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Haptoglobin phenotype modulates lipoprotein-associated risk for preeclampsia in women with Type 1 diabetes.

Clare B Kelly,Jeremy Y Yu,A. Jenkins,A. Nankervis,K. Hanssen,S. Garg,J. Scardo,A. Basu,S. Hammad,C. Aston,T. Lyons

Published 2019 in Journal of Clinical Endocrinology and Metabolism

ABSTRACT

CONTEXT The incidence of preeclampsia (PE) is increased in women with diabetes (∼20% vs ∼5% in general population), and first trimester lipoprotein profiles are predictive. Haptoglobin (Hp), a protein with functional genetic polymorphisms, has antioxidant, anti-inflammatory, and angiogenic effects. Among people with diabetes, Hp 2-2 phenotype is associated with cardio-renal disease. OBJECTIVE To investigate whether Hp phenotype is associated with PE in type 1 diabetes (T1DM), and/or modulates lipoprotein-associated risks. DESIGN AND SETTING Multicentre prospective study of T1DM pregnancy. PATIENTS Pregnant women with T1DM (normal albuminuria, normotensive at enrolment, n=47) studied at three visits (V1-V3), all preceding PE onset: 12.3±1.9, 21.8±1.5, and 31.5±1.6 weeks gestation (mean ± SD). MAIN OUTCOME MEASURE(S) Hp phenotype and lipoprotein profiles in women with (n=23) vs. without (n=24) subsequent PE. RESULTS Hp phenotype did not predict PE, but lipoprotein associations with subsequent PE were confined to Hp 2-2 women, in whom the following associations with PE were observed: increased LDL-cholesterol, LDL particle concentration, APOB, triacylglycerol/high density lipoprotein cholesterol ratio, and APOB:APOA1 ratio; decreased HDL-cholesterol, APOA1, large HDL particle concentration, and peripheral lipoprotein lipolysis (all p<0.05). In women with one or two Hp-1 alleles, no such associations were observed. CONCLUSIONS In T1DM women, although Hp phenotype did not predict PE risk, lipoprotein-related risks for PE were limited to those with the Hp 2-2 phenotype. Hp phenotype may modulate PE risk in diabetes.

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