Healthy BMI diabetes patients can ‘achieve remission’ with weight loss

They said the finding should be a “wake up call” to clinicians, with “no time to be lost in getting the message across” to the one in 10 people with type 2 diabetes who had a healthy body mass index (BMI) at diagnosis.

“Weight loss by calorie restriction is powerful in achieving remission of type 2 diabetes”

Ahmad Al-Mrabeh

The researchers argued that type 2 diabetes was not caused by being obese and was instead triggered by being too heavy for your body, whatever a patient’s BMI.

They found eight out of the 12 participants in their study achieved remission after losing 10-15% of their body weight, despite having a BMI that fell in the normal weight range.

Levels of fat in the liver and pancreas fell substantially and the activity of the insulin-producing cells in the pancreas was restored, they said.

The preliminary findings from the small study, funded by Diabetes UK, were presented this week at the annual meeting of the European Association for the Study of Diabetes (EASD).

Lead investigator Professor Roy Taylor, from Newcastle University, said they clearly demonstrated that weight loss could be beneficial in type 2 diabetes, even for those of normal weight.

The findings also supported the idea that we each have a “personal fat threshold” – a level of body fat we can cope with – and if we go above it, we will develop type 2 diabetes, he suggested.

Professor Taylor said that clinicians tended to “assume” that type 2 diabetes had a different cause in those who were not overweight and they were usually started on drug treatment and insulin at a much earlier stage.

“What we’ve shown is that if those of normal weight lose 10-15% of their weight, they have a very good chance of getting rid of their diabetes,” he said in relation to the latest findings.

The Diabetes Remission Clinical Trial (DiRECT), involving Glasgow and Newcastle universities, has previously shown that an intensive weight loss programme delivered by GPs could put type 2 diabetes into remission in people who were overweight.

The latest results come from the Reversal of Type 2 Diabetes upon Normalisation of Energy Intake in the Non-obese (ReTUNE) trial, which is looking at whether weight loss can also reverse the condition in people of normal weight.

In the trial, 12 men and women with diabetes and an average BMI of 24.5 took part in a weight loss programme where they consumed 800 calories a day via low calorie soups and shakes for two weeks, followed by four to six weeks of support to maintain their new weight.

They completed up to three rounds of this dieting and maintenance cycle until they had lost 10-15% of their weight.

“These results, while preliminary, demonstrate very clearly that diabetes is not caused by obesity but by being too heavy for your own body”

Roy Taylor

Their results at the end of the study were compared to those of a group of controls without diabetes, who were matched for age, sex and BMI.

Average weight fell by 8.2kg, from 69kg to 61.8kg – a reduction of 11.9%. Total body fat fell from 33.1% to 27.4%, compared to 25.4% for the controls.

Scans showed that the average amount of fat in the liver fell from 4.4% – more than twice as high as in the controls – to 1.4%, noted the researchers.

They highlighted that fat in the pancreas fell from an average of 5.1% to 4.5% and average levels of triglycerides fell dramatically from 1.6mmol/L to 1.0mmol/L – on a par with the controls.

In 67% of patients, diabetes went into remission, a similar proportion to previous studies involving overweight and obese participants, according to the researchers.

Remission was defined as HbA1c of less than 48mmol/mol and off all diabetes medication.

Professor Taylor said: “These results, while preliminary, demonstrate very clearly that diabetes is not caused by obesity but by being too heavy for your own body. It’s due to having too much fat in your liver and pancreas, whatever your BMI.

“In the liver, this excess fat prevents insulin from working normally. In the pancreas, it causes the beta cells to stop producing insulin,” he noted.

Dr Ahmad Al-Mrabeh, the study’s first author and co-investigator, said: “Weight loss by calorie restriction is powerful in achieving remission of type 2 diabetes and it is remarkable to have 67% remission in this non-obese group.

“However, this approach is challenging for many people including those with normal BMI,” noted Dr Al-Mrabeh, who has recently moved from Newcastle University to the University of Edinburgh.

Meanwhile, speaking at the same conference and in The Lancet, researchers said weight loss of 15% or more should become a central focus of managing type 2 diabetes due to its potential to slow progress and even reverse cases.

They cited evidence of the benefits of weight loss in type 2 diabetes management comes from several sources, including the DiRECT trial.

It assessed an intensive lifestyle intervention in patients with overweight or obesity and diabetes of less than six years’ duration showed remission at two years in 70% of those who lost 15kg or more.

Studies of bariatric surgery have also shown both immediate and sustained benefits to patients with diabetes and obesity, reducing the need for glucose lowering drugs within days of surgery, the paper’s authors noted.

They also discuss the various drug treatments available for weight management. For example, five agents – orlistat, phentermine-topiramate, naltrexone-bupropion, liraglutide 3·0 mg, and semaglutide 2·4 mg – are approved by one or more regulatory authorities worldwide.

In addition, they highlighted that there were many other drugs being developed, such as tirzepatide – an agonist of receptors for both glucagon-like-peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP).

Studies of these new drugs, such as semaglutide 2·4mg and tirzepatide 15mg, have reported that 15% of bodyweight can be readily lost in more than 25% of participants with diabetes, and near normalisation of blood glucose control in most, noted the paper’s authors.

Dr Lucy Chambers, head of research communications at Diabetes UK, said: “For people living with type 2 diabetes and obesity, or overweight, losing even a small amount of weight can be life changing.

“For some, losing 10-15% of their bodyweight can mean that their type 2 diabetes goes into remission – so they no longer need to take medications to keep their blood sugars in the healthy range,” she noted.

“Diabetes UK’s landmark Counterpoint and DiRECT trials first showed that the function of the insulin-producing cells of the pancreas can be restored by weight loss and that this is key to improving health and putting type 2 into remission.”

She added: “Weight loss in these trials was achieved through a low-calorie, weight loss programme, and we know other treatments, such as bariatric surgery, can also result in type 2 remission.”