The Prediabetic State, Its Nature and Consequences—A Look Toward the Future

Abstract

The prediabetic state is characterized by normal glucose tolerance but decreased insulin secretion following glucose stimulation. In spite of our earlier beliefs, this state is not always devoid of metabolic consequences. Thus, the disappearance rate of intravenously administered glucose (k-value), although within the normal range, is significantly lower than in the control group. In a few prediabetics the regulation of hepatic glucose output resembles that of diabetics. In some, the lipolytic response to physical exercise is increased to the extent found in manifest diabetes. Furthermore, prediabetic mothers may give birth to children with diabetic fetopathy. Many of the newborns of these women show high k-values as do children of diabetic women. The decreased insulin output of prediabetics and mild diabetics is probably due to a decreased sensitivity for glucose of a specific receptor of the beta cells of the pancreas. This suggestion is supported by the finding that both prediabetics and mild diabetics can release normal amounts of insulin provided blood glucose is raised to 500–1,000 mg./ 100 ml. The transition from prediabetes to diabetes may be induced by several factors such as progressive deterioration of insulin output or addition of diabetogenic factors like obesity and overproduction of human growth hormone. Hepatic glucose output in the prediabetic is regulated with a higher than normal efficiency, thus compensating for the deficient insulin secretion. The failure of this important mechanism may be a major precipitating factor for diabetes. The future prevention and treatment of diabetes mellitus will depend on the development of agents that (a) correct the sensitivity of the glucose receptor of the beta cells and (b) stimulate the ability of the liver to suppress its glucose output.