Persistent abnormalities of the metabolism of an oral glucose load in insulin-treated type I diabetics

We have compared disposal of an oral glucose load in 12 normal subjects and 10 c-peptide-negative, type I-diabetic subjects, who were treated with insulin (by overnight intravenous insulin infusion followed by a dose of subcutaneous insulin prior to the oral glucose load) to achieve a blood glucose profile that approximated the glucose intolerance commonly seen in insulin-treated diabetics. We used a combination of the dual-isotope and forearm techniques, together with whole-body indirect calorimetry, to quantify the various determinants of glucose tolerance. The diabetic subjects had impaired glucose tolerance in that, despite similar fasting plasma glucose levels (5.46 ± 0.17 mol/L v 5.35 ± 0.10 mmol/L in the normal subjects), they had a higher peak glucose (14.3 ± 1.2 mmol/L v 10.0 ± 0.7 mmol/L P < .01) and area under the glucose curve (2,483 ± 197 mmol · min/L v 1,525 ± 43 mmol · min/L P < .001). Up to 120 minutes after the oral glucose load, the amount of glucose entering the systemic circulation exceeded that leaving by 14.6 ± 2.3 g in the diabetics and only by 2.6 ± 0.5 g in the normal subjects ( P < .001), accounting for the higher plasma glucose peak in the diabetics. Total systemic glucose appearance rates were significantly greater in the diabetics between 60 and 120 minutes, and endogenous glucose production suppressed more slowly in diabetics than in the normal subjects. Over the 210 minutes of the study, glucose oxidation was markedly reduced in the diabetic subjects (17.3 ± 3.2 g v 29.9 ± 2.9 g P < .01), whereas urinary glucose losses were only significant in the diabetics (3.5 ± 0.9 g). Forearm glucose uptake was slightly, but not significantly, less in the diabetic subjects ( 342 ± 50 μ mol 100 mL forearm v 433 ± 47 μ mol 100 mL P = NS ), despite a higher plasma glucose. There was attenuation of the normal postprandial arterial lactate peak in the diabetic subjects. We conclude that residual glucose intolerance in these diabetic subjects resulted from a combination of abnormalities of the time course and routes of glucose metabolism with (1) reduced glucose oxidation, (2) increased systemic glucose appearance, and (3) abnormal splanchnic glucose handling. This study shows the considerable residual abnormalities of many pathways of glucose metabolism in type I diabetic subjects with moderate hyperglycemia following treatment with subcutaneous insulin.