Risk factors

Reversing diabetes restores normal pancreas morphology

The shrunken, mis-shapen pancreas seen in people with type 2 diabetes is restored to normal morphology following weight-loss induced remission of the condition, UK research has shown.

Using MRI scans to follow up participants in the DIabetes REmission Clinical Trial (DIRECT), investigators observed that pancreas volume increased in people with T2D following a two year weight loss program that resulted in restoration of normal insulin secretion.

The findings, published in Lancet Diabetes and Endocrinology, support the hypothesis that abnormal pancreas morphology is secondary to the disease process in T2D rather than a risk factor for development of the condition, the study authors say.

In their paper they note that pancreas volume is typically about 30% lower than normal in people with T2D, with irregularity of shape.

Their study followed up 64 obese adults (BMI of 27–45 kg/m2) with T2D who underwent a 3-5 month low-calorie diet followed by a supervised weight loss program and a matched group of 25 people who did not have diabetes who also took part in a similar program .

At baseline, mean pancreas volume was 61·7cm3 in all participants with type 2 diabetes and 79·8 cm3 in the non-diabetes control group. After 24 months, pancreas volume had increased by 9·4cm3 in responders compared with 6·4cm3 (in non-responders.

This represented an increase in volume of the irregular diabetic pancreas to 89% of that of the non-diabetic control]  group, the authors said.

Pancreas borders at baseline were more irregular in participants with T2D than in the non-diabetes control group, but normalised by 24 months in responders to the weight loss program. There was also a non-significant decrease in intrapancreatic fat  – by 1·02 percentage points in the responders  – compared to non-responders.

The study investigators said the pancreas was a relatively unstudied organ because of its inaccessible position, but most of its volume comprised acinar cell mass, with islets and ducts contributing only around 5%.

In T2D it was believed that loss of β-cell function is associated with acinar cell fibrosis  and fat replacement of the acinar cells.

They postulated that the restoration of pancreatic morphology after remission of diabetes was a long term process reflecting recovery of acinar cell mass, mediated by the trophic effects of insulin and insulin growth factor-1 (IGF-1).

“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,” they wrote.

“In people with established type 2 diabetes, long-term return to non-diabetic blood glucose control after weight loss is well documented but is not yet universally accepted. Concurrence of morphological and functional restoration of the pancreas provides a solid basis for the concept.”

“These data show that type 2 diabetes is a potentially reversible disease affecting the whole pancreas with gradual morphological and functional recovery during remission,” they concluded.

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