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  • 1. Alvarsson, M
    et al.
    Sundkvist, G
    Lager, I
    Henricsson, M
    Berntorp, K
    Fernqvist-Forbes, E
    Steen, L
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Westermark, P
    Orn, T
    Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 8, p. 2231-2237Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment. RESEARCH DESIGN AND METHODS - ▀-Cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0-2 years before inclusion in a Swedish multicenter randomized clinical trial. Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5-10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2-3 days of temporary withdrawal of treatment. RESULTS - After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 ▒ 0.08 nmol/l, whereas it was decreased by 0.12 ▒ 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups. After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA1c levels decreased significantly during the first year in both groups, however, at the end of the second year, HbA1c had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA1c during the second year was significant between groups, P < 0.02 A questionnaire indicated no difference in well-being related to treatment. CONCLUSIONS - Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.

  • 2.
    Axelsson, Stina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Cheramy, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Åkerman, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Pihl, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Cellular and Humoral Immune responses in Type 1 Diabetic patients participating in a Phase III GAD-alum Intervention Trial2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 11, p. 3418-3424Article in journal (Refereed)
    Abstract [en]

    OBJECTIVEGAD formulated in aluminum hydroxide (GAD-alum) has previously been shown to induce preservation of residual insulin secretion in recent-onset type 1 diabetes, but recent phase II and III GAD-alum trials failed to reach primary outcomes. The European phase III study was therefore closed after 15 months, and only a minority of patients completed the 30 months of follow-up.RESEARCH DESIGN AND METHODSThis study aimed to characterize cellular and humoral responses in the Swedish patients (n = 148) participating in the phase III trial, receiving four (4D) or two (2D) GAD-alum doses or placebo. Serum GAD(65) antibody (GADA) levels, GADA IgG1-4 subclass distribution, cytokine secretion, and proliferative responses in peripheral blood mononuclear cells (PBMCs) were analyzed.RESULTSThe GAD(65)-induced cytokine profile tended to switch toward a predominant Th2-associated profile over time both in the 2D and 4D group. The groups also displayed increased GADA levels and PBMC proliferation compared with placebo, whereas GADA IgG subclass distribution changed in 4D patients.CONCLUSIONSBoth 2D and 4D patients displayed GAD(65)-specifc cellular and humoral effects after GAD-alum treatment, but at different time points and magnitudes. No specific immune markers could be associated with treatment efficacy.

  • 3.
    Besser, Rachel E J
    et al.
    University of Exeter, England .
    Shields, Beverley M
    University of Exeter, England .
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hattersley, Andrew T.
    University of Exeter, England .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Lessons From the Mixed-Meal Tolerance Test Use of 90-minute and fasting C-peptide in pediatric diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 2, p. 195-201Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Mixed-meal tolerance test (MMTT) area under the curve C-peptide (AUC CP) is the gold-standard measure of endogenous insulin secretion in type 1 diabetes but is intensive and invasive to perform. The 90-minMMTT-stimulated CP andgt;= 0.2 nmol/L (90CP) is related to improved clinical outcomes, and CP andgt;= 0.1 nmol/L is the equivalent fasting measure (FCP). We assessed whether 90CP or FCP are alternatives to a full MMTT. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-CP was measured during 1,334 MMTTs in 421 type 1 diabetes patients aged, 18 years at 3, 9, 18, 48, and 72 months duration. We assessed: 1) correlation between mean AUC CP and 90CP or FCP; 2) sensitivity and specificity of 90CP andgt;= 0.2 nmol/L and FCP andgt;= 0.1 nmol/L to detect peak CP andgt;= 0.2 nmol/L and the equivalent AUC CP; and 3) how the time taken to reach the CP peak varied with age of diagnosis and diabetes duration. less thanbrgreater than less thanbrgreater thanRESULTS-AUC CP was highly correlated to 90CP (r(s) = 0.96; P andlt; 0.0001) and strongly correlated to FCP (r(s) = 0.84; P andlt; 0.0001). AUC CP andgt;= 23 nmol/L/150 min was the equivalent cutoff for peak CP andgt;= 0.2 nmol/L (98% sensitivity/97% specificity). A 90CP andgt;= 0.2 nmol/L correctly classified 96% patients using AUC or peak CP, whereas FCP andgt;= 0.1 nmol/L classified 83 and 85% patients, respectively. There was only a small difference seen between peak and 90CP (median 0.02 nmol/L). The CP peak occurred earlier in patients with longer diabetes duration (6.1 min each 1-year increase in duration) and younger age (2.5 min each 1-year increase). less thanbrgreater than less thanbrgreater thanCONCLUSIONS-90CP is a highly sensitive and specific measure of AUC and peak CP in children and adolescents with type 1 diabetes and offers a practical alternative to a full MMTT. Diabetes Care 36:195-201, 2013

  • 4.
    Birkebaek, Niels H.
    et al.
    Aarhus Univ Hosp, Denmark.
    Hermann, Julia M.
    Univ Ulm, Germany; German Ctr Diabet Res, Germany.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Charalampopoulos, Dimitrios
    UCL, England.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Ctr Diabet Res, Germany.
    Skrivarhaug, Torild
    Oslo Univ Hosp, Norway.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Warner, Justin T.
    Childrens Hosp Wales, Wales.
    Drivvoll, Ann K.
    Oslo Univ Hosp, Norway.
    Svensson, Ann-Marie
    Reg Vastra Gotaland, Sweden.
    Stephenson, Terence
    UCL, England.
    Hofer, Sabine E.
    Med Univ Innsbruck, Austria.
    Fredheim, Siri
    Herlev Univ Hosp, Denmark.
    Kummernes, Siv J.
    Oslo Univ Hosp, Norway.
    Amin, Rakesh
    UCL, England.
    Rami-Merhar, Birgit
    Med Univ Vienna, Austria.
    Johansen, Anders
    Rigshosp, Denmark.
    Kapellen, Thomas M.
    Univ Childrens Hosp Leipzig, Germany.
    Hilgard, Doerte
    Pediat Diabetol Practice, Germany.
    Dahl-Jorgensen, Knut
    Univ Oslo, Norway; Univ Oslo, Norway.
    Froehlich-Reiterer, Elke
    Med Univ Graz, Austria.
    Fritsch, Maria
    Med Univ Vienna, Austria.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Svensson, Jannet
    Herlev Univ Hosp, Denmark.
    Letter: Center Size and Glycemic Control: An International Study With 504 Centers From Seven Countries in DIABETES CARE, vol 42, issue 3, pp E37-E392019In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 3, p. E37-E39Article in journal (Other academic)
    Abstract [en]

    n/a

  • 5.
    Bojestig, M
    et al.
    Linkoping Univ Hosp, Dept Med & Care, SE-58185 Linkoping, Sweden.
    Karlberg, BE
    Lindström, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes2001In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, no 5, p. 919-924Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Ramipril was administered double blind at two different doses(1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo [n = 18] after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55, women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA). RESULTS - Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups. CONCLUSIONS - Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated.

  • 6.
    Cardwell, Chris R
    et al.
    Queens University of Belfast, North Ireland .
    Stene, Lars C
    Norwegian Institute Public Heatlh, Norway Oslo University Hospital, Norway .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Rosenbauer, Joachim
    University of Dusseldorf, Germany .
    Cinek, Ondrej
    Charles University of Prague, Czech Republic University Hospital Motol, Czech Republic .
    Svensson, Jannet
    Herlev University Hospital, Denmark .
    Perez-Bravo, Francisco
    University of Chile, Chile .
    Memon, Anjum
    Brighton and Sussex Medical School and NHS Brighton and Hove, England .
    Gimeno, Suely G
    University of Federal Sao Paulo, Brazil .
    Wadsworth, Emma J K
    Cardiff University, Wales .
    Strotmeyer, Elsa S
    University of Pittsburgh, PA USA .
    Goldacre, Michael J
    University of Oxford, England .
    Radon, Katja
    Hospital Ludwig Maximilian University of Munich, Germany .
    Chuang, Lee-Ming
    National Taiwan University Hospital, Taiwan .
    Parslow, Roger C
    University of Leeds, England .
    Chetwynd, Amanda
    University of Lancaster, England .
    Karavanaki, Kyriaki
    University of Athens, Greece .
    Brigis, Girts
    Riga Stradins University, Latvia .
    Pozzilli, Paolo
    University of Campus Biomed, Italy .
    Urbonaite, Brone
    Lithuanian University of Health Science, Lithuania .
    Schober, Edith
    Medical University of Vienna, Austria .
    Devoti, Gabriele
    University of Salento, Italy .
    Sipetic, Sandra
    University of Belgrade, Serbia .
    Joner, Geir
    University of Oslo, Norway Oslo University Hospital, Norway .
    Ionescu-Tirgoviste, Constantin
    N Paulescu Institute Diabet, Romania .
    de Beaufort, Carine E
    Clin Pediat Luxembourg, Luxembourg .
    Harrild, Kirsten
    University of Aberdeen, Scotland .
    Benson, Victoria
    University of Oxford, England .
    Savilahti, Erkki
    University of Helsinki, Finland .
    Ponsonby, Anne-Louise
    Royal Childrens Hospital, Australia .
    Salem, Mona
    Ain Shams University, Egypt .
    Rabiei, Samira
    Shahid Beheshti University of Medical Science and Health Serv, Iran .
    C Patterson, Chris
    Queens University of Belfast, North Ireland .
    Breast-Feeding and Childhood-Onset Type 1 Diabetes A pooled analysis of individual participant data from 43 observational studies2012In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 35, no 11, p. 2215-2225Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. less thanbrgreater than less thanbrgreater thanRESULTS-Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for andgt;2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for andgt;3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for andgt;2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or andgt;3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I-2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for andgt;2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I-2 = 0%). Adjustments for potential confounders altered these estimates very little. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.

  • 7.
    Charalampopoulos, Dimitrios
    et al.
    UCL, England.
    Hermann, Julia M.
    Ulm Univ, Germany; German Ctr Diabet Res DZD, Germany.
    Svensson, Jannet
    Herlev Univ Hosp, Denmark.
    Skrivarhaug, Torild
    Oslo Univ Hosp, Norway.
    Maahs, David M.
    Stanford Univ, CA 94305 USA.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Warner, Justin T.
    Childrens Hosp Wales, Wales.
    Holl, Reinhard W.
    Ulm Univ, Germany; German Ctr Diabet Res DZD, Germany.
    Birkebaek, Niels H.
    Aarhus Univ Hosp, Denmark.
    Drivvoll, Ann K.
    Oslo Univ Hosp, Norway.
    Miller, Kellee M.
    Jaeb Ctr Hlth Res, FL USA.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden.
    Stephenson, Terence
    University College London, London, U.K..
    Hofer, Sabine E.
    Med Univ Innsbruck, Austria.
    Fredheim, Siri
    Herlev University Hospital, Herlev, Denmark.
    Kummernes, Siv J.
    Oslo Univ Hosp, Norway.
    Foster, Nicole
    Jaeb Ctr Hlth Res, FL USA.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Amin, Rakesh
    UCL, England.
    Rami-Merhar, Birgit
    Med Univ Vienna, Austria.
    Johansen, Anders
    Univ Copenhagen, Denmark.
    Dahl-Jorgensen, Knut
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Clements, Mark
    Childrens Mercy Hosp, MO 64108 USA; Univ Missouri Kansas City, MO USA; Univ Kansas, KS 66103 USA.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes2018In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 41, no 6, p. 1180-1187Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.

  • 8. Ekberg, Karin
    et al.
    Brismar, Tom
    Johansson, Bo-Lennart
    Lindström, Per
    Juntti-Berggren, Lisa
    Norrby, Anders
    Berne, Christian
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bolinder, Jan
    Wahren, John
    C-peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy2007In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 30, no 1, p. 71-76Article in journal (Refereed)
    Abstract [en]

    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. © 2007 by the American Diabetes Association.

  • 9.
    Elding Larsson, Helena
    et al.
    Lund University.
    Vehik, Kendra
    University of S Florida.
    Bell, Ronny
    Wake Forest University.
    Dabelea, Dana
    Colorado School Public Heatlh.
    Dolan, Lawrence
    University of Cincinnati.
    Pihoker, Catherine
    University of Washington.
    Knip, Mikael
    Tampere University Hospital.
    Veijola, Riitta
    University of Oulu.
    Lindblad, Bengt
    University of Gothenburg.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Holl, Reinhard
    University of Ulm.
    J Haller, Michael
    University of Florida.
    Reduced Prevalence of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Young Children Participating in Longitudinal Follow-Up2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 11, p. 2347-2352Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Young children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type I. diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged andlt;2 and andlt;5 years compared with population-based incidence studies and registries. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Symptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register). less thanbrgreater than less thanbrgreater thanRESULTS-A total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children andlt;2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P andlt; 0.0001; Swediabkids, P = 0.02; SEARCH, P andlt; 0.0001; Finnish Register, P andlt; 0.0001). The prevalence of DKA in TEDDY children diagnosed at andlt;5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) (P andlt; 0.0001) and the German DPV Register (32.2%) (P andlt; 0.0001) but not compared with Swediabkids or the Finnish Register. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-Participation in the TEDDY study is associated with reduced risk of DMA at diagnosis of type 1 diabetes in young children.

  • 10. Greenbaum, Carla
    et al.
    Mandrup-Poulsen, Thomas
    Friedenberg McGee, Paula
    Battelino, Tadej
    Haastert, Burkhard
    Ludvigsson, Johnny
    The Biostatistics Center, Rockville, Maryland.
    Pozzilli, Paolo
    Lachin, John M
    Kolb, Hubert
    and the European C-peptide Trial Study Group, The Type 1 Diabetes Trial Net Research Group
    Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 10, p. 1966-1971Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS: In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects completed 348 tests (up to 3 each) with either two MMTTs or two GSTs. RESULTS: Among individuals with up to 4 years' duration of type 1 diabetes, >85% had measurable stimulated C-peptide values. The MMTT stimulus produced significantly higher concentrations of C-peptide than the GST. Whereas both tests were highly reproducible, the MMTT was significantly more so (R(2) = 0.96 for peak C-peptide response). Overall, the majority of subjects preferred the MMTT, and there were few adverse events. Some older subjects preferred the shorter duration of the GST. Nausea was reported in the majority of GST studies, particularly in the young age-group. CONCLUSIONS: The MMTT is preferred for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.

  • 11.
    Hanberger, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindblad, Bengt
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    AlC in children and adolescents with diabetes in relation to certain clinical parameters - The Swedish Childhood Diabetes Registry SWEDIABKIDS2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 5, p. 927-929Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - We explored the relationship between AlC and insulin regimen, duration of diabetes, age, sex, and BMI as well as the differences between clinical mean AlC levels at pediatric diabetes clinics in Sweden. RESEARCH DESIGN AND METHODS - Data from 18,651 clinical outpatient visits (1,033 girls and 1,147 boys) at 20 pediatric clinics during 2001 and 2002 registered in the Swedish Childhood Diabetes Registry SWEDIABKIDS, a national quality registry, were analyzed. RESULTS - AlC was < 7.0% (target value similar to 8% per Diabetes Control and Complications Trial/National Glycohemoglobin Standardization Program standards) at 35% of the visits. Girls had significantly higher mean AlC than boys during adolescence. High mean AlC was correlated with high mean insulin dose, long duration of diabetes, and older age. Mean AlC varied between clinics (6.8-8.2%). Differences between centers could not be explained by differences in diabetes duration, age, BMI, or insulin dose. CONCLUSIONS - Adolescents with a high insulin dose and a long duration of diabetes, especially girls, need to be focused on, Differences in mean values between centers remained inexplicable and require further investigation.

  • 12.
    Hanås, Ragnar
    et al.
    Department of Pediatrics, Uddevalla Hospital, Uddevalla.
    Carlsson, Sten
    Department of Medical Physics, Uddevalla Hospital, Uddevalla.
    Frid, Anders
    Department of Internal Medicine, University of Lund, Lund.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Unchanged Insulin Absorption After 4 Days' Use of Subcutaneous Indwelling Catheters for Insulin Injections1997In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 20, no 4, p. 487-490Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Since 1985, we have used indwelling catheters (Insuflon, Maersk Medical, Lynge, Denmark; Chronimed, Minnetonka, MN) to lessen pain when injecting insulin. However, some patients experience a rise in blood glucose after using indwelling catheters for a few days. We therefore studied the absorption of 125I-labeled insulin when using indwelling catheters.

    RESEARCH DESIGN AND METHODS Five men and five women participated (age 18–25 years, C-peptide negative, HbA1c 9.0 ± 1.0% [mean ± SD, DCA-2000 method], diabetes duration 5–21 [median 9.5] years). After thyroid blockage with potassium iodide, we injected 5IU of 125I-labeled short-acting insulin subcutaneously in the abdomen (“ordinary injection”) and 5 IU on the contralateral side through an indwelling catheter (“catheter injection”). The injection/insertion area was free of lipohyper- and lipohypotrophies. Disappearance rate was measured for 180 min with a gamma camera. The patients injected all premeal injections of short-acting insulin through the same indwelling catheter in the following 4 days. The investigation procedure was repeated day 3 and 5.

    RESULTS We found no statistically or clinically (95% CI) significant difference in residual activity of 125I-insulin after 60 min or in time for 50% of the injected depot to disappear (T-50%) among catheter injections on day 1, 3, and 5; ordinary injections on days 1, 3, and 5; or catheter and ordinary injections on days 1, 3, and 5, respectively. HbA1c correlated both to T-50% (r = 0.73, P = 0.016) and residual activity of 125I-insulin after 60 min (r = 0.69, P = 0.028), indicating that patients with a slower absorption will have a less ideal metabolic control when using premeal bolus injections.

    CONCLUSIONS We conclude that using indwelling subcutaneous catheters for insulin injections for up to 4 days does not affect the absorption of short-acting insulin.

  • 13.
    Hanås, Ragnar
    et al.
    Department of Pediatrics, Uddevalla Hospital, Uddevalla.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Metabolic Control Is Not Altered When Using Indwelling Catheters for Insulin Inactions1994In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 17, no 7, p. 716-718Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To determine if the use of indwelling catheters for insulin injections affects the long- and short-term metabolic control of insulin-dependent diabetes mellitus (IDDM).

    RESEARCH DESIGN AND METHODS Sixteen children and adolescents 9–20 years of age were included in a randomized 10-week crossover study using indwelling catheters (Insuflon, Pharma-Plast, Lynge, Denmark; CHRONIMED, Minnetonka, Minnesota) for insulin injections. Their diabetes duration was 7.5 ± 3.3 years (range 2–14), and they used multiple injection therapy with 4–5 doses/day. C-peptide was <0.15 nM fasting and ≤0.30 nM postprandial.

    RESULTS We found no significant difference between those with and without Insuflon in degree of metabolic control reflected by HbA1c (with Insuflon, 7.3 ± 2.6%; without, 7.1 ± 2.2%), 24-h profiles of blood glucose and free insulin, 24-h samples of glucosuria, or ketonuria. Weight, insulin doses per kilogram per 24 h, and insulin antibodies were all the same in the two groups.

    CONCLUSIONS The long- and short-term metabolic control of IDDM was not altered by the use of indwelling catheters for insulin injections. Insuflon can be offered as an alternative to patients with IDDM who find regular injections uncomfortable.

  • 14.
    Hedman, Christina
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Direct comparison of insulin lispro and aspart shows small differences in plasma insulin profiles after subcutaneous injection in type 1 diabetes2001In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, p. 1120-1121Article in journal (Refereed)
    Abstract [en]

    No abstract available.

  • 15. Henricsson, Marianne
    et al.
    Nyström, Lennarth
    Blohmé, Göran
    Östman, Jan
    Kullberg, Carin
    Svensson, Maria
    Schölin, Anna
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Björk, Elisabeth
    Bolinder, Jan
    Eriksson, Jan
    Sundkvist, Göran
    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)2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 2, p. 349-354Article in journal (Refereed)
    Abstract [en]

    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.

  • 16.
    Hyllienmark, Lars
    et al.
    Karolinska Institute, Sweden .
    Alstrand, Nils
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Jonsson, Bjorn
    Uppsala University, Sweden .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Cooray, Gerald
    Karolinska Institute, Sweden .
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Early Electrophysiological Abnormalities and Clinical Neuropathy A prospective study in patients with type 1 diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 10, p. 3187-3194Article in journal (Refereed)
    Abstract [en]

    OBJECTIVEThe aim of this study was to elucidate whether subclinical nerve dysfunction as reflected by neurophysiological testing predicts the development of clinical neuropathy in patients with type 1 diabetes.RESEARCH DESIGN AND METHODSFifty-nine patients were studied twice with neurophysiological measurements at baseline and at follow-up. At baseline, patients were 15.5 3.22 years (range 7-22 years) of age, and duration of diabetes was 6.8 3.3 years. At follow-up, patients were 20-35 years of age, and disease duration was 20 +/- 5.3 years (range 10-31 years).RESULTSAt baseline, patients showed modestly reduced nerve conduction velocities and amplitudes compared with healthy subjects, but all were free of clinical neuropathy. At follow-up, clinical neuropathy was present in nine (15%) patients. These patients had a more pronounced reduction in peroneal motor nerve conduction velocity (MCV), median MCV, and sural sensory nerve action potential at baseline (P andlt; 0.010-0.003). In simple logistic regression analyses, the predictor with the strongest association with clinical neuropathy was baseline HbA(1c) (R-2 = 48%, odds ratio 7.9, P andlt; 0.002) followed by peroneal MCV at baseline (R-2 = 38%, odds ratio 0.6, P andlt; 0.006). With the use of a stepwise forward analysis that included all predictors, first baseline HbA(1c) and then only peroneal MCV at baseline entered significantly (R-2 = 61%). Neuropathy impairment assessment showed a stronger correlation with baseline HbA(1c) ( = 0.40, P andlt; 0.002) than with follow-up HbA(1c) ( = 0.034, P andlt; 0.007).CONCLUSIONSEarly defects in nerve conduction velocity predict the development of diabetic neuropathy. However, the strongest predictor was HbA(1c) during the first years of the disease.

  • 17. Johansson, Unn-Britt
    et al.
    Amsberg, Susanne
    Hannerz, Lena
    Wredling, Regina
    Adamson, Ulf
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Lins, Per-Eric
    Impaired absorption of insulin aspart from lipohypertrophic injection sites2005In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 8, p. 2025-2027Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 18.
    Lindenberger, Marcus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindström, Torbjörn
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Decreased circulatory response to hypovolemic stress in young women with type 1 diabetes2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 12, p. 4076-4082Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Diabetes is associated with hemodynamic instability during different situations involving acute circulatory stress in daily life. Young men with type 1 diabetes have been shown to have impaired circulatory response to hypovolemic stress. The effect of type 1 diabetes on cardiovascular response to hypovolemia in young women is unknown, however.

    RESEARCH DESIGN AND METHODS:

    Lower body negative pressure of 30 cm H2O was used to create rapid hypovolemic stress in 15 young women with type 1 diabetes (DW) and 16 healthy women (control subjects [C]). Compensatory mobilization of venous capacitance blood (capacitance response) and net fluid absorption from tissue to blood were measured with a volumetric technique. Overall cardiovascular responses and plasma norepinephrine levels were measured.

    RESULTS:

    Capacitance response was reduced (DW, 0.67 ± 0.05; C, 0.92 ± 0.06) and developed slower in DW (P < 0.01). Capacitance response was further reduced with increasing levels of HbA1c. Fluid absorption was almost halved in DW (P < 0.01). The initial vasoconstrictor response was reduced and developed slower in DW (P < 0.05). Arterial vasoconstriction was further reduced in the presence of microvascular complications (P < 0.05).

    CONCLUSIONS:

    DW present with decreased and slower mobilization of venous capacitance blood and decreased net fluid absorption from tissue to blood during hypovolemic circulatory stress. Collectively, this indicates that DW are prone to hemodynamic instability, especially in the presence of microvascular complications and poor glycemic control.

  • 19.
    Lindström, Torbjörn
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Hedman, Christina
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Use of a novel double-antibody technique to describe the pharmacokinetics of rapid-acting insulin analogs2002In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 25, no 6, p. 1049-1054Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE—To measure the contribution of bedtime intermediate-acting human insulin on the morning plasma insulin profiles after injection of the rapid-acting insulin analogs lispro and aspart in patients with type 1 diabetes.

    RESEARCH DESIGN AND METHODS—A total of 14 patients with type 1 diabetes, aged 35 ± 13 years (mean ± SD), participated in this single-blind, randomized crossover study. After taking their usual injection of human intermediate-acting insulin the night before, they were given insulin aspart or insulin lispro (10 units) before a standardized breakfast. The contribution of continuing absorption of the human insulin was measured using a monoclonal antibody not cross-reacting with insulin aspart or lispro, whereas the contribution of the analogs was estimated by subtraction after measurement of all plasma free insulin using an antibody cross-reacting equally with human insulin and both analogs.

    RESULTS—The correlation coefficient of the fasting free insulin concentrations measured with both insulin methods was 0.95. Fasting free insulin was 95 ± 25 pmol/l before administration of insulin aspart, when determined with enzyme-linked immunosorbent assay detecting only human insulin, and 71 ± 20 pmol/l before administration of insulin lispro (NS). Both insulin analogs gave marked peaks of free insulin concentrations, lispro at 40 ± 3 min and aspart at 55 ± 6 min after injection (P = 0.01). The later part of the profiles, from 4.5 to 5.5 h after injection, were similar and showed almost no contribution of the insulin analogs.

    CONCLUSIONS—The combination of insulin assays that detect human insulin only or both human insulin and analogs provides a new tool for studying insulin pharmacokinetics. Using this technique, we showed that 4.5 h after administration of the rapid-acting insulin analogs lispro and aspart, the free insulin levels are almost only attributable to the intermediate-acting insulin given at bedtime.

  • 20. Littorin, B
    et al.
    Sundkvist, G
    Hagopian, W
    Landin-Olsson, M
    Lernmark, Å
    Östman, J
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Lithner, F
    Scherstén, B
    Wibell, L
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Islet cell and glutamic acid decarboxylase antibodies present at diagnosis of diabetes predict the need for insulin treatment.1999In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 22, p. 409-412Article in journal (Refereed)
  • 21. Littorin, Bengt
    et al.
    Sundkvist, Göran
    Nyström, Lennarth
    Carlson, Anita
    Landin-Olsson, Mona
    Östman, Jan
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Björk, Elisabeth
    Blohmé, Göran
    Bolinder, Jan
    Eriksson, Jan W
    Scherstén, Bengt
    Wibell, Lars
    Family characteristics and life events before the onset of autoimmune type 1 diabetes in young adults: A nationwide study2001In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 24, no 6, p. 1033-1037Article in journal (Refereed)
    Abstract [en]

    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.

  • 22.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Increasing Incidence but Decreasing Awareness of Type 1 Diabetes in Sweden2017In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 40, no 10, p. E143-E144Article in journal (Other academic)
    Abstract [en]

    n/a

  • 23.
    Ludvigsson, Jonas
    et al.
    Dept of Pediatrics, University Hospital Örebro.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ekbom, Anders
    Montgomery, SM
    Celiac disease and risk of subsequent type 1 diabetes: A general population cohort study of children and adolescents2006In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 29, no 11, p. 2483-2488Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - Earlier studies suggest that children with type 1 diabetes are more likely to have a subsequent diagnosis of celiac disease. However, research is sparse on the risk of subsequent type 1 diabetes in individuals with celiac disease. We sought to determine the risk of subsequent type 1 diabetes diagnosed before the age of 20 years in children and adolescents with celiac disease in a national, general population-based cohort. RESEARCH DESIGN AND METHODS - We identified 9,243 children with a diagnosis of celiac disease in the Swedish national inpatient register between 1964 and 2003. We then identified five reference individuals matched at time of diagnosis for age, calendar year, sex, and county (n = 45,680). Only individuals with >1 year of follow-up after study entry (diagnosis of celiac disease) were included in the analyses. RESULTS - Celiac disease was associated with a statistically significantly increased risk of subsequent type 1 diabetes before age 20 years (hazard ratio 2.4 [95% CI 1.9-3.0], P > 0.001). This risk increase was seen regardless of whether celiac disease was first diagnosed between 0 and 2 (2.2 [1.7-2.9], P > 0.001) or 3 and 20 (3.4 [1.9-6.1], P < 0.001) years of age. Individuals with prior celiac disease were also at increased risk of ketoacidosis or diabetic coma before the age of 20 years (2.3 [1.4-3.9], P = 0.001). CONCLUSIONS - Children with celiac disease are at increased risk of subsequent type 1 diabetes. This risk increase is low considering that 95% of individuals with celiac disease are HLA-DQ2 positive. © 2006 by the American Diabetes Association.

  • 24.
    Malmstedt, Jonas
    et al.
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Leander, Karin
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wahlberg, Eric
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Karlström, Lars
    Department of Vascular Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Alfredsson, Lars
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Swedenborg, Jesper
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Outcome after leg bypass surgery for critical limb ischemia is poor in patients with diabetes2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 5, p. 887-892Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE—Our aim was to assess the risk of major amputation or death after leg bypass surgery for critical limb ischemia in patients with diabetes versus those without.

    RESEARCH DESIGN AND METHODS—We did a population-based cohort study by linking nationwide databases in Sweden. We identified 1,840 patients in the Swedish Vascular Registry who had their first leg bypass procedure for critical lower-limb ischemia between 1 January 2001 and 31 December 2003—742 with and 1,098 without diabetes. Our primary end point was first major amputation of the limb on which bypass was done or death. Individuals were followed up until 31 December 2005 through the National Hospital Patient Registry and the Cause-of-Death Registry.

    RESULTS—Incidence of ipsilateral amputation or death was higher in patients with diabetes than in patients without (30.2 vs. 22 events/100 person-years; crude hazard ratio [HR] 1.32 [95% CI 1.17–1.50]). Similarly, individuals with diabetes had a shorter amputation-free survival period than individuals without (2.3 years, range 1.9–2.8 vs. 3.4 years, range 3.1–3.7). Adjustment for demographic characteristics, comorbidities, and risk factors for amputation or death did not substantially affect the risk (HR 1.46 [95% CI 1.26–1.69]). The effect was more pronounced in male (1.75 [1.47–2.08]) than in female (1.35 [1.11–1.64]) patients after adjustment for age.

    CONCLUSIONS—Diabetes is associated with lower amputation–free survival after leg bypass for critical limb ischemia. Patients with diabetes and limb ischemia need intensified treatment of diabetes-related risk factors to improve outcome.

  • 25.
    Mollazadegan, Kaziwe
    et al.
    Karolinska Institutet, Stockholm, Sweden .
    Kugelberg, Maria
    St. Erik Eye Hospital, Karolinska Institutet, Stockholm, Sweden .
    Montgomery, Scott M.
    Karolinska Institutet, Stockholm, Sweden and Örebro University Hospital, Örebro, Sweden .
    Sanders, David S.
    Royal Hallamshire Hospital and University of Sheffield, Sheffield, U.K. .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Jonas
    Karolinska Institutet, Stockholm, Sweden and Örebro University Hospital.
    A Population-Based Study of the Risk of Diabetic Retinopathy in Patients With Type 1 Diabetes and Celiac Disease2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 2, p. 316-321Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Celiac disease (CD) is associated with type 1 diabetes (T1D). In the current study, we examined whether CD affects the risk of diabetic retinopathy (DRP) in patients with T1D.

    RESEARCH DESIGN AND METHODS This was a population-based cohort study. Through the Swedish National Patient Register, we identified 41,566 patients diagnosed with diabetes in 1964–2009 and who were ≤30 years of age at diagnosis. CD was defined as having villous atrophy (Marsh stage 3) according to small intestinal biopsies performed between 1969 and 2008, with biopsy reports obtained from Sweden’s 28 pathology departments. During follow-up, 947 T1D patients had a diagnosis of CD. We used Cox regression analysis with CD as a time-dependent covariate to estimate adjusted hazard ratios (aHRs) for DRP in patients with T1D and CD and compared them with patients with T1D but no CD.

    RESULTS Duration of CD correlated with the risk of DRP. When results were stratified by time since CD diagnosis, individuals with T1D and CD were at a lower risk of DRP in the first 5 years after CD diagnosis (aHR 0.57 [95% CI 0.36–0.91]), followed by a neutral risk in years 5 to <10 (1.03 [0.68–1.57]). With longer follow-up, coexisting CD was a risk factor for DRP (10 to <15 years of follow-up, aHR 2.83 [95% CI 1.95–4.11]; ≥15 years of follow-up, 3.01 [1.43–6.32]).

    CONCLUSIONS Having a diagnosis of CD for >10 years is a risk factor for the development of DRP in T1D. Long-standing CD in patients with T1D merits intense monitoring of DRP.

  • 26.
    Nordfeldt, Sam
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Child and Adolescent Psychiatry. Östergötlands Läns Landsting, CPS - Centrum för psykiatri och samhällsmedicin, BUP - Barn- och ungdomspsykiatri.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Serum ACE predicts severe hypoglycemia in children and adolescents with type 1 diabetes2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 2, p. 274-278Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - To investigate whether risk of severe hypoglycemia is related to serum (S) ACE level during intensive treatment in type 1 diabetic children. RESEARCH DESIGN AND METHODS - A cohort of 86 intensively treated type 1 diabetic patients was studied during 1999-2000. In 1999, the age range was 7-19 years (median 12.8), diabetes duration was 1.2-14.7 years (5.3), insulin dose was 0,4-1.7 units ╖ kg-1 ╖ 24 h-1 (1.0), and the HbA1c year mean was 4.7-10.2% (6.8). HbA1c, insulin doses, and events of severe hypoglycemia (needing assistance from another person) were prospectively registered at regular visits, scheduled quarterly. S-ACE was determined once. RESULTS - Severe hypoglycemia was correlated to S-ACE (r = 0.22, 95% CI 0.0I-0.41, P = 0.0093). The square root of severe hypoglycemia was correlated to S-ACE (r = 0.27, 95% CI 0.06-0.45, P = 0.0093). Patients with S-ACE at the median level or above (n = 44) reported a mean of 3.0 yearly events of severe hypoglycemia compared with 0.5 events in patients with S-ACE lower than the median (n = 42) (P = 0.0079). Of the patients with an S-ACE at the median level or above, 27 (61%) reported severe hypoglycemia, compared with 17 (40%) patients with an S-ACE lower than the median (P = 0.0527). Insulin dose, HbA1c, age, onset age, duration, C-peptide, and sex did not differ between these two groups. S-ACE was negatively correlated with age (r = -0.27, 95% CI -0.46 to 0.07, P = 0.0265) but not with HbA1c, duration, or blood pressure. CONCLUSIONS - The elevated rate of severe hypoglycemia among patients with higher S-ACE suggests, among other factors, that a genetic determinant for severe hypoglycemia exists. Further evaluation is needed before the clinical usefulness of this test can be elucidated.

  • 27.
    Nordwall, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Abrahamsson, Mariann
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Norrköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dhir, Meryl
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Norrköping.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Impact of HbA(1c), Followed From Onset of Type 1 Diabetes, on the Development of Severe Retinopathy and Nephropathy: The VISS Study (Vascular Diabetic Complications in Southeast Sweden)2015In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, no 2, p. 308-315Article in journal (Refereed)
    Abstract [en]

    OBJECTIVEHbA(1c) is strongly related to the development of diabetes complications, but it is still controversial which HbA(1c) level to strive for in the treatment of type 1 diabetes. The aim of the current study was to evaluate HbA(1c), followed from diagnosis, as a predictor of severe microvascular complications and to formulate HbA(1c) target levels for treatment.RESEARCH DESIGN AND METHODSA longitudinal observation study followed an unselected population of 451 patients diagnosed with type 1 diabetes during 1983-1987 before the age of 35 years in a region of Southeast Sweden. Retinopathy was evaluated by fundus photography and nephropathy data collected from medical records. HbA(1c) was measured starting from diagnosis and during the whole follow-up period of 20-24 years. Long-term weighted mean HbA(1c) was then calculated. Complications were analyzed in relation to HbA(1c) levels.RESULTSThe incidence of proliferative retinopathy and persistent macroalbuminuria increased sharply and occurred earlier with increasing long-term mean HbA(1c). None of the 451 patients developed proliferative retinopathy or persistent macroalbuminuria below long-term weighted mean HbA(1c) 7.6% (60 mmol/mol); 51% of the patients with long-term mean HbA(1c) above 9.5% (80 mmol/mol) developed proliferative retinopathy and 23% persistent macroalbuminuria.CONCLUSIONSLong-term weighted mean HbA(1c), measured from diagnosis, is closely associated with the development of severe complications in type 1 diabetes. Keeping HbA(1c) below 7.6% (60 mmol/mol) as a treatment target seems to prevent proliferative retinopathy and persistent macroalbuminuria for up to 20 years.

  • 28.
    Nordwall, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Norrköping.
    Abrahamsson, Mariann
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Norrköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dhir, Meryl
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Norrköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Arnqvist, Hans J.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Comment: Response to Comment on Nordwall et al. Impact of HbA1c, Followed From Onset of Type 1 Diabetes, on the Development of Severe Retinopathy and Nephropathy: The VISS Study (Vascular Diabetic Complications in Southeast Sweden). Diabetes Care 2015;38:308-3152015In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, no 8, p. e124-Article in journal (Other academic)
    Abstract [en]

    We thank Dr. Takahara (1) for the comment on our recent article exploring the impact of HbA1c, followed from diabetes onset, on the development of severe microvascular complications (2). As suggested, we have validated our results with Cox hazards analysis with severe microvascular events, i.e., laser-treated proliferative retinopathy and macroalbuminuria as a dependent variable and HbA1c (mmol/mol) as a time-dependent covariate.

    For laser-treated proliferative retinopathy, we found a hazard ratio of 1.038 (95% CI 1.025–1.052, P < 0.001) and for macroalbuminuria, a hazard ratio of 1.075 (95% CI 1.050–1.100, P < 0.001).

    Analyzing our data with Cox hazards analysis thus shows the strong influence of long-term HbA1c on severe microvascular complications, in agreement with our previous conclusions.

    In our article, we chose to analyze and present the results in a way that was perhaps easier for a clinician to interpret and apply in clinical routine. With life-table analysis we found that the incidence of both laser-treated proliferative retinopathy and macroalbuminuria increased sharply and occurred earlier with increasing long-term weighted mean HbA1c. In the same manner, the prevalence of microvascular complications increased steeply with higher long-term weighted mean HbA1c, categorized in different groups.

    In conclusion, our study irrespective of statistical methods shows a strong association between development of late complications and long-term mean HbA1c, and keeping the average HbA1c below 7.6% (60 mmol/mol) seemed sufficient to prevent microvascular complications for at least up to 20 years.

  • 29.
    Schwartz, G.G.
    et al.
    Cardiology Section, VA Medical Center, Denver, CO, United States, University of Colorado Health Sciences Center, Denver, CO, United States, Denver VA Medical Center (111B), Denver, CO 80220, United States.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Szarek, M.
    Pfizer, New York, NY, United States.
    Sasiela, W.J.
    Pfizer, New York, NY, United States.
    Relation of characteristics of metabolic syndrome to short-term prognosis and effects of intensive statin therapy after acute coronary syndrome: An analysis of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial2005In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 10, p. 2508-2513Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - We examined relations between characteristics of the metabolic syndrome, early cardiovascular risk, and effect of early, intensive statin therapy after acute coronary syndrome. RESEARCH DESIGN AND METHODS - A total of 3,038 patients in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial were characterized by the presence or absence of a history of diabetes, a history of hypertension and/or blood pressure =130/=85, BMI > 30 kg/m2, HDL cholesterol <40 mg/dl (men) or <50 mg/dl (women), and triglycerides =150 mg/dl. Patients with three or more of these characteristics were categorized as having metabolic syndrome. RESULTS - A total of 38% of patients (n = 1,161) met criteria for metabolic syndrome as defined in this study and had a 19% incidence of a primary end point event (death, nonfatal myocardial infarction, cardiac arrest, or recurrent unstable myocardial ischemia) during the 16-week trial. Patients with two or fewer characteristics (n = 1,877) were classified as not having metabolic syndrome and had a 14% incidence of a primary end point event. In univariate analysis, the individual characteristics that bore a significant relation to risk were diabetes and low HDL cholesterol. In a multivariable model including age, sex, and randomized treatment assignment, presence of metabolic syndrome was associated with a hazard ratio of 1.49 (95% Cl 1.24-1.79, P < 0.0001). Relative risk reduction with 80 mg atorvastatin daily compared with placebo was similar in patients with and without metabolic syndrome. CONCLUSIONS - Metabolic syndrome, as defined in the context of this clinical trial, is a strong predictor of early recurrent ischemic events after acute coronary syndrome. © 2005 by the American Diabetes Association.

  • 30.
    Sepa, Anneli
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Frodi, Ann
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Mothers' experiences of serious life events increase the risk of diabetes-related autoimmunity in their children2005In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 10, p. 2394-2399Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE—Stressful life events have been shown to constitute a risk factor for type 1 diabetes during childhood. Our aim was to investigate in the general child population (i.e., irrespective of genetic risk for type 1 diabetes) whether mothers’ experiences of serious life events, such as divorce and violence, were associated with diabetes-related autoimmunity in their children at age 2.5 years.

    RESEARCH DESIGN AND METHODS—The study cohort was comprised of the first 5,986 consecutive children and their families from the prospective population-based All Babies in Southeast Sweden project for whom 2.5-year study data were available. Data were drawn from parental questionnaires that included questions about experiences of serious life events and the blood samples taken from the children when the children were age 2.5 years. The blood samples were analyzed for diabetes-related autoantibodies against tyrosine phosphatase and GAD.

    RESULTS—Mothers’ experiences of divorce (odds ratio 3.6, 95% CI 1.4–9.6, P < 0.05) and violence (2.9, 1.0–7.8, P < 0.05) were associated with diabetes-related autoimmunity in the children, independent of a family history of type 1 diabetes.

    CONCLUSIONS—The results support the ß-cell stress hypothesis and suggest that maternal experiences of serious life events such as divorce and violence seem to be involved in the induction or progression of diabetes-related autoimmunity in children at age 2.5 years, independent of family history of type 1 diabetes.

  • 31.
    Sepa, Anneli
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Frodi, Ann
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Psychological stress may induce diabetes-related autoimmunity in infancy2005In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 28, no 2, p. 290-295Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE— In retrospective studies, a number of disparate environmental factors (including experiences of serious life events) have been proposed as trigger mechanisms for type 1 diabetes or the autoimmune process behind the disease. Psychosocial stress in families may affect children negatively due to a link to hormonal levels and nervous signals that in turn influence both insulin sensitivity/insulin need and the immune system. Our aim was to investigate whether psychological stress, measured as psychosocial strain in families, is associated with diabetes-related autoimmunity during infancy.

    RESEARCH DESIGN AND METHODS— The first 4,400 consecutive 1-year-old children from a large prospective population-based project participated in the study. Parents completed questionnaires at birth and at 1 year, including various measures of psychosocial stress (e.g., parenting stress) and sociodemographic background. Blood samples drawn from the children at 1 year were analyzed for type 1 diabetes–associated autoantibodies toward tyrosine phosphatase and GAD. Antibodies toward tetanus toxoid were used as non–diabetes-related control antibodies.

    RESULTS— Psychosocial factors, i.e., high parenting stress (odds ratio 1.8 [95% CI 1.2–2.9], P < 0.01), experiences of a serious life event (2.3 [1.3–4.0], P < 0.01), foreign origin of the mother (2.1 [1.3–3.3], P < 0.001), and low paternal education (1.6 [1.1–2.3], P < 0.01) were associated with diabetes-related autoimmunity in the child, independent of family history of diabetes.

    CONCLUSIONS— Psychological stress, measured as psychosocial strain in the family, seems to be involved in the induction, or progression, of diabetes-related autoimmunity in the child during the 1st year of life.

  • 32.
    Shields, Beverley M
    et al.
    University of Exeter, England .
    Henley, William
    University of Exeter, England .
    Besser, Rachel E J
    University of Exeter, England .
    Hattersley, Andrew T
    University of Exeter, England .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Letter: Response to Comment on: Besser et al. Lessons From the Mixed-Meal Tolerance Test: Use of 90-Minute and Fasting C-Peptide in Pediatric Diabetes.2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 12, p. E222-E222Article in journal (Other academic)
    Abstract [en]

    n/a

  • 33. Svensson, Maria
    et al.
    Sundqvist, Göran
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MC - Medicincentrum, EMT-endo.
    Björk, Elisabeth
    Blohmé, Göran
    Bolinder, Jan
    Henricsson, Marianne
    Nyström, Lennarth
    Torffvit, Ole
    Waernbaum, Ingeborg
    Östman, Jan
    Eriksson, Jan W
    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)2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 10, p. 2903-2909Article in journal (Refereed)
    Abstract [en]

    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.

  • 34.
    Wilkin, Terry
    et al.
    Department of Endocrinology and Metabolism, Peninsula Medical School, Plymouth, U.K..
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Greenbaum, Carla
    Department of Diabetes, Benaroya Research Institute, Seattle, Washington, USA.
    Palmer, Jerry
    Department of Diabetes, VA Medical Center, Seattle, Washington, USA.
    Becker, Dorothy
    Department of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
    Bruining, Jan
    Department of Pediatrics, Sophia Children’s Hospital, Rotterdam, the Netherlands.
    Future intervention trials in type 1 diabetes2004In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 27, no 4, p. 996-997Article in journal (Other academic)
    Abstract [en]

    n/a

  • 35.
    Örtqvist, Eva
    et al.
    Astrid Lindgrens Barnsjukhus Stockholm.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Åman, Jan
    Barnkliniken Universitetssjukhuset, Örebro.
    Johansson, Calle
    Barnkliniken Ryhovs sjukhus, Jönköping.
    Karlsson, Anders
    Medicinkliniken Akademiska sjukhuset, Uppsala.
    Forsander, Gun
    Barnkliniken Lasarettet, Falun.
    Lindgren, Fredrik
    Sachsska Barnsjukhuset Stockholm.
    Persson, Bengt
    Astrid Lindgrens Barnsjukhus Stockholm.
    Berglund, Lars
    Clinical Research Centre Uppsala Universitet.
    Berne, Christian
    Medicinkliniken Akademiska sjukhuset, Uppsala.
    Bengtsson, Mats
    Klinisk Immunologi Uppsala Universitet.
    Björk, Elisabeth
    Medicinkliniken Akademiska sjukhuset, Uppsala.
    Wallensteen, Måna
    Astrid Lindgrens Barnsjukhus Stockholm.
    Temporary preservation of β-cell function by diazoxide treatment in childhood type 1 diabetes2004In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 27, no 9, p. 2191-2197Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - We examined the effect of diazoxide, an ATP-sensitive K + channel opener and inhibitor of insulin secretion, on β-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS - A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years. RESULTS - Diazoxide decreased circulating C-peptide concentrations by ∼50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 ± 0.22 vs. 0.31 ± 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. Placebo-treated patients (-0.05 ± 0.24 vs. -0.18 ± 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 ± 0.20 and 0.20 ± 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent. CONCLUSIONS - This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of β-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.

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