Fibrocalculous pancreatic diabetes

Fibrocalculous pancreatic diabetes (FCPD) is a unique form of diabetes reported from tropical countries, associated with both endocrine and exocrine disease of the pancreas. The pre-diabetic phase of the disease is called tropical chronic pancreatitis (TCP). Currently FCPD is classified as a secondary form of diabetes called pancreatic diabetes, because essentially the disease is caused by pancreatic damage. There is an overlap of these subjects with idiopathic, non-alcoholic pancreatitis. This review will cover the etiopathogenesis, diagnosis and management of this clinical condition. FCPD could lead to endocrine dysfunction (diabetes and its complications) as well as exocrine dysfunction, and is associated with a higher risk of pancreatic cancer, for which early detection is important.     

The ketosis-resistance in fibro-calculous-pancreatic-diabetes. 1. Clinical observations and endocrine-metabolic measurements during oral glucose tolerance test.

We measured circulating levels of C-peptide, pancreatic glucagon, cortisol, growth hormone and metabolites (glucose, non-esterified fatty acids, glycerol and 3-hydroxybutyrate) in fibro-calculous-pancreatic diabetic (FCPD, n = 28), insulin-dependent diabetic (IDDM, n = 28) and non-diabetic control (n = 27) subjects during an oral glucose tolerance test. There was no difference in the two diabetic groups in age (FCPD 24 +/- 2, IDDM 21 +/- 2 years, mean +/- SEM), BMI (FCPD 16.0 +/- 0.6, IDDM 15.7 +/- 0.4 kg/m2), triceps skinfold thickness (FCPD 8 +/- 1, IDDM 7 +/- 1 mm), glycaemic status (fasting plasma glucose, FCPD 12.5 +/- 1.5, IDDM 14.5 +/- 1.2 mmol/l), fasting plasma C-peptide (FCPD 0.13 +/- 0.03, IDDM 0.08 +/- 0.01 nmol/l), peak plasma C-peptide during OGTT (FCPD 0.36 +/- 0.10, IDDM 0.08 +/- 0.03 nmol/l) and fasting plasma glucagon (FCPD 35 +/- 4, IDDM 37 +/- 4 ng/l). FCPD patients, however, showed lower circulating concentrations of non-esterified fatty acids (0.73 +/- 0.11 mmol/l), glycerol (0.11 +/- 0.02 mmol/l) and 3-hydroxybutyrate (0.15 +/- 0.03 mmol/l) compared to IDDM patients (1.13 +/- 0.14, 0.25 +/- 0.05 and 0.29 +/- 0.08 mmol/l, respectively). This could be due to enhanced sensitivity of adipose tissue lipolysis to the suppressive action of circulating insulin and possibly also to insensitivity of hepatic ketogenesis to glucagon. Our results also demonstrate preservation of alpha-cell function in FCPD patients when beta-cell function is severely diminished, suggesting a more selective beta-cell dysfunction or destruction than hitherto believed.     

Tropical calcific pancreatitis and fibrocalculus pancreatic diabetes in Bangladesh

The relationship between tropical calcific pancreatitis (TCP) and fibrocalculus pancreatic diabetes (FCPD) is still unclear. The clinical, biochemical and radiological data of age-matched TCP and FCPD subjects have been briefly discussed in the present review. Fibrocalculus pancreatic diabetes patients present with a significantly lower BMI compared with TCP patients. Analysis of the family history reveals that some kind of environmental factors seem to play a predominant role in the development of diabetes in FCPD patients, although these factors remain to be identified. Both TCP and FCPD patients predominantly come from a rural background. Fasting and 2 h blood glucose values as well as fructosamine levels in FCPD patients are approximately four-times higher than those of TCP patients. Measurements of early renal haemodynamic and microvascular changes (glomerular filtration rate, kidney size, microalbuminuria and microtransferrinuria) indicate an early renal involvement in FCPD patients. Tropical calcific pancreatitis subjects have approximately twice as high fasting C-peptide values compared with FCPD patients. Findings of single stranded DNA measurements suggest the involvement of oxidative damage in FCPD patients. Ketosis resistance is the most conspicuous clinical feature in the FCPD group and this relative absence of ketosis is probably due to a defect in the ketone body synthesis pathway and/or in the regulation of counterbalancing hormones. Endoscopic retrograde pancreatography findings of TCP and FCPD patients suggest that FCPD should not be considered only as a form of secondary diabetes consequent to generalized pancreatic damage in TCP.     

A SPINK1 gene mutation in a Thai patient with fibrocalculous pancreatic diabetes

Fibrocalculous pancreatitis diabetes (FCPD), a late stage of tropical chronic pancreatitis (TCP), is classified as a secondary cause of diabetes mellitus resulting from pancreatic exocrine dysfunction. The distinctive features of FCPD and TCP are young age at onset, presence of large intraductal pancreatic calculi, and reported mainly in tropical developing countries. Their etiology is still obscure, but the autodigestion due to aberrant intraductal activation of zymogens by trypsin is thought to be a primary common event. Recently, mutations in SPINKI gene encoding a pancreatic secretory trypsin inhibitor have been reported in association with an increased risk of pancreatitis. We describe a heterozygous mutation, IVS3+2 T>C, of SPINK1 gene in a young Thai female patient with typical presentation of FCPD. To our knowledge, this is the first report of the SPINK1 gene mutation in a FCPD patient in Southeast Asia.     

Anthropometric studies in diabetes in the Tropics

Summary Anthropometric studies were carried out in three groups of diabetics seen in southern India, namely fibrocalculous pancreatic diabetes (FCPD) (n=49) (a subtype of malnutrition related diabetes), insulin dependent diabetes mellitus (IDDM) (n=55) and non-insulin dependent diabetes mellitus (NIDDM) (n=104). Both FCPD and IDDM had significantly lower body mass index, skinfold thickness (triceps, biceps, subscapular and suprailiac), mid-arm circumference and fat mass compared to controls and NIDDM patients, (p<0.001 for all parameters). FCPD and IDDM males did not show any significant differences in any of the anthropometric parameters studied. Among the females, FCPD had lower triceps skinfold measurements (p=0.007) and mid-arm circumferences (p<0.05) compared to IDDM patients. Patients with NIDDM did not show any significant difference compared to the control group. This study shows that both FCPD and IDDM patients have lower body mass and fat mass compared to NIDDM patients and control subjects.     

Nutritional profile of fibrocalculous pancreatic diabetes and primary forms of diabetes seen in southern India

Plasma levels of retinol binding protein (RBP), prealbumin, total protein, albumin, transferrin and ferritin were estimated in three groups of diabetic patients seen at a diabetes centre in S. India. The groups consisted of patients with fibrocalculous pancreatic diabetes (FCPD), non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). Mean RBP levels were lower in FCPD and IDDM patients compared to controls but this did not reach statistical significance. Prealbumin levels were normal in FCPD patients, but low in IDDM compared to controls (P less than 0.005) and NIDDM (P less than 0.05). FCPD patients had lower transferrin levels compared to controls (P less than 0.05). There were no differences in the levels of total protein, albumin and ferritin in any of the study groups. The study shows that biochemical evidence of undernutrition is seen in FCPD and IDDM patients while NIDDM patients are not significantly different from non-diabetic control subjects.     

Natural history of endocrine failure in tropical chronic pancreatitis: a longitudinal follow-up study

BACKGROUND AND AIMS: Diabetes in tropical chronic pancreatitis (TCP), also known as fibrocalculous pancreatic diabetes (FCPD), is frequently seen at diagnosis. The aim of the present study was to determine the natural history of endocrine failure in TCP subjects without diabetes at baseline. METHODS: Of 73 TCP subjects without diabetes according to World Health Organization (WHO) criteria at baseline who were seen at an out-patient center, 54 (74.0%) underwent periodic oral glucose tolerance tests on follow up. Another 54 sex-matched, non-diabetic subjects without chronic pancreatitis served as controls. Baseline demographic and clinical characteristics were noted. RESULTS: After a median follow up of 5.0 years in TCP subjects and 7.0 years in controls, 27 of 54 TCP subjects (50%) developed diabetes compared with 14 of 54 controls (25.9%). Of the TCP subjects, those who developed diabetes on follow up were older (31 +/- 12 vs 23 +/- 11 years; P = 0.013), had a higher body mass index (21.7 +/- 4.4 vs 18.2 +/- 3.5 kg/m2; P = 0.004), higher 2 h post-load plasma glucose (8.8 +/- 1.9 vs 6.7 +/- 1.4 mmol/L; P < 0.001) and lower fecal chymotrypsin (2.1 +/- 1.2 vs 4.3 +/- 2.5 U/g; P < 0.001) at baseline compared with those who did not develop diabetes. The median time for the development of diabetes after diagnosis of TCP was 9.6 years (compared with 14.4 years among controls). Only 2 of 13 TCP subjects (15.4%) who had undergone surgical interventions during the normal glucose tolerance phase developed diabetes during follow up. CONCLUSIONS: In TCP, there is progressive deterioration of endocrine pancreatic function, with development of diabetes in 50% of patients upon follow up, suggesting that FCPD is merely a later stage in the course of TCP. Early surgery may prevent the development of diabetes in TCP subjects.     

Fibrocalculous pancreatic diabetes

Fibrocalculous pancreatic diabetes (FCPD) is a unique form of diabetes secondary to chronic pancreatitis seen in developing countries of the world associated with either overt protein–calorie malnutrition or, more likely, with deficiency of certain micronutrients. FCPD affects young individuals and runs an aggressive course to reach the endpoints of diabetes, pancreatic calculi and exocrine pancreatic dysfunction (steatorrhoea) in the majority of cases. There are characteristic features of FCPD radiologically, ultrasonographically, on endoscopic retrograde cholangiopancreatography and on histopathology which distinguish it from chronic pancreatitis of other aetiologies seen in temperate zones, e.g. alcoholic chronic pancreatitis. Although a secondary form of diabetes, specific diabetes-related complications like retinopathy and nephropathy do occur in FCPD. There appears to be a high risk of developing pancreatic carcinoma. Although the aetiology of FCPD is still unclear, the role of micronutrient (antioxidant) deficiency is emerging as a possible aetiological or predisposing factor. The contribution of genetic factors and environmental toxins, e.g. cyanogenic glycosides or other nutritional/toxic factors, merit further study. Studies on FCPD, a good model of a secondary form of diabetes, could lead to improved understanding of other primary forms of diabetes as well. If the underlying aetiological factors are identified, it may also be possible to prevent this type of diabetes. © 1998 John Wiley & Sons, Ltd.     

Assessment of a rapid pancreatic isoamylase assay as a screening test for chronic pancreatic disease

A new, rapid assay for pancreatic isoamylase (PIA) has been evaluated in normal subjects and patients with either proven chronic pancreatic disease or diseases in which chronic pancreatitis commonly enters the differential diagnosis. A wide normal range limited the diagnostic usefulness of the test. In non-pancreatic disease the serum levels of PIA were normal in 107 of 109 patients with non-pancreatic disease, but only 3 of 16 patients with chronic pancreatitis and proven exocrine insufficiency had a low PIA level, and variable levels occurred in pancreatic carcinoma. These results suggest that measurement of serum PIA is of limited value as a screening test for chronic pancreatic disease.     

Fecal immunoreactive lipase: a new tubeless pancreatic function test.

Immunoreactive lipase (IRL) was measured in 368 stool samples from 231 individuals by means of a new enzyme-linked immunoabsorbent assay technic, to test its validity as an indicator of exocrine pancreatic insufficiency. Ninety-seven stool samples from 64 healthy volunteers showed a logarithmically normal distribution of IRL values and a median IRL concentration of 17 micrograms/g (range, 2.75-117.3 micrograms/g) with a statistically calculated lower normal limit of 4 micrograms/g. In 100 stool samples from patients with chronic pancreatitis and proven steatorrhea the median IRL concentration of 6 micrograms/g (range, 0.002-107 micrograms/g) was significantly lower than that of normal controls and of 52 stool samples from patients with chronic pancreatitis without steatorrhea (IRL, 40 micrograms/g; range, 0.55-302 micrograms/g), 45 stool samples from 23 patients with celiac disease (IRL, 96 micrograms/g; range, 6.05-563 micrograms/g), and 30 stool samples from 26 patients with chronic diarrhea (IRL, 57 micrograms/g; range, 4.2-573 micrograms/g). It is concluded that fecal IRL is a promising new enzyme test with low diagnostic sensitivity (34%) but excellent diagnostic specificity (98%) in chronic pancreatitis and for diagnostic study of chronic diarrheal disorders. In contrast to fecal chymotrypsin, the test results are unaffected by pancreatic enzyme replacement therapy.     

The fecal chymotrypsin photometric assay in the evaluation of exocrine pancreatic capacity. Comparison with other direct and indirect pancreatic function tests

Fecal chymotrypsin (FCT) has been measured by a new photometric method (Monotest Chymotrypsin; Boehringer, Mannheim) in 78 patients: 44 with chronic pancreatitis and 34 not affected by any pancreatic disease. The results were compared with those from other tests of pancreatic secretory (secretin-cerulein test) and digestive [serum and urinary p-aminobenzoic acid (PABA) and pancreolauryl] capacity. When FCT values were severely reduced (below 6.7 U/g), from 90 to 100% of the patients also presented abnormal pancreatic secretory and digestive capacity. On the other hand, 87% of the patients with normal FCT (above 20 U/g) presented normal secretory and digestive capacity. Patients with intermediate FCT values (between 6.7 and 20 U/g) showed normal or abnormal pancreatic secretory and digestive capacity with the same probability. Therefore, FCT, carried out as a first test, seems to identify subjects that need no further pancreatic function tests (normal and severely impaired FCT) and patients who need other more complex functional investigations (intermediate FCT values).     

Stimulation of immunoglobulin E formation in chronic pancreatitis by alcohol drinking and exocrine pancreatic insufficiency

Many patients with chronic pancreatitis (CP) complain of several types of food intolerance despite elimination of fat and alcohol. Since there are no data on serum immunoglobulin E (IgE) concentrations in CP, IgE concentrations in serum were detected in 97 persons with CP and 50 controls. IgE was analyzed by the use of a highly sensitive fluoro-enzyme-immunoassay. In CP, a significantly raised IgE level (mean +/- SEM; 286.1 +/- 49 KU/L; p < 0.0001) was detected compared with controls (65.2 +/- 13 KU/L). CP-patients without alcohol consumption and normal exocrine pancreatic function were found to have only slightly elevated serum IgE values (120.2 +/- 54 KU/L), whereas patients with exocrine insufficiency treated with enzyme supplementation showed an IgE level of 153.7 +/- 51 and exocrine insufficient patients without treatment of 261.0 +/- 173 KU/L (p = 0.01). IgE levels were far more elevated in the corresponding groups with continued alcohol consumption (> 25 g/day). Alcohol consuming patients with CP and normal pancreatic function had a mean serum IgE of 295.0 +/- 114 KU/L, while patients with alcohol consumption and sufficiently treated exocrine pancreatic insufficiency showed a serum IgE of 393.7 +/- 147 KU/L (p = 0.03). Non-enzyme supplemented patients with CP and exocrine pancreatic insufficiency were characterized by approximately 10-fold increased serum IgE (1080.0 +/- 313 KU/L; p = 0.001). Non-allergic, alcohol consuming patients with CP have significantly increased serum IgE values. Since patients without alcohol consumption and normal pancreatic function or sufficiently treated exocrine insufficiency showed clearly lower IgE values than non-compliant patients with manifest exocrine pancreatic insufficiency, these results are compatible with the assumption that a reduced rate of antigen digestion in exocrine pancreatic insufficiency may lead to an increased intestinal antigen load, stimulating an abnormal humoral immune response with IgE production. Alcohol may further contribute to this by damaging the mucosal barrier.     

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis

Summary Conclusion Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled, that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes). Background We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis. Methods Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied. Results The urinary CPR excetion in controls was 94.9±20.5 μg/d. The urinary CPR excretion in calcific pancreatitis was 12.8±7.4 μg/d and it resembled that in IDDM (9.4±5.8 μg/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5±30.1 μg/d, being similar to that in NIDDM (49.3±21.0 μg/d). The plasma glucagon level in calcific pancreatitis was 64.1±15.9 ρg/mL, which was significantly lower than the values in IDDM (111.2±50.2 ρg/mL) and NIDDM (96.7±21.9 ρg/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4±29.6 ρg/mL) were significantly lower than that in controls (12.9±21.6 ρg/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.     

Faecal chymotrypsin assay in tropical and alcoholic chronic pancreatitis

Faecal chymotrypsin (FCT) levels were estimated in a group of patients with tropical chronic pancreatitis (TCP) and compared with patients with alcoholic chronic pancreatitis (ACP), 'gastrointestinal' controls and 'healthy' subjects. Exocrine pancreatic insufficiency as assessed by low faecal chymotrypsin levels (less than 5.8 mu/g) were present in 85.7 per cent of TPC and 84.6 per cent of ACP patients. Mean FCT levels as well as the distribution of FCT values were similar in TCP and ACP patients and significantly lower than the two control groups (P less than 0.001). There was also no difference with respect to mean FCT levels between subgroups of TCP patients with and without diabetes and those with and without calcification. Faecal chymotrypsin assay is a simple test for diagnosis of chronic pancreatitis in gastroenterological centres in tropical countries.     

Effects of synthetic human gastrin-releasing peptide on pancreatic exocrine secretion and release of pancreatic polypeptide in conscious rats

The effects of a newly synthesized peptide, human gastrin-releasing peptide (hGRP), on the pancreatic exocrine secretion and the release of pancreatic polypeptide (PP) were examined in the conscious rat. Plasma PP concentrations were determined by a recently established specific radioimmunoassay for rat PP. Amounts of 0.18, 0.35, and 3.5 nmol/kg/h hGRP significantly stimulated both pancreatic exocrine secretion and 0.35 nmol/kg/h of hGRP increased PP release. Simultaneously infused proglumide (300 mg/kg/h) did not affect either pancreatic exocrine secretion or PP release. However, simultaneous infusion of atropine (100 micrograms/kg/h) slightly inhibited PP release, but did not restrict the incremental response of pancreatic protein secretion to hGRP. These results suggest that hGRP directly stimulates pancreatic exocrine secretion and PP release.     

Trypsin and lactoferrin levels in pure pancreatic juice in patients with pancreatic disease.

Levels of immunoreactive trypsin were measured in pure pancreatic juice obtained endoscopically from 44 patients with suspected pancreatic disease. Patients with pancreatic cancer all had low trypsin concentrations (median 3.6 micrograms/ml, range 0.6--12.0), but those with chronic pancreatitis had very variable levels (median 14.2 micrograms/ml, range 3.2--76.8), showing a considerable overlap with patients without pancreatic disease (median 37.1 micrograms/ml, range 10.4--66.0). When levels of lactoferrin in pancreatic juice were measured, all patients with chronic pancreatitis were found to have much higher levels (all greater than 900 ng/ml) than control subjects or patients with pancreatic cancer (all less than 400 ng/ml). The combined measurement of trypsin and lactoferrin in pure pancreatic juice appeared to be more promising than any other currently available test for the separation of patients with pancreatic cancer from those with chronic pancreatitis.     

Serum immunoreactive cationic trypsinogen: a useful indicator of severe exocrine dysfunction in the paediatric patient without cystic fibrosis.

We evaluated serum cationic trypsinogen as a marker of exocrine pancreatic function in children without cystic fibrosis. The ability of this test to determine steatorrhoea of pancreatic origin, and its relationship to a wide range of exocrine pancreatic function were assessed. Serum trypsinogen was measured in 32 children with steatorrhoea, 10 with pancreatic and 22 with non-pancreatic causes. In patients with pancreatic steatorrhoea, serum cationic trypsinogen was 4.9 +/- 4.9 micrograms/l (mean +/- SD), significantly below values in patients with non-pancreatic steatorrhoea (47.0 +/- 22.1 micrograms/l, p less than 0.001) and 50 control subjects (31.4 +/- 7.4 micrograms/l, p less than 0.001). Serum cationic trypsinogen values in patients with pancreatic steatorrhoea all fell below the lower limit of our control range and below all values for patients with non-pancreatic steatorrhoea. Serum cationic trypsinogen was also evaluated against pancreatic trypsin output in 47 patients (range 0.2-17.0 yr who underwent a hormonal pancreatic stimulation test. In 17 patients, serum cationic trypsinogen was low (less than -2SD or less than 16.6 micrograms/l), and associated with greatly impaired pancreatic trypsin output, ranging from 0-8% of mean normal trypsin output. Five of these 17 patients did not have steatorrhoea. In 30 patients with normal or raised serum cationic trypsinogen (greater than or equal to 16.6 micrograms/l), pancreatic trypsin output ranged from 15-183% of mean normal values. In conclusion, low serum cationic trypsinogen suggests severely impaired exocrine pancreatic function, with sensitivity extending above the steatorrhoeic threshold. In the presence of steatorrhoea, low serum cationic trypsinogen indicates a pancreatic aetiology. Normal serum cationic trypsinogen, however, does not exclude impaired pancreatic function, above the steatorrhoeic threshold.     

Somatostatin analog, SMS 201-995, inhibits pancreatic exocrine secretion and release of secretin and cholecystokinin in rats.

We studied the effect of a synthetic octapeptide somatostatin analog, SMS 201-995 (sandostatin), on pancreatic exocrine secretion and on plasma secretin and cholecystokinin (CCK) levels in vivo in anesthetized rats. The exocrine pancreas was stimulated by either intravenous infusion of both secretin (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 micrograms/kg/h) or intraduodenal infusion of oleic acid (pH 6.5) in a dose of 0.25 mmol/h. Intravenous administration of SMS 201-995 in three different doses of 100, 200, and 400 ng/kg/h resulted in dose-related inhibition of pancreatic secretion in terms of volume, bicarbonate, and amylase stimulated by exogenous secretin and CCK. Intraduodenal oleic acid stimulated pancreatic secretion, including volume, bicarbonate, and amylase, and this was accompanied by a significant elevation in the plasma concentrations of secretin and CCK. Intravenous administration of SMS 201-995 in the three different doses described above caused dose-dependent suppression of the increase in pancreatic exocrine secretion as well as the plasma concentration of secretin and CCK induced by intraduodenal infusion of oleic acid. It is concluded that SMS 201-995 inhibits pancreatic exocrine secretion and the release of endogenous hormones, such as secretin and CCK, in rats.     

Fecal pancreatic elastase: a reproducible marker for severe exocrine pancreatic insufficiency

Background In order to apply fecal pancreatic elastase for follow-up of exocrine pancreatic function in chronic pancreatitis and cystic fibrosis, we examined the sensitivity, specificity, and long-term variability of a new polyclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Methods Patients with definite chronic pancreatitis (n = 23), probable or possible chronic pancreatitis (n = 14), autoimmune pancreatitis (n = 7), or acute pancreatitis (n = 11), and 51 healthy subjects and 11 healthy infants participated in this study. Pancreatic function was graded as normal (n = 3), mild (n = 18), moderate (n = 9), or severe (n = 18) exocrine insufficiency on the basis of secretin tests. Fecal pancreatic elastase was measured by a new ELISA. Results Fecal pancreatic elastase concentration in control subjects varied widely, with a median of 478 μg/g. The specificity of this test was 90.2% with a cutoff value of >200 μg/g. The sensitivities were 60.9% for detecting definite chronic pancreatitis, 76.5% for calcifying pancreatitis, 71.4% for autoimmune pancreatitis, and 7.1% for probable or possible chronic pancreatitis. The sensitivities were 16.7% for mild, 12.5% for moderate, and 72.2% for severe exocrine pancreatic insufficiency. Forty patients were reexamined after a median interval of 347 days. The fecal pancreatic elastase levels between the first and second tests were not significantly different. Two infants, 4.5 and 5 months old, had abnormally low values, but after a median of 304 days all infants showed normal levels (median, 444 μg/g). Conclusions Fecal pancreatic elastase is a reproducible marker for severe exocrine pancreatic insufficiency. This test is valuable for longitudinal follow-up of exocrine pancreatic function.     

Serum concentrations of trypsin-like immunoreactivity and pancreatic isoamylase in insulin dependent diabetic patients

Serum trypsin-like immunoreactivity and pancreatic isoamylase were measured in 302 insulin-dependent diabetic patients (166 men) using radioimmunoassay for the former and a photocolorimetric method for the latter. There was a significant correlation between the two enzymes (r = 0.67, p less than 0.0001) with lower concentrations of both trypsin-like immunoreactivity (208.8 micrograms/L) and pancreatic isoamylase (67.5 U/L) in diabetic patients as compared to controls (p less than 0.0001). Using multiple regression analysis, a statistically significant association was only apparent between enzyme concentrations and age at onset of diabetes (r = 0.31, p less than 0.0001). The results suggest that impaired exocrine pancreatic function may occur in an appreciable proportion of diabetic patients and also that a primary insult to the exocrine pancreas occurring at the time of endocrine injury may be a contributory factor.