Biomedical subjects

G Sundkvist

Publications and source records attributed to G Sundkvist.

At least 109 records · Page 6Linked to original sources

PubMed1993

Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type.

At and before onset, most insulin-dependent diabetics (IDDM) have islet GAD65 autoantibodies (GAD65Ab). Since IDDM also occurs in older patients where non-insulin-dependent diabetes is common, we studied GAD65Ab at onset to classify diabetes type. Our quantitative immunoprecipitation assay uses recombinant human islet GAD65 stably expressed in hamster fibroblasts. Electrophoretic mobility was identical to native islet GAD65. Like native antigen, recombinant GAD65 migrated as two bands during electrophoresis, but converted to one under stronger reduction. Immunoprecipitation was linear with respect to antibody or antigen concentration. In 120 population-based diabetic patients of all ages grouped by treatment at onset and after 18 mo, GAD65Ab were present in 70% on insulin (n = 37), 10% on oral agent (n = 62, P < 0.0001), 69% changing from oral agent to insulin (n = 16, P < 0.001), and 1 of 33 controls. 65% with GAD65Ab, versus 8% without, changed from oral agent to insulin (P < 0.01). The GAD65Ab quantitative index was remarkably stable, and only 2 of 32 patients changed antibody status during follow-up. Concordance between GAD65Ab and islet cell antibodies was 93%. Quantitative correlation was approximate but significant. This highly sensitive, quantitative, high capacity assay for GAD65Ab reveals treatment requirements better than clinical criteria, perhaps guiding immunomodulatory therapy.

Adult↗

PubMed1993

Autonomic neuropathy predicts deterioration in glomerular filtration rate in patients with IDDM.

OBJECTIVE: To evaluate whether autonomic neuropathy predicts deterioration in glomerular filtration rate in IDDM patients. RESEARCH DESIGN AND METHODS: A prospective study in which 35 IDDM patients have been followed for 10-11 yr. Autonomic nerve function tests included heart-rate reactions to deep breathing (expiration-to-inspiration ratio) and to tilt (acceleration and brake indexes). GFR was evaluated by the 51Cr-EDTA plasma clearance method. RESULTS: At entry to the study, no significant differences were noted in age (39 +/- 2 [mean +/- SE] vs. 42 +/- 4 yr), duration of diabetes (20 +/- 3 vs. 23 +/- 4 yr), supine blood pressures (120/79 +/- 3/2 mmHg vs. 121/78 +/- 6/3 mmHg), and GFR (113 +/- 6 vs. 107 +/- 3 ml.min-1.1.73 m-2) between 20 patients with and 15 without autonomic neuropathy (age-corrected criteria). After 10-11 yr, GFR had decreased significantly (22 +/- 4 ml.min-1.1.73 m-2, P < 0.001) in patients with autonomic neuropathy but not (8 +/- 5 ml.min-1.1.73 m-2, NS) in patients without. In keeping with this, GFR decreased more than expected (difference in GFR/expected decrease in GFR) in patients with autonomic neuropathy, compared with those without (4.46 +/- 0.98 vs. 0.48 +/- 0.73, P < 0.005). CONCLUSIONS: Autonomic neuropathy predicts future deterioration in GFR in IDDM patients.

Adult↗

PubMed1993

Beta-cell function in relation to islet cell antibodies during the first 3 yr after clinical diagnosis of diabetes in type II diabetic patients.

OBJECTIVE: To determine the effects of islet cell antibodies on beta-cell function during the first 3 yr after diagnosis in type II diabetic patients. RESEARCH DESIGN AND METHODS: beta-cell function in type II diabetic patients with (n = 11, 50 +/- 5 yr of age) and without (n = 10, 52 +/- 4 yr of age) ICA was followed prospectively and compared with beta-cell function in type I adult diabetic patients (n = 17, 37 +/- 5 yr of age) and in healthy control subjects (n = 34, age 45 +/- 3 yr). beta-cell function was evaluated as fasting C-peptide, 1 + 3 min C-peptide after intravenous glucose, and delta C-peptide after glucagon. RESULTS: Fasting C-peptide was equal in type II diabetic patients with ICA (0.30 +/- 0.03 nM) and type I diabetic patients (0.24 +/- 0.03 nM) at diagnosis, and decreased (P < 0.05) during 3 yr in these groups but not in type II diabetic patients without ICA. At diagnosis, type II diabetic patients with ICA showed a 1 + 3 min C-peptide (0.92 +/- 0.17 nM) lower (P < 0.001) than control subjects but higher (P < 0.05) than type I diabetic patients (0.53 +/- 0.11 nM). After 1 yr, 1 + 3 min C-peptide in type II diabetic patients with ICA had decreased (P < 0.05) to 0.18 +/- 0.11 nM and was equal to type I diabetic patients (0.38 +/- 0.10 nM). delta C-peptide after glucagon was equally impaired in type II diabetic patients with ICA (0.38 +/- 0.06 nM) and type I diabetic patients (0.35 +/- 0.11 nM) at diagnosis. After 3 yr, type II diabetic patients with ICA had fasting C-peptide of 0.09 +/- 0.04 nM, 1 + 3 min C-peptide of 0.18 +/- 0.10 nM, and delta C-peptide after glucagon of 0.20 +/- 0.09 nM, values equal to type I diabetic patients but lower (P < 0.01) than in type II diabetic patients without ICA, whose values remained unchanged; fasting C-peptide of 0.97 +/- 0.17 nM, 1 + 3 min C-peptide of 2.31 +/- 0.50 nM, and delta C-peptide after glucagon of 1.76 +/- 0.28 nM. CONCLUSIONS: In patients considered type II diabetic with ICA, beta-cell function progressively decreased after diagnosis, and after 3 yr was similar to type I diabetic patients, whereas beta-cell function in type II diabetic patients without ICA was unchanged.

Adolescent↗

PubMed1993

Autonomic vagal nerve dysfunction in patients with ulcerative colitis.

Autonomic nerve function was evaluated in 40 patients with total ulcerative colitis and in 25 patients with irritable bowel syndrome by three established non-invasive tests based on the heart reactions to deep breathing (E/I ratio) and tilt (acceleration and brake index). None of the patients were diabetic. Most of the patients with ulcerative colitis were clinically and biochemically inactive; 10 had previously undergone colectomy. The results were compared with a control group consisting of 56 healthy individuals and 33 previously investigated patients with Crohn's disease, 45% of whom demonstrated autonomic neuropathy (AN). Patients with ulcerative colitis had a significantly lower E/I ratio than controls in age-corrected values, indicating vagal nerve dysfunction. Altogether, 35% had signs of AN. In patients with irritable bowel syndrome 36% had evidence of AN, a figure in agreement with observations from other investigators. We conclude that AN is common in patients with ulcerative colitis, regardless of disease activity and previous colectomy. In contrast to a predominantly sympathetic dysfunction in Crohn's disease, AN in ulcerative colitis was vagal.

Adult↗

PubMed1992

Predictive value of islet cell and insulin autoantibodies for type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children.

Most studies evaluating immune markers for prediction of Type 1 (insulin-dependent) diabetes mellitus have focused on first degree relatives, although only 10% of newly-diagnosed patients have an affected first degree relative. The Swedish Childhood Diabetes Register identifies 99% of all diabetic children at diagnosis. In this population-based study, islet cell antibodies and insulin autoantibodies in 0-14-year-old Swedish consecutively-diagnosed patients and control subjects were analysed to define their sensitivity and specificity. Over 16 months (1986-1987), 515 Swedish children developed diabetes. Plasma samples were obtained from 494 (96%) patients, and 420 matched control children. Among patients, the frequency of islet cell antibodies was 84% (415 of 494), insulin autoantibodies 43% (145 of 334); 40% (135 of 334) were positive for both and 88% (294 of 334) were positive for one or both. Among control children, 3% (14 of 420) had islet cell antibodies, 1% (4 of 390) insulin autoantibodies, and 4% (16 of 390) had either autoantibody marker. The predictive value of finding a patient with the disease was only 7% since 4% of the control children were antibody-positive and the cumulative incidence rate up to 15 years of age is 0.38%. None of the autoantibody-positive (n = 21) or negative control children developed diabetes during 3 to 5 years of follow-up. Longitudinal investigations of islet cell or insulin-autoantibody-positive healthy children are necessary to accurately determine the conversion rate from marker positivity to disease onset.

Adolescent↗

PubMed1992

Plasma neuropeptide Y (NPY) and galanin before and during exercise in type 1 diabetic patients with autonomic dysfunction.

Plasma neuropeptide Y (NPY), plasma galanin and plasma catecholamines were determined before and during an ergometer exercise test in 11 type 1 diabetic patients (age 19-36 years, mean 30; duration of diabetes 2-18 years, mean 9) with autonomic dysfunction and in 13 age-matched healthy controls (age 24-36 years, mean 29). Before exercise, plasma NPY (100 +/- 6 pmol/l vs 144 +/- 7 pmol/l; P less than 0.001) and plasma galanin (54 +/- 3 pmol/l vs 77 +/- 5 pmol/l; P less than 0.005) were significantly lower in patients than in controls. During exercise, plasma NPY, plasma adrenaline, and plasma noradrenaline increased in patients and controls while galanin only increased in patients. Since there was a direct correlation between plasma NPY before exercise and the increment (delta 80%) in noradrenaline during exercise (r = 0.54; P less than 0.01), it is suggested that plasma NPY determined in the basal situation may be a useful marker of sympathetic nerve failure in diabetic patients.

Adult↗

PubMed1992

Islet cell and thyrogastric antibodies in 633 consecutive 15- to 34-yr-old patients in the diabetes incidence study in Sweden.

The effect of age on ICA and thyrogastric antibodies at diagnosis of IDDM was evaluated in 633 consecutively diagnosed Swedish diabetic patients aged 15-34 yr and in 282 volunteers of the same age. ICAs were present in 61% (383 of 633) of the patients and in 2% (5 of 282) of control subjects. When the initial classification was considered, ICAs were detected in 69% (327 of 473) of patients with IDDM, 23% (19 of 83) of those with NIDDM, 50% (36 of 72) of those with unclassifiable diabetes, and 20% (1 of 5) of those with secondary diabetes. The frequency of ICA fell significantly (P less than 0.001) with age in IDDM patients from 77% (104/135) in those 15-19 yr old to 52% (50 of 96) in 30- to 34-yr-old IDDM patients. The low frequency of ICA in 30- to 34-yr-old IDDM patients was confined to men (42%, 28 of 66). The frequency of gastric (H+, K(+)-ATPase) antibodies was significantly (P less than 0.05) higher in IDDM patients (10%, 47 of 449) than in patients with NIDDM (3%, 3 of 80) and unclassifiable diabetes (4%, 3 of 72). In conclusion, the frequency of ICA at the diagnosis of IDDM in young adult subjects decreases with increasing age, particularly in men. The frequent finding of ICA in patients considered to have NIDDM or unclassifiable diabetes indicates that misclassification of diabetes is frequent in young adult patients recently diagnosed with diabetes.

Adolescent↗

PubMed1992

Pancreatic beta-cell function evaluated by intravenous glucose and glucagon stimulation. A comparison between insulin and C-peptide to measure insulin secretion.

Insulin and C-peptide responses to 0.5 g kg-1 intravenous glucose and 1.0 mg glucagon were studied in 34 healthy subjects (age 19-78 years, mean 45). Fasting blood glucose (r = 0.59; p < 0.001) and glycosylated haemoglobin (r = 0.61; p < 0.001) increased with age, but not the initial C-peptide and insulin responses to the glucose infusion. However, the C-peptide response at 70 min (r = 0.36; p < 0.05), 80 min (r = 0.41; p < 0.05), and 90 min (r = 0.46; p < 0.01) after the glucose infusion correlated with age as well as both insulin (r = 0.42; p < 0.05) and C-peptide (r = 0.45; p < 0.05) responses to the glucagon injection. Reproducibility of insulin and C-peptide responses was evaluated by duplicate tests, separated 2-143 days in time, in 10 healthy subjects (age 19-48 years, mean 32 years) showing no significant differences in median within-subject variation between the initial (1 + 3 min) or overall (0-90 min area under curve) insulin (24% and 17%, respectively) and C-peptide (15% and 14%, respectively) responses to glucose, while the within-subject variation for the fasting values and the response to glucagon was higher (p < 0.05) for insulin (47% and 32%, respectively) than C-peptide (13% and 14%, respectively). Between-subject variation was also lower (p < 0.001) for C-peptide than for insulin. Thus, C-peptide measurements in healthy subjects are more reproducible than insulin measurements in determination of beta-cell function.

Adult↗

PubMed1992

Quantitative analysis of islet glutamic acid decarboxylase p64 autoantibodies in insulin-dependent diabetes mellitus.

Autoantibodies against the beta-cell M(r) 64,000 protein (p64), recently identified as an isoform of glutamic acid decarboxylase (GAD), are prevalent in patients with insulin-dependent diabetes mellitus (IDDM). Dog islets were found to represent an abundant source of native p64 allowing the study of antigen-antibody interactions in IDDM. A quantitative, standardized assay for p64 antibodies based on dog islets was developed and evaluated. Utilizing dog and human islets the p64 antibodies were detected in 17/19 (89%) new onset 15-32-year-old patients, compared to 15/19 (79%) in a rat islet assay. ICA were detected in 15/19 (79%) patients and correlated with the presence of p64 antibodies (rs = 0.59, P < 0.004) but not with age at onset, sex, or C-peptide levels. Sensitivity therefore is improved with the dog islet p64 antibody assay which will allow future studies requiring native p64 antigen in larger quantities are possible based on our findings.

Adolescent↗

PubMed1991

Relating homology between the Epstein-Barr virus BOLF1 molecule and HLA-DQw8 beta chain to recent onset type 1 (insulin-dependent) diabetes mellitus.

A role for the Epstein-Barr virus in initiating Type 1 (insulin-dependent) diabetes mellitus has been proposed since Epstein-Barr virus BOLF1 (497-513) AVTPL RIFIVPPAAEY has an 11 amino acid identity with HLA-DQw8 beta (49-60) AVTPL GPPAAEY. Rabbit antisera to the BOLF1 (496-515) peptide crossreacted with the homologous DQw8 beta (44-63) peptide but not with the related DQw7 beta (44-63) peptide, which differed from the DQw8 peptide only in an ALA to ASP substitution in position 57. Antisera to DQw8 beta (49-60) reacted with the DQw8 beta (44-63) peptide and BOLF1 (496-515), but not with DQw7 beta (44-63). The antiserum to the BOLF1 peptide bound to denatured class II major histocompatibility complex beta chains from Epstein-Barr virus-transformed DQw8-positive lymphocytes in an immunoblotting analysis. Epstein-Barr virus antibodies were detected at equal frequencies and similar titres in sera of 30 patients with Type 1 diabetes (16 of 30; 63%) and in sera of 20 non-diabetic control subjects (13 of 20; 65%). Sera from diabetic patients did not bind to DQw8 beta (44-63) or BOLF1 (496-515) peptides. From these data we conclude that there is no simple relationship between serological evidence of Epstein-Barr virus infection and crossreactions between homologous Epstein-Barr virus and class II major histocompatibility complex peptides.

Adolescent↗

PubMed1991

Islet cell antibody reactivity with human fetal pancreatic islets.

To evaluate the possibility of autoimmune processes against pancreatic islets in fetal life, we tested islet cell antibody (ICA) reactivity with 14 fetal pancreata obtained after abortion at the 15th up to the 19th week of gestation. Pancreatic islets positive for a monoclonal proinsulin antibody but non-reactive with ICA negative control serum were found in 9/14 pancreata and all (9/9) of them showed a positive reaction with the ICA standard. It is concluded that ICA reactivity may be detected in fetal human pancreata. Further studies on fetal islet cell antibody reactivity in the development of insulin dependent diabetes mellitus (IDDM) are warranted.

Autoantibodies↗

PubMed1991

Pancreatic autoantibodies and pancreatic function in Sjögren's syndrome.

Pancreatic autoantibodies were determined in 49 patients with Sjögren's syndrome and related to functional parameters. Pancreatic duct autoantibodies (PDA) were detected in the sera of three patients, and all showed abnormal exocrine pancreatic function. Islet cell antibodies (ICA) were not detected in the sera of the 49 patients, including two individuals with diabetes mellitus. In conclusion, PDA occur in patients with Sjögren's syndrome, and may be associated with exocrine pancreatic dysfunction.

Autoantibodies↗

PubMed1991

Autonomic nerve antibodies and autonomic nerve function in type 1 and type 2 diabetic patients.

Complement-fixing adrenal medulla (CF-ADM), sympathetic ganglion (CF-SG), and vagal (CF-V) nerve antibodies were determined in diabetic patients. Among 74 patients with Type 1 diabetes, CF-ADM was detected in 7 (10%) cases, CF-SG in 14 (19%) cases, and CF-V in 8 (11%) cases. Among 38 patients with Type 2 diabetes, CF-ADM was detected in 5 (13%) cases, CF-SG in 4 (11%) cases, and CF-V in 6 (16%) cases. There were associations between autonomic nerve antibodies and autonomic nerve function. CF-ADM and/or CF-SG were significantly (P less than 0.002) less prevalent in Type 1 diabetic patients with autonomic neuropathy than in those without [5/44 (11%) vs. 14/30 (47%)] and, in agreement with this, the brake index, a sign of parasympathetic and sympathetic autonomic nerve function, was significantly (P less than 0.005) higher (more normal) in these patients (-0.56 +/- 0.13 vs. -1.04 +/- 0.12). In Type 2 diabetic patients, the E/I ratio, an index of parasympathetic nerve function, was significantly (P less than 0.03) lower (more abnormal) in those with CF-V than in those without (-1.81 +/- 0.17 vs. -1.20 +/- 0.11). In conclusion, the frequency of sympathetic nerve antibodies was decreased in Type 1 diabetic patients with autonomic neuropathy, while in Type 2 diabetic patients parasympathetic nerve antibodies were related to severe parasympathetic neuropathy.

Adrenal Medulla↗

PubMed1991

A study of peripheral diabetic neuropathy. The application of age-related reference values.

The standardization of methodology and the provision of age-related reference values have been addressed for the design of and interpretation of data from a multicentre neuropathy trial. Age-related reference values were generated from 120 healthy volunteers. Vibration perception thresholds (VPT) deteriorated significantly with age (p less than 0.001). Patients were selected on the basis of age-related abnormal VPT and peroneal motor nerve conduction velocity. They were assessed at the beginning and end of a placebo run-in period (baseline data). The coefficients of variation (CV%) for VPT at the medial malleolus (16.81 per cent, n = 316) and great toe (19.23 per cent, n = 313) were lower compared to results in healthy volunteers (29.7 per cent and 20.8 per cent, respectively, n = 49). The CV% for expiratory:inspiratory (E:I) ratio (4.82 per cent, n = 215), Valsalva manoeuvre (10.84 per cent, n = 249) and 30:15 ratio (7.73 per cent, n = 292) from patients corresponded to those recorded in volunteers (7.6 per cent, n = 45 11.0 per cent, n = 49 9.5 per cent, n = 48, respectively). Most patient values for VPT at the great toe fell beyond the 95 centile line for volunteers. E:I ratio for volunteers showed a more variable relationship with age, although patient values appeared to be located below the 5 centile line for volunteer data.

Adult↗

PubMed1991

Disturbed autonomic nerve function in patients with Crohn's disease.

Autonomic nerve function was evaluated in 33 patients with Crohn's disease (age range, 19-66 years; mean, 36 years) by three established non-invasive tests based on the heart reactions to deep breathing (E/I ratio) and to tilt (acceleration and brake indices). Peripheral nerve function was evaluated neurographically and by measuring thresholds to vibration and temperature changes. None of the patients were diabetic, and all had normal thyroid function. In spite of normal peripheral nerve function, almost half of the patients, 48% (16/33), showed signs of autonomic neuropathy (AN). The occurrence of AN was not related to duration or severity of Crohn's disease or to biochemical evidence of inflammation or malabsorption of vitamins and trace elements. We conclude that autonomic nerve dysfunction is a feature of Crohn's disease which may be relevant with regard to the frequent disturbance in bowel function in patients with this disorder.

Adolescent↗

PubMed1990

The activity of the renin-angiotensin-aldosterone system before and during submaximal bicycle exercise in relation to circulatory catecholamines in patients with type 1 (insulin-dependent) diabetes mellitus.

To evaluate the renin-angiotensin-aldosterone system in relation to circulatory catecholamines, we determined renin activity, angiotensin II, aldosterone, adrenaline, and noradrenaline in plasma before and during a submaximal bicycle exercise test in 23 Type 1 (insulin-dependent) diabetic patients (aged 19-57 years, mean 37; duration of diabetes 2-32 years, mean 16), 17 with signs of cardiac autonomic neuropathy, and in 18 healthy non-diabetic subjects (aged 24-41 years, mean 29). At rest, Type 1 diabetic patients showed significantly lower aldosterone values than control subjects (0.14 +/- 0.02 nmol/l and 0.22 +/- 0.02 nmol/l; p less than 0.01) while renin activity (1.0 +/- 0.1 nmol.l-1.h-1 and 0.9 +/- 0.1 nmol.l-1.h-1) and angiotensin II (14 +/- 1 nmol/l and 18 +/- 2 nmol/l) did not differ significantly between patients and control subjects. During exercise, increments (increase from the resting value to the value at 80% of maximal working capacity) in renin (1.5 +/- 0.4 nmol.l-1.h-1 and 3.7 +/- 0.5 nmol.l-1.h-1; p less than 0.001), angiotensin II (28 +/- 8 nmol/l and 60 +/- 8 nmol/l; p less than 0.001), aldosterone (0.16 +/- 0.04 nmol/l and 0.25 +/- 0.05 nmol/l; p less than 0.05), adrenaline (1.96 +/- 0.49 nmol/l and 2.92 +/- 0.51 nmol/l; p less than 0.05), and noradrenaline (12.01 +/- 1.25 nmol/l and 18.74 +/- 1.45 nmol/l; p less than 0.01) were significantly lower in the patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Islet cell antibodies and fasting C-peptide predict insulin requirement at diagnosis of diabetes mellitus.

The differential diagnosis between Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes is complicated since no specific markers are available for either disease. In this study, 244 consecutive patients were diagnosed with diabetes mellitus during two years in Malmö (230,000 inhabitants), corresponding to an incidence rate of 53.100,000(-1).year-1. Age, body mass index, HbA1c, C-peptide, and levels of islet cell antibodies were determined at the clinical onset, and related to the classification at diagnosis and at follow-up (n = 233) after a median time of 31 (range 1-49) months. After diagnosis, 42 of 244 (17%) were started on insulin while 202 of 244 (83%) were not. Islet cell antibodies were present in 25 of 42 (60%), and in 18 of 183 (10%), respectively. In the non-insulin treated group, patients with islet cell antibodies had lower body mass index (p less than 0.001), higher HbA1c (p less than 0.004), and lower C-peptide (p less than 0.001) than patients without. At follow-up, 11 of 18 (61%) islet cell positive patients were changed to insulin treatment, as were six other patients. Insulin was discontinued in five initially insulin-treated but islet cell antibody negative patients. The sensitivity, specificity and predictive value for insulin treatment at follow-up were for islet cell antibody positivity; 72%, 96% and 84%, respectively, and for low C-peptide value; 60%, 96%, and 80%, respectively. Islet cell antibodies and low C-peptide at diagnosis of diabetes mellitus are concluded to be useful markers to predict insulin dependence.

Adolescent↗

PubMed1990

Immunoreactive trypsin(ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls. The Swedish Childhood Diabetes Group.

To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive anodal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) micrograms/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) micrograms/L in control subjects (p less than 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) micrograms/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) micrograms/L in control subjects (p less than 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p less than 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.

Adolescent↗