Measurement of Cord Insulin and Insulin-Related Peptides Suggests That Girls Are More Insulin Resistant Than Boys at Birth

Abstract

OBJECTIVE -We aimed to examine sex differences in insulin and insulin propeptide concentrations at birth using validated cord blood collection.RESEARCH DESIGN AND METHODS -We tested the impact on insulin and insulin propeptides of taking 13 cord blood samples in heparin and EDTA and then centrifuging and separating plasma after 1, 2, 24, or 48 h at room temperature (heparin) or 4°C (EDTA). Cord plasma insulin and insulin propeptides concentrations were measured in 440 babies and correlated with offspring anthropometry measured at birth.RESULTS -Cord insulin concentrations significantly decreased (74% those at baseline by 24 h; P ϭ 0.01) in the samples taken in heparin and stored at room temperature, but those taken on EDTA and refrigerated remained stable for up to 48 h. Insulin propeptides were stable in both. Cord plasma insulin and insulin propeptides measured in EDTA were related to all measures of birth size and maternal glycemia and BMI (r Ͼ 0.11; P Ͻ 0.03 for all) and were higher in those delivered via caesarean section. Girls were lighter (3,497 vs. 3,608 g; P ϭ 0.01) but had higher cord insulin (46.7 vs. 41.2 pmol/l; P ϭ 0.031), total proinsulin (34.1 vs. 25.8 pmol/l; P Ͻ 0.001), and intact proinsulin (9.5 vs. 8.3 pmol/l; P ϭ 0.004) concentrations than boys; this was further confirmed when cord insulin concentrations of boys and girls were compared after pair matching for birth weight (insulin 49.7 vs. 42.1 pmol/l; P ϭ 0.004).CONCLUSIONS -When using appropriate sample collection methods, female newborns have higher insulin concentrations than male newborns, despite being smaller, suggesting intrinsic insulin resistance in girls. Diabetes Care 30:2661-2666, 2007I ncreasing evidence suggests that girls are more insulin resistant than boys. This has been shown in fasting insulin measurements, frequently sampled intravenous glucose tolerance tests, and euglycemic clamps in children from age 5 years (1) through late childhood (2,3) and puberty and adolescence (4 -6). The increase in insulin resistance is seen in Caucasian, Afro-Caribbean, and AsianIndian races (1-4,6). Furthermore, type 2 diabetes in children is far more common in girls than boys (7-9).That sex differences are seen early in life could reflect differences in intrinsic insulin resistance or differences in postnatal behavior. In a study of 307 subjects, Murphy et al. (1) were unable to explain sex differences at 5 years of age by looking at differences in anthropometry and physical activity. If insulin resistance is intrinsic, this would suggest that it is genetically determined and should be apparent from birth. An insulin-resistant phenotype at birth has previously been described in Indian babies (10), who have higher umbilical cord insulin concentrations and more subcutaneous fat than U.K. babies, despite being lighter. If girls are more insulin resistant than boys, one might expect to observe a similar phenotype at birth, with girls having higher cord insulin concentrations even though they are lighter than boys. Girls are consistently ligh...

Determinants of birth weight in boys and girls

“…These findings are in accordance with a previous study which found girls to be intrinsically more insulin resistance than boys at birth (Shields et al 2007). Despite weighing less at birth, the girls had significantly higher insulin and proinsulin concentrations in cord blood than boys, whereas there was no difference in cord glucose concentrations between girls and boys.…”

“…Despite weighing less at birth, the girls had significantly higher insulin and proinsulin concentrations in cord blood than boys, whereas there was no difference in cord glucose concentrations between girls and boys. the same study also found that girls had significantly more subcutaneous fat measured by triceps and subscapular skinfold thicknesses (Shields et al 2007). We preferred not to use relative birth weight in the present work.…”

“…No difference in cord glucose concentrations was found between newborn girls and boys (Shields et al 2007).…”

Mutations in the Glucokinase Gene of the Fetus Result in Reduced Placental Weight

“…In brief, mothers were seen by the research midwife at 28 weeks of gestation, and a fasting blood sample was taken for glucose and insulin measurement. Umbilical cord blood was obtained from the placental end of the cord after the placenta was delivered and centrifuged as soon as possible (18). Plasma aliquots were stored at Ϫ80°C.…”

Influence of maternal HbA1C on fetal insulin levels

“…12 Beverly at al conducted a study on insulin, insulin resistance, insulin related peptides and found insulin concentrations to be significantly correlated with all measures like birth weight, length, head circumference and also found maternal glucose to be significantly associated with increased insulin concentration, reflecting that maternal glycemia was a major determinant of fetal insulin secretion. 13 Limitations of the study were the sample size was smaller and further studies with larger sample size and long term follow up is required to establish the effect of insulin levels at birth with metabolic effects occurring in later childhood and adolescents.…”