Modifiable risk factors and long term risk of type 2 diabetes among individuals with a history of gestational diabetes mellitus: prospective cohort study

Jiaxi Yang; Frank Qian; Jorge E Chavarro; Sylvia H Ley; Deirdre K Tobias; Edwina Yeung; Stefanie N Hinkle; Wei Bao; Mengying Li; Aiyi Liu; James L Mills; Qi Sun; Walter C Willett; Frank B Hu; Cuilin Zhang

doi:10.1136/bmj-2022-070312

Modifiable risk factors and long term risk of type 2 diabetes among individuals with a history of gestational diabetes mellitus: prospective cohort study

BMJ. 2022 Sep 21:378:e070312. doi: 10.1136/bmj-2022-070312.

Authors

Jiaxi Yang^{1

2

3

4}, Frank Qian^{5

6}, Jorge E Chavarro^{4

5

7}, Sylvia H Ley⁸, Deirdre K Tobias^{5

9}, Edwina Yeung¹⁰, Stefanie N Hinkle¹¹, Wei Bao¹², Mengying Li¹⁰, Aiyi Liu¹³, James L Mills¹⁰, Qi Sun^{5

7}, Walter C Willett^{4

5

9}, Frank B Hu^{5

7

9}, Cuilin Zhang^{14

2

3

10}

Affiliations

¹ Global Centre for Asian Women's Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
² Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
³ Bia-Echo Asia Centre for Reproductive Longevity and Equality, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁴ Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
⁵ Department of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
⁶ Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
⁷ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
⁹ Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹⁰ Epidemiology Branch, Division of Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, USA.
¹¹ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
¹² Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
¹³ Biostatistics & Bioinformatics Branch, Division of Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD, USA.
¹⁴ Global Centre for Asian Women's Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore obgzc@nus.edu.sg.

Abstract

Objectives: To evaluate the individual and combined associations of five modifiable risk factors with risk of type 2 diabetes among women with a history of gestational diabetes mellitus and examine whether these associations differ by obesity and genetic predisposition to type 2 diabetes.

Design: Prospective cohort study.

Setting: Nurses' Health Study II, US.

Participants: 4275 women with a history of gestational diabetes mellitus, with repeated measurements of weight and lifestyle factors and followed up between 1991 and 2009.

Main outcome measure: Self-reported, clinically diagnosed type 2 diabetes. Five modifiable risk factors were assessed, including not being overweight or obese (body mass index <25.0), high quality diet (top two fifthsof the modified Alternate Healthy Eating Index), regular exercise (≥150 min/week of moderate intensity or ≥75 min/week of vigorous intensity), moderate alcohol consumption (5.0-14.9 g/day), and no current smoking. Genetic susceptibility for type 2 diabetes was characterised by a genetic risk score based on 59 single nucleotide polymorphisms associated with type 2 diabetes in a subset of participants (n=1372).

Results: Over a median 27.9 years of follow-up, 924 women developed type 2 diabetes. Compared with participants who did not have optimal levels of any of the risk factors for the development of type 2 diabetes, those who had optimal levels of all five factors had >90% lower risk of the disorder. Hazard ratios of type 2 diabetes for those with one, two, three, four, and five optimal levels of modifiable factors compared with none was 0.94 (95% confidence interval 0.59 to 1.49), 0.61 (0.38 to 0.96), 0.32 (0.20 to 0.51), 0.15 (0.09 to 0.26), and 0.08 (0.03 to 0.23), respectively (P_trend<0.001). The inverse association of the number of optimal modifiable factors with risk of type 2 diabetes was seen even in participants who were overweight/obese or with higher genetic susceptibility (P_trend<0.001). Among women with body mass index ≥25 (n=2227), the hazard ratio for achieving optimal levels of all the other four risk factors was 0.40 (95% confidence interval 0.18 to 0.91). Among women with higher genetic susceptibility, the hazard ratio of developing type 2 diabetes for having four optimal factors was 0.11 (0.04 to 0.29); in the group with optimal levels of all five factors, no type 2 diabetes events were observed.

Conclusions: Among women with a history of gestational diabetes mellitus, each additional optimal modifiable factor was associated with an incrementally lower risk of type 2 diabetes. These associations were seen even among individuals who were overweight/obese or were at greater genetic susceptibility.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Body Mass Index
Diabetes Mellitus, Type 2* / etiology
Diabetes Mellitus, Type 2* / genetics
Diabetes, Gestational* / epidemiology
Diabetes, Gestational* / etiology
Female
Genetic Predisposition to Disease
Humans
Obesity / complications
Obesity / epidemiology
Overweight / complications
Overweight / epidemiology
Pregnancy
Prospective Studies
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding