Philip D. Hardt

Severe hypertriglyceridemia and pancreatitis: presentation and management

Purpose of review Hypertriglyceridemia (HTG) is a well recognized cause of acute pancreatitis accounting for approximately up to 10% of all cases and even up to 50% of all cases in pregnancy. Both primary and secondary disorders of lipoprotein metabolism may be associated with hypertriglyceridemic pancreatitis (HTGP). The purpose of this review is to provide an overview of the current studies on presentation and management of HTGP. Recent findings/conclusion Hydrolysis of triglycerides by pancreatic lipase and formation of free fatty acids that induce inflammatory changes are postulated to account for the development of HTGP, yet the exact pathophysiology remains unclear. The clinical features of patients with HTGP are generally not different from patients with acute pancreatitis of other causes, and there is some evidence that HTGP is associated with a higher severity or a higher complication rate. There is no clear evidence as to which HTG patients will develop pancreatitis. Several studies have evaluated the effect of apheresis, the benefit of insulin and/or heparin treatment and the use of different antihyperlipidemic agents in HTGP. Dietary modifications resemble the key features in the long-term management of HTG. Whether HTG may cause chronic pancreatitis in the long-term follow-up remains controversial.

Prevalence of diabetes mellitus secondary to pancreatic diseases (type 3c)

Diabetes mellitus secondary to pancreatic diseases is a condition seldom thought of in clinical practice. Yet, a high percentage of exocrine pancreatic insufficiency has been reported for the general population and especially for diabetic subjects. Thus, we investigated the prevalence of diabetes mellitus due to pancreatic diseases.

High prevalence of exocrine pancreatic insufficiency in diabetes mellitus: A multicenter study screening fecal elastase 1 concentrations in 1,021 diabetic patients

Background: There have been numerous reports on pancreatic exocrine dysfunction in diabetes mellitus using either direct or indirect function tests. The measurement of fecal elastase 1 concentrations (FEC) has been used as a screening tool for exocrine pancreatic disease in different patient groups indicating a high prevalence of exocrine dysfunction in diabetic populations. In this study we had the opportunity to study more than 1,000 diabetic patients to confirm recent observations in smaller populations. Methods: FEC were measured by ELISA in 323 patients with type 1 and 697 type 2 diabetes mellitus. Subjects with a history of alcohol abuse, gastrointestinal surgery, cancer or inflammatory diseases were not included. Diabetes history and clinical data were recorded using a standard case report form. Findings: 1,021 patients (334 female, 687 male; mean age 50 years; mean diabetes duration 11 years; mean age at onset of diabetes 39 years) were studied. FEC was normal (>200 µg/g) in 59.3% and severely reduced (<100 µg/g) in 22.9%. There were significant differences between type 1 and type 2 patients as well as between insulin-treated and non-insulin-treated patients. Furthermore, there were weak associations between FEC and diabetes duration, age at onset of diabetes and body mass index, respectively. Interpretation: We could confirm that both type 1 and type 2 diabetic patients show pathological exocrine function in high prevalence. Exocrine insufficiency seems to be correlated to early onset of endocrine failure, long-lasting diabetes mellitus and low body mass index levels.

Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus.

Abstract Reduced exocrine pancreatic function has been observed in a high percentage of patients with type 1 diabetes in the past. There are only few data for type 2 diabetes available and they are contradictory. In this study we investigated exocrine pancreatic function in 105 controls and 114 with type 1 or type 2 diabetes mellitus by means of an indirect test (faecal elastase-1 concentration). This test has good sensitivity and specificity for moderate and severe pancreatic insufficiency as compared to the gold standard. Reduced faecal elastase-1 concentrations were found in 56.7% of type 1 patients, 35% of type 2 patients and 18.1% of the controls. Elastase-1 concentrations did not correlate with alcohol consumption, diabetes duration or diabetes therapy. The data found for type 1 patients correspond to those reported in earlier studies. The results for type 2 diabetics show that exocrine pancreatic function is also impaired in a high percentage in this group of patients. Pathogenic concepts to explain these findings as consequences of diabetes complications or insulin deficiency are still under debate. Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem. In consequence, diabetes secondary to exocrine disease could be much more frequent than believed so far.

Prevalence and determinants of exocrine pancreatic insufficiency among older adults: Results of a population-based study

Objective The prevalence and main determinants of exocrine pancreatic insufficiency were investigated in a large population-based sample of older adults by measuring pancreatic elastase-1 in stool. Material and methods The study comprised 914 participants aged 50 to 75 years recruited by their general practitioner during a general health examination. All participants and their physicians were asked to fill out a standardized questionnaire which contained information on socio-demographic and lifestyle factors as well as medical history. Native stool was examined for pancreatic elastase-1 with a commercially available ELISA (ScheBo® Tech, Giessen, Germany). Results Overall, 524 women and 390 men aged 50 to 75 years (mean age 61.9 years) were included in the analysis. In total, 105 (11.5%) of the 914 subjects showed signs of exocrine pancreatic insufficiency (EPI) with ≤200 μg elastase-1/g stool, and 47 (5.1%) subjects showed signs of a severe exocrine pancreatic insufficiency (SEPI, <100 μg elastase-1/g stool). There was a clear increase in EPI with age. Patients taking angiotensin-converting enzyme (ACE) inhibitors had a lower prevalence than subjects without this medication; these associations persisted after adjustment for covariates. Conclusions Prevalence of EPI increases with age and seems to be tentatively higher in men than in women. However, smoking seems to be an independent risk factor for EPI and SEPI whereas ACE-inhibitor intake might be a protective factor. The latter finding may even point to new options in the treatment of chronic pancreatitis.

Exocrine pancreatic insufficiency in diabetes mellitus: a complication of diabetic neuropathy or a different type of diabetes?

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.

High Prevalence of Steatorrhea in 101 Diabetic Patients Likely to Suffer from Exocrine Pancreatic Insufficiency According to Low Fecal Elastase 1 Concentrations: A Prospective Multicenter Study

Impaired exocrine pancreatic secretion has been frequently observed in diabetic patients by different methods, including direct function tests. However, the clinical importance remained unclear. In the present study, the fecal fat excretion in patients with type 1 or type 2 diabetes mellitus and exocrine dysfunction according to fecal elastase 1 concentrations <100 μg/g was investigated. Subjects with a history of gastrointestinal cancer, gastrointestinal surgery, alcohol abuse, or inflammatory diseases were excluded. In 101 patients the mean (±SD) fat excretion was 9.19 ± 5.39 g. Only 41 patients (40.6%) had normal fat excretion <7 g/day. In 40 patients (39.6%), it was higher than 10 g/day, indicating relevant steatorrhea. The fat excretion did not correlate with diabetes type, duration, or clinical symptoms. This finding is of some clinical importance and might influence pathophysiological concepts and the management of diabetic patients.

Diagnosis and treatment of diabetes mellitus in chronic pancreatitis

Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus. It is a clinically relevant condition with a prevalence of 5%-10% among all diabetic subjects in Western populations. In nearly 80% of all type 3c diabetes mellitus cases, chronic pancreatitis seems to be the underlying disease. The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far. In contrast to the management of type 1 or type 2 diabetes mellitus, the endocrinopathy in type 3c is very complex. The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition. General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus (up to 90% of all cases) is rather good. However, in a patient first presenting with diabetes mellitus, chronic pancreatitis as a potential causative condition is seldom considered. Thus many patients are misdiagnosed. The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy. In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency, preventing or treating a lack of fat-soluble vitamins (especially vitamin D) and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.

Chronic Pancreatitis and Diabetes mellitus

Background: Pancreatic exocrine dysfunction has been described frequently in IDDM and NIDDM patients. Most authors tried to explain this finding as a diabetic complication. On the other hand, diabetes secondary to chronic pancreatitis (CP) might be more common than believed so far. Aim of the Study: In this study we evaluated pancreatograms of patients with known diabetes mellitus in order to detect ductal morphology changes characteristic for CP. Methods: Consecutive diabetic patients admitted for ERCP for different reasons were evaluated retrospectively concerning ERCP findings, especially pancreatic duct changes (Cambridge classification), diabetes type, duration and therapy. Results: 156 patients (76 male, 80 female; mean age 60 years (19–93)) were studied (38 IDDM; 118 NIDDM). Pancreatic ducts were classified as normal in 23.3%, CP°I in 22.7%, CP°II in 32.7% and CP°III in 21.3%. The duct changes did not correlate with diabetes type (p = 0.19), diabetes duration (p = 0.38), diabetes therapy (p = 0.5) or age (p = 0.48). Conclusion: Since CP should be defined by morphological and functional changes, it must be concluded that a substantial number of patients with a primary diagnosis of diabetes mellitus may have CP as a concomitant disease or, more likely, as a cause for their diabetic state.

Pancreatin therapy in patients with insulin-treated diabetes mellitus and exocrine pancreatic insufficiency according to low fecal elastase 1 concentrations. Results of a prospective multi-centre trial.

Recently, high prevalence of exocrine dysfunction in diabetic populations has been reported. Patients with fecal elastase 1 concentration (FEC) <100 µg/g have also been demonstrated to suffer from steatorrhea in about 60% of cases, indicating the need of pancreatic enzyme replacement therapy. Until now, there have only been a few reports on the use of enzyme replacement therapy in diabetic patients with exocrine pancreatic insufficiency. This investigation was designed to evaluate the impact of enzyme‐replacement therapy on glucose metabolism and diabetes treatment in a prospective study of insulin‐treated patients with diabetes mellitus.