Skip to main content
Top
Published in: Diabetology & Metabolic Syndrome 1/2017

Open Access 01-12-2017 | Research

Type II diabetes mellitus and hyperhomocysteinemia: a complex interaction

Authors: Daniel E. Platt, Essa Hariri, Pascale Salameh, Mahmoud Merhi, Nada Sabbah, Mariana Helou, Francis Mouzaya, Rita Nemer, Yasser Al-Sarraj, Hatem El-Shanti, Antoine B. Abchee, Pierre A. Zalloua

Published in: Diabetology & Metabolic Syndrome | Issue 1/2017

Login to get access

Abstract

Background

Elevated homocysteine (Hc) levels have a well-established and clear causal relationship to epithelial damage leading to coronary artery disease. Furthermore, it is strongly associated with other metabolic syndrome variables, such as hypertension, which is correlated with type II diabetes mellitus (T2DM). Studies on T2DM in relation to Hc levels have shown both positive and negative associations. The aim of the present study is to examine the relationship between Hc levels and risk of T2DM in the Lebanese population.

Methods

We sought to identify whether Hc associates positively or negatively with diabetes in a case–control study, where 2755 subjects enrolled from patients who had been catheterized for coronary artery diagnosis and treatment. We further sought to identify whether the gene variant MTHFR 667C>T is associated with T2DM, and how Hc and MTHFR 667C>T also impact other correlates of T2DM, including the widely used diuretics in this study population.

Results

We found that Hc levels were significantly reduced among subjects with diabetes compared to those without diabetes when adjusted for all potential confounders (OR 0.640; 95% CI [0.44–0.92]; p = 0.0200). The associations between Hc levels and other variates contradicted the result: hypertension associates positively with high Hc levels, and with T2DM. The MTHFR 667C>T only associated significantly with high Hc levels.

Conclusion

These results suggest population-specific variations among a range of mechanisms that modulate the association of Hc and T2DM, providing a probe for future studies.
Literature
1.
go back to reference Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103:137–49.CrossRefPubMed Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract. 2014;103:137–49.CrossRefPubMed
2.
go back to reference International Diabetes Federation. International Diabetes Federatio. IDF Diabetes Atlas. 6th ed. Brussels: International Diabetes Federation; 2013. International Diabetes Federation. International Diabetes Federatio. IDF Diabetes Atlas. 6th ed. Brussels: International Diabetes Federation; 2013.
3.
go back to reference Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87:4–14.CrossRefPubMed Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87:4–14.CrossRefPubMed
4.
go back to reference Costanian C, Bennett K, Hwalla N, Assaad S, Sibai AM. Prevalence, correlates and management of type 2 diabetes mellitus in Lebanon: findings from a national population-based study. Diabetes Res Clin Pract. 2014;105:408–15.CrossRefPubMed Costanian C, Bennett K, Hwalla N, Assaad S, Sibai AM. Prevalence, correlates and management of type 2 diabetes mellitus in Lebanon: findings from a national population-based study. Diabetes Res Clin Pract. 2014;105:408–15.CrossRefPubMed
5.
go back to reference Al-Khudairy L, Stranges S, Kumar S, Al-Daghri N, Rees K. Dietary factors and type 2 diabetes in the Middle East: what is the evidence for an association?–a systematic review. Nutrients. 2013;5:3871–97.CrossRefPubMedPubMedCentral Al-Khudairy L, Stranges S, Kumar S, Al-Daghri N, Rees K. Dietary factors and type 2 diabetes in the Middle East: what is the evidence for an association?–a systematic review. Nutrients. 2013;5:3871–97.CrossRefPubMedPubMedCentral
6.
go back to reference Ghassibe-Sabbagh M, Deeb M, Salloum AK, Mouzaya F, Haber M, Al-Sarraj Y, Chami Y, Akle Y, Hirbli K, Nemr R, et al. Multivariate epidemiologic analysis of type 2 diabetes mellitus risks in the Lebanese population. Diabetol Metab Syndr. 2014;6:89.CrossRefPubMedPubMedCentral Ghassibe-Sabbagh M, Deeb M, Salloum AK, Mouzaya F, Haber M, Al-Sarraj Y, Chami Y, Akle Y, Hirbli K, Nemr R, et al. Multivariate epidemiologic analysis of type 2 diabetes mellitus risks in the Lebanese population. Diabetol Metab Syndr. 2014;6:89.CrossRefPubMedPubMedCentral
7.
go back to reference Buysschaert M, Dramais AS, Wallemacq PE, Hermans MP. Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance. Diabetes Care. 2000;23:1816–22.CrossRefPubMed Buysschaert M, Dramais AS, Wallemacq PE, Hermans MP. Hyperhomocysteinemia in type 2 diabetes: relationship to macroangiopathy, nephropathy, and insulin resistance. Diabetes Care. 2000;23:1816–22.CrossRefPubMed
8.
go back to reference Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CD. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol. 1998;18:133–8.CrossRefPubMed Hoogeveen EK, Kostense PJ, Beks PJ, Mackaay AJ, Jakobs C, Bouter LM, Heine RJ, Stehouwer CD. Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study. Arterioscler Thromb Vasc Biol. 1998;18:133–8.CrossRefPubMed
9.
go back to reference Meigs JB, Jacques PF, Selhub J, Singer DE, Nathan DM, Rifai N, D’Agostino RB Sr, Wilson PW, Framingham Offspring S. Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study. Diabetes Care. 2001;24:1403–10.CrossRefPubMed Meigs JB, Jacques PF, Selhub J, Singer DE, Nathan DM, Rifai N, D’Agostino RB Sr, Wilson PW, Framingham Offspring S. Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study. Diabetes Care. 2001;24:1403–10.CrossRefPubMed
10.
go back to reference Agullo-Ortuno MT, Albaladejo MD, Parra S, Rodriguez-Manotas M, Fenollar M, Ruiz-Espejo F, Tebar J, Martinez P. Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus. Clin Chim Acta. 2002;326:105–12.CrossRefPubMed Agullo-Ortuno MT, Albaladejo MD, Parra S, Rodriguez-Manotas M, Fenollar M, Ruiz-Espejo F, Tebar J, Martinez P. Plasmatic homocysteine concentration and its relationship with complications associated to diabetes mellitus. Clin Chim Acta. 2002;326:105–12.CrossRefPubMed
11.
go back to reference Folsom AR, Nieto FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH, Hess DL, Davis CE. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the atherosclerosis risk in communities (ARIC) study. Circulation. 1998;98:204–10.CrossRefPubMed Folsom AR, Nieto FJ, McGovern PG, Tsai MY, Malinow MR, Eckfeldt JH, Hess DL, Davis CE. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the atherosclerosis risk in communities (ARIC) study. Circulation. 1998;98:204–10.CrossRefPubMed
12.
go back to reference Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation. 2000;101:1506–11.CrossRefPubMed Hoogeveen EK, Kostense PJ, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CD. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation. 2000;101:1506–11.CrossRefPubMed
13.
go back to reference Mazza A, Bossone E, Mazza F, Distante A. Reduced serum homocysteine levels in type 2 diabetes. Nutr Metab Cardiovasc Dis. 2005;15:118–24.CrossRefPubMed Mazza A, Bossone E, Mazza F, Distante A. Reduced serum homocysteine levels in type 2 diabetes. Nutr Metab Cardiovasc Dis. 2005;15:118–24.CrossRefPubMed
14.
go back to reference Emoto M, Kanda H, Shoji T, Kawagishi T, Komatsu M, Mori K, Tahara H, Ishimura E, Inaba M, Okuno Y. Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes. Diabetes Care. 2001;24:533–8.CrossRefPubMed Emoto M, Kanda H, Shoji T, Kawagishi T, Komatsu M, Mori K, Tahara H, Ishimura E, Inaba M, Okuno Y. Impact of insulin resistance and nephropathy on homocysteine in type 2 diabetes. Diabetes Care. 2001;24:533–8.CrossRefPubMed
17.
go back to reference Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, Rozen R. Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification. Nat Genet. 1994;7:551.CrossRefPubMed Goyette P, Sumner JS, Milos R, Duncan AM, Rosenblatt DS, Matthews RG, Rozen R. Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification. Nat Genet. 1994;7:551.CrossRefPubMed
18.
go back to reference Manolescu BN, Oprea E, Farcasanu IC, Berteanu M, Cercasov C. Homocysteine and vitamin therapy in stroke prevention and treatment: a review. Acta Biochim Pol. 2010;57:467–77.PubMed Manolescu BN, Oprea E, Farcasanu IC, Berteanu M, Cercasov C. Homocysteine and vitamin therapy in stroke prevention and treatment: a review. Acta Biochim Pol. 2010;57:467–77.PubMed
19.
go back to reference Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E, Heart Outcomes Prevention Evaluation I. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009;40:1365–72.CrossRefPubMed Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E, Heart Outcomes Prevention Evaluation I. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009;40:1365–72.CrossRefPubMed
20.
go back to reference Harmon DL, Doyle RM, Meleady R, Doyle M, Shields DC, Barry R, Coakley D, Graham IM, Whitehead AS. Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke. Arterioscler Thromb Vasc Biol. 1999;19:208–11.CrossRefPubMed Harmon DL, Doyle RM, Meleady R, Doyle M, Shields DC, Barry R, Coakley D, Graham IM, Whitehead AS. Genetic analysis of the thermolabile variant of 5, 10-methylenetetrahydrofolate reductase as a risk factor for ischemic stroke. Arterioscler Thromb Vasc Biol. 1999;19:208–11.CrossRefPubMed
21.
go back to reference Lievers KJ, Boers GH, Verhoef P, den Heijer M, Kluijtmans LA, van der Put NM, Trijbels FJ, Blom HJ. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J Mol Med (Berl). 2001;79:522–8.CrossRef Lievers KJ, Boers GH, Verhoef P, den Heijer M, Kluijtmans LA, van der Put NM, Trijbels FJ, Blom HJ. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. J Mol Med (Berl). 2001;79:522–8.CrossRef
22.
go back to reference Kluijtmans LA, Whitehead AS. Methylenetetrahydrofolate reductase genotypes and predisposition to atherothrombotic disease; evidence that all three MTHFR C677T genotypes confer different levels of risk. Eur Heart J. 2001;22:294–9.CrossRefPubMed Kluijtmans LA, Whitehead AS. Methylenetetrahydrofolate reductase genotypes and predisposition to atherothrombotic disease; evidence that all three MTHFR C677T genotypes confer different levels of risk. Eur Heart J. 2001;22:294–9.CrossRefPubMed
23.
go back to reference Patterson S, Flatt PR, Brennan L, Newsholme P, McClenaghan NH. Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic beta-cell glucose metabolism and insulin secretion. J Endocrinol. 2006;189:301–10.CrossRefPubMed Patterson S, Flatt PR, Brennan L, Newsholme P, McClenaghan NH. Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic beta-cell glucose metabolism and insulin secretion. J Endocrinol. 2006;189:301–10.CrossRefPubMed
24.
go back to reference Scullion SM, Gurgul-Convey E, Elsner M, Lenzen S, Flatt PR, McClenaghan NH. Enhancement of homocysteine toxicity to insulin-secreting BRIN-BD11 cells in combination with alloxan. J Endocrinol. 2012;214:233–8.CrossRefPubMed Scullion SM, Gurgul-Convey E, Elsner M, Lenzen S, Flatt PR, McClenaghan NH. Enhancement of homocysteine toxicity to insulin-secreting BRIN-BD11 cells in combination with alloxan. J Endocrinol. 2012;214:233–8.CrossRefPubMed
25.
go back to reference Motti C, Gnasso A, Bernardini S, Massoud R, Pastore A, Rampa P, Federici G, Cortese C. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine and other risk factors for vascular disease. Atherosclerosis. 1998;139:377–83.CrossRefPubMed Motti C, Gnasso A, Bernardini S, Massoud R, Pastore A, Rampa P, Federici G, Cortese C. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine and other risk factors for vascular disease. Atherosclerosis. 1998;139:377–83.CrossRefPubMed
26.
go back to reference Ghassibe-Sabbagh M, Platt DE, Youhanna S, Abchee AB, Stewart K, Badro DA, Haber M, Salloum AK, Douaihy B, el Bayeh H, et al. Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk. Atherosclerosis. 2012;222:180–6.CrossRefPubMed Ghassibe-Sabbagh M, Platt DE, Youhanna S, Abchee AB, Stewart K, Badro DA, Haber M, Salloum AK, Douaihy B, el Bayeh H, et al. Genetic and environmental influences on total plasma homocysteine and its role in coronary artery disease risk. Atherosclerosis. 2012;222:180–6.CrossRefPubMed
27.
go back to reference Sonkar SK, Sonkar GK, Soni D, Soni D, Usman K. Plasma Homocysteine level and its clinical correlation with type 2 diabetes mellitus and its complications. Int J Diabetes Develop Ctries. 2014;34:3–6.CrossRef Sonkar SK, Sonkar GK, Soni D, Soni D, Usman K. Plasma Homocysteine level and its clinical correlation with type 2 diabetes mellitus and its complications. Int J Diabetes Develop Ctries. 2014;34:3–6.CrossRef
28.
go back to reference Soinio M, Marniemi J, Laakso M, Lehto S, Ronnemaa T. Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus. Ann Intern Med. 2004;140:94–100.CrossRefPubMed Soinio M, Marniemi J, Laakso M, Lehto S, Ronnemaa T. Elevated plasma homocysteine level is an independent predictor of coronary heart disease events in patients with type 2 diabetes mellitus. Ann Intern Med. 2004;140:94–100.CrossRefPubMed
29.
go back to reference Looker HC, Fagot-Campagna A, Gunter EW, Pfeiffer CM, Narayan KM, Knowler WC, Hanson RL. Homocysteine as a risk factor for nephropathy and retinopathy in type 2 diabetes. Diabetologia. 2003;46:766–72.CrossRefPubMed Looker HC, Fagot-Campagna A, Gunter EW, Pfeiffer CM, Narayan KM, Knowler WC, Hanson RL. Homocysteine as a risk factor for nephropathy and retinopathy in type 2 diabetes. Diabetologia. 2003;46:766–72.CrossRefPubMed
30.
go back to reference Huang T, Ren J, Huang J, Li D. Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach. BMC Genom. 2013;14:867.CrossRef Huang T, Ren J, Huang J, Li D. Association of homocysteine with type 2 diabetes: a meta-analysis implementing Mendelian randomization approach. BMC Genom. 2013;14:867.CrossRef
31.
go back to reference Diakoumopoulou E, Tentolouris N, Kirlaki E, Perrea D, Kitsou E, Psallas M, Doulgerakis D, Katsilambros N. Plasma homocysteine levels in patients with type 2 diabetes in a Mediterranean population: relation with nutritional and other factors. Nutr Metab Cardiovasc Dis. 2005;15:109–17.CrossRefPubMed Diakoumopoulou E, Tentolouris N, Kirlaki E, Perrea D, Kitsou E, Psallas M, Doulgerakis D, Katsilambros N. Plasma homocysteine levels in patients with type 2 diabetes in a Mediterranean population: relation with nutritional and other factors. Nutr Metab Cardiovasc Dis. 2005;15:109–17.CrossRefPubMed
32.
go back to reference Russo GT, Di Benedetto A, Alessi E, Giandalia A, Gaudio A, Ientile R, Horvath KV, Asztalos B, Raimondo G, Cucinotta D. Menopause modulates homocysteine levels in diabetic and non-diabetic women. J Endocrinol Invest. 2008;31:546–51.CrossRefPubMed Russo GT, Di Benedetto A, Alessi E, Giandalia A, Gaudio A, Ientile R, Horvath KV, Asztalos B, Raimondo G, Cucinotta D. Menopause modulates homocysteine levels in diabetic and non-diabetic women. J Endocrinol Invest. 2008;31:546–51.CrossRefPubMed
33.
go back to reference Kumar J, Ingelsson E, Lind L, Fall T. No Evidence of a causal relationship between plasma homocysteine and type 2 diabetes: a Mendelian randomization study. Front Cardiovasc Med. 2015;2:11.CrossRefPubMedPubMedCentral Kumar J, Ingelsson E, Lind L, Fall T. No Evidence of a causal relationship between plasma homocysteine and type 2 diabetes: a Mendelian randomization study. Front Cardiovasc Med. 2015;2:11.CrossRefPubMedPubMedCentral
34.
go back to reference Dicker-Brown A, Fonseca VA, Fink LM, Kern PA. The effect of glucose and insulin on the activity of methylene tetrahydrofolate reductase and cystathionine-beta-synthase: studies in hepatocytes. Atherosclerosis. 2001;158:297–301.CrossRefPubMed Dicker-Brown A, Fonseca VA, Fink LM, Kern PA. The effect of glucose and insulin on the activity of methylene tetrahydrofolate reductase and cystathionine-beta-synthase: studies in hepatocytes. Atherosclerosis. 2001;158:297–301.CrossRefPubMed
35.
go back to reference Ksiazek P, Bednarek-Skublewska A, Buraczynska M. The C677T methylenetetrahydrofolate reductase gene mutation and nephropathy in type 2 diabetes mellitus. Med Sci Monit. 2004;10:Br47–51.PubMed Ksiazek P, Bednarek-Skublewska A, Buraczynska M. The C677T methylenetetrahydrofolate reductase gene mutation and nephropathy in type 2 diabetes mellitus. Med Sci Monit. 2004;10:Br47–51.PubMed
36.
go back to reference Maeda M, Yamamoto I, Fukuda M, Nishida M, Fujitsu J, Nonen S, Igarashi T, Motomura T, Inaba M, Fujio Y, Azuma J. MTHFR gene polymorphism as a risk factor for diabetic retinopathy in type 2 diabetic patients without serum creatinine elevation. Diabetes Care. 2003;26:547–8.CrossRefPubMed Maeda M, Yamamoto I, Fukuda M, Nishida M, Fujitsu J, Nonen S, Igarashi T, Motomura T, Inaba M, Fujio Y, Azuma J. MTHFR gene polymorphism as a risk factor for diabetic retinopathy in type 2 diabetic patients without serum creatinine elevation. Diabetes Care. 2003;26:547–8.CrossRefPubMed
37.
go back to reference Chen H, Wei F, Wang L, Wang Z, Meng J, Jia L, Sun G, Zhang R, Li B, Yu H, et al. MTHFR gene C677T polymorphism and type 2 diabetic nephropathy in Asian populations: a meta-analysis. Int J Clin Exp Med. 2015;8:3662–70.PubMedPubMedCentral Chen H, Wei F, Wang L, Wang Z, Meng J, Jia L, Sun G, Zhang R, Li B, Yu H, et al. MTHFR gene C677T polymorphism and type 2 diabetic nephropathy in Asian populations: a meta-analysis. Int J Clin Exp Med. 2015;8:3662–70.PubMedPubMedCentral
38.
go back to reference Russo GT, Di Benedetto A, Magazzu D, Giandalia A, Giorda CB, Ientile R, Previti M, Di Cesare E, Cucinotta D. Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study. Acta Diabetol. 2011;48:95–101.CrossRefPubMed Russo GT, Di Benedetto A, Magazzu D, Giandalia A, Giorda CB, Ientile R, Previti M, Di Cesare E, Cucinotta D. Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study. Acta Diabetol. 2011;48:95–101.CrossRefPubMed
39.
go back to reference Benrahma H, Abidi O, Melouk L, Ajjemami M, Rouba H, Chadli A, Oudghiri M, Farouqui A, Barakat A. Association of the C677T polymorphism in the human methylenetetrahydrofolate reductase (MTHFR) gene with the genetic predisposition for type 2 diabetes mellitus in a Moroccan population. Genet Test Mol Biomarkers. 2012;16:383–7.CrossRefPubMed Benrahma H, Abidi O, Melouk L, Ajjemami M, Rouba H, Chadli A, Oudghiri M, Farouqui A, Barakat A. Association of the C677T polymorphism in the human methylenetetrahydrofolate reductase (MTHFR) gene with the genetic predisposition for type 2 diabetes mellitus in a Moroccan population. Genet Test Mol Biomarkers. 2012;16:383–7.CrossRefPubMed
40.
go back to reference Sun J, Xu Y, Zhu Y, Lu H. Genetic polymorphism of methylenetetrahydrofolate reductase as a risk factor for diabetic nephropathy in Chinese type 2 diabetic patients. Diabetes Res Clin Pract. 2004;64:185–90.CrossRefPubMed Sun J, Xu Y, Zhu Y, Lu H. Genetic polymorphism of methylenetetrahydrofolate reductase as a risk factor for diabetic nephropathy in Chinese type 2 diabetic patients. Diabetes Res Clin Pract. 2004;64:185–90.CrossRefPubMed
41.
go back to reference Zhong JH, Rodriguez AC, Yang NN, Li LQ. Methylenetetrahydrofolate reductase gene polymorphism and risk of type 2 diabetes mellitus. PLoS ONE. 2013;8:e74521.CrossRefPubMedPubMedCentral Zhong JH, Rodriguez AC, Yang NN, Li LQ. Methylenetetrahydrofolate reductase gene polymorphism and risk of type 2 diabetes mellitus. PLoS ONE. 2013;8:e74521.CrossRefPubMedPubMedCentral
Metadata
Title
Type II diabetes mellitus and hyperhomocysteinemia: a complex interaction
Authors
Daniel E. Platt
Essa Hariri
Pascale Salameh
Mahmoud Merhi
Nada Sabbah
Mariana Helou
Francis Mouzaya
Rita Nemer
Yasser Al-Sarraj
Hatem El-Shanti
Antoine B. Abchee
Pierre A. Zalloua
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2017
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-017-0218-0

Other articles of this Issue 1/2017

Diabetology & Metabolic Syndrome 1/2017 Go to the issue