| 1. |
- Ahrén, Bo, et al.
(författare)
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Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.
- 2002
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 25:5, s. 869-75
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.RESEARCH DESIGN AND METHODS: A total of 93 patients (61 men and 32 women), aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/- 0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).RESULTS: Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups.CONCLUSIONS: We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.
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| 2. |
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| 3. |
- Home, Philip, et al.
(författare)
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Insulin Detemir Offers Improved Glycemic Control Compared With NPH Insulin in People With Type 1 Diabetes: A randomized clinical trial.
- 2004
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 27:5, s. 1081-1087
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—Insulin detemir is a soluble long-acting basal insulin analog designed to overcome the limitations of conventional basal insulin formulations. Accordingly, insulin detemir has been compared with NPH insulin with respect to glycemic control (HbA1c, prebreakfast glucose levels and variability, and hypoglycemia) and timing of administration. RESEARCH DESIGN AND METHODS—People with type 1 diabetes (n = 408) were randomized in an open-label, parallel-group trial of 16-week treatment duration using either insulin detemir or NPH insulin. Insulin detemir was administered twice daily using two different regimens, either before breakfast and at bedtime (IDetmorn+bed) or at a 12-h interval (IDet12h). NPH insulin was administered before breakfast and at bedtime. Mealtime insulin was given as the rapid-acting insulin analog insulin aspart. RESULTS—With both insulin detemir groups, clinic fasting plasma glucose was lower than with NPH insulin (IDet12h vs. NPH, −1.5 mmol/l [95% CI −2.51 to −0.48], P = 0.004; IDetmorn+bed vs. NPH, −2.3 mmol/l (−3.32 to −1.29), P < 0.001), as was self-measured prebreakfast plasma glucose (P = 0.006 and P = 0.004, respectively). The risk of minor hypoglycemia was lower in both insulin detemir groups (25%, P = 0.046; 32%, P = 0.002; respectively) compared with NPH insulin in the last 12 weeks of treatment, this being mainly attributable to a 53% reduction in nocturnal hypoglycemia in the IDetmorn+bed group (P < 0.001). Although HbA1c for each insulin detemir group was not different from the NPH group, HbA1c for the pooled insulin detemir groups was significantly lower than for the NPH group (mean difference −0.18% [−0.34 to −0.02], P = 0.027). Within-person between-day variation in self-measured prebreakfast plasma glucose was lower for both detemir groups (both P < 0.001). The NPH group gained weight during the study, but there was no change in weight in either of the insulin detemir groups (IDet12h vs. NPH, −0.8 kg [−1.44 to −0.24], P = 0.006; IDetmorn+bed vs. NPH, −0.6 kg [−1.23 to −0.03], P = 0.040). CONCLUSIONS—Overall glycemic control with insulin detemir was improved compared with NPH insulin. The data provide a basis for tailoring the timing of administration of insulin detemir to the individual person’s needs.
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| 4. |
- Littorin, Bengt, et al.
(författare)
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Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults : A nationwide study
- 2001
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 24:6, s. 1033-1037
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To elucidate whether family characteristics and stressful life events were associated with onset of autoimmune type 1 diabetes in young adults. RESEARCH DESIGN AND METHODS - This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of newly diagnosed patients aged 15-34 years. Patients clinically classified as type 1 diabetic with antibodies to islet cells and/or to GAD65 were compared with age- and sex-matched control subjects via questionnaire. The questionnaire covered diabetes heredity, social environment, educational level, and life events experienced during the 12 months before diagnosis. RESULTS - The rate of response was 82% for the diabetic patients and 65% for the control subjects. Questionnaires from 349 diabetic patients and 979 control subjects were considered. Diabetes in relatives was more frequent in the patients (odds ratio [OR] 2.6) who were born in Sweden and whose mothers were of Swedish origin. No major stress factors were detected in the diabetic patients, however, in comparison with the control subjects, the diabetic patients had experienced fewer conflicts with their parents and had less often broken contacts with friends. CONCLUSIONS - Young adults with recent-onset type 1 diabetes were more exposed to heredity for diabetes, but no major prediabetic stress factors were detected. Our study does not directly support the concept that psychosocial stressful life events are involved in the development of autoimmune type 1 diabetes in young adults.
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| 5. |
- Littorin, Bengt, et al.
(författare)
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Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment : A cohort study in young adults whose disease was initially labeled as type 2 or unclassifiable diabetes
- 1999
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 22:3, s. 409-412
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To clarify the predictive value of islet cell antibody (ICA) and GAD65 antibody (GADA) present at diagnosis with respect to the need for insulin treatment 6 years after diagnosis in young adults initially considered to have type 2 or unclassifiable diabetes.RESEARCH DESIGN AND METHODS:The patient material was representative of the entire Swedish population, consisting of patients who were 15-34 years old at diagnosis of diabetes in 1987-1988 but were not considered to have type 1 diabetes at onset. At follow-up, 6 years after the diagnosis, it was noted whether the patient was treated with insulin. The presence of ICA was determined by an immunofluorescence assay, and GADAs were measured by a radioligand assay.RESULTS:Six years after diagnosis, 70 of 97 patients were treated with insulin, and 27 of 97 patients were treated with oral drugs or diet alone. At diagnosis, ICAs and GADAs were present in 41 (59%) of 70 patients and 41 (60%) of 68 patients, respectively, of those now treated with insulin, compared with only 1 (4%) of 26 patients and 2 (7%) of 27 patients who were still not treated with insulin. For either ICA or GADA, the corresponding frequencies were 50 (74%) of 68 for patients who were later treated with insulin and 3 (12%) of 26 for those who were still not treated with insulin, respectively. The sensitivity for later insulin treatment was highest (74%) for the presence of ICA or GADA, and the specificity was highest (100%) for ICA and GADA. The positive predictive value was 100% for the combination of ICA and GADA, 98% for ICA alone, and approximately 95% for GADA alone.CONCLUSIONS:Determination of the presence of ICA and GADA at diagnosis of diabetes improves the classification of diabetes and predicts the future need of insulin in young adults.
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| 6. |
- Nilsson, Charlotta, et al.
(författare)
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Presence of GAD-antibodies during gestational diabetes predicts type 1 diabetes.
- 2007
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 30:8, s. 1968-1971
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - we sought to study the frequency of P-cell-specific autoantibody markers in women with gestational diabetes mellitus (GDM) and to follow these women to estimate the risk of later development of type I diabetes. RESEARCH DESIGN AND METHODS - Of 385 pregnant women with GDM during 1995-2005 in the district of Lund, 24 (6%) women were found positive for at least one of the following: islet cell antibody (ICA), GAD antibody (GADA), or tyrosine phosphatase antibody(IA-2A). The women were followed and autoantibodies reanalyzed. Those who had not developed diabetes did an oral glucose tolerance test. The frequencies of known risk factors; for GD were compared in women with GDM with and without pancreatic autoantibodies. RESULTS - Among the autoantibody-positive women, 50% had developed type I diabetes compared with none among the GDM control subjects (P = 0. 00 1), 2 1 % had impaired fasting glucose or impaired glucose tolerance compared with 12.5% among control subjects (P = 0.3), and none had developed type 2 diabetes compared with 12.5% among control subjects (P 0.1). CONCLUSIONS - Autoantibody screening in pregnant women with GDM and follow-up after delivery should be considered for early recognition of type I diabetes.
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| 7. |
- Rosenstock, J, et al.
(författare)
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Effects of the DPP-4 Inhibitor Vildagliptin on Incretin Hormones, Islet Function, and Postprandial Glycemia in Subjects with Impaired Glucose Tolerance
- 2008
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 31:1, s. 30-35
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study was conducted to determine the effects of vildagliptin on incretin hormone levels, islet function, and postprandial glucose control in subjects with impaired glucose tolerance (IGT). Research Design and Methods: A 12-week double-blind, randomized, parallel-group study comparing vildagliptin (50 mg qd) and placebo was conducted in 179 subjects with IGT (2-h glucose= 9.1 mmol/l, A1C= 5.9%). Plasma levels of intact GLP-1 and GIP, glucose, insulin, C-peptide, and glucagon were measured during standard meal tests performed at baseline and Week 12. Insulin secretory rate (ISR) was estimated by C-peptide deconvolution. The between-group differences (vildagliptin - placebo) in the adjusted mean changes from baseline to endpoint in the total and incremental (Delta) AUC(0-2h) for these analytes were assessed by ANCOVA; glucose AUC(0-2h) was the primary outcome variable. Results: Relative to placebo, vildagliptin increased GLP-1 (DeltaAUC, +6.0+/-1.2 pmol/l*h, P<0.001) and GIP (DeltaAUC, +46.8+/-5.4 pmol/l*h, P<0.001) and decreased glucagon (DeltaAUC, -3.0 +/- 1.0 pmol/l*h, P=0.003). Although postprandial insulin levels were unaffected (DeltaAUC, +20.8+/-35.7 pmol/l*h, P=0.561), prandial glucose excursions were reduced (DeltaAUC, -1.0+/-0.3 mmol/l*h, P<0.001), representing approximately 30% decrease relative to placebo. Beta-cell function as assessed by the ISR AUC(0-2h)/glucose AUC(0-2h) was significantly increased (+6.4 +/- 2.0 pmol*min(-1)*m(-2)*mM(-1), P=0.002). Adverse event profiles were similar in the two treatment groups and no hypoglycemia was reported. Conclusions: The known effects of vildagliptin on incretin levels and islet function in type 2 diabetes were reproduced in subjects with IGT with a 32% reduction in postprandial glucose excursions and no evidence of hypoglycemia or weight gain.
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| 8. |
- Toppe, Cecilia, et al.
(författare)
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Decreasing cumulative incidence of end-stage renal disease in young patients with type 1 diabetes in Sweden : A 38-year prospective nationwide study
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:1, s. 27-31
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Diabetic nephropathy is a serious complication of type 1 diabetes. Recent studies indicate that end-stage renal disease (ESRD) incidence has decreased or that the onset of ESRD has been postponed; therefore, we wanted to analyze the incidence and time trends of ESRD in Sweden. RESEARCH DESIGN AND METHODS In this study, patients with duration of type 1 diabetes >14 years and age at onset of diabetes 0–34 years were included. Three national diabetes registers were used: the Swedish Childhood Diabetes Register, the Diabetes Incidence Study in Sweden, and the National Diabetes Register. The Swedish Renal Registry, a national register on renal replacement therapy, was used to identify patients who developed ESRD. RESULTS We found that the cumulative incidence of ESRD in Sweden was low after up to 38 years of diabetes duration (5.6%). The incidence of ESRD was lower in patients with type 1 diabetes onset in 1991–2001 compared with onset in 1977–1984 and 1985–1990, independent of diabetes duration. CONCLUSIONS The risk of developing ESRD in Sweden in this population is still low and also seems to decrease with time.
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