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Look AHEAD study: T2DM remission associated with lower rates of heart and kidney disease

Updated: Jan 22

Patients that took part in the Look AHEAD study and who subsequently lost weight and experienced remission in T2DM (using diet and lifestyle), had a 40% lower rate of cardiovascular disease (CVD) and 33% lower rate of chronic kidney disease (CKD).

Edward Gregg (Credit: Imperial College)

"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,” commented Professor Edward Gregg, Head of the School of Population Health, RCSI University of Medicine and Health Sciences, Dublin, Ireland. “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."

The Look AHEAD study was a multi-centre RCT that compared the effect of a 12-year intensive lifestyle intervention (ILI) with that of diabetes support and education (DSE) on CVD and other long-term health conditions. The study, carried out between 2001 and 2016, recruited and randomised 5,145 adults with overweight or obesity (BMI >25 kg/m2 for non-insulin users or BMI >27 kg/m2 for insulin users) aged 45–76 years with type 2 diabetes.

The authors conducted an observational post hoc analysis of participants in both groups, classified them based on remission status, and then compared long-term outcomes based on any remission, and the duration of remission, over a period of 12 years. They compared the incidence of CVD and CKD among more than 4,000 participants, respectively, based on achievement and duration of diabetes remission.

Participants were 58% female, and had a mean age of 59 years, a mean duration of diabetes of 6 years, and a mean BMI of 35.8 kg/m2 (in the range of severe obesity). The authors applied an epidemiological definition of remission: taking no diabetes medications and having a glycated haemoglobin (HbA1c—a measure of blood sugar control) of <48 mmol/mol (6.5%) at a single point in time.

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

Compared to participants without remission, participants with evidence of any diabetes remission during follow-up had a 33% lower rate of CKD and a 40% lower rate of CVD in analyses adjusting for HbA1c, blood pressure, blood fats, CVD history, diabetes duration and intervention arm. The magnitude of risk reduction was greatest for participants with evidence of longer-term remission.

The authors say they observed three main findings related to the implications of achieving diabetes remission. First, although 18% of participants achieved remission at some point during follow-up, the percentage of participants with current remission had decreased to 3% by the eighth year of the study, underlining the challenges of keeping weight off using lifestyle interventions.

Second, despite the relatively short-lived durations of most episodes of remission, they found that any achievement of remission was associated with 33% and 40% lower rates of CKD and CVD, respectively, compared with participants who did not achieve remission, and risk reduction was even greater (55% and 49%, respectively) among those who had evidence of at least 4 years of remission.

Third, participants with a short duration of diabetes, low starting HbA1c and a large magnitude of weight loss were most likely to experience remission. The authors conclude that the associations they found "may be explained by post-baseline improvements in weight, fitness, HbA1c and LDL (bad) cholesterol."

The findings were reported in the paper, ‘Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study’, published in Diabetologia. To access this paper, please click here


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