| 1. |
- Landin-Olsson, Mona, et al.
(författare)
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Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls
- 1990
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Ingår i: Pancreas. - : Ovid Technologies (Wolters Kluwer Health). - 0885-3177. ; 5:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal 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) µg/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) µg/L in control subjects (p < 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) µg/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) µg/L in control subjects (p < 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 < 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.
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| 2. |
- Gottsater, A., et al.
(författare)
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Islet cell antibodies and fasting plasma C-peptide during the first 10 yr after diagnosis in patients with diabetes mellitus diagnosed in adult age
- 1992
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Ingår i: Diabetes, Nutrition and Metabolism - Clinical and Experimental. - 0394-3402. ; 5:4, s. 243-248
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Tidskriftsartikel (refereegranskat)abstract
- Islet cell antibodies (ICA), fasting plasma C-peptide, and HbA(1c) were evaluated up to 10 years after diagnosis in 52 patients with diabetes diagnosed in adult age (mean age at diagnosis 53 ± 2 yr, range 21-76 yr) with a high (>20 IU/day) insulin requirement (group A) and in 50 matched control patients with diabetes diagnosed in adult age (mean age at diagnosis 54 ± 2 yr, range 24-73 yr) with low or no (<20 IU/day) insulin requirement (group B) during the first 3 yrs after diagnosis. Patients in group A showed a significantly higher frequency of ICA (37% [19/52] vs 10% [5/50]; p < 0.05), lower C-peptide (0.33 ± 0.06 nmol/l vs 0.56 ± 0.05 nmol/l; p < 0.001) and higher HbA(1c) (8.15 ± 0.35% vs 6.81 ± 0.25%; p < 0.01) values than group B patients. ICA positive group A patients (0.22 ± 0.06 nmol/l) showed significantly lower C-peptide values than ICA negative group A (0.40 ± 0.09 nmol/l; p < 0.05) patients. C-peptide values correlated with body mass index (BMI) in ICA negative patients both in group A (r = 0.66; p < 0.001) and in group B (r = 0.34; p < 0.05) but not in ICA positive group A patients in whom C-peptide values correlated with age (r = 0.48; p < 0.05). There was a correlation between HbA(1c) and C-peptide values in ICA negative (n = 78; r = -0.31; p < 0.01) but not in ICA positive patients (n = 24; r = -0.17; NS). ICA were most frequent in females (20/59 females vs 4/43 males; p < 0.01). ICA is associated with decreased pancreatic β-cell function in patients with diabetes diagnosed in adult age and may be detected up to 10 yr after diagnosis. Determination of ICA in patients with diabetes diagnosed in adult age improve the classification and etiological diagnosis of diabetes.
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| 3. |
- Gottsater, A., et al.
(författare)
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β-cell function in relation to islet cell antibodies during the first 3 yr after clinical diagnosis of diabetes in type II diabetic patients
- 1993
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 16:6, s. 902-910
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To determine the effects of islet cell antibodies on β-cell function during the first 3 yr after diagnosis in type II diabetic patients. RESEARCH DESIGN AND METHODS - β-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 β-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). β-cell function was evaluated as fasting C- peptide, 1 + 3 min C-peptide after intravenous glucose, and Δ 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). Δ 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 Δ 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 Δ C-peptide after glucagon of 1.76 ± 0.28 nM. CONCLUSIONS - In patients considered type II diabetic with ICA, β-cell function progressively decreased after diagnosis, and after 3 yr was similar to type I diabetic patients, whereas β-cell function in type II diabetic patients without ICA was unchanged.
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| 4. |
- Grubin, C. E., et al.
(författare)
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A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM
- 1994
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Ingår i: Diabetologia. - 0012-186X. ; 37:4, s. 344-350
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n=10) and control (n=50) standard sera were used to develop quantitative antibody assays with in vitro synthesized recombinant 35S-methionine-labelled GAD65 and GAD67, respectively, and protein A-Sepharose to separate free from antibody-bound ligand. Binding levels were not normally distributed (p<0.0001) and therefore, the diagnostic accuracy of GAD antibodies was analysed by the ROC plots in population-based, consecutively-diagnosed, recent onset, 0-14 year-old patients (n=105), and matched, healthy control subjects (n=157). The ROC plots showed that the diagnostic sensitivity of GAD65 antibodies was 77% and the specificity 92% compared with 8% and 98%, respectively for GAD67 antibodies. In the IDDM sera, GAD65 and GAD67 antibodies were concordant in 7% (6 of 81) and GAD65 antibodies and ICA in 89% (72 of 81) without a correlation between the autoantibody levels. Autoantibodies to recombinant human islet GAD65 are specific and sensitive markers for childhood IDDM in this immunoassay with in vitro synthesized 35S-methioninelabelled recombinant GAD.
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| 5. |
- Landin-Olsson, M., et al.
(författare)
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Islet cell and thyrogastric antibodies in 633 consecutive 15- to 34-yr-old patients in the diabetes incidence study in Sweden
- 1992
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 41:8, s. 1022-1027
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Tidskriftsartikel (refereegranskat)abstract
- 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 < 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 < 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.
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| 6. |
- Wilson, C. A., et al.
(författare)
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IL-1β modulation of spontaneous autoimmune diabetes and thyroiditis in the BB rat
- 1990
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Ingår i: Journal of Immunology. - 0022-1767. ; 144:10, s. 3784-3788
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Tidskriftsartikel (refereegranskat)abstract
- Long term effects of in vivo treatment with human rIL-1β on diabetogenesis and thyroid disease were determined in the Biobreeding rat. Administration of high dose (10 μg/kg) IL-1β accelerated the onset of insulin-dependent diabetes mellitus compared to saline-injected controls. High dose treatment resulted in goiter development, pronounced LT, reduced serum T4 levels, and overall growth reduction. In contrast, low dose IL-1β (0.5 μg/kg) administration significantly reduced the frequency of insulin-dependent diabetes mellitus (48%) compared to placebo (86%) and high dose IL-1β (93%) treatment groups. Rats protected by low dose IL-1β had unaffected growth rates and minimal to no pancreatic and thyroid pathology. Our results demonstrate that exogenous administration of IL-1β modulates Biobreeding rat idiopathic autoimmune diabetes and thyroid disease in a dose-dependent manner.
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| 7. |
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| 8. |
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| 9. |
- Gottsäter, A., et al.
(författare)
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Islet cell antibodies are associated with β-cell failure also in obese adult onset diabetic patients
- 1994
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Ingår i: Acta Diabetologica. - 0940-5429. ; 31:4, s. 226-231
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Tidskriftsartikel (refereegranskat)abstract
- To clarify the utility of islet cell antibodies (ICA) to correctly classify and predict insulin treatment in newly diagnosed diabetic subjects, ICA, body mass index (BMI), glycated hemoglobin (HbA1c), and fasting plasma C-peptide values were evaluated at and 3 years after diagnosis in 233 new, consecutively diagnosed, adult diabetic patients classified as obese or nonobese (National Diabetes Data Group, NDDG criteria). Among the 233 patients, 31 were nonobese ICA-positive (mean age at diagnosis 43±3 years), 55 nonobese ICA-negative (mean age at diagnosis 58±2 years), 7 obese ICA-positive (mean age at diagnosis 57±5 years), and 139 obese ICA-negative (mean age at diagnosis 58±1 years). Fasting C-peptide decreased (P<0.05) in nonobese ICA-positive patients who after 3 years showed lower BMI (22.6±0.6 versus 24.5±0.4;P<0.05), lower fasting C-peptide (0.14±0.06 nmol/l versus 0.71±0.07 nmol/l;P<0.001), and higher frequency of insulin treatment [28/31 (90%) versus 6/45 (13%);P<0.001] than nonobese ICA-negative patients. In obese ICA-positive patients, fasting C-peptide also decreased (Δ C-peptide 0.17±0.04 nmol/l;P<0.05) after diagnosis, and 3 years after diagnosis, obese ICA-positive patients showed lower BMI (25.7±1.2 versus 29.8±0.4;P<0.01) and fasting C-peptide (0.08±0.04 nmol/l versus 1.06±0.05 nmol/l;P<0.001) and higher HbA1c values (9.92%±0.68% versus 7.39%±0.21%;P<0.01) and a higher frequency of insulin treatment [7/7 (100%) versus 5/121 (4%);P<0.001] than obese ICA-negative patients. Therefore, ICA detected at diagnosis of diabetes in both obese and nonobese adult patients indicate β-cell dysfunction, high HbA1c levels, and progression to insulin dependency.
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| 10. |
- Gottsäter, A., et al.
(författare)
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Pancreatic beta-cell function evaluated by intravenous glucose and glucagon stimulation. A comparison between insulin and c-peptide to measure insulin secretion
- 1992
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 52:7, s. 631-639
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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