Forearm glucose uptake and lactate balance across the forearm were determined in normal subjects during 100-gm. oral glucose tolerance tests (GTT) before and after a lowcarbohydrate diet; in addition, β-hydroxybutyrate and acetoacetateresponses were measured following carbohydrate restriction. After a low-carbohydrate diet, glucose tolerance was significantly impaired (dietary diabetes) and the rise in seruminsulin levels was frequently, but not invariably, delayed. Forearm glucose utilization, however, was not significantly decreased at any phase of the GTT or during the GTT as a whole.
With a normal diet, lactate levels rose immediately after glucose loading, reaching peak concentrations at sixty minutes and falling progressively thereafter; this rise was associated with lactate utilization by the forearm and the subsequent fall in plasma concentrations with lactate release. In contrast, following carbohydrate restriction lactate concentrations were initially reduced by glucose administration, this reduction taking place despite continuing lactate release from the forearm. These results suggest that after glucose loading the shape of the lactate response curve is not determined primarily by changes in peripheral lactate balance.
Marked elevation in basal FFA, β-hydroxybutyrate, and acetoacetate levels accompanied carbohydrate restriction. FFA and β-hydroxybutyrate concentrations were immediately decreased and acetoacetate levels initially increased by glucose loading, the latter declining only during the second hour of the GTT; throughout the test, acetoacetate was taken up by the forearm while β-hydroxybutyrate was released. Basal FFA and β-hydroxybutyrate concentrations were not correlated with the degree of glucose intolerance induced in the volunteers.
The results show that the impairment of glucose tolerance following carbohydrate restriction is not the result of decreased peripheral glucose utilization. It is suggested that the major cause of dietary diabetes is a delay in the hepatic uptake of the glucose load and that this is primarily the. result of low hepatic glucokinase activity rather than delayed insulin secretion.