Augmented insulin secretory response in early pregnancy
This study aimed to examine changes in the insulin secretory response in early pregnancy, while accounting for changes in insulin sensitivity.
This is a secondary analysis of a previously conducted longitudinal physiological study. In 34 women, insulin secretory response (by IVGTT) and insulin sensitivity (by euglycaemic clamp) were assessed prior to pregnancy, in early pregnancy (12–14 weeks gestation) and in late pregnancy (34–36 weeks gestation). Using mixed-effects models, we compared insulin secretory response and sensitivity in early pregnancy to the same variables prior to pregnancy and in late pregnancy, with adjustment for age, obesity status and gestational diabetes mellitus (GDM). We examined changes in insulin secretory response after adjustment for insulin sensitivity using both multivariate modelling and the disposition index (DI). We explored the relationship between insulin secretory response and circulating hormones.
The insulin secretory response increased from prior to pregnancy to early pregnancy (unadjusted mean [SD] first-phase insulin response 465.1 [268.5] to 720 [358.2], p < 0.0001) and from early pregnancy to late pregnancy (to 924 [494.6], p = 0.01). Insulin sensitivity increased from prior to pregnancy to early pregnancy (insulin sensitivity index 0.10 [0.04] to 0.12 [0.05], p = 0.001) and decreased in late pregnancy (to 0.06 [0.03], p < 0.0001). Accounting for changes in insulin sensitivity, using either multivariate modelling or the DI, did not attenuate the early-pregnancy augmentation of insulin secretory response. Leptin was positively associated with insulin secretory response, independent of insulin sensitivity and adiposity (p = 0.004). Adjustment for leptin attenuated the observed augmentation of insulin secretory response in early pregnancy (adjusted mean change 121.5, p = 0.13).
The insulin secretory response increases markedly in early pregnancy, prior to and independent of changes in insulin sensitivity. Circulating hormones may mediate this metabolic adaptation. Identifying mediators of this physiological effect could have therapeutic implications for treating hyperglycaemia during and outside of pregnancy.
KeywordsGestational diabetes Glucose metabolism Insulin secretion Physiology Pregnancy
Gestational diabetes mellitus
Human chorionic gonadotropin
Human placental lactogen
The authors thank the clinical staff of the Clinical Research Unit of the Clinical Translational Science Center at MetroHealth Medical Center for their support in performing the laboratory assays and for research, nutritional and nursing support. We also thank S. Kalhan (Cleveland Clinic Foundation, Cleveland, OH, USA) for performing the stable isotopes assays of glucose.
CEP contributed to the conception and design of the analysis, the analysis and interpretation of data and drafting of the manuscript. LPHP contributed to the acquisition of data and its analysis and interpretation. JLL led the statistical analysis and contributed to the interpretation of data. PMC contributed to the conception and design of the analysis, the acquisition of data, the analysis and interpretation of data and drafting of the manuscript. All authors revised the manuscript and gave final approval of the version to be published. PMC is the guarantor of this work.
This work was supported in part by NICHD HD22965 (PMC) and NCRR CTSA Ul1 RR 024989. CEP is supported by career development awards from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (K23DK113218) and the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Program (74256). The data analysis was supported by Harvard Catalyst/Harvard University’s Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centres.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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