Fig. 1.

Vicious cycle of hyperglycemia. Poor lifestyle and/or metabolic dysfunction syndrome leads to elevated triglycerides, non-esterified fatty acids (a). Excessive lipids is deposited in non-adipose tissue, blocking the insulin signaling pathways, then resulting in insulin resistance, especially in the liver which increase the liver’s glucose production and weakens uptake of glucose, thereby increasing blood glucose and basal insulin levels, and the elevated insulin promotes lipid deposition, further aggravating insulin resistance and forming a vicious circle; elevated glucose and lipids produce hyperglucolipotoxicity to islet β cells and lipid deposition in islets, damaging the secretion function and number of pancreatic β cells, and further increasing blood glucose (b). MDS metabolic dysfunction syndrome, MASLD metabolic associated steatotic liver disease, TG triglycerides, NEFAs non-esterified fatty acids, GSIS glucose-stimulated insulin secretion