Dietary AGEs and Their Role in Health and Disease

Jaime Uribarri

• Publisher: CRC Press
• Year: 2017
• Print ISBN: 9781498721516
• eBook ISBN: 9781351646352
• Topic: Medicine
• Subtopic: Nutrition, Dietics & Bariatrics

Of the many dietary factors associated with inflammation and oxidative stress, a specific group are food-derived pro-inflammatory and pro-oxidant compounds, so-called advanced glycation end products (AGEs). While AGEs have been recognized as factors in the pathogenesis of diabetic complications, the importance of AGEs of dietary origin as a factor in human disease is of more recent concern. This book presents data from the past two decades on the role of AGEs in causing chronic disease. It starts by defining the compounds passing through all the clinical diseases that have been associated with them and finishes by offering different therapeutic options to deal with the problem.

Section III

Role of Ages in the Pathogenesis of Chronic Diseases

9

Role of Advanced Glycation Products in Health and Disease in Children

Anshu Gupta, and Tasnim Rahman

Virginia Commonwealth University

Richmond, VA

CONTENTS

9.1 Introduction

9.2 Healthy Infants and Children

9.3 Children with Obesity and Prediabetes (at Risk of Diabetes)

9.4 Children with Newly Diagnosed Type 1 Diabetes

9.5 Children with Long-Standing DM and Its Complications

9.6 Ages and Childhood Renal Disease

9.7 Conclusions

References

KEY POINTS

• Obesity and diabetes in children have risen to epidemic proportions.
• Caloric excess and increasing consumption of processed foods play a major role in the pathogenesis of obesity and diabetes in children.
• Advanced glycation end products (AGEs) derived from diet are implicated in the pathogenesis of both type 1 and type 2 diabetes as well as in complications resulting from long-standing hyperglycemia.
• Dietary AGEs are suggested to play a role in adipogenesis and insulin resistance as early as infancy.
• Future studies are needed to clarify the interactions between genetic polymorphisms and secretory isoforms, protective and pathogenic, and the AGE-rich environment.

9.1 Introduction

The ever decreasing age at onset of obesity and diabetes in the modern world predicts shortened life expectancy for mankind if not deterred with urgent measures. While the role of genetic predisposition in these rapidly spreading modern epidemics is generally recognized, it has also brought the issue of food environment, both in terms of food quantity and quality, to the forefront of scientific debate. Most of the scientific community now agrees that we need to address not only the caloric content of a food but also the quality in terms of macronutrient composition as well as presence of prooxidative compounds; viz. agents used to add flavor and increase palatability, but that might be deleterious to an individual’s health in the long term. One such category of products is a heterogeneous group of compounds, collectively known as advanced glycation end products (AGEs). The role played by AGEs generated from chronic hyperglycemia in long-standing type 1 diabetes mellitus (T1DM) in children in the pathogenesis of microvascular and macrovascular complications has been studied extensively. Recent studies have added further evidence in support of adverse effects of AGEs derived exogenously from diet in obesity and its comorbidities as well as in destruction of β-cells that produce insulin, thus highlighting their hitherto unrecognized contribution in the pathogenesis of diabetes. Also, the role of AGEs in renal injury in children in the absence of diabetes is under active investigation. In this chapter, we will focus on studies pertaining to AGEs in healthy infants and children, those with obesity, prediabetes as well as in newly diagnosed and long-standing diabetes with complications such as atherosclerosis, nephropathy, neuropathy, and retinopathy. Further, we will briefly review evidence supporting a role of AGEs and their receptor in children with renal disease without pre-existing diabetes.

9.2 Healthy Infants and Children

In other chapters of this book, it has been shown that exogenous AGEs derived from diet and tobacco exposure can be at least partially absorbed into the circulation and that the dietary AGE intake correlates with blood levels of AGEs as well as markers of inflammation and insulin resistance in adults. This has implications for women during pregnancy since these prooxidants in the maternal circulation can create an adverse intrauterine environment for the fetus; this can bear a negative impact on fetal development as well as enhance risk of future adulthood cardiovascular diseases and type 2 diabetes mellitus (T2DM) as suggested by Barker [1]. In support of this hypothesis, animal studies demonstrated an earlier onset of adiposity and increased insulin resistance in neonatal mice (third-generation offspring) when first-generation dams were fed a diet high in methylglyoxal (MG), an intermediate reactive glycation product, generated by exposure of food to high heat and dry conditions [2]. In order to examine this further in humans, investigators studied mother–infant pairs at birth, as well as at 6 and 12 months of age after infant foods (a source of AGEs) were introduced [3]. They noted a strong correlation of maternal serum AGE levels (represented by N-ε carboxy methyllysine [CML] and MG) with those of neonates, suggesting that AGEs can be transferred across the placenta from the mother to the fetus and contribute to an adverse intrauterine environment. Further, as expected, with introduction of processed infant foods, there was a parallel rise in both dietary AGE consumption and serum AGE level in infants at 6 and 12 months. This positive relationship was also not only demonstrated with isoprostane-8, a circulating oxidative stress marker, but notably a negative correlation of serum AGEs was found with adiponectin, an anti-inflammatory adipokine in the infants. These findings suggest a potential role of AGEs in pathogenesis of future obesity in these children. In fact, a study by Monden et al. [4] in mice showed a central role of the receptor for AGEs (RAGE) in adipocyte hypertrophy and differentiation and that RAGE deficiency ameliorated the adverse effect of a high-fat diet replete with AGEs. Similarly, Klenovics et al. independently confirmed higher serum CML levels and lower insulin sensitivity in formula-fed infants at age 3–6 months compared with breastfed infants, although these differences did not persist at follow-up at age 12–14 months [5]. In another study of infants, while dietary AGEs were not measured, Boor et al. compared insulin sensitivity and soluble cell adhesion molecule (siCAM-1), an inflammatory marker, in formula-fed and breastfed infants and its interaction with RAGE gene polymorphisms [6]. The authors observed that minor allele of 374A/T RAGE gene polymorphism was associated with increased siCAM-1 level and decreased insulin sensitivity in mothers; similar results were noted in older children as well as in infants who were formula-fed compared with those who were breastfed. Additionally, children who carried the major allele were noted be more insulin-sensitive if breastfed compared with those who were formula-fed. Interestingly, those who carried the major allele had improved insulin resistance measure at follow-up; this suggests an interaction of diet and RAGE polymorphism and warrants further investigation. In summary, the above studies suggest a possible relationship of dietary AGEs, adipogenesis, and insulin sensitivity in infancy, likely moderated by genetic makeup.

Given the implications of intrauterine and early neonatal environments on the long-term health of an individual, it is imperative to answer the important questions raised by the aforementioned studies in relation to the perinatal and postnatal programming effects of AGEs. Also, the interaction of genetic factors such as RAGE polymorphism with dietary AGEs should be assessed in studies designed to investigate these interactions.

9.3 Children with Obesity and Prediabetes (at Risk of Diabetes)

While studies in healthy adults and those without diabetes [7] have shown a positive correlation of dietary AGEs with circulating levels of CML and MG as well as with inflammatory markers and indices of insulin resistance, data are limited in children. Investigators are now beginning to examine the role of AGEs in younger cohorts and its impact on obesity, inflammatory markers, indices of insulin secretion, and sensitivity.

In a study of middle school children, when comparing lean children and those with obesity, AGE levels in blood (represented by CML) were noted to be 10%–15% lower in the group with obesity; this finding was intriguing since children with obesity showed higher levels of C-reactive protein (CRP) and IL-6 and comparable renal function. These results are in contrast with those observed in adults. The authors noted that children with obesity manifested higher renal creatinine clearance and suggested renal hyperfiltration of AGEs as a compensatory mechanism that might explain the paradoxical results in chil...

Table of contents

• Title Page
• Copyright Page
• Table of Contents
• Preface
• Editor
• Contributors
• Section I What Are AGEs?
• Section II The Modern Diet & AGEs: How Do Exogenous AGEs Become Incorporated into Our Body?
• Section III Role of AGEs in the Pathogenesis of Chronic Diseases
• Section IV Therapeutic Alternatives to Deal with Dietary AGEs
• Index