Although muscle is considered to be the most important site for postprandial glucose disposal, the metabolic fate of oral glucose taken up by muscle remains unclear. We, therefore, employed the dual isotope technique (intravenous, [6-3HJ-glucose; oral, l1-'4Clglucose), indirect calorimetry, and forearm balance measurements of glucose, lactate, alanine, pyruvate, 02, and CO2 in nine normal volunteers to determine the relative importance of muscle glycogenic, glycolytic, and oxidative pathways in disposal of an oral glucose load. During the 5 h after glucose ingestion (1 g/kg), 37±3% (24.9±2.3 g) of the load was oxidized and 63±3% (42.8±2.7 g) was stored. At least 29% (19.4±1.3 g) was taken up by splanchnic tissues. Muscle took up 26% (17.9±2.9 g) of the oral glucose coincident with a 50% reduction in its oxidation of fat. 15% of the oral glucose taken up by muscle (2.5±0.9 g) was released as lactate, alanine, or pyruvate; 50% (8.9±1.4 g) was oxidized, and 35% (6.4±2.3 g) was available for storage. We conclude that muscle and splanchnic tissues take up a comparable percentage of an oral glucose load and that oxidation is the predominant fate of glucose taken up by muscle, with storage in muscle accounting for < 10% of the oral load. Thus, contrary to the prevailing view, muscle is neither the major site of storage nor the predominant site of disposal of an oral glucose load.

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The limited success achieved in controlling diabetes and its complications with conventional insulin therapy suggests the need for reevaluation of the appropriateness of insulin administration protocols. Indeed, conventional subcutaneous insulin administration produces slowly changing blood insulin levels and suboptimal hepatocyte insulinization resulting in impaired hepatic capacity for processing incoming dietary glucose. The novel approach to insulin administration known as chronic intermittent intravenous insulin therapy (CIIIT) delivers insulin in a pulsatile fashion and achieves physiological insulin concentration in the portal vein. Done as a weekly outpatient procedure combined with daily intensive subcutaneous insulin therapy, this procedure has been shown to (1) significantly improve glycemic control while decreasing the incidence of hypoglycemic events, (2) improve hypertension control, (3) slow the progression of overt diabetic nephropathy, and (4) reverse some manifestations of diabetic autonomic neuropathy (e.g., abnormal circadian blood pressure pattern, severe postural hypotension, and hypoglycemia unawareness).

Studies of substrate flux, isotope activity and metabolic balance frequently require arterial sampling. We evaluated: (1) whether substrate concentrations obtained from heated dorsal hand veins (HDHV) were comparable to samples obtained from the radial artery, (2) whether heat sufficient to arterialize HDHV altered contralateral forearm blood flow thus affecting flux calculations, (3) whether a +14 heating pad equaled a cumbersome +700 heating chamber, and (4) whether HDHV showed a dose-response curve to varying heat loads. In 12 normals, dorsal hand temperature was raised from 31.8 +/- 0.6 degrees C to 39.8 +/- 0.8 degrees C (chamber) and 39.3 +/- 0.3 degrees C (pad). Basal contralateral forearm blood flow (3.37 +/- 0.7 ml/100 ml tissue/min) was not significantly altered in the chamber (3.39 +/- 0.5 ml) or the pad (3.44 +/- 0.5 ml). Skin temperature of the unheated hand, an index of superficial blood flow (31.5 +/- 0.7 degrees C) did not change significantly in the chamber (31.6 +/- 0.7 degrees C) or the pad (31.2 +/- 0.7 degrees C). Forearm blood flow did not change with heating in eight postoperative patients. Comparative arterial and HDHV blood gases and 10 metabolic substrates from simultaneously drawn samples at various temperatures showed HDHV PO2 approached but did not equal arterial PO2 at temperatures greater than 39 degrees C. Glucose, amino acid, and substrate concentrations were comparable at 39 degrees C and did not change with increasing temperature. HDHV can reliably determine arterial substrate concentrations using an inexpensive heating pad. In cool environments (20-22 degrees C), contralateral forearm blood flow is not significantly altered. There is no benefit to heating the hand above 39 degrees C.