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Pregnancy‐associated plasma protein A in a large cohort of Type 1 diabetic patients with and without diabetic nephropathy—a prospective follow‐up study
Author(s) -
Astrup A. S.,
Tarnow L.,
Christiansen M.,
Hansen P. R.,
Parving H.H.,
Rossing P.
Publication year - 2007
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/j.1464-5491.2007.02283.x
Subject(s) - medicine , diabetic nephropathy , prospective cohort study , hazard ratio , nephropathy , diabetes mellitus , pregnancy associated plasma protein a , gastroenterology , cohort , type 2 diabetes , endocrinology , pregnancy , confidence interval , gestation , first trimester , biology , genetics
Aim Pregnancy‐associated plasma protein A (PAPP‐A) has been implicated in the aetiology of acute coronary syndromes and carotid and peripheral artherosclerosis. Diabetic nephropathy is characterized by increased cardiovascular risk. We investigated the prognostic value of PAPP‐A in a large cohort of Type 1 diabetic patients. Methods In a prospective observational follow‐up study, 197 Type 1 diabetic patients with diabetic nephropathy and a matched group of 178 patients with normoalbuminuria were followed for 10.1 (0–10.3) years. PAPP‐A was determined at baseline. Results In patients with diabetic nephropathy, plasma PAPP‐A was elevated 3.6 (0.4–51.1) mIU/l [median (range)] vs. 2.1 (0.4–46.6) mIU/l in normoalbuminuric patients, P < 0.0001. For acute coronary syndromes, a PAPP‐A threshold of 10 mIU/l has been suggested. Thirty‐seven patients were above the threshold and of these 13 patients (35%) died, compared with 60 of 338 patients (18%) below the threshold; log rank test P = 0.007. PAPP‐A significantly predicted mortality after adjustment for presence of nephropathy; hazard ratio for dying when PAPP‐A was above the threshold 2.1 (95% CI 1.13–3.9); P = 0.019. After adjusting for traditional risk factors, the results were attenuated. When only patients with nephropathy were analysed, PAPP‐A was significantly predictive of all‐cause mortality [ P = 0.008; 2.43 (1.26–4.67)] in unadjusted analysis. After adjustment, the predictive value of PAPP‐A for all‐cause mortality was attenuated ( P = 0.064). Conclusion We find PAPP‐A to be associated with increased mortality in Type 1 diabetic patients with nephropathy in unadjusted analysis. After adjustment for traditional risk factors, the prognostic value of PAPP‐A was no longer significant.