Pathogenesis and remission of type 2 diabetes: what has the twin cycle hypothesis taught us?

Type 2 diabetes has been regarded a complex multifactorial disease that lead to serious health complications including high cardiovascular risks. The twin cycle hypothesis postulated that both hepatic insulin resistance and dysfunction rather than death of beta (β) cell determine diabetes onset. Several studies were carried out to test this hypothesis, and all demonstrated that chronic excess calorie intake and ectopic fat accumulation within the liver and pancreas are fundamental to the development of this disease. However, these recent research advances cannot determine the exact cause of this disease. In this review, the major factors that contribute to the pathogenesis and remission of type 2 diabetes will be outlined. Importantly, the effect of disordered lipid metabolism, characterized by altered hepatic triglyceride export will be discussed. Additionally, the observed changes in pancreas morphology in type 2 diabetes will be highlighted and discussed in relation to β cell function.