1. Decreased Adiponectin is Associated with Gestational Diabetes in Chinese Americans Vanessa Sy 1, So-Young Kim 1, Takako Araki 1, Diana Huang 2, Anjit Khurana 1, Emilia Liao 1, Doris Tan 2, George Liu 1, Stephen Wan 2, Leonid Poretsky 1, Donna Seto-Young 1 1 Division of Endocrinology and Friedman Diabetes Institute, Department of Medicine; 2 Department of Obstetrics and Gynecology, Beth Israel Medical Center and Albert Einstein College of Medicine, New York, NY 10003

2. Introduction  Gestational diabetes mellitus (GDM) is defined as persistent hyperglycemia diagnosed during pregnancy.  GDM carries short-term and long-term risks, including pre-eclampsia, fetal macrosomia, birth trauma, metabolic complications in newborn, and subsequent development of type 2 diabetes mellitus (DM2) in the mother.  GDM is estimated to complicate 3.2 to 5% of the pregnancies; this number may be as high as 14% in certain ethnic groups (1).

3. Introduction  Previously published study in South Asian population showed that South Asians have higher lipid levels, fasting glucose, hemoglobin A1c (HbA1c), and fasting plasma insulin at a lower body mass index (BMI) (2).  Similar to South Asian Study, a different study found that at a lower BMI, Chinese Americans have (3): Higher fasting insulin level Increased chronic inflammatory markers Altered circulating adipokines

4. Introduction  Green et al. showed that the prevalence of GDM was significantly greater in Chinese women (7.3%) as compared to Caucasian women (1.6%).  Herman et al. showed that a higher percentage of Chinese population failed the 50-gram glucose challenge test (GCT) compared to Hispanic, African-American, and White Non-Hispanic women.

5. Introduction  Previously published studies showed that insulin, Insulin-like Growth Factor-1(IGF-1), leptin, C-Reactive Protein (CRP) and Retinol Binding Protein 4 (RBP 4 ) are elevated in patients with DM2 or GDM  Adiponectin levels are decreased in Caucasians with GDM  There are controversial findings regarding the biomarkers IGFBP-1, resistin, and Fibroblast Growth Factor-21 (FGF-21) in GDM  To our knowledge, there has not yet been a report that examined all of the above mentioned biomarkers in GDM subjects and compared them to non-GDM subjects in a single study of Chinese Americans.

6. Goals of the Study  To identify specific markers associated with GDM in Chinese Americans at 24-28 weeks of gestation :  Insulin  Insulin-like Growth Factor-I (IGF-I), Insulin-like Growth Factor Binding Protein-1 (IGFBP-1)  Adipocytokines: Adiponectin monomer, adiponectin multimer, Retinol Binding Protein 4 (RBP4), leptin  Inflammatory mediator C-Reactive Protein (CRP)  Atherosclerotic endothelial dysfunction factor - Resistin  Fibroblast Growth Factor-21 (FGF-21)

7. Methods Beth Israel Medical Center’s Institutional Review Broad approval was obtained for this project and all consent forms were translated into Chinese.  Inclusion Criteria: - 18 to 40 years of age - Pregnant (24-28 weeks of pregnancy) - Chinese ethnicity

8. Methods  Exclusion Criteria: Cognitive impairment Prior established diagnosis of DM2 Hepatitis B and other infectious diseases Thyroid dysfunction Thalassemia History of miscarriages Infertility with use of In-Vitro Fertilization

9. Methods  Information collected: Family history of DM2 or previous GDM Age Height Weight Blood pressure 1-hour GCT (50-gram) 3-hour GTT (100-gram) HgA1C

10. Methods  For the ELISA procedures, blood samples were drawn 1 hour after the 50- gram oral glucose challenge  Blood samples were centrifuged at 2000 rpm for 10 min, and sera were collected and stored at -80  C until ELISA was performed  ELISA kits were obtained from the American Laboratory Products Company (ALPCO, Salem, NH), and included the following: Insulin Leptin Resistin IGF-I Adiponectin (monomer) RBP4 IGFBP-1 Adiponectin (multimer) CRP FGF-21

11. Statistical Analysis Student T-test was used to compare mean values of the markers between the groups.

12. RESULTS Table I Without Gestational Diabetes N=120 With Gestational Diabetes N=16 Age 30.7  5.1032.6  4.61 BMI 24.37  2.8524.4  2.54 Systolic BP 109.38  7.83108.69  12.61 HgA 1C 5.25  0.265.33  0.47 1H OGCT (mg/dL) 113.24  18.3151.29  9.01 (p<0.001) Insulin (  U/ml)62.68  70.40133.80  102.81(p<0.018) IGF-I (ng/ml) 174.91  87.37198.26  80.14 IGFBP-I (ng/ml) 164.45  98.76162.82  101.64 Leptin (ng/ml) 19.87  10.8217.36  10.41 Adiponectin monomer (  g/ml)8.63  2.435.57  4.44(p<0.027) Adiponectin multimer (  g/ml)3.69  1.342.81  1.48(p<0.041) CRP (  g/ml)3.71  3.083.21  2.82 RBP 4 (  g/L)32.81  7.2129.44  9.45 Resistin (ng/ml) 8.10  5.017.85  3.00 FGF-21 (pg/ml) 48.63  51.434.31  21.42

13. As shown in Table 1:  In comparison to non-GDM subjects, GDM subjects had: Higher 1-hour glucose (151.29 vs. 113.24, p<0.001) Higher Insulin level (133.8 vs. 62.68, p<0.018) Lower adiponectin monomer (5.57 vs. 8.63, p<0.027) Lower adiponectin multimer (2.81 vs. 3.69, p<0.041) Results

15. As shown in Table 2:  Comparison among non-GDM subjects: In comparison to non-GDM subjects that passed 1-hr GCT, those that failed 1-hr GCT had:  Higher glucose (105.88 vs 154.50, p<0.001)  Higher levels of insulin (108.62 vs. 54.58, p<0.006)  Lower adiponectin monomer (6.83 vs. 8.94, p<0.045).

16. Results

17. As shown in Table 3: In comparison to non-GDM subjects with HbA1c 5.5% had:  Higher Systolic BP (113.5 vs. 107.7, p<0.01)  Higher HbA1c (5.75 vs. 5.08, p<0.001)  Lower adiponectin monomer (5.75 vs. 9.98, p<0.004)  Lower resistin (5.78 vs. 8.9, p<0.001).

18. Discussion  Our primary goal was to identify biochemical markers associated with GDM in Chinese Americans The patients with GDM in our study had higher glucose and insulin, and lower adiponectin monomer and multimer 11.76% of study sample had GDM (under our recruiting criteria)

19. Discussion  Compared to non-GDM subjects that passed 1-hr GCT, those who failed 1-hr GCT had: Higher glucose and insulin levels Lower adiponectin monomer levels, but normal adiponectin multimer

20. Discussion  Non-GDM: The patients who passed 1-hr GCT were subdivided into two groups: 1) HbA1c> 5.5% 2) HbA1c< 5.5% The group with HbA1C>5.5%had:  Higher HbA1c  Higher systolic BP  Lower adiponectin monomer  Normal adiponectin multimer  Lower resistin

21. Discussion  In our study, the biomarkers other than glucose, insulin and adiponectin did not show any significant differences when compared amongst non-GDM and GDM.  Resistin was low in the group with HbA1c > 5.5%. Resistin is a subject of much controversy regarding its role in DM2. Previous studies showed contradictory results. While some studies showed decreased resistin levels in patients with high insulin resistance, others reported no significant change at all. (6-9)  IGF-I, IGFBP-1, leptin, CRP, RBP 4, and FGF-21 did not show any significant difference when we subdivided the non-GDM patients in Chinese American population.  Further investigation regarding the role of these biochemical markers in insulin resistance is needed.

22. Limitation  Study was limited by: Small sample size of 16 GDM and 120 non-GDM Chinese- Americans. All study subjects were Chinese American women.

23. Conclusion  Our study of Chinese American women at 24-weeks of pregnancy revealed that insulin and both monomer and multimer of adiponectin are significantly different between the non-GDM and the GDM groups. The findings were similar to that of the Caucasian population.  Adiponectin monomer was decreased in non-GDM patients with HbA1c>5.5% and in those who failed 1-h GCT but passed 3 h GTT.

24. Acknowledgements  The Gerald J. Friedman Diabetes Institute  Chinese American Medical Society & Chinese American Independent Practice Association Research Fund  Yen Family Foundation

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