Grand Rounds

Can We Predict Which Women with GDM Using a Genetic Risk Score Will Develop Type 2 Diabetes?

BACKGROUND AND PURPOSE:

Li et al. (BMJ Open Diabetes Research and Care, 2020) investigated the association between a genetic risk score (GRS) and the risk for women with GDM of developing type 2 diabetes (T2D) in the future

Cohort study
- 2 databases: Nurses’ Health Study II (NHSII) and the Danish National Birth Cohort (DNBC)
Participants
- Women with history of GDM
Study design
- Genetic risk score (GRS) calculated using 59 SNPs for T2D
  - These candidate SNPs for T2D were identified from genome-wide association studies in European populations
- A Healthy Eating Index (AHEI) score was derived to reflect dietary quality after the pregnancy

2,434 women with a history of GDM were included
- NHSII: 1,884 women | Average follow-up 21 years | 23.7% developed T2D
- DNBC: 550 women | Average follow-up 13 years | 28.2% developed T2D
GRS was positively associated with T2D risk in both cohorts
Relative risk (RR) for increasing quartiles of GRS (pooled analysis): 1.00, 0.97, 1.25 and 1.19 (p trend=0.02)
There was a trend for GRS scores to be more strongly associated with poorer dietary quality (AHEI <median) vs better dietary quality (AHEI >median)
- However, this interaction was not significant (p trend=0.06)

In this cohort of women who had a history of GDM, a higher GRS was associated with an increased risk of T2D
- However, association “was modest”
The study enrolled white women due to limitations of current variant databases | With increasing worldwide data, sufficient SNP data will become available for other racial and ethnic groups
Considering the small effect of the genetic score and the potentially positive impact of healthful diet (although not significant in this study), the authors that that these results support

…public health efforts of encouraging a healthful diet to prevent T2D among the high-risk population—women with a history of GDM

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