Remaining Free of Diabetes for at Least 4 Years Improves Long-Term Health in Persons with Impaired Glucose Tolerance

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Individuals who remained diabetes-free for at least 4 years through lifestyle intervention after an initial diagnosis of impaired glucose tolerance (IGT) had a significantly lower risk of long-term death and macro- and microvascular complications compared to those who progressed to diabetes, according to new findings published in PLOS Medicine.

In the post hoc analysis of the Da Qing Diabetes Prevention Study (DQDPS)—a 6-year lifestyle intervention trial in individuals with IGT—researchers reported that the long-term risk of all-cause death decreased by 26% in persons who remained diabetes-free for 4 years (HR 0.74, 95% CI 0.57-0.97; P = .026) after they adjusted for age, sex, smoking status, body mass index (BMI) blood pressure, total cholesterol levels, blood glucose, medications, and intervention. The risk for macro- and microvascular complications decreased by 40% in these participants after adjusting for the same confounders (HR 0.63, 95% CI 0.49-0.82; P < .001; HR 0.62, 95% CI 0.45-0.86; P = .004, respectively).

In addition, investigators found that at the end of 6 years, the risk of cardiovascular death decreased by 44% among persons in the non-diabetes group after adjusting for confounders (HR 0.56, 95% CI 0.39-0.81; P = .002).

These results suggest that “taking action, including but not limited to lifestyle intervention, to prolong the diabetes-free time in people with prediabetes may be crucial,” corresponding author Guangwei Li, of the China-Japan Friendship Hospital, and colleagues wrote in the study published online July 9, 2024.

According to researchers, lifestyle interventions, such as diet and exercise, can decrease or delay the incidence of diabetes in persons with IGT. Major clinical trials, including DQDPS, have shown that lifestyle intervention can improve microvascular complications and cardiovascular risk factors. However, it is unclear how long individuals with IGT must delay diabetes to ensure better long-term health.

“To our knowledge, this is the first study that investigates the association between the diabetes-free years after diagnosis of IGT and the risk of long-term death and cardiovascular outcomes,” investigators stated.

The post hoc analysis included 540 participants from the original DQDPS, which was started in 1986 in Qa Qing City, China. All participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to a control group or 1 of 3 lifestyle intervention groups that involved diet, physical activity, or both. Death, cardiovascular events (eg, stroke, coronary heart disease), and microvascular complications were monitored over a 30-year follow-up.

The researchers found that results for participants in the original lifestyle intervention group were similar to those of the full study cohort. Hazard ratios, ie, non-diabetes vs diabetes, for all of the outcomes at the end of 2-, 4- and 6-years in the former were lower than those observed in the latter. Although they can’t identify the underlying mechanism, Li et al suggest that the “difference in long-term diabetes status transformation between individuals with or without intervention may be involved. To some degree, the intervention-induced longer maintenance of non-diabetes status may contribute to the association with the risk reduction,” they wrote.

The authors acknowledged the main limitations of the post hoc analysis, pointing to the small number of participants, the fact that it was conducted solely in a Chinese population, and the potential influence of other unmeasured confounders on the observed association.

Despite these, however, Li and colleagues concluded, that “the implementation of effective interventions targeting those with IGT should be considered as part of preventative management for diabetes and diabetes-related vascular complications.”

Reference: Qian X, Wang J, Gong Q, et al. Non-diabetes status after diagnosis of impaired glucose tolerance and risk of long-term death and vascular complications: A post hoc analysis of the Da Qing Diabetes Prevention Outcome Study. PLoS Med. Published online July 9, 2024. doi:10.1371/journal.pmed.1004419