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Am J Perinatol 2020; 37(11): 1094-1101
DOI: 10.1055/s-0040-1702988
SMFM Fellowship Series Article

Characterizing the Effects of Diabetes and Obesity on Insulin and Leptin Levels amongst Pregnant Women

Andrea W. Johnson
1   Department of Obstetrics, Gynecology and Reproductive Sciences, Section of Maternal-Fetal Medicine, Yale School of Medicine, New Haven, Connecticut
,
Denis Snegovskikh
2   Division of Obstetric and Gynecological Anesthesiology, Department of Anesthesiology, Yale School of Medicine, New Haven, Connecticut
,
Lisa Parikh
3   Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale School of Medicine, New Haven, Connecticut
,
Renata B. DeAguiar
3   Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale School of Medicine, New Haven, Connecticut
,
Christina S. Han 
1   Department of Obstetrics, Gynecology and Reproductive Sciences, Section of Maternal-Fetal Medicine, Yale School of Medicine, New Haven, Connecticut
,
Janice J. Hwang
3   Department of Internal Medicine, Section of Endocrinology and Metabolism, Yale School of Medicine, New Haven, Connecticut
› Author Affiliations Funding This research was funded by HD 047018 (C.S.H.), the Endocrine Fellows Foundation Marilyn Fishman Grant (J.J.H.)
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Abstract

Objective In this study, we assess the impact of obesity and diabetes on maternal brain and periphery, as well as fetal exposure to insulin and leptin, and two hormones that play an important role in regulating energy homeostasis.

Study Design Fasting maternal plasma, fetal cord vein and artery plasma, and maternal cerebrospinal fluid (CSF) were collected in 37 women (12 lean, nondiabetic [prepregnancy body mass index (BMI): 22.9 ± 1.7 kg/m2]; 12 overweight/obese nondiabetic [BMI: 37.8 ± 7.3 kg/m2]; 13 gestational/type 2 diabetes mellitus [BMI: 29.8 ± 7.3 kg/m2]) with uncomplicated singleton pregnancies undergoing elective Cesarean delivery. HbA1C, insulin, glucose, and leptin levels were measured.

Results Compared with lean mothers, mothers with obesity and diabetes mellitus (DM) had significantly lower CSF-to-plasma ratios of insulin. Moreover, mothers with obesity and DM had significantly lower cord arterial and cord venous to maternal plasma ratios of insulin, but not leptin, compared with lean mothers. There were no differences in CSF and cord blood insulin and leptin levels between obese and DM mothers.

Conclusion Compared with lean individuals, mothers with obesity and DM have relative deficiencies in insulin exposure. The patterns observed in mothers with obesity and diabetes were similar highlighting the importance of the maternal metabolic environment in obesity and suggesting obese patients warrant further clinical focus.

Keywords

insulin - leptin - pregnancy - central nervous system - obesity

Authors' Contributions

A.W.J. and J.J.H. conceived and performed the experiments, data collection, data analysis, and manuscript preparation. C.S.H. conceived the experiments and was involved in data analysis and manuscript preparation. D.S., L.P., and R.B.D.A. collected and analyzed the data. All authors were involved in writing the paper and had final approval of the submitted and published versions.




Publication History

Received: 05 September 2019

Accepted: 19 January 2020

Article published online:
02 March 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.

 

  • References

  • 1 Boden G. Fuel metabolism in pregnancy and in gestational diabetes mellitus. Obstet Gynecol Clin North Am 1996; 23 (01) 1-10
    CrossrefPubMedSearch in Google Scholar
  • 2 Butte NF. Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr 2000; 71 (5, Suppl): 1256S-1261S
    CrossrefPubMedSearch in Google Scholar
  • 3 Obesity in pregnancy. practice bulletin no. 156. American College of Obstetricans and Gynecologists. Obstet Gynecol 2015; 126: e112-e126
    CrossrefPubMedSearch in Google Scholar
  • 4 Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 2012; 307 (05) 491-497
    CrossrefPubMedSearch in Google Scholar
  • 5 Harlev A, Wiznitzer A. New insights on glucose pathophysiology in gestational diabetes and insulin resistance. Curr Diab Rep 2010; 10 (03) 242-247
    CrossrefPubMedSearch in Google Scholar
  • 6 Gestational diabetes melllitus. ACOG Practice Bulletin No. 190. American College of Obstetricians and Gynecologists. Obstet Gynecol 2018; 131: e49-e64
    CrossrefPubMedSearch in Google Scholar
  • 7 Masuzaki H, Ogawa Y, Sagawa N. , et al. Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans. Nat Med 1997; 3 (09) 1029-1033
    CrossrefPubMedSearch in Google Scholar
  • 8 Page-Wilson G, Reitman-Ivashkov E, Meece K. , et al. Cerebrospinal fluid levels of leptin, proopiomelanocortin, and agouti-related protein in human pregnancy: evidence for leptin resistance. J Clin Endocrinol Metab 2013; 98 (01) 264-271
    CrossrefPubMedSearch in Google Scholar
  • 9 Gustavsson C, Andersson Hall U, Pelanis A. , et al. Cerebrospinal fluid levels of insulin, leptin, and agouti-related protein in relation to BMI in pregnant women. Obesity (Silver Spring) 2016; 24 (06) 1299-1304
    CrossrefPubMedSearch in Google Scholar
  • 10 Kaiyala KJ, Woods SC, Schwartz MW. New model for the regulation of energy balance and adiposity by the central nervous system. Am J Clin Nutr 1995; 62 (5, Suppl): 1123S-1134S
    CrossrefPubMedSearch in Google Scholar
  • 11 Schwartz MW, Figlewicz DP, Baskin DG, Woods SC, Porte Jr D. Insulin in the brain: a hormonal regulator of energy balance. Endocr Rev 1992; 13 (03) 387-414
    PubMedSearch in Google Scholar
  • 12 Baskin DG, Figlewicz DP, Woods SC, Porte Jr. D, Dorsa DM. Insulin in the brain. Annu Rev Physiol 1987; 49: 335-347
    CrossrefPubMedSearch in Google Scholar
  • 13 Israel PA, Park CR, Schwartz MW. , et al. Effect of diet-induced obesity and experimental hyperinsulinemia on insulin uptake into CSF of the rat. Brain Res Bull 1993; 30 (5,6): 571-575
    CrossrefPubMedSearch in Google Scholar
  • 14 Banks WA. The source of cerebral insulin. Eur J Pharmacol 2004; 490 (1–3): 5-12
    CrossrefPubMedSearch in Google Scholar
  • 15 Kern W, Benedict C, Schultes B. , et al. Low cerebrospinal fluid insulin levels in obese humans. Diabetologia 2006; 49 (11) 2790-2792
    CrossrefPubMedSearch in Google Scholar
  • 16 Caro JF, Kolaczynski JW, Nyce MR. , et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996; 348 (9021): 159-161
    CrossrefPubMedSearch in Google Scholar
  • 17 Linnemann K, Malek A, Sager R, Blum WF, Schneider H, Fusch C. Leptin production and release in the dually in vitro perfused human placenta. J Clin Endocrinol Metab 2000; 85 (11) 4298-4301
    PubMedSearch in Google Scholar
  • 18 Hoggard N, Haggarty P, Thomas L, Lea RG. Leptin expression in placental and fetal tissues: does leptin have a functional role?. Biochem Soc Trans 2001; 29 (Pt 2): 57-63
    CrossrefPubMedSearch in Google Scholar
  • 19 Lepercq J, Challier JC, Guerre-Millo M, Cauzac M, Vidal H, Hauguel-de Mouzon S. Prenatal leptin production: evidence that fetal adipose tissue produces leptin. J Clin Endocrinol Metab 2001; 86 (06) 2409-2413
    CrossrefPubMedSearch in Google Scholar
  • 20 Sagawa N, Yura S, Itoh H. , et al. Possible role of placental leptin in pregnancy: a review. Endocrine 2002; 19 (01) 65-71
    CrossrefPubMedSearch in Google Scholar
  • 21 Ahmad A, Rukmini MS, Yadav C, Agarwal A, Manjrekar PA, Hegde A. Indices of glucose homeostasis in cord blood in term and preterm newborns. J Clin Res Pediatr Endocrinol 2016; 8 (03) 270-275
    CrossrefPubMedSearch in Google Scholar
  • 22 Wang Q, Huang R, Yu B. , et al. Higher fetal insulin resistance in Chinese pregnant women with gestational diabetes mellitus and correlation with maternal insulin resistance. PLoS One 2013; 8 (04) e59845
    CrossrefPubMedSearch in Google Scholar
  • 23 Gesteiro E, Bastida S, Sánchez-Muniz FJ. Cord-blood lipoproteins, homocysteine, insulin sensitivity/resistance marker profile, and concurrence of dysglycaemia and dyslipaemia in full-term neonates of the Mérida Study. Eur J Pediatr 2013; 172 (07) 883-894
    CrossrefPubMedSearch in Google Scholar