Remission of diabetes from weight-loss significantly reduces cardiovascular disease risk

While several trials have shown that substantial weight loss using diet and lifestyle can reverse type 2 diabetes, new research published in Diabetologia (the journal of the European Association of the Study of Diabetes [EASD]) is among the first to show the subsequent impact of remission on cardiovascular outcomes. The study is by Professor Edward Gregg, Head of the School of Population Health, RCSI University of Medicine and Health Sciences, Dublin, Ireland, and colleagues.

The new study shows that in patients that took part in the Look AHEAD study, those with any evidence of remission had a 40% lower rate of cardiovascular disease (CVD) and 33% lower rate of chronic kidney disease (CKD).

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 5145 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 (described below) 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 4000 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 hemoglobin (HbA_1c – 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.

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 HbA_1c, blood pressure, blood fats, CVD history, diabetes duration and intervention arm, compared to participants without remission. 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 8th 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 (see table 2 and figure 2 of full paper) Third, participants with a short duration of diabetes, low starting HbA_1c 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, HbA_1c and LDL (bad) cholesterol."

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. 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."

Professor Edward Gregg, Head of the School of Population Health, RCSI University of Medicine and Health Sciences, Dublin, Ireland