Pancreatic morphology normalizes with sustained type 2 diabetes remission
medwireNews: Sustained remission of type 2 diabetes in DiRECT was accompanied by normalization of pancreatic morphology, say the researchers.
“[O]ur results suggest that the small, irregular pancreas typical of type 2 diabetes is secondary to the disease state itself and returns towards normal during 2 years of dietary weight loss-induced remission,” write Ahmad Al-Mrabeh (Newcastle University, UK) and colleagues.
This post-hoc analysis included 90 DiRECT participants who underwent magnetic resonance imaging of the pancreas at baseline. At this point, their average pancreas volume was 61.7 cm3, significantly lower than the average 79.8 cm3 observed in 25 people without diabetes. They also had a significantly more irregular pancreatic border, with an average fractal dimension of 1.138 versus 1.097.
Sixty-four of the participants were randomly assigned to undergo the study intervention of a very-low-calorie total meal replacement diet, followed by phased food reintroduction; 55 of these were reassessed after 5 months, at which point 39 had glycated hemoglobin levels below 6.5% (48 mmol/mol) with no glucose-lowering medications required, and were classed as responders. This remained true for 32 of the 46 people scanned at 12 months and 32 of the 45 assessed at 24 months.
At 5 months, pancreatic volume did not differ between responders, nonresponders, and people with diabetes who had continued to receive usual care (controls), the team reports in The Lancet Diabetes & Endocrinology.
But at 12 months the first signs of change began to appear, with pancreatic volume being an average of 3.8 cm3 greater in responders than controls, although this difference was not significant. For nonresponders, the difference was just 0.76 cm3.
And by 24 months, pancreatic volume was a significant 6.6 cm3 larger in responders than controls, whereas the difference for nonresponders was a nonsignificant 0.26 cm3.
Average pancreatic volume remained significantly reduced relative to that in people without diabetes even at 24 months; however, the researchers say that “the slow, gradual return towards normal in pancreas volume suggests that even the 2-year time course of this study might be insufficient to fully observe the impact of the return to the non-diabetic state.”
Fractal dimension, on the other hand, returned to normal values in responders by 24 months. There was also a “modest” improvement in the nonresponders, with the greatest improvements seen in those with the largest reductions in glycated hemoglobin.
Although nonresponders did not achieve the necessary glycemic thresholds to be considered free of type 2 diabetes, they did achieve significant weight loss and reductions in insulin resistance, fasting insulin, and pancreatic fat.
“Our findings show that recovery of acinar cell mass is associated with smoothing of the pancreatic borders,” write the researchers. “The simplest explanation could be that this reflects the re-expansion of the whole organ and at least partial correction of the atrophied state associated with diabetes.”
First-phase insulin response improved only in responders, from 5 months, and the change in first-phase insulin secretion at 24 months correlated with change in pancreatic volume. Maximal insulin response took longer to improve, but responders achieved normal values by 24 months.
“To our knowledge, this study is the first to show normalisation of the gross morphology of the pancreas in people with type 2 diabetes and underpins a frame-shift of understanding of the nature of type 2 diabetes,” Al-Mrabeh and team conclude.
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