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1 Interaction of Polymorphism rs35652124 With Curcumin Supplementation on NFE2L2 Gene Expression, Antioxidant Capacity and Renal Function in Patients With Early Diabetic Nephropathy

The increase in the prevalence of diabetes mellitus (DM) is one of the greatest public health challenges worldwide. Epidemiological studies have shown that DM is the leading cause of chronic kidney disease (CKD) in patients initiating renal replacement therapy. In our country, diabetes accounts for about 60% of all incidents of dialysis. On the other hand, CKD is currently considered a noxious disease because patients not only have the likelihood of progression to end-stage renal disease (ESRD), but because these renal alterations are associated with an increased risk of cardiovascular complications and premature death for the same cause. Most studies have focused on traditional risk factors (poor diet, physical inactivity and obesity) for the development and progression of renal damage, and less information exists on non-traditional factors such as oxidative stress and mainly, the low antioxidant response that characterizes both DM and nephropathy. In addition, there is a great variation in the susceptibility to and progression of kidney disease between different populations that is not explained by the presence of traditional factors and that could be triggered by genetic variations and its interaction with other components related to the environment and lifestyle. Fortunately, there is sufficient scientific evidence that early detection and modification of negative lifestyle factors can not only delay or halt the progression of the renal function decline to ESRD but can also significantly reduce the incidence of cardiovascular disease leading to premature death in most of these patients. Therefore, it is suggested that this risk may be determined by the interaction of lifestyle factors with the presence of susceptibility alleles, which may vary from one population to another. It is now known that hyperglycemia causes a state of oxidative stress and inflammation that can be counteracted by diet supplementation with some natural antioxidants such as curcumin. It has been shown that this molecule has multiple pharmacological properties: antioxidant, anti-inflammatory, cardioprotective, renoprotective, among others. In clinical trials a positive effect of curcumin has been seen in the treatment of diabetes and its complications. This has generated a relative optimism in the search for new curcumin treatment targets where oxidative stress is of great relevance, as is the case with CKD. However, there are still doubts about its efficacy as an adjuvant in the prevention of CKD. Additionally, the role played by interindividual variability in genes involved in the mechanism of action of curcumin is still incipient, more studies in this knowledge area are necessary.

NCT03262363 Chronic Kidney Diseases Diabetes Mellitus, Type 2 Polymorphism Combination Product: Curcumin/NFE2L2 A>G Combination Product: Placebo/NFE2L2 A>G

MeSH:Kidney Diseases Renal Insufficiency, Chronic Diabetic Nephropa Diabetic Nephropathies Diabetes Mellitus, Type 2

HPO:Abnormality of the kidney Chronic kidney disease Nephropathy Type II diabetes mellitus

Interaction of Polymorphism rs35652124 With Curcumin Supplementation on NFE2L2 Gene Expression, Antioxidant Capacity and Renal Function in Patients With Early Diabetic Nephropathy.

Curcumin on NFE2L2 Gene Expression, Antioxidant Capacity and Renal Function According to rs35652124 in Diabetic Nephropathy The increase in the prevalence of diabetes mellitus (DM) is one of the greatest public health challenges worldwide.

Inclusion Criteria: - With T2DM according to the American Diabetes Association - With any time of T2DM evolution - With CKD stage 1-3a according to the K/DIGO guidelines Exclusion Criteria: - Incomplete evaluations - That they have not been attached to the assigned intervention with an established frequency of <80% - Decide to withdraw from the study Inclusion Criteria: - With T2DM according to the American Diabetes Association - With any time of T2DM evolution - With CKD stage 1-3a according to the K/DIGO guidelines Exclusion Criteria: - Incomplete evaluations - That they have not been attached to the assigned intervention with an established frequency of <80% - Decide to withdraw from the study Chronic Kidney Diseases Diabetes Mellitus, Type 2 Polymorphism Kidney Diseases Renal Insufficiency, Chronic Diabetic Nephropa Diabetic Nephropathies Diabetes Mellitus, Type 2 Aim: To evaluate the interaction between rs35652124 polymorphism and curcumin supplementation on the levels of NFE2L2 gene expression, antioxidant capacity and renal function in patients with early diabetic nephropathy (EDN).

Once they have signed the written consent they will be cited for the first blood sample collecting (5 mL) to be used for genomic DNA extraction and genotyping for the rs35652124 polymorphism.

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