The beneficial effects of exercise in patients with type 1 diabetes (T1D) are not fully proven, given that it may occasionally induce acute metabolic disturbances. Indeed, the metabolic disturbances associated with sustained exercise may lead to worsening control unless great care is taken to adjust carbohydrate intake and insulin dosage. In this work, pre- and postexercise metabolites were analyzed using a 1H-NMR and GC-MS untargeted metabolomics approach assayed in serum. We studied ten men with T1D and eleven controls matched for age, body mass index, body fat composition, and cardiorespiratory capacity, participated in the study. The participants performed 30 minutes of exercise on a cycleergometer at 80% VO2max. In response to exercise, both groups had increased concentrations of gluconeogenic precursors (alanine and lactate) and tricarboxylic acid cycle intermediates (citrate, malate, fumarate and succinate). The T1D group, however, showed attenuation in the response of these metabolites to exercise. Conversely to T1D, the control group also presented increases in a-ketoglutarate, alpha-ketoisocaproic acid, and lipolysis products (glycerol and oleic and linoleic acids), as well as a reduction in branched chain amino acids (valine and leucine) determinations. The T1D patients presented a blunted metabolic response to acute exercise as compared to controls. This attenuated response may interfere in the healthy performance or fitness of T1D patients, something that further studies should elucidate.
|Publication status||Published (in print/issue) - 1 Jul 2012|
Bibliographical noteReference text: 1. DCCT/EDIC - Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353: 2643–2653.
2. DPP - Diabetes Prevention Program Research Group (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med 346: 393–403.
3. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, et al. (1997) Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 20: 537–544.
4. Tuomilehto J, Lindstro¨m J, Eriksson J, Valle TT, Ha¨ma¨ la¨ inen H, et al. (2001) Prevention of type 2 diabetes by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344: 1343–1350.
5. Thompson PD, Buchner D, Pin˜a IL, Balady GJ, Williams MA, et al. (2003) Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease - a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation 107: 3109–3116.
6. Leon AS, Rice T, Mandel S, Despre´s JP, Bergeron J, et al. (2000) Blood lipid response to 20 weeks of supervised exercise in a large biracial population: the HERITAGE Family Study. Metabolism 49: 513–529. 7. Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, et al. (2007) Physical activity and public health updated recommendation for adults. From the American College of Sports Medicine and the American Heart Association. Circulation 116: 1081–1093.
8. Valerio G, Spagnuolo MI, Lombardi F, Spadaro R, Siano M, et al. (2007) Physical activity and sports participation in children and adolescents with type 1 diabetes mellitus. Nutr Metab Cardiovasc Dis 17: 376–382.
9. Lindon JNJ, Holmes E (2007) The handbook of metabonomics and metabolomics. 1 ed. UK: Elsevier.
10. Ma¨kinen VP, Soininen P, Forsblom C, Parkkonen M, Ingman P, et al. (2006) Diagnosing diabetic nephropathy by 1H-NMR metabonomics of serum. Magn Reson Mater Phy 19: 281–296.
11. Bain JR, Stevens RD, Wenner BR, Ilkayeva O, Muioi DM, et al. (2009) Metabolomics applies to diabetes research. Moving from information to knowledge. Diabetes, 58: 2429 2443.
12. Lanza IR, Zhang S, Ward LE, Karakelides H, Raftery D, et al. (2010) Quantitative metabolomics by 1H-NMR and LC-MS/MS confirms altered metabolic pathways in diabetes. PLoS ONE 5: e10538, 1–10.
13. Farrell L, Wood MJ, Martinovic M, Arany Z, et al. (2010) Metabolic signatures of exercise in human plasma. Sci Transl Med 2: 33ra37. doi:10.1126/ scitranslmed.3001006.
14. Enea C, Seguin F, Petitpas-Mulliez J, Boildieu N, Boisseau N, et al. (2010) 1H NMR-based metabolomics approach for exploring urinary metabolome modifications after acute and chronic physical exercise. Anal Bioanal Chem 396: 1167–1176.
15. Pechlivanis A, Kostidis S, Saraslanidis P, Petridou A, Tsalis G, et al. (2010) 1H NMR-Based metabonomic investigation of the effect of two different exercise sessions on the metabolic fingerprint of human urine. J Proteome Res 9: 6405–6516.
16. Zhang S, Zheng C, Lanza IR, Nair S, Raftery D, et al. (2009) Interdependence of signal processing and analysis of urine 1H NMR spectra for metabolomic profiling. Anal Chem, 81: 6080–6088.
17. Devlin J, Scrimgeour A, Brodsky I, Fuller S (1994) Decreased protein catabolism after exercise in subjects with IDDM. Diabetologia 37: 358–364.
18. Palmieri V, Pezzullo S, Arezzi E, D’Andrea C, Cassese S, et al. (2008) Cycleergometry stress testing and use of chronotropic reserve adjustment of ST depression for identification of significant coronary artery disease in clinical practice. Int J Cardiol 127: 390–392.
19. IPAQ - International Physical Activity Questionnaires, Available: http://www.ipaq.ki.se/ipaq.htm.
20. Palazoglu M, Fiehn O (2009) Metabolite identification in blood plasma using GC/MS and the agilent fiehn GC/MS metabolomics RTL Library. Agilent Application Note.
21. Albers M J, Butler TN, Rahwa I, Bao N, Keshari KR, et al. (2009) Evaluation of the ERETIC Method as an improved quantitative reference for H-1 HR-MAS spectroscopy of prostate tissue. Magnetic Resonance in Medicine 61, 525–532.
22. Storey JD, Tibshirani R (2003). Statistical significance for genomewide studies. Proc Nat Acad Sci USA 100: 9440–9445.
23. Sahlin K (1990) Muscle carnitine metabolism during incremental dynamic exercise in humans. Acta Physiol Scand, 138, 259–262.
24. Bowtell JL, Marwood S, Bruce M, Constantin-Teodosiu D, Greenhaff PL (2007) Tricarboxylic acid cycle intermediate pool size: functional importance for oxidative metabolism in exercising human skeletal muscle. Sports Medicine 37:1071–1088.
25. Gibala MJ, MacLean DA, Graham TE, Saltin B (1998) Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise. Am J of Physiol - End And Metab 275: E235–E242.
26. Chatzinikolaou A, Fatouros I, Petridou A, Jamurtas A, Avloniti A, et al. (2008) Adipose tissue lipolysis is upregulated in lean and obese men during acute resistance exercise. Diabetes Care 31: 1397–1399.
27. Jacob S, Hauer B, Becker R, Artzner S, Grauer P, et al. (1999) Lipolysis in skeletal muscle is rapidly regulated by low physiological doses of insulin. Diabetologia 42: 1171–1174.
28. Stumvoll M, Jacob S, Wahl HG, Hauer B, Lo¨blein K, et al. (2000) Suppression of systemic, intramuscular, and subcutaneous adipose tissue lipolysis by insulin in humans J Clin Endocrinol Metab 85: 3740–3745.
29. Henriksson J (1991) Effect of exercise on amino acid concentrations in skeletal muscle and plasma J Exp Biol. 1991 Oct;160: 149–65.
30. Gelfand RA, Barrett EJ (1987) Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man. J Clin Invest 80: 1–6.
31. Biolo G, Williams BD, Fleming RY, Wolfe RR (1999) Insulin action on muscle protein kinetics and amino acid transport during recovery after resistance exercise. Diabetes 48: 949–957.
32. Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, et al. (2000) Pharmacokinetics and pharmacodynamics of subcutaneous injection of longacting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes 49: 2142–2148.
33. Davison GW, George L, Jackson SK, Young IS, Davies B, et al. (2002) Exercise, free radicals, and lipid peroxidation in type 1 diabetes mellitus. Free Radic Biol Med 33: 1543–1551.
34. Yki-Ja¨rvinen H, Mott D, Young AA, Stone K, Bogardus C (1987) Regulation of glycogen synthase and phosphorylase activities by glucose and insulin in human skeletal muscle. J Clin Invest 80: 95–100.
35. Yki-Ja¨rvinen H, Helve E, Koivisto VA (1987) Hyperglycemia decreases glucose uptake in type I diabetes. Diabetes: 36: 892–896.
36. Schauer IE, Snell-Bergeon JK, Bergman BC, Maahs DM, Kretowski A, et al. (2011) Insulin resistance, defective insulin-mediated fatty acid suppression, and coronary artery calcification in subjects with and without type 1 diabetes: The CACTI study. Diabetes 60: 306–314.
37. Bergman BC, Howard D, Schauer IE, Maahs DM, Snell-Bergeon JK, et al. (2012) Features of Hepatic and Skeletal Muscle Insulin Resistance Unique to Type 1 Diabetes. J Clin Endocrinol Metab. 2012, doi: 10.1210/jc.2011–3172.
38. Nadeau KJ, Regensteiner JG, Bauer TA, Brown MS, Dorosz JL, et al. (2010) Insulin resistance in adolescents with type 1 diabetes and its relationship to cardiovascular function. J Clin Endocrinol Metab, 95: 513–521.
39. Perseghin G, Lattuada G, Danna M, Sereni LP, Maffi P, et al. (2003) Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes. Am J Physiol Endocrinol Metab 285: E1174–1181.
40. Levin K, Daa Schroeder H, Alford FP, Beck-Nielsen H (2001) Morphometric documentation of abnormal intramyocellular fat storage and reduced glycogen in obese patients with Type II diabetes. Diabetologia, 44: 824–833.
41. Kelley DE, Mandarino LJ (2000) Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49: 677–683.
42. Galgani JE, Moro C, Ravussin E (2008) Metabolic flexibility and insulin resistance. Am J Physiol Endocrinol Metab 295: E1009–1017.
43. Mogensen M, Sahlin K, Fernstro¨m M, Glintborg D, Vind BF, et al. (2007) Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 56: 1592–1599.
44. Befroy DE, Petersen KF, Dufour S, Mason GF, de Graaf RA, et al. (2007) Impaired mitochondrial substrate oxidation in muscle of insulin-resistant offspring of type 2 diabetic patients. Diabetes 56: 1376–1381.
45. Item F, Heinzer-Schweize S, Wyss M, Fontana P, Lehmann R, et al. (2011) Mitochondrial capacity is affected by glycemic status in young untrained women with type 1 diabetes but is not impaired relative to healthy untrained women Am J Physiol Regul Integr Comp Physiol 301: R60–R66.
46. Morino K, Petersen KF, Shulman GI (2006) Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes 55 (Suppl 2): S9–S15.
47. Farhy LS, Chan A, Breton MD, Anderson SM, Kovatchev BP, et al. (2012) Association of Basal hyperglucagonemia with impaired glucagon counterregulation in type 1 diabetes. Front Physiol.3:40, doi: 10.3389/fphys.2012.00040.
48. Divertie GD, Jensen MD, Cryer PE, Miles JM (1997) Lipolytic responsiveness to epinephrine in nondiabetic and diabetic humans. Am J Physiol, 272: E1130–1135.
49. Komatsu WR, Gabbay MA, Castro ML, Saraiva GL, Chacra AR, et al. (2005) Aerobic exercise capacity in normal adolescents and those with type 1 diabetes mellitus. Pediatr Diabetes 6: 145–149.
50. Gusso S, Hofman P, Lalande S, Cutfield W, Robinson E, et al. (2008) Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus. Diabetologia 51: 1317–1320.
51. Vervoort G, Wetzels JF, Lutterman JA, van Doorn LG, Berden JH, et al. (1999) Elevated skeletal muscle blood flow in noncomplicated type 1 diabetes mellitus: role of nitric oxide and sympathetic tone. Hypertension 34: 1080–1085.