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Insulin and insulin propeptides at birth in offspring of diabetic mothers
R S Lindsay1, J D Walker, I Halsall
1MedStar Research Institute (R.S.L.), Washington, DC 20010, USA. robert.lindsay@medstar.net
Insights
Insulin propeptides in cord blood are better indicators of fetal growth and leptin in infants of mothers with diabetes. These molecules may help assess maternal hyperglycemia's impact on newborns.
Area of Science:
- Endocrinology
- Neonatal Medicine
- Metabolic Disorders
Background:
- Maternal diabetes during pregnancy can lead to excessive fetal growth and increased fetal insulin production.
- Insulin propeptides, including proinsulin and 32-33 split proinsulin, are precursors to insulin.
- The utility of insulin propeptides as indicators of fetal insulin overproduction in diabetic pregnancies is not fully understood.
Purpose of the Study:
- To investigate whether insulin propeptides are more robust indicators of chronic fetal insulin overproduction compared to insulin.
- To examine the relationship between insulin-like molecules (insulin, proinsulin, 32-33 split proinsulin) in cord blood and birth weight, maternal glycemia, and cord glucose.
- To assess the degradation of insulin-like molecules under sampling conditions.
Main Methods:
- Analysis of insulin, proinsulin, and 32-33 split proinsulin in cord blood from 140 offspring of mothers with type 1 diabetes (ODM) and 49 controls.
- Correlation analysis between insulin-like molecules, birth weight, maternal glycemia, cord glucose, and fetal leptin.
- Assessment of insulin-like molecule degradation during sample handling.
Main Results:
- Insulin propeptides were abundant in cord blood (36-50% of insulin-like molecules) and more resistant to degradation than insulin.
- Concentrations of all measured insulin-like molecules were significantly higher in ODM compared to controls.
- In ODM, 32-33 split proinsulin and proinsulin showed stronger correlations with birth weight and fetal leptin than insulin.
- Insulin demonstrated a closer relationship with cord glucose compared to insulin propeptides.
Conclusions:
- Insulin propeptides (32-33 split proinsulin and proinsulin) are more closely related to fetal growth and leptin levels in infants of mothers with diabetes than insulin.
- Measurement of insulin propeptides may offer a more advantageous assessment of maternal hyperglycemia's influence on the newborn.
- These findings highlight the potential of insulin propeptides as biomarkers in pregnancies complicated by diabetes.
Abstract:
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(INSULIN)P < 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(INSULIN)P < 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(PROINSULIN)P < 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(INSULIN)P < 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.
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