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Diabetes mellitus is a metabolic disease clinically-characterized as acute and chronic hyperglycemia. It is emerging as one of the common conditions associated with incident liver disease in the US. The mechanism by which diabetes drives liver disease has become an intense topic of discussion and a highly sought-after therapeutic target. Insulin resistance (IR) appears early in the progression of type 2 diabetes (T2D), particularly in obese individuals. One of the co-morbid conditions of obesity-associated diabetes that is on the rise globally is referred to as non-alcoholic fatty liver disease (NAFLD). IR is one of a number of known and suspected mechanism that underlie the progression of NAFLD which concurrently exhibits hepatic inflammation, particularly enriched in cells of the innate arm of the immune system. In this review we focus on the known mechanisms that are suspected to play a role in the cause-effect relationship between hepatic IR and hepatic inflammation and its role in the progression of T2D-associated NAFLD. Uncoupling hepatic IR/hepatic inflammation may break an intra-hepatic vicious cycle, facilitating the attenuation or prevention of NAFLD with a concurrent restoration of physiologic glycemic control. As part of this review, we therefore also assess the potential of a number of existing and emerging therapeutic interventions that can target both conditions simultaneously as treatment options to break this cycle. [ABSTRACT FROM AUTHOR]

Type 1 Diabetes is an autoimmune disease most often associated with elevated and uncontrolled blood glucose levels. Therefore patient education and treatment compliance is often focused on disease maintenance through insulin treatment and blood glucose control. Unfortunately insulin therapy alone does not prevent the formation of diabetic complications. In order to find a real cure, the underlying pathology of the disease must be directly addressed. Diabetes is caused by the initial rapid destruction of the insulin producing beta cells of the pancreas by autoreactive T-cells. The autoimmune process is also maintained through dendritic cell auto-antigen presentation and the production of autoantibodies by B cells. Only through some forms of immunotherapy can the immune system be rebalanced to assure the survival of the remaining beta cell population. These techniques include cell ablation, competitive decoy auto-antigens, reduced cell activation, and auto-antigen introduction. Here we will review the current state of these different technologies and their progression through clinical trials for the treatment of type 1 diabetes.

Diabetes is a state of imbalance in insulin secretion and tissue sensitivity resulting in hyperglycemia and a host of other metabolic changes. Increased patient morbidity and mortality are caused in part by diabetic complications that include cardio-vascular complications, retinopathy, neuropathy, and nephropathy (1). The early onset of disease in type 1 diabetes mellitus increases the effects of these complications since the risk of development increases with disease duration. Clinical agents are currently available for type 2 diabetic patients to increase both secretion and sensitivity to insulin. These compounds are ineffective in type 1 diabetic patients due to the destruction of the insulin producing beta cells in the pancreatic islets of Langerhans, making type 1 and non-responsive type 2 diabetic patients dependent on insulin replacement therapy. Intensive insulin treatment delays onset of these complications, but does not eliminate them (1). Insulin replacement therapy is not a cure for type 1 diabetes; to establish a cure, the destruction of the beta cells themselves must be directly addressed. Here we will focus on immunoregulatory techniques to prevent beta cell loss due to the autoimmunity found in type 1 diabetes mellitus.