Impact of Inflammation and Innate Immunity Response in Obesity Mediated Diabetes

Impaired glucose metabolism and persistent hyperglycemia are known to cause diabetes complications. Diabetic hyperglycemia has been correlated with complications such as retinopathy, nephropathy, neuropathy, and increased the risk of myocardial infarction, stroke, premature peripheral arterial disease, atherosclerosis, and cardiomyopathy. Insulin resistance is the root cause of hyperglycemia, and insulin resistance is caused by obesity and tied to causative inflammatory factors. Many new pathways that impact this inflammation have been observed in the last decade. It is clear that obesity increases the likelihood of inflammation, alters the response of the adipose, and increases the risk of lipidemia and hyperglycemia. Hyperglycemia leads to oxidative stress which causes molecular damage. Adipose tissue under fatty acid stress is now implicated as a source of innate immunity signaling of inflammation. These stress factors caused by obesity correlate with a mild but chronic inflammatory state with activation of the innate immune system. This inflammatory state signals innate immune cells to mediate tissue and organ damage. Vascular dysfunction and altered cellular proliferation repair responses are observed. The pathways in innate immunity activation are herein reviewed and connections are made to both well-known diagnostic markers and to new markers. Immune mediated inflammation is common to all diabetic complications. Recent discoveries shown in the volume reveal a new level of complexity in the innate immune molecular role in diabetic disease. These multiple pathways allow a new understanding how diabetes complications progress. This chapter reviews the molecular pathways connecting hyperglycemia to obesity and inflammation.