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Type 3c diabetes mellitus (T3cDM) is a clinically relevant condition with a prevalence of 5-10% among all diabetic subjects in Western populations. Its prevalence and clinical importance have been underestimated and underappreciated so far. In contrast to the management of type 1 or type 2 diabetes, the endocrinopathy in T3cDM is very complex and complicated by additional present comorbidities such as maldigestion and concommitant qualitative malnutrition. The failure to correctly diagnose T3cDM leads to failure to implement an appropriate medical therapy of these patients. Physicians should screen for important and easily reversable pathological conditions such as exocrine insufficiency, lack of fat-soluble vitamins (especially vitamin D) and impairment of fat hydrolysis and incretin secretion which are found very commonly in T3cDM. Since most patients with T3cDM suffer from chronic pancreatitis, physicians must additionally be aware of the elevated risk of pancreatic cancer in this subset of patients., (Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Pancreatic exocrine insufficiency is a frequently observed phenomenon in type 1 and type 2 diabetes mellitus. Alterations of exocrine pancreatic morphology can also be found frequently in diabetic patients. Several hypotheses try to explain these findings, including lack of insulin as a trophic factor for exocrine tissue, changes in secretion and/or action of other islet hormones, and autoimmunity against common endocrine and exocrine antigens. Another explanation might be that diabetes mellitus could also be a consequence of underlying pancreatic diseases (e.g., chronic pancreatitis). Another pathophysiological concept proposes the functional and morphological alterations as a consequence of diabetic neuropathy. This paper discusses the currently available studies on this subject and tries to provide an overview of the current concepts of exocrine pancreatic insufficiency in diabetes mellitus.

Objective: Recently it has been shown that there is not only endocrine insufficiency in diabetic patients, but a frequent co-morbidity of both, the endocrine and exocrine pancreas. The present study was performed to further analyse the determinants of exocrine pancreatic function in patients with diabetes mellitus., Methods: The records of 1992 patients with diabetes mellitus who had been treated in our hospital during a 2-year period were re-evaluated. Defined parameters were documented in standardized data sheets. Records were further checked for the results of imaging procedures of the pancreas. In 307 patients FEC had been performed and documented. Only these patients were included in further evaluation., Results: FEC was inversely correlated with diabetes duration and HbA1c-levels but not with age. C-peptide levels correlated positively with FEC. BMI and FEC were also significantly correlated. There was no correlation between diabetes therapy and exocrine pancreatic function as there was no correlation with any concomitant medication. The presence of diabetes-associated antibodies was not related to FEC. According to the documented data 38 were classified as type-1 diabetes (12.4%), 167 as type-2 (54.4%), and 88 patients met the diagnostic criteria of type-3 (28.7%). Fourteen patients could not be classified because of lacking information (4.6%)., Conclusions: Exocrine insufficiency might be explained as a complication of diabetes mellitus. However, it is more likely that type-3 diabetes is much more frequent than previously believed. Consequently the evaluation of exocrine function and morphology should be included into the clinical workup of any diabetic patient at least at the time of manifestation.

Purpose of Review: To learn about the prevalence, pathophysiology, and treatment of exocrine pancreatic involvement in critically ill patients., Recent Findings: Elevations in the levels of pancreatic enzymes are observed in up to 80% of intensive care patients. Most of these patients do not develop clinically relevant pancreatitis. However, elevations in enzyme levels do represent pancreatic damage with a risk of complications. Different factors have been discussed, which may contribute to pancreatic damage in critically ill patients. These include splanchnic hypoperfusion during shock or major surgery, bacterial translocation, elevated triglyceride levels, development of biliary sluge, and biliary pancreatitis, as well as several drugs. Imaging procedures and inflammatory markers help to identify relevant disease. Several therapeutic options have been discussed recently with a focus on early enteral nutrition., Summary: Pancreatic damage is frequently observed in critically ill patients. Although in most of these patients, this is without major clinical consequences, some patients develop relevant pancreatitis, which contributes to morbidity and mortality. Risk factors have been identified and therapeutic strategies have been changed.

Context: Histopathological analysis has demonstrated lymphocytic infiltration in both the endocrine and the exocrine pancreas in some patients with type 1 diabetes and non-alcoholic chronic pancreatitis, suggesting an immune-mediated mechanism which affects both diabetes mellitus and chronic pancreatitis., Objective: The examination of exocrine pancreatic humoral markers in Caucasian patients with respect to the interactions between exocrine and endocrine pancreatic diseases., Patients: One hundred and thirty-six European Caucasian subjects subdivided into three groups: type 1 diabetes (n=48); non-alcoholic chronic pancreatitis (n=48); controls (n=40)., Main Outcome Measure: Autoantibodies against carbonic anhydrase II (CAIIAb) and lactoferrin (LACAb) (both of which are exocrine pancreatic antigens) were analyzed by enzyme-linked immunosorbent assay., Results: No positivity for CAIIAb and LACAb were found in the controls. Patients with type 1 diabetes had a significantly higher prevalence of CAIIAb (25.0%) than the controls while the prevalence of LACAb (8.3%) was not significantly higher than the controls. The prevalence of CAIIAb (12.5%) and LACAb (20.8%) in the patients with non-alcoholic chronic pancreatitis was significantly higher than that in the controls. A significantly higher prevalence of CAIIAb and/or LACAb was found in patients with type 1 diabetes (29.2%) and non-alcoholic chronic pancreatitis (22.9%) compared to that in the controls (0%). There was a significant association between CAIIAb and LACAb titers both in patients with type 1 diabetes (P=0.042) and in patients with non-alcoholic chronic pancreatitis (P<0.001)., Conclusion: We have clearly demonstrated that some European Caucasian patients with type 1 diabetes and non-alcoholic chronic pancreatitis have autoantibodies against the exocrine pancreatic antigens CAIIAb and LACAb.

Aim: To investigate retrospectively the long-term effect of endoscopic sphincterotomy (ES) including exocrine pancreatic function in patients with stenosis of ampulla of Vater., Methods: After diagnostic endoscopic retrograde cholangiopancreatography (ERCP) and ES because of stenosis of the ampulla of Vater (SOD Type I), follow-up examinations were performed in 60 patients (mean follow-up time 37.7 mo). Patients were asked about clinical signs and symptoms at present and before intervention using a standard questionnaire. Before and after ES exocrine pancreatic function was assessed by determination of immunoreactive fecal elastase 1. Serum enzymes indicating cholestasis as well as serum lipase and amylase were measured., Results: Eighty percent of patients reported an improvement in their general condition after ES. The fecal elastase 1 concentrations (FEC) in all patients increased significantly after ES. This effect was even more marked in patients with pathologically low concentrations (< 200 microg/g) of fecal elastase prior to ES. The levels of serum lipase and amylase as well as serum alcaline phosphatase (AP) and gamma-glutamyltranspeptidase (GGT) decreased significantly after ES., Conclusion: The results of this study demonstrate that patients with stenosis of the ampulla of Vater can be successfully treated with endoscopic sphincterotomy. The positive effect is not only indicated by sustained improvement of clinical symptoms and cholestasis but also by improvement of exocrine pancreatic function.