DiRECT: Beta cells ‘not dead’ in type 2 diabetes
medwireNews: People who achieved sustained remission of type 2 diabetes via substantial weight loss in the DiRECT trial regained normal maximal beta-cell capacity, the investigators report.
“It has been believed that by time of diagnosis people have already lost 50% of beta cells,” Roy Taylor (Newcastle University, UK) told the press at the 79th ADA Scientific Sessions in San Francisco, California, USA. “And it goes downhill from there.”
In line with this, when beta-cell function was measured at baseline in a subgroup of 56 DiRECT trial participants, they had an absent first-phase insulin response (to a glucose bolus from a fasting state) and a much reduced maximal response (to additional glucose plus arginine) compared with matched people without diabetes. At this point they had an average diabetes duration of about 3 to 4 years.
As previously reported, 36% of the total 149 people assigned to undertake a very-low-calorie total meal replacement intervention achieved remission (glycated hemoglobin <6.5% [48 mmol/mol] without medication) and maintained it for 2 years. The likelihood of this was linked to the amount of weight lost, ranging from 5% of people who lost less than 5 kg to 70% of those who lost more than 15 kg.
When beta-cell function was re-assessed in the subgroup at 5 months, the first-phase insulin response had significantly improved in the 38 responders (people who had remission of diabetes at 12 months) but not in the 18 nonresponders, although it remained significantly reduced compared with control levels. This remained the situation at the 12- and 24-month assessments.
The maximal beta-cell capacity took longer to recover, but by 12 months it had improved in responders (but not nonresponders) to a level that was not significantly below that of controls.
“These beta cells are not dead,” said Taylor. “Rumors of their death have been much exaggerated!”
Explaining the likely underlying processes, he referred to the work of Domenico Accili’s group, at Columbia University in New York, USA, suggesting that beta cells dedifferentiate in people with type 2 diabetes. In other words, said Taylor, “they’ve gone into a survival mode under the metabolic stress” of excessive nutrition.
“By taking that stress away, we see the cell able to reconstitute its specialist function,” he said.
The Chair of the news briefing, Alvin Powers (Vanderbilt University Medical Center, Nashville, Tennessee, USA), noted that it is not clear whether the measurements reported by Taylor represent a return to pre-diabetic numbers of beta cells or a reduced number of beta cells with an enhanced performance.
However, Taylor stressed: “There’s a clinical bottom line here, which is quite important: if people lose 10 kg and keep it off for 2 years, there is a two-thirds chance of them escaping from type 2 diabetes.”
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