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Decreased Adiponectin is Associated with Gestational Diabetes in Chinese Americans

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.

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Decreased Adiponectin is Associated with Gestational Diabetes in Chinese Americans

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  1. Decreased Adiponectin is Associated with Gestational Diabetes in Chinese Americans Vanessa Sy1, So-Young Kim1, Takako Araki1, Diana Huang2, Anjit Khurana1, Emilia Liao1, Doris Tan2, George Liu1, Stephen Wan2, Leonid Poretsky1, Donna Seto-Young1 1Division of Endocrinology and Friedman Diabetes Institute, Department of Medicine; 2Department 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 (RBP4) 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

  13. Results 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)

  14. Results

  15. Results 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. Results As shown in Table 3: • In comparison to non-GDM subjects with HbA1c<5.5%, 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 isa 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, RBP4, 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

  25. References • 1) Sadikot SM, 2008 Screening of gestational diabetes mellitus: Does one size fit all? Diabetes & Metabolic Syndrome: Clinical Research Review 2:202-207 • 2) Takeuchi M, OkamotoK, Takagi T, Ishii H. 2008 Ethnic difference in patients with type 2 diabetes mellitus in inter-East Asian populations: A systematic review and meta-analysis focusing on fasting serum insulin. Diabetes Res Clin Practice 81:370-376 • 3) Liew CF, Seah ES, Yeo KP, Lee KO, Wise SD. 2003 Len, nondiabetic Asian Indians have decreased insulin sensitivity and insulin clearance • 4) Green J, Pawson I, Schumacher L. 1990 Glucose tolerance in pregnancy: ethnic variation and influence of body habitus. Am J Obste Gyneco 163:86-92 • 5) Herman WH, Dungan KM, Wolffenbuttel BHR, Buse JB, Aahrbach JL, Jiang H, Martin S. 2009. Racial and ethnic differences in mean plasma glucose, hemoglobin A1c. amd 1.5-anhydrogllucitol in over 2000 patients with type 2 diabetes. Endocrine Care 94(5):1689-1694 • 6) Kusminski CM, McTernan PG, Kumar S. Role of resistin in obesity, insulin resistance and Type II diabetes. Clinical Science (2005). 109:243-256  REVIEW ARTICLE • 7) Vendrell J, Broch M, Vilarrasa N. Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obe. Res. 2004; 12: 962-971 • 8) Schaffler A, Buchler C, Muller-Ladner U. Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus. Horm. Metab. Res. 2004; 36: 702-707 • 9) Degawa-Yamauchi M, Bovenkerk JE, Juliar BE. Serum resistin (FIZZ3) protein is icreased in obese humans. J. Clin. Endocrinol. Metab. 2003; 88: 5452-5455

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