Fasting and Post-Methionine Homocysteine Levels in NIDDM

IDDM is associated with a sharplyi n c r eased risk of cardiovascular dis-ease and mort a l i t y . It is estimated that65% of all patients die from card i o v a s c u -lar complications (1,2). Part of thisi n c r eased risk is explained by clustering ofNIDDM with established risk factors fora t h e ro s c l e r osis, such as hypertension, obe-s i t y , and dyslipidemia, in the insulin-re s i s -tance syndrome. It appears, however, thatthese associated risk factors explain onlyp a r t of the excess cardiovascular disease inNIDDM patients (3,4). Whether the dia-betic hyperglycemic state itself completesthe risk pro fi le or whether other factors areinvolved is a matter of debate. NIDDMpatients with microalbuminuria are part i c -ularly at risk of developing card i o v a s c u l a rdisease (5–8). The underlying mechanismof this association is unknown, but it isclear that NIDDM patients with micro a l -buminuria have an even higher incidenceof hypertension, dyslipidemia, and thro m -bogenic disorders than do norm o a l b u m i n -uric NIDDM patients (9–13).Classic homocystinuria due to cys-tathionine -synthase deficiency associateswith early athero s c l e r osis and card i o v a s c u -lar mort a l i t y . Recently, mild elevations ofplasma homocysteine (Hcy) have beeni d e n t i fi ed as an independent risk factor forearly athero s c l e r otic vascular disease(14–19) and thromboembolic disease (20).Mild hyperhomocysteinemia has a com-plex etiology, including insufficient intakeof vitamins B6 and B12 and folate (21) andgenetic factors, of which a therm o l a b i l ef o r m of methylene-tetrahydrofolate re d u c -tase (MTHFR) is probably the most impor-tant one. The mechanism of pre m a t u r ec a r diovascular disease in this context is notp r ecisely known, but may relate toi n c r eased vulnerability to lipid toxicity, vas-cular smooth muscle cell growth factorp ro p e r ties of Hcy, endothelial damage, orvasomotor dysfunction or to disorders ofplatelet aggregation and coagulation (22).The possible role of mild hyperh o m o -cysteinemia in NIDDM is unclear. Fewstudies have addressed this issue, with con-