In the foregoing discussion we have tried to define the nature of OxS and then, using that definition, to assess the status of OxS in diabetes. Based on analysis of various biomarkers of OxS in long-lived proteins, we conclude that OxS is not overtly or systemically increased in diabetes, except at later stages in the development of complications. Metabolic derangements in diabetes lead to an increase in concentration of oxidizable substrates and compromised detoxification pathways. The resulting increase in reactive carbonyls in tissues, known as carbonyl stress, leads directly to increased chemical modification of proteins in diabetes. Efforts directed at decreasing substrate concentration (maintenance of euglycemia and normolipidemia), bolstering detoxification pathways (GSH precursors or enhancers), and trapping reactive carbonyl species (AGE inhibitors, carbonyl traps) represent reasonable therapeutic approaches for limiting the chemical modification and crosslinking of proteins in diabetes and inhibiting the development of diabetic complications. Antioxidant vitamins and drugs may spare coenzymes for detoxification pathways during early stages of diabetes and may be useful as supportive therapy at later stages of the disease.
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