People with type 2 diabetes who go into remission for any length of time have lower rates of chronic kidney disease and cardiovascular disease, according to a new study.
The research published this week in the journal Diabetologia reports that people who experienced remission had a 40% lower rate of cardiovascular disease and a 33% lower rate of chronic kidney disease compared with those who lost weight but did not experience remission from type 2 diabetes.
“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,” Edward Gregg, PhD, a co-author of the study and a professor in the School of Population Health at the RCSI University of Medicine and Health Sciences in Dublin, Ireland, said in a press statement.
“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,” he added.
What is diabetes remission?
Remission from type 2 diabetes is considered attainable by many patients. Although diabetes remission is typically associated with bariatric surgery, lifestyle interventions have also been effective in achieving remission from prediabetes and diabetes.
Diabetes remission following bariatric surgery can lead to chronic kidney disease (CKD) and cardiovascular disease (CVD). Nevertheless, bariatric surgery results in longer and greater glucose normalization than remission through lifestyle interventions.
To date, no studies have assessed the impact of lifestyle-based remission from diabetes on long-term outcomes.
What does the research suggest?
Very few patients with type 2 diabetes (T2D) achieve and sustain diabetes remission via weight loss alone, new research suggests.
Among more than 37,000 people with T2D in Hong Kong, only 6% had achieved and sustained diabetes remission solely through weight loss up to 8 years after diagnosis. Among those who initially achieved remission, 67% had hyperglycemia at 3 years.
People who lost the most weight (10% of their body weight or more) in the first year after diagnosis were most likely to have sustained remission.
The study was published on January 23, 2024, in PLOS Medicine.
Early Weight Management Works
Recent clinical trials have demonstrated that T2D remission can be achieved following sustained weight loss through bariatric surgery or lifestyle interventions, the authors noted. In this study, they investigated the association of weight change at 1 year after a diabetes diagnosis with the long-term incidence and sustainability of T2D remission in real-world settings, using data from the territory-wide Risk Assessment and Management Programme-Diabetes Mellitus (RAMP-DM).
Weight loss may not be enough to sustain Type 2 Diabetes remission
A total of 37,326 people with newly diagnosed T2D who were enrolled in the RAMP-DM between 2000 and 2017 were included and followed until 2019.
At baseline, participants’ mean age was 56.6 years, mean body mass index (BMI) was 26.4 kg/m2, and mean A1c was 7.7%, and 65% were using glucose-lowering drugs (GLDs).
T2D remission was defined as two consecutive A1c < 6.5% measurements at least 6 months apart without GLDs currently or in the previous 3 months.
During a median follow-up of 7.9 years, 6.1% of people achieved remission, with an incidence rate of 7.8 per 1000 person-years. The proportion was higher among those with greater weight loss: 14.4% of people who lost 10% of their body weight or more achieved remission compared with 9.9% of those with 5%-9.9% weight loss, 6.5% of those with 0%-4.9% weight loss, and 4.5% of those who gained weight.
After adjustment for age at diagnosis, sex, assessment year, BMI, other metabolic indices, smoking, alcohol drinking, and medication use, the hazard ratio (HR) for diabetes remission was 3.28 for those with 10% or greater weight loss within 1 year of diagnosis, 2.29 for 5%-9.9% weight loss, and 1.34 for 0%-4.9% weight loss compared to weight gain.
The incidence of diabetes remission in the study was significantly lower than that in clinical trials, possibly because trial participants were in structured programs that included intensive lifestyle interventions, regular monitoring and feedback, and reinforcement of a holistic approach to managing diabetes, the authors noted. Real-world settings may or may not include such interventions.
Further analyses showed that within a median follow-up of 3.1 years, 67.2% of people who had achieved diabetes remission returned to hyperglycemia — an incidence rate of 184.8 per 1000 person-years.
The adjusted HR for returning to hyperglycemia was 0.52 for people with 10% or greater weight loss, 0.78 for those with 5%-9.9% weight loss, and 0.90 for those with 0%-4.9% weight loss compared to people with weight gain.
In addition, diabetes remission was associated with a 31% (HR, 0.69) decreased risk for all-cause mortality.
The study “provides evidence for policymakers to design and implement early weight management interventions” for people diagnosed with T2D, the authors concluded.
Clinicians also have a role to play, Luk said. “At the first encounter with an individual with newly diagnosed T2D, clinicians should emphasize the importance of weight reduction and guide the individual on how this can be achieved through making healthy lifestyle choices. Pharmacotherapy and metabolic surgery for weight management can be considered in appropriate individuals.”
Overall, she added, “clinicians should be informed that the likelihood of achieving and maintaining diabetes remission is low, and patients should be counseled accordingly.”
Study findings
Overall, 4,448 participants from the Look AHEAD study were retained in this analysis after excluding those with insufficient follow-up data, bariatric surgery, and remission at baseline. About 12.7% of participants met the definition of remission for at least one follow-up visit. Remission prevalence was 11.2% in the first year for the ILI group and declined by 0.7 percentage points every year.
By contrast, remission prevalence was about 2% yearly in the DSE group. Remission status and duration were significantly associated with baseline disease duration, medication use, and fasting plasma glucose, HbA 1c, and systolic blood pressure levels. Individuals who attained remission were highly likely to have used medications at baseline.
Individuals with remission for two or more follow-up visits were less likely to have CVD. Furthermore, longer remission periods were associated with shorter diabetes durations.
Remission was associated with changes in risk factors and weight over four years. The average weight loss was four kilograms after one year and 2.2 kg after four years for individuals without remission. By contrast, average weight loss was 12.3 kg and 9.6 kg after one and four years, respectively, for subjects with remission for at least four visits.
Participants who achieved remission exhibited greater improvements in fitness and high-density lipoprotein (HDL)-cholesterol levels after one and four years than those without remission. However, individuals with remission had smaller reductions in low-density lipoprotein (LDL)-cholesterol. Participants with remission had a 40% and 33% reduced rate of CVD and CKD, respectively, as compared to those without remission.
In analyses with the DSE group as the reference, ILI subjects with remission had a 23% reduced rate of CVD and 40% lower rate of CKD. In analyses stratified by randomization, remission was associated with a 68% reduction in CVD but not CKD in the DSE group, whereas the LIL group was associated with a 34% decrease in CKD but not CVD.
Conclusions
About 11% of study participants achieved remission by the first year, which was reduced to 4% by the eighth year. Despite the short-lived remission period, remission was associated with 40% and 33% lower CVD and CKD rates than in participants without remission, respectively.
Individuals with a shorter diabetes period, greater weight loss, or low baseline HbA 1c were most likely to achieve remission. The magnitude of risk reduction was highest for those with longer-term remission.
References:
- Gregg, E. W., Chen, H., Bancks, M. P., et al. (2024). Impact of remission from type 2 diabetes on long-term health outcomes: findings from the Look AHEAD study. Diabetologia. doi:10.1007/s00125-023-06048-6
- Wu H, Yang A, Lau ESH, Zhang X, Fan B, Ma RCW, et al. (2024) 1-year weight change after diabetes diagnosis and long-term incidence and sustainability of remission of type 2 diabetes in real-world settings in Hong Kong: An observational cohort study. PLoS Med 21(1): e1004327. doi:10.1371/journal.pmed.1004327