2-year remission of type 2 diabetes and pancreas morphology: a post-hoc analysis of the DIRECT open-label, cluster-randomized trial
As per previous observations, it is unclear whether smaller, dysmorphic pancreas from birth leads to type 2 diabetes or this morphology of pancreas is secondary to type 2 diabetes. Ph.D. scholar Ahmad Al-Mrabeh and Kieren G Hollingsworth along with a group of professors have conducted a randomized trial titled “2-year remission of type 2 diabetes and pancreas morphology: a post-hoc analysis of the DIRECT open-label, cluster-randomized trial” published in The Lancet Diabetes and Endocrinology Journal. A brief summary of the study is given below:
Objective:
To determine whether 2 years of type 2 diabetes remission can lead to change in pancreas volume and shape.
Method:
A subset of the adult participants of the Diabetes Remission Clinical trial (DiRECT), who had Type 2 Diabetes were included. Weight management intervention or routine diabetes management were randomly assigned to the participant.
Participants were divided into two categories – Responders (HbA1c <6·5% [48 mmol/mol] and fasting blood glucose <7·0 mmol/L, off all anti-diabetes medication) and Non-responders (diabetic). Baseline, 5 months, 12 months, and 24 months data on pancreas volume and pancreas border irregularity were compared between these two categories.
Additionally, a comparison between a control group participants who were Type 2 diabetic and Non-Diabetic Comparator (NDC) was conducted.
For potential cofounding, a mixed-effect regression model, which is based on repeated measure ANOVA with correction was used. For quantifying pancreas volume, irregularity of pancreas border and intrapancreatic fat content magnetic resonance technique were employed. Additional measures of β-cell function and biomarkers of tissue growth were included.
Findings:
The study reported that small, irregular pancreas of type 2 diabetes is improved in volume after 24 months of remission. Total pancreas volume reflects acinar cell mass while 5% contribution from islet and ducts. This recovery in the acinar cell is associated with the occurrence of a smooth pancreatic border. Intrapancreatic fat is found to be reduced due to remission. Comparison between diabetic and NDC group reports decrease in Insulin-like growth factor 1 (IGF-1) with diabetes and aging on one hand and increased Growth and Developmental Factor (GDF-15) level with type 2 diabetes on other. Fibroblast Growth Factor (FGF 21) is found to be decreased with weight loss. This decrease is irrespective of change in pancreas volume.
Limitations:
As there is a slow improvement in pancreatic volume, the authors suggest that 2 years observational period might be insufficient. Although the study found clear improving pancreatic volume in responders and non-responders, the authors didn’t find a significant change in border irregularity as per ANOVA analysis. The authors look forward to the measurement of fecal elastase in future studies to study pancreas insufficiency. 98% white population took part in this study. Hence, the direct study of other ethnicities is being put forward.
Image Credit: Medicine photo created by KamranAydinov – www.freepik.com