2Background: Type 2 diabetes mellitus is widely considered to be associated with pancreatic cancer.Objective: To determine the incidence of pancreatic cancer in new-onset type 2 diabetic patients by measuring the serum level of CA 19-9 and performing abdominal ultrasonography (US). Patients and Methods:Consecutive type 2 diabetic patients in whom diabetes was diagnosed within 36 months were included in this prospective study. Serum CA 19-9 measurement and US were performed in all patients. If any of two was positive, abdominal computer tomography (CT) was carried out. Endoscopic ultrasound-guided fine needle aspiration or direct surgical referral was performed on patients with CT-identified lesions.Results: A total of 115 patients were enrolled. CA 19-9 was elevated in 10 patients but pancreatic cancer diagnosed in neither of them. Pancreatic cancer was revealed by morphological means in three patients without elevated CA 19-9 level. The sensitivity, specificity, positive-, negative predictive values and validity were 0%, 90.4%, 0%, 97.9% and 87.9% for CA 19-9, 66.7%, 100%, 100%, 99% and 99% for US, respectively. The value of the Standardized Incidence Ratio for pancreatic cancer in new-onset type-2 diabetic patients was 198.6 (95% CI=6.25-46.9). Conclusions:The prevalence of pancreatic cancer in patients with new-onset type-2 diabetes is significantly higher than that in the general population and screening is beneficial for detecting PaC in this patient population. CA 19-9 and US is not reliable screening modality for pancreatic cancer screening in this population.

Nine new analogues of acetyl-CCK-heptapeptide (Ac-Tyr(SO3H)2-Met3-Gly4-Trp5-Met6-Asp7-Phe8-NH2 ) were synthesized by solid-phase methodology. In a first series, the Asp7 residue was replaced by hydroxy amino acid sulfate esters. In another series, Gly4 was substituted by D-Ala, while Trp5 and Met6 were replaced by their D enantiomer. The introduction of the sulfate ester was performed with a new, mild, crystalline, and stable reagent, pyridinium acetyl sulfate. Each analogue that contained Tyr(SO3H)2 and a hydroxy amino acid sulfate ester [Ser(SO3H), Thr(SO3H), or Hyp(SO3H)] in position 7 proved to be more potent (1.9, 1.7, and 3.0 times, respectively) than CCK-8 in vitro (isolated gallbladder strips). While devoid of gastrin-like activity in vivo, these analogues had potent anticonvulsive activity. The analogues containing a D-amino acid residue were less potent than the parent compound in vitro. The D-Ala4 replacement, however, yielded a compound that was 40% as potent as CCK-8 in the in vitro test but showed prolonged duration of action on sphincter Oddi. While the 7-substituted Ac-CCK heptapeptides are among the most potent CCK analogues reported so far, the D-Ala4 replacement resulted, for the first time, in prolonged activity in vivo.

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.

IntroductionPancreatic 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 analysisThis 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 disseminationThe 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 numberClinicalTrials.gov NCT04164602

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Non-Alcoholic Fatty Pancreas and Liver Disease (NAFPD and NAFLD) are often associated with Type 2 Diabetes Mellitus (T2DM). Our aim was to evaluate the incidence rate of NAFLD and NAFPD, the size of Pericardial Adipose Tissue (PAT) and the effect of metformin treatment on NAFLD, NAFPD and PAT in new-onset T2DM. 19 patients with new-onset T2DM and 10 subjects as control group were involved. Computed tomography and laboratory tests were performed before the beginning of metformin therapy and 4 months afterwards. The PAT and the amount of fat in the pancreas and liver was determined by the Xray attenuation on unenhanced CT examination and compared with values for control subjects. Metabolic parameters improved significantly after the metformin therapy. The radiation absorption of the liver was significantly lower in patients with T2DM as compared to the control group (33.52±19.38 vs 53.1±8.31 HU) and significantly increased after the metformin therapy as compared to the baseline values (46.12±13.33 vs 33.52±19.38 HU). The radiation absorption of the pancreas was lower but not significant in patients with T2DM (32.76±9.55 vs 34.2±12.1 HU) and did not change significantly during the treatment (35.64±9.07 vs 32.76±9.55 HU). The size of the PAT was significantly larger in T2DM patients (2053.1±1136 vs 1223.9±312.9 mm2) but did not change significantly after the treatment (2053.1±1136 vs 2026.2±1032 mm2). Metformin therapy decreased the amount of fat in the liver parallel with the improvement of the metabolic parameters and may be beneficial for the prevention of the late consequences of NAFLD.