| 1. |
- Henricsson, Marianne, et al.
(author)
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The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS).
- 2003
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 26:2, s. 349-354
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Journal article (peer-reviewed)abstract
- OBJECTIVE—To estimate the prevalence and severity of diabetic retinopathy (DR) 10 years after diagnosis in a nationwide population-based cohort study of young adult diabetic patients in Sweden. RESEARCH DESIGN AND METHODS—The Diabetes Incidence Study in Sweden (DISS) aims to register all incident cases of diabetes aged 15–34 years in Sweden. In 1987–1988, 806 cases were reported, and 627 (78%) of them were followed up with regard to retinopathy 8–10 years later. The assessment was based on retinal photographs in most cases (86%). RESULTS—Ten years after diagnosis, retinopathy was found in 247 patients (39%). The retinopathy was mild in 206 (33%), whereas 30 (4.8%) patients had moderate nonproliferative DR (NPDR) and 11 (1.8%) had proliferative DR (PDR). Patients with retinopathy had worse glycemic control during the years than patients without (HbA1c 8.1 ± 1.5% and 6.8 ± 1.2%, respectively; P < 0.001). In a Cox regression analysis, time to retinopathy was related to high HbA1c (P < 0.001) and high BMI (P = 0.001). Patients with type 2 diabetes had an increased prevalence of severe retinopathy (NPDR or PDR) compared with those with type 1 diabetes (14 of 93 [15%] versus no or mild 24 of 471 [5%], respectively; P < 0.001). CONCLUSIONS—Despite modern diabetes management, 39% of young adult diabetic patients developed retinopathy within the first 10 years of the disease. Nevertheless, compared with the prevalence of retinopathy (63%), after a similar duration of diabetes before the Diabetes Control and Complications Trial, this prevalence was clearly lower. Current treatment aimed to achieve strict glycemic control has reduced the risk for developing retinopathy.
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| 2. |
- Littorin, Bengt, et al.
(author)
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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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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 24:6, s. 1033-1037
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Journal article (peer-reviewed)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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| 3. |
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| 4. |
- Svensson, Maria, et al.
(author)
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Signs of nephropathy may occur early in young adults with diabetes despite modern diabetes management : Results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS)
- 2003
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:10, s. 2903-2909
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Journal article (peer-reviewed)abstract
- OBJECTIVE - To estimate the occurrence of early-onset renal involvement in a nationwide population-based cohort of young adults with diabetes in Sweden and relate the findings to glycemic control, type of diabetes, sex, smoking, and blood pressure. RESEARCH DESIGN AND METHODS - The Diabetes Incidence Study in Sweden aims to register all incident cases of diabetes in the age-group 15-34 years. In 1987-1988, 806 patients were reported and invited to participate in a follow-up study focusing on microvascular complications. Of them, 469 subjects participated. The assessment was based on questionnaires (n = 469), blood samples (n = 424), urine samples (n = 251) and, when appropriate, medical records (n = 186). RESULTS - During the follow-up time, median 9 years (range 6-12), 31 of 469 patients (6.6%) with incipient or overt diabetic nephropathy (i.e., micro- or macroalbuminuria) were found, 24 of 426 (5.6%) in type 1 and 7 of 43 (16%) in type 2 diabetic subjects (P = 0.016). Additionally, 24 of 31 patients (77%) had microalbuminuria and 7 (23%) had macroalbuminuria, which mainly occurred in patients with type 2 diabetes. In a Cox regression analysis, high mean HbA1c during the follow-up period and high blood pressure at follow-up increased the risk of developing signs of nephropathy (P = 0.020 and P = 0.003, respectively). Compared with patients with type 1 diabetes, those with type 2 diabetes tended to have an increased risk of renal involvement (P = 0.054) when adjusting for sex, tobacco use, glycemic control, and blood pressure. CONCLUSIONS - Despite modern treatment and self-monitoring of blood glucose, young adult patients with diabetes may still develop renal involvement during the first 10 years of diabetes duration. Inadequate HbA 1c high blood pressure, and type 2 diabetes appear to be risk markers for early occurrence of diabetic nephropathy.
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| 5. |
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| 6. |
- Torffvit, Ole, et al.
(author)
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Early changes in glomerular size selectivity in young adults with type 1 diabetes and retinopathy. Results from the Diabetes Incidence Study in Sweden.
- 2007
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In: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 21:4, s. 246-251
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Journal article (peer-reviewed)abstract
- Objective: To investigate the relationship between early-onset retinopathy and urinary markers of renal dysfunction. Research Design and Methods: The Diabetes Incidence Study in Sweden (DISS) aims to register all new cases of diabetes in young adults (15-34 years). In 1987-1988, 806 patients were reported and later invited to participate in a follow-up study focusing on microvascular complications after similar to 10 years of diabetes. In the present study, 149 patients with type I diabetes, completed eye examination, and urine sampling were included. Results: The patients with retinopathy (n=58, 39%) had higher HbA(1c), (P<.001) and urinary IgG2/creatinine (P<.05) and IgG2/IgG4 ratios (P<.05). Patients with maculopathy had the highest levels. No significant differences in urinary albumin/creatinine, glycosaminoglycans (GAGs)/creatinine, Tamm-Horsfall protein (THP)/creatinine, and IgG4/creatinine ratios were found. Women had higher urinary albumin/ creatinine (P<.01) and urinary IgG2/creatinine ratios (P<.01) than men. Conclusions: Young adults with type I diabetes and early-onset retinopathy had higher IgG2/creatinine and IgG2/IgG4 ratios than patients without retinopathy indicating that retinopathy is associated with a change in glomerular size selectivity. This was found in association with normal urinary albumin and THP excretion and may be suspected to reflect early general vascular changes. (C) 2007 Elsevier Inc. All rights reserved.
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| 7. |
- Törn, Carina, et al.
(author)
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Glutamic acid decarboxylase antibodies (GADA) is the most important factor for prediction of insulin therapy within 3 years in young adult diabetic patients not classified as Type 1 diabetes on clinical grounds
- 2000
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In: Diabetes/Metabolism Research and Reviews. - 1520-7552 .- 1520-7560. ; 16:6, s. 442-447
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Journal article (peer-reviewed)abstract
- Background Differentiation between Type 1 and Type 2 diabetes in adults is difficult at diagnosis. In this study we tested the hypothesis that autoantibodies at diagnosis are predictive for insulin treatment within 3 years in patients initially not classified as Type 1 diabetes. Methods In a nationwide population-based study, blood samples were obtained from 764 patients, all diagnosed with diabetes during a 2-year period. At diagnosis, 583 (76%) were classified as Type 1, 110 (14%) as Type 2 and 71 (9.3%) could not be classified. Results Among patients not classified as Type 1 diabetes, 52 (47%) of Type 2 and 42 (59%) of unclassified patients were positive for islet cell antibodies CICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A). These patients (n=94) had lower body mass index (BMI) (p<0.001) and lower C-peptide (p<0.001) compared to the autoantibody negative patients (n=87). Compared to clinically classified Type 1 diabetes patients positive for autoantibodies (n=477), they have higher BMI (p<0.001), higher C-peptide (p<0.001) and the same levels of ICA, GADA and IA-2A. After 3 years, 93% of autoantibody positive patients initially not classified as Type 1 were on insulin. When ICA, GADA, IA-2A, BMI and C-peptide were tested in a multiple logistic regression, only GADA was signiificant for insulin treatment within 3 years (OR = 18.8; 95% CI 1.8-191) in patients treated with diet or oral drugs at diagnosis. Conclusions A correct classification is difficult in adult diabetic patients. The presence of pancreatic autoantibodies, especially GADA, at diagnosis of diabetes are highly predictive for insulin therapy within 3 years from diagnosis.
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| 8. |
- Anderbro, Therese, et al.
(author)
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Fear of hypoglycemia : relationship to hypoglycemic risk and psychological factors
- 2014
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In: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233.
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Journal article (peer-reviewed)abstract
- OBJECTIVE: The major aims of this study were to examine (1) the association between fear of hypoglycemia (FOH) in adults with type 1 diabetes with demographic, psychological (anxiety and depression), and disease-specific clinical factors (hypoglycemia history and unawareness, A1c), including severe hypoglycemia (SH), and (2) differences in patient subgroups categorized by level of FOH and risk of SH.RESEARCH DESIGN AND METHODS: Questionnaires were mailed to 764 patients with type 1 diabetes including the Swedish translation of the Hypoglycemia Fear Survey (HFS) and other psychological measures including the Perceived Stress Scale, Hospital Anxiety and Depression Scale, Anxiety Sensitivity Index, Social Phobia Scale, and Fear of Complications Scale. A questionnaire to assess hypoglycemia history was also included and A1c measures were obtained from medical records. Statistical analyses included univariate approaches, multiple stepwise linear regressions, Chi-square t tests, and ANOVAs.RESULTS: Regressions showed that several clinical factors (SH history, frequency of nocturnal hypoglycemia, self-monitoring) were significantly associated with FOH but R (2) increased from 16.25 to 39.2 % when anxiety measures were added to the model. When patients were categorized by level of FOH (low, high) and SH risk (low, high), subgroups showed significant differences in non-diabetes-related anxiety, hypoglycemia history, self-monitoring, and glycemic control.CONCLUSION: There is a strong link between FOH and non-diabetes-related anxiety, as well as hypoglycemia history. Comparison of patient subgroups categorized according to level of FOH and SH risk demonstrated the complexity of FOH and identified important differences in psychological and clinical variables, which have implications for clinical interventions.
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| 9. |
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| 10. |
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| 11. |
- Särnblad, Stefan, 1963-
(author)
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Body Composition in Adolescents with Type 1 Diabetes : Aspects of Glycaemic Control and Insulin Sensitivity
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Excessive weight gain has frequently been reported in adolescents with type 1 diabetes, especially in girls. In general, puberty is associated with reduced insulin sensitivity that is further diminished by overweight. The causes and consequences of excessive weight gain in adolescents with type 1 diabetes are not fully understood. The studies described in this thesis addressed body composition in adolescents with type 1 diabetes and the relationships between physical activity, energy intake and changes in body composition. Furthermore, the effect of metformin as additional therapy on glycaemic control and insulin sensitivity was examined in a randomised placebo-controlled study. Body mass index (BMI) and percentage body fat (%BF) were significantly higher in girls with type 1 diabetes compared to healthy control girls. Mean HbA1c during puberty, but not mean insulin dose, was positively related to BMI at the age of 18 in girls with diabetes. A centralised fat distribution was associated with poor glycaemic control, increased daily dosage of insulin and elevated cholesterol and triglyceride levels. Neither total physical activity nor total energy intake differed between adolescent girls with type 1 diabetes and healthy age-matched control girls. A high dietary fat intake was positively related to gain in %BF in girls with type 1 diabetes. Additional therapy with metformin for three months improved glycaemic control and peripheral insulin sensitivity in adolescents with poorly controlled type 1 diabetes. The improvement in glycaemic control was related to insulin sensitivity at baseline, implying that the most insulin resistant subjects benefited most from the metformin therapy. It is concluded that the excessive weight gain observed in girls with type 1 diabetes is mainly attributable to an increased fat mass and that dietary fat intake is of importance for this gain in body fat. Additional treatment with metformin improves glycaemic control in adolescents with poorly controlled type 1 diabetes.
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| 12. |
- Anderbro, Therese, et al.
(author)
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Fear of hypoglycaemia in adults with type 1 diabetes
- 2010
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 27:10, s. 1151-8
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Research review (peer-reviewed)abstract
- Aims The aim of this study was to examine the fear of hypoglycaemia and its association with demographic and disease-specific variables in a large and unselective population of adult patients with Type 1 diabetes. Methods Questionnaires were sent by post to all patients with Type 1 diabetes who were identified in the local diabetes registries of two hospitals in Stockholm, Sweden (n = 1387). Fear of hypoglycaemia was measured using the Swedish Hypoglycaemia Fear Survey, the Worry subscale and the Aloneness subscale. Demographic variables and disease-specific factors were collected from patients' self reports and medical records. Univariate analysis and multiple stepwise linear regression analysis were used in the statistical analyses of the data. Results Seven hundred and sixty-four (55%) patients participated in the study (mean age 43.3 years and mean HbA(1c) 7.0%, normal < 5.0%). The Hypoglycaemia Fear Survey - Worry subscale was significantly associated with frequency of severe hypoglycaemia, number of symptoms during mild hypoglycaemia, gender, hypoglycaemic symptoms during hyperglycaemia and hypoglycaemic unawareness. The Hypoglycaemia Fear Survey - Aloneness subscale was significantly associated with frequency of severe hypoglycaemia, number of symptoms during mild hypoglycaemia, gender, frequency of mild hypoglycaemia, HbA(1c) , hypoglycaemic unawareness and visits to the emergency room because of severe hypoglycaemia. Fear of hypoglycaemia proved to be more prevalent in females and indicated a different pattern between genders in relation to factors associated with fear of hypoglycaemia. Conclusions This study identifies the frequency of severe hypoglycaemia as the most important factor associated with fear of hypoglycaemia. Moreover, for the first time, we document gender differences in fear of hypoglycaemia, suggesting that females are more affected by fear of hypoglycaemia than men.
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| 13. |
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| 14. |
- Bakhtadze, Ekaterine, et al.
(author)
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Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15-34 years) but not in middle-aged (40-59 years) diabetic patients
- 2008
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 51:12, s. 2224-2232
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Journal article (peer-reviewed)abstract
- Type 1 diabetes in children is characterised by autoimmune destruction of pancreatic beta cells and the presence of certain risk genotypes. In adults the same situation is often referred to as latent autoimmune diabetes in adults (LADA). We tested whether genetic markers associated with type 1 or type 2 diabetes could help to discriminate between autoimmune and non-autoimmune diabetes in young (15-34 years) and middle-aged (40-59 years) diabetic patients. In 1,642 young and 1,619 middle-aged patients we determined: (1) HLA-DQB1 genotypes; (2) PTPN22 and INS variable-number tandem repeat (VNTR) polymorphisms; (3) two single nucleotide polymorphisms (rs7903146 and rs10885406) in the TCF7L2 gene; (4) glutamic acid decarboxylase (GAD) and IA-2-protein tyrosine phosphatase-like protein (IA-2) antibodies; and (5) fasting plasma C-peptide. Frequency of risk genotypes HLA-DQB1 (60% vs 25%, p =9.4x10(-34); 45% vs 18%, p= 1.4x10(-16)), PTPN22 CT/TT (34% vs 26%, p=0.0023; 31% vs 23%, p=0.034), INS VNTR class I/I (69% vs 53%, p=1.3x10(-8); 69% vs 51%, p=8.5x10(-5)) and INS VNTR class IIIA/IIIA (75% vs 63%, p=4.3x10(-6); 73% vs 60%, p=0.008) was increased in young and middle-aged GAD antibodies (GADA)-positive compared with GADA-negative patients. The type 2 diabetes-associated genotypes of TCF7L2 CT/TT of rs7903146 were significantly more common in young GADA-negative than in GADA-positive patients (53% vs 43%; p=0.0004). No such difference was seen in middle-aged patients, in whom the frequency of the CT/TT genotypes of TCF7L2 was similarly increased in GADA-negative and GADA-positive groups (55% vs 56%). Common variants in the TCF7L2 gene help to differentiate young but not middle-aged GADA-positive and GADA-negative diabetic patients, suggesting that young GADA-negative patients have type 2 diabetes and that middle-aged GADA-positive patients are different from their young GADA-positive counterparts and share genetic features with type 2 diabetes.
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| 15. |
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| 16. |
- Bolinder, Jan, et al.
(author)
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Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin
- 2012
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 97:3, s. 1020-1031
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Journal article (peer-reviewed)abstract
- Context:Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding.Objectives:Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.Design and Setting:This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries.Patients:Included were 182 patients with T2DM (mean values: women 63.3 and men 58.6 yr of age; hemoglobin A1c 7.17%, body mass index 31.9 kg/m2, and body weight 91.5 kg) inadequately controlled on metformin.Intervention:Dapagliflozin 10 mg/d or placebo was added to open-label metformin for 24 wk.Main Outcome Measures:Primary endpoint was total body weight (TBW) change from baseline at wk 24. Key secondary endpoints were waist circumference and dual-energy x-ray absorptiometry total-body fat mass (FM) changes from baseline at wk 24, and patient proportion achieving body weight reduction of at least 5% at wk 24. In a subset of patients, magnetic resonance assessment of visceral adipose tissue (VAT) and sc adipose tissue (SAT) volume and hepatic lipid content were also evaluated.Results:At wk 24, placebo-corrected changes with dapagliflozin were as follows: TBW, −2.08 kg [95% confidence interval (CI) = −2.84 to −1.31; P < 0.0001]; waist circumference, −1.52 cm (95% CI = −2.74 to −0.31; P = 0.0143); FM, −1.48 kg (95% CI = −2.22 to −0.74; P = 0.0001); proportion of patients achieving weight reduction of at least 5%, +26.2% (95% CI = 15.5 to 36.7; P < 0.0001); VAT, −258.4 cm3 (95% CI = −448.1 to −68.6; nominal P = 0.0084); SAT, −184.9 cm3 (95% CI = −359.7 to −10.1; nominal P = 0.0385). In the dapagliflozin vs. placebo groups, respectively, serious adverse events were reported in 6.6 vs. 1.1%; events suggestive of vulvovaginitis, balanitis, and related genital infection in 3.3 vs. 0%; and lower urinary tract infections in 6.6 vs. 2.2%.Conclusions:Dapagliflozin reduces TBW, predominantly by reducing FM, VAT and SAT in T2DM inadequately controlled with metformin.
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| 17. |
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| 18. |
- Borg, Henrik, et al.
(author)
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Evaluation of the new ADA and WHO criteria for classification of diabetes mellitus in young adult people (15-34 yrs) in the Diabetes Incidence Study in Sweden (DISS)
- 2003
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 46:2, s. 173-181
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Journal article (peer-reviewed)abstract
- Aims/hypothesis. We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years. Methods. During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide. Results. In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up. Conclusion/interpretation. Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.
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| 19. |
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| 20. |
- Chaurasia, Chandra S., et al.
(author)
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AAPS-FDA workshop white paper : microdialysis principles, application and regulatory perspectives
- 2007
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In: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 24:5, s. 1014-1025
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Journal article (peer-reviewed)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of microD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on microD as a tool in drug research and development.
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| 21. |
- Chaurasia, Chandra S., et al.
(author)
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AAPS-FDA Workshop White Paper : microdialysis principles, application, and regulatory perspectives
- 2007
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In: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:5, s. 589-603
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Journal article (peer-reviewed)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (μD) is the only tool available that explicitly provides data on the extracellular space. Although μD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of μD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of μD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on μD as a tool in drug research and development.
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| 22. |
- Ekberg, Karin, et al.
(author)
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C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy
- 2007
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 30:1, s. 71-76
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Journal article (peer-reviewed)abstract
- OBJECTIVE - C-peptide replacement in animals results in amelioration of diabetes-induced functional and structural abnormalities in peripheral nerves. The present study was undertaken to examine whether C-peptide administration to patients with type 1 diabetes and peripheral neuropathy improves sensory nerve function. RESEARCH DESIGN AND METHODS - This was an exploratory, double-blinded, randomized, and placebo-controlled study with three study groups that was carried out at five centers in Sweden. C-peptide was given as a replacement dose (1.5 mg/day, divided into four subcutaneous doses) or a dose three times higher (4.5 mg/day) during 6 months. Neurological examination and neurophysiological measurements were performed before and after 6 months of treatment with C-peptide or placebo. RESULTS - The age of the 139 patients who completed the protocol was 44.2 ± 0.6 (mean ± SE) years and their duration of diabetes was 30.6 ± 0.8 years. Clinical neurological impairment (NIA) (score >7 points) of the lower extremities was present in 86% of the patients at baseline. Sensory nerve conduction velocity (SCV) was 2.6 ± 0.08 SD below body height-corrected normal values at baseline and improved similarly within the two C-peptide groups (P < 0.007). The number of patients responding with a SCV peak potential improvement >1.0 m/s was greater in C-peptide-treated patients than in those receiving placebo (P < 0.03). In the least severely affected patients (SCV < 2.5 SD below normal at baseline, n = 70) SCV improved by 1.0 m/s (P < 0.014 vs. placebo). NIA score and vibration perception both improved within the C-peptide-treated groups (P < 0.011 and P < 0.002). A1C levels (7.6 ± 0.1% at baseline) decreased slightly but similarly in C-peptide- and placebo-treated patients during the study. CONCLUSIONS - C-peptide treatment for 6 months improves sensory nerve function in early-stage type 1 diabetic neuropathy.
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| 23. |
- Enoksson, Staffan, et al.
(author)
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Marked Re-Utilization of Free Fatty Acids During Activated Lipolysis in Human Skeletal Muscle.
- 2005
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 90:2, s. 1189-1195
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Journal article (peer-reviewed)abstract
- Release of glycerol and free fatty acids (FFA) was investigated in human skeletal muscle strips. In the basal state, glycerol and FFA were released at almost equimolar rates (0.3 nmol/ng tissue.90 min). A nonselective beta-adrenoceptor agonist, isoprenaline, caused a concentration-dependent stimulation of glycerol release, whereas FFA release was unaffected. Basal and isoprenaline-induced glycerol release correlated positively with the age of the donors (r = 0.5, P < 0.005) but not with their body mass index (P > or = 0.4). Biochemical experiments with hormone-sensitive lipase (HSL) showed that most enzyme activity was both in the cytosol and mitochondrial fraction and that it constituted the common long and active form of the protein. Electron microscopy studies in rat skeletal muscle using labeled highly specific HSL antibodies verified the cytosolic location of HSL and, furthermore, indicated an accumulation of HSL-adjoining mitochondria. These results suggest that FFA produced in myocytes during catecholamine-induced lipolysis are retained by the muscle and, therefore by inference, reused. It is conceivable that efficient hydrolysis of acylglycerol by HSL located in the cytosol as well as near the mitochondria may facilitate mitochondrial FFA oxidation. In addition, muscle lipolysis activity increases during aging and may be independent of total body fat.
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| 24. |
- Isaksson, Sofia Sterner, et al.
(author)
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Discordance between mean glucose and time in range in relation to HbA1c in individuals with type 1 diabetes: results from the GOLD and SILVER trials
- 2024
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In: DIABETOLOGIA. - : SPRINGER. - 0012-186X .- 1432-0428.
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Journal article (peer-reviewed)abstract
- Aims/hypothesis Previous studies have shown that individuals with similar mean glucose levels (MG) or percentage of time in range (TIR) may have different HbA(1c) values. The aim of this study was to further elucidate how MG and TIR are associated with HbA(1c). Methods Data from the randomised clinical GOLD trial (n=144) and the follow-up SILVER trial (n=98) of adults with type 1 diabetes followed for 2.5 years were analysed. A total of 596 paired HbA(1c)/continuous glucose monitoring measurements were included. Linear mixed-effects models were used to account for intra-individual correlations in repeated-measures data. Results In the GOLD trial, the mean age of the participants (+/- SD) was 44 +/- 13 years, 63 (44%) were female, and the mean HbA(1c) (+/- SD) was 72 +/- 9.8 mmol/mol (8.7 +/- 0.9%). When correlating MG with HbA(1c), MG explained 63% of the variation in HbA(1c) (r=0.79, p<0.001). The variation in HbA(1c) explained by MG increased to 88% (r=0.94, p value for improvement of fit <0.001) when accounting for person-to-person variation in the MG-HbA(1c) relationship. Time below range (TBR; <3.9 mmol/l), time above range (TAR) level 2 (>13.9 mmol/l) and glycaemic variability had little or no effect on the association. For a given MG and TIR, the HbA(1c) of 10% of individuals deviated by >8 mmol/mol (0.8%) from their estimated HbA(1c) based on the overall association between MG and TIR with HbA(1c). TBR and TAR level 2 significantly influenced the association between TIR and HbA(1c). At a given TIR, each 1% increase in TBR was related to a 0.6 mmol/mol lower HbA(1c) (95% CI 0.4, 0.9; p<0.001), and each 2% increase in TAR level 2 was related to a 0.4 mmol/mol higher HbA(1c) (95% CI 0.1, 0.6; p=0.003). However, neither TIR, TBR nor TAR level 2 were significantly associated with HbA(1c) when accounting for MG. Conclusions/interpretation Inter-individual variations exist between MG and HbA(1c), as well as between TIR and HbA(1c), with clinically important deviations in relatively large groups of individuals with type 1 diabetes. These results may provide important information to both healthcare providers and individuals with diabetes in terms of prognosis and when making diabetes management decisions.
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| 25. |
- Lind, Marcus, 1976, et al.
(author)
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Design and Methods of a Randomized Trial of Continuous Glucose Monitoring in Persons With Type 1 Diabetes With Impaired Glycemic Control Treated With Multiple Daily Insulin Injections (GOLD Study).
- 2016
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In: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 10:3, s. 754-61
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Journal article (peer-reviewed)abstract
- The majority of individuals with type 1 diabetes today have glucose levels exceeding guidelines. The primary aim of this study was to evaluate whether continuous glucose monitoring (CGM), using the Dexcom G4 stand-alone system, improves glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections (MDI).Individuals with type 1 diabetes and inadequate glycemic control (HbA1c ≥ 7.5% = 58 mmol/mol) treated with MDI were randomized in a cross-over design to the Dexcom G4 versus conventional care for 6 months followed by a 4-month wash-out period. Masked CGM was performed before randomization, during conventional treatment, and during the wash-out period to evaluate effects on hypoglycemia, hyperglycemia, and glycemic variability. Questionnaires were used to evaluate diabetes treatment satisfaction, fear of hypoglycemia, hypoglycemia confidence, diabetes-related distress, overall well-being, and physical activity during the different phases of the trial. The primary endpoint was the difference in HbA1c at the end of each treatment phase.A total of 205 patients were screened, of whom 161 were randomized between February and December 2014. Study completion is anticipated in April 2016.It is expected that the results of this study will establish whether using the Dexcom G4 stand-alone system in individuals with type 1 diabetes treated with MDI improves glycemic control, reduces hypoglycemia, and influences quality-of-life indicators and glycemic variability.
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| 26. |
- Lind, Marcus, 1976, et al.
(author)
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Sustained Intensive Treatment and Long-term Effects on HbA(1c) Reduction (SILVER Study) by CGM in People With Type 1 Diabetes Treated With MDI
- 2021
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In: Diabetes Care. - Arlington, VA, United States : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:1, s. 141-149
-
Journal article (peer-reviewed)abstract
- OBJECTIVE Continuous glucose monitoring (CGM) reduces HbA(1c) and time spent in hypoglycemia in people with type 1 diabetes (T1D) treated with multiple daily insulin injections (MDI) when evaluated over shorter time periods. It is unclear to what extent CGM improves and helps to maintain glucose control, treatment satisfaction, diabetes distress, hypoglycemic concerns, and overall well-being over longer periods of time. RESEARCH DESIGN AND METHODS The GOLD trial was a randomized crossover trial performed over 16 months of CGM treatment in people with T1D treated with MDI. People completing the trial (n = 141) were invited to participate in the current SILVER extension study in which 107 patients continued CGM treatment over 1 year along with the support of a diabetes nurse every 3 months. RESULTS The primary end point of the change in HbA(1c) over 1.0-1.5 years of CGM use compared with previous self-monitoring of blood glucose during GOLD showed a decrease in HbA(1c) of 0.35% (95% CI 0.19-0.50, P < 0.001). Time spent in hypoglycemia <3.0 mmol/L (54 mg/dL) and <4.0 mmol/L (72 mg/dL) decreased from 2.1% to 0.6% (P < 0.001) and from 5.4% to 2.9% (P < 0.001), respectively. Overall well-being (World Health Organization 5-item well-being index, P = 0.009), treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire, P < 0.001), and hypoglycemic confidence (P < 0.001) increased, while hypoglycemic fear (Hypoglycemia Fear Survey-Worry, P = 0.016) decreased and diabetes distress tended to decrease (Problem Areas in Diabetes Scale, P = 0.06). From randomization and screening in GOLD, HbA(1c) was lowered by 0.45% (P < 0.001) and 0.68% (P < 0.001) after 2.3 and 2.5 years, respectively. CONCLUSIONS The SILVER study supports beneficial long-term effects from CGM on HbA(1c), hypoglycemia, treatment satisfaction, well-being, and hypoglycemic confidence in people with T1D managed with MDI.
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| 27. |
- Littorin, Bengt, et al.
(author)
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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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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 22:3, s. 409-412
-
Journal article (peer-reviewed)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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| 28. |
- Littorin, Bengt, et al.
(author)
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Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects : results from the nationwide Diabetes Incidence Study in Sweden (DISS)
- 2006
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 49:12, s. 2847-2852
-
Journal article (peer-reviewed)abstract
- Low plasma vitamin D concentrations may promote the development of type 1 diabetes. To test this hypothesis, we measured plasma 25-hydroxyvitamin D (25OHD) in young adults with type 1 diabetes.The nationwide Diabetes Incidence Study in Sweden (DISS) covers 15- to 34-year-old people with newly diagnosed diabetes. Blood samples at diagnosis were collected during the 2-year period 1987/1988. Patients with islet antibodies (islet cell antibodies, GAD antibodies or tyrosine phosphatase-like protein antibodies) were defined as having autoimmune type 1 diabetes. Plasma 25OHD was measured in samples taken from 459 patients at the time of diagnosis, and in 138 of these subjects 8 years later. The results were compared with age- and sex-matched control subjects (n=208).At diagnosis, plasma 25OHD levels were significantly lower in patients with type 1 diabetes than in control subjects (82.5 +/- 1.3 vs 96.7 +/- 2.0 nmol/l; p < 0.0001). Eight years later, plasma 25OHD had decreased in patients (81.5 +/- 2.6 nmol/l; p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9 +/- 1.4 vs 90.1 +/- 2.4 nmol/l; p < 0.0001) and at follow-up (77.1 +/- 2.8 nmol/l vs 87.2 +/- 4.5 nmol/l; p=0.048). 81.5 +/- 2.6 nmol/l; p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9 +/- 1.4 vs 90.1 +/- 2.4 nmol/l; p < 0.0001) and at follow-up (77.1 +/- 2.8 nmol/l vs 87.2 +/- 4.5 nmol/l; p=0.048). Conclusions/interpretation The plasma 25OHD level was lower at diagnosis of autoimmune type 1 diabetes than in control subjects, and may have a role in the development of type 1 diabetes. Plasma 25OHD levels were lower in men than in women with type 1 diabetes. This difference may be relevant to the high incidence of type 1 diabetes among young adult men.
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| 29. |
- Nilsson, Mikael, et al.
(author)
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Does individual learning styles influence the choice to use a web-based ECG learning programme in a blended learning setting?
- 2012
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In: BMC Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 12, s. 5-
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Journal article (peer-reviewed)abstract
- Background: The compressed curriculum in modern knowledge-intensive medicine demands useful tools to achieve approved learning aims in a limited space of time. Web-based learning can be used in different ways to enhance learning. Little is however known regarding its optimal utilisation. Our aim was to investigate if the individual learning styles of medical students influence the choice to use a web-based ECG learning programme in a blended learning setting. Methods: The programme, with three types of modules (learning content, self-assessment questions and interactive ECG interpretation training), was offered on a voluntary basis during a face to face ECG learning course for undergraduate medical students. The Index of Learning Styles (ILS) and a general questionnaire including questions about computer and Internet usage, preferred future speciality and prior experience of E-learning were used to explore different factors related to the choice of using the programme or not. Results: 93 (76%) out of 123 students answered the ILS instrument and 91 the general questionnaire. 55 students (59%) were defined as users of the web-based ECG-interpretation programme. Cronbach's alpha was analysed with coefficients above 0.7 in all of the four dimensions of ILS. There were no significant differences with regard to learning styles, as assessed by ILS, between the user and non-user groups; Active/Reflective; Visual/Verbal; Sensing/Intuitive; and Sequential/Global (p = 0.56-0.96). Neither did gender, prior experience of E-learning or preference for future speciality differ between groups. Conclusion: Among medical students, neither learning styles according to ILS, nor a number of other characteristics seem to influence the choice to use a web-based ECG programme. This finding was consistent also when the usage of the different modules in the programme were considered. Thus, the findings suggest that web-based learning may attract a broad variety of medical students.
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| 30. |
- Nilsson, Mikael, et al.
(author)
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Evaluation of a web-based ECG-interpretation programme for undergraduate medical students
- 2008
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In: BMC Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 8, s. 25-
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Most clinicians and teachers agree that knowledge about ECG is of importance in the medical curriculum. Students at Karolinska Institute have asked for more training in ECG-interpretation during their undergraduate studies. Clinical tutors, however, have difficulties in meeting these demands due to shortage of time. Thus, alternative ways to learn and practice ECG-interpretation are needed. Education offered via the Internet is readily available, geographically independent and flexible. Furthermore, the quality of education may increase and become more effective through a superior educational approach, improved visualization and interactivity. METHODS: A Web-based comprehensive ECG-interpretation programme has been evaluated. Medical students from the sixth semester were given an optional opportunity to access the programme from the start of their course. Usage logs and an initial evaluation survey were obtained from each student. A diagnostic test was performed in order to assess the effect on skills in ECG interpretation. Students from the corresponding course, at another teaching hospital and without access to the ECG-programme but with conventional teaching of ECG served as a control group. RESULTS: 20 of the 32 students in the intervention group had tested the programme after 2 months. On a five-graded scale (1- bad to 5 - very good) they ranked the utility of a web-based programme for this purpose as 4.1 and the quality of the programme software as 3.9. At the diagnostic test (maximal points 16) by the end of the 5-month course at the 6th semester the mean result for the students in the intervention group was 9.7 compared with 8.1 for the control group (p = 0.03). CONCLUSION: Students ranked the Web-based ECG-interpretation programme as a useful instrument to learn ECG. Furthermore, Internet-delivered education may be more effective than traditional teaching methods due to greater immediacy, improved visualisation and interactivity.
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| 31. |
- Nilsson, Mikael, et al.
(author)
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Why Medical Students Choose to Use or Not to Use a Web-Based Electrocardiogram Learning Resource : Mixed Methods Study
- 2019
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In: JMIR Medical Education. - : JMIR Publications Inc.. - 2369-3762. ; 5:2, s. e12791:1-e12791:12
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Journal article (peer-reviewed)abstract
- Background: Electrocardiogram (ECG) interpretation is a core competence and can make a significant difference to patient outcomes. However, ECG interpretation is a complex skill to learn, and research has showed that students often lack enough competence. Web-based learning has been shown to be effective. However, little is known regarding why and how students use Web-based learning when offered in a blended learning situation.Objective: The aim of this paper was to study students’ use of Web-based ECG learning resources which has not previously been studied in relation to study strategies.Methods: A qualitative explanatory design using mixed methods was adopted to explore how medical students reason around their choice to use or not to use a Web-based ECG learning resource. Overall, 15 of 33 undergraduate medical students attending a course in clinical medicine were interviewed. Data on usage of the resource were obtained via the learning management system for all students. At the final examination, all the students answered a questionnaire on study strategies and questions about internet access and estimated their own skills in ECG interpretation. Furthermore, study strategies and use patterns were correlated with results from an ECG Objective Structured Clinical Examination (OSCE) and a written course examination.Results: In total, 2 themes were central in the students’ reasoning about usage of Web-based ECG: assessment of learning needs and planning according to learning goals. Reasons for using the Web resource were to train in skills, regarding it as a valuable complement to books and lectures. The main reasons for not using the resource were believing they already had good enough skills and a lack of awareness of its availability. Usage data showed that 21 students (63%) used the Web resource. Of these, 11 were minimal users and 10 were major users based on usage activity. Large variations were found in the time spent in different functional parts of the resource. No differences were found between users and nonusers regarding the OSCE score, final examination score, self-estimate of knowledge, or favoring self-regulated learning.Conclusions: To use or not to use a Web-based ECG learning resource is largely based on self-regulated learning aspects. Decisions to use such a resource are based on multifactorial aspects such as experiences during clinical rotations, former study experiences, and perceived learning needs. The students’ own judgment of whether there was a need for a Web-based resource to achieve the learning goals and to pass the examination was crucial for their decisions to use it or not. An increased understanding of students’ regulation of learning and awareness of variations in their ECG learning needs can contribute to the improvement of course design for blended learning of ECG contexts for medical students.
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| 32. |
- Nyström, Thomas, et al.
(author)
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Evaluation of Effects of Continuous Glucose Monitoring on Physical Activity Habits and Blood Lipid Levels in Persons With Type 1 Diabetes Managed With MDI: An Analysis Based on the GOLD Randomized Trial (GOLD 8)
- 2024
-
In: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 18:1, s. 89-98
-
Journal article (peer-reviewed)abstract
- Background: People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation. Method: The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG. Results: There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 (P =.16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment (P <.001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG. Conclusion: Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG.
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| 33. |
- Poeplau, Christopher, et al.
(author)
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Positive trends in organic carbon storage in Swedish agricultural soils due to unexpected socio-economic drivers
- 2015
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In: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 12, s. 3241-3251
-
Journal article (peer-reviewed)abstract
- Soil organic carbon (SOC) plays a crucial role in the global carbon cycle as a potential sink or source. Land management influences SOC storage, so the European Parliament decided in 2013 that changes in carbon stocks within a certain land use type, including arable land, must be reported by all member countries in their national inventory reports for greenhouse gas emissions. Here we show the temporal dynamics of SOC during the past 2 decades in Swedish agricultural soils, based on soil inventories conducted in 19881997 (Inventory I), 2001-2007 (Inventory II) and from 2010 onwards (Inventory III), and link SOC changes with trends in agricultural management. From Inventory I to Inventory II, SOC increased in 16 out of 21 Swedish counties, while from Inventory I to Inventory III it increased in 18 out of 21 counties. Mean topsoil (0-20 cm) SOC concentration for the entire country increased from 2.48 to 2.67% C (a relative increase of 7.7 %, or 0.38% yr(-1)) over the whole period. We attributed this to a substantial increase in ley as a proportion of total agricultural area in all counties. The horse population in Sweden has more than doubled since 1981 and was identified as the main driver for this management change (R-2 = 0.72). Due to subsidies introduced in the early 1990s, the area of long-term set-aside (mostly old leys) also contributed to the increase in area of ley. The carbon sink function of Swedish agricultural soils demonstrated in this study differs from trends found in neighbouring countries. This indicates that country-specific or local socio-economic drivers for land management must be accounted for in larger-scale predictions.
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| 34. |
- Pundziute-Lyckå, A, et al.
(author)
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The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983-1998.
- 2002
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 45:6, s. 783-91
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Journal article (peer-reviewed)abstract
- AIMS/HYPOTHESIS: To analyse the incidence of Type I (insulin-dependent) diabetes mellitus in the 0-34 years age group in Sweden 1983-1998.METHODS: Incidence and cumulative incidence per 100 000 and Poisson regression analysis of age-period effects was carried out using 11 751 cases from two nation-wide prospective registers.RESULTS: Incidence (95%-CI) was 21.4 (20.8-21.9) in men and 17.1 (16.6-17.5) in women between 0 and 34 years of age. In boys aged 0-14 and girls aged 0-12 years the incidence increased over time, but it tended to decrease at older age groups, especially in men. Average cumulative incidence at 35 years was 748 in men and 598 in women. Cumulative incidence in men was rather stable during four 4-year periods (736, 732, 762, 756), while in women it varied more (592, 542, 617, 631). In males aged 0-34 years, the incidence did not vary between the 4-year periods ( p=0.63), but time changes among the 3-year age groups differed ( p<0.001). In females the incidence between the periods varied ( p<0.001), being lower in 1987-1990 compared to 1983-1986, but time changes in the age groups did not differ ( p=0.08). For both sexes median age at diagnosis was higher in 1983-1986 than in 1995-1998 ( p<0.001) (15.0 and 12.5 years in males; 11.9 and 10.4 in females, respectively).CONCLUSION/INTERPRETATION: During a 16-year period the incidence of Type I diabetes did not increase in the 0-34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes.
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| 35. |
- Rawshani, Araz, et al.
(author)
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The incidence of diabetes among 0-34 year olds in Sweden: new data and better methods
- 2014
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 57:7, s. 1375-1381
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Journal article (peer-reviewed)abstract
- Aims/hypothesis We reassessed the validity of previously reported incidence rates for type 1 diabetes in 0-34 year olds in Sweden. We estimated new incidence rates through three nationwide registers. Methods We used capture-recapture methods to assess ascertainment in the Diabetes Incidence Study in Sweden (DISS) and estimated incidence rates in the 20-34 year age group for 2007-2009. We examined whether incidence rates in patients aged 34 and younger could be estimated through the Prescribed Drug Register (PDR) via a proxy for diagnosis of type 1 diabetes; men with at least one and women with at least three prescriptions for insulin were included if they had not been given oral glucose-lowering drugs. We scrutinised the proxy by comparing incidence rates in patients aged 14 and younger with the Swedish Childhood Diabetes Register (SCDR), which has 95-99% ascertainment, and by assessing diabetes type among 18-34 year olds in the National Diabetes Register (NDR). Results Incidence rates were two to three times higher than previously reported. The absolute number of cases (2007-2009, age 20-34) was 435 in the DISS, 923 in the NDR, 1,217 in the PDR, 1,431 in all three and 1,617 per the capture-recapture method. Ascertainment in the DISS was similar to 29% for 2007-2009. The proxy diagnosis in the PDR was highly reliable, while the capture-recapture method presumably generated an overestimate. Conclusions/interpretation The incidence of type 1 diabetes in patients aged 34 and younger was two to three times higher than previously reported. The PDR can be used to reliably assess incidence rates in this age group.
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| 36. |
- Schölin, Anna, et al.
(author)
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Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults : a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden
- 2004
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 255:3, s. 384-391
-
Journal article (other academic/artistic)abstract
- ObjectivesTo establish the prevalence of remaining β-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later.DesignPopulation-based cohort study.SettingNationwide from all Departments of Medicine and Endocrinology in Sweden.SubjectsA total of 312 young (15–34 years old) adults diagnosed with diabetes during 1987–88.Main outcome measurePlasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved β-cell function was defined as measurable C-peptide levels. Three islet antibodies – cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies – were measured.ResultsAmongst 269 islet antibody positives (ab+) at diagnosis, preserved β-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m−2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining β-cell function. Amongst the 241 patients without detectable β-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up.ConclusionsSixteen per cent of patients with autoimmune type 1 diabetes had remaining β-cell function 8 years after diagnosis whereas 5.8% with β-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.
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| 37. |
- Schölin, Anna, et al.
(author)
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Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes
- 2004
-
In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 21:5, s. 447-455
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Journal article (other academic/artistic)abstract
- Aim To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM).Methods In Sweden, 362 patients (15–34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA1c and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose ≤ 0.3 U/kg/24 h and HbA1c within the normal range, was analysed in relation to characteristics at diagnosis.Results Remissions were seen in 43% of the patients with a median duration of 8 months (range 1–73). Sixteen per cent had a remission with a duration > 12 months. Among patients with antibodies (ab+), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20–24.9 kg/m2) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab+ remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions.Conclusion In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.
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| 38. |
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| 39. |
- Svensson, M.K, 1965, et al.
(author)
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The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors
- 2015
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In: Diabetes-Metabolism Research and Reviews. - : Wiley. - 1520-7560 .- 1520-7552. ; 31:2, s. 138-146
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Journal article (peer-reviewed)abstract
- AimsThe main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34years). MethodsAll 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. ResultsAfter median 17years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1kg/m(2)), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p=0.041), BMI (p=0.012) and HbA1c (p<0.001) were significant predictors of developing diabetic nephropathy between 9 and 17years of diabetes. At 17years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.051.12 per 1mmHg increase) were associated with DN. ConclusionsPatients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9years of follow-up was a risk marker for later development of diabetic nephropathy. Copyright (c) 2014 John Wiley & Sons, Ltd.
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| 40. |
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| 41. |
- Tyrberg, M., et al.
(author)
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Overweight, hyperglycemia and tobacco use are modifiable risk factors for onset of retinopathy 9 and 17 years after the diagnosis of diabetes – A retrospective observational nation-wide cohort study
- 2017
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 133, s. 21-29
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Journal article (peer-reviewed)abstract
- Background The aims of this study were to estimate the risk for diabetic retinopathy (DR) and to identify risk factors. We investigated a nationwide population-based cohort with diabetes diagnosed at age 15–34 years. Patients and methods Of 794 patients registered 1987–1988 in the Diabetes Incidence Study in Sweden (DISS) 444 (56%) patients with retinal photos available for classification of retinopathy participated in a follow-up study 15–19 (median 17) years after diagnosis. Mean age was 42.3 ± 5.7 years, BMI 26.1 ± 4.1 kg/m2, 62% were male and 91% had type 1 diabetes. A sub-study was performed in 367 patients with retinal photos from both the 9 and 17 year follow up and the risk for development of retinopathy between 9 and 17 years of follow up was calculated. Results After median 17 years 324/444 (73%, 67% of T1D and 71% of T2D), had developed any DR but only 5.4% proliferative DR. Male sex increased the risk of developing retinopathy (OR 1.9, 95% CI 1.2–2.9). In the sub-study obesity (OR 1.2, 95% CI 1.04–1.4), hyperglycemia (OR 2.5, 95% CI 1.6–3.8) and tobacco use (OR 2.9, 95% CI 1.1–7.3) predicted onset of retinopathy between 9 and 17 years after diagnosis of diabetes. Conclusion The number of patients with severe retinopathy after 17 years of diabetes disease was small. The risk of developing retinopathy with onset between 9 and 17 years after diagnosis of diabetes was strongly associated to modifiable risk factors such as glycemic control, obesity and tobacco use.
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- Östman, Jan, et al.
(author)
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Ketoacidosis in young adults is not related to the islet antibodies at the diagnosis of Type 1 diabetes mellitus - A nationwide study
- 2000
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 17, s. 269-
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Journal article (peer-reviewed)abstract
- Aims: To test the hypothesis that there is lower prevalence of islet antibodies in subjects with newly diagnosed Type 1 diabetes mellitus in young adulthood than in children is associated with less severe diabetes at time of diagnosis. Methods: This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of 15-34-year-old newly diagnosed diabetic subjects. During 1992-1993, all diabetic subjects (excluding secondary and gestational diabetes) were reported on standardized forms, with information about clinical characteristics at diagnosis. The study examined islet cell antibodies (ICA) by indirect immunofluorescence, and autoantibodies to glutamic acid decarboxylase (GADA), tyrosine phosphatase- like antigen (IA-2A) and insulin (IAA) as well as C-peptide by radioimmunoassay. Results: Blood samples were available from 78 patients with diabetic ketoacidosis (DKA) and 517 non-acidotic patients. The prevalence of ICA (63% vs. 57%), GADA (63% vs. 66%), IA-2A (35% vs. 44%) and IAA (20% vs. 15%) were very similar in patients with or without DKA. The median levels of the four autoantibodies did not differ between the two groups. High blood glucose (P < 0.001) and low C-peptide levels (P < 0.001) were the only parameters found to be related to DKA. Conclusions: The similarities in findings of newly diagnosed diabetic patients with or without DKA regarding ICA, GADA, IA-2A and IAA suggest that there is no relationship between the expression of antigenicity and the severity of β-cell dysfunction. The lower prevalence of the four autoantibodies in 15-34-year-old diabetic subjects compared with previous findings in children is not explained by misclassification of diabetes type.
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