medwireNews: The findings of the ReTUNE study show that losing a substantial amount of weight can reverse type 2 diabetes even in people who are only mildly overweight.
“Regardless of body mass index, people who are diagnosed with type 2 diabetes simply have more fat inside the body than they are able to cope with,” said Alison Barnes (Newcastle University, UK), who presented the findings at the 58th EASD Annual Meeting in Stockholm, Sweden.
This makes weight loss “a valid therapeutic option” for people with relatively low BMIs, she added.
ReTUNE recruited people with type 2 diabetes who had a BMI of 21–27 kg/m2, with the average being 24.8 kg/m2. By contrast, in the DiRECT trial, which definitively showed that type 2 diabetes can be reversed with diet-induced weight loss, the average BMI was approximately 35 kg/m2.
As in DiRECT, the ReTUNE participants had a diabetes duration of less than 6 years (average 2.8 years). The researchers initially recruited 24 participants, but two proved to have type 1 diabetes and two maturity-onset diabetes of the young (MODY), leaving 20 people – 13 women and seven men.
The participants undertook 2–3 weeks of consuming just 800 kcal/day in the form of meal replacements and vegetables, aiming to lose 5% of their starting bodyweight, followed by 5–6 weeks of weight loss maintenance, with this cycle repeated up to three times.
This led to remission of type 2 diabetes in 14 (70%) of the participants, with glycated hemoglobin falling significantly from an average of 54 to 46 mmol/mol (7.1 to 6.4%), with only eight of them requiring all three weight loss cycles.
Bodyweight fell from an average of 71.8 to 64.1 kg and BMI from 24.8 to 22.4 kg/m2 over 12 months of follow-up.
Average body fat across the whole cohort fell from 32.1% to 27.6%, which was within the range of 20 controls matched for age, sex, and BMI after weight loss, but Barnes noted that normalization was only actually achieved in male participants.
Waist circumference significantly reduced, from an average of 90.0 to 79.7 cm, again normalizing in men but not women, and liver fat also decreased, from 4.1% to 1.5%, with the majority of the increase occurring after the first cycle of weight loss.
Barnes noted that the level of baseline liver fat “doesn’t appear elevated if we think of what would be considered a normal liver fat content,” but stressed that it was 2.5 times the level in the controls, similar to the increase found in people with higher BMIs.
Liver fat drives the production of very-low-density-lipoprotein triglycerides, and levels of these decreased in line with the reduction in liver fat. The presented observed that this was reflected in a decline in the levels of total triglycerides, which are easier to measure in clinical practice.
There was “a moderate but significant decrease” in pancreas fat, with levels gradually declining from an average of 5.8% to 4.3%, in line with the team’s previous experience that this is slower to decrease than liver fat in people losing weight.
In magnetic resonance imaging scans, participants’ visceral fat remained “markedly elevated” compared with matched controls, despite diabetes remission.
Barnes stressed that these results in relatively lean people with type 2 diabetes are in line with those in people with higher BMIs, which “permits a frame shift” in how clinicians can think about type 2 diabetes.
In the UK, she said, around 15% of people diagnosed with type 2 diabetes have a BMI within the range of the ReTUNE participants, and while “they may seem small numbers in individual practices […] that’s not an insignificant number of people, who largely don’t know why they’ve developed type 2 diabetes or what they can do about it.”
But the presenter stressed the importance of thorough screening for type 1 diabetes and MODY in this relatively lean population.
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