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Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes.
Diabetologia. 2017 12; 60(12):2514-2524.D

Abstract

AIMS/HYPOTHESIS

The incidence of pre-eclampsia, a multisystem disorder of pregnancy, is fourfold higher in type 1 diabetic than non-diabetic women; it is also increased in women with features of the metabolic syndrome and insulin resistance. In a prospective study of pregnant women with type 1 diabetes, we measured plasma levels of adipokines known to be associated with insulin resistance: leptin, fatty acid binding protein 4 (FABP4), adiponectin (total and high molecular weight [HMW]; also known as high molecular mass), retinol binding protein 4 (RBP4) and resistin and evaluated associations with the subsequent development of pre-eclampsia.

METHODS

From an established prospective cohort of pregnant type 1 diabetic women, we studied 23 who developed pre-eclampsia and 24 who remained normotensive; for reference values we included 19 healthy non-diabetic normotensive pregnant women. Plasma adipokines were measured (by ELISA) in stored samples from three study visits (Visit 1- Visit 3) at different gestational ages (mean ± SD): Visit 1, 12.4 ± 1.8 weeks; Visit 2, 21.7 ± 1.4 weeks; and Visit 3, 31.4 ± 1.5 weeks. All the women were free of microalbuminuria and hypertension at enrolment. All study visits preceded the clinical onset of pre-eclampsia.

RESULTS

In all groups, leptin, the ratio of leptin to total or HMW adiponectin, FABP4 concentration, ratio of FABP4 to total or HMW adiponectin and resistin level increased, while total and HMW adiponectin decreased, with gestational age. At Visit 1: (1) in diabetic women with vs without subsequent pre-eclampsia, leptin, ratio of leptin to total or HMW adiponectin, and ratio of FABP4 to total or HMW adiponectin, were increased (p < 0.05), while total adiponectin was decreased (p < 0.05); and (2) in normotensive diabetic vs non-diabetic women, total adiponectin was elevated (p < 0.05). At Visits 2 and 3: (1) the primary findings in the two diabetic groups persisted, and FABP4 also increased in women with subsequent pre-eclampsia (p < 0.05); and (2) there were no differences between the two normotensive groups. By logistic regression analyses after covariate adjustment (HbA1c, insulin kg-1 day-1 and gestational age), the best predictive models for pre-eclampsia were as follows: Visit 1, doubling of leptin, OR 9.0 (p < 0.01); Visit 2, doubling of the leptin:total adiponectin ratio, OR 3.7 (p < 0.05); and Visit 3, doubling of FABP4 concentration, OR 25.1 (p < 0.01). The associations were independent of BMI.

CONCLUSIONS/INTERPRETATION

As early as the first trimester in type 1 diabetic women, adipokine profiles that suggest insulin resistance are associated with subsequent pre-eclampsia, possibly reflecting maternal characteristics that precede pregnancy. These associations persist in the second and third trimesters, and are independent of BMI. Insulin resistance may predispose women with type 1 diabetes to pre-eclampsia.

Authors+Show Affiliations

Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK. Division of Endocrinology and Diabetes, CSB Suite 822, Medical University of South Carolina, Charleston, SC, 29425, USA.Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK. The Department of Clinical Biochemistry, Royal Victoria Hospital, Belfast, Northern Ireland, UK.Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK. Division of Endocrinology and Diabetes, CSB Suite 822, Medical University of South Carolina, Charleston, SC, 29425, USA.Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.Section of Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.Division of Endocrinology and Diabetes, CSB Suite 822, Medical University of South Carolina, Charleston, SC, 29425, USA. University of Sydney, NHMRC Clinical Trials Centre, Camperdown, Sydney, NSW, Australia.Royal Women's Hospital, Melbourne, VIC, Australia.Department of Endocrinology, Oslo University Hospital, Oslo, Norway. Institute of Clinical Medicine, University of Oslo, Oslo, Norway.Institute of Clinical Medicine, University of Oslo, Oslo, Norway.Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, CO, USA.Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.Spartanburg Regional Hospital, Spartanburg, SC, USA.Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland, UK.Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK. lyonstj@musc.edu. Division of Endocrinology and Diabetes, CSB Suite 822, Medical University of South Carolina, Charleston, SC, 29425, USA. lyonstj@musc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28875223

Citation

Kelly, Clare B., et al. "Circulating Adipokines Are Associated With Pre-eclampsia in Women With Type 1 Diabetes." Diabetologia, vol. 60, no. 12, 2017, pp. 2514-2524.
Kelly CB, Hookham MB, Yu JY, et al. Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes. Diabetologia. 2017;60(12):2514-2524.
Kelly, C. B., Hookham, M. B., Yu, J. Y., Lockhart, S. M., Du, M., Jenkins, A. J., Nankervis, A., Hanssen, K. F., Henriksen, T., Garg, S. K., Hammad, S. M., Scardo, J. A., Aston, C. E., Patterson, C. C., & Lyons, T. J. (2017). Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes. Diabetologia, 60(12), 2514-2524. https://doi.org/10.1007/s00125-017-4415-z
Kelly CB, et al. Circulating Adipokines Are Associated With Pre-eclampsia in Women With Type 1 Diabetes. Diabetologia. 2017;60(12):2514-2524. PubMed PMID: 28875223.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes. AU - Kelly,Clare B, AU - Hookham,Michelle B, AU - Yu,Jeremy Y, AU - Lockhart,Samuel M, AU - Du,Mei, AU - Jenkins,Alicia J, AU - Nankervis,Alison, AU - Hanssen,Kristian F, AU - Henriksen,Tore, AU - Garg,Satish K, AU - Hammad,Samar M, AU - Scardo,James A, AU - Aston,Christopher E, AU - Patterson,Christopher C, AU - Lyons,Timothy J, Y1 - 2017/09/05/ PY - 2017/05/16/received PY - 2017/07/13/accepted PY - 2017/9/7/pubmed PY - 2018/6/26/medline PY - 2017/9/7/entrez KW - Adipokine KW - Adiponectin KW - Diabetes KW - Fatty acid binding protein KW - Leptin KW - Pre-eclampsia KW - Pregnancy SP - 2514 EP - 2524 JF - Diabetologia JO - Diabetologia VL - 60 IS - 12 N2 - AIMS/HYPOTHESIS: The incidence of pre-eclampsia, a multisystem disorder of pregnancy, is fourfold higher in type 1 diabetic than non-diabetic women; it is also increased in women with features of the metabolic syndrome and insulin resistance. In a prospective study of pregnant women with type 1 diabetes, we measured plasma levels of adipokines known to be associated with insulin resistance: leptin, fatty acid binding protein 4 (FABP4), adiponectin (total and high molecular weight [HMW]; also known as high molecular mass), retinol binding protein 4 (RBP4) and resistin and evaluated associations with the subsequent development of pre-eclampsia. METHODS: From an established prospective cohort of pregnant type 1 diabetic women, we studied 23 who developed pre-eclampsia and 24 who remained normotensive; for reference values we included 19 healthy non-diabetic normotensive pregnant women. Plasma adipokines were measured (by ELISA) in stored samples from three study visits (Visit 1- Visit 3) at different gestational ages (mean ± SD): Visit 1, 12.4 ± 1.8 weeks; Visit 2, 21.7 ± 1.4 weeks; and Visit 3, 31.4 ± 1.5 weeks. All the women were free of microalbuminuria and hypertension at enrolment. All study visits preceded the clinical onset of pre-eclampsia. RESULTS: In all groups, leptin, the ratio of leptin to total or HMW adiponectin, FABP4 concentration, ratio of FABP4 to total or HMW adiponectin and resistin level increased, while total and HMW adiponectin decreased, with gestational age. At Visit 1: (1) in diabetic women with vs without subsequent pre-eclampsia, leptin, ratio of leptin to total or HMW adiponectin, and ratio of FABP4 to total or HMW adiponectin, were increased (p < 0.05), while total adiponectin was decreased (p < 0.05); and (2) in normotensive diabetic vs non-diabetic women, total adiponectin was elevated (p < 0.05). At Visits 2 and 3: (1) the primary findings in the two diabetic groups persisted, and FABP4 also increased in women with subsequent pre-eclampsia (p < 0.05); and (2) there were no differences between the two normotensive groups. By logistic regression analyses after covariate adjustment (HbA1c, insulin kg-1 day-1 and gestational age), the best predictive models for pre-eclampsia were as follows: Visit 1, doubling of leptin, OR 9.0 (p < 0.01); Visit 2, doubling of the leptin:total adiponectin ratio, OR 3.7 (p < 0.05); and Visit 3, doubling of FABP4 concentration, OR 25.1 (p < 0.01). The associations were independent of BMI. CONCLUSIONS/INTERPRETATION: As early as the first trimester in type 1 diabetic women, adipokine profiles that suggest insulin resistance are associated with subsequent pre-eclampsia, possibly reflecting maternal characteristics that precede pregnancy. These associations persist in the second and third trimesters, and are independent of BMI. Insulin resistance may predispose women with type 1 diabetes to pre-eclampsia. SN - 1432-0428 UR - https://www.unboundmedicine.com/medline/citation/28875223/Circulating_adipokines_are_associated_with_pre_eclampsia_in_women_with_type_1_diabetes_ L2 - https://doi.org/10.1007/s00125-017-4415-z DB - PRIME DP - Unbound Medicine ER -