Elevated Pregnancy-Associated Plasma Protein-A in Sera from Type 2 Diabetic Patients with Hypercholesterolemia: Associations with Carotid Atherosclerosis and Toe-Brachial Index

• Published in: The journal of clinical endocrinology and metabolism 2004-11, Vol.89 (11), p.5713-5717
• Main Authors: Aso, Yoshimasa, Okumura, Ki-ichi, Wakabayashi, Sadao, Takebayashi, Kohzo, Taki, Setsuko, Inukai, Toshihiko
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Carotid Arteries - pathology; Carotid Artery Diseases - blood; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Diabetes Mellitus, Type 2 - blood; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Humans; Hypercholesterolemia - blood; Male; Medical sciences; Middle Aged; Pregnancy-Associated Plasma Protein-A - analysis; Systole; Tunica Media - pathology; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2004-0787

Pregnancy-associated plasma protein (PAPP)-A, a superfamily of metalloproteinase, has been implicated in acute coronary syndrome. We compared PAPP-A concentrations in sera from patients with type 2 diabetes with those in sera from age-matched control subjects and also investigated whether serum PAPP-A was associated with carotid intima-media wall thickness (IMT), an early marker of atherosclerosis, and indices of peripheral vascular disease in the diabetic patients. Serum PAPP-A was measured by an ELISA in 103 type 2 diabetic patients and 32 age-matched control subjects. All subjects were not pregnant. IMT was evaluated ultrasonographically in both common carotid arteries. As measures of peripheral vascular disease, we also determined the ankle-brachial index and toe-brachial index (TBI) for systolic blood pressure. Hypercholesterolemia was defined as a serum low-density lipoprotein-cholesterol concentration exceeding 3.6 mmol/liter or alternatively as a treatment with hydroxymethylglutaryl coenzyme A reductase inhibitor. Serum PAPP-A was significantly higher in diabetic patients than control subjects (P < 0.0001). In diabetic patients, serum PAPP-A correlated positively with serum total cholesterol (r = 0.289, P = 0.0041) and IMT (r = 0.315, P = 0.0017) and negatively with TBI (r = −0.294, P = 0.0039) but not ankle-brachial index. Diabetic patients with hypercholesterolemia had higher PAPP-A concentrations than those without hypercholesterolemia [median (interquartile ranges): 8.37 (6.93, 11.6) vs. 7.29 (5.65, 9.21) mIU/liter; P = 0.0209]. Multivariate analysis identified only serum total cholesterol as an independent determinant of serum PAPP-A in patients with type 2 diabetes (partial coefficient 0.454, P = 0.020). In conclusion, serum PAPP-A concentrations were significantly elevated in diabetic patients with hypercholesterolemia and were associated positively with carotid atherosclerosis and negatively with TBI in type 2 diabetes.