EFFECT OF STRICT METABOLIC CONTROL ON GLUCOSE HANDLING BY THE LIVER AND PERIPHERAL-TISSUES IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

To examine the effect of strict glycemic control on the insulin resist ance of non-insulin-dependent diabetes mellitus (NIDDM), we applied eu glycemic hyperinsulinemic clamp combined with an oral glucose load (OG L) to nine nonobese subjects with NIDDM and quantitated insulin-mediat ed glucose uptake by the liver (HGU) and peripheral tissues (PGU) simu ltaneously before and after 3 to 4 weeks of intimate glycemic control by preprandial regular insulin injections 3 times a day. The glucose i nfusion rate (GIR) required to maintain euglycemia during the clamp be fore OGL was considered as PGU. After OGL, the fraction of ingested gl ucose that is not extracted by the liver enters the systemic circulati on and reduces the GIR required for the clamp. HGU was calculated from the difference between the amount of OGL and the cumulative decrement s in GIR after OGL and was expressed as the ratio to the amount of OGL (%). Three to 4 weeks after initiation of strict metabolic control, F PG and HbA Ic levels significantly improved (9.1 +/- 0.5 vs. 6.4 +/- 0 .4 mmol/l, and 11.2 +/- 0.8 vs. 8.3 +/- 0.3%, P < 0.05). HGU significa ntly increased to 33.1 +/- 9.5 from 14.5 +/- 4.8%, while PGU did not c hange (38.2 +/- 5.2 vs. 37.4 +/- 3.9 mu mol/kg min). These data sugges t that shortterm strict metabolic control ameliorates insulin resistan ce in NIDDM mainly at the hepatic level.