Subcutaneous infusion and capillary "finger stick" sampling of stable isotope tracer in metabolic studies

Authors: HERTEL, PAULA - BAYLOR COLLEGE OF MED; CHACKO, SHAJI - BAYLOR COLLEGE OF MED; PAL, SUNITA - BAYLOR COLLEGE OF MED; Sunehag, Agneta; Haymond, Morey

Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/8/2006
Publication Date: 11/1/2006
Citation: Hertel, P.M., Chacko, S.K., Pal, S., Sunehag, A.L., Haymond, M.W. 2006. Subcutaneous infusion and capillary "finger stick" sampling of stable isotope tracer in metabolic studies. Pediatric Research. 60(5):597-601.

Interpretive Summary: Insulin-like growth factor 1 (IGF-I) mediates some, but not all of the metabolic actions of human growth hormone (GH). It has been known for some time that IGF-I has both GH-like and insulin-like actions in vivo. GH and IGF-I both have been demonstrated to enhance whole body protein synthesis over a period of weeks and perhaps months. Both hormones favorably improve body composition in GH deficient subjects by increasing lean body mass and decreasing fat mass. This is also observed when IGF-I is given to patients with GH-receptor mutations, which interferes with GH binding to the receptor. However GH and IGF-1 have divergent effects on carbohydrate metabolism. IGF-I administration leads to a lowering of plasma glucose and improved insulin sensitivity in the face of a marked lowering of circulating insulin concentrations, whereas GH therapy is associated increased plasma insulin concentrations, a reflection of relative insulin resistance. The latter observation makes IGF-I a potentially more convenient anabolic agent to use in conditions where carbohydrate metabolism is more likely to be impaired. GH increases fat mobilization as a direct effect of GH on the fat cell, as well as fat oxidation by increasing fatty acid availability. However IGF-I increases lipid oxidation only when given chronically, most likely as a result of the chronic lower insulin concentrations. These compounds used in a variety of catabolic conditions in man. Both hormones have been effective in reducing the protein wasting effects of steroids (glucocorticosteroids) and decrease some of the protein loss in men with very low plasma testosterone. A comparison of these and other effects of these two hormones is provided in this brief review. Subsequent studies are still needed to fully elucidate the safety and efficacy of IGF-I for use in humans.

Technical Abstract: Metabolic studies utilizing stable isotope tracer in humans have typically used intravenous tracer infusions and venous blood sampling. These studies explore subcutaneous infusion of isotope and "finger stick" capillary blood sampling to measure glucose turnover. Five subjects received simultaneous 8-h infusions of glucose labeled with isotope: [1-13C]glucose subcutaneously and [6,6-2H2]glucose intravenously. At regular intervals, venous and finger stick blood specimens were obtained. Finger stick blood was applied to filter paper. Substrate and isotopic steady state was reached after 7.0 h with both routes of infusion. The isotopic enrichments of finger stick and venous specimens did not differ significantly for the subcutaneously infused [1-13C]glucose (p = 0.33 and p = 0.23, respectively) but the finger stick [6,6-2H2]glucose enrichment was slightly higher (p < 0.03) than that of the venous sample. Using [6,6-2H2]glucose infusion and venous plasma sampling as the reference method, the [1-13C]glucose gave estimates of glucose Ra that were 13% (plasma) and 17% (finger stick) lower (p < 0.001 and p < 0.02, respectively). This difference could be attributed to recycling of 13C label. In conclusion, subcutaneous infusion and finger stick specimen collection onto filter paper represent a potential method of conducting in vivo studies of substrate metabolism outside of a hospital-based research unit.