Combined intervention with pioglitazone and n-3 fatty acids in metformin-treated type 2 diabetic patients: improvement of lipid metabolism
Status PubMed-not-MEDLINE Jazyk angličtina Země Velká Británie, Anglie Médium electronic-ecollection
Typ dokumentu časopisecké články
PubMed
26633989
PubMed Central
PMC4667423
DOI
10.1186/s12986-015-0047-9
PII: 47
Knihovny.cz E-zdroje
- Klíčová slova
- Docosahexaenoic acid, Eicosapentaenoic acid, Humans, Hyperinsulinemic-euglycemic clamp, Indirect calorimetry, Meal test,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The marine n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) exert numerous beneficial effects on health, but their potency to improve treatment of type 2 diabetic (T2D) patients remains poorly characterized. We aimed to evaluate the effect of a combination intervention using EPA + DHA and the insulin-sensitizing drug pioglitazone in overweight/obese T2D patients already treated with metformin. METHODS: In a parallel-group, four-arm, randomized trial, 69 patients (66 % men) were assigned to 24-week-intervention using: (i) corn oil (5 g/day; Placebo), (ii) pioglitazone (15 mg/day; Pio), (iii) EPA + DHA concentrate (5 g/day, containing ~2.8 g EPA + DHA; Omega-3), or (iv) pioglitazone and EPA + DHA concentrate (Pio& Omega-3). Data from 60 patients were used for the final evaluation. At baseline and after intervention, various metabolic markers, adiponectin and cytokines were evaluated in serum using standard procedures, EPA + DHA content in serum phospholipids was evaluated using shotgun lipidomics and mass spectrometry, and hyperinsulinemic-euglycemic clamp and meal test were also performed. Indirect calorimetry was conducted after the intervention. Primary endpoints were changes from baseline in insulin sensitivity evaluated using hyperinsulinemic-euglycemic clamp and in serum triacylglycerol concentrations in fasting state. Secondary endpoints included changes in fasting glycemia and glycated hemoglobin (HbA1c), changes in postprandial glucose, free fatty acid and triacylglycerol concentrations, metabolic flexibility assessed by indirect calorimetry, and inflammatory markers. RESULTS: Omega-3 and Pio& Omega-3 increased EPA + DHA content in serum phospholipids. Pio and Pio& Omega-3 increased body weight and adiponectin levels. Both fasting glycemia and HbA1c were increased by Omega-3, but were unchanged by Pio& Omega-3. Insulin sensitivity was not affected by Omega-3, while it was improved by Pio& Omega-3. Fasting triacylglycerol concentrations and inflammatory markers were not significantly affected by any of the interventions. Lipid metabolism in the meal test and metabolic flexibility were additively improved by Pio& Omega-3. CONCLUSION: Besides preventing a modest negative effect of n-3 fatty acids on glycemic control, the combination of pioglitazone and EPA + DHA can be used to improve lipid metabolism in T2D patients on stable metformin therapy. TRIAL REGISTRATION: EudraCT number 2009-011106-42.
Department of Physical Performance Norwegian School of Sport Sciences Oslo Norway
Institute for Clinical and Experimental Medicine Prague Czech Republic
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Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycaemia in type 2 diabetes, 2015: a patient-centred approach. Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015;58:429–442. doi: 10.1007/s00125-014-3460-0. PubMed DOI
American DA. Standards of medical care in diabetes--2014. Diabetes Care. 2014;37(Suppl 1):S14–80. doi: 10.2337/dc14-S014. PubMed DOI
Kim J, Kwak HJ, Cha JY, Jeong YS, Rhee SD, Kim KR, et al. Metformin suppresses lipopolysaccharide (LPS)-induced inflammatory response in murine macrophages via activating transcription factor-3 (ATF-3) induction. J Biol Chem. 2014;289:23246–23255. doi: 10.1074/jbc.M114.577908. PubMed DOI PMC
Mirmiranpour H, Mousavizadeh M, Noshad S, Ghavami M, Ebadi M, Ghasemiesfe M, et al. Comparative effects of pioglitazone and metformin on oxidative stress markers in newly diagnosed type 2 diabetes patients: a randomized clinical trial. J Diabetes Complications. 2013;27:501–507. doi: 10.1016/j.jdiacomp.2013.05.006. PubMed DOI
Rodriguez A, Reviriego J, Karamanos V, del Canizo FJ, Vlachogiannis N, Drossinos V, et al. Management of cardiovascular risk factors with pioglitazone combination therapies in type 2 diabetes: an observational cohort study. Cardiovasc Diabetol. 2011;10:18. doi: 10.1186/1475-2840-10-18. PubMed DOI PMC
Kus V, Flachs P, Kuda O, Bardova K, Janovska P, Svobodova M, et al. Unmasking Differential Effects of Rosiglitazone and Pioglitazone in the Combination Treatment with n-3 Fatty Acids in Mice Fed a High-Fat Diet. Plos One. 2011;6:e27126–e27127. doi: 10.1371/journal.pone.0027126. PubMed DOI PMC
Kuda O, Jelenik T, Jilkova Z, Flachs P, Rossmeisl M, Hensler M, et al. n-3 Fatty acids and rosiglitazone improve insulin sensitivity through additive stimulatory effects on muscle glycogen synthesis in mice fed a high-fat diet. Diabetologia. 2009;52:941–951. doi: 10.1007/s00125-009-1305-z. PubMed DOI
Yang J, Vallarino C, Bron M, Perez A, Liang H, Joseph G, et al. A comparison of all-cause mortality with pioglitazone and insulin in type 2 diabetes: an expanded analysis from a retrospective cohort study. Curr Med Res Opin. 2014;30:2223–2231. doi: 10.1185/03007995.2014.941054. PubMed DOI
Anagnostis P, Karras SN. Should we stop prescribing pioglitazone? Br J Clin Pharmacol. 2014;78:438–439. doi: 10.1111/bcp.12342. PubMed DOI PMC
Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies. BMJ. 2006;332:73–78. doi: 10.1136/bmj.38678.389583.7C. PubMed DOI PMC
Flachs P, Rossmeisl M, Kopecky J. The Effect of n-3 Fatty Acids on Glucose Homeostasis and Insulin Sensivity. Physiol Res. 2014;63:93–118. PubMed
Rakhshandehroo M, Hooiveld G, Muller M, Kersten S. Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. Plos One. 2009;4:e6796. doi: 10.1371/journal.pone.0006796. PubMed DOI PMC
Kris-Etherton PM, Harris WS, Appel LJ, Association AHANCAH. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol. 2003;23:151–152. doi: 10.1161/01.ATV.0000057393.97337.AE. PubMed DOI
Scorletti E, Bhatia L, McCormick KG, Clough GF, Nash K, Hodson L, et al. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study. Hepatology. 2014;60:1211–1221. doi: 10.1002/hep.27289. PubMed DOI
Mozaffarian D, Lemaitre RN, King IB, Song X, Huang H, Sacks FM, et al. Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific mortality in older adults: a cohort study. Ann Intern Med. 2013;158:515–525. doi: 10.7326/0003-4819-158-7-201304020-00003. PubMed DOI PMC
Calder PC, Yaqoob P. Omega-3 (n-3) fatty acids, cardiovascular disease and stability of atherosclerotic plaques. Cell Mol Biol (Noisy-le-Grand) 2010;56:28–37. PubMed
Authors/Task Force M. Ryden L, Grant PJ, Anker SD, Berne C, Cosentino F, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD) Eur Heart J. 2013;34:3035–3087. doi: 10.1093/eurheartj/eht108. PubMed DOI
Kromhout D, Geleijnse JM, de Goede J, Oude Griep LM, Mulder BJ, de Boer MJ, et al. n-3 fatty acids, ventricular arrhythmia-related events, and fatal myocardial infarction in postmyocardial infarction patients with diabetes. Diabetes Care. 2011;34:2515–2520. doi: 10.2337/dc11-0896. PubMed DOI PMC
Dangardt F, Chen Y, Gronowitz E, Dahlgren J, Friberg P, Strandvik B. High physiological omega-3 Fatty Acid supplementation affects muscle Fatty Acid composition and glucose and insulin homeostasis in obese adolescents. J Nutr Metab. 2012;2012:395757. doi: 10.1155/2012/395757. PubMed DOI PMC
Horakova O, Medrikova D, van Schothorst EM, Bunschoten A, Flachs P, Kus V, et al. Preservation of Metabolic Flexibility in Skeletal Muscle by a Combined Use of n-3 PUFA and Rosiglitazone in Dietary Obese Mice. Plos One. 2012;7:e43764. doi: 10.1371/journal.pone.0043764. PubMed DOI PMC
Pelikanova T, Smrckova I, Krizova J, Stribrna J, Lanska V. Effects of insulin and lipid emulsion on renal haemodynamics and renal sodium handling in IDDM patients. Diabetologia. 1996;39:1074–1082. doi: 10.1007/BF00400657. PubMed DOI
Golay A, DeFronzo RA, Ferrannini E, Simonson DC, Thorin D, Acheson K, et al. Oxidative and non-oxidative glucose metabolism in non-obese type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1988;31:585–591. doi: 10.1007/BF00264764. PubMed DOI
Ejsing CS, Duchoslav E, Sampaio J, Simons K, Bonner R, Thiele C, et al. Automated identification and quantification of glycerophospholipid molecular species by multiple precursor ion scanning. Anal Chem. 2006;78:6202–6214. doi: 10.1021/ac060545x. PubMed DOI
Kahleova H, Matoulek M, Malinska H, Oliyarnyk O, Kazdova L, Neskudla T, et al. Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes. Diabet Med. 2011;28:549–559. doi: 10.1111/j.1464-5491.2010.03209.x. PubMed DOI PMC
Jagadeesh B, Bharathi DV, Pankaj C, Narayana VS, Venkateswarulu V. Development and validation of highly selective and robust method for simultaneous estimation of pioglitazone, hydroxypioglitazone and metformin in human plasma by LC-MS/MS: application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2013;930:136–145. doi: 10.1016/j.jchromb.2013.04.024. PubMed DOI
Harris WS, Von Schacky C. The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med. 2004;39:212–220. doi: 10.1016/j.ypmed.2004.02.030. PubMed DOI
Galgani JE, Moro C, Ravussin E. Metabolic flexibility and insulin resistance. Am J Physiol Endocrinol Metab. 2008;295:E1009–1017. doi: 10.1152/ajpendo.90558.2008. PubMed DOI PMC
Riachi M, Himms-Hagen J, Harper ME. Percent relative cumulative frequency analysis in indirect calorimetry: application to studies of transgenic mice. Can J Physiol Pharmacol. 2004;82:1075–1083. doi: 10.1139/y04-117. PubMed DOI
Burdge GC, Calder PC. Plasma cytokine response during the postprandial period: a potential causal process in vascular disease? Br J Nutr. 2005;93:3–9. doi: 10.1079/BJN20041282. PubMed DOI
Wulffele MG, Kooy A, de Zeeuw D, Stehouwer CD, Gansevoort RT. The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus: a systematic review. J Intern Med. 2004;256:1–14. doi: 10.1111/j.1365-2796.2004.01328.x. PubMed DOI
Chan DC, Watts GF, Mori TA, Barrett PH, Beilin LJ, Redgrave TG. Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity. Eur J Clin Invest. 2002;32:429–436. doi: 10.1046/j.1365-2362.2002.01001.x. PubMed DOI
Flachs P, Rossmeisl M, Kuda O, Kopecky J. Stimulation of mitochondrial oxidative capacity in white fat independent of UCP1: A key to lean phenotype. Biochim Biophys Acta. 1831;2013:986–1003. PubMed
Wong AT, Chan DC, Ooi EM, Ng TW, Watts GF, Barrett PH. Omega-3 fatty acid ethyl ester supplementation decreases very-low-density lipoprotein triacylglycerol secretion in obese men. Clin Sci (Lond) 2013;125:45–51. doi: 10.1042/CS20120587. PubMed DOI
Miles EA, Rees D, Banerjee T, Cazzola R, Lewis S, Wood R, et al. Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations. Atherosclerosis. 2008;196:298–305. doi: 10.1016/j.atherosclerosis.2006.11.002. PubMed DOI
Hue L, Taegtmeyer H. The Randle cycle revisited: a new head for an old hat. Am J Physiol Endocrinol Metab. 2009;297:E578–E591. doi: 10.1152/ajpendo.00093.2009. PubMed DOI PMC
Williamson JR, Kreisberg RA, Felts PW. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A. 1966;56:247–254. doi: 10.1073/pnas.56.1.247. PubMed DOI PMC
Mostad IL, Bjerve KS, Basu S, Sutton P, Frayn KN, Grill V. Addition of n-3 fatty acids to a 4-hour lipid infusion does not affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus. Metabolism. 2009;58:1753–1761. doi: 10.1016/j.metabol.2009.06.003. PubMed DOI
Mostad IL, Bjerve KS, Bjorgaas MR, Lydersen S, Grill V. Effects of n-3 fatty acids in subjects with type 2 diabetes: reduction of insulin sensitivity and time-dependent alteration from carbohydrate to fat oxidation. Am J Clin Nutr. 2006;84:540–550. PubMed
Levin D, Bell S, Sund R, Hartikainen SA, Tuomilehto J, Pukkala E, et al. Pioglitazone and bladder cancer risk: a multipopulation pooled, cumulative exposure analysis. Diabetologia. 2015;58:493–504. doi: 10.1007/s00125-014-3456-9. PubMed DOI