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- 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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| 3. |
- 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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- Hagopian, William A., et al.
(författare)
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Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type
- 1993
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 91:1, s. 368-374
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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