Failure in the regulation of glyceroneogenesis may lead to type 2 diabetes, a metabolic disorder that results in high levels of blood glucose and blood lipid. Type 2 diabetes, in addition to a decreased sensitivity to insulin, is associated with the overproduction of triglycerides in the liver, due to excessively active glyceroneogenesis and excess release of fatty acids from adipose tissues. Glyceroneogenesis can be regulated by controlling the gene expression of PEPC-K. 
Overexpressing PEPC-K in the liver will overproduce triglycerides and elevate the lipid level in the bloodstream, increasing the risk of fatty liver disease (hepatic steatosis). Conversely, in adipose tissue, down-regulated glyceroneogenesis may decrease de novo lipogenesis, increasing the export of free fatty acids to the bloodstream, leading to lipodystrophy. Both of these conditions are highly associated with type 2 diabetes.