Reversion from prediabetes to normoglycemia only reduces all-cause mortality if physical activity increases

1. In a cohort of patients with prediabetes, reversion to normoglycemia did not reduce the risk of all-cause mortality or cardiovascular disease-related mortality compared to remaining prediabetic, though progression to diabetes was associated with increased all-cause mortality and cardiovascular disease-related mortality

2. Reversion to normoglycemia in addition to greater physical activity reduced the risk of mortality compared to those with persistent prediabetes and physical inactivity. 

Evidence Rating Level: 1 (Excellent)

Study Rundown: Pre-diabetes well-known to be a high-risk state for the development of type 2 diabetes mellitus (T2DM), with approximately 70% of those with pre-diabetes progressing to T2DM in their lifetime. Similar to diabetics, prediabetics are at an increased risk of developing cardiovascular disease (CVD), chronic kidney disease, cancer, dementia, and death. Previous research has not adequately addressed whether reversion to normoglycemia alters the mortality risk for prediabetics. In this large prospective cohort study, the authors used data from the prospective Taiwan MJ cohort study. They grouped participants based on changes to their diabetes status, including progression to diabetes, persistent prediabetes, and reversion to normoglycemia. Progression to diabetes was associated with an increased risk of all-cause death and CVD-related death compared to remaining pre-diabetic. Reversion to normoglycemia was not found to be associated with lower mortality risk compared to remaining pre-diabetic. Those who reverted to normoglycemia and were physically active had a lower mortality risk and longer life expectancy compared to those who remained pre-diabetic and were physically inactive. As well, BMI >28 was associated with increased risk of all-cause mortality for those who remained pre-diabetic and those who progressed to diabetes compared to prediabetics with BMI <24. The findings of this study are clinically relevant, stressing the importance of encouraging pre-diabetic patients to adopt healthy lifestyle changes, including increasing physical activity levels and reducing BMI, as this may have a greater impact on mortality risk for prediabetics compared to improving glycemic control alone.

Click here to read the study in Jama Network Open

In-Depth [Prospective cohort]: It has previously been established that those with prediabetes have greater risk of mortality, cardiovascular disease, cancer, dementia, and kidney disease compared to those with normal glycemic control. Previous research has not adequately addressed whether reversion to normoglcemia reduces the mortality risk for individuals with prediabetes. In this large prospective cohort study, the authors used data from the prospective Taiwan MJ cohort study, including 45,782 adults with prediabetes at their first clinical assessment between 1996 and 2007. Participants were followed until 2011. They were divided into three groups based on changes to their diabetes status in the first 1-3 years, including progression to diabetes (3.9%), persistent prediabetes (58.9%), and reversion to normoglycemia (37.2%).  Compared to remaining pre-diabetic, progression to T2DM was associated with an increased risk of all-cause death (HR 1.50, 95% CI 1.25-1.79) and CVD-related death (HR 1.61, 95% CI 1.12-2.33). Reversion to normoglycemia was not associated with a lower risk of all-cause death (HR 0.99, 95% CI 0.88-1.10) or CVD-related death (HR 0.97, 95% CI 0.75-1.25) compared to remaining pre-diabetic. There was no association between reversion to normoglycemia (HR 0.91, 95% CI 0.77-1.08) or progression to diabetes (HR 1.12, 95% CI 0.83-1.52) and the risk of cancer-related death. The authors also assessed the impact of lifestyle modifications on prediabetes status and risk of death. Those who were physically active were less likely to progress to T2DM (OR 0.88, 95% CI 0.78-0.99) and more likely to become normoglycemic (OR 1.05, 95% CI 1.00-1.11). Additionally, those who reverted to normoglycemia and were physically active had a lower risk of death (HR 0.72, 95% CI 0.59-0.87) and longer life expectancy (2.5 years longer, 95% CI 1.0-3.9 years) compared to those who remained pre-diabetic and were physically inactive. Obesity (BMI >28) was associated with an increased risk of all-cause mortality for those with persistent pre-diabetes (1.33, 95% CI 1.10-1.62) and those who progressed to diabetes (HR 2.01, 95% CI 1.40-2.88), compared to those who remained pre-diabetic with a BMI <24. When adjusting for confounding variables (hypertension and total cholesterol), there were no substantial differences in results of this study.

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