Absolute neonatal insulin levels in children of insulin-requiring diabetic patients F.
I.
R.
Melbourne, This
MARTIN Victoria,
report
Australia
describes
the relationship between cord plasma insulin and neonatal blood of diabetic patients treated during pregnancy with Plasma insulin in cord blood was similar to that found in with gestational diabetes and was not related to either neonatal blood glucose diabetic control.
glucose in nine children monocomponent insulins. patients maternal
THE ESTIMATION OF insulin in children born to diabetic patients receiving insulin has been difficult due to the presence of insulin/antibody complexes which cross the placenta. l-3 The use of highly purified insulin therapeutically reduces antibody formation, and it is possible to study neonatal insulin-glucose homeostasis more precisely. This preliminary report describes the relationship between cord plasma insulin and neonatal blood glucose in nine children of diabetic patients treated during pregnancy with monocomponent (MC) insulins*; plasma insulin in cord blood was similar to that found in gestational diabetic patients and was not related to either neonatal blood glucose or maternal diabetic control. MC insulin, either lente or semilente, was commenced at between eight and 14 weeks’ gestation and continued until delivery. The management of pregnancy, assessment of diabetic control by mean blood glucose and insulin assays in maternal and cord blood, and neonatal management were similar to those methods described elsewhere.3 The patients were 18 to 30 years old, with a duration of diabetes from 3 to 16 years. The initial insulin dose was 16 to 144 U., and the final insulin dose was 12 to 84 U. per day. Classification of disease according to White was as follows: B, 7; C, 1; F. 1. Seven patients had vaginal delivery, and cesarean section was performed in two; 5 per cent dextrose was From the Diabetic Clinic, Royal Women’s Department of Medicine, Royal Melbourne Received
for
Accepted
October
publication
June
infused at rates of 100 to 140 mg. per minute for 1 to 14 hours before delivery. During pregnancy, both plasma insulin (I.R.I.) and insulin antibody binding of insulin I-125 (per cent of AB) were monitored. There was a decrease in I.R.I. in all, which was more marked in those with higher initial levels of I.R.I.; per cent of AB also declined but less consistently. Neither was related to a change in insulin dose. Insulin requirement fell significantly in only two women, and the over-all insulin requirements did not differ from that with commercial grade insulin. In Table I, the relationships between various maternal and neonatal indices are shown. I.R.I. in cord blood was between 11 and 2 18 s U. per milliliter and less than 65 pU. per milliliter in six of nine children. Cord insulin was unexpectedly significantly higher in infants with neonatal hypoglycemia (blood glucose less than 20 mg. per cent in the first six hours); I.R.I. versus neonatal blood glucose: r = 0.66; p = ~0.05. There was no relationship between maternal blood glucose in the clinic or ward or at delivery and either cord insulin or neonatal blood glucose. The level of I.R.I. in cord blood in this small series was less than in a comparable series of 34 infants of diabetic patients treated with conventional insulin.3 With the methods used, plasma insulin in the cord blood of normal infants was 24.4 + 10.6 (range 12 to 44) pU. per milliliter, and in 11 patients with gestational diabetes, it was 35.6 ? 23.8 (range 14 to 92) $J. per milliliter. Thus, in the majority of the infants studied here, I.R.I. was similar to that seen in patients with gestational diabetes, suggesting that the higher levels,observed previously’s 3 are due to transplacental passage of insulin bound to antibody and not to stimulation of the fetal pancreas by high glucose levels. In this respect, there is also a highly significant
Hospital, and Hospital.
1 I, 1975.
2, 1975.
Reprint requests: Dr. F. I. R. Martin, The Royal Melbourne Hospital, Grattan St., Parkville, Victoria, Ax&a&a. *Nova,
Copenhagen,
or
Denmark. 71
Table I. Maternal and insulin I-125
and neonatal blood glucose (milligrams per cent), I.R.I. (microunits per milliliter). binding (percent) in nine women treated with MC insulin in pregnancy Maternal
Patient
Birth weight (gram4
Clinic (mean)
Ward (mean)
36.4 35.3 36.6 30.3 36.8 37.0 34.5 36.2 37.5
3,230 2,040 2,830 2,500 3,100 4,100 2,970 2,960 3,640
99 200 119 165 113 127 166 168 161
131 133 142 178 100 164 176 136
M. N. K. D. D. I,. P. L. J. W. H. B. N. N. M. L. H. I. B. The
blood glucose
Estimated gestation (weeks)
normal
range
of insulin
I-125
per
cent
AB
=
I.
R.
Melbourne, This
MARTIN Victoria,
report
Australia
describes
the relationship between cord plasma insulin and neonatal blood of diabetic patients treated during pregnancy with Plasma insulin in cord blood was similar to that found in with gestational diabetes and was not related to either neonatal blood glucose diabetic control.
glucose in nine children monocomponent insulins. patients maternal
THE ESTIMATION OF insulin in children born to diabetic patients receiving insulin has been difficult due to the presence of insulin/antibody complexes which cross the placenta. l-3 The use of highly purified insulin therapeutically reduces antibody formation, and it is possible to study neonatal insulin-glucose homeostasis more precisely. This preliminary report describes the relationship between cord plasma insulin and neonatal blood glucose in nine children of diabetic patients treated during pregnancy with monocomponent (MC) insulins*; plasma insulin in cord blood was similar to that found in gestational diabetic patients and was not related to either neonatal blood glucose or maternal diabetic control. MC insulin, either lente or semilente, was commenced at between eight and 14 weeks’ gestation and continued until delivery. The management of pregnancy, assessment of diabetic control by mean blood glucose and insulin assays in maternal and cord blood, and neonatal management were similar to those methods described elsewhere.3 The patients were 18 to 30 years old, with a duration of diabetes from 3 to 16 years. The initial insulin dose was 16 to 144 U., and the final insulin dose was 12 to 84 U. per day. Classification of disease according to White was as follows: B, 7; C, 1; F. 1. Seven patients had vaginal delivery, and cesarean section was performed in two; 5 per cent dextrose was From the Diabetic Clinic, Royal Women’s Department of Medicine, Royal Melbourne Received
for
Accepted
October
publication
June
infused at rates of 100 to 140 mg. per minute for 1 to 14 hours before delivery. During pregnancy, both plasma insulin (I.R.I.) and insulin antibody binding of insulin I-125 (per cent of AB) were monitored. There was a decrease in I.R.I. in all, which was more marked in those with higher initial levels of I.R.I.; per cent of AB also declined but less consistently. Neither was related to a change in insulin dose. Insulin requirement fell significantly in only two women, and the over-all insulin requirements did not differ from that with commercial grade insulin. In Table I, the relationships between various maternal and neonatal indices are shown. I.R.I. in cord blood was between 11 and 2 18 s U. per milliliter and less than 65 pU. per milliliter in six of nine children. Cord insulin was unexpectedly significantly higher in infants with neonatal hypoglycemia (blood glucose less than 20 mg. per cent in the first six hours); I.R.I. versus neonatal blood glucose: r = 0.66; p = ~0.05. There was no relationship between maternal blood glucose in the clinic or ward or at delivery and either cord insulin or neonatal blood glucose. The level of I.R.I. in cord blood in this small series was less than in a comparable series of 34 infants of diabetic patients treated with conventional insulin.3 With the methods used, plasma insulin in the cord blood of normal infants was 24.4 + 10.6 (range 12 to 44) pU. per milliliter, and in 11 patients with gestational diabetes, it was 35.6 ? 23.8 (range 14 to 92) $J. per milliliter. Thus, in the majority of the infants studied here, I.R.I. was similar to that seen in patients with gestational diabetes, suggesting that the higher levels,observed previously’s 3 are due to transplacental passage of insulin bound to antibody and not to stimulation of the fetal pancreas by high glucose levels. In this respect, there is also a highly significant
Hospital, and Hospital.
1 I, 1975.
2, 1975.
Reprint requests: Dr. F. I. R. Martin, The Royal Melbourne Hospital, Grattan St., Parkville, Victoria, Ax&a&a. *Nova,
Copenhagen,
or
Denmark. 71
Table I. Maternal and insulin I-125
and neonatal blood glucose (milligrams per cent), I.R.I. (microunits per milliliter). binding (percent) in nine women treated with MC insulin in pregnancy Maternal
Patient
Birth weight (gram4
Clinic (mean)
Ward (mean)
36.4 35.3 36.6 30.3 36.8 37.0 34.5 36.2 37.5
3,230 2,040 2,830 2,500 3,100 4,100 2,970 2,960 3,640
99 200 119 165 113 127 166 168 161
131 133 142 178 100 164 176 136
M. N. K. D. D. I,. P. L. J. W. H. B. N. N. M. L. H. I. B. The
blood glucose
Estimated gestation (weeks)
normal
range
of insulin
I-125
per
cent
AB
=
