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Exp Clin Endocrinol Diabetes 2022; 130(05): 335-342
DOI: 10.1055/a-1375-4176
Article

Impact of Smoking, Obesity and Maternal Diabetes on SHBG Levels in Newborns

Banu Kucukemre Aydin   *
1   Division of Pediatric Endocrinology, Metabolism and Diabetes, Istanbul University, Istanbul, Turkey
,
Beril Yasa   *
2   Division of Neonatology, Istanbul University, Istanbul, Turkey
,
Joseph P. Moore
3   Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, Kentucky, USA
,
Cenk Yasa
4   Department of Obstetrics, Gynecology and Women’s Health, Istanbul University, Istanbul, Turkey
,
Sukran Poyrazoglu
1   Division of Pediatric Endocrinology, Metabolism and Diabetes, Istanbul University, Istanbul, Turkey
,
Firdevs Bas
1   Division of Pediatric Endocrinology, Metabolism and Diabetes, Istanbul University, Istanbul, Turkey
,
Asuman Coban
2   Division of Neonatology, Istanbul University, Istanbul, Turkey
,
Feyza Darendeliler
1   Division of Pediatric Endocrinology, Metabolism and Diabetes, Istanbul University, Istanbul, Turkey
,
Stephen J. Winters
5   Division of Endocrinology, Metabolism and Diabetes. University of Louisville, Louisville, Kentucky, USA
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Abstract

Background Low levels of SHBG have become a marker for insulin resistance and diabetes. Babies born to mothers who are obese, have diabetes, or smoke during pregnancy are at greater risk of developing obesity and diabetes later in life.

Aims To examine the impact of maternal obesity, diabetes and smoking on SHBG levels in newborns.

Study design This cross-sectional study is part of an ongoing multicenter, longitudinal study.

Subjects 98 healthy newborns and their parents, including 16 mothers with diabetes and 31 mothers with a smoking history.

Outcome measures Cord blood and second day venipuncture samples were collected for measurement of SHBG and insulin.

Results Babies born to mothers with diabetes had lower SHBG levels in cord blood [14.0 (8.9–20.4) vs. 19.6 (14.9–25.1) nmol/L; p=0.011] and on day 2 [18.8 (12.6–21.2) vs. 22.9 (17.1–29.1) nmol/L; p=0.015] than controls. Maternal diabetes remained negatively associated with SHBG levels in cord blood (p=0.02) and on day 2 (p=0.04) when adjusted for mothers’ age, smoking status, pre-pregnancy weight and weight gain during pregnancy. SHBG levels in cord blood and day 2 samples were similar in babies born to mothers who were overweight-obese but not diabetic vs. normal weight, or were smokers when compared to non-smokers.

Conclusions: SHBG levels are lower in newborns born to mothers with diabetes than without diabetes, and may be a marker for babies’ life-long risk for abnormal metabolic health. On the other hand, the adverse effects of tobacco smoke on the fetus do not appear to directly influence SHBG levels.

Key words

obesity - diabetes - metabolic syndrome - SHBG - smoking.

* Banu Kucukemre Aydin and Beril Yasa contributed equally and are co-first authors on this manuscript.


Supplementary Material



Publication History

Received: 09 October 2020
Received: 08 January 2021

Accepted: 27 January 2021

Article published online:
22 February 2021

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Barker DJ. Fetal origins of cardiovascular disease. Ann Med 1999; 31 Suppl 1 3-6
    CrossrefPubMedGoogle Scholar
  • 2 Glass AR, Swerdloff RS, Bray GA. et al. Low serum testosterone and sex-hormone-binding-globulin in massively obese men. J Clin Endocrinol Metab 1977; 45: 1211-1219
    CrossrefPubMedGoogle Scholar
  • 3 Hammond GL, Wu TS, Simard M. Evolving utility of sex hormone-binding globulin measurements in clinical medicine. Curr Opin Endocrinol Diabetes Obes 2012; 19: 183-189
    CrossrefPubMedGoogle Scholar
  • 4 Krishnasamy SS, Chang C, Wang C. et al. Sex hormone-binding globulin and the risk for metabolic syndrome in children of South Asian Origin. Endocr Pract 2012; 1-23
    PubMedGoogle Scholar
  • 5 Ibanez L, Lopez-Bermejo A, Diaz M. et al. Catch-up growth in girls born small for gestational age precedes childhood progression to high adiposity. Fertil Steril 2011; 96: 220-223
    CrossrefPubMedGoogle Scholar
  • 6 Agirbasli M, Agaoglu NB, Orak N. et al. Sex hormones and metabolic syndrome in children and adolescents. Metabolism 2009; 58: 1256-1262
    CrossrefPubMedGoogle Scholar
  • 7 Winters SJ, Gogineni J, Karegar M. et al. Sex hormone-binding globulin gene expression and insulin resistance. J Clin Endocrinol Metab 2014; 99: E2780-E2788
    CrossrefPubMedGoogle Scholar
  • 8 Janne M, Hammond GL. Hepatocyte nuclear factor-4 controls transcription from a TATA-less human sex hormone-binding globulin gene promoter. J Biol Chem 1998; 273: 34105-34114
    CrossrefPubMedGoogle Scholar
  • 9 Xie X, Liao H, Dang H. et al. Down-regulation of hepatic HNF4alpha gene expression during hyperinsulinemia via SREBPs. Mol Endocrinol 2009; 23: 434-443
    CrossrefPubMedGoogle Scholar
  • 10 Nikolaidou-Neokosmidou V, Zannis VI, Kardassis D. Inhibition of hepatocyte nuclear factor 4 transcriptional activity by the nuclear factor kappaB pathway. Biochem J 2006; 398: 439-450
    CrossrefPubMedGoogle Scholar
  • 11 Simo R, Barbosa-Desongles A, Saez-Lopez C. et al. Molecular mechanism of TNFalpha-Induced down-regulation of SHBG expression. Mol Endocrinol 2012; 26: 438-446
    CrossrefPubMedGoogle Scholar
  • 12 Babeu JP, Boudreau F. Hepatocyte nuclear factor 4-alpha involvement in liver and intestinal inflammatory networks. World J Gastroenterol 2014; 20: 22-30
    CrossrefPubMedGoogle Scholar
  • 13 Aydin B, Winters SJ. Sex hormone-binding globulin in children and adolescents. J Clin Res Pediatr Endocrinol 2016; 8: 1-12
    CrossrefPubMedGoogle Scholar
  • 14 Keelan JA, Mattes E, Tan H. et al. Androgen concentrations in umbilical cord blood and their association with maternal, fetal and obstetric factors. PLoS One 2012; 7: e42827
    CrossrefPubMedGoogle Scholar
  • 15 Maffeis C, Moghetti P, Vettor R. et al. Leptin concentration in newborns' cord blood: Relationship to gender and growth-regulating hormones. Int J Obes Relat Metab Disord 1999; 23: 943-947
    CrossrefPubMedGoogle Scholar
  • 16 Rohrmann S, Sutcliffe CG, Bienstock JL. et al. Racial variation in sex steroid hormones and the insulin-like growth factor axis in umbilical cord blood of male neonates. Cancer Epidemiol Biomarkers Prev 2009; 18: 1484-1491
    CrossrefPubMedGoogle Scholar
  • 17 Jin Z, Guan X, Gao H. et al. The change in sex hormone binding globulin and the influence by gestational diabetes mellitus in fetal period. Gynecol Endocrinol 2009; 25: 647-652
    CrossrefPubMedGoogle Scholar
  • 18 Simmons D. Interrelation between umbilical cord serum sex hormones, sex hormone-binding globulin, insulin-like growth factor I, and insulin in neonates from normal pregnancies and pregnancies complicated by diabetes. J Clin Endocrinol Metab 1995; 80: 2217-2221
    PubMedGoogle Scholar
  • 19 Agurs-Collins T, Rohrmann S, Sutcliffe C. et al. Racial variation in umbilical cord blood sex steroid hormones and the insulin-like growth factor axis in African-American and white female neonates. Cancer Causes Control 2012; 23: 445-454
    CrossrefPubMedGoogle Scholar
  • 20 Lagiou P, Samoli E, Okulicz W. et al. Maternal and cord blood hormone levels in the United States and China and the intrauterine origin of breast cancer. Ann Oncol 2011; 22: 1102-1108
    CrossrefPubMedGoogle Scholar
  • 21 Dharashivkar S, Wasser L, Baumgartner RN. et al. Obesity, maternal smoking and SHBG in neonates. Diabetol Metab Syndr 2016; 8: 47 DOI: 10.1186/s13098-016-0158-0.. eCollection 2016
    CrossrefPubMedGoogle Scholar
  • 22 Liu B, Xu Y, Liang JM. et al. Intrauterine insulin resistance in fetuses of overweight mothers. J Obstet Gynaecol Res 2013; 39: 132-138
    CrossrefPubMedGoogle Scholar
  • 23 Sun L, Jin Z, Teng W. et al. SHBG in GDM maternal serum, placental tissues and umbilical cord serum expression changes and its significance. Diabetes Res Clin Pract 2013; 99: 168-173
    CrossrefPubMedGoogle Scholar
  • 24 Bernstein IM, Plociennik K, Stahle S. et al. Impact of maternal cigarette smoking on fetal growth and body composition. Am J Obstet Gynecol 2000; 183: 883-886
    CrossrefPubMedGoogle Scholar
  • 25 Riedel C, Fenske N, Müller MJ. et al. Differences in BMI z-scores between offspring of smoking and nonsmoking mothers: A longitudinal study of German children from birth through 14 years of age. Environ Health Perspect 2014; 122: 761-767
    CrossrefPubMedGoogle Scholar
  • 26 La Merrill MA, Cirillo PM, Krigbaum NY. et al. The impact of prenatal parental tobacco smoking on risk of diabetes mellitus in middle-aged women. J Dev Orig Health Dis 2015; 6: 242-249
    CrossrefPubMedGoogle Scholar
  • 27 Kovess V, Keyes KM, Hamilton A. et al. Maternal smoking and offspring inattention and hyperactivity: results from a cross-national European survey. Eur Child Adolesc Psychiatry 2015; 24: 919-929
    CrossrefPubMedGoogle Scholar
  • 28 Karaçam Z, Çelİk D. The prevalence and risk factors of gestational diabetes mellitus in Turkey: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2019; 1-11
    PubMedGoogle Scholar
  • 29 Kurtoglu S, Hatipoglu N, Mazicioglu MM. et al. Body weight, length and head circumference at birth in a cohort of Turkish newborns. J Clin Res Pediatr Endocrinol 2012; 4: 132-139
    CrossrefPubMedGoogle Scholar
  • 30 Bartha JL, Comino-Delgado R, Romero-Carmona R. et al. Sex hormone-binding globulin in gestational diabetes. Acta Obstet Gynecol Scand 2000; 79: 839-845
    PubMedGoogle Scholar
  • 31 Thadhani R, Wolf M, Hsu-Blatman K. et al. First-trimester sex hormone binding globulin and subsequent gestational diabetes mellitus. Am J Obstet Gynecol 2003; 189: 171-176
    CrossrefPubMedGoogle Scholar
  • 32 Bolton NJ, Tapanainen J, Koivisto M. et al. Circulating sex hormone-binding globulin and testosterone in newborns and infants. Clin Endocrinol (Oxf) 1989; 31: 201-207
    CrossrefPubMedGoogle Scholar
  • 33 Davis SM, Kaar JL, Ringham BM. et al. Sex differences in infant body composition emerge in the first 5 months of life. J Pediatr Endocrinol Metab 2019; 32: 1235-1239
    CrossrefPubMedGoogle Scholar
  • 34 Elmlinger MW, Kuhnel W, Wormstall H. et al. Reference intervals for testosterone, androstenedione and SHBG levels in healthy females and males from birth until old age. Clin Lab 2005; 51: 625-632
    PubMedGoogle Scholar
  • 35 Madsen A, Oehme NB, Roelants M. et al. Testicular ultrasound to stratify hormone references in a cross-sectional Norwegian study of male puberty. J Clin Endocrinol Metab 2020; 105: dgz094. DOI: 10.1210/clinem/dgz094.
    CrossrefPubMedGoogle Scholar
  • 36 Lindstedt G, Lundberg PA, Lapidus L. et al. Low sex-hormone-binding globulin concentration as independent risk factor for development of NIDDM. 12-yr follow-up of population study of women in Gothenburg, Sweden. Diabetes 1991; 40: 123-128
    CrossrefPubMedGoogle Scholar
  • 37 Faal S, Abedi P, Jahanfar S. et al. Sex hormone binding globulin for prediction of gestational diabetes mellitus in pre-conception and pregnancy: A systematic review. Diabetes Res Clin Pract 2019; 152: 39-52
    CrossrefPubMedGoogle Scholar
  • 38 Lee SM, Kwak SH, Koo JN. et al. Non-alcoholic fatty liver disease in the first trimester and subsequent development of gestational diabetes mellitus. Diabetologia 2019; 62: 238-248
    CrossrefPubMedGoogle Scholar
  • 39 Brumbaugh DE, Tearse P, Cree-Green M. et al. Intrahepatic fat is increased in the neonatal offspring of obese women with gestational diabetes. J Pediatr 2013; 162: 930-936.e931
    CrossrefPubMedGoogle Scholar
  • 40 Lee SM, Kim BJ, Koo JN. et al. Nonalcoholic fatty liver disease is a risk factor for large-for-gestational-age birthweight. PLoS One 2019; 14: e0221400
    CrossrefPubMedGoogle Scholar
  • 41 Catalano PM, McIntyre HD, Cruickshank JK. et al. The hyperglycemia and adverse pregnancy outcome study: associations of GDM and obesity with pregnancy outcomes. Diabetes care 2012; 35: 780-786
    CrossrefPubMedGoogle Scholar
  • 42 Josefson JL, Catalano PM, Lowe WL. et al. The Joint Associations of Maternal BMI and Glycemia with Childhood Adiposity. J Clin Endocrinol Metab 2020; 105: 2177-2188. DOI: 10.1210/clinem/dgaa180.
    CrossrefPubMedGoogle Scholar
  • 43 Scholtens DM, Kuang A, Lowe LP. et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal glycemia and childhood glucose metabolism. Diabetes Care 2019; 42: 381-392
    CrossrefPubMedGoogle Scholar
  • 44 Lowe WL, Scholtens DM, Kuang A. et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal gestational diabetes mellitus and childhood glucose metabolism. Diabetes Care 2019; 42: 372-380
    CrossrefPubMedGoogle Scholar
  • 45 Fang H, Judd RL. Adiponectin regulation and function. Compr Physiol 2018; 8: 1031-1063
    CrossrefPubMedGoogle Scholar
  • 46 Gannagé-Yared MH, Khalife S, Semaan M. et al. Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men. Eur J Endocrinol 2006; 155: 167-176
    CrossrefPubMedGoogle Scholar
  • 47 Yasui T, Tomita J, Miyatani Y. et al. Associations of adiponectin with sex hormone-binding globulin levels in aging male and female populations. Clin Chim Acta 2007; 386: 69-75
    CrossrefPubMedGoogle Scholar
  • 48 Simó R, Saez-Lopez C, Lecube A. et al. Adiponectin upregulates SHBG production: Molecular mechanisms and potential implications. Endocrinology 2014; 155: 2820-2830
    CrossrefPubMedGoogle Scholar
  • 49 Mantzoros CS, Rifas-Shiman SL, Williams CJ. et al. Cord blood leptin and adiponectin as predictors of adiposity in children at 3 years of age: A prospective cohort study. Pediatrics 2009; 123: 682-689
    CrossrefPubMedGoogle Scholar
  • 50 Salmasi G, Grady R, Jones J. et al. Environmental tobacco smoke exposure and perinatal outcomes: A systematic review and meta-analyses. Acta Obstet Gynecol Scand 2010; 89: 423-441
    CrossrefPubMedGoogle Scholar
  • 51 Behl M, Rao D, Aagaard K. et al. Evaluation of the association between maternal smoking, childhood obesity, and metabolic disorders: A national toxicology program workshop review. Environ Health Perspect 2013; 121: 170-180
    CrossrefPubMedGoogle Scholar
  • 52 O'Shaughnessy PJ, Monteiro A, Bhattacharya S. et al. Maternal smoking and fetal sex significantly affect metabolic enzyme expression in the human fetal liver. J Clin Endocrinol Metab 2011; 96: 2851-2860
    CrossrefPubMedGoogle Scholar
  • 53 Filis P, Nagrath N, Fraser M. et al. Maternal smoking dysregulates protein expression in second trimester human fetal livers in a sex-specific manner. J Clin Endocrinol Metab 2015; 100: E861-E870. DOI: 10.1210/jc.2014-3941.
    CrossrefPubMedGoogle Scholar