Skip to main content

Increased basal insulin sensitivity in late pregnancy in women carrying a male fetus: a cohort study



It has been suggested that fetal sex may be able to modify maternal metabolism and physiology during pregnancy. Recently pregnant women carrying a male fetus were reported to be more insulin sensitive than those carrying females, although related evidence is inconsistent.


In this study we administered a 75 g oral glucose tolerance test at around week 28 of pregnancy in 813 pregnant women from a contemporary birth cohort (the Cambridge Baby Growth Study), derived surrogate indices of insulin secretion and sensitivity, and related them to the fetal sex.


Carrying a male fetus was associated with lower fasting glucose (difference in mean concentrations ≈ 0.1 mmol/L; β′ = 0.063; p = 0.02) and insulin (≈ 1.1 pmol/L; β′ = 0.075; p = 0.01) concentrations but not with post-load glucose or insulin concentrations. Male fetal sex was also associated with lower HOMA IR (≈ 1.08 units; β′ = 0.071; p = 0.02) and higher QUICKI (≈ 1.06 units; β′ = 0.080; p = 0.007) values suggesting increased basal insulin sensitivity. There were no differences in indices of insulin secretion, except for the insulin disposition index which was higher in women carrying a male fetus (≈ 1.15 units; β′ = 0.090; p = 0.007). Birth weights were higher in male offspring.


Women carrying a male fetus were relatively more insulin sensitive in the fasting state and secreted more insulin relative to this degree of insulin sensitivity. These results are consistent with the idea that the fetal sex may be able to modify the maternal glucose-insulin axis.


  • Pregnant women carrying a male fetus were more insulin sensitive than those carrying a female at around week 28 of pregnancy in a contemporary birth cohort.

  • They also appeared to secrete more insulin relative to their degree of insulin sensitivity.

  • The differences in glucose and insulin concentrations were evident in the basal state but disappeared after the consumption of a glucose load.

  • Fetal sex appears to be able to influence maternal glucose and insulin concentrations in pregnancy.


Pregnancy represents an almost unique phase of human life where circulatory systems associated with two different individuals are able to directly interact with each other; the only other scenario when this can occur is in conjoined twins. In pregnancy the interaction between circulatory systems primarily involves the mother’s metabolism supplying the fetus with oxygen and nutrients via the placenta once it has developed, and then the safe removal of toxins and waste products from the fetal circulatory system. While the fetus is totally dependent upon the maternal metabolism for these actions, there is evidence that the fetus can modify the maternal metabolism and physiology [1].

One way that the fetus appears to be able to modify the maternal metabolism and physiology is via imprinted genes, which are expressed in the fetus in a parent-of-origin specific manner (one copy of the gene not being expressed, which one depending upon the gene and tissue in question, and the stage of development). Many of these genes are only expressed in utero [2] and they appear to be able to regulate placental endocrine function [3]. Thus, we have found associations between polymorphic variation in parental-specific fetal imprinted gene alleles and maternal glucose [4, 5], lipid species [6] and circulating DLK1 protein [7] concentrations in pregnancy. Similar results regarding glucose concentrations were also found using a knockout mouse model [8]. We have also found associations between various fetal imprinted gene alleles at polymorphic loci and maternal blood pressure in pregnancy [9]. We suggested that the mechanism underpinning the associations between parental-specific fetal imprinted gene alleles and changes in maternal metabolism and physiology may be via the alteration of placental hormone concentrations secreted into the maternal circulation [1], especially since much of the placenta is fetal in origin [10].

Another way that the fetus might be able to modify maternal metabolism and physiology (again possibly via alterations in placental endocrine function [11]) relates to the sex of the fetus. As examples of this, systematic reviews and meta-analyses of individual studies, as well as certain individual studies, have shown that mothers carrying male fetuses are more likely to develop gestational diabetes (GDM) than those carrying female fetuses [12,13,14]. However, in one recent study, independent of GDM risk, markers of insulin resistance were lower in pregnant women carrying male fetuses [15]. An earlier study failed to find a fetal sex effect on maternal insulin sensitivity [16], instead finding mothers carrying male fetuses having higher circulating glucose concentrations but lower pancreatic β-cell function. Another study found that mothers carrying male fetuses were actually more insulin resistant than those carrying females, when tested early in pregnancy [17]. A recent review of how placental endocrine function varies according to fetal sex called for more studies of fetal sex-mediated differences in the regulation of glucose metabolism in pregnancy in relatively homogeneous populations to try and clarify discrepancies in the literature in this area [18]. We therefore sought clarification of this matter using a largely ethnically homogeneous contemporary birth cohort, the Cambridge Baby Growth Study (CBGS).


Cambridge baby growth study

Between the years 2001 and 2009 early pregnancy ultrasound clinics held at the Rosie Maternity Hospital, Cambridge, U.K. (a single centre) were used to recruit 2229 pregnant women (and subsequently their babies and partners) to the observational CBGS [19]. All the women were over 16 years of age and were able to give consent for themselves and their baby. The CBGS was run prospectively and longitudinally. A total of 1658 of the women still wanted to be part of this study at the birth of their baby (571 women withdrew prior to this). A vast majority (95.3%) of the babies were ethnically White. Other babies were Black (African or Caribbean) (1.3%), Asian (1.7%) or mixed race (1.7%).

Oral glucose tolerance tests

Oral glucose tolerance tests (OGTTs) were performed in 1071 of the CBGS participants at a median (interquartile range) of 28.4 (28.1–28.7) weeks of gestation [4]. The 75 g glucose load was administered orally after an overnight fast and collection of venous blood samples for the measurement of circulating glucose and insulin concentrations. Further blood samples were collected for additional glucose measurements one hour after the administration of the glucose. Capillary glucose measurements were made using an Abbott Freestyle Mini (Abbott Diagnostics, Maidenhead, U.K.) 0, 30, 60, 90 and 120 min. after the administration of glucose [4] and the 120-min. glucose concentrations were used in this analysis. From March 2007 onwards a second set of venous samples was collected two hours after the glucose load. GDM in this study was classified from these venous (OGTT fasting and 60 min.) and capillary (OGTT 120 min.) glucose concentrations using International Association of Diabetes and Pregnancy Study Group criteria [20]. Biomarkers of fasting insulin resistance (HOMA IR, QUICKI, reciprocal fasting insulin concentration), pancreatic β-cell function (HOMA B) and insulin secretion (insulin increment, insulinogenic index and insulin disposition index) were calculated.

Offspring size at birth

Birth weight was recorded from the hospital notes. Other measurements in newborns, such as the length, head circumference and various skinfolds thicknesses, were made as soon as possible after birth [at a median (interquartile range) age of 2 (1–16) days of age] by trained paediatric research nurses. Each measurement was performed in triplicate and the mean of these measurements used for statistical analyses. Body length was measured using a SECA 416 Infantometer (Hamburg, Germany). Skinfolds thicknesses at the subscapular, flank, triceps and quadriceps regions of the left side of the body were measured using Holtain calipers and head circumferences were measured using a tape measure (both Chasmors Ltd., London, U.K.) [21]. Intra- and inter-observer technical errors of measurement were 0.4–2.8% and 2.0–3.2%, respectively, for the skinfold thicknesses.

Laboratory measurements

OGTT plasma insulin concentrations were measured using a Dako enzyme-linked immunosorbent assay (Dako UK Ltd., Ely, Cambs, UK). Intra-assay imprecision (%CV) values were 4.3% at 82 pmol/L, 3.0% at 402 pmol/L and 5.7% at 907 pmol/. Equivalent inter-assay imprecision values were 4.3, 5.1 and 5.4%, respectively. Venous blood glucose measurements were made using a routine glucose oxidase-based method (Yellow Springs International Inc., Yellow Springs, OH, USA).


The index of multiple deprivation was derived and imputed from the postcode of the participants’ home addresses as described [22]. HOMA IR and B were calculated using the fasting glucose and insulin concentrations and the online HOMA calculator [23]. QUICKI was also calculated using the fasting glucose and insulin concentrations, and the following equation (using insulin and glucose concentrations expressed in SI units): 1/(((log (insulin/6)) + (log (glucose*18))) [24]. The insulin increment was calculated as the OGTT fasting insulin concentration subtracted from the OGTT 60-min. insulin concentration. The insulinogenic index was calculated as the insulin increment divided by the rise in glucose concentrations over the first hour of the OGTT. The insulin disposition index was calculated as the insulinogenic index divided by the fasting insulin concentration. Dividing the maternal (pre-pregnancy) or baby weights by their height squared was used to calculate the body mass indexes (BMI).

Statistical analysis

This analysis was restricted to those women who underwent OGTTs and for whom data relating to the gestational age of the baby when the OGTT was performed, pre-pregnancy BMI and maternal age were available (n = 813). Continuous variables were analysed in statistical models using linear and/or quadratic regression models, adjusted for confounders where appropriate. Where the dependent variable residuals were skewed, the models were analysed with prior (generally logarithmic) transformation of the data so that the residuals were normally distributed. Categorical variables were analysed using the χ2-test or Fisher’s exact test (as appropriate) or logistic regression. The risk ratio (RR) was calculated using Stata’s binreg function. p < 0.05 was considered statistically significant throughout. The statistical analyses were performed using either R (version 4.0.3; The R Foundation for Statistical Computing, Vienna, Austria) or Stata (version 13.1; Stata Corp., from Timberlake Consultants Ltd., Richmond, Surrey, U.K.). Data are mean (95% confidence interval) unless stated otherwise.


Clinical characteristics of study participants

Those women who were included in this study largely shared similar clinical characteristics to those CBGS participants who were excluded from this study (Table 1), with the exception that there were more women who had not had a previous pregnancy, a lower proportion of these women smoked and they tended to put on more weight during pregnancy and gave birth around one day later. In those women who were included in this analysis, clinical characteristics were similar between those carrying a male fetus and those carrying a female fetus (Table 2).

Table 1 Clinical characteristics of the CBGS women included in this study and those excluded from it
Table 2 Clinical characteristics of the study participants according to the fetal sex

Assessment of the glucose-insulin axis during pregnancy by fetal sex

OGTT fasting glucose concentrations were lower in women carrying male babies than in those carrying females (Fig. 1). There were no differences in circulating 60- or 120-min. glucose concentrations between those carrying male and female fetuses (Fig. 2). Surrogate markers of insulin resistance (higher HOMA IR, lower QUICKI, higher fasting insulin concentrations) were lower in women carrying male fetuses than in those carrying females (Fig. 1). Some of the surrogate markers of insulin secretion (insulin increment, insulinogenic index) showed no association with the fetal sex (Table 3). Neither was there a difference in the surrogate marker of pancreatic β-cell function (HOMA B). However, the insulin disposition index was higher in those women carrying males. There was no association between the fetal sex and the risk of GDM [RR (male to female) 1.4 (0.9–2.0); n = 813; p = 0.2].

Fig. 1
figure 1

Fasting a glucose and b insulin concentrations, c HOMA IR values and d QUICKI values by fetal sex (all adjusted for pre-pregnancy BMI, maternal age, gestational age of the fetus and multi-fetal pregnancy). Data are mean ± 95% confidence interval. *p < 0.05, **p < 0.01

Fig. 2
figure 2

Circulating glucose concentrations (adjusted for pre-pregnancy BMI, maternal age, gestational age of fetus and multi-fetal pregnancy) in 75 g OGTTs by fetal sex. Data are mean ± SEM. *p < 0.05

Table 3 Selected OGTT assessment of the glucose-insulin axis, including surrogate indices of insulin secretion

Offspring birth characteristics by fetal sex

As expected, male offspring were heavier, longer and had bigger head circumferences at birth (Table 4). Visual inspection of the data suggested that there were both linear and quadratic elements in both male and female offspring to the relationship between maternal fasting glucose concentrations and offspring birth weights. In interactive models (adjusted for maternal BMI, age, gestational age at OGTT and at birth, parity and multi-fetal pregnancies) the linear relationship was evident in both male (β′ = 2.013; p = 9.4 × 10–4) and female (β′ = 1.614; p = 6.8 × 10–4) offspring. Similarly, the quadratic relationship was also evident in both male (β′ = -0.763; p = 0.02) and female (β′ = − 0.517; p = 4.7 × 10–3) offspring. There was no difference in offspring BMI or ponderal index by sex of the offspring. However, skinfold thicknesses of the flank, quadriceps and subscapular regions were lower in boys than in girls. There were no differences in triceps skinfold thicknesses by sex.

Table 4 Offspring birth characteristics according to fetal sex


In this study we have found pregnant women carrying male fetuses had lower fasting circulating glucose and insulin concentrations than those carrying females at around week 28 of pregnancy. Surrogate indices also suggest that those carrying male fetuses were more insulin sensitive, which is consistent with some [15, 25] but not all [16, 17] published studies. We also found that women carrying male fetuses had higher insulin disposition indices, suggesting higher insulin secretion for their degree of insulin sensitivity. We hypothesise that higher insulin sensitivity and lower glucose concentrations may reduce growth stimulation in male fetuses, given the observed relationship between maternal fasting glucose concentrations and offspring birth weights. This could enhance survival, with male fetuses being more prone to high birth weights [26] and such babies being at increased risk of neonatal death [27].

Despite the differences in fasting concentrations, we observed no associations between the fetal sex and OGTT post-load glucose and insulin concentrations, so there was no evidence of altered non-basal insulin sensitivity. The reduced insulin resistance and circulating glucose concentrations observed in the fasting state of pregnant women carrying male fetuses may therefore relate more to reduced hepatic glucose output than to increased insulin-stimulated glucose uptake into muscle or adipose tissue [28] as hepatic glucose output is thought to have a greater influence on fasting than post-prandial glucose concentrations. One plausible mechanism of this involves differences in placental structure or function, most of the placenta being fetal in origin [10, 18], leading to differential secretion of placental hormones and/or other biologically active molecules into the maternal circulation. Of the various placental hormones whose maternal circulating concentrations differ according to fetal sex [18], one candidate which has been shown to be secreted in decreased amounts into the circulation with male fetuses [11] is human placental lactogen (hPL). hPL stimulates increased circulating non-esterified fatty acid levels [29], which in turn can increase hepatic glucose output [30] and glucose-stimulated insulin secretion [31]. All these lead to hPL inhibiting insulin sensitivity [32]. However, it also increases β-cell mass and function [18], which is inconsistent with the present results. Testosterone, a candidate hormone secreted into the circulation in increased amounts in women carrying male fetuses [33] (although not universally [34]), is unlikely to mediate the observed associations since it has been associated with insulin resistance [35, 36]. Another potential candidate hormone is oestradiol, whose circulating concentrations are lower in women carrying males, at least in early pregnancy [37]. These reduced oestradiol concentrations are associated with increased insulin sensitivity [18]. Like the role of hPL, therefore, the role of oestradiol in affecting insulin sensitivity and secretion in pregnancy is only partially consistent with what was observed in the present analysis. Non-hormonal candidate molecules that may alter insulin sensitivity in pregnancy [38] and show fetal sex-related differences [39] include regulatory cytokines, although these are less well studied in terms of effects on the glucose-insulin axis in pregnancy.

In the present study there was no observable significant association between fetal sex and risk of GDM, which is inconsistent with meta-analyses of the subject [12, 13]. However, the direction and magnitude of the non-significant association in the present study was consistent with these studies. Also, closer inspection of those original studies included in the meta-analyses show that 15 out of 21 exhibited no significant risk according to fetal sex in one publication [12] and 21 out of 28 in another [13].

As expected, in the present study there were differences in size at birth by offspring sex. Males had higher birth weights, lengths and head circumferences. Females had regions of greater adiposity, as suggested by increased skinfold thicknesses in the flank, quadriceps and subscapular regions, as observed previously [17, 40]. This decreased adiposity in males was regionalised as it was not observed with the triceps region. Neither were there any differences in overall adiposity in terms of the ponderal index and BMI. The decreased adiposity observed in the three other skinfolds regions may relate to the increased insulin sensitivity in women carrying males, as it has previously been observed to relate to the offspring fat mass [41].

The strengths of this study include the use of a relatively large contemporary birth cohort with detailed measurements relating to the maternal glucose-insulin axis and offspring birth characteristics. Its limitations include possible biases introduced by only studying a proportion of the full cohort. However, there was no apparent (fetal) sex bias in clinical characteristics that showed differences between those included and excluded from this study. Another limitation is that the cohort itself may not be representative of the general population. However, the demographics of the cohort are very similar to those of pregnancies of the Rosie Maternity Hospital overall [19]. A third limitation is the lack of OGTT 30-min. insulin concentrations, which are usually used for the calculation of indices of insulin secretion. Nevertheless, in previous OGTT studies the 60-min. insulins correlate well with the 30-min. values [42] suggesting that our calculated values should still be useful surrogates.


In conclusion our results from this study are consistent with the idea that the fetal sex may be able to influence the maternal glucose-insulin axis, with pregnant women carrying males having slightly lower glucose concentrations and being more insulin sensitive in the basal state than those carrying females. Our results suggest that this may only be evident when fasted, although further work is needed to clarify this.

Perspectives and significance

Results from the present analysis add to those in the literature suggesting that in pregnancy the maternal glucose-insulin axis can be influenced by the fetal sex, albeit our associations had modest effect sizes. Unfortunately, these actual potential effects of fetal sex appear to vary according to the makeup of the populations tested [12,13,14,15,16,17,18]. Our results come from a relatively homogeneous cohort living in a comparatively affluent area of England [19], potentially limiting confounding. Further analyses could usefully delineate what mediates the heterogeneity of results from different studies and which placental hormones and/or bioactive molecules mediate the associations.

Availability of Data and Materials

The dataset analysed during the current study is available in the Apollo repository,


  1. Petry CJ, Ong KK, Dunger DB. Does the fetal genotype affect maternal physiology during pregnancy? Trends Mol Med. 2007;13:414–21.

    CAS  PubMed  Article  Google Scholar 

  2. Moore GE, Ishida M, Demetriou C, Al-Olabi L, Leon LJ, Thomas AC, et al. The role and interaction of imprinted genes in human fetal growth. Philos Trans R Soc Lond B. 2015;370:20140074.

    CAS  Article  Google Scholar 

  3. John RM. Imprinted genes and the regulation of placental endocrine function: pregnancy and beyond. Placenta. 2017;56:86–90.

    CAS  PubMed  Article  Google Scholar 

  4. Petry CJ, Seear RV, Wingate DL, Manico L, Acerini CL, Ong KK, et al. Associations between paternally transmitted fetal IGF2 variants and maternal circulating glucose concentrations in pregnancy. Diabetes. 2011;60:3090–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. Petry CJ, Mooslehner K, Prentice P, Hayes MG, Nodzenski M, Scholtens DM, et al. Associations between a fetal imprinted gene allele score and late pregnancy maternal glucose concentrations. Diabetes Metab. 2017;43:323–31.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. Petry CJ, Koulman A, Lu L, Jenkins B, Furse S, Prentice P, et al. Associations between the maternal circulating lipid profile in pregnancy and fetal imprinted gene alleles: a cohort study. Reprod Biol Endocrinol. 2018;16:82.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  7. Petry CJ, Burling KA, Barker P, Hughes IA, Ong KK, Dunger DB. Pregnancy serum DLK1 concentrations are associated with indices of insulin resistance and secretion. J Clin Endocrinol Metab. 2021;106:e2413–22.

    PubMed  PubMed Central  Article  Google Scholar 

  8. Petry CJ, Evans ML, Wingate DL, Ong KK, Reik W, Constância M, Dunger DB. Raised late pregnancy glucose concentrations in mice carrying pups with targeted disruption of H19delta13. Diabetes. 2010;59:282–6.

    CAS  PubMed  Article  Google Scholar 

  9. Petry CJ, Sanz Marcos N, Pimentel G, Hayes MG, Nodzenski M, Scholtens DM, et al. Associations between fetal imprinted genes and maternal blood pressure in pregnancy. Hypertension. 2016;68:1459–66.

    CAS  PubMed  Article  Google Scholar 

  10. Turco MY, Moffett A. Development of the human placenta. Development. 2019;146:dev163428.

    CAS  PubMed  Article  Google Scholar 

  11. Houghton DJ, Shackleton P, Obiekwe BC, Chard T. Relationship of maternal and fetal levels of human placental lactogen to the weight and sex of the fetus. Placenta. 1984;5:455–8.

    CAS  PubMed  Article  Google Scholar 

  12. Jaskolka D, Retnakaran R, Zinman B, Kramer CK. Sex of the baby and risk of gestational diabetes mellitus in the mother: a systematic review and meta-analysis. Diabetologia. 2015;58:2469–75.

    PubMed  Article  Google Scholar 

  13. Broere-Brown ZA, Adank MC, Benschop L, Tielemans M, Muka T, Gonçalves R, et al. Fetal sex and maternal pregnancy outcomes: a systematic review and meta-analysis. Biol Sex Differ. 2020;11:26.

    PubMed  PubMed Central  Article  Google Scholar 

  14. Seghieri G, Di Cianni G, Gualdani E, De Bellis A, Franconi F, Francesconi P. The impact of fetal sex on risk factors for gestational diabetes and related adverse pregnancy outcomes. Acta Diabetol. 2022.

    Article  PubMed  Google Scholar 

  15. Yamashita H, Yasuhi I, Koga M, Sugimi S, Umezaki Y, Fukuoka M, et al. Fetal sex and maternal insulin resistance during mid-pregnancy: a retrospective cohort study. BMC Pregnancy Childbirth. 2020;20:560.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. Geng X, Geng L, Zhang Y, Lu H, Shen Y, Chen R, et al. Fetal sex influences maternal fasting plasma glucose levels and basal β-cell function in pregnant women with normal glucose tolerance. Acta Diabetol. 2017;54:1131–8.

    CAS  PubMed  Article  Google Scholar 

  17. Walsh JM, Segurado R, Mahony RM, Foley ME, McAuliffe FM. The effects of fetal gender on maternal and fetal insulin resistance. PLoS ONE. 2015;10: e0137215.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  18. Stern C, Schwarz S, Moser G, Cvitic S, Jantscher-Krenn E, Gauster M, et al. Placental endocrine activity: adaptation and disruption of maternal glucose metabolism in pregnancy and the influence of fetal sex. Int J Mol Sci. 2021;22:12722.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. Prentice P, Acerini CL, Eleftheriou A, Hughes IA, Ong KK, Dunger DB. Cohort profile: the Cambridge Baby Growth Study (CBGS). Int J Epidemiol. 2016;45:35.

    PubMed  Article  Google Scholar 

  20. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy, Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, et al. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010;33:676–82.

    Article  CAS  Google Scholar 

  21. De Lucia RE, Modi N, Uthaya S, Hughes IA, Dunger DB, Acerini C, et al. Ultrasound estimates of visceral and subcutaneous-abdominal adipose tissues in infancy. J Obes. 2013;2013: 951954.

    Google Scholar 

  22. de Lauzon-Guillain B, Wijndaele K, Clark M, Acerini CL, Hughes IA, Dunger DB, et al. Breastfeeding and infant temperament at age three months. PLoS ONE. 2012;7: e29326.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  23. Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care. 1998;21:2191–2.

    CAS  PubMed  Article  Google Scholar 

  24. Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, et al. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000;85:2402–10.

    CAS  PubMed  Article  Google Scholar 

  25. Xiao L, Zhao JP, Nuyt AM, Fraser WD, Luo ZC. Female fetus is associated with greater maternal insulin resistance in pregnancy. Diabet Med. 2014;31:1696–701.

    CAS  PubMed  Article  Google Scholar 

  26. Delgado-Rodríguez M, Pérez-Iglesias R, Gómez-Olmedo M, Bueno-Cavanillas A, Gálvez-Vargas R. Risk factors for low birth weight: Results from a case–control study in southern Spain. Am J Phys Antropol. 1998;105:419–24.

    Article  Google Scholar 

  27. UNICEF, WHO. Low birth weight: country, regional and global estimates. New York: UNICEF; 2004.

    Google Scholar 

  28. Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectrum. 2004;17:183–90.

    Article  Google Scholar 

  29. Williams C, Coltart TM. Adipose tissue metabolism in pregnancy: the lipolytic effect of human placental lactogen. Br J Obstet Gynaecol. 1978;85:43–6.

    CAS  PubMed  Article  Google Scholar 

  30. Wilcox G. Insulin and insulin resistance. Clin Biochem Rev. 2005;26:19–39.

    PubMed  PubMed Central  Google Scholar 

  31. Amery CM, Nattrass M. Fatty acids and insulin secretion. Diabetes Obes Metab. 2000;2:213–21.

    CAS  PubMed  Article  Google Scholar 

  32. Beck P, Daughaday WH. Human placental lactogen: studies of its acute metabolic effects and disposition in normal man. J Clin Invest. 1967;46:103–10.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. Steier JA, Ulstein M, Myking OL. Human chorionic gonadotropin and testosterone in normal and preeclamptic pregnancies in relation to fetal sex. Obstet Gynecol. 2002;100:552–6.

    CAS  PubMed  Google Scholar 

  34. Kuijper EA, Ket JC, Caanen MR, Lambalk CB. Reproductive hormone concentrations in pregnancy and neonates: a systematic review. Reprod Biomed Online. 2013;27:33–63.

    CAS  PubMed  Article  Google Scholar 

  35. Vejrazkova D, Vcelak J, Vankova M, Lukasova P, Bradnova O, Halkova T, et al. Steroids and insulin resistance in pregnancy. J Steroid Biochem Mol Biol. 2014;139:122–9.

    CAS  PubMed  Article  Google Scholar 

  36. Ackerman CM, Lowe LP, Dyer AR, Hayes MG, Metzger BE, Lowe WL, et al. Maternal testosterone levels are associated with C-peptide levels in the Mexican American subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study cohort. Horm Metab Res. 2013;45:617–20.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Toriola AT, Vääräsmäki M, Lehtinen M, Zeleniuch-Jacquotte A, Lundin E, Rodgers K-G, et al. Determinants of maternal sex steroids during the first half of pregnancy. Obstet Gynecol. 2011;118:1029–36.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. Kampmann U, Knorr S, Fuglsang J, Ovesen P. Determinants of maternal insulin resistance during pregnancy: an updated overview. J Diabetes Res. 2019;2019:5320156.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  39. Enninga EA, Nevala WK, Creedon DJ, Markovic SN, Holtan SG. Fetal sex-based differences in maternal hormones, angiogenic factors, and immune mediators during pregnancy and the postpartum period. Am J Reprod Immunol. 2015;73:251–62.

    CAS  PubMed  Article  Google Scholar 

  40. Harrington TA, Thomas EL, Frost G, Modi N, Bell JD. Distribution of adipose tissue in the newborn. Pediatr Res. 2004;55:437–41.

    PubMed  Article  Google Scholar 

  41. Catalano PM, Drago NM, Amini SB. Maternal carbohydrate metabolism and its relationship to fetal growth and body composition. Am J Obstet Gynecol. 1995;172:1464–70.

    CAS  PubMed  Article  Google Scholar 

  42. Phillips DI, Clark PM, Hales CN, Osmond C. Understanding oral glucose tolerance: comparison of glucose or insulin measurements during the oral glucose tolerance test with specific measurements of insulin resistance and insulin secretion. Diabet Med. 1994;11:286–92.

    CAS  PubMed  Article  Google Scholar 

Download references


The authors acknowledge the huge contribution made to this study by Dr. Carlo Acerini and Prof. David Dunger, who were Principal Investigators of the Cambridge Baby Growth Study prior to their deaths in May 2019 and July 2021, respectively. The authors would like to thank Angie Watts, Dianne Wingate and Karen Whitehead (all University of Cambridge, Department of Paediatrics) for their excellent technical assistance in this study. In addition, the authors would like to thank the families that participated in the Cambridge Baby Growth Study, and acknowledge the vital part played by the research nurses especially Ann-Marie Wardell, Suzanne Smith and Karen Forbes (all University of Cambridge, Department of Paediatrics), staff at the Addenbrooke’s Wellcome Trust Clinical Research Facility, and midwives at the Rosie Maternity Hospital.


The Cambridge Baby Growth Study has received funding from the World Cancer Research Fund International (Grant No. 2004/03); the European Union Framework 5 (Grant No. QLK4-1999-01422); the Medical Research Council (Grant No. G1001995, 7500001180, U106179472); the Newlife Foundation for Disabled Children (Grant No. 07/20) and the Mothercare Charitable Foundation (Grant No. RG54608). The authors have also received support from National Institute for Health Research Cambridge Biomedical Research Centre. KKO receives support from the Medical Research Council (Unit Programme Numbers: MC_UU_12015/2 and MC_UU_00006/2).

Author information

Authors and Affiliations



CJP contributed to conception, methodology, formal analysis, investigation, data curation and writing—original draft preparation. IAH contributed to methodology, resources, writing—review and editing, project administration and funding acquisition. KKO contributed to methodology, resources, writing—review and editing, project administration and funding acquisition. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Clive J. Petry.

Ethics declarations

Ethics approval and consent to participate

Ethical approval for the Cambridge Baby Growth Study was granted by the Cambridge Local Research Ethics Committee, Addenbrooke’s Hospital, Cambridge, U.K. (00/325). All procedures followed were in accordance with both institutional and international guidelines. Written informed consent was obtained from all women (on their own behalf and on behalf of their baby).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Petry, C.J., Hughes, I.A. & Ong, K.K. Increased basal insulin sensitivity in late pregnancy in women carrying a male fetus: a cohort study. Biol Sex Differ 13, 20 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI:


  • Development
  • Fetal sex
  • Gestational diabetes
  • Insulin secretion
  • Glucose