liu.seSearch for publications in DiVA
Change search
Refine search result
123 51 - 100 of 105
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Johansson, Git S
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans J
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Insulin and IGF-I action on insulin receptors, IGF-I receptors, and hybrid insulin/IGF-I receptors in vascular smooth muscle cells2006In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 291, no 5, p. 1124-1130Article in journal (Refereed)
    Abstract [en]

    Insulin and insulin-like growth factor I (IGF-I) are known to affect cardiovascular disease. We have investigated ligand binding and the dose-response relationship for insulin and IGF-I on vascular smooth muscle cells (VSMCs) at the receptor level. VSMCs from rat thoracic aorta were serum starved, stimulated with IGF-I or insulin, lysed, immunoprecipitated, and analyzed by Western blot. D-[U-14C]Glucose accumulation and [6-3H]thymidine incorporation into DNA were also measured. Specific binding of both insulin and IGF-I was demonstrated, being higher for IGF-I. Both IGF-I receptor (IGF-IR) and insulin receptor (IR) β-subunits were detected and coprecipitated after immunoprecipitation (IP) against either of the two. No coprecipitation was found after reduction of disulphide bonds with dithiotreitol before IP. After stimulation with 10–10–10–9 M IGF-I, IP of the IGF-IR, or IR β-subunit and immunoblot with anti-phosphotyrosine antibody, we found two distinct bands indicating phosphorylation of both the IGF-IR and the IR β-subunit. Stimulation with 10–10–10–9 M insulin and IP against the IGF-IR did not show phosphorylation of either β-subunit, whereas after IP of the IR we found phosphorylation of the IR β-subunit. [14C]Glucose accumulation and [3H]thymidine incorporation were elevated in cells stimulated with IGF-I at 10–10–10–7 M, reaching maximum by 10–9 M. Insulin stimulation showed measurable effects only at supraphysiological concentrations, 10–8–10–7 M. In conclusion, coprecipitation of both the IGF-IR and the IR β-subunit indicates the presence of hybrid insulin/IGF-I receptors in VSMC. At a physiological concentration, insulin activates the IR but does not affect either glucose metabolism or DNA synthesis, whereas IGF-I both activates the receptor and elicits biological effect.

  • 52.
    Johansson, Git
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Simona Chisalita, Ioana
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Human microvascular endothelial cells are sensitive to IGF-I but resistant to insulin at the receptor level2008In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 296, no 1-2, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Human microvascular endothelial cells (HMVEC) are sensitive to IGF-I but insulin resistant and express several times more IGF-I receptors (IGF-IR) than insulin receptors (IR). Our aim was to investigate the mechanism of this insulin resistance in cultured HMVEC by studying receptor activation and signal propagation downstream.

    propagation downstream. The IGF-IR β-subunit and the IR β-subunitwere detected and found to co-precipitate. IRAwas themajor IR isoformexpressed in HMVEC. IGF-I 10−9 to 10−8M phosphorylated its cognate receptor β-subunit. IGF- I also phosphorylated the IR β-subunit at 10−9 M. Phosphorylation of insulin receptor substrate 1 was obtained by IGF-I 10−9 to 10−8 M. Akt was phosphorylated by IGF-I at 10−8 to 10−7M and by insulin 10−7M. IGF-I at 10−8 to 10−6M significantly increased DNA-synthesis. We conclude that microvascular endothelial cells are sensitive to IGF-I but resistant to insulin due to a preponderance of IGF-I receptors and sequestration of insulin receptors into insulin/IGF-I hybrid receptors.

  • 53.
    Johansson, Git
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Svedjeholm, Rolf
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    High expression of IGF-I receptors compared to insulin receptors in human mammary arteryManuscript (preprint) (Other academic)
    Abstract [en]

    Aims/hypothesis: Cultured endothelial and vascular smooth muscle cells from different vascular beds express several fold more IGF-I receptors (IGF-IR) than insulin receptors (IR). The aim of this study was to investigate the gene expression of IR and IGF-IR in tissue samples from the left internal mammary artery (LIMA) to see if there is a higher gene expression of IGF-IR compared to IR in arterial tissue in vivo.

    Methods: Samples from LIMA (n=16) were obtained at coronary bypass surgery, immediately frozen in liquid nitrogen and stored at -70°C until analysis. The samples were thawed, placed on ice and dissected free from surrounding connective tissue and fat, homogenized and total RNA was extracted. Receptor mRNA was analyzed by quantitative real time RT-PCR and comparison of CT-values.

    Results: LIMA samples were obtained from 16 patients, 10 non-diabetic and 6 diabetic patients. Gene expression of IGF-IR was detected in all LIMA samples, however, the insulin receptor mRNA was under the detection limit in 4 samples. Compared to IR the gene expression of IGF-IR was 36 fold higher (n=12. p <0.0001). The relative gene expression of IGF-IR to IR in LIMA from non-diabetic patients (n=9) and diabetic patients (n=3) was similar, 39 and 32 fold, respectively.

    Conclusions/interpretation: Our results in mammary artery samples indicate that IGF-IR are more expressed than IR in arterial tissue in vivo.

  • 54. 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]

  • 55. Kullberg, C
    et al.
    Abrahamsson, M
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-endokrin.
    Finnström, Kerstin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Ophthalmology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Ophthalmology UHL/MH.
    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, Barn.
    Prevalence of retinopathy differs with age at onset of diabetes in a population of patients with Type 1 diabetes2002In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 19, no 11, p. 924-931Article in journal (Refereed)
    Abstract [en]

    Aim. The VISS study (Vascular complications in South-east Sweden) investigates prevalence and incidence of vascular complications in a population with Type 1 diabetes, from a well-defined geographical area and followed from diag-nosis with HbA1c measurement. Method. The study population comprised all 440 patients with Type 1 diabetes onset before the age of 36 years, onset during 1983-1987, and at the time of onset living within the counties of J÷nk÷ping, Kalmar or ╓sterg÷tland. Retinopathy was examined with fundus photography 1994-1995, and classified according to a modified Airlie House protocol. Results. Fundus photographs from 390 patients were evaluated. In 277 (71%) patients no retinopathy was seen. The prevalence of retinopathy increased from 11% among patients < 5 years old at diabetes onset, to 48% among those 15-19 years old at diabetes onset, and then decreased to 30% for patients 30-35 years old at diabetes onset (P for ?2 for linear trend for all ages 0.017, for age at onset 0-19 yearsP = 0.0003), without corresponding differences in duration or HbA1c between patients with different onset age. Patients with HbA1c in the highest quartile (> 8.3% HbA1c) had a relative risk of 2.4 (95% confidence) interval (CI) 1.7-3.2) of having any retinopathy compared with patients with lower HbA1c, and a relative risk of 7.1 (95% CI 3.0-16.7) of having other forms of retinopathy than microaneurysms. Conclusion. In patients with diabetes duration of 6-13 years, the prevalence of retinopathy is clearly related to glycaemic control. Furthermore, the risk of retinopathy varies with different age at onset, independently of differences in duration or glycaemic control.

  • 56. Landin-Olsson, M
    et al.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Blohmé, G
    Littorin, B
    Lithner, F
    Nyström, L
    Scherstén, B
    Sundkvist, G
    Wibell, L
    Östman, J
    Lernmark, Å
    Appearance of islet cell autoantibodies after clinical diagnosis of diabetes mellitus.1999In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 29, p. 57-63Article in journal (Refereed)
  • 57.
    Liefvendahl, Ellinor
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Mitogenic effect of the insulin analogue glargine in malignant cells in comparison with insulin and IGF-I2008In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 40, no 6, p. 369-374Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate if the insulin analogue glargine, with an increased affinity for the IGF-I receptor (ICF-IR), affects the cell growth to a larger extent than human insulin in malignant cells expressing IGF-IRs. The breast cancer cell lines MCF-7 and SKBR-3, and the osteosarcoma cell line SaOS-2 were used. Gene expression was determined by real-time RT-PCR and receptor protein quantified by ELISAs. Receptor phosphorylation was assessed by immuno-precipitation and Western blot. Mitogenic effect was determined as 3H-thymidine incorporation into DNA. The gene expression of insulin receptor (IR) varied between 4.3-7.5-10-3 and the expression of IGF-IR between 7.7-147.7 10-3 in relation to GAPDH (glyceraldehyde-3-phosphate dehydrogenase). Insulin receptor and IGF-IR protein varied between 2.0-4.1 ng/mg protein and 2.0-40.4 ng/mg protein, respectively. The IGF-IR was phosphorylated by IGF-I at a concentration of 10 -10-10-10M. All three polypeptides stimulated DNA synthesis in MCF-7, SKBR-3, and SaOS-2 cells. SaOS-2 cells were more sensitive to IGF-I than to insulin and glargine. MCF-7 cells were more sensitive to des(l-3)IGF-I than to IGF-I. In SKBR-3 and SaOS-2 cells, glargine tended to be more potent than human insulin to stimulate DNA synthesis. Our results suggest that glargine, compared to human insulin, has little or no increased mitogenic effect in malignant cells expressing IGF-IRs. © Georg Thieme Verlag KG Stuttgart · New York.

  • 58.
    Lindström, Torbjörn
    et al.
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Frystyk, Jan
    The Medical Research Laboratories, Clinical Institute and Medical Department M, Aarhus University Hospital, Aarhus, Denmark.
    Hedman, Christina
    Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Flyvbjerg, Allan
    The Medical Research Laboratories, Clinical Institute and Medical Department M, Aarhus University Hospital, Aarhus, Denmark.
    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.
    Elevated circulating adiponectin in type 1 diabetes is associated with long diabetes duration2006In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 65, no 6, p. 776-782Article in journal (Refereed)
    Abstract [en]

    Objective  To study circulating adiponectin concentrations in relation to diabetes duration and endogenous insulin secretion in patients with type 1 diabetes.

    Patients  Patients with haemoglobin A1c (HbA1c) < 6% (reference range 3·6–5·4%) were selected for the study. Twenty-two men and 24 women [age 41·3 ± 13·8 years (mean ± SD), diabetes duration 4 months to 52 years] participated. Healthy controls (15 women and nine men, age 41·3 ± 13·0 years) were also included. Overnight fasting serum samples were analysed for adiponectin, HbA1c, C-peptide and lipoproteins.

    Results  Significant positive associations were found between adiponectin concentrations and diabetes duration in univariate and multiple regression analyses. Serum adiponectin averaged 9·7 ± 5·3 [median 8·1, interquartile range (IQR) 3·6] mg/l in patients with diabetes duration less than 10 years and 17·8 ± 10·7 (median 14·7, IQR 7·5) mg/l in patients with longer duration (P = 0·0001). Among the patients, 24 were without detectable (< 100 pmol/l) and 22 with detectable C-peptide levels (185 ± 91 pmol/l). C-peptide levels in controls averaged 492 ± 177 pmol/l. HbA1c was 5·7 ± 0·6% in patients without detectable C-peptide and 5·6 ± 0·4% in patients with detectable C-peptide (ns). Serum adiponectin was higher in patients without detectable C-peptide than in patients with detectable C-peptide [17·3 ± 11·1 vs. 10·6 ± 5·8 mg/l (P < 0·005)] and in the controls [10·1 ± 2·9 mg/l (P < 0·001 vs. patients without detectable C-peptide)].

    Conclusions  The increase in circulating adiponectin concentrations in patients with type 1 diabetes appears to be strongly associated with long diabetes duration, irrespective of the metabolic control. Among other factors, a putative role for residual β-cell function in the regulation of circulating adiponectin levels can be considered but we did not find sufficient evidence for this in the present study.

  • 59.
    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.

  • 60.
    Lindström, Torbjörn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Olsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Ottosson, A-M
    Med Norrköping.
    The lipoprotein profile differs during insulin treatment alone and combination therapy with insulin and sulphonylureas in patients with type2 diabetes mellitus.1999In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 16, p. 820-826Article in journal (Refereed)
  • 61.
    Lindström, Torbjörn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Olsson, P-O
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    The use of human ultralente is limited by great intraindividual variability in overnight plasma insulin profiles2000In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 60, no 5, p. 341-348Article in journal (Refereed)
    Abstract [en]

    Our objective was to investigate the usefulness of human ultralente insulin as basal substitution overnight in patients with Type 1 diabetes treated with multiple insulin injection therapy by evaluating the free insulin and glucose profiles, the day-to-day variability and the impact of the time of injection. Methods: Ten patients with Type 1 diabetes and with good metabolic control (mean HbAlc 6.0%), treated with regular human insulin before breakfast, lunch and dinner and human ultralente (Ultratard«) before dinner or at bedtime, were studied. Plasma profiles of blood glucose and free insulin were measured on three occasions from 16.00 h until noon the next day. On two of these occasions Ultratard« was injected before dinner and once it was injected at bedtime in randomized order. Results: Injection of regular insulin before dinner resulted in a high insulin peak during the evening but no insulin peak was found that could be attributed to ultralente. The plasma concentration of free insulin at 03.00 h was 11.0▒1.9 mU/L and it slowly decreased to 6.4▒1.4 at 12.00 h after administration of ultralente at 17.00 h. There were no differences in the mean plasma insulin profiles compared to the other occasion when insulin was given at 17.00 h or at 22.00 h. On the other hand, the intra-individual day-to-day variability of mean insulin concentration during the night was considerable, often exceeding 50%. No differences were noted in the mean blood glucose profiles between the three occasions. Conclusion: Human ultralente insulin gives an insulin profile suitable for overnight substitution, but the great day-to-day variability limits its usefulness. It can be injected before dinner or at bedtime without any change in the insulin profile during the night.

  • 62. Littorin, B
    et al.
    Blom, P
    Schölin, A
    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.
    Blohmé, G
    Bolinder, J
    Ekbom-Schnell, A
    Eriksson, JW
    Gudbjörnsdottir, S
    Nyström, L
    Östman, J
    Sundkvist, G
    Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: Results from the nationwide Diabetes Incidence Study in Sweden (DISS)2006In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 49, no 12, p. 2847-2852Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: Low plasma vitamin D concentrations may promote the development of type 1 diabetes. To test this hypothesis, we measured plasma 25-hydroxyvitamin D (25OHD) in young adults with type 1 diabetes. Methods: The nationwide Diabetes Incidence Study in Sweden (DISS) covers 15- to 34-year-old people with newly diagnosed diabetes. Blood samples at diagnosis were collected during the 2-year period 1987/1988. Patients with islet antibodies (islet cell antibodies, GAD antibodies or tyrosine phosphatase-like protein antibodies) were defined as having autoimmune type 1 diabetes. Plasma 25OHD was measured in samples taken from 459 patients at the time of diagnosis, and in 138 of these subjects 8 years later. The results were compared with age- and sex-matched control subjects (n=208). Results: At diagnosis, plasma 25OHD levels were significantly lower in patients with type 1 diabetes than in control subjects (82.5±1.3 vs 96.7±2.0 nmol/l, p<0.0001). Eight years later, plasma 25OHD had decreased in patients (81.5±2.6 nmol/l, p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9±1.4 vs 90.1±2.4 nmol/l, p<0.0001) and at follow-up (77.1±2.8 nmol/l vs 87.2±4.5 nmol/l, p=0.048). Conclusions/interpretation: The plasma 25OHD level was lower at diagnosis of autoimmune type 1 diabetes than in control subjects, and may have a role in the development of type 1 diabetes. Plasma 25OHD levels were lower in men than in women with type 1 diabetes. This difference may be relevant to the high incidence of type 1 diabetes among young adult men. © 2006 Springer-Verlag.

  • 63. Littorin, B
    et al.
    Nyström, L
    Gullberg, B
    Råstam, L
    Östman, J
    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, E
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Scherstén, B
    Sundkvist, G
    Increasing body mass index at diagnosis of diabetes in young adult people during 1983-1999 in the Diabetes Incidence Study in Sweden (DISS)2003In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 254, no 3, p. 251-256Article in journal (Refereed)
    Abstract [en]

    Objective. To study trends in body mass index (BMI) at diagnosis of diabetes in all young Swedish adults in the age range of 15-34 years registered in a nation-based registry. Design. The BMI was assessed at diagnosis in diabetic patients 15-34 years of age at diagnosis, for a period of 17 years (1983-1999). Islet cell antibodies (ICA) were measured during three periods (1987-1988, 1992-1993 and 1998-1999). Setting. A nationwide study (Diabetes Incidence Study in Sweden). Subjects. A total of 4727 type 1 and 1083 type 2 diabetic patients. Main outcome measures. Incidence-year specific BMI adjusted for age, gender and time of diagnosis (month). Results. Body mass index at diagnosis increased significantly both in type 1 (21.4 ▒ 3.6 to 22.5 ▒ 4.0: P < 0.0001) and in type 2 (27.4 ▒ 6.8 to 32.0 ▒ 6.0, P < 0.0001) diabetic patients, also when adjusted for age, gender and month of diagnosis. A similar significant increase in BMI was found in type 1 diabetic patients and in type 2 diabetic patients in the periods 1987-1988, 1992-1993 and 1998-1999, years when ICA were assessed and considered in the classification of diabetes. Despite this increase in BMI, there was no increase in the incidence of diabetes in young-adult people in Sweden. Conclusion. Body mass index at diagnosis of diabetes in subjects 15-34 years of age has substantially increased during 1983-1999 in Sweden when adjusted for age, gender and month of diagnosis.

  • 64. 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)
  • 65. 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.

  • 66.
    Mollsten, A
    et al.
    Umea University.
    Svensson, M
    Sahlgrens University Hospital.
    Berhan, Y
    Sunderby Hospital.
    Schon, S
    Ryhov County Hospital.
    Nystrom, L
    Umea University.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Dahlquist, G
    Umea University.
    Age at onset and sex influence the risk of developing end-stage renal disease in young patients with type 1 diabetes2009In: in DIABETOLOGIA, vol 52, 2009, Vol. 52, p. S25-S26Conference paper (Refereed)
    Abstract [en]

    n/a

  • 67.
    Mollsten, Anna
    et al.
    Umeå University.
    Svensson, Maria
    Sahlgrens University Hospital.
    Waernbaum, Ingeborg
    Umeå University.
    Berhan, Yonas
    Umeå University.
    Schon, Staffan
    Ryhov County Hospital.
    Nystrom, Lennarth
    Umeå University.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Dahlquist, Gisela
    Umeå University.
    Cumulative Risk, Age at Onset, and Sex-Specific Differences for Developing End-Stage Renal Disease in Young Patients With Type 1 Diabetes: A Nationwide Population-Based Cohort Study2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 7, p. 1803-1808Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE This study aimed to estimate the current cumulative risk of end-stage renal disease (ESRD) due to diabetic nephropathy in a large, nationwide, population-based prospective type 1 diabetes cohort and specifically study the effects of sex and age at onset. RESEARCH DESIGN AND METHODS In Sweden, all incident cases of type 1 diabetes aged 0-14 years and 15-34 years are recorded in validated research registers since 1977 and 1983, respectively. These registers were linked to the Swedish Renal Registry, which, since 1991, collects data on patients who receive active uremia treatment. Patients with years duration of type 1 diabetes were included (n = 11,681). RESULTS During a median time of follow-up of 20 years, 127 patients had developed ESRD due to diabetic nephropathy. The cumulative incidence at 30 years of type 1 diabetes duration was low, with a male predominance (4.1% [95% CI 3.1-5.3] vs. 2.5% [1.7-3.5]). In both male and female subjects, onset of type I diabetes before 10 years of age was associated with the lowest risk of developing ESRD. The highest risk of ESRD was found in male subjects diagnosed at age 20-34 years (hazard ratio 3.0 [95% CI 1.5-5.7]). In female subjects with onset at age 20-34 years, the risk was similar to patients diagnosed before age 10 years. CONCLUSIONS The cumulative incidence of ESRD is exceptionally low in young type 1 diabetic patients in Sweden. There is a striking difference in risk for male compared with female patients. The different patterns of risk by age at onset and sex suggest a role for puberty and sex hormones.

  • 68.
    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.

  • 69.
    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.

  • 70.
    Nordwall, Maria
    et al.
    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 Norrköping.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bojestig, Mats
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    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.
    Good glycemic control remains crucial in prevention of late diabetic complications - the Linkoping Diabetes Complications Study2009In: PEDIATRIC DIABETES, ISSN 1399-543X, Vol. 10, no 3, p. 168-176Article in journal (Refereed)
    Abstract [en]

    Several intervention studies have convincingly demonstrated the importance of good glycemic control to avoid long-term diabetic complications, but the importance of other risk factors remains controversial. We previously reported a markedly reduced incidence of severe retinopathy and nephropathy during the past decades in an unselected population of type 1 diabetes mellitus diagnosed in childhood. The aim of the present study was to analyze possible risk factors, which could explain the improved prognosis.

    In this longitudinal population-based cohort study, we followed all 269 patients in whom type 1 diabetes mellitus was diagnosed in childhood 1961-1985 in a well-defined geographical area in Sweden. The patients were followed until the end of 1990s. Multivariable regression models were used to analyze the importance of hemoglobin A1c (HbA(1c)), diabetes duration, blood pressure, cardiovascular risk factors and persisting C-peptide secretion for the development of diabetic retinopathy and nephropathy.

    Beside longer duration and higher HbA(1c), blood pressure and lipid values were higher and cardiovascular disease and smoking were more common in patients with severe complications. However, multivariable analysis abolished these associations. Diabetes duration and long-term HbA(1c) were the only significant independent risk factors for both retinopathy and nephropathy. The risk of overt nephropathy increased substantially when HbA(1c) was above 9.6% [Diabetes Control and Complications Trial (DCCT) corrected value], while the risk of severe retinopathy increased already when HbA(1c) exceeded 8.6%.

    In this unselected population, glycemic control was the only significant risk factor for the development of long-term complications.

  • 71.
    Nordwall, Maria
    et al.
    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 Norrköping.
    Bojestig, M
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    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.
    Declining incidence of severe retinopathy in a population of Type 1 diabetes2001In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44, p. 1095-Conference paper (Other academic)
  • 72.
    Nordwall, Maria
    et al.
    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 Norrköping.
    Bojestig, M
    Linkoping Univ Hosp, Div Internal Med, S-58185 Linkoping, Sweden Linkoping Univ Hosp, Div Paediat, S-58185 Linkoping, Sweden.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    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.
    Persistent decrease in nephropathy in Type 1 diabetes2000In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 43, p. 971-Conference paper (Other academic)
  • 73.
    Nordwall, Maria
    et al.
    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 Norrköping.
    Bojestig, Mats
    Division of Internal Medicine and Diabetes Research Centre, Department of Medicine and Care, University Hospital, Linköping, Sweden.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    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.
    Declining incidence of severe retinopathy in an unselected population of Type 1 diabetes: the Linköping Diabetes Complications Study2004In: Diabetologia, ISSN 0012-186X, Vol. 47, no 7, p. 1266-1272Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: In a previous study conducted over the last decades we found a decreased incidence of nephropathy but unchanged incidence of severe retinopathy among patients with Type 1 diabetes diagnosed in childhood and with 20 years duration of diabetes. The aim of our current study was to investigate the incidence 5 to10 years later in the same population.

    Methods: We studied all 269 patients in whom Type 1 diabetes was diagnosed in childhood between 1961 and 1985 in a district in southeastern Sweden. Ninety-one percent were monitored for retinopathy until at least 1997 and 95% were monitored for nephropathy. Severe retinopathy was defined as laser-treated retinopathy and nephropathy as persistent proteinuria. Survival analysis was used and the patients divided into five cohorts according to the time of onset of diabetes.

    Results: The cumulative proportion of severe retinopathy had declined (p=0.006). After 25 years it was 47% (95% CI 34–61), 28% (15–40) and 24% (12–36) in the cohorts 1961 to 1965, 1966 to 1970 and 1971 to 1975 respectively. After 30 years it was 53% (40–66) and 44% (28–59) in the oldest cohorts. The cumulative proportion of nephropathy after 25 years duration was 30% (18–42), 8% (1–16) and 13% (4–23) in the cohorts 1961 to 1965, 1966 to 1970 and 1971 to 1975 respectively. After 30 years, it was 32% (20–44) and 11% (2–20) for the oldest cohorts (p<0.0001).

    Conclusions/interpretation: In an unselected population with Type 1 diabetes diagnosed in childhood, modern diabetes care markedly reduced the incidence of severe retinopathy and nephropathy.

  • 74.
    Nyström, Fredrik H.
    et al.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Department of Medicine and Care, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Öhmar, Peter K.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences.
    Ekman, Bertil Å.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences.
    Österlund, Maria K.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences.
    Karlberg, Bengt E.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans J.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences.
    Population-based reference values for IGF-I and IGF-binding protein-1: Relations with metabolic and anthropometric variables1997In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 136, no 2, p. 165-172Article in journal (Refereed)
    Abstract [en]

    Population-based reference values for IGF-I and IGF-binding protein-1 (IGFBP-1) have been established. One hundred and one women and the same number of men, 20–70 years old, were randomly selected from the population registry in the community of Linköping. Participation rate was 67%. Venous blood was drawn in the fasting state. Serum IGF-I was measured by RIA after acid-ethanol extraction and IGFBP-1 was determined by ELISA. IGF-I levels did not differ between genders and the decline with age was similar in men and women (men: Y=366–3·28×age (years), r =−0·61, P<0·0001; women: Y=386–3·49×age, r =−0·57, P<0·0001, P=0·4 for difference in slope). There were negative correlations between IGF-I and plasma lipids and blood pressure in both genders, but none was independent of age. Serum angiotensin-converting enzyme activity correlated positively with IGF-I in men independently from age (r =0·21, P=0·01). The distribution of IGFBP-1 was positively skewed and it was higher in women than in men (5·9±4·8 μg/l and 4·0±3·3 μg/l respectively; Mann–Whitney, P=0·002). In men and in the women not taking oestrogen, IGFBP-1 correlated positively with age (Spearman rank correlation (Spearman): men: r=0·32, P=0·002; women: r=0·24, P=0·03). C-peptide correlated negatively (Spearman: men: r =−0·38, P=0·002; women: r =−0·49, P<0·000) and sex hormone binding globulin positively with IGFBP-1 (Spearman: men: r=0·50, P<0·0001; women: r =0·55, P<0·0001).

  • 75. Orre-Pettersson, A-C
    et al.
    Lindström, T
    Bergmark, V
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    The snack is critical for the blood glucose profile during treatment with regular insulin preprandially.1999In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 245, p. 41-45Article in journal (Refereed)
  • 76. Pundziute-Lycka, A
    et al.
    Dahlquist, G
    Nystrom, L
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bjork, E
    Blohme, G
    Bolinder, J
    Eriksson, JW
    Sundkvist, G
    Ostman, J
    The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983 to 19982002In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 45, no 6, p. 783-791Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis. To analyse the incidence of Type I (insulin-dependent) diabetes mellitus in the 0-34 years age group in Sweden 1983-1998. Methods. Incidence and cumulative incidence per 100 000 and Poisson regression analysis of age-period effects was carried out using 11 751 cases from two nation-wide prospective registers. Results. Incidence (95%-CI) was 21.4 (20.8-21.9) in men and 17.1 (16.6-17.5) in women between 0 and 34 years of age. In boys aged 0-14 and girls aged 0-12 years the incidence increased over time, but it tended to decrease at older age groups, especially in men. Average cumulative incidence at 35 years was 748 in men and 598 in women. Cumulative incidence in men was rather stable during four 4-year periods (736, 732, 762, 756), while in women it varied more (592, 542, 617, 631). In males aged 0-34 years, the incidence did not vary between the 4-year periods (p=0.63), but time changes among the 3-year age groups differed (p<0.001). In females the incidence between the periods varied (p<0.001), being lower in 1987-1990 compared to 1983-1986, but time changes in the age groups did not differ (p=0.08). For both sexes median age at diagnosis was higher in 1983-1986 than in 1995-1998 (p<0.001) (15.0 and 12.5 years in males, 11.9 and 10.4 in females, respectively). Conclusion/interpretation. During a 16-year period the incidence of Type I diabetes did not increase in the 0-34 years age group in Sweden, while median age at diagnosis decreased. A shift to younger age at diagnosis seems to explain the increasing incidence of childhood Type I diabetes.

  • 77.
    Rawshani, Araz
    et al.
    Nationella Diabetesregistret, Registercentrum VGR, Gothenburg, Sweden.
    Landin-Olsson, Mona
    Lund University, Sweden .
    Svensson, Ann-Marie
    Nationella Diabetesregistret, Registercentrum VGR, Gothenburg, Sweden.
    Nystrom, Lennarth
    Umeå University, Sweden .
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Bolinder, Jan
    Karolinska Institute, Stockholm, Sweden .
    Gudbjornsdottir, Soffia
    Nationella Diabetesregistret, Registercentrum VGR, Gothenburg, Sweden.
    The incidence of diabetes among 0-34 year olds in Sweden: new data and better methods2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no 7, p. 1375-1381Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS:

    We reassessed the validity of previously reported incidence rates for type 1 diabetes in 0-34 year olds in Sweden. We estimated new incidence rates through three nationwide registers.

    METHODS:

    We used capture-recapture methods to assess ascertainment in the Diabetes Incidence Study in Sweden (DISS) and estimated incidence rates in the 20-34 year age group for 2007-2009. We examined whether incidence rates in patients aged 34 and younger could be estimated through the Prescribed Drug Register (PDR) via a proxy for diagnosis of type 1 diabetes; men with at least one and women with at least three prescriptions for insulin were included if they had not been given oral glucose-lowering drugs. We scrutinised the proxy by comparing incidence rates in patients aged 14 and younger with the Swedish Childhood Diabetes Register (SCDR), which has 95-99% ascertainment, and by assessing diabetes type among 18-34 year olds in the National Diabetes Register (NDR).

    RESULTS:

    Incidence rates were two to three times higher than previously reported. The absolute number of cases (2007-2009, age 20-34) was 435 in the DISS, 923 in the NDR, 1,217 in the PDR, 1,431 in all three and 1,617 per the capture-recapture method. Ascertainment in the DISS was ~29% for 2007-2009. The proxy diagnosis in the PDR was highly reliable, while the capture-recapture method presumably generated an overestimate.

    CONCLUSIONS/INTERPRETATION:

    The incidence of type 1 diabetes in patients aged 34 and younger was two to three times higher than previously reported. The PDR can be used to reliably assess incidence rates in this age group.

  • 78.
    Scholin, A
    et al.
    Uppsala University.
    Nystrom, L
    Umea University.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bolinder, J
    Karolinska University.
    Bjork, E
    Uppsala University.
    Berne, C
    Uppsala University.
    A Karlsson, F
    Uppsala University.
    Proinsulin/C-peptide ratio, glucagon and remission in new-onset Type 1 diabetes mellitus in young adults2011In: DIABETIC MEDICINE, ISSN 0742-3071, Vol. 28, no 2, p. 156-161Article in journal (Refereed)
    Abstract [en]

    Pandgt;Aims After initiation of treatment in Type 1 diabetes, a period with lower insulin requirement often follows, reflecting increased insulin sensitivity and improved insulin secretion. We explored if efficiency of proinsulin processing is associated with the remission phenomenon. Methods Seventy-eight patients with new-onset Type 1 diabetes were followed prospectively for 3 years. Daily insulin dosage, HbA(1c), plasma glucose, proinsulin, C-peptide, glucagon concentrations and islet antibodies were determined at diagnosis and after 3, 6, 9, 12, 18, 24, 30 and 36 months. We studied remission, defined as an insulin dose andlt; 0.3 U kg-1 24 h-1 and HbA(1c) within the normal range, in relation to the above-mentioned variables. Results A rise and subsequent decline in plasma proinsulin and C-peptide concentrations was observed. Forty-five per cent of the patients experienced remission at one or more times, characterized by higher proinsulin and C-peptide levels, and lower proinsulin/C-peptide ratios, indicating more efficient proinsulin processing, compared with those not in remission. Non-remission also tended to be associated with higher glucagon values. Patients entering remission were more often men, had higher BMI at diagnosis, but did not differ at baseline with respect to islet antibody titres compared with patients with no remission. Conclusions Remissions after diagnosis of Type 1 diabetes were associated with lower proinsulin/C-peptide ratios, suggesting more efficient proinsulin processing, and tended to have lower glucagon release than non-remissions. This indicates that, in remission, the residual islets maintain a secretion of insulin and glucagon of benefit for control of hepatic glucose production.

  • 79. Schölin, A
    et al.
    Björklund, L
    Borg, H
    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.
    Björk, E
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Gudbjörnsdottir, S
    Nyström, L
    Östman, J
    Karlsson, AF
    Sundkvist, G
    Islet antibodies and remaining β-cell function 8 years after diagnosis of diabetes in young adults: A prospective follow-up of the nationwide Diabetes Incidence Study in Sweden2004In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 255, no 3, p. 384-391Article in journal (Refereed)
    Abstract [en]

    Objectives. To establish the prevalence of remaining β-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. Design. Population-based cohort study. Setting. Nationwide from all Departments of Medicine and Endocrinology in Sweden. Subjects. A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. Main outcome measure. Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved β-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies -were measured. Results. Amongst 269 islet antibody positives (ab+) at diagnosis, preserved β-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2,respectively, P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively, P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively, P = 0.007) at diagnosis compared with ab+ without remaining β-cell function. Amongst the 241 patients without detectable β-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. Conclusions. Sixteen per cent of patients with autoimmune type 1 diabetes had remaining β-cell function 8 years after diagnosis whereas 5.8% with β-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.

  • 80. Schölin, A
    et al.
    Törn, C
    Nyström, L
    Berne, C
    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.
    Blohmé, G
    Bolinder, J
    Eriksson, JW
    Kockum, I
    Landin-Olsson, M
    Östman, J
    Karlsson, FA
    Sundkvist, G
    Björk, E
    Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes2004In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 21, no 5, p. 447-455Article in journal (Refereed)
    Abstract [en]

    Aim: To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM). Methods: In Sweden, 362 patients (15-34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA1c and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose ≤ 0.3 U/kg/24 h and HbA1c within the normal range, was analysed in relation to characteristics at diagnosis. Results: Remissions were seen in 43% of the patients with a median duration of 8 months (range 1-73). Sixteen per cent had a remission with a duration > 12 months. Among patients with antibodies (ab+), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20-24.9 kg/m2) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab+ remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions. Conclusion: In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.

  • 81.
    Sjöstrand, M
    et al.
    RandD AstraZeneca.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Eriksson, J W
    RandD AstraZeneca.
    Gudbjornsdottir, S
    Sahlgrenska University Hospital.
    Lindmark, S
    Umeå University.
    Landin-Olsson, M
    Lund University Hospital.
    Nyström, L
    Umeå University.
    Svensson, M K
    Sahlgrenska University Hospital.
    Adolfsson, P
    RandD AstraZeneca.
    Arneklev, K
    RandD AstraZeneca.
    Bolinder, J
    Karolinska University Hospital.
    Dynamic beta cell function in young type 2 diabetes patients (15-34 years) in the Diabetes Incidence Study in Sweden register in DIABETOLOGIA, vol 53, issue , pp2010In: DIABETOLOGIA, Springer Science Business Media , 2010, Vol. 53Conference paper (Refereed)
    Abstract [en]

    n/a

  • 82.
    Sjöstrand, M
    et al.
    AstraZeneca R&D, Mölndal, Sweden.
    Carlson, K
    AstraZeneca R&D, Mölndal, Sweden.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Gudbjörnsdottir, S
    Sahlgrenska Academy Hospital, Gothenburg, Sweden.
    Landin-Olsson, M
    Lund University Hospital, Sweden.
    Lindmark, S
    Umeå University, Sweden .
    Nyström, L
    Umeå University, Sweden .
    Svensson, M K
    Sahlgrenska Academy Hospital, Gothenburg, Sweden.
    Eriksson, J W
    AstraZeneca R&D, Mölndal, Sweden.
    Bolinder, J
    Karolinska Institute, Stockholm, Sweden.
    Assessment of beta-cell function in young patients with type 2 diabetes: arginine-stimulated insulin secretion may reflect beta-cell reserve2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, no 1, p. 39-48Article in journal (Refereed)
    Abstract [en]

    Objective

    Simple methods for the evaluation of dynamic β-cell function in epidemiological and clinical studies of patients with type 2 diabetes (T2D) are needed. The aim of this study was to evaluate the dynamic beta-cell function in young patients with T2D with different disease durations and treatments.

    Methods

    Overall, 54 subjects with T2D from the Diabetes Incidence Study in Sweden (DISS) and 23 healthy control participants were included in this cross-sectional study. Beta-cell function was assessed by intravenous (i.v.) administration of arginine followed by i.v. glucose. The acute insulin and C-peptide responses to arginine (AIRarg and Ac-pepRarg, respectively) and to glucose (AIRglu and Ac-pepRglu, respectively) were estimated. Homeostasis model assessment of β-cell function (HOMA-β) and C-peptide assessments were also used for comparisons between patients with T2D and control participants.

    Results

    AIRarg and Ac-pepRarg, but not AIRglu and Ac-pepRglu, could differentiate between patients with different disease durations. AIRglu values were 89% (P < 0.001) lower and AIRarg values were 29% (P < 0.01) lower in patients with T2D compared with control participants. HOMA-β and fasting plasma C-peptide levels did not differ between the T2D and control groups.

    Conclusion

    In young patients with T2D, the insulin secretory response to i.v. glucose is markedly attenuated, whereas i.v. arginine-stimulated insulin release is better preserved and can distinguish between patients with different disease duration and antidiabetic therapies. This suggests that the i.v. arginine stimulation test may provide an estimate of functional beta-cell reserve.

  • 83.
    Steen Carlsson, K
    et al.
    Malmö University Hospital.
    Landin-Olsson, M
    Lund University Hospital.
    Nystrom, L
    Umea University.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Bolinder, J
    Karolinska University Hospital.
    Ostman, J
    Karolinska University Hospital.
    Gudbjornsdottir, S
    Nordic School of Public Health, Gothenburg.
    Long-term detrimental consequences of the onset of type 1 diabetes on annual earnings-evidence from annual registry data in 1990-20052010In: DIABETOLOGIA, ISSN 0012-186X, Vol. 53, no 6, p. 1084-1092Article in journal (Refereed)
    Abstract [en]

    Young adults in the early stages of their participation in the labour market may be particularly vulnerable to the effects of onset of a chronic disease. Our aim was to quantify the consequences of the onset of type 1 diabetes in young adults on annual earnings, using individual-level longitudinal data before and after the onset of diabetes. The Econ-DISS database contains annual socioeconomic information for 1990-2005 from Statistics Sweden. Econ-DISS includes data for persons with diabetes onset at the age of 15-34 years between 1983 and 2005, registered in the national Diabetes Incidence Study in Sweden (DISS) database, and for controls. Considering the onset of type 1 diabetes as an unanticipated and significant life event, we compared the progression of annual earnings for 3,650 cases born between 1949 and 1970 before and after onset of diabetes with that of 14,629 controls. Possible confounders-education, participation in the labour market, sick leave and parental education-were analysed. We found no differences between the groups in annual earnings or participation in the labour market before onset of diabetes. After onset, persons with type 1 diabetes gradually lagged behind the controls. Their median annual earnings were lower in each year from 1995 to 2005 (p andlt; 0.01). The difference in 2005 was euro (EUR) 1,411 (5.3%). Controlling for confounders, duration of type 1 diabetes a parts per thousand yen10 years was associated with 4.2% (men) and 8.1% (women) lower average annual earnings for persons with upper secondary education only who were active in the labour market. The onset of type 1 diabetes in young adults has long-term detrimental consequences on earnings that cannot be attributed to confounders.

  • 84.
    Svensson, M. K.
    et al.
    University of Gothenburg, Sweden.
    Tyrberg, M.
    Lund University, Sweden.
    Nystrom, L.
    Umeå University, Sweden.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Bolinder, J.
    Karolinska Institute, Sweden.
    Ostman, J.
    Karolinska Institute, Sweden.
    Gudbjornsdottir, S.
    University of Gothenburg, Sweden.
    Landin-Olsson, M.
    Lund University, Sweden.
    Eriksson, J. W.
    Uppsala University, Sweden.
    The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors2015In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 31, no 2, p. 138-146Article in journal (Refereed)
    Abstract [en]

    AimsThe main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34years). MethodsAll 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. ResultsAfter median 17years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1kg/m(2)), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p=0.041), BMI (p=0.012) and HbA1c (pless than0.001) were significant predictors of developing diabetic nephropathy between 9 and 17years of diabetes. At 17years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.051.12 per 1mmHg increase) were associated with DN. ConclusionsPatients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9years of follow-up was a risk marker for later development of diabetic nephropathy.

  • 85. 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.

  • 86.
    Szabó, Zoltan
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Rolf
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Intraoperative muscle and fat metabolism in diabetic patients during coronary artery bypass grafting surgery: a parallel microdialysis and organ balance study2009In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 103, no 2, p. 166-172Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Surgical trauma causes stress and inflammatory reactions with elevated serum free fatty acids (FFA) and glucose levels characteristic of intraoperative insulin resistance. Our aim was to compare microdialysis findings with those using the classical organ balance technique and to test the clinical feasibility of microdialysis during cardiac surgery. METHODS: Nine diabetic and nine non-diabetic patients, undergoing routine coronary artery bypass grafting surgery, were studied using both microdialysis and the organ balance technique in the brachio-radial muscle of the forearm, and microdialysis in the pre-pectoral fat tissue. Glucose, lactate, and glycerol were measured in arterial and venous plasma and in the microdialysate before administration of heparin, at the release of the aortic cross-clamp, and before transfer to the intensive care unit. RESULTS: Glucose release from the diabetic muscle at the last sampling time was detected. This was confirmed by a negative glucose A-I (arterial-interstitial difference) in the muscle. No differences were observed regarding lipolysis in the fat tissue in terms of A-I of glycerol. Intergroup differences were detected at the first sampling time, where arterial plasma glucose and plasma insulin levels were higher and muscle interstitial glucose lower in the diabetic patients. Plasma insulin was higher in the diabetic patients even at the final measurement time. CONCLUSIONS: In terms of lipolysis in the fat tissue and glucose transport in the muscle, the non-diabetic patients were metabolically 'diabetics' during surgery. Despite strict blood glucose control, disturbances in glucose homeostasis in the diabetic muscle persist. Microdialysis was easy to use during cardiac surgery.

  • 87.
    Szabó, Zoltán
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Rolf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    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.
    Insulin resistance during coronary surgery in diabetic and non-diabetic patients-parallel microdialysis and organ balance technique studying skeletal muscle (preliminary results)2007In: Diabetologia(ISSN 0012-186X), vol 50, 2007, Vol. 50, p. 275-276Conference paper (Refereed)
  • 88.
    Szabó, Zoltán
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Andersson, Rolf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    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.
    Insulin resistance during coronary surgery in diabetic and non-diabetic patients-parallel microdialysis and organ balance technique studying skeletal muscle (preliminary results)2007In: European Association for the Study of Diabetes EASD,2007, 2007Conference paper (Refereed)
    Abstract [en]

        

  • 89.
    Szabó, Zoltán
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    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.
    Intraoperative insulin resistance during coronary surgery in diabetic and non-diabetic patients- preliminary results2007In: EASD: Diabetes Cardiovascular Disease Study Group Meeting,2007, 2007Conference paper (Other academic)
  • 90.
    Szabó, Zoltán
    et al.
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Håkanson, Erik
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Jorfeldt, Lennart
    Department of Thoracic Physiology, Karolinska Hospital, Stockholm, Sweden.
    Svedjeholm, Rolf
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Effects of high-dose glucose–insulin–potassium on myocardial metabolism after coronary surgery in patients with Type II diabetes2001In: Clinical Science, ISSN 0143-5221, Vol. 101, no 1, p. 37-43Article in journal (Refereed)
    Abstract [en]

    The effects of glucose–insulin–potassium (GIK) on cardiac metabolism have been studied previously in non-diabetic patients after cardiac surgery. Although patients with diabetes mellitus can be expected to benefit most from such treatment, the impact of GIK in diabetic patients undergoing cardiac surgery remains unexplored. Therefore the present study investigates the effects of high-dose GIK on myocardial substrate utilization after coronary surgery in patients with Type II diabetes. A total of 20 patients with Type II diabetes undergoing elective coronary surgery were randomly allocated to either post-operative high-dose GIK or standard post-operative care, including insulin infusion if necessary to keep blood glucose below 10 mmol/l. Myocardial substrate utilization was studied using the coronary sinus catheter technique. Haemodynamic state was assessed with the aid of Swan–Ganz catheters. High-dose GIK caused a shift towards carbohydrate utilization, with significant lactate uptake throughout the study period and significant uptake of glucose after 4 h. Arterial levels of non-esterified fatty acids and b-hydroxybutyric acid decreased, and after 1 h no significant uptake of these substrates was found. Increases in the cardiac index and stroke volume index were found in patients treated with high-dose GIK. A decrease in systemic vascular resistance was found both in the control group and in the high-dose GIK group. We conclude that high-dose GIK can be used in diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of non-esterified fatty acids and b-hydroxybutyric acid. This could have implications for treatment of the diabetic heart in association with surgery and ischaemia.

  • 91. Söderlund, Gustav
    et al.
    Haarhaus, Mathias
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Chisalita, Ioana Simona
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    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.
    Inhibition of puromycin-induced apoptosis in breast cancer cells by IGF-I occurs simultaneously with increased protein synthesis2004In: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317, Vol. 51, no 1Article in journal (Refereed)
    Abstract [en]

    The objective of the following work was to study the apoptosis inducing effect of puromycin in MCF-7 breast cancer cells and compare this effect with cycloheximide and emetine, 2 other inhibitors of protein synthesis. We also wished to investigate if the apoptosis modulating effect of insulin-like growth factor-1 (IGF-I) was similar for the 3 inhibitors. An immunological assay, quantifying mono- and oligonucleosome fragments and morphological criteria after nuclear staining, were used to study apoptosis. Protein synthesis was measured by incorporation of 3H-leucine in the cells, and solution hybridization and Western blot were performed to estimate IGF-I receptor m-RNA and IGF-I receptor protein respectively. Puromycin at 0.5 μg/ml induced a high level of apoptosis in MCF-7 breast cancer cells, although there was still a non-negligible amount of synthesized protein. In the case of cycloheximide and emetine, apoptosis occured when protein synthesis was almost completely blocked. IGF-I at a concentration of 10 ng/ml significantly reduced the level of apoptosis induced by puromycin, emetine, or cycloheximide. We also noticed a parallel increase in 3H-leucine incorporation when apoptosis induced by puromycin was lowered as an effect of IGF-I, in contrast to cycloheximide and emetine where IGF-I reduced the apoptosis level without increasing the 3H-leucine incorporation. At a higher concentration of puromycin (5. 7 μg/ml), which blocked protein synthesis, IGF-I at 10 ng/ml did not reduce apoptosis. The level of IGF-I receptor m-RNA was not influenced by the use of a concentration of puromycin (0.5 μg/ml) inducing a high degree of apoptosis. These results suggest, that reduction of puromycin-induced apoptosis by IGF-I occurs simultaneously with increased protein synthesis, in contrast to emetine and cycloheximide. Furthermore it would appear that puromycin-induced apoptosis is not caused by reduced levels of IGF-I receptors.

  • 92. Torffvit, Ole
    et al.
    Eriksson, Jan W
    Henricsson, Marianne
    Sundkvist, Göran
    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.
    Blohmé, Göran
    Bolinder, Jan
    Nyström, Lennart
    Östman, Jan
    Svensson, Maria
    Early changes in glomerular size selectivity in young adults with type 1 diabetes and retinopathy. Results from the Diabetes Incidence Study in Sweden2007In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 21, no 4, p. 246-251Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the relationship between early-onset retinopathy and urinary markers of renal dysfunction. Research Design and Methods: The Diabetes Incidence Study in Sweden (DISS) aims to register all new cases of diabetes in young adults (15-34 years). In 1987-1988, 806 patients were reported and later invited to participate in a follow-up study focusing on microvascular complications after ∼10 years of diabetes. In the present study, 149 patients with type 1 diabetes, completed eye examination, and urine sampling were included. Results: The patients with retinopathy (n=58, 39%) had higher HbA1c (P<.001) and urinary IgG2/creatinine (P<.05) and IgG2/IgG4 ratios (P<.05). Patients with maculopathy had the highest levels. No significant differences in urinary albumin/creatinine, glycosaminoglycans (GAGs)/creatinine, Tamm-Horsfall protein (THP)/creatinine, and IgG4/creatinine ratios were found. Women had higher urinary albumin/creatinine (P<.01) and urinary IgG2/creatinine ratios (P<.01) than men. Conclusions: Young adults with type 1 diabetes and early-onset retinopathy had higher IgG2/creatinine and IgG2/IgG4 ratios than patients without retinopathy indicating that retinopathy is associated with a change in glomerular size selectivity. This was found in association with normal urinary albumin and THP excretion and may be suspected to reflect early general vascular changes. © 2007 Elsevier Inc. All rights reserved.

  • 93. Törn, C
    et al.
    Landin-Olsson, M
    Lernmark, Å
    Palmer, JP
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Blohmé, G
    Lithner, F
    Littorin, B
    Nyström, L
    Scherstén, B
    Sundkvist, G
    Wibell, L
    Östman, J
    Prognostic factors for the course of beta cell function in autoimmune diabetes2000In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 85, no 12, p. 4619-4623Article in journal (Refereed)
    Abstract [en]

    This study presents a 2-yr follow-up of 281 patients, aged 15-34 yr, diagnosed with diabetes between 1992 and 1993. At diagnosis, 224 (80%) patients were positive for at least one of the following autoantibodies: islet cell antibodies (ICAs), glutamic acid decarboxylase antibodies (GADAs), or tyrosine phosphatase antibodies (IA-2As), the remaining 57 (20%) patients were negative for all three autoantibodies. At diagnosis, C-peptide levels were lower (0.27, 0.16-0.40 nmol/L) in autoantibody-positive patients compared with autoantibody-negative patients (0.51, 0.28-0.78 nmol/L, P < 0.001). After 2 yr, C-peptide levels had decreased significantly in patients with autoimmune diabetes (0.20, 0.10-0.37 nmol/L, P = 0.0018), but not in autoantibody-negative patients. In patients with autoimmune diabetes, a low initial level of C-peptide (odds ratio, 2.6, 95% confidence interval, 1.7-4.0) and a high level of GADAs (odds ratio, 2.5, 95% confidence interval, 1.1-5.7) were risk factors for a C-peptide level below the reference level of 0.25 nmol/L 2 yr after diagnosis. Body mass index had a significant effect in the multivariate analysis only when initial C-peptide was not considered. Factors such as age, gender, levels of ICA or IA-2A or insulin autoantibodies (analyzed in a subset of 180 patients) had no effect on the decrease in ▀-cell function. It is concluded that the absence of pancreatic islet autoantibodies at diagnosis were highly predictive for a maintained ▀-cell function during the 2 yr after diagnosis, whereas high levels of GADA indicated a course of decreased ▀-cell function with low levels of C-peptide. In autoimmune diabetes, an initial low level of C-peptide was a strong risk factor for a decrease in ▀-cell function and conversely high C-peptide levels were protective. Other factors such as age, gender, body mass index, levels of ICA, IA-2A or IAA had no prognostic importance.

  • 94. Törn, C
    et al.
    Landin-Olsson, M
    Lernmark, Å
    Scherstén, B
    Östman, J
    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, E
    Blohmé, G
    Bolinder, J
    Eriksson, J
    Littorin, B
    Nyström, L
    Sundkvist, G
    Combinations of beta cell specific autoantibodies at diagnosis of diabetes in young adults reflects different courses of beta cell damage.2001In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 33, p. 115-120Article in journal (Refereed)
  • 95. Törn, Carina
    et al.
    Landin-Olsson, Mona
    Östman, Jan
    Scherstén, Bengt
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Blohmé, Göran
    Björk, Elisabeth
    Bolinder, Jan
    Eriksson, Jan
    Littorin, Bengt
    Nyström, Lennarth
    Sundkvist, Göran
    Lernmark, Åke
    Glutamic acid decarboxylase antibodies (GADA) is the most important factor for prediction of insulin therapy within 3 years in young adult diabetic patients not classified as Type 1 diabetes on clinical grounds2000In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 16, no 6, p. 442-447Article in journal (Refereed)
    Abstract [en]

    Background Differentiation between Type 1 and Type 2 diabetes in adults is difficult at diagnosis. In this study we tested the hypothesis that autoantibodies at diagnosis are predictive for insulin treatment within 3 years in patients initially not classified as Type 1 diabetes. Methods In a nationwide population-based study, blood samples were obtained from 764 patients, all diagnosed with diabetes during a 2-year period. At diagnosis, 583 (76%) were classified as Type 1, 110 (14%) as Type 2 and 71 (9.3%) could not be classified. Results Among patients not classified as Type 1 diabetes, 52 (47%) of Type 2 and 42 (59%) of unclassified patients were positive for islet cell antibodies CICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A). These patients (n=94) had lower body mass index (BMI) (p<0.001) and lower C-peptide (p<0.001) compared to the autoantibody negative patients (n=87). Compared to clinically classified Type 1 diabetes patients positive for autoantibodies (n=477), they have higher BMI (p<0.001), higher C-peptide (p<0.001) and the same levels of ICA, GADA and IA-2A. After 3 years, 93% of autoantibody positive patients initially not classified as Type 1 were on insulin. When ICA, GADA, IA-2A, BMI and C-peptide were tested in a multiple logistic regression, only GADA was signiificant for insulin treatment within 3 years (OR = 18.8, 95% CI 1.8-191) in patients treated with diet or oral drugs at diagnosis. Conclusions A correct classification is difficult in adult diabetic patients. The presence of pancreatic autoantibodies, especially GADA, at diagnosis of diabetes are highly predictive for insulin therapy within 3 years from diagnosis. Copyright ⌐ 2000 John Wiley & Sons, Ltd.

  • 96.
    Valdimarsson, Trausti
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Toss, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Järnerot, G
    IHM Gastroenterologi och hepatologi.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC-2, GE: endomed.
    Ström, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, GE: gastromed.
    Low circulating insulin-like growth factor I in coeliac disease and its relation to bone mineral density.1999In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 34, no 9, p. 904-908Article in journal (Refereed)
  • 97.
    van Dijk, P R
    et al.
    Diabetes Centre, Zwolle, The Netherlands .
    Logtenberg, S J J
    University Medical Center Groningen, The Netherlands.
    Groenier, K H
    Diabetes Centre, Zwolle. University Medical Center Groningen, The Netherlands.
    Kleefstra, N
    University Medical Center Groningen, The Netherlands.
    Bilo, H J G
    University Medical Center Groningen, The Netherlands.
    Arnqvist, Hans
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Effect of i.p. insulin administration on IGF1 and IGFBP1 in type 1 diabetes.2014In: Endocrine connections, ISSN 2049-3614, Vol. 3, no 1, p. 17-23Article in journal (Refereed)
    Abstract [en]

    In type 1 diabetes mellitus (T1DM), low concentrations of IGF1 and high concentrations of IGF-binding protein 1 (IGFBP1) have been reported. It has been suggested that these abnormalities in the GH-IGF1 axis are due to low insulin concentrations in the portal vein. We hypothesized that the i.p. route of insulin administration increases IGF1 concentrations when compared with the s.c. route of insulin administration. IGF1 and IGFBP1 concentrations in samples derived from an open-label, randomized cross-over trial comparing the effects of s.c. and i.p. insulin delivery on glycaemia were determined. T1DM patients were randomized to receive either 6 months of continuous i.p. insulin infusion (CIPII) through an implantable pump (MIP 2007C, Medtronic) followed by 6 months of s.c. insulin infusion or vice versa with a washout phase in between. Data from 16 patients who had complete measurements during both treatment phases were analysed. The change in IGF1 concentrations during CIPII treatment was 10.4 μg/l (95% CI -0.94, 21.7 μg/l; P=0.06) and during s.c. insulin treatment was -2.2 μg/l (95% CI -13.5, 9.2 μg/l; P=0.69). When taking the effect of treatment order into account, the estimated change in IGF1 concentrations was found to be 12.6 μg/l (95% CI -3.1, 28.5 μg/l; P=0.11) with CIPII treatment compared with that with s.c. insulin treatment. IGFBP1 concentrations decreased to -100.7 μg/l (95% CI -143.0, -58.3 μg/l; P<0.01) with CIPII treatment. During CIPII treatment, parts of the GH-IGF1 axis changed compared with that observed during s.c. insulin treatment. This supports the hypothesis that the i.p. route of insulin administration is of importance in the IGF1 system.

  • 98.
    Van dijk, Peter R
    et al.
    Isala, Diabetes Centre, Zwolle, The Netherlands.
    Logtenberg, Susan J J
    University Medical Center Groningen, The Netherlands.
    Chisalita, Ioana Simona
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Hedman, Christina A.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Groenier, Klaas H
    University Medical Center Groningen, The Netherlands.
    Gans, Reinold O B
    University Medical Center Groningen, The Netherlands.
    Kleefstra, Nanne
    University Medical Center Groningen, The Netherlands.
    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.
    Bilo, Henk J G
    University Medical Center Groningen, The Netherlands.
    After 6years of intraperitoneal insulin administration IGF-I concentrations in T1DM patients are at low-normal level.2015In: Growth Hormone & IGF Research, ISSN 1096-6374, E-ISSN 1532-2238, Vol. 25, no 6, p. 316-319Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Low concentrations of insulin-like growth factor-I (IGFI) have been reported in type 1 diabetes mellitus (T1DM), suggested to be due to low insulin concentrations in the portal vein. The aim was to describe the long-term course of IGFI concentrations among T1DM subjects treated with continuous intraperitoneal (IP) insulin infusion (CIPII).

    DESIGN: Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) insulin therapy in 2006 were followed until 2012. IGF-I measurements were performed at the start of the 2006 study, after the 6month SC- and CIPII treatment phase in 2006 and during CIPII therapy in 2012. Z-scores were calculated to compare the IGF-I concentrations with age-specific normative range values of a non-DM reference population.

    RESULTS: In 2012, IGF-I Z-scores (-0.7; 95% confidence interval -1.3, -0.2) were significantly higher than at the start of the 2006 study (-2.5; -3.3, -1.8), the end of the SC (-2.0; -2.6, -1.5) and CIPII (-1.6; -2.1, -1.0) treatment phase with a mean difference of: 1.8 (0.9, 2.7), 1.3 (0.5, 2.1) and 0.8 (0.1, 1.6), respectively.

    CONCLUSION: After 6years of treatment with CIPII, IGF-I concentrations among T1DM patients increased to a level that is higher than during prior SC insulin treatment and is in the lower normal range compared to a non-DM reference population. The results of this study suggest that long-term IP insulin administration influences the IGF system in T1DM.

  • 99.
    van Dijk, Peter R.
    et al.
    Isala, Netherlands.
    Logtenberg, Susan J. J.
    Isala, Netherlands; Diakonessen Hospital, Netherlands.
    Chisalita, Ioana Simona
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Hedman, Christina
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Groenier, Klaas H.
    Isala, Netherlands; University of Groningen, Netherlands.
    Gans, Reinold O. B.
    University of Groningen, Netherlands.
    Kleefstra, Nanne
    Isala, Netherlands; University of Groningen, Netherlands; Langerhans Medical Research Grp, Netherlands.
    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.
    Bilo, Henk J. G.
    Isala, Netherlands; Isala, Netherlands; University of Groningen, Netherlands.
    Different Effects of Intraperitoneal and Subcutaneous Insulin Administration on the GH-IGF-1 Axis in Type 1 Diabetes2016In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 6, p. 2493-2501Article in journal (Refereed)
    Abstract [en]

    Context: In type 1 diabetes mellitus, low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of GH and IGFBP-1 are present, probably due to portal vein insulinopenia. Objective: To test the hypothesis that continuous ip insulin infusion (CIPII) has a more pronounced effect than sc insulin therapy on regulation of the GH-IGF-1 axis. Design: This was a prospective, observational case-control study. Measurements were performed twice at a 26-week interval. Setting: Two secondary care hospitals in the Netherlands participated in the study. Patients: There were a total of 184 patients, age-and gender-matched, of which 39 used CIPII and 145 sc insulin therapy for the past 4 years. Outcomes: Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1, and IGFBP-3. Results: IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 mu g/liter (95% confidence interval [CI], 111-138) vs 108 mu g/liter (95% CI 102-115) (P = .035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/liter (95% CI, 3.49 - 4.10) vs 3.31 mg/liter (95% CI, 3.173.47) for IGFBP-3, 50.9 mu g/liter (95% CI, 37.9 - 68.2) vs 102.6 mu g/liter (95% CI, 87.8 - 119.8) for IGFBP-1 and 0.68 mu g/liter (95% CI, 0.44 - 1.06) vs 1.21 mu g/liter (95% CI, 0.95-1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c. Conclusions: The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during sc insulin therapy.

  • 100.
    Vrethem, Magnus
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Boivie, Jörgen
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Arnqvist, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Cell biology.
    Holmgren, Helen
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lindström, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-endokrin.
    Painful polyneuropathy in patients with and without diabetes: Clinical, neurophysiologic, and quantitative sensory characteristics2002In: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 18, no 2, p. 122-127Article in journal (Refereed)
    Abstract [en]

    Objectives: To study pain characteristics and peripheral nerve involvement in patients with painful diabetic and nondiabetic polyneuropathy in comparison with patients with nonpainful polyneuropathy. Patients and Methods: Fifty-five patients with polyneuropathy (37 with painful polyneuropathy, of whom 19 had diabetes and 18 had no diabetes, and 18 with painless polyneuropathy of different etiologies) were examined clinically using quantitative sensory tests and neurophysiology. Pain intensity and characteristics were analyzed by daily ratings on a 10-step verbal scale and by a questionnaire. Results: Most patients experienced pain of more than one character. There was no clear difference in character or duration of pain between patients with and without diabetes. The mean value of the daily rating of pain intensity showed that pain was more severe in the evenings than in the mornings and that diabetic patients reported worse pain than nondiabetic patients. Thirty-two of the 37 patients with pain had paresthesias and/or dysesthesias, whereas only 7 of 18 patients without pain had paresthesias. Pain was always located in the feet, and, in most patients, also in the lower part of the legs. Some patients also experienced pain in the hands. Tactile sensibility, measured by quantitative tests, was more affected in both diabetic and nondiabetic patients with painful polyneuropathy compared with patients without pain (p = 0.02). Temperature, pain, and vibratory sensibility were equally affected in all patient groups. Nerve conduction velocity, amplitudes, and distal latency were equally affected in the pain group as compared with the control group, indicating that both thin and thick nerve afferents are affected in patients with painful as well as nonpainful polyneuropathy and that etiology has no clear impact on nerve involvement. Conclusions: Neuropathy pain was always located in the feet and more severe in diabetic patients compared with patients with neuropathy pain of other etiologies. The authors also found evidence for a greater tactile sensibility involvement in patients with neuropathy pain, irrespective of etiology, whereas other quantitative sensibility and neurography parameters were equally affected in all patient groups.

123 51 - 100 of 105
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf