Partially inconsistent data exist on mutual relations between nontraditional atherosclerotic risk factors, including the magnitude of
insulin resistance (IR), as well as on their relevance for
atherogenesis in the
metabolic syndrome. Subjects exhibiting combined impaired fasting
glucose and
impaired glucose tolerance (IFG/IGT) are exposed to an exceptionally high risk for
atherogenesis and development of
type 2 diabetes mellitus. Because of islet Beta-cell dysfunction, the usefulness of commonly used indices of IR is limited in IFG/IGT. Our aim was to assess the relationship between extent of angiographic
coronary artery disease (CAD) and nontraditional atherosclerotic risk factors (including IR by a clamp-based golden standard method) in IFG/IGT. Fifty-three subjects (32 men, 21 women; mean age, 55 +/- 11 years) with
stable angina, preserved left ventricular systolic function, and IFG/IGT were divided into 3 groups: group A (no
coronary stenoses >50%, n = 22), group B (1-vessel CAD, n = 15), and group C (2/3-vessel CAD, n = 16).
Insulin sensitivity was quantified by a hyperinsulinemic euglycemic clamp technique and expressed as M. M value, plasma
homocysteine (Hcy) level, and asymmetric
dimethyl-L-arginine (ADMA)/
L-arginine ratio were independent determinants of CAD extent as shown by forward stepwise discriminant function analysis. Compared with group A (M = 32.7 +/- 9.3 micromol/kg fat-free mass [FFM] per minute; Hcy, 8.1 +/- 1.4 micromol/L), lower M and higher Hcy levels were found in group B (M = 16.9 +/- 8.2 micromol/kg FFM per minute, P < .001; Hcy, 11.2 +/- 2.9 micromol/L, P = .003) and C (M = 16.4 +/- 7.8 micromol/kg FFM per minute, P < .001; Hcy, 12.8 +/- 3.9 micromol/L, P < .001). The ADMA/
L-arginine ratio was increased in group C (0.0078 +/- 0.0011) compared with group A (0.0063 +/- 0.0013, P = .03) and B (0.0058 +/- 0.0012, P = .01). Multivariate correlates (P < .05) of plasma Hcy concentrations were M (beta = -.34 +/- .12, P = .008),
creatinine clearance (beta = -.23 +/- .10, P = .03) and fasting
insulin (beta = .25 +/- .12, P = .04). This indicates an additive contribution of IR, plasma Hcy, and elevated ADMA/
L-arginine ratio to the extent of angiographic CAD in combined IFG/IGT.