Medical Journal of Obstetrics and Gynecology

Sex Hormone Binding Globulin in Gestational Diabetes Mellitus

Research Article | Open Access | Volume 3 | Issue 2

  • 1. Department of Obstetrics and Gynecology, Fujian Union Hospital, PR China
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Corresponding Authors
Saviour S. Anderson, Department of Obstetrics and Gynecology, Fujian Union Hospital, Fuzhou, Fujian, Province, PR China, Tel: +86-139-5036-1749.

Aims: The aim of this study was to measure and compare maternal plasma SHBG concentrations in normal pregnancy and in GDM patients, and thereafter determine the association between SHBG and GDM.

Materials and Methods: This was a prospective, case-control study with a total of 60 participants in their third trimester of pregnancy. The control group had 28 women versus 32 women in the GDM/case group. Maternal serum SHBG was measured and compared between the two groups.

Results: The mean age in all participants was 28.35±4.38 years. SHBG concentrations were lower in GDM group (n=32, SHBG= 53.64±31.91) compared to the control group (n=28, SHBG= 71.33±30.58) (p <0.05).

Conclusion: SHBG levels were significantly lower in pregnant women with GDM, therefore, SHBG can, in the future, be used as both a diagnostic and monitoring tool in patients with GDM.


Anderson SS, Zhiqun Z (2015) Sex Hormone Binding Globulin in Gestational Diabetes Mellitus. Med J Obstet Gynecol 3(2): 1057.


•    Gestational diabetes mellitus
•    Sex hormone binding globulin
•    Diabetes mellitus


ADA: American Diabetes Association; BMI: Body Mass Index; CRP: C Reactive Protein; DBP: Diastolic Blood Pressure; DHT: Dihydro Testosterone; DM: Diabetes Mellitus; FPG: Fasting Plasma Glucose; GDM: Gestational Diabetes Mellitus; GH: Growth Hormone; HAPO: Hyperglycemia and Adverse Pregnancy Outcomes; HIV: Human Immunodeficiency Virus; HOMA: Homeostasis Model Assessment; IADPSG: International Association of Diabetes and Pregnancy Study Groups; IGF: Insulin like Growth Factor; mRNA: messenger Ribo Nucleic Acid; OGTT: Oral Glucose Tolerance Test; PCOS: Poly Cystic Ovarian Syndrome; RPG: Random Plasma Glucose; SBP: Systolic Blood Pressure; SHBG: Sex Hormone Binding Globulin; T1DM: Type 1 Diabetes Mellitus; T2DM: Type 2 Diabetes Mellitus; WHO: World Health Organization


Sex Hormone

Introduction and structure: A hormone is a chemical structure that is released into the blood stream in small amounts and after delivery, elicits a typical physiologic response in the target cells [1]. Hormones are generally classified into three classes; 1: derivatives of amino acid tyrosine e.g. adrenaline, noradrenaline, thyroxine; 2: steroid hormones e.g. testosterone, estradiol; 3: peptides and proteins e.g. thyrotropin releasing hormone, prolactin releasing hormone [2]. According to Guyton and Hall [2], sex hormones are steroid hormones that are derived from cholesterol and hence their chemical structure is similar to that cholesterol. Sex hormones consist of three cyclohexyl rings and one cyclopentyl ring combined into a single structure and they are lipophilic [2].

Because sex hormones have low water solubility, they are bound to protein carriers in the blood and only the free and unbound fraction is biologically active, that is, is able to enter a cell and activate its receptor [1,3]. The protein carrier for the sex hormone is SHBG and as long as bound to the globulin, sex hormones remain inactive and these serve as a reservoir for future use [3,4]. However, protein binding is a reversible process [1].

Biosynthesis: Production of sex hormones is mainly in three endocrine organs; adrenal cortex, ovary and testis, however, during pregnancy, placenta acts as an additional source of the sex hormones [3].

Regulation: Concentration of the sex hormones fluctuates with a specific periodicity or as a response to either a physiological and/or pathological process [3,5]. Availability also depends on the biosynthesis and catabolism [5].

Sex Hormone Binding Globulin

Structure: SHBG is a plasma glycoprotein that is produced by the hepatocytes and has a high affinity for steroid hormones [6]. The liver is not the only source for SHBG because testes have also been shown to express SHBG mRNA [7]. SHBG exists as a dimer of two essentially identical monomers and the primary structure of SHBG monomer is a single peptide of 373 amino acids and 3 carbohydrates side chains and this structure binds only one steroid molecule [8].

Functions: SHBG binds sex hormones with high affinity: DHT>testosterone>estrogen [6]. It transports sex steroid hormones within the blood stream to extravascular target tissues [6,8]. It also regulates the bioavailability of sex steroid hormones to target cells [4,6]. Concentration of circulating plasma SHBG also serves as a major determinant of the metabolic clearance of sex hormones [4].

SHBG has been identified as a contributing factor and also implicated in the pathophysiology of T2DM [6-12]. A number of epidemiological studies have also demonstrated an inverse relationship between the lower levels of SHBG with T2DM [9-12]. SHBG concentrations have been consistently found to be lower in GDM patients [13-15]; however, these concentrations are neither related nor reflective of the peripheral insulin insensitivity [15].

Based on some recent molecular epidemiological studies, genetically determined concentrations of SHBG are inversely associated with T2DM and thus supporting evidence of the role of SHBG in the development of T2DM [9,12,16]. The exact mechanism by which SHBG influences the risk of DM is still unclear but according to Nestler and colleagues, SHBG may contribute to the impairment of glucose metabolism through modulation of sex hormones, bioavailability and direct activation of specific receptor for SHBG10. On the other end, Rosner et al. [17] found that plasma membranes of different types of cells are capable of binding specifically and with high affinity to SHBG and thus mediating sex hormones.

Regulation: Nestler and fellow authors also found that SHBG influences glucose homeostasis, and factors such as insulin and monosaccharides are implicated as possible regulators of SHBG transcription [10]. There are factors that may increase or decrease the plasma concentration of SHBG. Factors that decrease SHBG levels include, hyperinsulinaemia, high levels of GH, high levels of IGF, PCOS and obesity [6,18-20]. Some of the factors that may increase SHBG concentrations include, liver cirrhosis, hyperthyroidism, anorexia nervosa and high estrogen levels [6,18-21].

Diabetes Mellitus

Definition and classification: Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia from abnormalities in insulin secretion and/or insulin action [22-25]. DM is divided into two major groups based on the etiopathogenesis [22]; T1DM which is due absolute insulin deficiency and T2DM, due to a combination of insulin resistance and inadequate compensatory insulin secretory responses [22]. Diabetes mellitus can be classified into four clinical cases [26] which are: Type 1: This is secondary to β cell destruction resulting in absolute insulin deficiency.

Type 2: It is due to progressive defects in insulin secretin on the background of insulin resistance.

Type 3: other specific types due to other causes e.g. due to the exocrine pancreas defects such as in cystic fibrosis or chemical induced DM e.g. in treatment of HIV.

Type 4: GDM

Pathophysiology: Insulin is a major hormone that regulates the uptake of glucose from the blood, therefore, deficiency of this hormone or the insensitivity of its receptors plays a central role in all types of DM [27]. The body normally acquires glucose from three main sources; intestinal absorption of food, breakdown of glycogen (glycolysis) and gluconeogenesis [28]. Insulin can either inhibit glycolysis or gluconeogenesis. If insulin is produced in inadequate amounts, or if the cells are resistant to the effects of insulin (that is, insulin insensitivity or insulin resistance), then blood glucose remains high [28,29]. Excess glucose will then be excreted in the urine (glycosuria) [30]. This will in turn result in increased osmotic pressure and subsequent inhibition of reabsorption of water by the kidney, resulting in polyuria and because reabsorption of water by the kidneys is minimal, this will then lead to depleted plasma volume and thus causing dehydration and resultant polydipsia [28].

Diagnosis: According to WHO [31], DM is characterized by recurrent hyperglycemia and is diagnosed by either of the following:

FPG≥7.0mmol/l (≥126mg/dl)

RPG≥11.1mmol/l (200mg/dl)

Gestational Diabetes Mellitus

Definition: Gestational diabetes mellitus is defined as any degree of glucose intolerance with onset or first recognition during pregnancy [22,24]. The American Diabetes Association defines GDM as diabetes that is diagnosed during pregnancy, but that is not overt diabetes [26]. The IADPSG has recently recommended that high risk women found to have diabetes early in pregnancy be classified as ‘overt’ not as ‘gestational’ diabetes [25]. Overt diabetes has been described by the IADPSG as pre-pregnancy diabetes that is first noted during pregnancy [25].

Pathophysiology: Insulin resistance has been identified as the hallmark of GDM and therefore, it is etiologically similar to T2DM [32]. According to Bartha Jose and colleagues, because insulinaemia has been shown to be similar between normal and GDM women, they therefore suggested that GDM is characterized by increased peripheral insulin resistance and the development of insulin resistance might be explained by the elevated triglycerides during pregnancy [15]. Based on Alan H. Decheney and colleagues, GDM and T2DM are pathogenetically related and as such, GDM is considered to be T2DM that is unmasked during pregnancy due to the metabolic changes of pregnancy [32]. GDM is secondary to reduced pancreatic β cell function and is therefore characterized by insulin concentrations that are inadequate to meet the insulin demand [23].

Diagnosis: The IADPSG recommends one step approach to diagnose GDM and the diagnosis can be made if there are one or more abnormal values of the 75g OGTT [25].

Below is the table adapted from IADPSG consensus pan [25] 

1. At first visit, assign a diagnosis of preexisting diabetes if any of the following is present
  -FPG ≥6.99mmol/l (≥126mg/dl)
  -HbA1C ≥48mmol/mol (≥6.5%)
  -RPG ≥11.1mmol/l (200mg/dl)
2.  At first visit, assign a diagnosis of GDM if present: -FPG ≥5.11mmol/l (≥92mg/dl) and ?6.99mmol/l ( ?126mg/ dl)
3. At 24-28weeks gestational age, perform 75g OGTT, 2h OGTT and assign a diagnosis of GDM if one or more of the following plasma glucose values is met or exceeded.
  -FPG ≥5.11mmol/l(≥92mg/dl) and ?6.99mmol/l ( ?126mg/ dl)
  -1h ≥9.99mmol/l (≥180mg/dl)
  -2h ≥8.49mmol/l (≥153mg/dl)

This was a prospective, case-control study among pregnant women who were admitted to Fujian Union Hospital in the department of Obstetrics and Gynecology for routine delivery between May 2014 and July 2014. The study population consisted of the patients who eligible for the study during the period. All participants were carrying singleton pregnancies. Patients with known diabetes mellitus and hypertension were excluded from the study and those with multiple pregnancies. Patients with PCOS were also excluded from the study because according to Veltman-Verhulst and colleagues [33], PCOS is associated with lower SHBG levels and these pre-conceptual levels are strongly associated with the development of GDM.

Patients were diagnosed as GDM based on the IADPSG consensus panel. The diagnosis of GDM was made during antenatal visits between 24-28 weeks gestational age. Gestational age was calculated based on the participants` last normal menstrual period and first trimester (described as the first 13 weeks) ultrasound. Maternal weight, height, blood pressure, gestational age and fetal weight were obtained from the patients’ medical records. Maternal blood samples were collected into non heparinized tubes as part of the routine work up before admission. Samples were centrifuged by the hospital’s laboratory; serum was separated and frozen at -20°C until assayed for SHBG analyses. SHBG was measured by a quantitative sandwich enzyme- linked immunoassay (ELISA) technique. The sensitivity of the SHBG was 1.0nmol/l. The kit for SHBG analysis was supplied by the Shanghai Blue Gene biotech.

Ethical Issues

The research was approved by the Fujian Union Hospital Research Ethics committee. A waiver for informed consent was approved because the participants were not subjected to any study specific investigations beyond the routine clinical care. Participants were identified by their hospital number and names were only used to retrieve the clinical file and the laboratory results.


Data analysis was performed using SPSS for Windows, version 18. Data are shown as mean±SD or median (min-max), where applicable. The mean differences between the study groups were compared by Student’s t-test. The area under the curve (AUC) and 95% confidence interval (CI) for SHBG was evaluated by receiver-operator curve (ROC) analysis. Odds ratio and 95% CI for each independent variable were also calculated. A p value less than 0.05 was considered to be statistically significant.

There were a total of 60 participants and 28 of them were in the control group and the remaining 32 were in the GDM/cases group. The mean age in all participants (n=60) was 28.35±4.38 years. However, the women in the GDM group were found to be older than the control group, 29.63±4.93years in the GDM group versus 26.89±3.14 years in the control group (Table 1). Random plasma glucose levels were found to be statistically higher in the GDM group (5.25± 1.25mmol/l) when compared to the control group (4.71±0.77mmol/l) (Table 1). SHBG concentration in the combined participants was 61.89±32.28nmol/l and in the control group, it was 71.33±30.58nmol/l while in the GDM group it was significantly lowered with a mean of 53.64±31.91nmol/l (p= 0.03). There were no significant differences in the blood pressures between the two study groups. There were no women who were underweight and twenty-two (36.67%) of the participants were in the normal BMI category whilst twenty- seven (45%) were overweight and ten (16.67%) were class 1 obese and 1.67% were class 2 obese (Table 2).The correlation between SHBG levels, RPG, BMI and fetal weight was not statistically significant in both groups (Tables 3 and 4). However, the correlation between these parameters in the GDM group was found to be a slightly positive relationship even though this failed to reach levels of significance (Table 4).The predictive accuracy of SHBG as a marker for GDM was determined by receiver operator curve (ROC) analysis (AUC: 0.677; 95% CI: 0.531-0.803; Figure 1).


There are four main findings that can be drawn from our study:

  1. Women with GDM were significantly older than the women in the control group.
  2. Random plasma glucose concentrations were elevated in the GDM group.
  3. Sex hormone binding globulin serum concentrations were lower in the GDM group
  4. There were no significant differences between the BMI in the two study groups.

 In a study by Caglar S and colleagues [34], they found that women in the GDM group were older than those in the control group. And in a different study [14], the authors also found that the females in the GDM group were older. The age differences between the study groups were also observed in this current study. The mean age of the women in the control group was 26.89±3.14 years versus the mean age of 29.63±4.93 (p=0.01). This trend has in fact been shown in various studies done on SHBG and GDM [34-38].

In a study by Nanda S et al [35], the authors conducted a study with the objective of developing a model for the prediction of GDM from maternal factors and biochemical markers at 11 to 13 weeks. They found that found that maternal age, BMI, racial origin, history of previous GDM and macrosomic infant were significant independent predictors of the development of GDM. However, they found that in screening for GDM by maternal factors only, the detection rate was ~62% (with a high false positive rate of ~20%). The detection rate increased to ~74% when they added adiponectin and SHBG. Sminakis and colleagues36 compared three biomarkers; CRP, SHBG and measures of fasting glucose and insulin (HOMA) and of the three, SHBG was found to be an optimal marker for prediction of subsequent GDM. In the Saku diabetes study [11], the authors carried out a case-control study of 215 males and 85 females with DM versus 300 matched controls. And they found that after adjustments for age, family history of DM, smoking, physical inactivity, fatty liver index (FLI) and BMI, SHBG concentrations were inversely associated with DM in women but not in men. In contrast, they found that testosterone levels were inversely associated with DM in men but not women. They concluded that low levels of SHBG in females and low levels of testosterone in males are associated with diabetes mellitus.

Various studies have shown that there is a relationship between levels of sex hormones and T2DM. In a systematic review and meta-analysis by Ding EL et al [39], they demonstrated a sexually dimorphic relationship between testosterone and risk of development of T2DM, that is, lower testosterone levels in males were associated with diabetes mellitus while increased testosterone concentrations in females correlated with increased risk for diabetes mellitus in females. The authors also observed that females with T2DM had significantly lower SHBG levels compared with the control group [39]. They found that females with serum SHBG greater than 60nmol/l had a ~80% reduction in the risk of developing T2DM in contrast to those with lower levels. Other authors have also demonstrated this relationship [9,12]

SHBG levels have been shown to be consistently lower women with GDM [11,13-15,40]. According to Kim Catherine and co-authors, once diagnosed with GDM, women seemed to progress to T2DM and this progression increased steeply within the first five years after delivery41.In this current study, SHBG levels were found to be significantly lower in the GDM group than in the control group. SHBG concentration in the control group was 71.33±30.58nmol/l while in the GDM group was 53.64±31.91nmol/l. The difference between the two means was found to be statistically significant. The mean in the GDM group was lower than 60nmol/l and as already suggested by Ding et al [39], at this concentration, the women are at a higher risk for T2DM. This has also been demonstrated by Morisset AS et al [14], the authors observed that SHBG levels were lowered in GDM patients. This trend has been demonstrated by other studies [15,34-38]. In a study which was set to examine cross sectional associations of SHBG with glucose among women with recent GDM, the authors hypothesized that SHBG levels would be associated with both the FPG and 2hours post glucose challenge, however, the results showed that at baseline, lower SHBG levels were associated with higher FPG but no significant association with the 2hours glucose [40]. In our study, there was no measurement of FPG, however, RPG was found to be higher in women with GDM (5.25±1.25 versus 4.71±0.77) and the difference between the two study groups was statistically significant. There were no observed differences in the BMIs between the two study groups in our study, however, according to Morisset AS et al [14] they found that BMI was significantly increased in the GDM group. The authors also observed that during GDM screening, BMI was a better predictor for GDM than SHBG level. Sminakis KV et al [36] also found BMI to be higher in the GDM groups. But despite this, they concluded that SHBG was a better predictor.

Table 1: Baseline parameters of the control and GDM groups.

Parameters Combined (n=60) Control group (n=28) GDM group (n=32) P values
Age ( years) 28.35±4.38 26.89±3.14 29.63±4.93 0.012?
Weight (kg) 68.14±8.51 67.14±7.04 69.02±9.64 NS
Height ( cm) 160.32±4.81 160.11±5.53 160.50±4.16 NS
BMI (kg/m2) 26.53±3.26 26.20±2.53 26.82±3.79 NS
SBP (mmHg) 120.48±10.54 120.07±9.85 120.84±11.25 NS
DBP (mmHg) 74.35±8.91 74.11±8.27 74.56±9.565 NS
RPG (mmol/l) 5.00±1.09 4.71±0.77 5.25±1.25 0.05?
SHBG (nmol/l) 61.89±32.28 71.33±30.58 53.64±31.91 0.03?
Gestational Age (weeks) 38.5±1.86 38.96±1.32 38.09±2.18 NS
Gravidity 2 (1-7) 2 (1-3) 1.5 (1-7) NS
Parity 0 (0-3) 0.5 (0-2) 0 (0-3) NS

Note: All parameters are mean ± SD except for gravidity and parity which are median (min-max); SD, Standard Deviation; NS, Not Significant; ? statistically significant

Table 2: BMI Distribution in the two groups.

BMI Distribution (kg/m2) Combined (n=60) Control group (n=28) GDM group (n=32)
Underweight 16-18.4   0   0   0
Normal 18.5-24.9  22  11  11
Overweight 25-29.9  27  13  14
Obese Class 1 30-34.9  10   4   6
Obese Class 2 35-39.9   1   0   1
Obese Class 3 ≥40   0   0   0

Table 3: Pearson correlation coefficients between SHBG concentration and BMI, RPG and fetal weight in the control group.

Parameters SHBG Concentration
BMI 0.076 (P=0.701)
RPG 0.040 (P=0.839)
Fetal Weight 0.045 (P=0.820)

Table 4: Pearson correlation coefficients between SHBG concentration and BMI, RBS, and fetal weight in the GDM group.

Parameters SHBG Concentration
BMI 0.136 (P=0.458)
RPG 0.259 (P=0.153)
Fetal Weight 0.282 (P=0.118)



In our study, although the sample size was small (n=60) and the serum measurements were done in the third trimester (mean gestational age at the time of screening was 38.50±1.86weeks), SHBG was still observed to be significantly lowered in GDM. SHBG does not exhibit diurnal variations when compared to other biomarkers of insulin resistance [42]. Because of this, SHBG is reliable in non- fasting states. SHBG seems to be a more practical and sensitive tool in clinical situations in which it is not practical to routinely collect fasting blood samples such as during antenatal care. SHBG can thus be implored in both predicting and monitoring GDM. With SHBG, more women with GDM can be identified (if testing is done in early pregnancy) and this can provide an opportunity for interventions that could improve the pregnancy outcome. However, the following recommendations need to be considered:

  1. There should be standardization of the laboratory assay for analysis of SHBG and the concentration of the plasma SHBG should be determined for a constant gestational week.
  2. If SHBG is to be used as a diagnostic tool and predictor of GDM, screening should be done in early pregnancy, preferably in the first trimester so that there is adequate time for interventions and thus preventing the adverse outcomes of GDM.
  3. If SHBG is going to be used as a monitoring tool for GDM, more research is needed to determine SHBG in the puerperium.

The authors wish to thank the following; Dr Chen Rongrong for her assistance with data collection, Mr Akeem T. Ketlogetswe for data analysis and all the personnel at the Department of Obstetrics and Gynecology in Fujian Union Hospital for their contribution. And all the women who participated in this research study.


1. Johnson LR. Essential Medical Physiology. 3rd Edition, Academic Press.

2. Guyton AC, Hall JE. Medical Physiology. 11th Edition. Elseiver Saunders.

3. Hanukoglu I. Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis. J Steroid Biochem Mol Biol. 1992; 43: 779-804.

4. Xita N, Tsatsoulis A. Genetic variants of sex hormone-binding globulin and their biological consequences. Mol Cell Endocrinol. 2010; 316: 60- 65.

5. O’Malley BW, Strott CA. Steroid hormones in reproductive endocrinology. WB Saunders, Philadelphia 3rd Edition.

6. Anderson DC. Sex-hormone-binding globulin. Clin Endocrinol (Oxf). 1974; 3: 69-96.

7. Gershagen S, Lundwall A, Fernlund P. Characterization of the human sex hormone binding globulin (SHBG) gene and demonstration of two transcripts in both liver and testis. Nucleic Acids Res. 1989; 17: 9245- 9258.

8. Pugeat M, Nader N, Hogeveen K, Raverot G, Déchaud H, Grenot C. Sex hormone-binding globulin gene expression in the liver: drugs and the metabolic syndrome. Mol Cell Endocrinol. 2010; 316: 53-59.

9. Ding EL, Song Y, Manson JE, Hunter DJ, Lee CC, Rifai N, et al. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med. 2009; 361: 1152-1163.

10. Le TN, Nestler JE, Strauss JF 3rd, Wickham EP 3rd. Sex hormone-binding globulin and type 2 diabetes mellitus. Trends Endocrinol Metab. 2012; 23: 32-40.

11. Goto A, Morita A, Goto M, Sasaki S, Miyachi M, Aiba N, Terauchi Y. Associations of sex hormone-binding globulin and testosterone with diabetes among men and women (the Saku Diabetes study): a case control study. Cardiovasc Diabetol. 2012; 11: 130.

12. Perry JR, Weedon MN, Langenberg C, Jackson AU, Lyssenko V, Sparsø T, Thorleifsson G. Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes. Hum Mol Genet. 2010; 19: 535-544.

13. Hedderson MM, Xu F, Darbinian JA, Quesenberry CP, Sridhar S, Kim C, et al. Prepregnancy SHBG concentrations and risk for subsequently developing gestational diabetes mellitus. Diabetes Care. 2014; 37: 1296-1303.

14. Morisset AS, Dubé MC, Drolet R, Robitaille J, Weisnagel SJ, Tchernof A. Sex hormone-binding globulin levels and obesity in women with gestational diabetes: relationship with infant birthweight. Gynecol Endocrinol. 2011; 27: 905-909.

15. Bartha JL, Comino-Delgado R, Romero-Carmona R, Gomez-Jaen MC. Sex hormone-binding globulin in gestational diabetes. Acta Obstet Gynecol Scand. 2000; 79: 839-845.

16. Chen C, Smothers J, Lange A, Nestler JE, Strauss III JF, Wickham III EP. Sex hormone-binding globulin genetic variation: associations with type 2 diabetes mellitus and polycystic ovary syndrome. Minerva Endocrinol. 2010; 35: 271-280.

17. Rosner W, Hryb DJ, Kahn SM, Nakhla AM, Romas NA. Interactions of sex hormone-binding globulin with target cells. Mol Cell Endocrinol. 2010; 316: 79-85.

18. Selva DM, Hogeveen KN, Innis SM, Hammond GL. Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene. J Clin Invest. 2007; 117: 3979-3987.

19. Kalyani RR, Franco M, Dobs AS, Ouyang P, Vaidya D, Bertoni A, et al. The association of endognous sex hormones, adiposity, and insulin resistance with incident diabetes in postmenopausal women. J Clin Endocrinol Metab. 2009; 94: 4127-4135.

20. Ruokonen A, Alén M, Bolton N, Vihko R. Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man. J Steroid Biochem. 1985; 23: 33-38.

21. Cangemi R, Friedmann AJ, Holloszy JO, Fontana L. Long-term effects of calorie restriction on serum sex-hormone concentrations in men. Aging Cell. 2010; 9: 236-242.

22. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2007; 30 Suppl 1:S42-S47.

23. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008; 358: 1991-2002.

24. Metzger BE, Buchanan TA, Coustan DR, de Leiva A, Dunger DB, Hadden DR, et al. Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 2007; 30 Suppl 2: S251-260.

25. International Association of Diabetes and Pregnancy Study Groups Consensus Panel, 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: 676–682.

26. American Diabetes Association. Standards of medical care in diabetes--2013. Diabetes Care. 2013; 36 Suppl 1: S11-S66.

27. American Diabetes Association. Insulin Basics. Diabetes Care. 2014.

28. Gardner DG, Shoback D. Greenspan’s Basic and Clinical Endocrinology. 9th Edition. 2011. McGraw-Hill Medical: China. Yale J Biol Med. 2012; 85: 559.

29. Barret KE, Boitano S, Barman SM, Brooks HL. Ganong’s review of medical physiology. 24th Edn. McGraw Hill Lange. 2012.

30. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell VW, Weil A.Harper’s Illustrated Biochemistry. 24th Edn. McGraw Hill Lange. 2012.

31. World Health Organization (WHO). Definition of diabetes mellitus and intermediate hyperglycemia. 2006.

32. DeCherney AH, Nathan L, LauferN, Roman AS. CURRENT Diagnosis & Treatment: Obstetrics & Gynecology.11th Edn. McGraw Hill Lange.2013.

33. Veltman-Verhulst SM, van Haeften TW, Eijkemans MJ, de Valk HW, Fauser BC, Goverde AJ. Sex hormone-binding globulin concentrations before conception as a predictor for gestational diabetes in women with polycystic ovary syndrome. Hum Reprod. 2010; 25: 3123-3128.

34. Caglar GS, Ozdemir ED, Cengiz SD, Demirta? S. Sex-hormone-binding globulin early in pregnancy for the prediction of severe gestational diabetes mellitus and related complications. J Obstet Gynaecol Res. 2012; 38: 1286-1293.

35. Nanda S, Savvidou M, Syngelaki A, Akolekar R, Nicolaides KH. Prediction of gestational diabetes mellitus by maternal factors and biomarkers at 11 to 13 weeks. Prenat Diagn. 2011; 31: 135-141.

36. Smirnakis KV, Plati A, Wolf M, Thadhani R, Ecker JL. Predicting gestational diabetes: choosing the optimal early serum marker. Am J Obstet Gynecol. 2007; 196: 410.

37. Jin Z, Chi XS, Teng WP, Wang XY, Xu QW, Wang PT, et al. [Sex hormonebinding globulin of gestational diabetes mellitus pregnant women with well-controlled glucose and pregnancy outcomes]. Zhonghua Fu Chan Ke Za Zhi. 2011; 46: 422-426.

38. Sun L, Jin Z, Teng W, Chi X, Zhang Y, Ai W, Wang P. SHBG in GDM maternal serum, placental tissues and umbilical cord serum expression changes and its significance. Diabetes Res Clin Pract. 2013; 99: 168-173.

39. Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and metaanalysis. JAMA. 2006; 295: 1288-1299.

40. Kim C, Sen A, Osborne E, Lee JM, Richardson CR. Associations between glucose tolerance and sex hormone binding globulin among women with recent gestational diabetes mellitus. Diabetes Res Clin Pract. 2011; 93: e110-112.

41. Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care. 2002; 25: 1862- 1868.

42. Hamilton-Fairley D, White D, Griffiths M, Anyaoku V, Koistinen R, Seppälä M, et al. Diurnal variation of sex hormone binding globulin and insulin-like growth factor binding protein-1 in women with polycystic ovary syndrome. Clin Endocrinol (Oxf). 1995; 43: 159-165.

Anderson SS, Zhiqun Z (2015) Sex Hormone Binding Globulin in Gestational Diabetes Mellitus. Med J Obstet Gynecol 3(2): 1057.

Received : 20 Mar 2015
Accepted : 12 Apr 2015
Published : 14 Apr 2015
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ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
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