Ironing out the Details: Untangling Dietary Iron and Genetic Background in Diabetes

Abstract

The search for genetic risk factors in type-II diabetes has been hindered by a failure to consider dietary variables. Dietary nutrients impact metabolic disease risk and severity and are essential to maintaining metabolic health. Genetic variation between individuals confers differences in metabolism, which directly impacts response to diet. Most studies attempting to identify genetic risk factors in disease fail to incorporate dietary components, and thus are ill-equipped to capture the breadth of the genome’s impact on metabolism. Understanding how genetic background interacts with nutrients holds the key to predicting and preventing metabolic diseases through the implementation of personalized nutrition. Dysregulation of iron homeostasis is associated with type-II diabetes, but the link between dietary iron and metabolic dysfunction is poorly defined. High iron burden in adipose tissue induces insulin resistance, but the mechanisms underlying adipose iron accumulation remain unknown. Hepcidin controls dietary iron absorption and distribution in metabolic tissues, but it is unknown whether genetic variation influencing hepcidin expression modifies susceptibility to dietary iron-induced insulin resistance. This review highlights discoveries concerning the axis of iron homeostasis and adipose function and suggests that genetic variation underlying dietary iron metabolism is an understudied component of metabolic disease.

Inflammatory Mechanisms in the Pathophysiology of Diabetic Peripheral Neuropathy (DN)—New Aspects

“…A link between iron metabolism disorders and diabetes has already been proposed [ 48 ]. In several epidemiological studies, high serum ferritin and decreased transferrin levels were associated with a higher risk of type 2 diabetes, pre-diabetes, or gestational diabetes [ 49 , 50 , 51 ].…”

Leptin Receptor-Deficient db/db Mice Show Significant Heterogeneity in Response to High Non-heme Iron Diet

“…Therefore, it was surprising to observe the dual response of db/db diabetic mice to high iron diet ( 27 ). Notably, reports on the effect of iron on the patient diabetic status and development of the diabetic complications are contradictory ( 11 , 13 ). In the present work, we aim to investigate differences in the metabolic status, as well as inflammation markers in liver and adipose tissue between two high iron diet fed db/db mouse subgroups.…”

<p>BCc1 Nanomedicine Therapeutic Effects in Streptozotocin and High-Fat Diet Induced Diabetic Kidney Disease</p>

“…4 In recent decades, numerous studies have focused on the critical role of iron metabolism disruption (with or without iron overload) in diabetes, CKD, cancer and other chronic diseases initiation, progression and development. [5][6][7] Although iron as a trace element has vital roles in the physiology of human beings, it is a redox-active element, so a vicious cycle of iron dis-homeostasis, inflammation and oxidative stress is formed mostly through free radicals induced by iron in chronic diseases, [8][9][10][11][12] and therefore manipulation of iron homeostasis in chronic diseases, especially in DKD, is evaluated in dozens of studies using iron chelators to assess their impacts. [13][14][15][16][17] In fact, iron chelation in these situations means iron re-distribution, not iron excretion.…”