title: Elevated pregnancy-associated plasma protein-a in sera from type 2 diabetic patients with hypercholesterolemia: associations with carotid atherosclerosis and toe-brachial index.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Dokkyo University School of Medicine, Koshigaya Hospital, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan. yaso@dokkyomed.ac.jp.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Aso
authors.forename: Ki-ichi
authors.initials: K
authors.lastname: Okumura
authors.forename: Sadao
authors.initials: S
authors.lastname: Wakabayashi
authors.forename: Kohzo
authors.initials: K
authors.lastname: Takebayashi
authors.forename: Setsuko
authors.initials: S
authors.lastname: Taki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Inukai
mesh_terms: D000328:Adult; D000368:Aged; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D013599:Systole; D017540:Tunica Media / Q000473:pathology
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D011266:Pregnancy-Associated Plasma Protein-A