Diabetes RElated to Acute Pancreatitis and Its Mechanisms

Study Overview
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Brief Summary
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The overriding objective of DREAM is to conduct a prospective longitudinal (36 months) observational clinical study to investigate the incidence, etiology, and pathophysiology of diabetes mellitus (DM) following acute pancreatitis (AP).

Detailed Description
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The DREAM investigators will conduct dynamic metabolic testing that includes oral glucose tolerance testing (OGTT), mixed meal tolerance testing (MMTT), and frequently sampled intravenous glucose tolerance testing (FSIGTT). These tests will increase the sensitivity for DM diagnosis (with OGTT) and to assess beta cell function and other pancreatic and enteroendocrine hormones involved in maintaining glucose homeostasis (OGTT, MMTT and FSIGTT). The DREAM research hypotheses are as follows. There is a cumulative increase in the risk of any type of DM after an episode of AP, and the development of DM after AP is influenced by several patient and disease-related factors (e.g. age, etiology, disease severity). After AP is clinically resolved, there is ongoing subclinical beta cell damage that predisposes to delayed-onset of DM. AP triggers an altered immune state in a subset of individuals that predisposes to islet autoimmunity and DM.

Official Title
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Diabetes RElated to Acute Pancreatitis and Its Mechanisms (DREAM) An Observational Cohort Study From the Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC)

Conditions
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Acute Pancreatitis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute pancreatitis (AP) 0-90 days prior to enrollment date Participant fully understands and is able to participate in all aspects of the study, including providing informed consent, completion of case report forms (CRFs), telephone interviews, metabolic testing, and planned longitudinal follow-ups Exclusion Criteria: Diagnosis of definite chronic pancreatitis (CP) at enrollment based on either of the following criteria met by computed tomography (CT) scan (including non-contrast enhanced) or Magnetic resonance Imaging (MRI) or Magnetic Resonance Cholangiopancreatography (MRCP): (a) Parenchymal or ductal calcifications on CT scan (after excluding the possibility that calcifications are vascular); (b) Intraductal filling defects suggestive of calcifications on MRI and/or MRCP Potential participants with post-endoscopic retrograde cholangiopancreatography (post- ERCP) AP who are hospitalized for <48 hours. Prior (i.e., before enrollment) direct endoscopic necrosectomy of the pancreas or percutaneous necrosectomy or drainage of necrotic collection(s). Participants who require this during follow-up will remain in the study Pancreatic tumors, including ductal adenocarcinoma, neuroendocrine tumors, and metastasis Confirmed or suspected cystic tumor associated with main pancreatic duct dilation, or believed to be the cause of AP (in the site-PI's judgement) Prior pancreatic surgery, including, but not limited to: distal pancreatectomy, pancreaticoduodenectomy, pancreatic necrosectomy, Frey procedure Use of disallowed concomitant medications within 30 days prior to enrollment. A comprehensive list of disallowed medications will be included and routinely updated in the study's Manual of Procedures Severe systemic illness that in the judgement of the investigative team will confound outcome assessments of DM and immunological outcomes or pose additional risk for harms, including: history of solid organ transplant, acquired immunodeficiency syndrome (AIDS), active treatment for cancer (except non-melanoma skin cancer) within 12 months prior to enrollment, chronic kidney disease with estimate glomerular filtration rate (eGFR) < 30 or on dialysis prior to AP, and cirrhosis (based on imaging or biopsy), or any other medical condition that in the opinion of the site-PI carries a life expectancy of <12 months. Known pregnancy at the time of enrollment. Participants who become pregnant during follow-up will remain in the study, but may have modified study assessments for safety Incarceration Any other condition or factor that would compromise the participant's safety or the scientific integrity of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| diabetes mellitus (DM) following a qualifying episode of acute pancreatitis (AP) | time to onset of DM during the 36-month longitudinal follow-up period | any time during the 36-month longitudinal follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PROMIS Global Health | Patient Reported Outcomes Measurement Information System (PROMIS) Global Health, converted to a t-score with a mean of 50 and a standard deviation of 10 | months 3, 12, 24, and 36 | 
| PROMIS Pain Intensity | Patient Reported Outcomes Measurement Information System (PROMIS) Pain Intensity, measured on an 11-point scale from 0 (no pain ) to 10 (worst pain imaginable) | months 3, 12, 24, and 36 | 
| PROMIS-29 Physical Function | PROMIS-29 Physical Function, converted to a t-score with a mean of 50 and a standard deviation of 10 | months 3, 12, 24, and 36 | 
| PROMIS-29 Anxiety | PROMIS-29 Anxiety, converted to a t-score with a mean of 50 and a standard deviation of 10 | months 3, 12, 24, and 36 | 
| PROMIS-29 Depression | PROMIS-29 Depression, converted to a t-score with a mean of 50 and a standard deviation of 10 | months 3, 12, 24, and 36 | 
| PROMIS-29 Fatigue | PROMIS-29 Fatigue, converted to a t-score with a mean of 50 and a standard deviation of 10 | months 3, 12, 24, and 36 | 
| PROMIS-29 Sleep Disturbance | PROMIS-29 Sleep Disturbance, converted to a t-score with a mean of 50 and a standard deviation of 10 | months 3, 12, 24, and 36 | 
| PROMIS-29 Ability to Participate in Social Roles and Activities | PROMIS-29 Ability to Participate in Social Roles and Activities, converted to a t-score with a mean of 50 and a standard deviation of 10 | months 3, 12, 24, and 36 | 
| PROMIS-29 Pain Interference | PROMIS-29 Pain Interference, converted to a t-score with a mean of 50 and a standard deviation of 10 | months 3, 12, 24, and 36 | 
| OGTT Insulin Secretion | Oral Glucose Tolerance Testing (OGTT) Insulin Secretion, as measured by the insulin area under the curve relative to the glucose area under the curve | months 3, 12, 24, and 36 | 
| OGTT Insulin Sensitivity Index | Oral Glucose Tolerance Testing (OGTT) Insulin Sensitivity Index, as measured by the glucose disposal rate divided by the average plasma insulin concentration | months 3, 12, 24, and 36 | 
| MMTT Incretin Hormones: GIP and GLP-1 | Mixed Meal Tolerance Testing (MMTT) Incretin Hormones: Glucose-dependent Insulinotropic Polypeptide (GIP, pmol/L) and Glucagon-like Peptide-1 (GLP-1, pmol/L) | months 3, 12, 24, and 36 | 
| MMTT Glucagon | Mixed Meal Tolerance Testing (MMTT) Glucagon (pg/mL) | months 3, 12, 24, and 36 | 
| MMTT Pancreatic Polypeptide (PP) | Mixed Meal Tolerance Testing (MMTT) Pancreatic Polypeptide (PP, pg/mL) | months 3, 12, 24, and 36 | 
| FSIGTT Acute Insulin Response to Glucose (AIRglu) | Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Acute Insulin Response to Glucose (AIRglu) | months 3 and 12 | 
| FSIGTT Acute C-peptide Response to Glucose (ACRglu) | Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Acute C-peptide Response to Glucose (ACRglu) | months 3 and 12 | 
| FSIGTT Total Body Insulin Sensitivity Index (SI) | Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Total Body Insulin Sensitivity Index (SI) | months 3 and 12 | 
| FSIGTT Total Body Insulin Sensitivity Index (SI) Disposition Index | Frequently Sampled Intravenous Glucose Tolerance Testing (FSIGTT) Disposition Index (DI), calculated as the product of the AIRglu and the Total Body Insulin SI | months 3 and 12 | 
| Islet Autoantibodies | Islet Autoantibodies | months 3, 12, 24, and 36 | 
| Fecal Elastase | Fecal Elastase (ug/g) | months 3, 12, 24, and 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes