IMPORTANCE OF EARLY INSULIN LEVELS ON PRANDIAL GLYCEMIC RESPONSES ANDTHERMOGENESIS IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

To examine the effect of different profiles of insulin administration on glycaemia and thermogenesis, we studied 10 subjects with mild non-i nsulin-dependent diabetes mellitus on four occasions after a standard mixed meal: (1) with no supplementary insulin (control), (2) with intr avenous insulin (1.8U over 15 min = short), (3) as for short but exten ded over 30 min to simulate the normal initial rise in portal vein ins ulin levels (medium), (4) as for medium with additional insulin to nor malize the profile from 30-60 min (3.6U over 60 min, long). All studie s in which supplemental insulin was administered lowered the integrate d glucose response above baseline versus the control study (short 76%, medium 71%, and long 56% of control, p = 0.003). The insulin infusion s also increased the non-protein respiratory quotient in the first hou r following the meal (0.82 +/- 0.01 (control) vs 0.87 +/- 0.01 (short) , 0.86 +/- 0.01 (medium) and 0.87 +/- 0.01 (long), p = 0.003) and augm ented thermogenesis (7.6 +/- 1.5 (control) vs 10.5 +/- 2.9 (short), 13 .0 +/- 1.9 (medium) and 13.2 +/- 2.8% (long), p = 0.02). Total integra ted insulin area above baseline was significantly greater in the long study (short 121, medium 111 vs long 179% of control, p = 0.02). Thus the greatest glycaemic benefit in relation to insulinaemia was obtaine d with the two shorter insulin infusions (short and medium). In conclu sion, this study confirms the role of early prandial insulin secretion (or delivery) in limiting prandial glycaemia in NIDDM and increasing thermogenesis and highlights the pivotal role of the timing of elevati on of insulin levels in modulating hyperglycaemia and hyperinsulinaemi a.