medwireNews: Losing at least 10% of bodyweight within 5 years of type 2 diabetes diagnosis is associated with significant improvements in glycated hemoglobin (HbA1c) levels and cardiometabolic parameters, and an increased chance of remission, study findings indicate.
However, only remission, and not weight loss, impacted the long-term risk for diabetes complications, which the researchers say highlights “the need for comprehensive diabetes care beyond weight management.”
The study, by Gian Paolo Fadini (University of Padova, Italy) and colleagues, included data for two cohorts of people with newly diagnosed type 2 diabetes. Cohort 1 included 1934 individuals followed for up to 25 years, while cohort 2 comprised 13,277 individuals followed for up to 10 years.
Together, the participants had a baseline mean age of 62 years, a mean diabetes duration of less than 2 years, mean HbA1c of 7.4–8.0% (57–64 mmol/mol), and a mean BMI of approximately 30 kg/m2. Just over half (58%) were men.
The researchers report in Diabetologia that 15.9% of participants in cohort 1 and 8.8% of those in cohort 2 achieved 10% or greater weight loss within 5 years of diagnosis.
In cohort 1, HbA1c values declined rapidly during the first year for all participants, but the decline was greater for those with more weight loss. Specifically, HbA1c fell from from 8.2% to 6.8% (66 to 51 mmol/mol) in participants with 10% or greater weight loss, and from 8.0% to 7.2% (64 to 55 mmol/mol) in those with less than 10% weight loss.
“The early divergence of HbA1c curves between the groups suggests that substantial weight loss can exert an immediate impact on glucose metabolism, possibly due to restored beta cell function, enhanced insulin sensitivity and reduced hepatic glucose output,” Fadini et al remark.
They note that the two HbA1c trajectories remained separated for at least 10 years, and the adjusted mean difference between the two weight loss groups over time was a significant 0.2 percentage points (2.1 mmol/mol).
The researchers also found that individuals with at least 10% weight loss were a significant 4.2 times more likely to achieve diabetes remission within 5 years of diagnosis than those with less than 10% weight loss when remission was defined as two consecutive HbA1c values below 6.5% (<48 mmol/mol) at least 90 days apart while off therapy. The remission rates were 20.2% and 5.5%, respectively, with a mean remission duration of 1.8 years, which did not differ significantly between the two groups.
Similar results were observed in cohort 2, with HbA1c levels an average 0.3 percentage points (2.8 mmol/mol) lower over time in the 10% or greater weight loss group than in the less than 10% group, although the HbA1c curves converged after 6 years.
Remission rates were 13.2% among the people who lost at least 10% body weight and 4.1% in those with less than 10% weight loss, corresponding to a significant 2.6-fold increased likelihood of remission in the greater weight loss arm. Median duration of remission was 1.3 years and similar in the two arms.
In both cohorts, weight loss of at least 10% was associated with significantly greater improvements in systolic blood pressure and levels of high-density lipoprotein cholesterol and triglyceride, while remission was associated with a significant reduction in the likelihood of insulin initiation.
Looking at diabetes complications in cohort 2 only, the investigators found that weight loss of 10% or more was not associated with the risk for new-onset microangiopathy or macroangiopathy, after adjustment for potential confounders.
By contrast, remission was associated with a significant 16% lower risk for microangiopathy versus no remission. There was also a trend for a lower risk for macroangiopathy with remission, but this was not statistically significant upon adjustment for confounders.
Fadini et al remark: “Considering that remission could occur even with minimal weight change, it is noteworthy that remission, more than weight loss, was necessary for long-term benefits for complications.”
They add: “We observed that body weight and HbA1c are interconnected but followed different long-term trajectories. This highlights that weight loss can influence HbA1c but may not be sufficient to sustain long-term remission, as the progressive nature of type 2 diabetes likely erodes early benefits unless additional strategies are implemented to mitigate beta cell dysfunction.”
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