New Onset of DiabetEs in aSsociation with pancreatic ductal adenocarcinoma (NODES Trial): protocol of a prospective, multicentre observational trial.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with an overall 5-year survival of approximately 8%. The success in reducing the mortality rate of PDAC is related to the discovery of new therapeutic agents, and to a significant extent to the development of early detection and prevention programmes. Patients with new-onset diabetes mellitus (DM) represent a high-risk group for PDAC as they have an eightfold higher risk of PDAC than the general population. The proposed screening programme may allow the detection of PDAC in the early, operable stage. Diagnosing more patients in the curable stage might decrease the morbidity and mortality rates of PDAC and additionally reduce the burden of the healthcare. METHODS AND ANALYSIS: This is a prospective, multicentre observational cohort study. Patients ≥60 years old diagnosed with new-onset (≤6 months) diabetes will be included. Exclusion criteria are (1) Continuous alcohol abuse; (2) Chronic pancreatitis; (3) Previous pancreas operation/pancreatectomy; (4) Pregnancy; (5) Present malignant disease and (6) Type 1 DM. Follow-up visits are scheduled every 6 months for up to 36 months. Data collection is based on questionnaires. Clinical symptoms, body weight and fasting blood will be collected at each, carbohydrate antigen 19-9 and blood to biobank at every second visit. The blood samples will be processed to plasma and analysed with mass spectrometry (MS)-based metabolomics. The metabolomic data will be used for biomarker validation for early detection of PDAC in the high-risk group patients with new-onset diabetes. Patients with worrisome features will undergo MRI or endoscopic ultrasound investigation, and surgical referral depending on the radiological findings. One of the secondary end points is the incidence of PDAC in patients with newly diagnosed DM. ETHICS AND DISSEMINATION: The study has been approved by the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (41085-6/2019). We plan to disseminate the results to several members of the healthcare system includining medical doctors, dietitians, nurses, patients and so on. We plan to publish the results in a peer-reviewed high-quality journal for professionals. In addition, we also plan to publish it for lay readers in order to maximalise the dissemination and benefits of this trial. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04164602.

In New-Onset Diabetes Mellitus, Metformin Reduces Fat Accumulation in the Liver, But Not in the Pancreas or Pericardium.

Background: Nonalcoholic fatty pancreas and liver disease (NAFPD and NAFLD) and pericardial adipose tissue (PAT) are often associated with type 2 diabetes mellitus (T2DM). Our aim was to evaluate the incidence rate of NAFLD and NAFPD, PAT size, and the effect of metformin treatment on NAFLD, NAFPD, and PAT in new-onset T2DM (NODM). Methods: Seventeen patients with NODM and 10 subjects used as a control group were involved in the study. Computed tomography (CT) and laboratory tests were performed before the beginning of metformin therapy and 4 months afterward. PAT and the amount of fat in the pancreas and liver were determined by X-ray attenuation during unenhanced CT examination and compared with the values for the control subjects. Results: Metabolic parameters improved significantly after metformin therapy. NAFLD was diagnosed in 64.7% of the patients with NODM and in 10% of the control subjects. The radiation absorption of the liver was significantly lower in the patients with NODM compared with the control group and significantly higher after metformin therapy compared with the baseline values. Only six patients (35.3%) had NAFLD after metformin therapy. NAFPD was diagnosed in 82.3% of the patients with NODM and in 20% of the control subjects. The radiation absorption of the pancreas was significantly lower in the patients with NODM compared with the control group but did not change significantly after treatment. PAT size was significantly larger in the patients with NODM and did not change significantly after metformin treatment. Conclusions: NAFLD, NAFPD, and increased PAT were detected in the majority of patients with NODM. Metformin therapy decreased the amount of fat in the liver in parallel with an improvement in the metabolic parameters and may, thus, be beneficial for preventing the late consequences of NAFLD.