Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer

Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes. It is important to note that type 3c diabetes is not a single entity; it occurs because of a variety of exocrine pancreatic diseases with varying mechanisms of hyperglycaemia. The most commonly identified causes of type 3c diabetes are chronic pancreatitis, pancreatic ductal adenocarcinoma, haemochromatosis, cystic fibrosis, and previous pancreatic surgery. In this Review, we discuss the epidemiology, pathogenesis, and clinical relevance of type 3c diabetes secondary to chronic pancreatitis and pancreatic ductal adenocarcinoma, and highlight several important knowledge gaps

Internet Cognitive-Behavioral Therapy for Painful Chronic Pancreatitis: A Pilot Feasibility Randomized Controlled Trial

Introduction: Severe abdominal pain is a cardinal symptom of chronic pancreatitis (CP) associated with a high economic and societal burden. In other chronic pain conditions, cognitive-behavioral therapy (CBT) has demonstrated efficacy in improving patient outcomes (e.g., pain-related disability and depression). However, CBT has not yet been evaluated in adult patients with painful CP. We aimed to (i) evaluate the feasibility and acceptability of an adapted Internet CBT program for CP and (ii) generate pilot data regarding the effects of treatment on patient pain outcomes. Methods: Thirty adults (mean age = 49.8 years, SD = 12.5; 80% women) with suspected or definite CP were randomized to Internet CBT (Pancreatitis Pain Course) versus control. The Pancreatitis Pain Course has 5 CBT lessons (e.g., thought challenging, relaxation, and activity pacing) delivered over 8 weeks. Pain interference, pain intensity, and quality of life were assessed at pretreatment, posttreatment, and the 3-month follow-up. Qualitative interviews were conducted at posttreatment with a subset of participants. Results: Eighty percent of participants rated the program as highly acceptable; 64.3% completed all 5 lessons. Qualitative data revealed positive perceptions of program features, relevancy, and skills. Patients randomized to Internet CBT demonstrated moderate to large effects in reducing pain intensity and pain interference from baseline to 3 months. The proportion of treatment responders (>30% improvement) was significantly greater in the Internet-CBT group than in the control group (50% vs 13%, Fisher exact t test P = 0.04). Discussion: In this first trial of CBT pain self-management in CP, feasibility, acceptability, and preliminary efficacy for reducing pain and disability were demonstrated. Future definitive trials of CBT are needed

High Prevalence of Osteopathy in Chronic Pancreatitis: A Cross-sectional Analysis From the PROCEED Study

Background & aims: Chronic pancreatitis (CP) is associated with osteopathy (osteoporosis or osteopenia). However, existing literature is mostly limited to retrospective or administrative studies that have not clearly defined the prevalence and risk factors. Our aim was to identify patient- and disease-related associations with osteopathy in a prospective cohort study of CP. Methods: We studied 282 subjects with definitive CP enrolled in the PROCEED study who had a baseline dual-energy X-ray absorptiometry (DXA) scan. Osteopenia and osteoporosis were defined using the lowest T-scores. Clinical data were collected using standardized case report forms. Comparisons were performed with a multivariate logistic regression model with forward selection to identify risk factors for osteopathy. Results: The majority of subjects had osteopathy on DXA scan (56.0%; 17.0% osteoporosis; 39.0% osteopenia). Subjects with osteopathy had a higher prevalence of traumatic (40.0% vs 26.4%; P = .02) and spontaneous fractures (3.9% vs 0; P = .04). On multivariate analysis, older age (odds ratio [OR], 1.29 per 5 years; 95% confidence interval [CI], 1.15-1.45), female sex (OR, 3.08; 95% CI, 1.75-5.43), white race (OR, 2.68; 95% CI, 1.20-6.01), and underweight body mass index category (OR, 7.40; 95% CI, 1.56-34.99) were associated with higher probability of osteopathy. There were no significant associations between osteopathy and other patient and disease-related features of CP. Conclusion: In the largest study of patients with CP who underwent DXA screening, the majority had osteopathy. There are overlapping risk factors with osteopathy in the general population, but the high prevalence in men and younger women supports the need for future investigations into the mechanisms of bone loss in CP

Interobserver Agreement for CT and MRI Findings of Chronic Pancreatitis in Children: A Multicenter Ancillary Study Under the INSPPIRE Consortium

Background: Imaging findings represent key criteria for diagnosing chronic pancreatitis in children. Understanding radiologists’ agreement for imaging findings is critical to standardizing and optimizing diagnostic criteria. Objective: To evaluate the interobserver agreement among experienced pediatric radiologists for subjective, quantitative, and semi-quantitative imaging findings of chronic pancreatitis in children. Methods: In this retrospective study, CT or MRI examinations performed in children with chronic pancreatitis were submitted by six sites participating in the INSPPIRE consortium. One pediatric radiologist from each of the six sites reviewed examinations; three of the radiologists independently reviewed all CT examinations, and the other three radiologists independently reviewed all MRI examinations. Reviewers recorded 13 categorical imaging findings of chronic pancreatitis and measured pancreas thickness and duct diameter. Agreement was assessed using kappa coefficients for the categorical variables and intraclass correlation coefficients (ICC) for the continuous measures. Results: A total of 76 CT and 80 MRI examinations performed in 110 children (mean age, 11.3±4.6 years; 65 girls, 45 boys) were reviewed. For CT, kappa coefficients for categorical findings ranged from −0.01 to 0.81, with relatively high kappa coefficients for parenchymal calcification (κ=0.81), main pancreatic duct dilation (κ=0.63), and atrophy (κ=0.52). ICCs for parenchymal thickness measurements ranged from 0.57 in the pancreas head to 0.80 in the body and tail. ICC for duct diameter was 0.85. For MRI, kappa coefficients for categorical findings ranged from −0.01 to 0.74, with relatively high kappa coefficients for main duct irregularity (κ=0.74), side branch dilation (κ=0.70), number of dilated side branches (κ=0.65), and main duct dilation (κ=0.64); kappa coefficient for atrophy was 0.52. ICCs for parenchymal thickness measurements ranged from 0.59 in the pancreas head to 0.68 in the tail. ICC for duct diameter was 0.77. Conclusion: Interobserver agreement was fair to moderate for most CT and MRI findings of chronic pancreatitis in children. Clinical Impact: This study highlights challenges for the imaging diagnosis of pediatric chronic pancreatitis. Standardized and/or objective criteria are needed given the importance of imaging in diagnosis

Association of Chronic Pancreatitis Pain Features With Physical, Mental, and Social Health

Background and aims: Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities. Methods: We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile, which captures 7 symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database. Results: Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes, 2.54-7.03) and had a higher prevalence of clinically significant depression, anxiety, sleep disturbance, and physical disability (odds ratios, 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes, 4.08-10.37) and clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, 2.80-5.38). Conclusions: Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP

Health-Related Quality of Life in Pediatric Acute Recurrent or Chronic Pancreatitis: Association With Biopsychosocial Risk Factors

ObjectivesAbdominal pain, emergency department visits, and hospitalizations impact lives of children with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Data on health-related quality of life (HRQOL) in this population, however, remains limited. We aimed to evaluate HRQOL in children with ARP or CP; and test biopsychosocial risk factors associated with low HRQOL.MethodsData were acquired from the INternational Study Group of Pediatric Pancreatitis: In search for a cuRE registry. Baseline demographic and clinical questionnaires, the Child Health Questionnaire (measures HRQOL) and Child Behavior Checklist (measures emotional and behavioral functioning) were completed at enrollment.ResultsThe sample included 368 children (54.3% girls, mean age = 12.7years, standard deviation [SD] = 3.3); 65.2% had ARP and 34.8% with CP. Low physical HRQOL (M = 38.5, SD = 16.0) was demonstrated while psychosocial HRQOL (M = 49.5, SD = 10.2) was in the normative range. Multivariate regression analysis revealed that clinical levels of emotional and behavioral problems (B = -10.28, P  < 0.001), episodic and constant abdominal pain (B = 04.66, P = 0.03; B = -13.25, P < 0.001) were associated with low physical HRQOL, after accounting for ARP/CP status, age, sex, exocrine, and endocrine disease (F [9, 271] = 8.34, P < 0.001). Borderline and clinical levels of emotional and behavioral problems (B = -10.18, P < 0.001; B = -15.98, P < 0.001), and constant pain (B = -4.46, P < 0.001) were associated with low psychosocial HRQOL (F [9, 271] = 17.18, P < 0.001).ConclusionsFindings highlight the importance of assessing HRQOL and treating pain and psychosocial problems in this vulnerable group of children