Prediction of type 2 diabetes in women with a history of gestational diabetes using a genetic risk score.
OBJECTIVE
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
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.
Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-Ro, Chongno-Gu, Seoul, 110-744, South Korea.
Soo Heon
SH
Kwak
Sung Hee
SH
Choi
Kyunga
K
Kim
Hye Seung
HS
Jung
Young Min
YM
Cho
Soo
S
Lim
Nam H
NH
Cho
Seong Yeon
SY
Kim
Kyong Soo
KS
Park
Hak C
HC
Jang
D000328:Adult; D002839:Chromans / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D016640:Diabetes, Gestational / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D049590:Postpartum Period; D011237:Predictive Value of Tests; D011247:Pregnancy; D011446:Prospective Studies; D056910:Republic of Korea / Q000453:epidemiology; D018570:Risk Assessment; D012307:Risk Factors; D040242:Risk Reduction Behavior; D045162:Thiazolidinediones / Q000627:therapeutic use; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin; D000077288:Troglitazone