Diabetes Remission of Any Duration May Reduce Risk of Renal and Cardiovascular Disease:

Remission from type 2 diabetes (T2D) of any duration after weight loss was associated with significant reductions in rates of cardiovascular disease (CVD) and chronic kidney disease (CKD), according to findings of a new post hoc analysis of data from the Look AHEAD study.¹

Look AHEAD, funded by the US National Institutes of Health, followed 5000 individuals with T2D to assess the effect of a 12-year intensive lifestyle intervention on CVD and other chronic health conditions. Among participants who achieved remission from T2D during the study, even though most episodes were “relatively short-lived” in duration, investigators reported that any time spent in remission was associated at the 1-year follow-up with a 33% lower rate of CKD and a 40% lower rate of CVD compared with Look AHEAD participants who did not achieve remission. Moreover, the decrease in risk was even more pronounced (55% and 49%, respectively) among those whose remission persisted for at least 4 years.¹

“As the first intervention study to associate remission with reduction of diabetes-related complications, this is encouraging news for those who can achieve remission from type 2 diabetes,” said Edward Gregg, PhD, head of the School of Population Health, RCSI University of Medicine and Health Sciences, in a university statement.²

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Launched in 2001, the multicenter, randomized Look AHEAD clinical trial was conducted at 16 US sites and was described by Gregg and colleagues as “the largest and longest trial of intensive weight loss ever conducted.”¹ The trial compared the long-term effects of an intensive lifestyle intervention with those of diabetes support and education (DSE) in participants with T2D and with overweight or obesity. While participants in the intervention group did reach weight loss goals, researchers reported no difference in CV events between the 2 groups. Participants in the lifestyle intervention/weight loss group, however, did reap other cardiometabolic health benefits, including improved blood pressure levels, blood glucose levels, and serum cholesterol levels.

Unique opportunity

Look AHEAD, Gregg et al explained in Diabetologia, provided a unique research opportunity. The post hoc analysis examined whether T2D remission in the setting of the lifestyle intervention trial reduced incidence of T2D-related CKD and CVD. They compared the incidence of CVD and CKD among 4402 and 4132 participants, respectively, based on reaching and the duration of T2D remission.

The team defined high-risk or very high-risk CKD based on the Kidney Disease Improving Global Outcomes criteria, and CVD incidence as any occurrence of non-fatal acute heart attack, stroke, admission for angina or CVD death.¹

From the original cohort of 5145 participants (aged 45-76 years) who were randomized in the original Look AHEAD study, 4488 (mean age 59 years, 58% women) qualified for inclusion in the current analysis.¹

FINDINGS¹

Among these participants, 12.7% met the definition for T2D remission for at least 1 follow-up visit. Slightly more than 10% (11.2%) of participants in the intensive lifestyle intervention group achieved remission at year 1, which declined approximately 0.7 percentage points every year after that. In contrast, prevalence of remission among those in the DSE group was approximately 2% at year 1 and remained in this range through the duration of the trial. At year 12, the prevalence of remission was approximately twice as high in the lifestyle intervention groups vs the DSE group, at 3.7% and 1.95%, respectively.

In multivariable analysis, adjusted for HbA1c, blood pressure, lipid levels, CVD history, T2D duration, and intervention arm, Gregg and colleagues, as noted above, reported the 33% lower rated of CKD (HR, 0.67; 95% CI, 0.52-0.87) and 40% lower rate of CVD (HR, 0.60; 95% CI, 0.47-0.79) among those with any evidence of diabetes remission compared with participants without remission.

The benefits of achieving remission were amplified following analysis that found participants who remained in remission from T2D for at least 4 years achieved significantly greater reduction in risk for both CKD (HR, 0.45; 95% CI, 0.25-0.82) and CVD (HR, 0.51; 95% CI, 0.30-0.89) vs those without remission.¹

“While our study is also a reminder that maintenance of weight loss and remission is difficult, our findings suggests any success with remission is associated with later health benefits.”²

References:

1. Gregg EW, Chen H, Bancks MP, et al. Impact of remission from type 2 diabetes on long‑term health outcomes: findings from the Look AHEAD study. Diabetologia. Published online January 18, 2024. doi:10.1007/s00125-023-06048-6

2. New study is one of first to show people with evidence of any remission of diabetes from weight-loss trial had a 40% lower rate of cardiovascular disease and 33% lower rate of chronic kidney disease. News release. Royal College of Medicine and Health Sciences. January 18, 2024. Accessed January 22, 2024. https://www.rcsi.com/dublin/news-and-events/news/news-article/2024/01/rcsi-research-shows-new-benefits-of-weight-loss-for-type-2-diabetes

3. Long-term lifestyle change for type 2 diabetes and obesity study: Look AHEAD. Obesity. National Institute of Diabetes and Digestive and Kidney Diseases. Accessed January 18, 2024. https://www.niddk.nih.gov/about-niddk/research-areas/obesity/long-term-lifestyle-change-type-2-diabetes-obesity-study