To analyze the effects of short-term fasting on postprandial glucose m
etabolism in non-insulin-dependent diabetes mellitus (NIDDM), two grou
ps of nine obese NIDDM patients and two comparable groups of control s
ubjects underwent a 5-h oral glucose tolerance test after either 14 h
or 4 days of fasting. The fluxes and the rates of oxidation and storag
e of glucose were measured using a dual isotope technique combined wit
h indirect calorimetry. The effect of fasting on insulin action and p-
cen responsiveness was tested in an additional group of six obese NIDD
M patients with a euglycemic hyperinsulinemic clamp followed by an int
ravenous glucagon test. In the diabetic patients, fasting enhanced bet
a-cell response to glucose and glucagon and did not modify insulin act
ion, This response differs from that of nondiabetic subjects in whom f
asting is known to impair insulin secretion and action. Regarding gluc
ose fluxes, it was observed that in the overnight-fasted state, the in
cremental tissular disposal following glucose ingestion was reduced by
similar to 50% in the diabetic versus control subjects in relation to
an similar to 62% impairment in glucose storage. After fasting, incre
mental tissular disposal was restored to normal, glucose oxidation was
virtually abolished, and storage was increased approximately threefol
d. Thus, in NIDDM patients, fasting corrects the defect in glycogen st
orage without modifying the action of insulin on glucose uptake and im
proves beta-cell responsiveness, the latter two effects being opposite
to those observed in nondiabetic subjects.