Serum homocysteine concentration is related to diabetes mellitus, but not to coronary heart disease, in Saudi Arabians M. Al-Nozah, 1 N. Al-Daghri, 2 W. A. Bartlett, 2 O. Al-Attas, 3 M. Al-Maatouq, 1 S.C.Martin, 2 S. Kumar 4 and A. F. Jones 2,4 1 College of Medicine, King Saud University, Riyadh, Saudi Arabia 2 Department of Clinical Biochemistry, Birmingham Heartlands Hospital, Birmingham, UK 3 College of Science, King Saud University, Riyadh, Saudi Arabia 4 Department of Medicine, Birmingham Heartlands Hospital, Birmingham, UK Introduction: Plasma homocysteine (HCYS) concentration is believed to be an independent risk factor for atherosclerosis. Methods: HCYS was measured in a cohort of 584 Saudi Arabians participating in a national screening study of coronaryheartdisease(CHD)riskfactors.Atotalof173subjects(114menand59women)hadclinicalCHD,ofwhom 82 (47.4%) had type 2 diabetes mellitus (56 men and 26 women). A further 127 subjects (60 men and 67 women) also had type 2 diabetes mellitus but no CHD. A total of 284 individuals (120 men and 164 women) were recruited as healthy controls, and had no previous history of CHD or diabetes. Serum HCYS was measured by high-performance liquid chromatography (HPLC) with electrochemical detection. Results: Univariate analysis showed HCYS concentrations were significantly lower in those with diabetes mellitus (DM) than in controls, for both men [8.7 (4.2±18.6) vs. 10.5 (4.5±20.5) mmol/l, median (5th95th percentiles, p  0.009] and women [6.3 (3.3±24.0) vs. 8.1 (4.0±17.9) mmol/l, p  0.049]. Stepwise multivariate regression analysis indicated a relationship between HCYS concentration and age, sex and the presence of DM, but not with CHD. Conclusions: In the Saudi Arabian population, serum HCYS is not a risk factor for CHD, but is lower in patients with DM. Keywords: homocysteine, diabetes mellitus, coronary heart disease Received 24 August 2000; returned for revision 5 October 2000; revised version accepted 20 August 2001 Introduction Homocysteine (HCYS) is a sulphur-containing amino acid that is an intermediary product in methionine metabolism. De-methylation of methionine produces HCYS, which can either be re-methylated to methionine inaprocessdependentuponfolicacidandvitaminB12, or converted to cystathionine in a reaction dependent upon vitamin B6. HCYS, like other thiols, readily auto-oxidizes to the disulphide homocysteine, or to other mixed disulphides, which together account for the major fraction of plasma HCYS. In the early 1960s, HCYS was first associated with pathological thrombotic disease in patients with homocysteinuria, an inborn error of HCYS metabolism in which the plasma HCYS concentration is grossly elevated [1,2]. In 1975, McCully and Wilson proposed that HCYS was also involved in the pathogenesis of atherosclerosis, a hypothesis based on the examination of autopsy material from children with homocystein- uria [3,4]. It is, however, only within the past six years that more moderate degrees of hyperhomocysteinaemia havebeenacceptedasamajorindependentriskfactorfor cardiovascular disease, being linked to the development Correspondence: Mr Nasser Al-Daghri, Department of Clinical Biochemistry, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK. E-mail: n.m.aldaghri@bham.ac.uk ORIGINAL ARTICLE 118 Diabetes, Obesity and Metabolism, 4, 2002, 118±123 # 2002 Blackwell Science Ltd