Morbidity and mortality after lifestyle intervention for people with impaired glucose tolerance: 30-year results of the Da Qing Diabetes Prevention Outcome Study

Abstract

Background: Lifestyle interventions can delay the onset of type 2 diabetes in people with impaired glucose tolerance, but whether this leads subsequently to fewer complications or to increased longevity is uncertain. We aimed to assess the long-term effects of lifestyle interventions in people with impaired glucose tolerance on the incidence of diabetes, its complications, and mortality.

Methods: The original study was a cluster randomised trial, started in 1986, in which 33 clinics in Da Qing, China, were randomly assigned to either be a control clinic or provide one of three interventions (diet, exercise, or diet plus exercise) for 6 years for 577 adults with impaired glucose tolerance who usually receive their medical care from the clinics. Subsequently, participants were followed for up to 30 years to assess the effects of intervention on the incidence of diabetes, cardiovascular disease events, composite microvascular complications, cardiovascular disease death, all-cause mortality, and life expectancy.

Findings: Of the 577 participants, 438 were assigned to an intervention group and 138 to the control group (one refused baseline examination). After 30 years of follow-up, 540 (94%) of 576 participants were assessed for outcomes (135 in the control group, 405 in the intervention group). During the 30-year follow-up, compared with control, the combined intervention group had a median delay in diabetes onset of 3·96 years (95% CI 1·25 to 6·67; p=0·0042), fewer cardiovascular disease events (hazard ratio 0·74, 95% CI 0·59-0·92; p=0·0060), a lower incidence of microvascular complications (0·65, 0·45-0·95; p=0·025), fewer cardiovascular disease deaths (0·67, 0·48-0·94; p=0·022), fewer all-cause deaths (0·74, 0·61-0·89; p=0·0015), and an average increase in life expectancy of 1·44 years (95% CI 0·20-2·68; p=0·023).

Interpretation: Lifestyle intervention in people with impaired glucose tolerance delayed the onset of type 2 diabetes and reduced the incidence of cardiovascular events, microvascular complications, and cardiovascular and all-cause mortality, and increased life expectancy. These findings provide strong justification to continue to implement and expand the use of such interventions to curb the global epidemic of type 2 diabetes and its consequences.

Funding: US Centers for Disease Control and Prevention, WHO, Chinese Center for Disease Control and Prevention, World Bank, Ministry of Public Health of the People's Republic of China, Da Qing First Hospital, China-Japan Friendship Hospital, and National Center for Cardiovascular Diseases & Fuwai Hospital.

Figure 1:. Study profile

After the original trial ended, all participants subsequently received routine medical care from their usual clinics and providers. *In 2009, review of death certificates and medical records only; no examinations were done. †Most loss to follow-up (31 of 36) occurred between 1986 and 1992, during the trial, when some participants were relocated to a newly discovered oil field and could no longer receive intervention or follow-up at their assigned clinics in Da Qing; in 2016, data were obtained for some participants who earlier had been reported as lost to follow-up.

Figure 2:. Kaplan–Meier plots of cumulative incidence of diabetes (A), cardiovascular disease events (B), composite microvascular disease (C), cardiovascular disease deaths (D), and all-cause mortality (E) during the 30-year follow-up

Diabetes was defined by use of an oral glucose tolerance test done every 2 years during the trial (1986–92) and in 2006 or 2016 at the follow-up examinations, or from self-reported physician-diagnosed diabetes, or evidence of increased plasma glucose concentrations in the medical record or of the participant receiving glucose-lowering medications. Cardiovascular disease (CVD) events were defined as non-fatal or fatal myocardial infarction or sudden death, hospital admission for heart failure, or non-fatal or fatal stroke. Composite microvascular disease was defined as an aggregate outcome of retinopathy, nephropathy, and neuropathy. CVD deaths were defined as death due to myocardial infarction, sudden death, heart failure, or stroke. HR=hazard ratio (intervention vs control); p values derived from Cox proportional-hazards models, controlled for clinic randomisation.

Figure 3:. Forest plot of primary and secondary outcome events at 30-year follow-up

The reference category is the control group. Hazard ratios (HRs) are derived from proportional-hazards models, controlled for clinic randomisation. CVD=cardiovascular disease. CHD=coronary heart disease.