157 results on '"Thorsteinsson, B."'
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2. Education North of 60; The Canadian Superintendent 1964.
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Canadian Association of School Superintendents and Inspectors, Ottawa (Ontario). and Thorsteinsson, B.
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The 1964 booklet is a report on the Canadian educational system in the Northwest Territories and northern Quebec. Prepared by the Canadian Association of School Superintendents and Inspectors of Northern Affairs and Resources, it is intended as a description rather than an analysis or philosophical treatment of education north of the 60th parallel. According to the report, the system is "the most recently organized, the most remote, the most expensive per pupil, and the most complex system of education in Canada." It includes schools ranging in size from 1 room and 20 pupils at Reindeer Station, to 41 rooms with 44 teachers at Inuvik. The system serves an area of approximately 1,300,000 square miles and a population of only 26,000 multicultural and multilingual inhabitants (mainly Eskimos and other American Indians), or 1 person for every 50 square miles. Among the aims of the system are (1) to make elementary, secondary, and higher education available to all; (2) to include programs of vocational and adult education; (3) to broaden horizons, yet preserve cultures, offering new skills, yet not discarding the old; and (4) to introduce a second language as the language of instruction while maintaining and strengthening the mother tongue. The 10 chapters deal with various aspects of the educational system. (EJ)
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- 1964
3. Effect of metformin and insulin vs. placebo and insulin on whole body composition in overweight patients with type 2 diabetes:a randomized placebo-controlled trial
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Nordklint, A. K., Almdal, T. P., Vestergaard, P., Lundby-Christensen, L., Boesgaard, T. W., Breum, L., Gade-Rasmussen, B., Sneppen, S. B., Gluud, C., Hemmingsen, B., Perrild, H., Madsbad, S., Mathiesen, E. R., Tarnow, L., Thorsteinsson, B., Vestergaard, H., Lund, S. S., Eiken, P., Nordklint, A. K., Almdal, T. P., Vestergaard, P., Lundby-Christensen, L., Boesgaard, T. W., Breum, L., Gade-Rasmussen, B., Sneppen, S. B., Gluud, C., Hemmingsen, B., Perrild, H., Madsbad, S., Mathiesen, E. R., Tarnow, L., Thorsteinsson, B., Vestergaard, H., Lund, S. S., and Eiken, P.
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Summary: Some studies indicate potential beneficial effects of metformin on body composition and bone. This trial compared metformin + insulin vs placebo + insulin. Metformin treatment had a small but positive effect on bone quality in the peripheral skeleton, reduced weight gain, and resulted in a more beneficial body composition compared with placebo in insulin-treated patients with type 2 diabetes. Introduction: Glucose-lowering medications affect body composition. We assessed the long-term effects of metformin compared with placebo on whole body bone and body composition measures in patients with type 2 diabetes mellitus. Methods: This was a sub-study of the Copenhagen Insulin and Metformin Therapy trial, which was a double-blinded randomized placebo-controlled trial assessing 18-month treatment with metformin compared with placebo, in combination with different insulin regimens in patients with type 2 diabetes mellitus (T2DM). The sub-study evaluates the effects on bone mineral content (BMC), density (BMD), and body composition from whole body dual-energy X-ray absorptiometry (DXA) scans which were assessed at baseline and after 18 months. Results: Metformin had a small, but positive, (p < 0.05) effect on subtotal, appendicular, and legs BMC and BMD compared with placebo. After adjustment for sex, age, vitamin D, smoking, BMI, T2DM duration, HbA1c, and insulin dose, the effects on appendicular BMC and BMD persisted (p < 0.05 for both). The changes in appendicular BMC and BMD corresponded approximately to a 0.7% and 0.5% increase in the metformin group and 0.4% and 0.4% decrease in the placebo group, respectively. These effects were mostly driven by an increase in BMC and BMD in the legs and a loss of BMC and BMD in the arms. During 18 months, all participants increased in weight, fat mass (FM), FM%, and lean mass (LM), but decreased in LM%. The metformin group increased less in weight (subtotal weight (weight-head) − 2.4 [− 3.5, − 1.4] kg, p value
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- 2021
4. A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes
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Ringholm, L., Pedersen-Bjergaard, U., Thorsteinsson, B., Boomsma, F., Damm, P., and Mathiesen, E. R.
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- 2011
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5. Comparison of Insulin Degludec and Glargine U100 in Patients with Type 1 Diabetes Prone to Severe Nocturnal Hypoglycaemia
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Agesen, R, Alibegovic, A, Andersen, H, Beck-Nielsen, H, Gustenhoff, P, Hansen, T, Hedetoft, C, Jensen, T, Juhl, C, Kryger, A, Lerche, S, Norgaard, K, Parving, H -H., Sorensen, A, Tarnow, L, Thorsteinsson, B, and Pedersen-Bjergaard, U
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- 2020
6. COMPARISON OF INSULIN DEGLUDEC AND GLARGINE U100 IN PATIENTS WITH TYPE 1 DIABETES PRONE TO SEVERE NOCTURNAL HYPOGLYCAEMIA
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Agesen, R., Alibegovic, A., Andersen, H., Beck-Nielsen, H., Gustenhoff, P., Hansen, T., Hedetoft, C., Jensen, T., Juhl, C., Kryger, A., Lerche, S., Norgaard, K., Parving, H. -H., Sørensen, A., Tarnow, L., Thorsteinsson, B., Pedersen-Bjergaard, U., Agesen, R., Alibegovic, A., Andersen, H., Beck-Nielsen, H., Gustenhoff, P., Hansen, T., Hedetoft, C., Jensen, T., Juhl, C., Kryger, A., Lerche, S., Norgaard, K., Parving, H. -H., Sørensen, A., Tarnow, L., Thorsteinsson, B., and Pedersen-Bjergaard, U.
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- 2020
7. Association between plasma activities of semicarbazide-sensitive amine oxidase and angiotensin-converting enzyme in patients with type 1 diabetes mellitus
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Boomsma, F., Pedersen-Bjergaard, U., Agerholm-Larsen, B., Hut, H., Dhamrait, S. S., Thorsteinsson, B., and van den Meiracker, A. H.
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- 2005
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8. Prediction of Severe Hypoglycaemia by Angiotensin-Converting Enzyme Activity and Genotype in Type 1 Diabetes
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Pedersen-Bjergaard, U., Agerholm-Larsen, B., Pramming, S., Hougaard, P., and Thorsteinsson, B.
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- 2003
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9. Liraglutide preserved insulin secretion in adults with newly diagnosed type 1 diabetes: the NewLira trial:[Meeting Abstract}
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Dejgaard, T. F., Frandsen, C., Kielgast, U., Andersen, H. U., Thorsteinsson, B., Krarup, T., Holst, J. J., Madsbad, S., Dejgaard, T. F., Frandsen, C., Kielgast, U., Andersen, H. U., Thorsteinsson, B., Krarup, T., Holst, J. J., and Madsbad, S.
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- 2019
10. Asymptomatic hypoglycaemia in Type 1 diabetes:incidence and risk factors
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Henriksen, M. M., Andersen, H. U., Thorsteinsson, B., Pedersen-Bjergaard, U., Henriksen, M. M., Andersen, H. U., Thorsteinsson, B., and Pedersen-Bjergaard, U.
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Aim: The epidemiology of asymptomatic (silent) hypoglycaemia is not well-described. We investigated incidence and risk factors for asymptomatic hypoglycaemia in Type 1 diabetes. Methods: A cohort of 153 people with Type 1 diabetes participated in 6 days of blinded continuous glucose monitoring (CGM) and recording of hypoglycaemia symptoms. At entry, hypoglycaemia awareness was classified (by three different methods) and HbA 1c and C-peptide were measured. Hypoglycaemic episodes were defined as interstitial glucose ≤ 3.9 mmol/l (IG 3.9 ) or ≤ 3.0 mmol/l (IG 3.0 ) for ≥ 15 min, and were considered asymptomatic if no hypoglycaemic symptoms were reported. Results: At thresholds IG 3.9 and IG 3.0 , the incidence rates of hypoglycaemic episodes were 5.0 (7.9) [median (IQR)] and 1.3 (3.4) episodes/person-week, respectively. Three-quarters of episodes were asymptomatic. In total, 77% and 52% of participants experienced one or more episode of asymptomatic hypoglycaemia at IG 3.9 and IG 3.0 [3.0 (6.2) and 1.0 (2.3) asymptomatic episodes/person-week]. At multivariate analysis, reduced awareness was positively associated with asymptomatic hypoglycaemia, particularly nocturnal events, and negatively with symptomatic hypoglycaemia. High insulin dose was associated with increased risk of both asymptomatic and symptomatic hypoglycaemia, whereas low HbA 1c and long diabetes duration were risk factors only for symptomatic hypoglycaemia. Conclusions: Asymptomatic hypoglycaemia constitutes the majority of hypoglycaemic events in Type 1 diabetes. Reduced hypoglycaemia awareness and high insulin dose are risk factors for asymptomatic hypoglycaemia but other conventional risk factors for severe hypoglycaemia do not correlate with risk of asymptomatic episodes.
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- 2019
11. The effect of metformin versus placebo in combination with insulin analogues on bone mineral density and trabecular bone score in patients with type 2 diabetes mellitus:a randomized placebo-controlled trial
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Nordklint, A. K., Almdal, T. P., Vestergaard, P., Lundby-Christensen, L., Boesgaard, T. W., Breum, L., Gade-Rasmussen, B., Sneppen, S. B., Gluud, C., Hemmingsen, B., Jensen, T., Krarup, T., Madsbad, S., Mathiesen, E. R., Perrild, H., Tarnow, L., Thorsteinsson, B., Vestergaard, H., Lund, S. S., Eiken, P., Nordklint, A. K., Almdal, T. P., Vestergaard, P., Lundby-Christensen, L., Boesgaard, T. W., Breum, L., Gade-Rasmussen, B., Sneppen, S. B., Gluud, C., Hemmingsen, B., Jensen, T., Krarup, T., Madsbad, S., Mathiesen, E. R., Perrild, H., Tarnow, L., Thorsteinsson, B., Vestergaard, H., Lund, S. S., and Eiken, P.
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- 2018
12. Reply to comment on: Høi-Hansen T, Pedersen-Bjergaard U, Thorsteinsson B (2005) The Somogyi phenomenon revisited using continuous glucose monitoring in daily life. Diabetologia 48:2437–2438
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Høi-Hansen, T., Pedersen-Bjergaard, U., and Thorsteinsson, B.
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- 2006
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13. The Somogyi phenomenon revisited using continuous glucose monitoring in daily life
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Høi-Hansen, T., Pedersen-Bjergaard, U., and Thorsteinsson, B.
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- 2005
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14. Comparing effects of insulin analogues and human insulin on nocturnal glycaemia in hypoglycaemia-prone people with Type 1 diabetes
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Kristensen, P. L., Tarnow, L., Bay, C., Nørgaard, K., Jensen, T., Parving, H. H., Perrild, H., Beck-Nielsen, H., Christiansen, J. S., Thorsteinsson, B., Pedersen-Bjergaard, U., Kristensen, P. L., Tarnow, L., Bay, C., Nørgaard, K., Jensen, T., Parving, H. H., Perrild, H., Beck-Nielsen, H., Christiansen, J. S., Thorsteinsson, B., and Pedersen-Bjergaard, U.
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Aims: To assess the difference between analogue and human insulin with regard to nocturnal glucose profiles and risk of hypoglycaemia in people with recurrent severe hypoglycaemia. Methods: A total of 72 people [46 men, mean ± sd age 54 ± 12 years, mean ± sd HbA1c 65 ± 12 mmol/mol (8.1 ± 1.1%), mean ± sd duration of diabetes 30 ± 14 years], who participated in a 2-year randomized, crossover trial of basal-bolus therapy with insulin detemir/insulin aspart or human NPH insulin/human regular insulin (the HypoAna trial) were studied for 2 nights during each treatment. Venous blood was drawn hourly during sleep. Primary endpoints were nocturnal glucose profiles and occurrence of hypoglycaemia (blood glucose ≤ 3.9 mmol/l). Results: During insulin analogue treatment, the mean nocturnal plasma glucose level was significantly higher than during treatment with human insulin (10.6 vs 8.1 mmol/l). The fasting plasma glucose level was similar between the treatments. Nocturnal hypoglycaemia was registered during 41/101 nights (41%) in the human insulin arm and 19/117 nights (16%) in the insulin analogue arm, corresponding to a hazard ratio of 0.26 (95% CI 0.14 to 0.45; P < 0.0001) with insulin analogue. Conclusions: Treatment with insulin analogue reduces the occurrence of nocturnal hypoglycaemia assessed by nocturnal glucose profiles in people with Type 1 diabetes prone to severe hypoglycaemia. Nocturnal glucose profiles provide a more comprehensive assessment of clinical benefit of insulin regimens as compared to conventional recording of hypoglycaemia.
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- 2017
15. Severe hypoglycaemia in unselected patients with type 1 diabetes: A cross-sectional multicentre survey
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Pramming, S, Pedersen-Bjergaard, U, Heller, SR, Wallace, T, Rasmussen, AK, Jorgensen, HV, Matthews, DR, and Thorsteinsson, B
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- 2016
16. Severe hypoglycaemia in 1076 adult patients with type 1 diabetes: influence of risk markers and selection
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Pedersen-Bjergaard, U, Pramming, S, Heller, SR, Wallace, TM, Rasmussen, AK, Jørgensen, HV, Matthews, DR, Hougaard, P, and Thorsteinsson, B
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endocrine system diseases ,nutritional and metabolic diseases ,macromolecular substances - Abstract
BACKGROUND: Differences between studies in rates of severe hypoglycaemia in type 1 diabetic cohorts are common and poorly understood. The purpose of this study was to assess the frequency of severe hypoglycaemia in unselected patients treated in different secondary care centres and to evaluate the influence of risk markers, clinical setting and selection. METHODS: Cross-sectional Danish-British multicentre survey of 1076 consecutive adult patients with clinical type 1 diabetes who completed a detailed questionnaire on hypoglycaemia and related issues. Key variable was the self-reported rate of severe hypoglycaemia during the preceding year. RESULTS: The overall rate of severe hypoglycaemia in the preceding year was 1.3 episodes/patient-year and episodes were reported by 36.7% of subjects. The distribution was highly skewed with 5% of subjects accounting for 54% of all episodes. There were no significant differences between countries or centres. Reduced hypoglycaemia awareness, peripheral neuropathy and smoking were the only significant risk markers of severe hypoglycaemia in a stepwise multivariate analysis. In a subgroup selected to be similar to the Diabetes Control and Complications Trial (DCCT) cohort, the rate of severe hypoglycaemia was 0.35 episodes/patient-year and only retinopathy was a significant risk marker together with state of awareness. CONCLUSION: Severe hypoglycaemia remains a significant clinical problem in type 1 diabetes. The rate of severe hypoglycaemia and the influence of risk markers are very sensitive to selection and differences in rates between centres or studies seem to disappear after correction for differences in clinical characteristics. Smoking is a novel overall risk marker of severe hypoglycaemia.
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- 2016
17. Association between hypoglycaemia and impaired hypoglycaemia awareness and mortality in people with Type 1 diabetes mellitus
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Sejling, A.S., Schouwenberg, B.J., Faerch, L.H., Thorsteinsson, B., Galan, B.E. de, Pedersen-Bjergaard, U., Sejling, A.S., Schouwenberg, B.J., Faerch, L.H., Thorsteinsson, B., Galan, B.E. de, and Pedersen-Bjergaard, U.
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Item does not contain fulltext, AIMS: To examine whether severe hypoglycaemia and impaired hypoglycaemic awareness, a principal predictor of severe hypoglycaemia, are associated with all-cause mortality or cardiovascular mortality in Type 1 diabetes mellitus. METHODS: Mortality was recorded in two cohorts, one in Denmark (n = 269, follow-up 12 years) and one in the Netherlands (n = 482, follow-up 6.5 years). In both cohorts, awareness class was characterized and numbers of episodes of severe hypoglycaemia either during lifetime (Danish cohort) or during the preceding year (Dutch cohort) were recorded. In addition, episodes of severe hypoglycaemia were prospectively recorded every month for 1 year in the Danish cohort. Follow-up data regarding mortality were obtained through medical reports and registries (Danish cohort). RESULTS: All-cause mortality was 14% (n = 39) in the Danish and 4% (n = 20) in the Dutch cohort. In either cohort, neither presence of episodes with severe hypoglycaemia nor impaired hypoglycaemia awareness were associated with increased mortality in age-truncated Cox proportional hazard regression models. Variables associated with increased risk of all-cause mortality in both cohorts were evidence of macrovascular disease and reduced kidney function. CONCLUSIONS: Severe hypoglycaemia and hypoglycaemia unawareness are not associated with increased risk of all-cause or cardiovascular mortality in people with Type 1 diabetes mellitus.
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- 2016
18. Association between hypoglycaemia and impaired hypoglycaemia awareness and mortality in people with Type 1 diabetes mellitus
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Sejling, A-S, Schouwenberg, B, Faerch, L H, Thorsteinsson, B, de Galan, B E, Pedersen-Bjergaard, U, Sejling, A-S, Schouwenberg, B, Faerch, L H, Thorsteinsson, B, de Galan, B E, and Pedersen-Bjergaard, U
- Abstract
AIMS: To examine whether severe hypoglycaemia and impaired hypoglycaemic awareness, a principal predictor of severe hypoglycaemia, are associated with all-cause mortality or cardiovascular mortality in Type 1 diabetes mellitus.METHODS: Mortality was recorded in two cohorts, one in Denmark (n = 269, follow-up 12 years) and one in the Netherlands (n = 482, follow-up 6.5 years). In both cohorts, awareness class was characterized and numbers of episodes of severe hypoglycaemia either during lifetime (Danish cohort) or during the preceding year (Dutch cohort) were recorded. In addition, episodes of severe hypoglycaemia were prospectively recorded every month for 1 year in the Danish cohort. Follow-up data regarding mortality were obtained through medical reports and registries (Danish cohort).RESULTS: All-cause mortality was 14% (n = 39) in the Danish and 4% (n = 20) in the Dutch cohort. In either cohort, neither presence of episodes with severe hypoglycaemia nor impaired hypoglycaemia awareness were associated with increased mortality in age-truncated Cox proportional hazard regression models. Variables associated with increased risk of all-cause mortality in both cohorts were evidence of macrovascular disease and reduced kidney function.CONCLUSIONS: Severe hypoglycaemia and hypoglycaemia unawareness are not associated with increased risk of all-cause or cardiovascular mortality in people with Type 1 diabetes mellitus.
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- 2016
19. Effect of insulin analogues on frequency of non-severe hypoglycaemia in patients with type 1 diabetes prone to severe hypoglycaemia:The HypoAna trial
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Agesen, R M, Kristensen, P L, Beck-Nielsen, H, Nørgaard, K, Perrild, H, Christiansen, J S, Jensen, T, Hougaard, P, Parving, H H, Thorsteinsson, B, Tarnow, L, Pedersen-Bjergaard, U, Agesen, R M, Kristensen, P L, Beck-Nielsen, H, Nørgaard, K, Perrild, H, Christiansen, J S, Jensen, T, Hougaard, P, Parving, H H, Thorsteinsson, B, Tarnow, L, and Pedersen-Bjergaard, U
- Abstract
AIM: Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night.METHODS: This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal-bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996).RESULTS: Analogue-based treatment resulted in a 6% (2-10%; P=0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32-46%; P<0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36-57%]; P<0.0001) and asymptomatic (28% [14-39%]; P=0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months.CONCLUSION: In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin.
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- 2016
20. Severe hypoglycaemia during treatment with sulphonylureas in patients with type 2 diabetes in the Capital Region of Denmark
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Pilemann-Lyberg, S, Thorsteinsson, B, Snorgaard, O, Zander, M, Vestergaard, H, Røder, M E, Pilemann-Lyberg, S, Thorsteinsson, B, Snorgaard, O, Zander, M, Vestergaard, H, and Røder, M E
- Abstract
AIMS: Sulphonylureas (SU) are currently recommended as a well-established second line treatment in guidelines for type 2 diabetes (T2DM). In the Capital Region of Denmark 16,865 patients were given SU as part of their treatment of T2DM in 2010-2011. To what extent SU are associated with hospitalizations due to severe hypoglycaemic episodes, defined as episodes with a need for external assistance, was investigated. The prevalence and characteristics of these patients and potential risk factors were studied.METHODS: ICD-10 diagnosis codes were used to identify patients hospitalized due to hypoglycaemia and T2DM for a period of 2 years (2010-2011). Inclusion criteria were T2DM, hospitalization due to hypoglycaemia and treatment with SU as monotherapy or in combination with other glucose-lowering drugs except insulin treatment.RESULTS: We identified 161 patients fulfilling the inclusion criteria. Their mean age was 76 (53-97) years and 54% were males. Sixty percent of the patients had diabetic complications, including 19% with diabetic nephropathy. The major reason for severe hypoglycaemia was an unchanged dose of SU despite of a significant decline in food intake (45%). In 22% of the patients more than one reason was listed, most commonly a concomitant infection associated with decreased food intake and unchanged dose of SU.CONCLUSION: The incidence of hospital admission-requiring severe hypoglycaemia in patients treated with SU was 0.48 episodes per 100 patient-years of SU-treated patients. It was mainly older patients with diminished food intake, excessive alcohol use or other medications, concomitant infection, and with diabetic complications.
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- 2015
21. ACTH stimulation test in patients with type 1 diabetes and recurrent severe hypoglycaemia
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Kristensen, P. L., Diemar, S. S., Bay, C., Pedersen-Bjergaard, U., Beck-Nielsen, H., Christiansen, J. S., Nørgaard, K., Perrild, H., Tonny, J., Parving, H. H., Thorsteinsson, B., Tarnow, L., Kristensen, P. L., Diemar, S. S., Bay, C., Pedersen-Bjergaard, U., Beck-Nielsen, H., Christiansen, J. S., Nørgaard, K., Perrild, H., Tonny, J., Parving, H. H., Thorsteinsson, B., and Tarnow, L.
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- 2015
22. The relationship between plasma concentration and plasma disappearance rate of immunoreactive insulin in normal subjects
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Fugleberg, S., Kølendorf, K., Thorsteinsson, B., Bliddal, H., Lund, B., and Bojsen, F.
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- 1982
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23. Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes
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Parving, Hh, Brenner, Bm, Mcmurray, Jj, de Zeeuw, D, Haffner, Sm, Solomon, Sd, Chaturvedi, N, Persson, F, Desai, As, Nicolaides, M, Richard, A, Xiang, Z, Brunel, P, Pfeffer, Ma, Viberti, G, Lachin, Jm, Zinman, B, Pedersen, Tr, Villamil, As, Juncos, L, Prager, R, Verpooten, G, Zanella, Mt, Leiter, L, Pan, C, Wang, H, Botero, R, Cifkova, R, Christiansen, Js, Groop, Ph, Marre, M, Haller, H, Nickenig, G, Siamopoulos, K, Gero, L, Maggioni, A, Remuzzi, G, Katayama, Ss, Kim, Sg, Petrulioniene, Z, Lok, D, Kooy, A, Jorde, R, Medina, F, Polonia, J, Wong, Ks, Dukat, A, Rayner, Bl, Ruilope, L, Weiss, L, Wuethrich, R, Sheu, W, Sritara, P, Comlekci, A, Bilous, R, Toto, R, Jamerson, K, Carillo, E, Orias, M, Kuschnir, E, Rusculleda, M, Garcia, S, Farias, E, Lema, L, Hominal, M, Montaña, O, Sala, J, Diaz, M, Piskorz, D, Vita, N, Litwak, L, Sinay, I, Marin, M, Massari, P, Majul, C, Aizemberg, D, Azize, Gm, Bartolacci, I, Reboredo, A, Vico, M, Milesi, R, Sessa, H, Wassermann, A, Margulis, F, Zangroniz, P, Watschinger, B, Toplak, H, Paulweber, B, Drexel, H, Francesconi, C, Foeger, B, Mayer, G, Braun, Rk, Brath, H, Gaal, Lv, Niepen, Pv, Persu, A, Vercammen, C, Vriese, Ad, Coucke, F, Mathieu, C, Fery, F, Treille, S, Meeus, G, Acker, Kv, Scheen, A, Tits, J, Ruige, J, Krzesinski, Jm, Hollanders, G, Liénart, F, Dendale, P, Quinonez, M, Arnouts, P, Vanuytsel, J, Zanella, M, Mion D., Jr, Forti, A, Almeida, F, Cunha, R, de Paula RB, Brandao, A, Rocha, J, Krieger, E, Feitosa, G, Saraiva, J, Martin, J, Hissa, Mn, Schmid, H, Felicio, J, Sgarbi, J, Oigman, W, Bowering, K, Garceau, C, Berlingieri, Jc, Weisnagel, Sj, Hardin, P, Powell, C, Turcot, R, Muirhead, N, Aronson, R, Barima, Yt, Steele, Aw, Pandey, S, Woo, V, Cha, J, Dattani, D, Godin, C, Gupta, M, Saunders, K, Tellier, G, Ting, R, Tobe, S, Chouinard, G, Schlosser, R, Khandwala, H, Ekoe, Jm, Harris, Sb, Pichette, V, Lachance, P, Ooi, Tc, Tildesley, H, Barrett, B, Cournoyer, S, Lu, J, Zhang, H, Liu, X, Yan, S, Qi, X, Li, Q, Li, H, Lv, X, Yang, J, Sun, N, Xia, W, Wang, N, Tong, N, Mei, C, Gu, S, Zhang, J, Chen, X, Li, L, Su, B, Wang, L, Qiu, M, Wu, X, Liu, Z, Jia, W, Xu, G, Dong, J, Zhu, D, Zhang, M, Yan, J, Liu, B, Chen, J, Fu, J, Yan, L, Zhan, X, Zhong, L, Yang, T, Ma, J, Xu, M, Xu, X, Shi, B, Ji, Q, Zhong, H, He, R, Yuan, Z, Zhou, Z, Lin, H, Yang, W, Ke, Y, Hong, T, Franco, C, Casas, L, Triana, A, Jaramillo, C, Hernandez, E, Barrera, C, Blanco, D, Stipal, R, Widimsky, P, Dohnalova, L, Komroskova, M, Kvapil, M, Belobradkova, J, Tesar, V, Vodnansky, P, Kocourkova, B, Lervang, Hh, Perrild, H, Rossing, P, Oestergaard, O, Juhl, H, Thorsteinsson, B, Snorgaard, O, Urhammer, S, Egstrup, K, Tikkanen, T, Helin, K, Rinne, J, Lahtela, J, Strand, J, Valtonen, E, Saari, M, Kananen, K, Savela, K, Blacher, J, Aldigier, Jc, Zaoui, P, Fauvel, Jp, Gouet, D, Valensi, Pe, Charpentier, G, Marechaud, R, Penfornis, A, Ovize, M, Kovalchuck, Aa, Dellanna, F, Schoen, N, Groeschel, W, Eickhoff, F, Hanefeld, M, Merke, J, Rambausek, M, Zimmermann, U, Stuetz, W, Vosskuehler, A, Hevendehl, G, Schax, U, Lehmann, G, Haack, A, Hilgenberg, J, Klausmann, G, Adelberger, V, Gessner, S, Fiesselmann, A, Oerter, E, Hohenstatt, T, Groeschel, A, Behnke, T, Sisting, Rt, Schoch, D, Bieler, T, Schleyer, S, Altes, U, Klepzig, C, Rudofsky, G, Mueller, G, Burkhardt, F, Reschke, K, Senftleber, I, Wiesweg, Ck, Herrmann, Hj, Brandstetter, R, Segner, A, Schmitt, H, Rippert, R, Goebel, R, Schreibmueller, F, Pencz, I, Ott, P, Migdalis, I, Pappas, S, Pagkalos, E, Yalouris, A, Tsapas, A, Maltezos, E, Tentolouris, N, Papadakis, I, Ioannidis, G, Goumenos, D, Corona, V, Gonzalez, R, Haase, F, Monterroso, V, Sánchez, V, Turcios, E, Wyss, F, Arango, Jl, Bako, B, Deak, L, Dömötör, E, Dudas, M, Fulop, T, Kiss, I, Koranyi, L, Lengyel, Z, Nyirati, G, Oroszlan, T, Aniko, S, Vörös, P, Kapocsi, J, Wittmann, I, Paragh, G, Abraham, G, Tandon, N, Thomas, N, Mohan, V, Sahay, R, Sethi, B, Rao, V, Kumar, S, Chowdhury, S, Dharmalingam, M, Seshiah, V, Bantwal, G, Viswanathan, V, Yajnik, C, Adhikari, P, Krishnan, U, Varthakavi, P, Hiremath, J, Bhattacharyya, A, Dani, S, Modi, Kk, Glorioso, N, Morosetti, M, Veglio, Franco, Perticone, F, Dotta, F, Quarello, F, Sesti, G, Aiello, A, D'Ospina, A, Giordano, C, Novo, S, Santoro, A, Ferri, C, Capuano, V, Trimarco, B, Tonolo, G, Villa, G, De Pellegrin, A, Zanette, G, Federici, M, Aucello, G, Piatti, P, Vinciguerra, A, Mannarino, E, Taddei, S, Filetti, S, Grandaliano, G, Marchionni, N, Lambiase, C, Locatelli, F, Scanferla, F, Lembo, G, Leotta, S, Mos, L, Calatola, P, Fogari, R, David, S, Pedrinelli, R, Pignone, Am, Cozzolino, D, Bevilacqua, Mt, Catena, C, Del Prato, S, Cerasola, G, Frontoni, S, Falcone, C, Porta, A, Bonora, E, Cocchi, R, Fucili, A, Frisinghelli, A, Volpe, M, Carugo, S, Gambardella, S, Spagnuolo, V, Maglia, G, D'Angelo, Ar, Corsi, A, Limone, Pp, Guarnieri, A, Ghigo, Ezio, Ronchi, E, Ravera, M, Scioli, Ga, Sekiguchi, M, Aoki, S, Ogawa, Y, Seino, H, Onishi, Y, Tojo, A, Narimiya, M, Iwaita, Y, Takeda, H, Shimizu, H, Yamada, T, Kojima, S, Zushi, S, Kaneko, S, Matsumoto, A, Kajiyama, S, Fujita, H, Shikata, K, Tone, A, Matsubayashi, S, Tanaka, S, Sekigami, T, Tatsukawa, Y, Abe, N, Kawahara, K, Kasahara, H, Maeda, Y, Suzuki, Y, Okamoto, H, Tachi, K, Yamada, K, Uzu, T, Itou, T, Fukui, T, Kim, S, Kim, Y, Cho, W, Kwak, I, Chae, D, Oh, H, Ha, S, Shin, Y, Cha, D, Kang, S, Lim, C, Song, J, Kwon, Y, Badariene, J, Labutiniene, Ip, Zabuliene, L, Poteliuniene, V, Miglinas, M, van den Meiracker AH, Gregoor, Pj, Luik, Aj, van Loon BJ, Feenstra, Hj, Kaasjager, Ha, Viergever, Pp, Woittiez, Aj, van Bemmel, T, Lieverse, Ag, Simsek, S, Gaillard, Ca, van der Zwaan, C, Lok, Dj, Spiering, W, Nierop, Pr, Baggen, Mg, Leendert, Rj, de Jong, A, Leurs, Pb, Vincent, Hh, Wins, Eh, Voors, Aa, Ronner, E, Heeg, Je, van Hal JM, Boermans, T, Feis, Wl, Mostard, G, Bakker, Rc, Dunselman, Ph, Skeie, S, Istad, H, Skjelvan, G, Gronert, J, Tomala, T, Gudnason, S, Torvik, Dt, Risberg, K, Abedini, S, Cabrera, W, Medina, B, Herrada, B, Saavedra, A, Polonia, Dj, Providencia, Dl, Carvalho, D, Vasconcelos, Mp, da Silva GF, Branco, P, Gil, Dv, da Costa AG, da Silva PM, Arez, L, Martins, L, Birne, R, Dzuponova, J, Surovcikova, M, Culak, J, Filipova, S, Andre, I, Stevlik, J, Uhliar, R, Fabryova, L, Benacka, J, Koleny, D, Szentivanyi, M, Spisak, V, Pella, D, Pastrnakova, E, Martinka, E, Chua, T, Lau, T, Ng, Tg, Yeoh, Ly, Bhana, Sa, Rayner, B, Wellmann, H, Amod, A, Ranjith, N, Ahmed, F, Rheeder, P, Makan, H, Naicker, P, Podgorski, G, De Teresa, E, Olivan, J, Fernandez, Vl, Povedano, St, Terns, M, Ricart, W, Gonzalez, Jm, Fernandez, P, Parreño Lde, T, Redon, J, Parra, J, Calvo, C, Lopez, I, Puig, Jg, Calle, A, Garcia, Jc, Lopez, Jm, Jimenez, Ml, Fraile, B, Perez, Js, Nadal, Jj, Guija, E, Calviño, J, Barrios, V, Iglesias, Jn, Armario, P, Garcia, M, Aranda, P, Brotons, C, Gomez, P, Catelao, Am, Cusachs, Ar, Sarro, M, Martinez, V, dell Valle MH, Trias, F, Comas, A, Salvador, N, Martinez, F, Hernandez, F, Martinez, J, Mateos, C, Peral, Jl, Tolosana, J, Sobrino, J, Isart, J, Vizcaino, J, Vega, Ff, Zamorano, Jl, Bacariza, M, Soubriet, A, Fernández Cruz, A, Querejeta, R, Leira, Vm, Iglesias, Fe, Ibrik, O, Martin, D, Nanclares, Ms, Mediavilla, Jd, Galceran, Jm, Lopez, A, Muros, T, Pascual, J, Casalla, F, Tornero, F, Fernandez, G, Pettersson, P, Olsen, H, Franke, F, Stroembom, U, Furuland, H, Larnefelt, H, Allemann, Y, Krapf, R, Gerber, P, Munger, R, Hayoz, D, Graf, Hj, Burnier, M, Petrillo, A, Batt, R, Constam, En, Moccetti, T, Bianda, T, Rickli, H, Bulliard, C, Wu, Kd, Lin, Sh, Wu, Cj, Sheu, Wh, Su, Sl, Chen, Sc, Chou, Cw, Lee, Ct, Yang, Tc, Chen, Hc, Sukonthasarn, A, Sriratanasathavorn, C, Eiam Ong, S, Supasyndh, O, Chanchairujira, T, Kitiyakara, C, Arici, M, Usalan, C, Guneri, S, Koc, M, Kalender, B, Ates, K, Gurgun, C, Araz, M, Demirbas, B, Biernacki, W, Calvert, J, Eavis, P, Kerrane, J, Litchfield, J, Middleton, A, Roberts, J, Simpson, H, Charles, H, Jardine, A, Fisher, M, Banerjee, D, Gallen, I, Gnudi, L, Harvey, J, O'Hare, P, Vora, J, Winocour, P, Soran, H, Browne, D, Darko, D, Mancebo, Jg, de Roa ER, Antepara, N, Carrillo, E, Berrizbeitia, M, Guevara, L, Pernalete, N, Ontiveros, C, Zigrang, W, Blakney, E, Rosenblit, P, Weinstein, R, Klaff, L, Lipetz, R, Busick, E, Tung, P, Cooperman, M, Michael, S, Sun, Ch, Hart, T, Maddux, A, Bowden, R, East, C, Arakaki, R, Villafuerte, B, Mamish, Z, Mendez, R, Connery, L, Nour, K, Wynne, A, Busch, R, Zamora, B, Sachson, R, Prasad, J, Lasala, G, Smith, M, Fitz Patrick, D, Ruiz Rivera, L, Barranco, E, Solomon, R, Woolley, A, Brown, C, Freedman, Z, Schmidt, S, Pollock, J, Ruddy, M, Kopyt, Np, Bazzi, A, Horowitz, B, Feng, W, Wahl, T, Duprez, D, Gilbert, J, Steigerwalt, S, Jacqmein, J, Gorton, S, 3rd, Allison J., Pino, J, Lock, J, Leimbach, W, Anderson, J, Beacom, M, Craig, W, Gorson, D, Kerstein, H, Segal, S, Downey, H, Ledger, G, Mcgill, J, Gabriel, J, Nolen, T, Levinson, L, Williams, T, Levenson, D, Lerman, S, Minehart, C, Agarwal, N, Verma, S, Valitutto, M, Demetry, K, Mersey, J, Koeper, D, Fanti, P, Eng, G, Grimm, R, Fagan, T, Bajaj, M, Katz, L, Portnay, G, Altschuller, A, Desai, V, Bilazarian, S, Ipp, E, Rodelas, R, Burstein, D, Berg, J, Velez, J, Lund, R, Rekhi, A, Martin, E, Robertson, D, Singh, N, Narayan, P, Moustafa, M, Lanier, D, Seidner, M, Phillips, A, Vaughters, B, Sprague, A, Swartz, S, Lopez, R, Kumar, J, Bressler, P, Sadler, L, Wise, J, Kilbane, A., and Groningen Kidney Center (GKC)
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Male ,Hyperkalemia ,CARDIOVASCULAR MORTALITY ,BLOOD-PRESSURE ,Angiotensin-Converting Enzyme Inhibitors ,Type 2 diabetes ,GLOMERULAR-FILTRATION-RATE ,DOUBLE-BLIND ,chemistry.chemical_compound ,Fumarates ,cardiovascular disease ,Renin ,Treatment Failure ,Settore MED/49 - Scienze Tecniche Dietetiche Applicate ,610 Medicine & health ,diabetes ,Medicine (all) ,Hazard ratio ,aliskiren ,diabete ,trial clinico ,Liter ,General Medicine ,Middle Aged ,hypertension ,Cardiovascular Diseases ,Combination ,HEART-FAILURE ,Drug Therapy, Combination ,Female ,Kidney Diseases ,type 2 diabetes ,medicine.symptom ,Type 2 ,medicine.medical_specialty ,Patient Dropouts ,Urology ,Hypokalemia ,Aliskiren ,chronic kidney disease ,Placebo ,Angiotensin Receptor Antagonists ,LEFT-VENTRICULAR DYSFUNCTION ,Drug Therapy ,Double-Blind Method ,Diabetes Mellitus ,medicine ,Humans ,CONVERTING-ENZYME INHIBITORS ,Antihypertensive Agents ,Aged ,Amides ,Diabetes Mellitus, Type 2 ,Follow-Up Studies ,business.industry ,medicine.disease ,Confidence interval ,Surgery ,Blood pressure ,MYOCARDIAL-INFARCTION ,chemistry ,SYSTOLIC DYSFUNCTION ,FOLLOW-UP ,business - Abstract
BACKGROUND This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P = 0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, = 6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P CONCLUSIONS The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.)
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- 2012
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24. The incidence of severe hypoglycaemia in pregnant women with type 1 diabetes mellitus can be reduced with unchanged HbA1c levels and pregnancy outcomes in a routine care setting
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Ringholm, Lene, Secher, A L, Pedersen-Bjergaard, U, Thorsteinsson, B, Andersen, H U, Damm, P, Mathiesen, E R, Ringholm, Lene, Secher, A L, Pedersen-Bjergaard, U, Thorsteinsson, B, Andersen, H U, Damm, P, and Mathiesen, E R
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- 2013
25. Evaluating the cost-effectiveness of reduced mild hypoglycaemia in subjects with Type 1 diabetes treated with insulin detemir or NPH insulin in Denmark, Sweden, Finland and the Netherlands
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Valentine, W J, Jendle, J, Saraheimo, M, Thorsteinsson, B, Pollock, R F, Lammert, M, Valentine, W J, Jendle, J, Saraheimo, M, Thorsteinsson, B, Pollock, R F, and Lammert, M
- Abstract
Diabet. Med. 29, 303-312 (2012) ABSTRACT: Aims To estimate short-term cost-effectiveness of insulin detemir vs. NPH insulin based on the incidence of mild hypoglycaemia in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Methods A model was developed to evaluate cost-effectiveness based on mild (self-treated) hypoglycaemia and pharmacy costs over 1 year. Published rates of mild hypoglycaemia were used for NPH insulin and insulin detemir. Effectiveness was calculated in terms of quality-adjusted life expectancy. Pharmacy costs were accounted using published prices and defined daily doses for both insulins. Costs were expressed in 2010 euros (€). Results Treatment with insulin detemir was associated with fewer mild hypoglycaemic events than NPH insulin (mean rates of 26.3 vs. 35.5 events per person-year), leading to an improvement in mean quality-adjusted life expectancy of approximately 0.019 (0.030) quality-adjusted life years (standard deviation). Annual costs were € 573.55 (110.42) vs. € 332.76 (62.18) in Denmark for insulin detemir and NPH insulin, respectively. These values were € 545.79 (106.54) vs. € 306.12 (57.78) in Sweden, € 720.10 (140.74) vs. € 408.73 (78.61) in Finland and € 584.01 (109.47) vs. € 359.60 (64.84) in the Netherlands. Incremental cost-effectiveness ratios were approximately € 12 644 (Denmark), € 12 612 (Sweden), € 16 568 (Finland) and € 12 216 (the Netherlands) per quality-adjusted life year gained for insulin detemir vs. NPH insulin. Conclusions Insulin detemir is likely to be cost-effective vs. NPH insulin in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Increased pharmacy costs with insulin detemir should not be a barrier to therapy based on these findings.
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- 2012
26. Insulin analogues and severe hypoglycaemia in type 1 diabetes
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Kristensen, P L, Hansen, L S, Jespersen, M J, Pedersen-Bjergaard, U, Beck-Nielsen, Henning, Christiansen, J S, Nørgaard, K, Perrild, H, Parving, Hans-Henrik Dyring, Thorsteinsson, B, Tarnow, Lise, Kristensen, P L, Hansen, L S, Jespersen, M J, Pedersen-Bjergaard, U, Beck-Nielsen, Henning, Christiansen, J S, Nørgaard, K, Perrild, H, Parving, Hans-Henrik Dyring, Thorsteinsson, B, and Tarnow, Lise
- Abstract
The effect of insulin analogues on glycaemic control is well-documented, whereas the effect on avoidance of severe hypoglycaemia remains tentative. We studied the frequency of severe hypoglycaemia in unselected patients with type 1 diabetes treated with insulin analogues, human insulin, or mixed regimens.
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- 2012
27. Hypoglycaemia during pregnancy in women with Type 1 diabetes
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Nielsen, Lene Ringholm, Pedersen-Bjergaard, U, Thorsteinsson, B, Damm, P, Mathiesen, E R, Nielsen, Lene Ringholm, Pedersen-Bjergaard, U, Thorsteinsson, B, Damm, P, and Mathiesen, E R
- Abstract
Diabet. Med. 29, 558-566 (2012) ABSTRACT: Aims To explore incidence, risk factors, possible pathophysiological factors and clinical management of hypoglycaemia during pregnancy in women with Type 1 diabetes. Methods Literature review. Results In women with Type 1 diabetes, severe hypoglycaemia occurs three to five times more frequently in early pregnancy than in the period prior to pregnancy, whereas in the third trimester the incidence of severe hypoglycaemia is lower than in the year preceding pregnancy. The frequency distribution of severe hypoglycaemia is much skewed, as 10% of the pregnant women account for 60% of all recorded events. Risk factors for severe hypoglycaemia during pregnancy include a history with severe hypoglycaemia in the year preceding pregnancy, impaired hypoglycaemia awareness, long duration of diabetes, low HbA(1c) in early pregnancy, fluctuating plasma glucose values (= 3.9 mmol/l or = 10.0 mmol/l) and excessive use of supplementary insulin injections between meals. Pregnancy-induced nausea and vomiting seem not to be contributing factors. Conclusions Striving for near-normoglycaemia with focus on reduction of plasma glucose fluctuations during pregnancy should have high priority among clinicians with the persistent aim of improving pregnancy outcome among women with Type 1 diabetes. Pre-conception counselling, carbohydrate counting, use of insulin analogues, continuous subcutaneous insulin infusion (insulin pump) therapy and real-time continuous glucose monitoring with alarms for low glucose values might be relevant tools to obtain near-normoglycaemia without episodes of severe hypoglycaemia.
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- 2012
28. Evaluating the cost-effectiveness of reduced mild hypoglycaemia in subjects with Type 1 diabetes treated with insulin detemir or NPH insulin in Denmark, Sweden, Finland and the Netherlands
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Valentine, W. J., Jendle, Johan, Saraheimo, M., Thorsteinsson, B., Pollock, R. F., Lammert, M., Valentine, W. J., Jendle, Johan, Saraheimo, M., Thorsteinsson, B., Pollock, R. F., and Lammert, M.
- Abstract
AIMS: To estimate short-term cost-effectiveness of insulin detemir vs. NPH insulin based on the incidence of mild hypoglycaemia in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. METHODS: A model was developed to evaluate cost-effectiveness based on mild (self-treated) hypoglycaemia and pharmacy costs over 1 year. Published rates of mild hypoglycaemia were used for NPH insulin and insulin detemir. Effectiveness was calculated in terms of quality-adjusted life expectancy. Pharmacy costs were accounted using published prices and defined daily doses for both insulins. Costs were expressed in 2010 euros (€). RESULTS: Treatment with insulin detemir was associated with fewer mild hypoglycaemic events than NPH insulin (mean rates of 26.3 vs. 35.5 events per person-year), leading to an improvement in mean quality-adjusted life expectancy of approximately 0.019 (0.030) quality-adjusted life years (standard deviation). Annual costs were € 573.55 (110.42) vs. € 332.76 (62.18) in Denmark for insulin detemir and NPH insulin, respectively. These values were € 545.79 (106.54) vs. € 306.12 (57.78) in Sweden, € 720.10 (140.74) vs. € 408.73 (78.61) in Finland and € 584.01 (109.47) vs. € 359.60 (64.84) in the Netherlands. Incremental cost-effectiveness ratios were approximately € 12,644 (Denmark), € 12,612 (Sweden), € 16,568 (Finland) and € 12,216 (the Netherlands) per quality-adjusted life year gained for insulin detemir vs. NPH insulin. CONCLUSIONS: Insulin detemir is likely to be cost-effective vs. NPH insulin in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. Increased pharmacy costs with insulin detemir should not be a barrier to therapy based on these findings., Funding agency:Novo Nordisk A/S
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- 2012
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29. A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes
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Ringholm, L, Pedersen-Bjergaard, U, Thorsteinsson, B, Boomsma (fhv. Kristoffersen), Trine Krogh, Damm, P, Mathiesen, E R, Ringholm, L, Pedersen-Bjergaard, U, Thorsteinsson, B, Boomsma (fhv. Kristoffersen), Trine Krogh, Damm, P, and Mathiesen, E R
- Abstract
AIMS/HYPOTHESIS: The aim of this study was to investigate whether components of the renin-angiotensin system and semicarbazide-sensitive amine oxidase (SSAO) are associated with the development of pre-eclampsia in women with type 1 diabetes. METHODS: This was an observational study of 107 consecutive pregnant women with type 1 diabetes (median duration 16 years [range 1-36 years], HbA(1c) 6.6% [range 4.9-10.5%]) in early pregnancy. At 8, 14, 21, 27 and 33 weeks and once within 5 days postpartum, blood was sampled for measurements of prorenin, renin, angiotensinogen, ACE and SSAO. HbA(1c), blood pressure and urinary albumin excretion were recorded. Pre-eclampsia was defined as blood pressure >140/90 mmHg and proteinuria =300 mg/24 h after 20 weeks. RESULTS: Pre-eclampsia developed in nine women (8%) with longer diabetes duration (median 20 [range 10-32] vs 16 [range 1-36] years, p¿=¿0.04), higher SSAO concentrations (592 [range 372-914] vs 522 [range 264-872] mU/l, p¿=¿0.04) and a tendency towards higher prorenin levels (136 [range 50-296] vs 101 [range 21-316] ng angiotensin I ml(-1) h(-1), p¿=¿0.06) at 8 weeks compared with women without pre-eclampsia. Levels of renin, angiotensinogen and ACE did not differ in the two groups. Throughout pregnancy, prorenin and SSAO levels were 30% (p¿=¿0.004) and 16% (p¿=¿0.04) higher, respectively, in women developing pre-eclampsia. Using multivariate logistic regression analysis, prorenin concentration at 8 weeks was associated with pre-eclampsia (OR 4.4 [95% CI 1.5-13.0], p¿=¿0.007), i.e. an increase of prorenin of 100 ng angiotensin I ml(-1) h(-1) implies a 4.4 times higher risk of subsequent pre-eclampsia. CONCLUSIONS/INTERPRETATION: In type 1 diabetic women with pre-eclampsia, a higher concentration of prorenin in early pregnancy and higher levels of prorenin and SSAO throughout pregnancy were seen.
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- 2011
30. Erythropoietin and vascular endothelial growth factor as risk markers for severe hypoglycaemia in type 1 diabetes
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Kristensen, P L, Pedersen-Bjergaard, U, Schalkwijk, C, Olsen, Niels Vidiendal, Thorsteinsson, B, Kristensen, P L, Pedersen-Bjergaard, U, Schalkwijk, C, Olsen, Niels Vidiendal, and Thorsteinsson, B
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OBJECTIVE: Circulating erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increase during hypoglycaemia and may represent protective hormonal counter-regulatory responses. We tested the hypothesis that low levels of EPO and VEGF are associated with a higher frequency of severe hypoglycaemia in a cohort of patients with type 1 diabetes.DESIGN: Prospective observational follow-up study.METHODS: Totally 219 patients with type 1 diabetes (41% females, age 46+/-13 years (mean+/-s.d.), duration of diabetes 21+/-12 years, and HbAlc 8.5+/-1.1%) were followed in a 1-year observational study. Plasma EPO and serum VEGF levels were measured at baseline with ELISA. Events of severe hypoglycaemia defined by third party assistance were recorded and validated in telephone interviews within 24 h.RESULTS: Totally 235 episodes of severe hypoglycaemia (1.1 episodes per patient-year) were reported by 82 patients (37%). At baseline, plasma EPO was 8.6 (3.1-34.3) U/l (median (range)), and serum VEGF was 52.2 (6.6-337) pg/ml. The levels of EPO and VEGF were not associated with frequency of severe and mild hypoglycaemia. The levels of EPO were not associated with age, sex, duration of diabetes, body mass index, HbAlc, C-peptide level or hypoglycaemia awareness status. The levels of VEGF were positively associated with age and female sex.CONCLUSIONS: Although several studies suggest that VEGF and EPO may affect brain function during hypoglycaemia, this study does not support random VEGF or EPO levels to determine future risk of severe hypoglycaemia in people with type 1 diabetes.
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- 2010
31. Prospective and retrospective recording of severe hypoglycaemia, and assessment of hypoglycaemia awareness in insulin-treated Type 2 diabetes
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Akram, K, Pedersen-Bjergaard, U, Carstensen, B, Borch-Johnsen, K, Thorsteinsson, B, Akram, K, Pedersen-Bjergaard, U, Carstensen, B, Borch-Johnsen, K, and Thorsteinsson, B
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Udgivelsesdato: 2009-Dec
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- 2009
32. Study rationale and design of the CIMT trial: the Copenhagen Insulin and Metformin Therapy trial
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Lundby Christensen, L, Almdal, T, Boesgaard, T, Breum, L, Dunn, E, Gade-Rasmussen, B, Gluud, C, Hedetoft, C, Jarloev, A, Jensen, T, Krarup, T, Johansen, L B, Lund, S S, Madsbad, S, Mathiesen, E, Moelvig, J, Nielsen, F, Perrild, H, Pedersen, O, Roeder, M, Snorgaard, O, Tarnow, L, Thorsteinsson, B, Vaag, A, Vestergaard, H, Wetterslev, J, Wiinberg, N, Lundby Christensen, L, Almdal, T, Boesgaard, T, Breum, L, Dunn, E, Gade-Rasmussen, B, Gluud, C, Hedetoft, C, Jarloev, A, Jensen, T, Krarup, T, Johansen, L B, Lund, S S, Madsbad, S, Mathiesen, E, Moelvig, J, Nielsen, F, Perrild, H, Pedersen, O, Roeder, M, Snorgaard, O, Tarnow, L, Thorsteinsson, B, Vaag, A, Vestergaard, H, Wetterslev, J, and Wiinberg, N
- Abstract
Udgivelsesdato: 2009-Apr, BACKGROUND: Patients with type 2 diabetes (T2DM) have an increased mortality rate primarily because of macrovascular disease. Where T2DM patients cannot be managed sufficiently through diet, exercise and peroral antidiabetic drugs, that is when haemoglobin A1c (HbA1c) is above 7.0%, it is yet unknown whether a combination of metformin and insulin analogues is superior to insulin analogues alone. Nor is it known which insulin analogue regimen is the optimal. OBJECTIVE: The primary objective of this trial is to evaluate the effect of an 18-month treatment with metformin vs. placebo in combination with one of three insulin analogue regimens, the primary outcome measure being carotid intima-media thickness (CIMT) in T2DM patients. DESIGN: A randomized, stratified, multicentre trial having a 2 x 3 factorial design. The metformin part is double masked and placebo controlled. The insulin treatment is open. The intervention period is 18 months. PATIENT POPULATION: Nine hundred and fifty patients with T2DM and HbA1c > or = 7.5% on treatment with oral hypoglycaemic agents or on insulin treatment and deemed able, by the investigator, to manage once-daily insulin therapy with a long-acting insulin analogue. RANDOMIZATION: Central randomization stratified for age (above 65 years), previous insulin treatment and treatment centre. INTERVENTIONS: Metformin 1 g x two times daily vs. placebo (approximately 475 patients vs. 475 patients) in combination with insulin detemir before bedtime (approximately 315 patients) or biphasic insulin aspart 30 before dinner with the possibility to increase to two or three injections daily (approximately 315 patients) or insulin aspart before the main meals (three times daily) and insulin detemir before bedtime (approximately 315 patients). Intervention follows a treat-to-target principle in all six arms aiming for an HbA1c < or = 7.0%. OUTCOME MEASURES: Primary outcome measure is the change in CIMT from baseline to 18 months. Secondary outcome
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- 2009
33. Severe hypoglycaemia during pregnancy in women with type 1 diabetes: possible role of renin-angiotensin system activity?
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Nielsen, L Ringholm, Pedersen-Bjergaard, U, Thorsteinsson, B, Boomsma, F, Damm, P, Mathiesen, E R, Nielsen, L Ringholm, Pedersen-Bjergaard, U, Thorsteinsson, B, Boomsma, F, Damm, P, and Mathiesen, E R
- Abstract
AIMS: To investigate whether increased risk of severe hypoglycaemia in early pregnancy is related to pregnancy-induced changes in renin-angiotensin system (RAS) activity in women with type 1 diabetes (T1DM). METHODS: Severe hypoglycaemic events the year preceding pregnancy were recorded retrospectively in 107 consecutive pregnant women with T1DM. Events during pregnancy were recorded prospectively. Measurements of ACE, renin and angiotensinogen were determined at 8, 14, 21, 27 and 33 weeks and postpartum. RESULTS: The rate of severe hypoglycaemia was 1.1 and 5.3 events/patient-year the year preceding pregnancy and in first trimester, respectively (p<0.0001). Levels of ACE, renin or angiotensinogen did not differ between women with and without severe hypoglycaemia during pregnancy. Multivariate regression analysis identified a positive association between rate of severe hypoglycaemia the year preceding pregnancy and postpartum ACE activity (relative rate of severe hypoglycaemia above versus below median ACE activity: 4.4 (CI: 1.7-11.9), p=0.003). No association was found between severe hypoglycaemia during pregnancy and renin angiotensin system activity at 8 weeks. CONCLUSIONS: In early pregnancy increased RAS activity does not explain the 5-fold increase in severe hypoglycaemia in women with T1DM. A positive association between occurrence of severe hypoglycaemia and ACE activity outside pregnancy was demonstrated Udgivelsesdato: 2009/4, AIMS: To investigate whether increased risk of severe hypoglycaemia in early pregnancy is related to pregnancy-induced changes in renin-angiotensin system (RAS) activity in women with type 1 diabetes (T1DM). METHODS: Severe hypoglycaemic events the year preceding pregnancy were recorded retrospectively in 107 consecutive pregnant women with T1DM. Events during pregnancy were recorded prospectively. Measurements of ACE, renin and angiotensinogen were determined at 8, 14, 21, 27 and 33 weeks and postpartum. RESULTS: The rate of severe hypoglycaemia was 1.1 and 5.3 events/patient-year the year preceding pregnancy and in first trimester, respectively (p<0.0001). Levels of ACE, renin or angiotensinogen did not differ between women with and without severe hypoglycaemia during pregnancy. Multivariate regression analysis identified a positive association between rate of severe hypoglycaemia the year preceding pregnancy and postpartum ACE activity (relative rate of severe hypoglycaemia above versus below median ACE activity: 4.4 (CI: 1.7-11.9), p=0.003). No association was found between severe hypoglycaemia during pregnancy and renin angiotensin system activity at 8 weeks. CONCLUSIONS: In early pregnancy increased RAS activity does not explain the 5-fold increase in severe hypoglycaemia in women with T1DM. A positive association between occurrence of severe hypoglycaemia and ACE activity outside pregnancy was demonstrated.
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- 2009
34. Frequency and motives of blood glucose self-monitoring in type 1 diabetes
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Hansen, M.V., Pedersen-Bjergaard, U., Heller, S.R., Wallace, T.M., Rasmussen, A.K., Jorgensen, H.V., Pramming, S., Thorsteinsson, B., Hansen, M.V., Pedersen-Bjergaard, U., Heller, S.R., Wallace, T.M., Rasmussen, A.K., Jorgensen, H.V., Pramming, S., and Thorsteinsson, B.
- Abstract
Udgivelsesdato: 2009-Aug, AIMS: Recommendations for self-monitoring of blood glucose (SMBG) from the DCCT have not been implemented with the same rigour as recommendations for intensifying insulin therapy. We assessed the frequency of and motives for SMBG and compared SMBG behaviour with clinical, behavioural and demographic characteristics. METHODS: Cross-sectional Danish-British multicentre survey of 1076 consecutive patients with type 1 diabetes, who completed a detailed questionnaire on SMBG and related issues. The key variables were test frequency and motive. RESULTS: SMBG was performed daily by 39% of the patients and less than weekly by 24%. Sixty-seven percent reported to perform routine testing, while the remaining 33% only tested when hypo- or hyperglycaemia was suspected. Age, gender, and level of diabetes-related concern were associated with test pattern. Reported frequencies of mild and severe hypoglycaemia and awareness of hypoglycaemia were independently associated with testing behaviour, whereas the presence of late diabetic complications was not. Lower HbA1c was associated with more frequent testing. CONCLUSION: Patient compliance regarding SMBG is limited. Thus, almost two thirds of the patients do not perform daily SMBG and one third do not perform routine tests.
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- 2009
35. NT-pro-BNP during hypoglycemia and hypoxemia in normal subjects: Impact of renin-angiotensin system activity
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Due-Andersen, R. (Rikke), Pedersen-Bjergaard, U. (Ullrik), Høi-Hansen, T. (Thomas), Olsen, N.V., Kistorp, C., Faber, J. (Joerg), Boomsma, F. (Frans), Thorsteinsson, B. (Birger), Due-Andersen, R. (Rikke), Pedersen-Bjergaard, U. (Ullrik), Høi-Hansen, T. (Thomas), Olsen, N.V., Kistorp, C., Faber, J. (Joerg), Boomsma, F. (Frans), and Thorsteinsson, B. (Birger)
- Abstract
Brain-derived natriuretic peptide (BNP) is a cardioprotective peptide released, together with the inactive NH2-terminal part of its prohormone (NT-pro-BNP), in response to different kinds of myocardial stress. Hypoglycemia and hypoxemia are conditions that threaten cellular function and hence potentially stimulate BNP release. BNP interacts with the renin-angiotensin system (RAS). The aim of this study was, therefore, to explore if basal RAS activity has an impact on NT-pro-BNP concentrations during myocardial stress induced by hypoglycemia and hypoxemia. From a cohort of 303 healthy young men, 10 subjects with high-RAS activity and 10 subjects with low-RAS activity (age 26 ± 1 yr; mean ± SE) were studied in a single-blinded, randomized, counter-balanced, crossover study on three occasions separated by at least 3 wk: 1) hypoglycemia (mean nadir plasma glucose 2.7 ± 0.5 mmol/l), 2) hypoxemia (mean nadir PO25.8 ± 0.5 kPa), and 3) normoglycemic normoxia (control). NT-pro-BNP was measured at baseline, during the stimuli, and in the recovery phase. Hypoxemia was associated with a 9% increase in NT-pro-BNP from 2.2 ± 1.5 pmol/l at baseline to 2.4 ± 1.5 pmol/l during hypoxemia (P < 0.001). Hypoglycemia did not affect the NT-pro-BNP level. RAS activity had no impact on NT-pro-BNP levels during hypoglycemia and hypoxemia. Hypoxemia, but not hypoglycemia, stimulates NT-pro-BNP. This indicates that cardiac defense mechanisms against hypoglycemia, if any, are probably different from those against hypoxemia. Basal RAS activity had no impact on NT-pro-BNP levels. Copyright
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- 2008
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36. Cardiac repolarization during hypoglycaemia in type 1 diabetes: Impact of basal renin-angiotensin system activity
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Due-Andersen, R. (Rikke), Høi-Hansen, T. (Thomas), Larroude, C.E., Olsen, N.V., Kanters, J.K., Boomsma, F. (Frans), Pedersen-Bjergaard, U. (Ullrik), Thorsteinsson, B. (Birger), Due-Andersen, R. (Rikke), Høi-Hansen, T. (Thomas), Larroude, C.E., Olsen, N.V., Kanters, J.K., Boomsma, F. (Frans), Pedersen-Bjergaard, U. (Ullrik), and Thorsteinsson, B. (Birger)
- Abstract
Aims: Hypoglycaemia-induced cardiac arrhythmias may be involved in the pathogenesis of the 'dead-in-bed syndrome' in patients with type 1 diabetes. Evidence suggests that the renin-angiotensin system (RAS) influences the occurrence of arrhythmias. The aim of this study was to explore if basal RAS activity affects cardiac repolarization during hypoglycaemia, thereby potentially carrying prognostic information on risk of the 'dead-in-bed syndrome'. Methods and results: Nine subjects with high RAS activity and nine subjects with low RAS activity were subjected to single-blinded placebo-controlled hypoglycaemia (nadir plasma glucose 2.4 mmol/L). QTc/QTcF and QT dynamics were registered by Holter monitoring. QTc prolonged during [8 (±2.3) ms, P < 0.01] and after [11 (±3) ms, P < 0.001] hypoglycaemia. Dynamic QT parameters reacted ambiguously. Low RAS activity was associated with a slightly more pronounced QT prolongation [6 (±3) ms, P = 0.04]. Adrenaline tended to increase more in the low-RAS group (P = 0.08) and was correlated to QTc (r = 0.67, P < 0.01) and QTcF (r = 0.58, P < 0.05) during hypoglycaemia. Conclusion: Low basal RAS activity may be associated with a slightly more pronounced QT prolongation during hypoglycaemia, when compared with high RAS activity. The impact, however, is modest and the clinical consequence is unclear.
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- 2008
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37. Cardiac repolarization during hypoglycaemia and hypoxaemia in healthy males: Impact of renin-angiotensin system activity
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Due-Andersen, R. (Rikke), Høi-Hansen, T. (Thomas), Olsen, N.V., Larroude, C.E., Kanters, J.K., Boomsma, F. (Frans), Pedersen-Bjergaard, U. (Ullrik), Thorsteinsson, B. (Birger), Due-Andersen, R. (Rikke), Høi-Hansen, T. (Thomas), Olsen, N.V., Larroude, C.E., Kanters, J.K., Boomsma, F. (Frans), Pedersen-Bjergaard, U. (Ullrik), and Thorsteinsson, B. (Birger)
- Abstract
Aims: Activity in the renin-angiotensin system (RAS) may influence the susceptibility to cardiac arrhythmia. To study the effect of basal RAS activity on cardiac repolarization during myocardial stress induced by hypoglycaemia or hypoxaemia in healthy humans. Methods and results: Ten subjects with high RAS activity and 10 subjects with low RAS activity were studied on three different occasions: (i) hypoglycaemia (nadir P-glucose 2.7 ± 0.5 mmol/L), (ii) hypoxaemia (nadir pO25.8 ± 0.5 kPa), and (iii) normoglycaemic normoxia (control day). QT parameters were registered by Holter monitoring. Hypoglycaemia and hypoxaemia induced QTc prolongation (P < 0.001, both stimuli). The QT/RR slope and the VR increased as a function of hypoglycaemia, but were unaffected by hypoxaemia. Low RAS activity was associated with a steeper QT/RR slope in the recovery phase after both stimuli: hypoglycaemia: P = 0.04; hypoxia: P = 0.03. RAS activity had no impact on QTc [P = 0.48 (hypoglycaemia) and P = 0.40 (hypoxaemia)] or any of the other outcome variables. Conclusion: Basal RAS activity has significant impact on QT dynamics, but not the corrected QT interval, during recovery from hypoglycaemia and hypoxaemia. The impact, however, is modest and more subtle than initially expected. The clinical relevance is unclear.
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- 2008
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38. Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 diabetes
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Pedersen-Bjergaard, U., Dhamrait, S.S., Sethi, A.A., Frandsen, E., Nordestgaard, B.G., Montgomery, H.E., Pramming, S., Hougaard, P., Thorsteinsson, B., Pedersen-Bjergaard, U., Dhamrait, S.S., Sethi, A.A., Frandsen, E., Nordestgaard, B.G., Montgomery, H.E., Pramming, S., Hougaard, P., and Thorsteinsson, B.
- Abstract
BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene and elevated ACE activity are associated with increased risk of severe hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic variations in other components of the renin-angiotensin system are similarly associated. METHODS: Episodes of severe hypoglycemia were recorded in 171 consecutive type 1 diabetic outpatients during a 1-year follow-up. Participants were characterized at baseline by gene polymorphisms in angiotensinogen, ACE, angiotensin-II receptor types 1 (AT1R) and 2 (AT2R), and by plasma angiotensinogen concentration and serum ACE activity. RESULTS: Three risk factors for severe hypoglycemia were identified: plasma angiotensinogen concentration in the upper quartile (relative rate [RR] vs. lower quartile 3.1, 95% confidence interval [CI,] 1.4-6.8), serum ACE activity in the upper quartile (RR vs. lower quartile 2.9, 95% CI, 1.3-6.2), and homo- or hemizygosity for the A-allele of the X chromosome-located AT2R 1675G/A polymorphism (RR vs. noncarriers 2.5, 95% CI, 1.4-5.0). The three risk factors contributed independently to prediction of severe hypoglycemia. A backward multiple regression analysis identified a high number of renin-angiotensin system-related risk factors and reduced ability to perceive hypoglycemic warning symptoms (impaired hypoglycemia awareness) as predictors of severe hypoglycemia. CONCLUSIONS: High renin-angiotensin system activity and the A-allele of the AT2R 1675G/A polymorphism associate with high risk of severe hypoglycemia in type 1 diabetes. A potential preventive effect of renin-angiotensin system blocking drugs in patients with recurrent severe hypoglycemia merits further investigation Udgivelsesdato: 2008/3
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- 2008
39. Hypoglycemia in pregnant women with type 1 diabetes - Predictors and role of metabolic control
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Nielsen, L.R., Johansen, M., Pedersen-Bjergaard, U., Damm, P., Thorsteinsson, B., Mathiesen, E.R., Nielsen, L.R., Johansen, M., Pedersen-Bjergaard, U., Damm, P., Thorsteinsson, B., and Mathiesen, E.R.
- Abstract
OBJECTIVE- In pregnancy with type 1 diabetes, we evaluated occurrence of mild and severe hypoglycemia and analyzed the influence of strict metabolic control, nausea, Vomiting, and other potential predictors of occurrence of severe hypoglycemia. RESEARCH DESIGN AND METHODS- A prospective observational study of 108 consecutive pregnant women with type 1 diabetes was conducted. At 8, 14, 21, 27, and 33 weeks of gestation, patients performed self-monitored plasma glucose (SMPG) (eight/day) for 3 days and completed a questionnaire on nausea, vomiting, hypoglycemia awareness, and history of mild (managed by the patient) and severe (requiring assistance from others) hypoglycemia. RESULTS- Forty-nine (45%) women experienced 178 severe hypoglycemic events, corresponding to 5.3, 2.4, and 0.5 events/patient-year in the first, second, and third trimesters, respectively. The incidence of mild hypoglycemia was 5.5 events/patient-week in early pregnancy and decreased throughout pregnancy (P < 0.0001), regardless of presence of severe hypoglycemia. Prevalence of nausea and vomiting, mild hypoglycemia, and fraction of SMPG readings <= 3.9 mmol/l did not differ between women with and without severe hypoglycemia. A1C, median SMPG, and fluctuations in SMPG decreased during pregnancy, with no differences between women with and without severe hypoglycemia. Logistic regression analysis identified history of severe hypoglycemia the year preceding pregnancy (odds ratio 3.3 [95% CI 1.2-9.2]) and impaired awareness or unawareness (3.2 [1.2-8.2]) as independent predictors for severe hypoglycemia. CONCLUSIONS - In pregnancy with type 1 diabetes, the incidence of mild and severe hypoglycemia was highest in early pregnancy, although metabolic control was tighter in the last part of pregnancy. Predictors for severe hypoglycemia were history of severe hypoglycemia and impaired awareness Udgivelsesdato: 2008/1
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- 2008
40. Varenicline may trigger severe hypoglycaemia in Type 1 diabetes
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Kristensen, P.L., Pedersen-Bjergaard, U., Thorsteinsson, B., Kristensen, P.L., Pedersen-Bjergaard, U., and Thorsteinsson, B.
- Abstract
Background Varenicline is a new drug indicated for smoking cessation. It has primarily been investigated in healthy adults. The commonest side-effects are nausea, headache, sleep disturbance, constipation, flatulence and vomiting. Hypoglycaemia has not been reported. As smoking cessation is important to reduce risk of cardiovascular morbidity, especially in diabetes, use of effective drugs indicated for smoking cessation is rational. Case report We report multiple episodes of severe hypoglycaemia after starting varenicline in a 53-year-old woman with Type 1 diabetes. Since onset of diabetes at age 25 years and until start of varenicline therapy, she had only experienced one episode of severe hypoglycaemia and hypoglycaemia awareness was not impaired. The severe hypoglycaemic episodes disappeared after withdrawal of varenicline. Conclusions We recommend cautious prescription of varenicline, intensified blood glucose monitoring and careful education of patients with diabetes treated with varenicline. Further investigation of the use of varenicline in patients with diabetes is warranted Udgivelsesdato: 2008/5
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- 2008
41. NT-pro-BNP during hypoglycemia and hypoxemia in normal subjects: impact of renin-angiotensin system activity
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Due-Andersen, R, Pedersen-Bjergaard, U, Høi-Hansen, T, Olsen, Niels Vidiendal, Kistorp, C, Faber, J, Boomsma, F, Thorsteinsson, B, Due-Andersen, R, Pedersen-Bjergaard, U, Høi-Hansen, T, Olsen, Niels Vidiendal, Kistorp, C, Faber, J, Boomsma, F, and Thorsteinsson, B
- Abstract
Brain-derived natriuretic peptide (BNP) is a cardioprotective peptide released, together with the inactive NH2-terminal part of its prohormone (NT-pro-BNP), in response to different kinds of myocardial stress. Hypoglycemia and hypoxemia are conditions that threaten cellular function and hence potentially stimulate BNP release. BNP interacts with the renin-angiotensin system (RAS). The aim of this study was, therefore, to explore if basal RAS activity has an impact on NT-pro-BNP concentrations during myocardial stress induced by hypoglycemia and hypoxemia. From a cohort of 303 healthy young men, 10 subjects with high-RAS activity and 10 subjects with low-RAS activity (age 26 +/- 1 yr; mean +/- SE) were studied in a single-blinded, randomized, counterbalanced, crossover study on three occasions separated by at least 3 wk: 1) hypoglycemia (mean nadir plasma glucose 2.7 +/- 0.5 mmol/l), 2) hypoxemia (mean nadir Po-2 5.8 +/- 0.5 kPa), and 3) normoglycemic normoxia (control). NT-pro-BNP was measured at baseline, during the stimuli, and in the recovery phase. Hypoxemia was associated with a 9% increase in NT-pro-BNP from 2.2 +/- 1.5 pmol/l at baseline to 2.4 +/- 1.5 pmol/l during hypoxemia (P < 0.001). Hypoglycemia did not affect the NT-pro-BNP level. RAS activity had no impact on NT-pro-BNP levels during hypoglycemia and hypoxemia. Hypoxemia, but not hypoglycemia, stimulates NT-pro-BNP. This indicates that cardiac defense mechanisms against hypoglycemia, if any, are probably different from those against hypoxemia. Basal RAS activity had no impact on NT-pro-BNP levels Udgivelsesdato: 2008/4
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- 2008
42. Lower levels of circulating IGF-I in Type 1 diabetic women with frequent severe hypoglycaemia during pregnancy
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Ringholm Nielsen, L, Juul, A, Pedersen-Bjergaard, U, Thorsteinsson, B, Damm, P, Mathiesen, E R, Ringholm Nielsen, L, Juul, A, Pedersen-Bjergaard, U, Thorsteinsson, B, Damm, P, and Mathiesen, E R
- Abstract
Aims Severe hypoglycaemia is a significant problem in pregnant women with Type 1 diabetes. We explored whether frequent severe hypoglycaemia during pregnancy in women with Type 1 diabetes is related to placental growth hormone (GH) and insulin-like growth factor I (IGF-I) levels. Methods A prospective, observational study of 107 consecutive pregnant women with Type 1 diabetes. Blood samples were drawn for IGF-I and placental GH analyses at 8, 14, 21, 27 and 33 weeks. Severe hypoglycaemic events were reported within 24 h. Results Eleven women (10%) experienced frequent severe hypoglycaemia (>= 5 events), accounting for 60% of all events. Throughout pregnancy, IGF-I levels were 25% lower in these women (P < 0.005) compared with the remaining women, despite similar placental GH levels. Eighty per cent of the severe hypoglycaemic events occurred before 20 weeks when IGF-I levels were at their lowest. This finding was not explained by differences in insulin dose, median plasma glucose levels or glycated haemoglobin. History of severe hypoglycaemia the year preceding pregnancy and impaired hypoglycaemia awareness-being the only predictors of frequent severe hypoglycaemia in a logistic regression analysis-were not associated with IGF-I or placental GH levels at 8 weeks. Conclusions In women with Type 1 diabetes experiencing frequent severe hypoglycaemia during pregnancy, IGF-I levels are significantly lower compared with the remaining women despite similar placental GH levels. IGF-I levels are lowest in early pregnancy where the incidence of severe hypoglycaemia is highest. IGF-I may be a novel factor of interest in the investigation of severe hypoglycaemia in patients with Type 1 diabetes Udgivelsesdato: 2008/7, Severe hypoglycaemia is a significant problem in pregnant women with Type 1 diabetes. We explored whether frequent severe hypoglycaemia during pregnancy in women with Type 1 diabetes is related to placental growth hormone (GH) and insulin-like growth factor I (IGF-I) levels.
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- 2008
43. RAS and severe hypoglycemia in type 1 diabetes
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Pedersen-Bjergaard, U., Thorsteinsson, B., Pedersen-Bjergaard, U., and Thorsteinsson, B.
- Abstract
Udgivelsesdato: 2008/6
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- 2008
44. Association between plasma activities of semicarbazide-sensitive amine oxidase and angiotensin-converting enzyme in patients with type 1 diabetes mellitus
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Boomsma, F. (Frans), Pedersen-Bjergaard, U. (Ullrik), Agerholm-Larsen, B. (B.), Hut, H., Dhamrait, S.S. (S.), Thorsteinsson, B. (Birger), Meiracker, A.H. (Anton) van den, Boomsma, F. (Frans), Pedersen-Bjergaard, U. (Ullrik), Agerholm-Larsen, B. (B.), Hut, H., Dhamrait, S.S. (S.), Thorsteinsson, B. (Birger), and Meiracker, A.H. (Anton) van den
- Abstract
Aims/hypothesis: Plasma semicarbazide-sensitive amine oxidase (SSAO) is elevated in patients with type 1 and type 2 diabetes and has been implicated in the pathophysiology of diabetic late complications. The regulation of SSAO production remains unknown. We studied correlations between plasma SSAO activity and parameters associated with diabetic late complications. Methods: Plasma SSAO was measured in a well-characterised group of 287 patients with type 1 diabetes. Standard statistical methods were used to investigate correlations with clinical parameters and components of the renin-angiotensin system. Results: Overall, plasma SSAO was elevated, at 693±196 mU/l (mean±SD; normal controls 352±102 mU/l). Plasma SSAO was higher in the group with late complications or hypertension, and in patients treated with ACE-inhibitors. In univariate analysis a significant positive correlation (p<0.001, r=0.27) was found between plasma SSAO and serum ACE activity in patients untreated with ACE inhibitors or angiotensin II receptor antagonists (n=221), but plasma SSAO did not differ by ACE I/D genotype. Plasma SSAO correlated positively with duration of diabetes, HbA1c and plasma renin, and negatively with plasma angiotensinogen and body mass index. A multiple regression analysis including these variables resulted in serum ACE activity (p<0.001), ACE genotype (negatively, p<0.001) and HbA 1c (p=0.023) as explaining variables. Conclusions/interpretation: Results suggest that a common factor is involved in the regulation of both plasma SSAO and serum ACE, which is different from the genetic determination of ACE activity.
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- 2005
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45. Association between plasma activities of semicarbazide-sensitive amine oxidase and angiotensin-converting enzyme in patients with type 1 diabetes mellitus
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Boomsma, F, Pedersen-Bjergaard, U, Agerholm-Larsen, B, Hut, H, Dhamrait, S, Thorsteinsson, B, van den Meiracker, Ton, Boomsma, F, Pedersen-Bjergaard, U, Agerholm-Larsen, B, Hut, H, Dhamrait, S, Thorsteinsson, B, and van den Meiracker, Ton
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- 2005
46. Type 2-diabetes :Medicinsk teknologivurdering af screening, diagnostik og behandling
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Gjørup, T, Henriksen, J E, Hansen, N W, Bek, T, Borch-Johnsen, B, Lauritzen, T, Madsbad, S, Olivarius, Niels de Fine, Juhl, H H, Thorsteinsson, B, Christiansen, J S, Holstein, P, Palmvig, B, Kjeldsen, K, Pedersen, O B, Carlsen, B, Madsen, L D, Krarup, T, Hansen, B, Madsen, P B, Bassett, B, Schou, H, Lange, M, Gjørup, T, Henriksen, J E, Hansen, N W, Bek, T, Borch-Johnsen, B, Lauritzen, T, Madsbad, S, Olivarius, Niels de Fine, Juhl, H H, Thorsteinsson, B, Christiansen, J S, Holstein, P, Palmvig, B, Kjeldsen, K, Pedersen, O B, Carlsen, B, Madsen, L D, Krarup, T, Hansen, B, Madsen, P B, Bassett, B, Schou, H, and Lange, M
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- 2003
47. Cardiac repolarization during hypoglycaemia in type 1 diabetes: impact of basal renin-angiotensin system activity
- Author
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Due-Andersen, R., primary, Hoi-Hansen, T., additional, Larroude, C. E., additional, Olsen, N. V., additional, Kanters, J. K., additional, Boomsma, F., additional, Pedersen-Bjergaard, U., additional, and Thorsteinsson, B., additional
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- 2008
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48. NT-pro-BNP during hypoglycemia and hypoxemia in normal subjects: impact of renin-angiotensin system activity
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Due-Andersen, R., primary, Pedersen-Bjergaard, U., additional, Høi-Hansen, T., additional, Olsen, N. V., additional, Kistorp, C., additional, Faber, J., additional, Boomsma, F., additional, and Thorsteinsson, B., additional
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- 2008
- Full Text
- View/download PDF
49. Cardiac repolarization during hypoglycaemia and hypoxaemia in healthy males: impact of renin-angiotensin system activity
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Due-Andersen, R., primary, Hoi-Hansen, T., additional, Olsen, N. V., additional, Larroude, C. E., additional, Kanters, J. K., additional, Boomsma, F., additional, Pedersen-Bjergaard, U., additional, and Thorsteinsson, B., additional
- Published
- 2008
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50. An Evaluation of Methods of Assessing Impaired Awareness of Hypoglycemia in Type 1 Diabetes: Response to Geddes et al.
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Pedersen-Bjergaard, U., primary, Hoi-Hansen, T., additional, and Thorsteinsson, B., additional
- Published
- 2007
- Full Text
- View/download PDF
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