be a protective factor against the development of cognitive impairment in observational studies. Diary phytate intake might reduce the micro- and macrovascular complications of patients with type 2 diabetes mellitus through different mechanisms. We describe the protocol of the first trial (the PHYND trial) that evaluate the effect of daily phytate supplementation over 56 weeks with a two-arm double-blind placebo-controlled study on the progression of mild cognitive impairment, cerebral iron deposition, and retinal involvement in patients with type 2 diabetes mellitus. Our hypothesis proposes that phytate, by inhibiting advanced glycation end product formation and chelating transition metals, will improve cognitive function and attenuate the progression from Mild Cognitive Impairment to dementia in individuals with type 2 diabetes mellitus and mild cognitive impairment. Additionally, we predict that phytate will reduce iron accumulation in the central nervous system, mitigate neurodegenerative changes in both the central nervous system and retina, and induce alterations in biochemical markers associated with neurodegeneration.

Metabolic-Associated Fatty Liver Disease and Cognitive Performance in Type 2 Diabetes: Basal Data from the Phytate, Neurodegeneration and Diabetes (PHYND) Study.

The effect of liver fibrosis on mild cognitive impairment (MCI) and dementia risk in type 2 diabetes mellitus (T2DM) patients is unclear. Therefore, we performed a prospective cross-sectional study on 219 patients with T2DM and older than 60 years to evaluate the association between liver fibrosis, liver steatosis, and cognitive impairment. The Montreal Cognitive Assessment (MoCA) was used to screen for MCI or dementia. Liver fibrosis was estimated using the non-invasive Fibrosis-4 (FIB-4) score, and liver steatosis was assessed with the hepatic steatosis index. The mean age was 71 ± 6 years, 47% were women and according to MoCA cut-off values, 53.88% had MCI and 16.43% had dementia. A moderate or high risk of advanced fibrosis was significantly higher in patients with MCI or dementia compared to those with normal cognition (p < 0.001). After adjusting for confounders, a FIB-4 score greater than 1.54 was associated with MCI or dementia (p = 0.039). Multivariate analysis identified age over 70.5 years, antiplatelet medication use, and a FIB-4 score above 1.54 as the most relevant risk factors. Liver fibrosis, but not liver steatosis, is associated with MCI or dementia in older T2DM patients, suggesting that FIB-4 score might be a simple biomarker for the detection of cognitive impairment.