Author
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CHIU, CHUNG-JUNG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University |
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TAYLOR, ALLEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University |
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Submitted to: Progress in Retinal and Eye Research
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 9/22/2010 Publication Date: 1/30/2011 Citation: Chiu, C., Taylor, A. 2011. Dietary hyperglycemia, glycemic index and age-related metabolic retinal diseases. Progress in Retinal and Eye Research. 30(1):18-53. Interpretive Summary: The glycemic index measures the ratio of blood sugar level after eating a specific amount of carbohydrate-containing food to that after consuming a specific amount of pure sugar. Previously we found that diets that raised blood sugar levels rapidly are associated with markedly increased risk for onset and progress of age related macular degeneration. Such diets are also associated with increased risk for heart disease, diabetes, and perhaps, cataract. Some of the tissues affected by these diseases, including the heart, vascular systems, and retina are subject to high exposure to oxygen, where as others (lens) confront relatively low oxygen levels. In this paper we explore the various pathways that might explain the effects of high glycemic diets in various tissues. Such information is important if we are to extract the maximum amount of information from the epidemiologic and clinical literature in order to optimize diets or dietary carbohydrate intakes. Technical Abstract: The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during the early postprandial stage (0-2h) and a compensatory hyperlipidemia associated with counter-regulatory hormone responses during late postprandial stage (4-6h). Over the past three decades, several human health disorders have been related to GI. The strongest relationship suggests that consuming low-GI foods prevents diabetic complications. Diabetic retinopathy (DR) is a complication of diabetes. In this aspect, GI appears to be useful as a practical guideline to help diabetic people choose foods. Abundant epidemiological evidence also indicates positive associations between GI and risk for type 2 diabetes, cardiovascular disease, and more recently, age-related macular degeneration (AMD) in people without diabetes. Although data from randomized controlled intervention trials are scanty, these observations are strongly supported by evolving molecular mechanisms which explain the pathogenesis of hyperglycemia. This wide range of evidence implies that dietary hyperglycemia is etiologically related to human aging and diseases, including DR and AMD. In this context, these diseases can be considered as metabolic retinal diseases. Molecular theories that explain hyperglycemic pathogenesis involve a mitochondria-associated pathway and four glycolysis-associated pathways, including advanced glycation end products formation, protein kinase C activation, polyol pathway, and hexosamine pathway. While the four glycolysis-associated pathways appear to be universal for both normoxic and hypoxic conditions, the mitochondria-associated mechanism appears to be most relevant to the hyperglycemic, normoxic pathogenesis. For diseases that affect tissues with highly active metabolism and that frequently face challenge from low oxygen tension, such as retina in which metabolism is determined by both glucose and oxygen homeostases, these theories appear to be insufficient. Several lines of evidence indicate that the retina is particularly vulnerable when hypoxia coincides with hyperglycemia. We propose a novel hyperglycemic, hypoxia-inducible factor (HIF) pathway, to complement the current theories regarding hyperglycemic pathogenesis. HIF is a transcription complex that responds to decrease oxygen in the cellular environment. In addition to playing a significant role in the regulation of glucose metabolism, under hyperglycemia HIF has been shown to increase the expression of HIF-inducible genes, such as vascular endothelial growth factor (VEGF) leading to angiogenesis. To this extent, we suggest that HIF can also be described as a hyperglycemia-inducible factor. In summary, while management of dietary GI appears to be an effective intervention for the prevention of metabolic diseases, specifically AMD and DR, more interventional data is needed to evaluate the efficacy of GI management. There is an urgent need to develop reliable biomarkers of exposure, surrogate endpoints, as well as susceptibility for GI. These insights would also be helpful in deciphering the detailed hyperglycemia-related biochemical mechanisms for the development of new therapeutic agents. |
