Cardiovascular complications are the leading causesof mortality in both insulin-dependent (IDDM) andnon-insulin-dependent diabetes mellitus (NIDDM).The severity of this problem is clearly illustrated bythe finding that IDDM patients suffer from mortalityrates many times higher than of the general popula-tion [1]. In spite of the gravity of this complication,there is a relative paucity of data specifically on thepathogenesis, prevention and the treatment of thecardiovascular lesions in diabetes. The goal of this ar-ticle is to highlight certain areas which are pertinentto diabetic cardiovascular complications and to sug-gest research goals which will bring understanding ofthe pathogenesis of this grave complication and itspotential treatments.George L. King: Hyperglycaemia and insulin resistance:how do they increase cardiovascular risk in diabeticpatients?A major cause of morbidity and mortality in diabeticpatients is macrovascular disease affecting the heartand large vessels. In diabetes there is an accelerationof atherosclerosis with excessive extracellular matrixthickening. In the heart, the major pathology is athe-rosclerosis of the coronary arteries, and the fibrosis,and hypertrophy of the myocardium. Hyperglycae-mia, hyperlipidaemia and insulin resistance are someof the recognized risk factors [2, 3]. The basic ab-normalities are in glucose metabolism and insulinaction which can lead to a whole range of vascularchanges in the areas of coagulation, contractility, leu-kocyte adhesions, and smooth muscle cell prolifera-tion. The mechanisms by which hyperglycaemia cau-ses vascular dysfunction are probably multiple. Thesemechanisms include non-enzymatic glycation, oxida-tive stress, polyol-myoinositol alteration, and activa-tion of diacylglycerol (DAG) and protein kinase C(PKC) pathways. The role of the DAG and PKCpathways which regulate many vascular functionswere discussed since this is the newest of the fourmain theories.Studies over the last 7 years have shown that thereis an increase in DAG levels and activation of PKCactivities in vascular cells from the retina, glomeruli,aorta and the heart when exposedto high glucose lev-els in culture or in the diabetic state in vivo [4]. In-creased glycolysis can elevate DAG which in turn ac-tivates protein kinase C in the vascular cells. The