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  • 1.
    Ahlqvist, E.
    et al.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Karajamaki, A.
    Vaasa Cent Hosp, Primary Hlth Care, Vaasa, Finland..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Storm, P.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Dorkhan, M.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Vikman, P.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Prasad, R. B.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Aly, D. Mansour
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Shaat, N.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Lindholm, E.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Tuomi, T.
    Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Rosengren, A. H.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Groop, L.
    Lund Univ, Ctr Diabet, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Clustering of diabetes into novel subgroups provides improved prediction of outcome2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S117-S117Article in journal (Other academic)
  • 2.
    Ahlqvist, Emma
    et al.
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Storm, Petter
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Käräjämäki, Annemarie
    Department of Primary Health Care, Vaasa Central Hospital, Finland.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Dorkhan, Mozhgan
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Carlsson, Annelie
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, SE-22185 Lund, Sweden.
    Vikman, Petter
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Prasad, Rashmi
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Mansour Aly, Dina
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Almgren, Peter
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Wessman, Ylva
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Shaat, Nael
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Spegel, Peter
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Mulder, Hindrik
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Lindholm, Eero
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Melander, Olle
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Hansson, Ola
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Malmqvist, Ulf
    Clinical Research and Trial Center, Lund University Hospital, Sweden.
    Lernmark, Åke
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Lahti, Kaj
    Department of Primary Health Care, Vaasa Central Hospital, Finland.
    Forsén, Tom
    Department of Primary Health Care, Vaasa Central Hospital, Finland.
    Tuomi, Tiinamaija
    Abdominal Center, Endocrinology, Helsinki University Central Hospital; Research Program for Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
    Rosengren, Anders
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Groop, Leif
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables2018In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 6, no 5, p. 361-369Article in journal (Refereed)
    Abstract [en]

     Background

    Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis.

    Methods

    We did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations.

    Findings

    We identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes.

    Interpretation

    We stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.

  • 3. Ambegaonkar, B
    et al.
    Pettersson, B
    Sazonov, V
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Prevalence of lipid abnormalities before and after the introduction of lipid modifying therapy among Swedish patients with type 2 diabetes and/or coronary heart disease (PRIMULA Sweden)2009In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, no Suppl. 1, p. S495-S495Article in journal (Refereed)
  • 4.
    Carlbom, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    [(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes2017In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, no 5, p. 1286-1292Article in journal (Refereed)
    Abstract [en]

    [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.

  • 5.
    Elksnis, Andris
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Eriksson, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Heterogeneity of Metabolic Defects in Type 2 Diabetes and Its Relation to Reactive Oxygen Species and Alterations in Beta-Cell Mass2019In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, article id 107Article, review/survey (Refereed)
    Abstract [en]

    Type 2 diabetes (T2D) is a complex and heterogeneous disease which affects millions of people worldwide. The classification of diabetes is at an interesting turning point and there have been several recent reports on sub-classification of T2D based on phenotypical and metabolic characteristics. An important, and perhaps so far underestimated, factor in the pathophysiology of T2D is the role of oxidative stress and reactive oxygen species (ROS). There are multiple pathways for excessive ROS formation in T2D and in addition, beta-cells have an inherent deficit in the capacity to cope with oxidative stress. ROS formation could be causal, but also contribute to a large number of the metabolic defects in T2D, including beta-cell dysfunction and loss. Currently, our knowledge on beta-cell mass is limited to autopsy studies and based on comparisons with healthy controls. The combined evidence suggests that beta-cell mass is unaltered at onset of T2D but that it declines progressively. In order to better understand the pathophysiology of T2D, to identify and evaluate novel treatments, there is a need for in vivo techniques able to quantify beta-cell mass. Positron emission tomography holds great potential for this purpose and can in addition map metabolic defects, including ROS activity, in specific tissue compartments. In this review, we highlight the different phenotypical features of T2D and how metabolic defects impact oxidative stress and ROS formation. In addition, we review the literature on alterations of beta-cell mass in T2D and discuss potential techniques to assess beta-cell mass and metabolic defects in vivo.

  • 6.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Increased Circulating Betatrophin Concentrations in Patients with Type 2 Diabetes2014In: International Journal of Endocrinology, ISSN 1687-8337, E-ISSN 1687-8345, Vol. 2014, p. 323407-Article in journal (Refereed)
    Abstract [en]

    Betatrophin has recently been described as a key hormone to stimulate beta-cell mass expansion in response to insulin resistance and obesity in mice. The finding has generated an interest in the development of antidiabetic drugs with betatrophin as the active component. However, the circulating levels of betatrophin in patients with type 2 diabetes are not well known. Betatrophin concentrations in plasma of 27 type 2 diabetes patients and 18 gender-, age-, and BMI-matched controls were measured. Study participants were characterized with regard to BMI, waist and hip circumference, blood pressure, and fasting plasma blood lipids, creatinine, glucose, HbA1c, and C-peptide. HOMA2 indices were calculated. Betatrophin was 40% higher in patients with type 2 diabetes (893 +/- 80 versus 639 +/- 66 pg/mL). Betatrophin positively correlated with age in the controls and with HbA1c in the type 2 diabetes patients. All study participants were insulin resistant with mean HOMA2B IR in both groups exceeding 2 and HOMA2% S < 50%. Control individuals had impaired fasting glucose concentrations. In this report on betatrophin concentrations in type 2 diabetes and insulin resistance, elevated betatrophin levels were measured in the patients with type 2 diabetes. Future studies are clearly needed to delineate the exact role, if any, of betatrophin in regulating human beta-cell mass.

  • 7.
    Espes, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Liljebäck, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Betatrophin in Diabetes Mellitus: the Epidemiological Evidence in Humans2015In: Current Diabetes Reports, ISSN 1534-4827, E-ISSN 1539-0829, Vol. 15, no 12, article id 104Article, review/survey (Refereed)
    Abstract [en]

    The prevalence of type 2 diabetes is increasing worldwide, and while numerous treatments exist, none of the current pharmacologic therapies is curative. Pharmacologic approaches that increase beta cell mass may present an avenue for actual cure. There have been numerous reports on factors that can induce beta cell proliferation in rodents, whereas there are still very limited data on the occurrence of beta cell proliferation in humans. The recent discovery of the hormone betatrophin, which in mice counteracted glucose intolerance induced by insulin resistance by potently stimulating beta cell proliferation, has boosted the hope for a new target for drug development for the treatment of diabetes mellitus in humans. With the encouraging preclinical findings as a background, this review presents the available clinical data on betatrophin and discusses its possible role in humans.

  • 8.
    Hjort, R.
    et al.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, S-17177 Stockholm, Sweden..
    Alfredsson, L.
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, Stockholm, Sweden..
    Andersson, T.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, S-17177 Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Grill, V.
    Norwegian Univ Sci & Technol, NTNU Inst Canc Res & Mol Med, Trondheim, Norway.;Trondheim Reg & Univ Hosp, Dept Endocrinol, Trondheim, Norway..
    Groop, L.
    Lund Univ, Clin Res Ctr, Dept Clin Sci Malmo, Malmo, Sweden..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Rasouli, B.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, S-17177 Stockholm, Sweden..
    Storm, P.
    Lund Univ, Clin Res Ctr, Dept Clin Sci Malmo, Malmo, Sweden..
    Tuomi, T.
    Univ Helsinki, Div Endocrinol, Abdominal Ctr, Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Res Program Diabet & Obes, Helsinki, Finland.;Helsinki Univ Hosp, Folkhalsan Res Ctr, Helsinki, Finland..
    Carlsson, S.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, S-17177 Stockholm, Sweden..
    Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)2017In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 43, no 6, p. 536-542Article in journal (Refereed)
    Abstract [en]

    Background. - A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. Methods. - Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age < 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. Results. - Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-Tl D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576). Conclusion. - The risk of LADA is substantially increased with FHD-Tl D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-Tl D had more T1D-like features, emphasizing the heterogeneity of LADA. (C) 2017 Elsevier Masson SAS. All rights reserved.

  • 9.
    Hjort, R.
    et al.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Lofvenborg, J. E.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Ahlqvist, E.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Alfredsson, L.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Andersson, T.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Groop, L.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Rasouli, B.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Rosengren, A.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Tuomi, T.
    Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Helsinki Univ Hosp, Res Program Diabet & Obes, Div Endocrinol,Abdominal Ctr, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Carlsson, S.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Overweight, obesity, genetic susceptibility and the risk of LADA: Latent Autoimmune Diabetes in Adults2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no S1, p. S118-S118, article id 252Article in journal (Other academic)
  • 10.
    Hjort, Rebecka
    et al.
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Box 210, S-17177 Stockholm, Sweden.
    Ahlqvist, Emma
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Grill, Valdemar
    Norwegian Univ Sci & Technol, Dept Clin & Mol Med, NTNU, Trondheim, Norway;Trondheim Reg & Univ Hosp, St Olavs Hosp, Dept Endocrinol, Trondheim, Norway.
    Groop, Leif
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Rasouli, Bahareh
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Box 210, S-17177 Stockholm, Sweden.
    Rosengren, Anders
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden.
    Tuomi, Tiinamaija
    Univ Helsinki, Helsinki Univ Hosp, Div Endocrinol, Abdominal Ctr,Res Program Diabet & Obes, Helsinki, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
    Asvold, Bjorn Olav
    Trondheim Reg & Univ Hosp, St Olavs Hosp, Dept Endocrinol, Trondheim, Norway;Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, KG Jebsen Ctr Genet Epidemiol, NTNU, Trondheim, Norway.
    Carlsson, Sofia
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Box 210, S-17177 Stockholm, Sweden.
    Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT Study2018In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 6, p. 1333-1343Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies. Methods Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case-control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984-2008). We present adjusted ORs and HRs with 95% CI. Results In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD. Conclusions/interpretation Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.

  • 11.
    Hjort, Rebecka
    et al.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-17177 Stockholm, Sweden..
    Alfredsson, Lars
    Karolinska Inst, Inst Environm Med, Unit Cardiovasc Epidemiol, S-17177 Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Groop, Leif
    Lund Univ, Clin Res Ctr, Dept Clin Sci Malmo, Malmo, Sweden..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Storm, Petter
    Lund Univ, Clin Res Ctr, Dept Clin Sci Malmo, Malmo, Sweden..
    Tuomi, Tiinamaija
    Helsinki Univ Hosp, Div Endocrinol, Abdominal Ctr, Helsinki, Finland.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Res Program Diabet & Obes, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Carlsson, Sofia
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-17177 Stockholm, Sweden..
    Low birthweight is associated with an increased risk of LADA and type 2 diabetes: results from a Swedish case-control study2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no 11, p. 2525-2532Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Our aim was to investigate the association between birthweight and latent autoimmune diabetes in adults (LADA), a common diabetes form with features of both type 1 and type 2 diabetes. Methods We used data from the Epidemiological Study of Risk Factors for LADA and Type 2 Diabetes (ESTRID), a Swedish population-based study. Eligible for the analysis were 134 incident LADA cases (glutamic acid decarboxylase antibody [GADA] positive), 350 incident type 2 diabetes cases (GADA negative) and 603 randomly selected controls. We present ORs and 95% CIs for LADA and type 2 diabetes in relation to birthweight, adjusted for sex, age, BMI and family history of diabetes. Results Low birthweight increased the risk of LADA as well as the risk of type 2 diabetes; OR per kg reduction was estimated as 1.52 (95% CI 1.12, 2.08) and 1.58 (1.23, 2.04), respectively. The OR for participants weighing < 3 kg compared with >= 4 kg at birth was estimated as 2.38 (1.23, 4.60) for LADA and 2.37 (1.37, 4.10) for type 2 diabetes. A combination of low birthweight (< 3 kg) and current overweight (BMI >= 25) further augmented the risk: LADA, OR 3.26 (1.69, 6.29); and type 2 diabetes, OR 39.93 (19.27, 82.71). Family history of diabetes had little impact on these estimates. Conclusions/interpretation Our results suggest that low birthweight may be a risk factor for LADA of the same strength as for type 2 diabetes. These findings support LADA, despite its autoimmune component, having an aetiology that includes factors related to type 2 diabetes.

  • 12. Lofvenborg, J. E.
    et al.
    Andersson, T.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Dorkhan, M.
    Groop, L.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Rasouli, B.
    Storm, P.
    Tuomi, T.
    Carlsson, S.
    Coffee consumption and the risk of latent autoimmune diabetes in adults-results from a Swedish case-control study2014In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 31, no 7, p. 799-805Article in journal (Refereed)
    Abstract [en]

    Aims Coffee consumption is associated with a reduced risk of Type2 diabetes. Our aim was to investigate if coffee intake may also reduce the risk of latent autoimmune diabetes in adults, an autoimmune form of diabetes with features of Type2 diabetes. Methods We used data from a population-based case-control study with incident cases of adult onset (35years) diabetes, including 245 cases of latent autoimmune diabetes in adults (glutamic acid decarboxylase antibody positive), 759 cases of Type2 diabetes (glutamic acid decarboxylase antibody negative), together with 990 control subjects without diabetes, randomly selected from the population. Using questionnaire information on coffee consumption, we estimated the odds ratio of latent autoimmune diabetes in adults and Type2 diabetes adjusted for age, sex, BMI, smoking, physical activity, alcohol, education and family history of diabetes. Results Coffee intake was inversely associated with Type2 diabetes (odds ratio0.92, 95%CI 0.87-0.98 per cup/day). With regard to latent autoimmune diabetes in adults, the general trend was weak (odds ratio1.04, 95%CI 0.96-1.13), but stratification by degree of autoimmunity (median glutamic acid decarboxylase antibody levels) suggested that coffee intake may be associated with an increased risk of high glutamic acid decarboxylase antibody latent autoimmune diabetes in adults (odds ratio1.11, 95%CI 1.00-1.23 per cup/day). Furthermore, for every additional cup of coffee consumed per day, there was a 15.2% (P=0.0268) increase in glutamic acid decarboxylase antibody levels. Conclusions Our findings confirm that coffee consumption is associated with a reduced risk of Type2 diabetes. Interestingly, the findings suggest that coffee may be associated with development of autoimmunity and possibly an increased risk of more Type1-like latent autoimmune diabetes in adults.

  • 13.
    Löfvenborg, Josefin E.
    et al.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Andersson, Tomas
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Dorkhan, Mozhgan
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Groop, Leif
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Tuomi, Tiinamaija
    Univ Helsinki, Res Program Diabet & Obes, Helsinki Univ Hosp, Abdominal Ctr,Endocrinol, Helsinki, Finland.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Carlsson, Sofia
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes2016In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 175, no 6, p. 605-614Article in journal (Refereed)
    Abstract [en]

    Objective: Sweetened beverage intake is associated with increased risk of type 2 diabetes, but its association with autoimmune diabetes is unclear. We aimed to investigate sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA); autoimmune diabetes with features of type 2 diabetes. Design/methods: Data from a Swedish population-based study was used, including incident cases of LADA (n = 357) and type 2 diabetes (n = 1136) and randomly selected controls (n = 1371). Diabetes classification was based on onset age (= 35), glutamic acid decarboxylase autoantibodies (GADA) and C-peptide. Sweetened beverage intake information was derived from a validated food frequency questionnaire. ORs adjusted for age, sex, family history of diabetes, education, lifestyle, diet, energy intake and BMI were estimated using logistic regression. Results: Daily intake of >2 servings of sweetened beverages (consumed by 6% of participants) was associated with increased risk of LADA (OR: 1.99, 95% CI: 1.11-3.56), and for each 200 mL daily serving, OR was 1.15 (95% CI: 1.02-1.29). Findings were similar for sugar-sweetened (OR: 1.18, 95% CI: 1.00-1.39) and artificially sweetened beverages (OR: 1.12, 95% CI: 0.95-1.32). Similarly, each daily serving increment in total sweetened beverage conferred 20% higher type 2 diabetes risk (95% CI: 1.07-1.34). In type 2 diabetes patients, high consumers displayed higher HOMA-IR levels (4.5 vs 3.5, P = 0.0002), but lower HOMA-B levels (55 vs 70, P = 0.0378) than non-consumers. Similar tendencies were seen in LADA. Conclusions: High intake of sweetened beverages was associated with increased risk of LADA. The observed relationship resembled that with type 2 diabetes, suggesting common pathways possibly involving insulin resistance.

  • 14.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Diabetes Mellitus at the Time for Diagnosis: Studies on Prognostic Factors2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim for this thesis was to identify prognostic factors for chronic diabetes complications that exist at the time of diabetes diagnosis.

    Low level of education (<12 years) and low income (<60% of median) was found to increase the risk to have high (>70 mmol/mol) HbA1c at the time of diagnosis with 34 % and 35 %, respectively.

    Prevalence of diabetic retinopathy (DR) was 12% in a cohort of patients newly diagnosed with diabetes. Diabetic macular edema was present in 11% of patients with type 2 diabetes (T2D) and 13% of those with Latent Autoimmune Diabetes in Adults (LADA). Low beta cell function and low level of education increased the risk for DR with 110% and 43%, respectively. For every unit of increase in body mass index, the risk for DR was reduced by 3%.

    The cellular immunology of LADA patients was a mixture of that observed in both type 1 (T1D) and T2D patients. Compared to patients with T1D, LADA patients had more B-regulatory lymphocytes and antigen presenting cells capable of producing interleukine-35. This indicates a higher anti-inflammatory capacity in LADA patients compared to type T1D patients.

    By imputing age, body mass index, HbA1c at diagnosis, beta cell function and insulin resistance in a cluster analysis, five distinct diabetes clusters were identified. The four clusters representing T2D patients differed in incidence of DR, nephropathy and non-alcoholic fatty liver disease. This was replicated with similar results in three geographically separate populations.

    By studying socioeconomic background and factors present at the time of diagnosis we can better predict prognosis for chronic diabetes complications. These findings may facilitate better-targeted diabetes screening programs and more individually tailored treatment regimes.

  • 15.
    Martinell, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Dorkhan, Mozhgan
    Lund Univ, Dept Clin Sci Malmo, Uppsala, Sweden..
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Storm, Petter
    Lund Univ, Dept Clin Sci Malmo, Uppsala, Sweden..
    Groop, Leif
    Lund Univ, Dept Clin Sci Malmo, Uppsala, Sweden..
    Gustavsson, Carin
    Lund Univ, Dept Clin Sci Malmo, Uppsala, Sweden..
    Prevalence and risk factors for diabetic retinopathy at diagnosis (DRAD) in patients recently diagnosed with type 2 diabetes (T2D) or latent autoimmune diabetes in the adult (LADA)2016In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 30, no 8, p. 1456-1461Article in journal (Refereed)
    Abstract [en]

    PURPOSE: 

    To study prevalence of diabetic retinopathy (DR) at diagnosis (DRAD) and to estimate contributing risk by sociodemographic, cardiovascular and metabolic characteristics present in patients recently diagnosed with type 2 diabetes (T2D) or latent autoimmune diabetes in the adult (LADA).

    METHODS: 

    Patients (n=2174) recently diagnosed T2D (93%) or LADA (7%) were included upon arrival for their baseline DR screening. Fundus photographs of 4902 eyes were graded by a senior ophthalmologist according to the International Diabetic Retinopathy Disease Severity Scale. Official registers held by Statistics Sweden provided sociodemographic variables. The National Patient Register and Swedish Prescribed Drug Register were used to assess cardiovascular risk. Beta cell function (HOMA2%b) and insulin sensitivity (HOMA2%s) were estimated from fasting (f) C-Peptide using the homeostasis model assessment (HOMA) 2 calculator. Odds ratios (OR) for DRAD were estimated using generalized estimating equation models.

    RESULTS: 

    The prevalence of DRAD was 12% (7% mild and 5% moderate) and of diabetic macular edema it was 11% (all within vascular arch). The prevalence did not significantly differ between T2D and LADA. Due to sample size, the regression analysis of LADA patients did not yield any significant estimates. In T2D low educational level (≤9years) increased risk for DRAD by 44% (OR 1.44; 95% CI 1.07-1.93) and <50% beta-cell function adjusted for HbA1c and insulin sensitivity at diagnosis increased the risk by 77% (OR 1.77; 95% CI 1.28-2.44). For every unit increase in BMI, risk for DRAD decreased by 3% (OR 0.97; 95% CI 0.95-0.99).

    CONCLUSIONS: 

    DRAD prevalence in patients recently diagnosed with T2D or is 12%. Low educational level and low beta cell function at diagnosis are risk factors for DRAD. Estimation of beta cell function from (f)C-Peptide and (f)P-Glucose may be a valuable tool in identifying patients at risk for DRAD.

  • 16.
    Martinell, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased Circulating Betatrophin Concentrations in Patients with Type 2 Diabetes2014In: Typ1 ?Typ x Språk: - Engelska Svenska Norska Arabiska Bokmål Bulgariska Danska Engelska Esperanto Estniska Finska Franska Färöiska Grönländska (Kalaallit oqaasi) Hebreiska Hindi Indonesiska Iriska Isländska Italienska Japanska Katalanska Kinesiska Koreanska Kroatiska Kurdiska Latin Lettiska Litauiska Madurese Makedonska Mongoliskt språk Nederländska Norska Nygrekiska (1453-) Nynorsk Odefinierat språk Persiska Polska Portugisiska Rumänska Ryska Samiskt språk Sanskrit Serbiska Slovakiska Slovenska Spanska Svenska Tjeckiska Turkiska Tyska Ukrainska Ungerska Urdu Vietnamesiska / [ed] Prof Ulf Eriksson, 2014Conference paper (Refereed)
    Abstract [en]

    Aim

    To test the hypothesis of a Betatrophin deficiency in patients with diabetes by measuring circulating Betatrophin in patients with type 2 diabetes (T2D) and non-diabetic, insulin resistant controls.

     

    Material and methods

    ELISA measured Betatrophin concentration in plasma of 27 patients with T2D and 18 matched controls. The participants were characterized by weight, height, waist-and hip (circumference and ratio), blood pressure, blood lipids, P-creatinine, fP-glucose, HbA1c, fC-peptide and family history of diabetes. Inputting fP-glucose and fC-peptide into the HOMA2 model assessed the beta-cell function, insulin sensitivity and insulin resistance.

     

    Results

    Betatrophin concentrations were approximately 40% higher in the patients with T2D and also correlated positively to HbA1c. In the control group, Betatrophin concentration increased with age. All T2D patients and controls were insulin resistant with mean insulin resistance in both groups well exceeding 2 and the insulin sensitivity being less than 50%.

     

    Conclusion

    In this first study to report on betatrophin concentrations in type 2 diabetes and insulin resistant patients, elevated betatrophin levels were measured in the diabetic individuals. There is no obvious betatrophin deficiency to substitute in these patients.

     

  • 17.
    Martinell, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Singh, Kailash
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Zhengkang, Luo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Sandler, Stellan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Characterization of Cellular Immunology in LADA PatientsManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: Patients with latent autoimmune diabetes mellitus in adults (LADA) have antibodies against the insulin-producing b-cells but at disease onset they are not insulin-dependent. This study presents cellular immunological differences between LADA, type 1, type 2 diabetes and healthy controls.

    Research Design and Methods: All patients and matched (by age, gender and body mass index) healthy controls were recruited from the County of Uppsala, Sweden. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine proportions of innate, adaptive and regulatory immune cells by using flow cytometry.

    Results: Included were 14 patients with LADA, 16 with type 1 diabetes, 16 with type 2 diabetes and 13 healthy controls. The proportion of CD11c+CD123- antigen presenting cells (APCs) was lower, whilst proportions of CD11c+CD123+ APCs and Interleukin (IL)-35+ tolerogenic APCs were higher in LADA patients compared to patients with type 1 diabetes. The proportion of CD3-CD56highCD16+ Natural Killer (NK) cells was higher in LADA patients than in both healthy controls and type 2 diabetes patients. IL-35+ Treg cell numbers were similar to those observed in both type 1 diabetes and type 2 diabetes patients, but a lower frequency of IL-35+ regulatory T (Treg) cells was observed in LADA patients than in healthy controls. The proportion of regulatory B (Breg) cells in LADA patients was higher than in healthy controls, type 1 and type 2 diabetes patients and IL-35+ Breg cell numbers were higher than in type 1 diabetes patients.

    Conclusions: LADA patients present a mixed cellular immunological pattern compared to type 1 and type 2 diabetes patients. Numbers of APCs, IL-35+ tolerogenic APCs and IL-35+ Breg cells in LADA patients are similar to those observed in type 2 diabetes patients, whereas the changes in NK cells are similar to those observed in type 1 diabetes patients. 

  • 18.
    Martinell, Mats
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Hallqvist, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Automated data extraction: A feasible way to construct patient registers of primary care utilization2012In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 1, p. 52-56Article in journal (Refereed)
    Abstract [en]

    Introduction. Electronic medical records (EMRs) enable analysis of health care data by using data mining techniques to build research databases. Though the reliability of the data extraction process is crucial for the credibility of the final analysis, there are few published validations of this process. In this paper we validate the performance of an automated data mining tool on EMR in a primary care setting.

    Methods. The Pygargus Customized eXtraction Program (CXP) was programmed to find and then extract data from patients meeting criteria for type 2 diabetes mellitus (T2DM) at one primary health care clinic (PHC). The ability of CXP to extract relevant cases was assessed by comparing cases extracted by an EMR integrated search engine. The concordance of extracted data with the original EMR source was manually controlled.

    Results. Prevalence of T2DM was 4.0%, which correspond well to previous estimations. By searching for drug prescriptions, diagnosis codes, and laboratory values, 38%, 53%, and 91% of relevant cases were found, respectively. The sensitivity of CXP regarding extraction of relevant cases was 100%. The specificity was 99.9% due to 12 non-T2DM cases extracted. The congruity at single-item level was 99.6%. The 13 incorrect data items were all located in the same structural module.

    Conclusion. The CXP is a reliable and accurate data mining tool to extract selective data from EMR.

  • 19. Pettersson, B
    et al.
    Lindgren, P
    Ringborg, A
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Resource consumption and cost of care the year before and after initiation of insulin theraphy in Swedish patients with type 2 diabetes2010In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 13, no 3, p. A58-A58Article in journal (Other academic)
  • 20. Pettersson, B.
    et al.
    Lindgren, P.
    Ringborg, A.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    RESOURCE CONSUMPTION AND COSTS OF CARE THE YEAR BEFORE AND AFTER INITIATION OF INSULIN THERAPY IN SWEDISH PATIENTS WITH TYPE 2 DIABETES2010In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 13, no 3, p. A58-A58Article in journal (Other academic)
  • 21. Pettersson, Billie
    et al.
    Ambegaonkar, Baishali
    Sazonov, Vasilisa
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Wändell, Per
    Prevalence of lipid abnormalities before and after introduction of lipid modifying therapy among Swedish patients with dyslipidemia (PRIMULA)2010In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 10, p. 737-Article in journal (Refereed)
    Abstract [en]

    Background. Data on the prevalence of dyslipidemia and attainment of goal/normal lipid levels in a Swedish population are scarce. The objective of this study is to estimate the prevalence of dyslipidemia and attainment of goal/normal lipid levels in patients treated with lipid modifying therapy (LMT). Methods. This longitudinal retrospective observational study covers time periods before and after treatment. Data were collected from 1994-2007 electronic patient records in public primary healthcare centers in Uppsala County, Sweden. Patients were included if they had been treated with LMT and had at least one lipid abnormality indicating dyslipidemia and if complete lipid profile data were available. Thresholds levels for lipids were defined as per Swedish guidelines. Results. Among 5,424 patients included, at baseline, the prevalence of dyslipidemia (1 lipid abnormality) was by definition 100%, while this figure was 82% at follow-up. At baseline, 60% had elevated low-density lipoprotein (LDL-C) combined with low high-density lipoprotein (HDL-C) and/or elevated triglycerides (TG s), corresponding figure at follow-up was 36%. Low HDL-C and/or elevated TGs at follow-up remained at 69% for patients with type 2 diabetes mellitus (T2DM), 50% among patients with coronary heart disease (CHD) and 66% among patients with 10 year CHD risk >20%. Of the total sample, 40% attained goal levels of LDL-C and 18% attained goal/normal levels on all three lipid parameters. Conclusions. Focusing therapy on LDL-C reduction allows 40% of patients to achieve LDL-C goal and helps reducing triglyceride levels. Almost 60% of patients experience persistent HDL-C and/or triglyceride abnormality independently of LDL-C levels and could be candidates for additional treatments.

  • 22. Rasouli, B
    et al.
    Ahlqvist, E
    Alfredsson, L
    Andersson, T
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Groop, L
    Löfvenborg, J E
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Rosengren, A
    Tuomi, T
    Wolk, Alicja
    Carlsson, S
    Coffee consumption, genetic susceptibility and risk of latent autoimmune diabetes in adults: A population-based case-control study.2018In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 44, no 4, p. 354-360, article id S1262-3636(18)30087-9Article in journal (Refereed)
    Abstract [en]

    AIM: Coffee consumption is inversely related to risk of type 2 diabetes (T2D). In contrast, an increased risk of latent autoimmune diabetes in adults (LADA) has been reported in heavy coffee consumers, primarily in a subgroup with stronger autoimmune characteristics. Our study aimed to investigate whether coffee consumption interacts with HLA genotypes in relation to risk of LADA.

    METHODS: This population-based study comprised incident cases of LADA (n=484) and T2D (n=1609), and also 885 healthy controls. Information on coffee consumption was collected by food frequency questionnaire. Odds ratios (ORs) with 95% CIs of diabetes were calculated and adjusted for age, gender, BMI, education level, smoking and alcohol intake. Potential interactions between coffee consumption and high-risk HLA genotypes were calculated by attributable proportion (AP) due to interaction.

    RESULTS: Coffee intake was positively associated with LADA in carriers of high-risk HLA genotypes (OR: 1.14 per cup/day, 95% CI: 1.02-1.28), whereas no association was observed in non-carriers (OR: 1.04, 95% CI: 0.93-1.17). Subjects with both heavy coffee consumption (≥4 cups/day) and high-risk HLA genotypes had an OR of 5.74 (95% CI: 3.34-9.88) with an estimated AP of 0.36 (95% CI: 0.01-0.71; P=0.04370).

    CONCLUSION: Our findings suggest that coffee consumption interacts with HLA to promote LADA.

  • 23.
    Rasouli, B.
    et al.
    Karolinska Inst, Inst Environm Med IMM, Stockholm, Sweden..
    Ahlqvist, E.
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Lund, Sweden..
    Andersson, T.
    Karolinska Inst, Inst Environm Med IMM, Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Groop, L.
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Lund, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Hjort, R.
    Karolinska Inst, Inst Environm Med IMM, Stockholm, Sweden..
    Lofvenborg, J. E.
    Karolinska Inst, Inst Environm Med IMM, Stockholm, Sweden..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Rosengren, A.
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Lund, Sweden..
    Tuomi, T.
    Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Helsinki Univ Hosp, Div Endocrinol, Abdominal Ctr, Helsinki, Finland..
    Wolk, A.
    Karolinska Inst, Inst Environm Med IMM, Stockholm, Sweden..
    Carlsson, S.
    Karolinska Inst, Inst Environm Med IMM, Stockholm, Sweden..
    Sodium intake and the risk of type 2 diabetes and Latent Autoimmune Diabetes in Adults (LADA)2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S103-S103Article in journal (Other academic)
  • 24.
    Rasouli, B.
    et al.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden..
    Andersson, T.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, P-O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Grill, V.
    Norwegian Univ Sci & Technol, NTNU Inst Canc Res & Mol Med, Trondheim, Norway.;Univ Trondheim Hosp, Dept Endocrinol, Trondheim, Norway..
    Groop, L.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Midthjell, K.
    Norwegian Univ Sci & Technol, Dept Community Med & Gen Practice, HUNT Res Ctr, Levanger, Norway..
    Storm, P.
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Tuomi, T.
    Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland.;Univ Helsinki, Res Program Diabet & Obes, Helsinki, Finland..
    Carlsson, S.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Stockholm, Sweden..
    Use of Swedish smokeless tobacco (snus) and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA)2017In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 34, no 4, p. 514-521Article in journal (Refereed)
    Abstract [en]

    AimsIt has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). MethodAnalyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population-based controls (n = 699) from a Swedish case-control study. Additional analyses were performed on cross-sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included. ResultsNo association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box-years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever-users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83). ConclusionThe risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke.

  • 25.
    Rasouli, B.
    et al.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Andersson, T.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, P-O
    Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Hjort, R.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Lofvenborg, J. E.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Groop, L.
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Tuomi, T.
    Univ Helsinki, Helsinki Univ Hosp, Abdominal Ctr, Res Program Diabet & Obes,Div Endocrinol, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Carlsson, S.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Serious life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes2017In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 34, no 9, p. 1259-1263Article in journal (Refereed)
    Abstract [en]

    AimIt has been suggested that experiencing serious life events may promote Type1 diabetes in children. Studies in adults are lacking, as are studies on the interaction of life events with genetic factors. We aimed to investigate life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes while taking into account HLA genotype. MethodsAnalysis was based on 425 incident cases of LADA, 1417 incident cases of Type 2 diabetes and 1702 population-based controls recruited in Sweden between 2010 and 2016. Self-reported information on life events including conflicts, divorce, illness/accidents, death and financial problems experienced during the 5years preceding diagnosis/index year was used. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated by logistic regression and adjusted for age, sex, BMI, family history of diabetes, smoking, physical activity and education. ResultsOverall there was no association between experience of any life event and either LADA (OR 0.86, 95% CI 0.68-1.08) or Type2 diabetes (OR 1.00, 95% CI 0.83-1.21). The results were similar for individual events as well as in separate analysis of men and women. Similar results were seen in more autoimmune LADA (glutamic acid decarboxylase antibodies >median) [OR (any life event) 0.88, 95% CI 0.64-1.21] and in LADA carriers of the high-risk HLADR4-DQ8 genotype (OR 0.89, 95% CI 0.61-1.29). ConclusionsOur findings indicate that experience of a serious life event, including the death of a family member, divorce or financial problems, is not associated with an increased risk of LADA, overall or in genetically susceptible individuals.

  • 26.
    Rasouli, Bahareh
    et al.
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-10401 Stockholm, Sweden..
    Andersson, Tomas
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-10401 Stockholm, Sweden.;Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Grill, Valdemar
    Norwegian Univ Sci & Technol, NTNU Inst Canc Res & Mol Med, N-7034 Trondheim, Norway.;Univ Trondheim Hosp, Dept Endocrinol, Trondheim, Norway..
    Groop, Leif
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Storm, Petter
    Lund Univ, Dept Clin Sci Malmo, Clin Res Ctr, Malmo, Sweden..
    Tuomi, Tiinamaija
    Helsinki Univ Hosp, Div Endocrinol, Helsinki, Finland.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Univ Helsinki, Res Program Diabet & Obes, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Carlsson, Sofia
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, S-10401 Stockholm, Sweden..
    Smoking and the Risk of LADA: Results From a Swedish Population-Based Case-Control Study2016In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 39, no 5, p. 794-800Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Smoking is an established risk factor for type 2 diabetes. In contrast, it has been proposed that smoking may reduce the risk of latent autoimmune diabetes in adults (LADA), but studies are scarce. We aimed to study the impact of smoking on LADA and type 2 diabetes risks. RESEARCH DESIGN AND METHODS We used data from a Swedish case-control study including incident case patients with LADA (GAD antibody [GADA] positive, n = 377) and type 2 diabetes (GADA negative, n = 1,188) and control subjects randomly selected from the population (n = 1,472). We calculated odds ratios (ORs) with 95% CIs by logistic regression, adjusted for age, sex, BMI, family history of diabetes, and alcohol consumption. RESULTS There was no indication of reduced risk of LADA in smokers; instead, heavy smoking was associated with an increased risk of LADA (OR 1.37, 95% CI 1.02-1.84). Heavy smokers had higher levels of HOMA of insulin resistance (9.89 vs. 4.38, P = 0.0479) and HOMA of beta-cell function (55.7 vs. 42.5, P = 0.0204), but lower levels of GADA (75 vs. 250, P = 0.0445), compared with never smokers. Smokers also displayed an increased risk of type 2 diabetes (OR in ever smokers 1.53, 95% CI 1.25-1.88). CONCLUSIONS In this large population of LADA patients, we did not observe a protective effect of smoking on autoimmunity and the risk of LADA. A protective effect could possibly be masked by a smoking-induced aggravation of insulin resistance, akin to the diabetogenic effect seen in individuals with type 2 diabetes.

  • 27. Ringborg, A.
    et al.
    Lindgren, P.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Yin, D. D.
    Schön, S.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Prevalence and incidence of Type 2 diabetes and its complications 1996-2003: estimates from a Swedish population-based study2008In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 25, no 10, p. 1178-1186Article in journal (Refereed)
    Abstract [en]

    AIMS

    To determine the prevalence and incidence of Type 2 diabetes and its complications in Uppsala county, Sweden between 1996 and 2003.

    METHODS

    Retrospective population-based study of patients with Type 2 diabetes identified in computerized medical records at 26 county primary care centres. Prevalence and incidence of Type 2 diabetes were estimated in the population aged 30-39, 40-49, 50-59, 60-69, 70-79 and > or = 80 years. Mortality, prevalence and incidence of complications in patients with Type 2 diabetes were determined through linkage to national inpatient, uraemia and cause-of-death registers.

    RESULTS

    Crude prevalence of Type 2 diabetes increased from 2.2 to 3.5% between 1996 and 2003. In the population aged > or = 30 years, the age- and sex-adjusted period increase was 53%[odds ratio (OR) 1.53, 95% confidence interval (CI) 1.47-1.58]. Crude population incidence was approximately stable after 1997 (3.7 cases/1000 residents in 1997 compared with 3.8/1000 in 2003). Age- and sex-adjusted mortality rates in Type 2 diabetic patients decreased by 4% per year (OR 0.96, 95% CI 0.94-0.97). Prevalence rates of cardiovascular disease in Type 2 diabetic patients were essentially stable, affecting 13.8% of females and 18.0% of males in 2003. No trend was detected for prevalence of renal failure or incidence of acute myocardial infarction, stroke and amputation.

    CONCLUSIONS

    Prevalence of Type 2 diabetes increased in Uppsala county between 1996 and 2003 as a consequence of approximately stable incidence since 1997 and declining mortality. Rates of diabetes-related complications, notably cardiovascular disease, continued to impose a substantial burden.

  • 28. Ringborg, A.
    et al.
    Lindgren, P.
    Yin, D. D.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Time to insulin treatment and factors associated with insulin prescription in Swedish patients with type 2 diabetes2010In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 36, no 3, p. 198-203Article in journal (Refereed)
    Abstract [en]

    Aims. - The purpose of this study was to investigate the time between the start of OAD treatment and the initiation of insulin therapy and to identify the factors associated with insulin prescription among Swedish patients with type 2 diabetes in Uppsala County. Methods. - Retrospective, population-based, primary-care data gathered within the Swedish RECAP-DM study were used to identify type 2 diabetic patients who initiated OAD treatment. A Kaplan-Meier survival estimate for time to initiation of insulin therapy was generated and factors associated with insulin prescription were tested using a Cox proportional-hazards model. Results. - Within 6 years of starting OAD treatment, an estimated 25% of Swedish patients with type 2 diabetes will be prescribed insulin (95% CI: 0.23-0.26) and, within 10 years, this figure will rise to 42% (95% CI: 0.39-0.45). The probability of insulin prescription was increased in patients aged less than 65 years (HR = 1.24, 95% CI: 1.03-1.50) and in those who initiated OAD treatment with more than one agent (HR = 2.71, 95% CI: 2.15-3.43). HbA(1c) at the time of starting OAD treatment was also related to the probability of insulin prescription (HR = 1.20, 95% CI: 1.146-1.25). Conclusion. - Many type 2 diabetic patients who begin treatment with an OAD will eventually be prescribed insulin. An, disease severity and the type of prior treatment may affect the rate of the transition.

  • 29. Ringborg, A.
    et al.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Yin, D. D.
    Lindgren, P.
    Resource use and costs of type 2 diabetes in Sweden: estimates from population-based register data2008In: International journal of clinical practice (Esher), ISSN 1368-5031, E-ISSN 1742-1241, Vol. 62, no 5, p. 708-716Article in journal (Refereed)
    Abstract [en]

    AIMS

    To examine medical resource use of Swedish patients with type 2 diabetes during 2000-2004 and to estimate annual costs of care.

    METHODS

    Retrospective population-based cohort study of patients with type 2 diabetes identified in computerised medical records at 26 primary care centres in Uppsala county, Sweden. Annual quantities of medical resources were determined for prevalent cases during 2000-2004 using register data from outpatient primary care, outpatient hospital care, the National Inpatient Register and a national register for treatment of uraemia. Average costs of care of patients with type 2 diabetes were estimated based on year 2004 resource quantities of 8230 prevalent study cases.

    RESULTS

    Annual quantities of medical resource use were stable in outpatient primary care and outpatient hospital care, with patients making an average of two General Practitioner visits and 3.5 outpatient hospital visits each year. Higher rates of hospitalisation [12% in 2000 (n = 6711) compared with 16% in 2004 (n = 8230)] led to an increase in the mean (SD) number of inpatient days from 2.3 (11.8) to 2.7 (11.9) (p = 0.040) between 2000 and 2004. Mean (SD) total costs of care in 2004 were EUR 3602 (EUR 9537). Inpatient care was the major contributor to costs, accounting for 57% of total costs while drug costs accounted for an average 7%.

    CONCLUSIONS

    Swedish type 2 diabetic patients in this large sample from Uppsala county required steady annual amounts of outpatient care and increasing amounts of inpatient care during 2000-2004. The associated costs in 2004 were substantial, with inpatient care identified as the most important component.

  • 30. Ringborg, Anna
    et al.
    Yin, Donald D
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology.
    Lindgren, Peter
    The impact of acute myocardial infarction and stroke on health care costs in patients with type 2 diabetes in Sweden2009In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, no 5, p. 576-582Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Estimates of the economic impact of cardiovascular events in patients with type 2 diabetes are scarce. The aim of this study was to determine the health care costs associated with acute myocardial infarction (AMI) and stroke in patients with type 2 diabetes in Sweden. DESIGN: Population-based open cohort study of 9941 patients with type 2 diabetes retrospectively identified in primary care records at 26 centres in Uppsala County. METHODS: Episodes of AMI and stroke suffered by study patients were tracked in the Swedish National Inpatient Register. Annual per patient costs of health care were computed for the years 2000-2004 using register data covering inpatient care, outpatient hospital care, primary care and drugs. Panel data regression was applied to determine the impact of suffering a first or repeat AMI or stroke on health care costs during the year of the event and in subsequent years. RESULTS: Total health care costs of patients suffering a first AMI/stroke increased by 4.1/6.5 during the year of the event [95% confidence interval (CI): 3.1-5.4/4.9-8.5] and by 1.1/1.4 during subsequent years (95% CI: 1.0-1.3/1.2-1.6), controlling for age, sex, the event of amputation and presence of renal failure, heart failure and diabetic eye disease. Total health care costs of patients suffering a first or repeat AMI/stroke increased by 4.1/6.4 during the year of an event (95% CI: 3.2-5.2/5.0-8.1) but were not significantly higher during subsequent years. CONCLUSION: Estimates of the costs related to major cardiovascular complications of type 2 diabetes are critical input to economic evaluations.

  • 31.
    Singh, Kailash
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Luo, Zhengkang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Sandler, Stellan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Cellular immunological changes in patients with LADA are a mixture of those seen in patients with type 1 and type 2 diabetes2019In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 197, no 1, p. 64-73Article in journal (Refereed)
    Abstract [en]

    There is currently scarce knowledge of the immunological profile of patients with latent autoimmune diabetes mellitus in the adult (LADA) when compared with healthy controls (HC) and patients with classical type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective of this study was to investigate the cellular immunological profile of LADA patients and compare to HC and patients with T1D and T2D. All patients and age-matched HC were recruited from Uppsala County. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine the proportions of immune cells by flow cytometry. Plasma concentrations of the cytokine interleukin (IL)-35 were measured by enzyme-linked immunosorbent assay (ELISA). The proportion of CD11c(+)CD123(-) antigen-presenting cells (APCs) was lower, while the proportions of CD11c(+)CD123(+) APCs and IL-35(+) tolerogenic APCs were higher in LADA patients than in T1D patients. The proportion of CD3(-)CD56(high)CD16(+) natural killer (NK) cells was higher in LADA patients than in both HC and T2D patients. The frequency of IL-35(+) regulatory T cells and plasma IL-35 concentrations in LADA patients were similar to those in T1D and T2D patients, but lower than in HC. The proportion of regulatory B cells in LADA patients was higher than in healthy controls, T1D and T2D patients, and the frequency of IL-35(+) regulatory B cells was higher than in T1D patients. LADA presents a mixed cellular immunological pattern with features overlapping with both T1D and T2D.

1 - 31 of 31
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