Serum Concentration of Cathodic Trypsin-Like Immunoreactivity and Pancreatic Isoamylase in Insulin-Dependent Diabetes Mellitus

ABSTRACT. The relationship between diabetes mellitus and the exocrine pancreatic function was evaluated in 29 patients with insulin-dependent diabetes mellitus by measuring cathodic trypsin-like immunoreactivity (TLI) and the enzymatic activity of pancreatic isoamylase in serum before and 90 min after breakfast and insulin. Thirty healthy subjects served as reference group. Median fasting serum concentrations in the diabetic subjects were significantly lower than in the reference subjects: for TLI 143 and 299 μg trypsin standard/I and for pancreatic isoamylase 43 and 101 U/I, respectively (p<0.001 for both). A positive correlation between TLI and pancreatic isoamylase was present in the diabetics (Sperman's rho=0.56, p<0.01). The serum concentrations of TLI and pancreatic isoamylase were not related to the duration of diabetes, daily insulin dose or glycemic control measured by blood glucose and total glycosylated hemoglobins. Cathodic TLI and pancreatic isoamylase in serum were not influenced by food and insulin.     

Serum lipase,isoamylase and pancreatic function test (PFT) in juvenile-onset insulin-dependent diabetes mellitus

Summary Significantly decreased activity of pancreatic isoamylase in serum was found in a group of 51 juvenile-onset insulin-dependent diabetics as compared to healthy subjects (p<0.005). No significant changes were observed for urinary p-aminobenzoic acid excretion in 20 of the juvenile-onset diabetics in whom the NBT-PABA test was performed, even though 25% of the values were below the normal limit. A highly significant decrease of serum lipase activity was found in juvenile-onset diabetics as compared to controls (p<0.001). No significant correlation was found in juvenile-onset diabetics between serum pancreatic isoamylase and lipase or marker of chymotrypsin activity expressed as the amount of p-aminobenzoic acid excreted into urine. The NBT-PABA test appears to be of small importance in the evaluation of changes of the exocrine pancreas in insulin-dependent diabetes mellitus. However, simultaneous evaluation of serum pancreatic isoamylase and lipase activities justified the suspicion of pancreatic damage in 50% of the patients tested.     

Sources of the serum isoamylases and their normal range of variation with age.

The isoamylases in various human tissue homogenates and body fluids were separated by agarose gel electrophoresis. Nothing suggested any significant production of amylase in the liver. Minute amounts of amylase belonging to the pancreatic group of isoamylases might be produced by the glands of the proximal duodenum. The specific group of isoamylases produced in the female genital tract could not be demonstrated in serum or urine. The activity of amylase in serum was derived from two groups of isoenzymes, one group originating from the salivary glands, the other from the pancreatic gland. The contribution of each of these two sources to the total serum amylase was determined from early foetal life to adult age. A very low activity of the salivary isoamylases was regularly found in serum from 14-week-old foetuses. The activity increased steadily with age and reached the normal adult level, about 80 U/l, at the age of 5 years. The pancreatic group of isoamylases in serum developed later; the majority of children below 3 months had no demonstrable pancreatic isoamylase activity. The activity rose slowly to reach adult level, about 80 U/l, at the age of 10 to 15 years. The activity did not vary with sex, and the diurnal variation of the isoamylase was negligible. In children with cystic fibrosis of the pancreas the activity of pancreatic isoamylases in serum was low.     

Acute alcohol intoxication: significance of the amylase level

To evaluate the effects of acute alcohol intoxication on serum amylase and isoamylase levels, 58 clinically intoxicated patients with blood alcohol levels greater than 100 mg/dL were studied. Comparisons were made to normal control and a sober chronic alcoholic group. Admitting serum isoamylase levels were determined by cellulose acetate membrane electrophoresis and serum amylase levels measured by the Amylochrome technique. The average blood alcohol level in the intoxicated group was 301 +/- 99 mg/dL. Thirty of the 58 patients had hyperamylasemia (greater than 207 IU). Twenty-five of these 30 patients had hyperamylasemia from nonpancreatic sources (increased salivary isoamylase). Two of the 30 patients had pancreatic hyperamylasemia and three patients had elevated levels of both isoamylases. Neither of the patients with pancreatic hyperamylasemia had clinical evidence of acute pancreatitis. Although nine of the 58 patients had abdominal pain and clinical symptoms suggestive of acute pancreatitis, none of these patients had elevated pancreatic isoamylase. The finding of hyperamylasemia in acutely intoxicated patients is common. This is most frequently due to a rise in the salivary (nonpancreatic) isoamylase. The reliability of the total serum amylase as an indication of pancreatic disease in the intoxicated patient is questioned.     

Determination and kinetic analysis of non-insulin mediated glucose uptake in Type 1 (insulin-dependent) diabetes mellitus

Summary In man, total glucose uptake is the sum of insulin mediated glucose uptake and non-insulin mediated glucose uptake. The latter pathway has not been examined in Type 1 (insulin-dependent) diabetes mellitus. In order to assess non-insulin mediated glucose uptake in Type 1 diabetes, we measured steady-state rates of glucose uptake during glucose clamps at 5.27, 9.71 and 12.5 mmol/l using low (0.25 mU· kg^–1·min^–1), intermediate (0.75 mU·kg^–1·min^–1) and high (1.50 mU·kg^–1·min^–1) insulin infusion rates in 10 subjects with Type 1 diabetes. For insulin infusion rates of 0.25, 0.75 and 1.50 mU·kg^–1·min^–1 as plasma glucose rose from 5.27 to 9.71 mmol/l, total glucose uptake increased by 35, 43 and 52 percent respectively (p<0.05 for each insulin infusion rate). For all three insulin infusion rates, there was no significant increase in total glucose uptake as plasma glucose increased from 9.71 to 12.5 mmol/l. At each glycaemic level, glucose uptake correlated significantly with plasma free insulin (r=0.81, p<0.01 at 5.71 mmol/l; r=0.84, p<0.01 at 9.71 mmol/l; r=0.73, p<0.02 at 12.5 mmol/l). Linear regression analysis to a point corresponding to plasma free insulin equalling zero, yielded values for non-insulin mediated glucose uptake (mmol·kg^–1·min^–1) of 0.11,0.14,0.18 at plasma glucose of 5.27, 9.7 and 12.5 mmol/l respectively. Thus, increasing plasma glucose concentrations were associated with increasing rates of non-insulin mediated glucose uptake. For each insulin infusion rate used, the percent of total glucose uptake accounted for by non-insulin mediated glucose uptake remained independent of plasma glucose concentration, but decreased as insulin infusion rate increased. During the insulin infusion at 0.25 mU·kg^–1·min^–1, this percentage ranged from 83.7 to 91.4%. Analysis of glucose uptake data derived for theoretical plasma insulin levels of 0, 40, 80 and 160 U/ml yielded linear Eadie-Hofstee plots (r=– 0.83 to – 0.99), suggesting that insulin increased Vmax but did not alter Km. Hence, in these subjects with Type 1 diabetes, glucose uptake, both insulin mediated and non-insulin mediated can be described by Michaelis-Menten kinetics. Comparison of values obtained for Vmax and Km in the present studies of Type 1 diabetes with those obtained from non-diabetic subjects indicates that non-insulin dependent glucose uptake in Type 1 diabetes is quantitatively similar to that of non-diabetic subjects.     

Relation between serum pancreatic isoamylase concentration and pancreatic exocrine function

Serum pancreatic isoamylase concentrations were compared to secretory and clinical evidence of pancreatic insufficiency in 19 consecutive alcoholic patients undergoing pancreatic stimulation testing for suspected pancreatic insufficiency. In patients with normal total serum amylase levels, there was a good correlation (r=0.83) between serum pancreatic isoamylase activity and stimulated pancreatic secretion of amylase and the 8 patients with a low pancreatic isoamylase concentration had markedly diminished pancreatic secretion of amylase, lipase, and bicarbonate. However, patients with elevated total serum amylase activity frequently had extremely poor pancreatic exocrine function despite normal or elevated levels of pancreatic serum isoamylase. Thus, the finding of a subnormal serum concentration of pancreatic isoamylase provides strong evidence for pancreatic exocrine insufficiency; however, a normal or elevated serum pancreatic isoamylase activity cannot be used as evidence for normal pancreatic exocrine function.     

Amylase,Pancreatic Isoamylase and Lipase in Serum before and after Endoscopic Pancreatography

ABSTRACT. Serum amylase, isoamylase and lipase were determined in 17 patients with pancreatic or biliary diseases before and after endoscopic retrograde pancreatography (ERP). Within ½-2 hours after cannulation of the pancreatic duct, serum lipase was increased to approximately 4 times the upper reference level and normalized almost completely at 24 hours. A much smaller increase was found in amylase and isoamylase. The elevation in enzyme activities was less in patients with abnormal than with normal ERP. The results suggest that lipase is a more sensitive indicator of pancreatic injury than amylase and isoamylase.     

Hepatic Glucose-6-Phosphatase Activity in Non-Insulin Dependent Diabetics

ABSTRACT The role of glucose-6-phosphatase (G6Pase) in postreceptional glucose handling in non-insulin dependent diabetics (NIDDs) was investigated by comparing the enzyme values in diagnostic liver biopsy samples with fasting blood glucose (BG), immunoreactive insulin (IRI) and plasma antipyrine half-life (T/2). The NIDDs, treated with sulphonylureas, had elevated serum aminotransferase and alkaline phosphatase values associated with fatty liver with or without fibrosis. G6Pase activity was reduced in the NIDDs compared with subjects who had undergone gallstone surgery (p<0.001), insulin dependent diabetics (p<0.001), and age- and sex-matched non-diabetics (p<0.001). G6Pase was inversely related to BG and antipyrine T/2, but not to IRI or conventional liver function tests. Therapy with phenobarbital and medroxyprogesterone acetate, known inducers, increased G6Pase activity, shortened antipyrine T/2, reduced BG and did not alter IRI, in four NIDDs. Low liver G6Pase activity in NIDDs may hence be one factor underlying the impaired glycemic control.     

Upper gastrointestinal endoscopy an unrecognized cause of hyperamylasemia

The prevalence of hyperamylasemia 2 hr and 24 hr after upper gastrointestinal endoscopy without attempts to cannulate the ampulla of Vater was prospectively studied in 50 consecutive patients. In the 2-hr sample, hyperamylasemia was observed in nine patients (18%) (serum amylase range 59–191 units/liter with a mean value of 102 units/liter; reference range: 12–46 units/liter). Five of the nine patients still had an increased serum amylase (range 54–118 units/liter, mean 78.4) 24 hr after endoscopy. When hyperamylasemia occurred, it always appeared in and was higher in the 2-hr sample. The increased serum amylase activity was due to a rise of S-type isoamylase. The cause of hyperamylasemia after gastrointestinal endoscopy is speculative but is probably due to an hypersalivation.     

The effect of residual insulin secretion on exocrine pancreatic function in juvenile-onset diabetes mellitus

Summary Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bicarbonate, amylase and trypsin were measured. Exocrine secretory pancreatic function was decreased in 14 patients. Fasting and maximal CPR showed that 9 patients had residual insulin secretion. For these CPR-secretors there was a strong correlation between CPR and output of bicarbonate (r = 0.87, p < 0.005) and amylase (r =0.7, p < 0.05), but not with trypsin. These results suggest the existence of an endocrine-exocrine relationship in the pancreas.     

INSULIN SECRETORY CAPACITY, β-THROMBOGLOBULIN and BLOOD VISCOSITY IN LONG STANDING, NON-INSULIN DEPENDENT DIABETICS WITH and WITHOUT MICROANGIOPATHY

A comparison was made of insulin secretion in response to i.v. glucose between non-insulin dependent diabetics with and without severe microangiopathy. During i.v. glucose tolerance testing those with complications had significantly lower serum insulin concentration (at 40 and 60 min 15.2 ± 2.9 and 11.7 ± 2.5 mll-1 respectively) than those without (26.1 ± 4.7 and 24.3 ± 3.6 mU-1, p <0.01). The differences were also significant when insulin increment above basal was determined. All subjects had raised plasma beta-thromboglobulin concentration (indicating increased tendency to platelet aggregation), but with no significant difference between the two groups. There was also no difference in fasting glucose, kg values, HbAI or blood viscosity. We conclude that non-insulin dependent diabetics with severe microangiopathy have significantly reduced insulin secretory capacity in response to i.v. glucose when compared with those without.     

Exocrine pancreatic function in the early period after pancreatoduodenectomy and effects of preoperative pancreatic duct obstruction

Exocrine pancreatic function in the early period after pancreatoduodenectomy was investigated. The effects of preoperative pancreatic duct obstruction on exocrine pancreatic function were also investigated. The volume of pancreatic juice and its amylase activity were investigated in 39 patients who underwent pancreatoduodenectomy (including pylorus-preserving pancreatoduodenectomy). TheN-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA) test was performed on 23 of 39 patients about 40 days after pancreatoduodenectomy. The exocrine pancreatic function was inhibited three to eight days after pancreatoduodenectomy (amylase activity: 23,700±4300 IU/day), and recovered on days 9–15 (48,000±8400 IU/day) in patients with a normal main pancreatic duct. In patients with pancreatic duct obstruction, the exocrine pancreatic function was almost eliminated (amylase activity: 440±260 IU/day) and BT-PABA test results were low (45±17%). In patients with narrowed pancreatic duct, amylase secretion was significantly inhibited even in patients with a normal number of acinar cells. There was a good positive correlation (Spearman's rank correlation coefficient,rs=0.715,P<0.01) between amylase secretion and BT-PABA test. Amylase secretion more than 10,000 IU/day is essential for a normal BT-PABA test and normal digestive function. The inhibited digestive function in patients with pancreatic duct obstruction may be due to the decreased number of acinar cells and the inhibition of exocrine pancreatic function.     

Metabolic profiles in closely controlled diabetic pregnancies during the third trimester

Summary In 5 closely controlled pregnant diabetics (duration of pregnancy 237–266 days) and 5 pregnant non-diabetics (duration of pregnancy 210–278 days) 4-hourly blood samples were taken throughout a 24 h period and analyzed for blood glucose, lactate, pyruvate, 3-hydroxybutyrate and acetoacetate, plasma non-esterified fatty acids (NEFA), glucagon and cortisol. 24 h urine specimen was analyzed for total catecholamines and 4-hydroxy-3-methoxymandelic acid. There were few significant differences in concentrations of metabolites and hormones in the two groups at any time, although the variations about the mean was usually greater in the diabetics. Thus for blood glucose in diabetics, mean value was 4.4 mmol/l, coefficient of variation 43%; in non-diabetics 4.1 mmol/l and 10% respectively. Mean plasma 3-hydroxybutyrate in diabetics was 0.47 mmol/l, coefficient of variation 55%; in non-diabetics 0.44 mmol/l and 37% respectively. Plasma non-esterified fatty acid levels were significantly higher in the diabetics (0.47 mmol/l) than in the non-diabetics (0.26 mmol/l). Coefficients of variation were 46% and 33% respectively. Two conclusions can be drawn; first, when near normal mean values for blood glucose are achieved, other metabolite and hormone levels are also near normal; second, even when the available means for diabetic control, strict diet and insulin-mixtures twice daily, are used at their maximum, metabolism in diabetics is more unstable than in non-diabetics.     

Diabetes mellitus induced inhibition of glucosaminyl N-deacetylase: effect of short-term blood glucose control in diabetic rats

Summary Inhibition of glucosaminyl N-deacetylase activity, a key enzyme in heparan sulphate sulphation, may be involved in the development of late diabetic vascular complications. We examined the effect of short- and long-term metabolic control on N-deacetylase activity in streptozotocin diabetic H and U rats. Spontaneously diabetic BB rats were included in parts of the study. Over a 3-week period blood glucose was maintained at predetermined levels (6–10 mmol/l or 10–20 mmol/l) by insulin treatment and then during the final 2 days rapidly reversed in half of each group. In the U rats, the hepatic N-deacetylase activity significantly decreased by 10–15% following short-and long-term poor metabolic control and the inhibition was entirely reversed by short-term good control. In the H rats a similar, not significant, effect was seen. BB rats in long-term poor control showed a 10% reduction in hepatic N-deacetylase activity (p=0.003). Glomerular N-deacetylase activity was reduced in U rats after long-term poor control (p=0.004) but not in H and BB rats. There was an overall correlation between urinary albumin excretion and glomerular N-deacetylase activity (r=–0.60, p<0.0001). We conclude that diabetes-induced inhibition of hepatic N-deacetylase is not restricted to the streptozotocin diabetic model, and that short-term blood glucose control is of major importance. Genetic factors and tissue specificity influence the vulnerability of the enzyme. Finally, the study suggests an association between N-deacetylase activity and urinary albumin excretion.     

High-density lipoprotein cholesterol and apolipoprotein A-I levels at diagnosis in patients with non-insulin dependent diabetes

Summary High-density lipoprotein (HDL) cholesterol levels were decreased in patients with non-insulin dependent diabetes at diagnosis when matched with a control population for sex, age, obesity, alcohol consumption and cigarette smoking. There was no association between serum HDL-cholesterol concentration and the percentage of glycosylated haemoglobin A₁ (HbA₁). Serum HDL-cholesterol levels were lower in diabetics over the whole range of serum triglyceride levels, and particularly in hypertriglyceridaemic diabetics. Serum apolipoprotein A-I levels were not decreased in diabetics with normal serum triglyceride levels, so that the ratio of HDL cholesterol to apolipoprotein A-I was significantly decreased in diabetics (p<0.005). Decreased HDL cholesterol levels in non-insulin dependent diabetes could be relevant to the subsequent development of atherosclerosis.     

Blood glucose,insulin and amylase levels in pancreatic lesion due to pancreatography

Summary Blood glucose, insulin and amylase levels were repeatedly determined in 8 patients developing pancreatic lesion after diagnostic pancreatography. The injection into the pancreatic duct of small amounts (2–8 ml) of contrast medium resulted invariably in a rise in blood amylase level, which was associated in some of the patients with insulin release and increased blood glucose. With larger doses of contrast medium (14–18 ml) blood amylase was considerably increased, the rise in plasma insulin level also being more marked. Elevation of blood insulin and glucose concentrations may be accounted for by the release of glucagon and insulin from the damaged islet cells. The biochemical changes observed in pancreatic lesions due to pancreatography might provide some information concerning the pathogenetic mechanism of spontaneous pancreatitis in man. Traduzione a cura di G. U.     

Circulating lymphocyte subpopulations in juvenile insulin-dependent diabetes

Summary Circulating lymphocytes from 39 juvenile insulin dependent diabetics of recent onset were studied by six membrane marker techniques and mitogen stimulation. Well controlled (n = 14) were grouped separately from poorly controlled (n = 25) patients. The total lymphocyte counts were not different from 50 control subjects. The percentage of T-cells detected by erythrocyte rosettes and B-cells detected by erythrocytes — antibody — complement rosettes was significantly decreased only in poorly-controlled diabetics (64.1 ± 1.3 and 9.7 ± 1.8, vs 71.0 ± 1.0 and 15.3 ± 0.6 in controls). Cells bearing receptors for the Fc fragment of IgG immunoglobulins were decreased in both groups. Mitogen stimulation was not different from controls but was significantly lower in poorly controlled than in well controlled diabetics. Optimal blood glucose control for 5 ± 2 days using an external artificial pancreas led to a rapid normalisation of membrane marker values and mitogen responsiveness of lymphocytes from previously poorly controlled diabetics. Separate in vitro experiments showed that glucose had an inhibitory effect on mitogen stimulation at concentrations 8.3 mmol/l and on T- and B-lymphocyte numbers at concentrations 55.6 mmol/l. DL 3-hydroxybutyrate tested at 17.1 and 34.2 mmol/l only depressed mitogen responsiveness. Such results suggest a rapidly reversible T-cell defect closely linked to the existing metabolic disturbances.     

Erythrocyte sodium-lithium countertransport activity and total body insulin-mediated glucose disposal in normoalbuminuric normotensive Type 1 (insulin-dependent) diabetic patients

Summary Insulin resistance in Type 1 (insulin-dependent) diabetes mellitus may be associated with raised erythrocyte sodium-lithium countertransport activity in patients with hypertension, or nephropathy, or both. However, in these circumstances it is difficult to separate the impact of hypertension, hyperlipidaemia and nephropathy on erythrocyte sodium-lithium countertransport from that of insulin resistance. We have therefore examined the relationship between insulin-mediated glucose disposal and erythrocyte sodiumlithium countertransport in 41 normotensive (mean blood pressure 120/74 mm Hg), normoalbuminuric (mean albumin excretion 6.2 g/min), normolipidaemic (mean serum cholesterol 4.3 mmol/l and mean serum triglycerides 1.0 mmol/l) Type 1 diabetic patients. Erythrocyte sodium-lithium countertransport was on average 0.31 mmol Li · h^–1 · l erythrocytes ^–1 (range 0.07–0.69). Nine patients had values above 0.40 mmol Li · h^–1 erythrocytes^–1 (0.51±0.10 mmol Li · h^–1 · l erythrocytes^–1). The patients with high erythrocyte sodium-lithium countertransport were matched for age, sex, BMI, HbA₁ and duration of diabetes, with nine patients with normal erythrocyte sodium-lithium countertransport. Insulin-mediated glucose disposal was evaluated during the last hour of a euglycaemic clamp (insulin 0.015 U · kg^–1 · h^–1; blood glucose clamped at 7.0 mmol/l). The free insulin levels were comparable between the patients with high and normal erythrocyte sodium-lithium countertransport (37.2±14.7 mU/l and 34.7±17.2 mU/l respectively). Insulin-mediated glucose disposal was on average 3.1±1.5 (range 0.8–6.8) mg · kg^–1 · min^–1. Erythrocyte sodium-lithium countertransport did not correlate with insulin-mediated glucose disposal in all 41 cases (r _s=–0.14), but when the matched groups were compared, patients with raised erythrocyte sodium-lithium countertransport had lower insulin-mediated glucose disposal rates compared to those with normal erythrocyte sodium-lithium countertransport (2.7±1.1 vs 3.9±1.3 mg · kg^–1 · min^–1; p=0.044). In these 18 patients a significant inverse relationship was found between erythrocyte sodium-lithium countertransport and insulin-mediated glucose disposal (r _s=–0.62; p=0.003). Raised erythrocyte sodium-lithium countertransport appears to be associated with insulin insensitivity in Type 1 diabetes, even in the absence of hyperlipidaemia, hypertension and nephropathy.     

Alterations of exocrine pancreas in end-stage renal disease do they reflect a clinically relevant uremic pancreopathy?

Serum pancreatic enzyme behavior, exocrine function, and morphology of the pancreas were studied in 28 patients with end-stage renal disease undergoing regular hemodialysis, in order to better delineate and assess the clinical relevance of the pancreatic alterations that occur in these patients. Twenty-eight healthy subjects served as controls. Initial studies included serum amylase, isoamylase, and lipase assays; fecal chymotrypsin measurement; and abdominal ultrasonography. The amylase, lipase, and chymotrypsin determinations, as well as ultrasound examination, were repeated four years later. None of the patients had clinical evidence of pancreatic disease at entry into the study, but one had had previous attacks of pancreatitis and another developed mild acute pancreatitis one month after entry. Initial mean serum enzyme levels were significantly higher in patients than in controls (amylase, pancreatic isoamylase, and lipase,P<0.001; salivary isoamylaseP<0.05). Serum amylase was raised in 16/28 patients; pancreatic isoamylase in 15/28, and lipase in 7/28; these elevations were generally mild. Mean fecal chymotrypsin was significantly lower (P<0.001) in patients than in controls: abnormally low values were found in 9/28 patients. Amylase, lipase and chymotrypsin measurements repeated after four years showed no significant difference with respect to the first study. Ultrasonographic changes were rare and mild: one patient had a small cyst in the pancreas head, another, an increase in echogenicity of the gland not related to age; these findings were unchanged at repeat examination. The results demonstrate that the frequent elevations of serum pancreatic enzymes and the rare sonographic changes found in patients undergoing hemodialysis do not generally reflect a relevant pancreopathy. However, the finding of significantly decreased fecal chymotrypsin may indicate the presence of pancreatic dysfunction in end-stage renal disease.The preliminary results of this study were presented in Ulm (Germany) at the European Pancreatic Club Meeting October 11–14, 1992.This study was partially supported by the University and Scientific Technological and Research Ministry in 1993.     

Behaviour of serum pancreatic enzymes in chronic pancreatitis

AIM: To establish whether serum pancreatic enzyme determination is useful in the identification of patients with chronic pancreatitis and in revealing the presence of exocrine pancreatic insufficiency PATIENTS AND METHODS: A total of 50 patients with chronic pancreatitis were included in the investigation: 19 were studied during a painful attack of the disease and 31 were observed during clinical remission of the disease and underwent a secretin-caerulein test; 21 of the 31 patients had severe pancreatic insufficiency. Thirty patients with non-pancreatic digestive diseases were also studied. Serum amylase, pancreatic isoamylase, lipase, trypsinogen and elastase- were determined in all patients. RESULTS: Serum levels of the 5 enzymes studied were significantly higher in patients with pancreatic pain than in those studied during a clinical remission of the disease, and in those with non-pancreatic digestive diseases. In patients with chronic pancreatitis studied during clinical remission of the disease serum levels of pancreatic isoamylase and trypsinogen were significantly lower than in those patients with non-pancreatic digestive diseases. Considering only low serum concentrations of the five enzymes studied in diagnosing chronic pancreatitis, trypsinogen showed a sensitivity of 28%, specificity of 100%, a predictive value of a positive test of 100% and a predictive value of a negative test of 96.4%. In the 21 patients with severe pancreatic insufficiency, abnormally low serum concentrations of trypsinogen were found in 12 patients (57%), of lipase and elastase-1 in 6 (29%), of pancreatic isoamylase in 5 (24%), and of amylase in 3 (14%). CONCLUSIONS: Serum pancreatic enzymes can not be considered a useful tool to identify patients with pancreatic insufficiency. However, of the five enzymes studied, serum trypsinogen appears to be a useful marker in the diagnostic work-up of chronic pancreatitis.