Extreme Urinary Betaine Losses in Type 2 Diabetes Combined with Bezafibrate Treatment are Associated with Losses of Dimethylglycine and Choline but not with Increased Losses of Other Osmolytes

Cardiovascular Drugs and Therapy

Volumn 28, Issue 5, 2014, Pages 459-468

  Lever, Michael ^a   McEntyre, Christopher J ^a   George, Peter M ^a   Slow, Sandy ^a   Elmslie, Jane L ^a   Lunt, Helen ^c   Chambers, Stephen T ^c   Parry Strong, Amber ^b   Krebs, Jeremy D ^b  

^a CANTERBURY HEALTH LABORATORIES   (New Zealand)

^b UNIVERSITY OF OTAGO WELLINGTON   (New Zealand)

^c UNIVERSITY OF OTAGO   (New Zealand)

Author keywords

Betaine excretion; Diabetes; Fibrates; Homocysteine; myo inositol; Osmolytes

Indexed keywords

ANTILIPEMIC AGENT; BETAINE; BEZAFIBRATE; CHOLINE; DIMETHYLGLYCINE; GLYCEROPHOSPHORYLCHOLINE; HOMOCYSTEINE; INOSITOL; SARCOSINE; TAURINE;

ADULT; AGED; ANALOGS AND DERIVATIVES; BLOOD; CLINICAL TRIAL; COMPARATIVE STUDY; FEMALE; HUMAN; MALE; MIDDLE AGED; NON INSULIN DEPENDENT DIABETES MELLITUS; URINE; YOUNG ADULT;

ADULT; AGED; BETAINE; BEZAFIBRATE; CHOLINE; DIABETES MELLITUS, TYPE 2; FEMALE; GLYCERYLPHOSPHORYLCHOLINE; HOMOCYSTEINE; HUMANS; HYPOLIPIDEMIC AGENTS; INOSITOL; MALE; MIDDLE AGED; SARCOSINE; TAURINE; YOUNG ADULT;

EID: 84930699311     PISSN: 09203206     EISSN: 15737241     Source Type: Journal    
DOI: 10.1007/s10557-014-6542-9     Document Type: Article

References (42)

1. Lever M, George PM, Elmslie JL, Atkinson W, Slow S, Molyneux SL, et al. Betaine and secondary events in an acute coronary syndrome cohort. PLoS One. 2012;7(5):e37883.
2. Svingen GFT, Ueland PM, Pedersen EKR, Schartum-Hansen H, Seifert R, Ebbing M, et al. Plasma dimethylglycine and risk of incident acute myocardial infarction in patients with stable angina pectoris. Arterioscler Thromb Vasc Biol. 2013;33:2041–8.
3. Lever M, Slow S. The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clin Biochem. 2010;43:732–44.
4. Lever M, George PM, Slow S, Elmslie JL, Scott RS, Richards AM, et al. Fibrates may cause an abnormal urinary betaine loss which is associated with elevations in plasma homocysteine. Cardiovasc Drugs Ther. 2009;23:395–40.
5. Schartum-Hansen H, Ueland PM, Pedersen ER, Meyer K, Ebbing M, Ovind B, et al. Assessment of urinary betaine as a marker of diabetes mellitus in cardiovascular patients. PLoS One. 2013;8:e469454.
6. Lever M, George PM, Dellow WJ, Scott RS, Chambers ST. Homocysteine, glycine betaine, and N, N-dimethylglycine in patients attending a lipid clinic. Metabolism. 2005;54:1–14.
7. Lever M, George PM, Atkinson W, Elmslie JL, Slow S, Molyneux SL, et al. The contrasting relationships between betaine and homocysteine in two clinical cohorts are associated with plasma lipids and drug treatments. PLoS One. 2012;7:e32460.
8. Lever M, Slow S, George PM, Chambers ST. Betaine excretion correlates with plasma homocysteine when plasma lipids are elevated. Clin Biochem. 2012;45:154–6.
9. Lever M, Sizeland PC, Bason LM, Hayman CM, Robson RA, Chambers ST. Abnormal glycine betaine content of the blood and urine of diabetic and renal patients. Clin Chim Acta. 1994;230:69–79.
10. Flory JH, Ellenberg S, Szapary PO, Strom BL, Hennessy S. Antidiabetic action of bezafibrate in a large observational database. Diabetes Care. 2009;32:547–51.
11. Wierzbicki AS. Fibrates: no ACCORD on their use in the treatment of dyslipidaemia. Curr Opin Lipidol. 2010;21:352–8.
12. Hamilton-Craig I, Kostner KM, Woodhouse S, Colquhoun D. Use of fibrates in clinical practice: Queensland lipid group consensus recommendations. Int J Evid Based Healthc. 2012;10:181–90.
13. Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, et al. Evaluation and treatment of hypertriglyceridemia: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:2969–89.
14. Jackevicius CA, Tu JV, Ross JS, Ko DT, Carreon D, Krumholz HM. Use of fibrates in the United States and Canada. JAMA. 2011;305:1217–24.
15. Lever M, McEntyre CJ, George PM, Slow S, Chambers ST, Foucher C. Fenofibrate causes elevation of betaine excretion but not excretion of other osmolytes by healthy adults. J Clin Lipidol 2014.
16. Krebs J, Elley C, Parry-Strong A, Lunt H, Drury PL, Bell DA, et al. The Diabetes Excess Weight Loss (DEWL) trial: a randomised controlled trial of high-protein versus high-carbohydrate diets over 2 years in type 2 diabetes. Diabetologia. 2012;55:905–14.
17. Fruchart J-C, Sacks FM, Hermans MP, et al. The residual risk reduction initiative: a call to action to reduce residual vascular risk in dyslipidaemic patients. Diab Vasc Dis Res. 2008;5:319–35.
18. Reiner Ž. Combined therapy in the treatment of dyslipidemia. Fundam Clin Pharmacol. 2010;24:19–28.
19. Barter PJ, Rye K-A. Is there a role for fibrates in the management of dyslipidemia in the metabolic syndrome? Arterioscler Thromb Vasc Biol. 2008;28:39–46.
20. Hottelart C, El Esper N, Archard JM, Pruna A, Fournier A. Fenofibrate increases blood creatinine, but dies not change the glomerular filtration rate in patients with mild renal insufficiency. Nephrologie. 1999;20:41–4.
21. Fruchart J-C, Davignon J, Hermans MP, et al. For the residual risk reduction initiative (R3i). Residual macrovascular risk in 2013: what have we learned? Cardiovasc Diabetol. 2014;13:26.
22. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63.
23. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, et al. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013;19:576–85.
24. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575–84.
25. Wang Z, Tang HW, Buffa JA, Fu X, Britt EB, Koeth RA, et al. Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J. 2014;35:904–10.
26. Bell JD, Lee JA, Lee HA, Sadler PJ, Wilkie, Woodham RH. Nuclear magnetic resonance studies of blood plasma and urine from subjects with chronic renal failure: identification of trimethylamine-N-oxide. Biochim Biophys Acta. 1991;1096:101–7.
27. Bain MA, Faull R, Fornasini G, Milne RW, Evans AM. Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis. Nephrol Dial Transplant. 2006;21:1300–4.
28. McGregor DO, Dellow WJ, Lever M, George PM, Robson RA, Chambers ST. Dimethylglycine accumulates in uremia and predicts elevated plasma homocysteine concentrations. Kidney Int. 2001;59:2267–72.
29. Lever M, George PM, Atkinson W, Molyneux SL, Elmslie JL, Slow S, et al. Plasma lipids and betaine are related in an acute coronary syndrome cohort. PLoS One. 2011;6:e21666.
30. Slow S, Donnaggio M, Cressey PJ, Lever M, George PM, Chambers ST. The betaine content of New Zealand foods and estimated intake in the New Zealand Diet. J Food Comp Anal. 2005;18:473–5.
31. Chiuve SE, Giovannucci EL, Hankinson SE, Zeisel SH, Dougherty LW, Willett WC, et al. The association between betaine and choline intakes and the plasma concentrations of homocysteine in women. Am J Clin Nutr. 2007;86:1073–81.
32. Detopoulou P, Panagiotakos DB, Antonopoulou S, Pitsavos C, Stefanadis C. Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study. Am J Clin Nutr. 2008;87:424–30.
33. Yonemori KM, Lim U, Koga KR, Wilkens LR, Au D, Carol J, et al. Dietary choline and betaine intakes vary in an adult multiethnic population. J Nutr. 2013;143:894–9.
34. Yoshii H, Uchino H, Ohmura C, Watanabe K, Tanaka Y, Kawamori R. Clinical usefulness of measuring urinary polyol excretion by gas-chromatography:mass-spectrometry in type 2 diabetes to assess polyol pathway activity. Diabetes Res Clin Pract. 2001;51:115–23.
35. Lever M, George PM, Atkinson W, Elmslie JL, Slow S, Molyneux SL, et al. The contrasting relationships between betaine and homocysteine in two clinical cohorts are associated with plasma lipids and drug treatments. PLoS One. 2012;7(3):e32460.
36. Brown JD, Plutzky J. Peroxisome proliferator-activated receptors as transcriptional nodal points and therapeutic targets. Circulation. 2007;115:518–33.
37. Sheikh K, Camejo G, Lanne B, Halvarsson T, Landergren MR, Oakes ND. Beyond lipids, pharmacological PPAR-alpha activation has important effects on amino acid metabolism as studied in the rat. Am J Physiol Endocrinol Metab. 2007;292:E1157–1165.
38. Hoffmann L, Brauers G, Gehrmann T, Häussinger D, Mayatepek E, Schliess F, et al. Osmotic regulation of hepatic betaine metabolism. Am J Physiol Gastrointest Liver Physiol. 2013;304:G835–46.
39. Wettstein M, Peters-Regehr T, Kubitz R, Fischer R, Holneicher C, Mönnighoff I, et al. Release of osmolytes induced by phagocytosis and hormones in rat liver. Am J Physiol Gastrointest Liver Physiol. 2000;278:G227–33.
40. Eisert R, Oftedal OT, Lever M, Ramdohr S, Breier BH, Barrell GK. Detection of food intake in a marine mammal using marine osmolytes and their analogues as dietary biomarkers. Mar Ecol Prog Ser. 2005;300:213–28.
41. European Food Safety Authority. Scientific Opinion on the substantiation of health claims related to betaine and contribution to normal homocysteine metabolism (ID 4325) pursuant to Article 13(1) of Regulation (EC) No 1924/2006. EFSA J. 2011;9(4):2052.
42. Lever M, George PM, Slow S, Elmslie JL, Shand BI, Scott RS, et al. Fibrates plus betaine: a winning combination? NZ Med J. 2010;123:74–8.