Impact of Remission From Type 2 Diabetes on Long-Term Health Outcomes
abstract
This abstract is available on the publisher's site.
Access this abstract nowAIMS/HYPOTHESIS
We examined the association of attainment of diabetes remission in the context of a 12 year intensive lifestyle intervention with subsequent incidence of chronic kidney disease (CKD) and CVD.
METHODS
The Look AHEAD study was a multi-centre RCT comparing the effect of a 12 year intensive lifestyle intervention with that of diabetes support and education on CVD and other long-term health conditions. We compared the incidence of CVD and CKD among 4402 and 4132 participants, respectively, based on achievement and duration of diabetes remission. Participants were 58% female, and had a mean age of 59 years, a duration of diabetes of 6 year and BMI of 35.8 kg/m2. We applied an epidemiological definition of remission: taking no diabetes medications and having HbA1c <48 mmol/mol (6.5%) at a single point in time. We 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 myocardial infarction, stroke, admission for angina or CVD death.
RESULTS
Participants with evidence of any remission during follow-up had a 33% lower rate of CKD (HR 0.67; 95% CI 0.52, 0.87) and a 40% lower rate of the composite CVD measure (HR 0.60; 95% CI 0.47, 0.79) in multivariate analyses adjusting for HbA1c, BP, lipid levels, CVD history, diabetes duration and intervention arm, compared with participants without remission. The magnitude of risk reduction was greatest for participants with evidence of longer-term remission.
CONCLUSIONS/INTERPRETATION
Participants with type 2 diabetes with evidence of remission had a substantially lower incidence of CKD and CVD, respectively, compared with participants who did not achieve remission. This association may be affected by post-baseline improvements in weight, fitness, HbA1c and LDL-cholesterol.
TRIAL REGISTRATION
ClinicalTrials.gov NCT00017953 DATA AVAILABILITY: https://repository.niddk.nih.gov/studies/look-ahead/.
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Additional Info
Disclosure statements are available on the authors' profiles:
Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study
Diabetologia 2024 Mar 01;67(3)459-469, EW Gregg, H Chen, MP Bancks, R Manalac, N Maruthur, M Munshi, R WingFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Remission from type 2 diabetes is a much-debated topic because, based on a number of studies, a state free of signs and symptoms of a previously diagnosed type 2 diabetes has been achieved, defined by HbA1c level <6.5 % in the absence of treatment with glucose-lowering medications for a minimum of 3 months. The Look AHEAD trial is a large clinical study comparing an intensive lifestyle management with standard care, originally with a focus on cardiovascular outcomes, a comparison that was nonsignificant for the overall population but significant for those losing more than 10 kg of weight (post hoc analysis). The present (again, post hoc) analysis compared composite endpoints representing CKD and cardiovascular events (MACE, non-fatal MI, and stroke and cardiovascular death) in Look AHEAD participants who reached the state of remission versus those who did not achieve remission (by modified criteria omitting proof of confirmation after 3 months because these data were not uniformly available). In line with the hypothesis, those achieving diabetes remission had a significantly lower risk for CKD (−37%) and MACE (−40%). Remission of longer duration was associated with larger effect sizes.
This study is among the first to demonstrate a robust health benefit associated with diabetes remission. For most participants undergoing remission, the period without fulfilling the diagnostic criteria for type 2 diabetes was relatively short. Overall, 569 out of 4488 patients (12.7 %) achieved remission, mainly of short duration, despite the very intensive program supporting weight loss and physical activity. In line with the results of the DiRECT trial, many participants agreeing to undergo an ambitious weight-loss program do not achieve diabetes remission, mainly those with a shorter known duration of diabetes and a lower baseline HbA1c. Another question arising from the present study is whether remission is necessary (the achievement of criteria delineating a category of glycaemic control indicating the absence of diabetes) or whether similar reductions in adverse outcomes can be observed in those with much improved glycaemic control, even if the achieved state falls short of a robust diagnosis of remission. According to what we know about the relationship between glycaemic control and the risk for diabetes complications (including CKD and MACE), this is a continuum without obvious thresholds that appear to be important to reach any benefit. Nevertheless, the present analysis will encourage the scientific community to further explore benefits associated with reaching type 2 diabetes remission. The low proportion of individuals benefiting from a demanding lifestyle intervention may lead to discussion of whether a less strict definition of remission (eg, achieved while on glucose- and weight-lowering medications) may help more people avoid diabetes complications.