Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-11T10:42:26.013Z Has data issue: false hasContentIssue false
  • English
  • Français

Dodecanedioic acid infusion induces a sparing effect on whole-body glucose uptake, mainly in non-insulin-dependent diabetes mellitus

Published online by Cambridge University Press:  09 March 2007

G. Mingrone ,
A. De Gaetano ,
A. V. Greco ,
E. Capristo ,
G. Benedetti ,
M. Castagneto  and
G. Gasbarrini
G. Mingrone
Affiliation:
Istituto di Medicina Interna e Geriatria and Istituto di Clinica Chirurgica, Università Cattolica S. Cuore, Rome, Italy
A. De Gaetano
Affiliation:
CNR, Centro di Studio per la Fisiopatologia dello Shock and Istituto di Clinica Chirurgica, Università Cattolica S. Cuore, Rome, Italy
A. V. Greco
Affiliation:
Istituto di Medicina Interna e Geriatria and Istituto di Clinica Chirurgica, Università Cattolica S. Cuore, Rome, Italy
E. Capristo
Affiliation:
Istituto di Medicina Interna e Geriatria and Istituto di Clinica Chirurgica, Università Cattolica S. Cuore, Rome, Italy
G. Benedetti
Affiliation:
Istituto di Medicina Interna e Geriatria and Istituto di Clinica Chirurgica, Università Cattolica S. Cuore, Rome, Italy
M. Castagneto
Affiliation:
CNR, Centro di Studio per la Fisiopatologia dello Shock and Istituto di Clinica Chirurgica, Università Cattolica S. Cuore, Rome, Italy
G. Gasbarrini
Affiliation:
Istituto di Medicina Interna e Geriatria and Istituto di Clinica Chirurgica, Università Cattolica S. Cuore, Rome, Italy
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Even-numbered dicarboxylic acids (DA) have been proposed as an alternative fuel substrate in parenteral nutrition. In particular, dodecanedioic acid (C12) shows a rapid plasma clearance from tissues, a very low urinary excretion compared with other DA and a high oxidation rate. The aim of the present study was to investigate the effect of C12 infusion on insulin-stimulated glucose uptake in patients with non-insulin-dependent diabetes mellitus (NIDDM) compared with healthy volunteers. A primed-constant infusion of C12 (0·39 mmol/min) was administered over 240 min, and at 120 min a 2 h euglycaemic hyperinsulinaemic clamp was performed. Blood specimens were sampled every 30 min and fractioned urines were collected over 24 h. The levels of C12 were measured by HPLC. Indirect calorimetry was performed continuously during the entire session. Body composition was assessed in all subjects studied to obtain fat-free mass (FFM) values. Whole-body glucose uptake decreased significantly during C12 infusion in both groups, although this effect was much more evident (P < 0·01) in NIDDM patients (52·4 (sd 15·8) % decrease compared with saline) than in controls (25·9 (sd 12·1) % decrease). The M value (μmol/kgffm per min) was reduced by C12 to lower levels in NIDDM patients than in normal controls (12·6 (sd 3·9) ν. 25·9 (sd 4·5), P < 0·01). Urinary excretion of C12 over 24 h was significantly lower in NIDDM patients than in controls (4·26 (sd 0·30) mmol ν. 5·43 (sd 0·48), P < 0·01), corresponding to less than 3 % of the administered dose. The infusion of C12 decreased non-protein RQ significantly in both groups of patients. In conclusion, this study shows, for the first time, that C12 significantly reduces glucose uptake in both normal controls and NIDDM patients, although this sparing effect on glucose uptake is much more pronounced in diabetic patients. These data suggest that C12 decreases glucose uptake and oxidation, mainly through a mechanism of substrate competition. Thus, it might be a useful alternative substrate in enteral or parenteral nutrition, sparing glucose utilization and increasing glycogen stores, in those clinical conditions, like NIDDM, where reduced insulin-induced glucose uptake and oxidation are observed.

Keywords

Dicarboxylic acidsDodecanedioic acidNon-insulin-dependent diabetes mellitus
Type
Human and Clinical Nutrition
Information
British Journal of Nutrition , Volume 78 , Issue 5 , November 1997 , pp. 723 - 735
Copyright
Copyright © The Nutrition Society 1997

References

REFERENCES

Bach, A. C. & Babayan, V. K. (1982) Medium-chain triglycerides: an update. American Journal of Clinical Nutrition 36, 950–962.Google Scholar
Beck-Nielsen, H. (1989) Insulin resistance in skeletal muscles of patients with diabetes mellitus. Diabetes Metabolism Review 5, 487–493.CrossRefGoogle ScholarPubMed
Beck-Nielsen, H., Vaag, A., Damsbo, P., Handberg, A., Nielsen, O. H., Henriksen, J. E. & Thye-Rønn, P. (1992) Insulin resistance in skeletal muscles in patients with NIDDM. Diabetes Care 15, 418–429.CrossRefGoogle ScholarPubMed
Beck-Nielsen, H., Wright, K., Verity, L., Bell, J. M., Kolterman, P. & Mandarino, L. J. (1987) Reduced glucose oxidation and pyruvate-dehydrogenase activity (PDH) in Type I diabetics (insulin-dependent) in poor control. Diabetes 36, Suppl. 1, 30A.Google Scholar
Bertuzzi, A., Gandolfi, A., Salinari, S., Mingrone, G., Arcieri-Mastromattei, E., Finotti, E. & Greco, A. V. (1991) Pharmacokinetic analysis of azelaic acid disodium salt: a proposed substrate for total parenteral nutrition. Clinical Pharmacokinetics 20, 411–419.Google Scholar
Bertuzzi, A., Mingrone, G., De Gaetano, A., Gandolfi, A., Greco, A. V. & Salinari, S. (1997) Kinetics of dodecanedioic acid and effect of its administration on glucose kinetics in rats. British Journal of Nutrition 78, 143–153.Google Scholar
Boden, G., Jadali, F., White, J., Liang, Y., Mozzoli, M., Chen, X., Coleman, E. & Smith, C. (1991) Effects of fat on insulin-stimulated carbohydrate metabolism in normal man. Journal of Clinical Investigation 88, 960–966.CrossRefGoogle Scholar
Bonadonna, R. C., Zych, K., Boni, C., Ferrannini, E. & De Fronzo, R. A. (1989) Time dependence of the interaction between lipid and glucose in man. American Journal of Physiology 257, E49–E56.Google Scholar
Bonora, E., Del Prato, S., Bonadonna, R. C., Gulli, G., Solini, A., Shank, M. L., Ghiatas, A. A., Lancaster, J. L., Kilcoyne, R. F., Alyassin, A. M. & De Fronzo, R. A. (1992) Total body fat content and fat topography are associated differently with in vivo glucose metabolism in nonobese and obese nondiabetic women. Diabetes 41, 1151–1159.Google Scholar
Damsbo, P., Vaag, A., Hother-Nielsen, O. & Beck-Nielsen, H. (1991) Reduced glycogen synthase activity in skeletal muscle from obese patients with and without Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 34, 239–245.Google Scholar
De Fronzo, R. A., Tobin, J. D. & Andres, R. (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. American Journal of Physiology 273, E214–E223.Google Scholar
De Gaetano, A., Castagneto, M., Mingrone, G., Gangeri, G., Sganga, G., Tataranni, P. A., Raguso, C. & Greco, A. V. (1994) Kinetics of medium chain triglycerides and free fatty acids in healthy volunteers and surgically stressed patients. Journal of Parenteral and Enteral Nutrition 18, 134–140.CrossRefGoogle ScholarPubMed
Ferrannini, E. (1988) The theoretical basis of indirect calorimetry: a review. Metabolism 3, 287–301.CrossRefGoogle Scholar
Ferrannini, E., Barrett, E. & Bevilacqua, S. (1983) Effect of fatty acids on glucose production and utilization in man. Journal of Clinical Investigation 72, 1737–1747.CrossRefGoogle ScholarPubMed
Freymond, D., Bogardus, C., Okubo, M., Stone, K. & Mott, D. (1988) Impaired insulin-stimulated muscle glycogen synthase activation in vivo in man is related to low fasting glycogen synthase phosphatase activity. Journal of Clinical Investigation 82, 1503–1509.CrossRefGoogle Scholar
Greco, A. V. & Mingrone, G. (1995) Dicarboxylic acids, an alternative fuel substrate in parenteral nutrition: an update. Clinical Nutrition 14, 143–148.CrossRefGoogle Scholar
Johnson, R. C. & Cotter, R. (1986) Metabolism of medium-chain triacylglycerol lipid emulsion. Nutrition International 2, 150–158.Google Scholar
Kelley, D. E. & Mandarino, L. J. (1990) Hyperglycemia normalizes insulin-stimulated skeletal muscle glucose oxidation and storage in noninsulin-dependent diabetes mellitus. Journal of Clinical Investigation 86, 1999–2007.Google Scholar
Kiens, B., Essen-Gustavson, B., Gad, P. & Lithell, H. (1987) Lipoprotein lipase activity and intramuscular triglyceride stores after long-term high-fat and high-carbohydrate diets in physically trained men. Clinical Physiology 7, 1–9.Google Scholar
Kou, Y. & Tserng Shiow-Jen, J. (1991) Metabolic conversion of dicarboxylic acids to succinate in rat liver homogenates. Journal of Biological Chemistry 266, 2924–2929.Google Scholar
Mingrone, G., De Gaetano, A., Greco, A. V., Benedetti, G., Capristo, E. & Castagneto, M. (1996) Plasma clearance and oxidation of dodecanedioic acid in man. Journal of Parenteral and Enteral Nutrition 20, 38–42.Google Scholar
Mingrone, G., Greco, A. V., De Gaetano, A., Tataranni, P. A., Raguso, C. & Castagneto, M. (1994) Pharmacokinetic profile of dodecanedioic acid, a proposed alternative fuel substrate. Journal of Parenteral and Enteral Nutrition 18, 225–230.Google Scholar
Petrides, A. S., Groop, L. C., Riely, C. A. & De Fronzo, R. A. (1991) Effect of physiologic hyperinsulinemia on glucose and lipid metabolism in cirrhosis. Journal of Clinical Investigation 88, 561–570.CrossRefGoogle ScholarPubMed
Pi-Sunyer, F. X., Hashim, S. A. & Van Itallie, T. B. (1969) Insulin and ketone responses to ingestion of medium and long-chain triglycerides in man. Diabetes 18, 96–100.Google Scholar
Raguso, C., Mingrone, G., Greco, A. V., Tataranni, A., De Gaetano, A. & Castagneto, M. (1994) Dicarboxylic acids and glucose utilization in humans: effect of sebacate. Journal of Parenteral and Enteral Nutrition 18, 9–13.Google Scholar
Randle, P. J., Garland, P. B., Hales, C. N. & Newsholme, E. A. (1964) The glucose fatty acid cycle and diabetes mellitus. In Ciba Foundation, Colloquia on Endocrinology 15, Aetiology of Diabetes Mellitus and its Complications, pp. 192–216. London: J. & A. Churchill, Ltd.Google Scholar
Sandström, R., Hyltander, A., Korner, U. & Lundholm, K. (1993) Structured triglycerides to postoperative patients: a safety and tolerance study. Journal of Parenteral and Enteral Nutrition 17, 153–157.CrossRefGoogle ScholarPubMed