THE MAGNITUDE, THE KINETICS AND THE METABOLIC EFFICIENCY OF 1ST-PHASE INSULIN-RESPONSE TO INTRAVENOUS GLUCOSE ARE RELATED

We investigated the relationship between the kinetics, the magnitude and the metabolic efficiency of first-phase insulin response (FPIR) to intravenous glucose. Twenty healthy control subjects and fifty first degree relatives of Type 1 diabetic patients were studied using a standardized protocol for the intravenous glucose tolerance test (IVGTT). The first significant increase in plasma insulin concentrations above baseline appeared as early as the 2nd min (1 min before the end of glucose injection, fast response) in 80% of controls and 70% of relatives, and at the 3rd min or later (delayed response) in the remaining subjects. The greatest delay in insulin release (5th min) was observed in 4 of 6 relatives of Type 1 diabetic patients with impaired FPIR. In the controls and the relatives, the subjects with a fast insulin response had a significantly higher FPIR (controls 215.4+/-93.5 vs 59.7+/-5.6 muU/ml, p<0.001 and relatives 143.5+/-61.8 vs 55.9+/-27.7 muU/ml, p<0.001) and showed better glucose assimilation (controls 3.05+/-1.05 vs 1.64 +/-0.1%/min, p < 0.05 and relatives 2.6+/-0.96 vs 1.6+/-0.85% /min, p<0.01) during IVGTT than the subjects with a delayed response. Moreover, for normal FPIR values in the group of relatives of Type 1 diabetic patients, a fast response was associated with a significantly better glucose assimilation as assessed by the incremental area under the glucose curve (358.6+/-64.7 vs 539.2+/-67.7 mmol/l per 90 min, p<0.001). These data show 1) that minor variations in the speed of early insulin release (i.e., 1 min) might have important effects on glucose tolerance during IVGTT in healthy subjects and 2) that an impaired FPIR to intravenous glucose is clearly associated to a delayed insulin release.