D. M. Bier

Glucose requirements following burn injury. Parameters of optimal glucose infusion and possible hepatic and respiratory abnormalities following excessive glucose intake.

Glucose and leucine metabolism in 18 severely burned patients were studied using the primed constant infusion of U-13C-glucose and l-13C-leucine, respectively. The leucine data were used to calculate rates of whole-body protein synthesis. In four additional burn patients and seven normal controls, the effects of exogenously infused insulin on the metabolism of infused glucose were evaluated. Also, the effect on leucine metabolism of adding insulin to infused glucose was tested and rates of protein synthesis were calculated. The protein studies were divided into two groups depending on the rate of glucose infusion. Protein synthesis was 4.3 + 0.54 g protein/kg/day during the lower infusion rates (1.4–4.5 mg/kg/min) and 5.17 + 0.19 g protein/kg/day during the higher infusion rates (4.7–9.3 mg/kg/min) (statistically different, p < 0.05). However, when the high infusion rate group was divided into two subgroups (high, 4.7–6.8 mg/kg/min, and very high, 7.03–9.31 mg/kg/min), there was no difference in the rate of protein synthesis. When U-13C-glucose was infused during varying rates of unlabeled glucose infusion, we found that the per cent of CO2 coming from the direct oxidation of glucose rose rapidly at the lower infusion rates but reached a plateau at approximately 55% as the infusion rates exceeded 5 mg/kg/min. Addition of insulin did not affect the rate of glucose oxidation but did seem to exert a stimulatory effect on protein synthesis. It was concluded that there appears to be a maximal rate of glucose infusion, beyond which physiologically significant increases in protein synthesis and direct oxidation of glucose cannot be expected. Furthermore, there appears to be a physiological cost of exceeding the optimal glucose infusion rate, as indicated by increased rates of CO2 production during infusion as well as large fat deposits in the liver at autopsy in patients infused with large amounts of glucose.

Leucine Metabolism in Type II Diabetes Mellitus

Severe muscle wasting is a well-recognized characteristic of untreated insulin-deficient diabetes mellitus, a condition in which leucine turnover and oxidation are accelerated. To ascertain whether a similar circumstance exists in type II diabetes when insulin is present but with reduced efficacy, we investigated leucine turnover and oxidation in five obese type II diabetic women by tracer infusion of L-[1-13C,15N]leucine in the postabsorptive state both before and after intensive insulin therapy. With conventional treatment, the type II diabetic women received 61 ± 33 (SD) U/day of insulin, and their fasting plasma glucose averaged 194 ± 41 (SD) mg/dl. Leucine carbon flux (Qc), nitrogen flux (QN), and oxidation (C) averaged 6.4 ± 1.2,15.6 ± 4.6, and 1.4 ± 0.3 mmol/h, respectively. These values were not different from the respective values of 6.6 ± 1.3, 17.0 ± 8.3, and 1.0 ± 0.2 mmol/h in matched obese nondiabetic controls, suggesting that leucine metabolism is not altered in insulin-treated type II diabetics. After a week of intensive insulin therapy in which the same diabetic subjects received 94 ± 36 U/day of insulin, postabsorptive plasma glucose declined to 117 ± 26 mg/dl. Leucine Qc(6.2 ± 1.0), QN (14.8 ± 3.7), and C (1.5 ± 0.5 mmol/h) were unaltered by the increased insulin therapy. Thus, obese type II diabetics had normal leucine kinetics but were hyperglycemic while receiving conventional insulin therapy. Additional intensive insulin therapy in these diabetic subjects improved plasma glucose but did not alter leucine kinetics. Thus, these data demonstrate a differential sensitivity of insulins action on carbohydrate versus amino acid metabolism in type II diabetics.

Quantitative aspects of glucose production and metabolism in healthy elderly subjects.

The metabolic basis for the reduced glucose tolerance that occurs during aging in humans has been explored with the aid of a primed constant intravenous infusion method of labeled glucose (6-3H; 6,6,2H- and U-13C-glucose). Healthy young adult men and women (24 ± 3 yr) and elderly men and women (75 ± 4 yr) participated in a series of studies designed to quantify rates of plasma glucose appearance, oxidation, and recycling while subjects were in the postabsorptive (basal) state and to determine rates of hepatic glucose production and glucose disappearance in response to intravenous glucose at approximately 1 and 2 mg · kg−1min−1 and also 4 mg · kg−1min−1 without or with a simultaneous infusion of insulin to maintain normoglycemia. Basal rates of glucose production were 2.41 ± 0.06 and 2.18 ± 0.05 mg · kg−1min−1 in the young adults and elderly, respectively (P < 0.05). Recycling of glucose carbon and glucose oxidation rates did not differ significantly between the two age groups. Infusion of unlabeled glucose reduced hepatic glucose production to the same extent in the two groups, indicating that the mechanisms responsible for altered hepatic glucose production with intravenous glucose administration remain intact during human aging. Plasma insulin changes were similar in young adult and elderly subjects receiving 4 mg · kg−1min−1 unlabeled glucose except that the higher plasma glucose levels in the elderly were associated with higher insulin levels. For elderly subjects, the amount of exogenous insulin required to maintain normoglycemia at the 4 mg · kg−1min−1 glucose infusion rate was about twice that necessary in young adults.