Associations of progression to diabetes and regression to normal glucose tolerance with development of cardiovascular and microvascular disease among people with impaired glucose tolerance: a secondary analysis of the 30 year Da Qing Diabetes Prevention Outcome Study

Abstract

Aims/hypothesis

We aimed to determine associations of regression to normal glucose tolerance (NGT), maintaining impaired glucose tolerance (IGT) or progression to diabetes with subsequent risks of CVD and microvascular disease among Chinese adults with IGT.

Methods

We conducted an observational study among 540 participants in the Da Qing Diabetes Prevention Study, a 6 year lifestyle intervention trial in people with IGT, defined by 1985 WHO criteria as fasting plasma glucose <7.8 mmol/l and 2 h post-load plasma glucose ≥7.8 and <11.1 mmol/l. At the end of the trial, the groups that had regressed to NGT, remained with IGT or progressed to diabetes were identified. Participants were then followed for 24 years after completion of the trial, during which we compared the incidence and hazard ratios for CVD and microvascular disease in each group and estimated the differences in their median time to onset from parametric Weibull distribution models.

Results

At the end of the 6 year trial, 252 (46.7%) participants had developed diabetes, 114 (21.1%) had remained with IGT and 174 (32.2%) had regressed to NGT. Compared with those who developed diabetes during the trial, the median time to onset of diabetes was delayed by 14.86 years (95% CI 12.49, 17.25) in the NGT and 9.87 years (95% CI 8.12, 11.68) in the IGT groups. After completion of the trial, among those with diabetes, IGT and NGT, the 24 year cumulative incidence of CVD was 64.5%, 48.5% and 45.1%, respectively, and 36.8%, 21.7% and 16.5% for microvascular diseases. Compared with participants who had progressed to diabetes during the trial, those who regressed to NGT had a 37% (HR 0.63; 95% CI 0.47, 0.85) reduction in CVD incidence and a median delay of 7.45 years (95% CI 1.91, 12.99) in onset, and those who remained with IGT had a 34% (HR 0.66; 95% CI 0.47, 0.91) lower CVD incidence with a median delay in onset of 5.69 years (95% CI 1.0, 10.38). Participants with NGT had a 66% (HR 0.34; 95% CI 0.20, 0.56) lower incidence of microvascular diseases and a median delay in the onset of 18.66 years (95% CI 6.08, 31.24), and those remaining with IGT had a 52% (HR 0.48; 95% CI 0.29, 0.81) lower incidence with a median delay of 12.56 years (95% CI 2.49, 22.63).

Conclusions/interpretation

People with IGT who reverted to NGT or remained with IGT at the end of the 6 year trial subsequently had significantly lower incidences of CVD and microvascular disease than those who had developed diabetes.

Graphical abstract

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

DPP:

Diabetes Prevention Program

DQDPS:

Da Qing Diabetes Prevention Study

IGT:

Impaired glucose tolerance

NGT:

Normal glucose tolerance

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Acknowledgements

We thank all the participants in the original Da Qing Diabetes Prevention Study and the Da Qing Diabetes Prevention Outcome Study. We also thank S. Li (Medical Research and Biometrics Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China) and S. Liu (Department of Global Health Management and Policy, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, USA) for their statistical assistance. We thank S. Yan (Department of Endocrinology, Harbin Fourth Hospital, Harbin, China), Y. Liu (Department of Endocrinology, 306 PLA Hospital, Beijing, China) and Y. Zhu (International Medical Department, China-Japan Friendship Hospital, Beijing, China) for their help with data collection. Special thanks are due to the late Professor Xiaoren Pan (Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China); this study would not have been possible without his leadership in the original Da Qing Diabetes Prevention Study.

Authors’ relationships and activities

The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

Funding

This study was supported from 1986 to 1992 by the World Bank, the Ministry of Public Health of the People’s Republic of China and Da Qing First Hospital; from 2004 to 2009 by CDC/WHO Cooperative Agreement No. U58/CCU424123-01-02, the China-Japan Friendship Hospital and Da Qing First Hospital; and from 2015 to 2018 by CDC/Chinese CDC Cooperative Agreement No. 5U19GH000636-05, the National Center of Cardiology, Fuwai Hospital, the China-Japan Friendship Hospital, Da Qing First Hospital and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (grant number: 2020-I2M-2-006). The sponsors had no role in any aspect of the study design; in the collection, analysis and interpretation of data; or in the development of the manuscript. The findings and conclusions in this study are those of the authors and do not necessarily represent the official positions of the Centers for Disease Control and Prevention or the National Institutes of Health.

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YC designed the study, collected data, did statistical analysis and participated in drafting and writing the report. PZ coordinated and designed the study, acquired funding, did statistical analysis and contributed to writing, preparing and editing the final report. JW, QG and YA participated in the study design, acquisition and analysis of data and revising the paper. XQ participated in the acquisition of data and drafting parts of the paper. BZ and HL participated in the acquisition of data and revising the paper. EWG designed the study, acquired funding and contributed to the statistical analysis and the writing and preparation of the report. PHB designed the study, guided the data analysis and participated in writing, preparing and editing the final report. GL designed and coordinated the study, acquired funding, collected data, did statistical analysis and participated in writing and editing the final report. All authors have approved the final version of the manuscript. GL is responsible for the integrity of the work as a whole.

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Correspondence to Guangwei Li.

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Chen, Y., Zhang, P., Wang, J. et al. Associations of progression to diabetes and regression to normal glucose tolerance with development of cardiovascular and microvascular disease among people with impaired glucose tolerance: a secondary analysis of the 30 year Da Qing Diabetes Prevention Outcome Study. Diabetologia (2021). https://doi.org/10.1007/s00125-021-05401-x

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Keywords

  • Cardiovascular disease
  • Diabetes
  • Impaired glucose tolerance
  • Microvascular disease
  • Normal glucose tolerance
  • Prevention
  • Progression
  • Regression