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Insulin and Insulin Propeptides at Birth in Offspring of Diabetic Mothers

MedStar Research Institute (R.S.L.), Washington, D.C. 20010; Diabetic Department (J.D.W.), Royal Infirmary of Edinburgh NHS Trust, Edinburgh EH3 9YW, United Kingdom, Department of Clinical Biochemistry (I.H., C.N.H.), Addenbrooke’s NHS Trust, Cambridge CB2 2QR, United Kingdom, and University Department of Obstetrics and Gynaecology (A.A.C., B.A.H., F.D.J.), Centre for Reproductive Biology, University of Edinburgh, Edinburgh EH3 9ET, United Kingdom

Address all correspondence and requests for reprints to: Robert Lindsay, MedStar Research Institute, 108 Irving Street NW, Washington, D.C. 20010. E-mail: robert.lindsay{at}medstar.net.

Maternal diabetes during pregnancy is associated with excess fetal growth and increased fetal insulin production. We hypothesized that insulin propeptides (proinsulin and 32–33 split proinsulin) might be more robust indicators of chronic fetal overproduction of insulin. We examined insulin-like molecules in cord blood (ILM) (insulin, proinsulin, and 32–33 split proinsulin) in relation to birth weight, maternal glycemia, and cord glucose in 140 offspring of mothers with type 1 diabetes (ODM) and 49 offspring of mothers who did not have diabetes (CONTROL) as well as degradation of ILM in response to sampling conditions at birth. Insulin propeptides were abundant in cord blood, comprising 50% of ILM in CONTROL and 36% in ODM (P < 0.0001) and more resistant to degradation than insulin (P < 0.05). Concentrations of all three ILM were highly intercorrelated with median values 2- to 5-fold higher in ODM than CONTROL [e.g. median (range): insulin ODM 110 (60–217) pmol/liter; CONTROL 22 (15–37) pmol/liter; P < 0.0001]. In ODM, 32–33 split proinsulin and proinsulin were more closely related to birth weight (Spearman r for ILM: r_{32–33 split}= 0.54; r_PROINSULIN: r = 0.54; r_INSULIN = 0.40: r_{32–33 split} and r_PROINSULIN > r_INSULINP < 0.05) and fetal leptin (r_{32–33 split}= 0.55; r_PROINSULIN; r = 0.54; r_INSULIN = 0.22: r_{32–33 split} and r_PROINSULIN > r_INSULINP < 0.05) than insulin). By contrast, insulin was more closely related to cord glucose (r_{32–33 split} = 0.15; r_PROINSULIN: r = 0.10; r_INSULIN = 0.42: r_INSULIN > r_{32–33 split} and r_PROINSULINP < 0.05). In CONTROL, 32–33 split proinsulin was also more closely related to fetal leptin r_{32–33 split}= 0.61; r_PROINSULIN: r = 0.29; r_INSULIN = 0.33: r_{32–33 split} > r_INSULINP < 0.05). In ODM, 32–33 split proinsulin and proinsulin have closer relationships to fetal growth and leptin concentrations at birth than insulin. Measurement of insulin propeptides may be advantageous in assessment of the influence of maternal hyperglycemia on the newborn.

This work was supported by a project grant from the Chief Scientist Office of the Scottish Office.

Abbreviations: CONTROL, Mothers who did not have diabetes; DR, diabetic retinopathy; HbA1c, hemoglobin A1c; ILM, insulin-like molecules in cord blood; LMP, last menstrual period; ODM, offspring of mothers with type 1 diabetes.

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