Diabetologia

, Volume 56, Issue 12, pp 2556–2563

Prediction of type 2 diabetes in women with a history of gestational diabetes using a genetic risk score

  • Soo Heon Kwak
  • Sung Hee Choi
  • Kyunga Kim
  • Hye Seung Jung
  • Young Min Cho
  • Soo Lim
  • Nam H. Cho
  • Seong Yeon Kim
  • Kyong Soo Park
  • Hak C. Jang
Article

DOI: 10.1007/s00125-013-3059-x

Cite this article as:
Kwak, S.H., Choi, S.H., Kim, K. et al. Diabetologia (2013) 56: 2556. doi:10.1007/s00125-013-3059-x

Abstract

Aims/hypothesis

Women with a history of gestational diabetes mellitus (GDM) are at increased risk of future development of type 2 diabetes. Recently, over 65 genetic variants have been confirmed to be associated with diabetes. We investigated whether this genetic information could improve the prediction of future diabetes in women with GDM.

Methods

This was a prospective cohort study consisting of 395 women with GDM who were followed annually with an OGTT. A weighted genetic risk score (wGRS), consisting of 48 variants, was assessed for improving discrimination (C statistic) and risk reclassification (continuous net reclassification improvement [NRI] index) when added to clinical risk factors.

Results

Among the 395 women with GDM, 116 (29.4%) developed diabetes during a median follow-up period of 45 months. Women with GDM who went on to develop diabetes had a significantly higher wGRS than those who did not (9.36 ± 0.92 vs 8.78 ± 1.07; p < 1.56 × 10−7). In a complex clinical model adjusted for age, prepregnancy BMI, family history of diabetes, blood pressure, fasting glucose and fasting insulin concentration, the C statistic marginally improved from 0.741 without the wGRS to 0.775 with the wGRS (p = 0.015). The addition of the wGRS to the clinical model resulted in a modest improvement in reclassification (continuous NRI 0.430 [95% CI 0.218, 0.642]; p = 7.0 × 10−5).

Conclusions/interpretation

In women with GDM, who are at high risk of diabetes, the wGRS was significantly associated with the future development of diabetes. Furthermore, it improved prediction over clinical risk factors.

Keywords

Genetic risk scoreGestational diabetesRisk predictionType 2 diabetes

Abbreviations

GDM

Gestational diabetes mellitus

GRS

Genetic risk score

GWA

Genome-wide association

IGT

Impaired glucose tolerance

IQR

Interquartile range

IR

Insulin resistance

IS

Insulin secretion

NGT

Normal glucose tolerance

NRI

Net reclassification improvement

SNP

Single nucleotide polymorphism

uGRS

Unweighted genetic risk score

wGRS

Weighted genetic risk score

Supplementary material

125_2013_3059_MOESM1_ESM.pdf (170 kb)
ESM Table 1(PDF 170 kb)
125_2013_3059_MOESM2_ESM.pdf (127 kb)
ESM Table 2(PDF 126 kb)
125_2013_3059_MOESM3_ESM.pdf (116 kb)
ESM Table 3(PDF 116 kb)
125_2013_3059_MOESM4_ESM.pdf (117 kb)
ESM Table 4(PDF 117 kb)
125_2013_3059_MOESM5_ESM.pdf (28 kb)
ESM Fig. 1(PDF 27 kb)
125_2013_3059_MOESM6_ESM.pdf (30 kb)
ESM Fig. 2(PDF 30 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Soo Heon Kwak
    • 1
  • Sung Hee Choi
    • 2
    • 3
  • Kyunga Kim
    • 4
  • Hye Seung Jung
    • 1
  • Young Min Cho
    • 1
    • 2
  • Soo Lim
    • 3
  • Nam H. Cho
    • 5
  • Seong Yeon Kim
    • 1
    • 2
  • Kyong Soo Park
    • 1
    • 2
    • 6
  • Hak C. Jang
    • 2
    • 3
  1. 1.Department of Internal MedicineSeoul National University HospitalSeoulSouth Korea
  2. 2.Department of Internal MedicineSeoul National University College of MedicineSeoulSouth Korea
  3. 3.Department of Internal MedicineSeoul National University Bundang HospitalSeongnam-SiSouth Korea
  4. 4.Department of StatisticsSookmyung Women’s UniversitySeoulSouth Korea
  5. 5.Department of Preventive MedicineAjou University School of MedicineSuwonSouth Korea
  6. 6.World Class University Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and TechnologySeoul National UniversitySeoulSouth Korea