We thank Conti et al. (1) for their interest in our recent article (2) and the editor for the opportunity to further discuss the role of the IGF system in atherosclerosis.

We found an inverse relation between IGF binding protein-1 (IGFBP-1) and carotid intima-media thickness (IMT) in type 2 diabetic patients. In the linear regression model for diabetic subjects with cardiovascular disease (CVD), IGFBP-1 was one of the main determinants of IMT (standardized coefficient β = −0.353, P = 0.027) together with age, Apo B, and pulse pressure; other determinants were diabetes duration, smoking, BMI, sex, and lipoprotein [Lp(a)]. This model explained 57.3% of maximum IMT variation. IGFBP-1 also remained in the linear regression model for IMT in subjects without CVD. Our cross-sectional study setting does not allow the interpretation to which extent these associations are causal. In agreement with previous data (3), IGFBP-1 concentration was inversely related to insulin resistance examined by homeostasis model assessment.

On the contrary, after adjusting for confounders, we found no association between total IGF-I and either IMT or presence of CVD. This indicates the relation between IGFBP-1 and IMT to be independent of IGF-I. Our results underline IGFBP-1 as a marker of insulin resistance and the metabolic syndrome, but this cannot be extrapolated to reflect an IGF-I effect on the vasculature. Similarly, Heald et al. (4) demonstrated an inverse correlation between IGFBP-1, but not IGF-I, and clinical cardiovascular disease in type 2 diabetic subjects.

Another finding was the positive correlation of total IGF-I with LDL cholesterol and Lp(a) and IGFBP-3 with LDL cholesterol, Lp(a), total cholesterol, and Apo B after controlling for age, sex, BMI, and diabetes duration. Thus, in hypercholesterolemic diabetic patients the IGF axis seems to be activated.

The relation of the IGF system to CVD is complex and awaits a conclusive answer after over 1,000 published articles (5). Therefore, we agree with Conti et al. that further research is needed to understand the entire picture.

1.
Conti E, Pitocco D, Capoluongo E, Zuppi C, Ghirlanda G, Crea F, Andreotti F: IGF-1 and macrovascular complications of diabetes: alternative interpretations of recently published data (Letter).
Diabetes Care
 
26
:
1653
–1654,
2003
2.
Leinonen ES, Salonen JT, Salonen RM, Koistinen RA, Leinonen PJ, Sarna SS, Taskinen MR: Reduced IGFBP-1 is associated with thickening of the carotid wall in type 2 diabetes.
Diabetes Care
 
25
:
1807
–1812,
2002
3.
Mohamed-Ali V, Pinkney JH, Panahloo A, Cwyfan-Hughes S, Holly JM, Yudkin JS: Insulin-like growth factor binding protein-1 in NIDDM: relationship with the insulin resistance syndrome.
Clin Endocrinol (Oxf)
 
50
:
221
–228,
1999
4.
Heald AH, Siddals KW, Fraser W, Taylor W, Kaushal K, Morris J, Young RJ, White A, Gibson JM: Low circulating levels of IGF binding protein-1 are closely associated with the presence of macrovascular disease and hypertension in type 2 diabetes.
Diabetes
 
51
:
2629
–2636,
2002
5.
Frystyk J, Ledet T, Møller N, Flyvbjerg A, Ørskov H: Cardiovascular disease and insulin-like growth factor I.
Circulation
 
106
:
893
–895,
2002

Address correspondence to Professor Marja-Riitta Taskinen, Helsinki University Hospital, Biomedicum, Haartmaninkatu 8, P.O. Box 700, 00029 Helsinki, Finland. E-mail: [email protected].

DIABETES CARE
2003