alpha-chymotrypsin and Diabetes-Mellitus--Type-1

Altered pancreatic exocrine function can be observed in patients with type 1 or type 2 diabetes. In the present study, we evaluated the potential nutritional consequences of this dysfunction.. Serum concentrations of nutritional markers, including albumin, cholesterol, triacylglycerol, vitamins A, D, and E, were assessed in a cohort of 468 patients (137 with type 1 diabetes and 331 with type 2 diabetes), after exclusion of the patients with a CRP > 10 mg/l. These patients were compared with 47 patients with diseases of the exocrine pancreas and diabetes (type 3c diabetes or pancreatogenic diabetes). Fecal elastase-1 and chymotrypsin concentrations were measured and patients with type 1 and type 2 diabetes were divided into three groups according to whether zero (group NN), one (group LN), or both (group LL) concentrations were decreased.. Several markers differed significantly between the groups of patients, including BMI, albumin, phosphorus, and fat-soluble vitamins. Patients with pancreatogenic diabetes had markedly more profound alterations than patients with type 1 or type 2 diabetes and altered exocrine function. However, patients with type 1 or type 2 diabetes and decreased concentrations of both elastase-1 and chymotrypsin had lower albumin, phosphorus, and vitamin A than patients with normal pancreatic exocrine function.. Modest nutritional alterations were found in patients with type 1 or type 2 diabetes and altered exocrine function. Patients with type 1 or type 2 diabetes and altered exocrine function may thus deserve to be screened for nutritional deficiencies.

Topics: Adult; Aged; Biomarkers; Chymotrypsin; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Male; Middle Aged; Pancreatic Elastase; Vitamins

Decreased function of the exocrine pancreas is frequent in patients with diabetes. Our aim was to investigate clinical correlates of pancreatic exocrine failure in patients with diabetes.. We investigated exocrine function by assaying both elastase-1 concentration and chymotrypsin activity in 667 patients. We conducted separate analysis on patients with Type 1 diabetes and patients with Type 2 diabetes. Patients were separated into three groups according to whether both elastase-1 concentration and chymotrypsin activity were normal, or one or both were altered.. A total of 667 consecutive patients were analysed, including 195 with Type 1 and 472 with Type 2 diabetes. Elastase-1 concentration was <200 μg/g in 23% of the patients. Chymotrypsin activity was <6 U/g in 26% of the patients. In 66% of the patients elastase-1 concentration was >200 ug/g and chymotrypsin activity >6 U/g. One test was below threshold in 19%, both in 15%. In patients with Type 1 diabetes, the three groups defined by results of elastase-1 concentration and chymotrypsin activity differed with regard to duration of diabetes and prevalence of glutamic acid decarboxylase antibodies, but not BMI or HbA(1c) , or prevalence of retinopathy, neuropathy, nephropathy or vascular disease. In patients with Type 2 diabetes, the three groups differed with regard to BMI, use of insulin and vascular disease, but not known duration.. Factors associated with pancreatic exocrine failure differ in patients with Type 1 diabetes compared with patients with type 2 diabetes. In patients with Type 2 diabetes, association of decreased pancreatic exocrine function with BMI and vascular disease suggests a role of pancreatic arteriopathy.

Topics: Adult; Aged; Antibodies; Body Mass Index; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exocrine Pancreatic Insufficiency; Feces; Female; Glutamate Decarboxylase; Humans; Male; Middle Aged; Pancreas, Exocrine; Pancreatic Elastase

Exocrine function has been described in patients with diabetes. We hypothetized that patients with exocrine dysfunction have pancreatic atrophy.. This is a cohort study of hospitalized patients. Thirty-five patients were selected after detection of impaired exocrine function in routine tests, and 17 patients were matched for age and body mass index to the previous cohort. The pancreatic volume was evaluated on sections of computed tomographic scans of the pancreas. Other investigations included a glucagon stimulation test and determination of fecal elastase-1 concentration and chymotrypsin activity.. Fifty-two patients participated in this study, 24 with type 1 diabetes and 28 with type 2 diabetes. Duration of diabetes was 15 years (5-26 years; median [interquartile range]). The pancreatic volume, 42 cm (25-57 cm), was decreased in most patients. It did not differ in patients with type 1 diabetes compared with those with type 2 diabetes. It was decreased in patients treated with insulin and in those with low elastase-1 concentration or low chymotrypsin activity. In the multiple linear regression analysis, the pancreatic volume correlated with chymotrypsin activity and stimulated C-peptide.. We have unraveled a link between 2 old observations in patients with diabetes: atrophy of the pancreas and exocrine deficiency. These observations give credence to the reality of the exocrine dysfunction in patients with diabetes.

Topics: Adult; Aged; Atrophy; C-Peptide; Chymotrypsin; Cohort Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Feces; Female; Glucagon; Humans; Islets of Langerhans; Male; Middle Aged; Organ Size; Pancreas; Pancreas, Exocrine; Pancreatic Elastase; Tomography, X-Ray Computed

In recent years, a number of studies have been carried out, the results of which suggest that the exocrine function of the pancreas is significantly more frequently impaired than is the case in healthy controls. In particular when a patient presents with gastrointestinal complaints of unclear origin, unexplained fluctuations in blood sugar, or loss of weight, the possibility of pancreatic exocrine insufficiencyshould be included in differential diagnostic considerations. Abnormal stools and intolerance of dietary fat can be clarified on the basis of a careful history. The diagnosis is confirmed with the aid of simple laboratory tests, for example the chemotrypsin test or the detection of elastase 1 in the stools. By way of treatment, pancreatic enzyme replacement can be applied.

Topics: Adolescent; Adult; Child; Cholangiopancreatography, Endoscopic Retrograde; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Enzyme Therapy; Exocrine Pancreatic Insufficiency; Feces; Humans; Pancreas; Pancreatic Elastase; Prevalence

To compare the pancreatic exocrine and beta-cell function in the two variants of malnutrition-related diabetes mellitus (MRDM): fibrocalculous pancreatic diabetes (FCPD) and protein-deficient pancreatic diabetes (PDPD).. Fecal chymotrypsin (FCT) and fasting C-peptide levels were measured in 20 consecutive patients with FCPD and 19 with PDPD. FCPD was diagnosed by pancreatic calcification on ultrasonography, while the diagnosis of PDPD was made on the basis of low body mass index, severe diabetes requiring insulin therapy, and ketosis resistance on interruption of insulin. Twenty patients with type I diabetes and 32 healthy subjects served as control subjects.. Both FCPD and PDPD patients had diminished levels of FCT when compared with those of control subjects and patients with type I diabetes. However, FCT levels were significantly lower in subjects with FCPD (median 0.4 U/g, range 0-8.9 U/g), in comparison with those with PDPD (4.7 U/g, 0.6-40.5 U/g; P < 0.001). Of the FCPD patients, 13 of 20 (65%) had severe exocrine pancreatic deficiency (FCT < 1 U/g) vs. 3 of 19 (15.8%) PDPD subjects (P < 0.01). In comparison with control subjects, fasting serum C-peptide levels were significantly diminished in both MRDM groups. However, C-peptide levels in subjects with FCPD (mean +/- SE, 0.22 +/- 0.04 nmol/l) and PDPD (0.26 +/- 0.04 nmol/l) were comparable.. Among the two variants of MRDM, subjects with FCPD have severe pancreatic exocrine deficiency in comparison with those with PDPD, even though their C-peptide levels are comparably diminished. This suggests that the pathogenesis of these two entities may differ or that the genetic and/or environmental factors leading to exocrine damage are different.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Chymotrypsin; Diabetes Mellitus; Diabetes Mellitus, Type 1; Feces; Female; Glycated Hemoglobin; Humans; India; Insulin; Insulin Secretion; Islets of Langerhans; Male; Nutrition Disorders; Pancreas; Pancreatic Diseases; Reference Values; Statistics, Nonparametric

The exocrine and endocrine pathophysiology of chronic calcific pancreatitis of the tropics (CCPT) remains elusive. The objective of this study was to evaluate the spectrum and correlates of the exocrine and endocrine pancreatic dysfunction in CCPT. Thirty-seven consecutive patients with a clinico-radiological diagnosis of CCPT were stratified into three subgroups: CCPT-normal glucose tolerance (NGT), CCPT-abnormal glucose tolerance (IGT) and CCPT-diabetes mellitus (DM). Ten ketosis resistant young diabetic (KRDY) patients, 10 classical insulin dependent diabetes mellitus (IDDM) patients and 18 healthy matched controls were included for comparison. Fecal chymotrypsin (FCT) levels and blood C-peptide levels (basal and post i.v. glucagon stimulation) were estimated for assessing the exocrine and endocrine pancreatic functions, respectively. Sonography was performed to evaluate the pancreatic size and ductal diameter. Pancreatic exocrine-endocrine correlation was examined by studying the C-peptide/fecal chymotrypsin ratio (CP/FCT) (CP/FCT of normal controls = 1). Mean FCT levels in all 3 subgroups of CCPT (NGT: 3.4 micrograms/g; IGT: 0.82 microgram/g; DM: 2.4 micrograms/g) were very low (87-96% reduction in exocrine pancreatic dysfunction; mean FCT in healthy controls was 22.8 micrograms/g) (P < 0.0001). In contrast, KRDY and IDDM patients displayed 50-54% reduction in pancreatic acinar function (P < 0.001). Basal and stimulated C-peptide levels progressively fell in the 3 CCPT subsets (NGT: 0.23 and 0.46 > IGT: 0.14 and 0.29 > DM 0.10 and 0.14) (P < 0.01). CCPT patients exhibited pancreatic atrophy and ductal dilation (> 3 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Age of Onset; Analysis of Variance; Blood Glucose; C-Peptide; Calcinosis; Chronic Disease; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Islets of Langerhans; Male; Pancreas; Pancreatitis; Reference Values; Tropical Climate; Ultrasonography

A subset of insulin requiring diabetes in the young (IRDY) is ketosis resistant. Its pathogenesis and pathophysiology remain ill defined. The current study was done to evaluate the exocrine and endocrine dysfunction in ketosis resistant young diabetics. Fecal chymotrypsin (unit/G), basal & stimulated c-peptide levels (pmol/ml) and sonographic evaluation of the pancreas were done in 59 IRDY patients: 34 ketosis resistant (KR) and 24 ketosis prone (KP). Fecal chymotrypsin levels in KR (11.1 +/- 3.4) and KP (10.3 +/- 5.1) were lower than in controls (22.4 +/- 7.3) (P < 0.01). KR subjects had better endogenous insulin reserves than KP subjects: the basal and stimulated c-peptide levels in KR patients (0.12 & 0.17) were higher than in KP subjects (0.06 and 0.07) (P < 0.05). A strong correlation was noted between the exocrine and beta cell dysfunction in KR subjects (r = 0.7, P < 0.05). Pancreas was smaller in KR and KP patients than in controls (P < 0.05) on sonography. Thus the resistance to ketosis is a reflection of the better preserved beta cell reserves in the KR patients. Loss of the trophic effect of insulin and associated malnutrition is responsible for their exocrine dysfunction.

Topics: Adult; Age of Onset; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Feces; Female; Humans; Islets of Langerhans; Ketosis; Male; Pancreas; Pancreatic Function Tests

A 'screening' test is needed to identify patients with chronic pancreatitis among diabetics in tropical field surveys. We have examined the potential diagnostic yield of the BT-PABA/PAS test of exocrine pancreatic function in this setting. The recoveries of both PABA and PAS in eight healthy controls from Madras, south India, were lower than in controls from Manchester, north west England (mean +/- S.D., 51 +/- 11 vs. 79 +/- 7%, P < 0.001 for PABA; 52 +/- 11% vs. 81 +/- 7%, P < 0.001 for PAS) but the % PABA/PAS excretion index (PEI) was similar (0.96 +/- 0.14 vs. 0.96 +/- 0.06). Using a cut-off value of 0.75 for the PEI in a study group including eight patients with chronic pancreatitis and 26 with primary forms of diabetes, test sensitivity was 75%, specificity 92%, positive predictive value 75%, negative predictive value 92% and efficiency 88%.

Topics: 4-Aminobenzoic Acid; Aminosalicylic Acid; Chronic Disease; Chymotrypsin; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Feces; Humans; India; Kinetics; Pancreatitis; para-Aminobenzoates; Tropical Climate

In a previous study (Frazier et al., 1990), it was demonstrated that two patients with type 1 (insulin-dependent) diabetes mellitus had antibodies in their serum which reacted with four 29 kDa pancreas-specific proteins on two-dimensional immunoblots. This paper reports on the purification and identification of these pancreatic proteins. The protein with the pI closest to pH7 was purified through the use of ammonium sulfate fractionation and ion-exchange chromatography. Gel filtration chromatography established that the protein's molecular weight was closer to 25 kDa. Amino acid composition and sequence analyses demonstrated homology between the protein and chymotrypsin. It is suggested that an abnormal regulation of chymotrypsin activity might be related to antibodies formed in some diabetic patients.

Topics: Adolescent; Amino Acid Sequence; Animals; Autoantibodies; Cattle; Chromatography, Gel; Chymotrypsin; Diabetes Mellitus, Type 1; Humans; Male; Molecular Sequence Data; Molecular Weight; Pancreas; Proteins; Rabbits; Ultracentrifugation

Exocrine pancreatic function was evaluated in 21 diabetic children on the basis of a p-aminobenzoic acid (PABA) test and a determination of fasting serum amylase, pancreatic isoamylase, lipase, trypsin and elastase levels. Fecal chymotrypsin was also measured. Compared to the controls, the diabetic children had significantly lower levels of trypsin (P less than 0.001) and elastase (P less than 0.02). Fecal chymotrypsin appeared to be significantly lower (P less than 0.01) in diabetic children than in controls but in all patients fecal chymotrypsin values registered above the limit considered to be normal. No significant correlation was observed between pancreatic enzyme concentrations, serum and urinary PABA values, and chronologic age, HbA1 and insulin requirement. Only for serum PABA a significant negative correlation with duration of disease (P less than 0.01) has been observed. These data show that exocrine pancreatic function may be abnormal in children with IDDM.

Topics: 4-Aminobenzoic Acid; Adolescent; Adult; Amylases; Child; Chymotrypsin; Diabetes Mellitus, Type 1; Feces; Female; Glycoside Hydrolases; Humans; Isoamylase; Lipase; Male; Pancreas; Pancreatic Elastase; Reference Values; Trypsin

Forty-nine patients with tropical calcific pancreatitis (TCP), 51 insulin-dependent diabetics (IDDMs), 87 non-insulin-dependent diabetics (NID-DMs), and 66 nondiabetic controls were studied to evaluate their exocrine pancreatic function by measurement of serum immunoreactive trypsin (IRT, normal for white caucasians from the U.K. of 140-414 micrograms/L), pancreatic isoamylase (PIA, normal of 35-125 U/L), and fecal chymotrypsin (FCT, normal of greater than 6.6 u/g). The majority of patients were studied within 1 year of diagnosis. TCP subjects included 7 nondiabetics, 6 with impaired glucose tolerance (IGT-TCP), and 36 diabetics [fibrocalculous pancreatic diabetes (FCPD)]. There was evidence of active pancreatitis (IRT greater than 800 micrograms/L) and partial preservation of function in nondiabetic TCP subjects [median IRT of 220 micrograms/L (range of 102-1,360 micrograms/L), FCT of 2.2 u/g (range 0.7-12.8 u/g)] and also in IGT-TCP subjects [IRT of 370 micrograms/L (range of 30-1,360 micrograms/L), FCT of 4.2 u/g (range of 1-38 u/g)]. FCPDs showed severely diminished exocrine function [IRT of 50 micrograms/L (range of 0-184 micrograms/L), FCT of 0.23 u/g (range of 0-10.4 u/g)]; none showed IRT greater than 800 micrograms/L. IDDMs and NIDDMs also showed diminished exocrine pancreatic function in approximately 30 and approximately 10%, respectively. Controls showed a wide range of IRT and FCT concentrations; IRT concentrations tended to be higher than those reported in white Caucasians from the U.K. Three controls, one IDDM, and two NIDDMs showed "pancreatic" IRT concentrations in the absence of symptoms. PIA concentrations were diminished in FCPD but were similar in IDDM and NIDDM subjects compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Electrophoresis; Feces; Humans; India; Isoamylase; Male; Middle Aged; Pancreas; Radioimmunoassay; Trypsin

Exocrine pancreatic function was studied by fecal chymotrypsin test in three groups of diabetic patients seen in southern India. Exocrine pancreatic insufficiency, as shown by low fecal chymotrypsin levels, was seen in 87.5% of patients with fibrocalculous pancreatic diabetes (FCPD), in 23.5% of insulin-dependent diabetes mellitus patients, and in 4.5% of non-insulin-dependent diabetes mellitus patients. There was no correlation between fecal chymotrypsin levels and serum amylase, serum lipase, age, body mass index, duration of diabetes, fasting plasma glucose, or glycosylated hemoglobin levels. The fecal chymotrypsin test is a useful additional investigation for the diagnosis of FCPD found in tropical countries.

Topics: Adult; Amylases; Blood Glucose; Chymotrypsin; Diabetes Mellitus, Type 1; Feces; Female; Glycated Hemoglobin; Humans; Lipase; Male; Pancreas; Pancreatic Diseases; Reference Values

Fibrinogen-platelet interaction was studied in suspensions of platelets obtained from patients with uncontrolled diabetes mellitus of long duration and from control individuals. Fibrinogen binding sites were exposed by stimulating platelets with ADP or with chymotrypsin. There was no significant difference in fibrinogen mediated aggregation between ADP-stimulated platelets of 80 control and 47 diabetic subjects. The Km values for fibrinogen mediated aggregation of ADP-stimulated platelets obtained from control and diabetic donors were 1.39 +/- 0.13 X 10(-7)M and 1.44 +/- 0.13 X 10(-7)M; the Vmax values (expressed in arbitrary light transmission units) were 87.8 +/- 3.14 and 92.8 +/- 4.5 (mean +/- S.E.M.). The analysis of variance showed no significant relationship between Km, Vmax, age and sex in control group; in patient group there was no significant relationship between Km, Vmax, age, sex, type of diabetes, presence of vascular complications and type of treatment (insulin and/or oral hypoglycemic agents). Fibrinogen mediated aggregation of chymotrypsin-treated platelets showed similar pattern in 25 control and in 25 diabetic donors. In 24 normal individuals and in 24 diabetic patients Scatchard analysis revealed 48,820 +/- 5350 fibrinogen binding sites per one normal platelet (Kd = 4.7 X 10(-7)M) and 45,350 +/- 4663 sites per one diabetic platelet (Kd = 3.5 X 10(-7)M). Our data suggest a normal pattern of interaction between fibrinogen and fully activated platelets of diabetic subjects.

Topics: Adenosine Diphosphate; Adult; Aged; Alprostadil; Antibodies, Monoclonal; Binding Sites; Blood Platelets; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Fibrinogen; Humans; Male; Middle Aged; Platelet Aggregation; Platelet Membrane Glycoproteins; Reference Values

In 11 juvenile diabetics and 13 control subjects, the secretin-pancreozymin test was performed. Duodenal-volume losses were corrected by use of radioactive vitamin B12 as marker substance. As compared to normal subjects, juvenile diabetics had significantly decreased pancreatic outputs of amylase, trypsin, chymotrypsin, and to a lesser degree, of bicarbonate. Clinical evidence of disease of the exocrine pancreas was missing. There was no discernible relationship between the abnormality of external pancreatic function and the duration of diabetes mellitus or the dose of insulin required. Possible factors that may be responsible for the exocrine deficiency of the pancreas in juvenile diabetics are discussed.

Topics: Adult; Amylases; Animals; Bicarbonates; Cholecystokinin; Chymotrypsin; Cobalt Radioisotopes; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Male; Pancreas; Pancreatic Juice; Rats; Secretin; Trypsin; Vitamin B 12

Topics: Adolescent; Adult; Amylases; Bicarbonates; Cholecystokinin; Chronic Disease; Chymotrypsin; Clinical Enzyme Tests; Cobalt Radioisotopes; Diabetes Mellitus, Type 1; Female; Humans; Injections, Intravenous; Lipase; Male; Pancreatic Diseases; Pancreatitis; Proteins; Secretin; Trypsin; Vitamin B 12

Topics: Adrenalectomy; Amino Sugars; Amylases; Animals; Anti-Bacterial Agents; Chymotrypsin; Dactinomycin; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diazoxide; Insulin; Leucine; Nitroso Compounds; Pancreas; Proteins; Rats; Rats, Inbred Strains; Trypsin