Kristian Folkvord Hanssen

• Mynarek, Ida Maria; Krogvold, Lars; Mørk, Freja B.; Lawaetz, Trine; Roald, Trine & Fagerland, Morten [Show all 14 contributors for this article] (2025). Three-Year Follow-up After Antiviral Treatment in New-Onset Type 1 Diabetes: Results From the Diabetes Virus Detection and Intervention Trial. Diabetes Care. ISSN 0149-5992. 48(3), p. 481–488. doi: 10.2337/dc24-2121. Full text in Research Archive
• Kelly, Clare B.; Karanchi, Harsha; Yu, Jeremy Y.; Leyva, Misti J.; Jenkins, Alicia J. & Nankervis, Alison J. [Show all 13 contributors for this article] (2023). Plasma AGE and Oxidation Products, Renal Function, and Preeclampsia in Pregnant Women with Type 1 Diabetes: A Prospective Observational Study. Journal of Diabetes Research. ISSN 2314-6745. 2023. doi: 10.1155/2023/8537693. Full text in Research Archive Show summary

  Aims.We aimed to determine whether plasma advanced glycation end products or oxidation products (AGE/oxidation-P) predict altered renal function and/or preeclampsia (PE) in pregnant women with type 1 diabetes. Methods. Prospectively, using a nested case-control design, we studied 47 pregnant women with type 1 diabetes, of whom 23 developed PE and 24 did not. Nineteen nondiabetic, normotensive pregnant women provided reference values. In plasma obtained at ~12, 22, and 32 weeks’ gestation (visits 1, 2, and 3; V1-V3), we measured five AGE products (carboxymethyllysine (CML), carboxyethyl-lysine (CEL), methylglyoxal-hydroimidazolone (MGH1), 3-deoxyglucosone hydroimidazolone (3DGH), and glyoxal-hydroimidazolone (GH1)) and four oxidation products (methionine sulfoxide (MetSO), 2-aminoadipic acid (2-AAA), 3-nitrotyrosine (3NT), and dityrosine (DT)), by liquid chromatography/mass spectroscopy. Clinical outcomes were “estimated glomerular filtration rate” (eGFR) at each visit and onset of PE. Results. In diabetic women, associations between AGE/oxidation-P and eGFR were found only in those who developed PE. In this group, CEL, MGH1, and GH1 at V2 and CML, CEL, MGH1, and GH1 at V3 were inversely associated with contemporaneous eGFR, while CEL, MGH1, 3DGH, and GH1 at V2 were inversely associated with eGFR at V3 (all p < 0:05). There were no associations of plasma AGE or oxidation-P with pregnancy-related development of proteinuria or PE. Conclusions. Inverse associations of second and early third trimester plasma AGE with eGFR among type 1 diabetic women who developed PE suggest that these patients constitute a subset susceptible to AGE-mediated injury and thus to cardiorenal complications later in life. However, AGE/oxidation-P did not predict PE in type 1 diabetic women.

• Krogvold, Lars; Mynarek, Ida Maria; Ponzi, Erica; Mørk, Freja Barrett; Hessel, Trine Witzner & Roald, Trine [Show all 14 contributors for this article] (2023). Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial. Nature Medicine. ISSN 1078-8956. 29(4), p. 2902-2908–2902-2908. doi: 10.1038/s41591-023-02576-1. Full text in Research Archive Show summary

  Previous studies showed a low-grade enterovirus infection in the pancreatic islets of patients with newly diagnosed type 1 diabetes (T1D). In the Diabetes Virus Detection (DiViD) Intervention, a phase 2, placebo-controlled, randomized, parallel group, double-blind trial, 96 children and adolescents (aged 6–15 years) with new-onset T1D received antiviral treatment with pleconaril and ribavirin (n = 47) or placebo (n = 49) for 6 months, with the aim of preserving β cell function. The primary endpoint was the mean stimulated C-peptide area under the curve (AUC) 12 months after the initiation of treatment (less than 3 weeks after diagnosis) using a mixed linear model. The model used longitudinal log-transformed serum C-peptide AUCs at baseline, at 3 months, 6 months and 1 year. The primary endpoint was met with the serum C-peptide AUC being higher in the pleconaril and ribavirin treatment group compared to the placebo group at 12 months (average marginal effect = 0.057 in the linear mixed model; 95% confidence interval = 0.004–0.11, P = 0.037). The treatment was well tolerated. The results show that antiviral treatment may preserve residual insulin production in children and adolescent with new-onset T1D. This provides a rationale for further evaluating antiviral strategies in the prevention and treatment of T1D. European Union Drug Regulating Authorities Clinical Trials identifier: 2015-003350-41.

• Sveen, Kari Anne; Holte, Kristine Bech; Svanteson, Mona; Hanssen, Kristian F.; Nilsson, Jan-Åke & Bengtsson, Eva [Show all 7 contributors for this article] (2021). Autoantibodies against methylglyoxal-modified apolipoprotein B100 and apob100 peptide are associated with less coronary artery atherosclerosis and retinopathy in long-term type 1 diabetes. Diabetes Care. ISSN 0149-5992. 44(6), p. 1402–1409. doi: 10.2337/dc20-2089. Full text in Research Archive
• Holte, Kristine Bech; Svanteson, Mona; Hanssen, Kristian Folkvord; Sveen, Kari Anne; Seljeflot, Ingebjørg & Solheim, Svein [Show all 9 contributors for this article] (2020). Collagen methionine sulfoxide and glucuronidine/LW-1 are markers of coronary artery disease in long-term survivors with type 1 diabetes. The Dialong study. PLOS ONE. doi: 10.1371/journal.pone.0233174. Full text in Research Archive Show summary

  Objectives Type 1 diabetes is a risk factor for coronary heart disease. The underlying mechanism behind the accelerated atherosclerosis formation is not fully understood but may be related to the formation of oxidation products and advanced glycation end-products (AGEs). We aimed to examine the associations between the collagen oxidation product methionine sulfoxide; the collagen AGEs methylglyoxal hydroimidazolone (MG-H1), glucosepane, pentosidine, glucuronidine/LW-1; and serum receptors for AGE (RAGE) with measures of coronary artery disease in patients with long-term type 1 diabetes. Methods In this cross-sectional study, 99 participants with type 1 diabetes of ≥ 45-year duration and 63 controls without diabetes had either established coronary heart disease (CHD) or underwent Computed Tomography Coronary Angiography (CTCA) measuring total, calcified and soft/mixed plaque volume. Skin collagen methionine sulfoxide and AGEs were measured by liquid chromatography-mass spectrometry and serum sRAGE/esRAGE by ELISA. Results In the diabetes group, low levels of methionine sulfoxide (adjusted for age, sex and mean HbA1c) were associated with normal coronary arteries, OR 0.48 (95% CI 0.27–0.88). Glucuronidine/LW-1 was associated with established CHD, OR 2.0 (1.16–3.49). MG-H1 and glucuronidine/LW-1 correlated with calcified plaque volume (r = 0.23–0.28, p<0.05), while pentosidine correlated with soft/mixed plaque volume (r = 0.29, p = 0.008), also in the adjusted analysis. Conclusions Low levels of collagen-bound methionine sulfoxide were associated with normal coronary arteries while glucuronidine/LW-1 was positively associated with established CHD in long-term type 1 diabetes, suggesting a role for metabolic and oxidative stress in the formation of atherosclerosis in diabetes.

• Kelly, Clare B.; Wagner, Carol L.; Shary, Judith R.; Leyva, Misti J.; Yu, Jeremy Y. & Jenkins, Alicia J. [Show all 13 contributors for this article] (2020). Vitamin D Metabolites and Binding Protein Predict Preeclampsia in Women with Type 1 Diabetes. Nutrients. 12(7), p. 1–12. doi: 10.3390/nu12072048. Full text in Research Archive Show summary

  The risk for preeclampsia (PE) is enhanced ~4-fold by the presence of maternal type 1 diabetes (T1DM). Vitamin D is essential for healthy pregnancy. We assessed the total, bioavailable, and free concentrations of plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and vitamin D binding protein (VDBP) at ~12, ~22, and ~32 weeks’ gestation (“Visits” (V) 1, 2, and 3, respectively) in 23 T1DM women who developed PE, 24 who remained normotensive, and 19 non-diabetic, normotensive women (reference controls). 25(OH)D deficiency was more frequent in diabetic than non-diabetic women (69% vs. 22%, p &lt; 0.05), but no measure of 25(OH)D predicted PE. By contrast, higher 1,25(OH)2D concentrations at V2 (total, bioavailable, and free: p &lt; 0.01) and V3 (bioavailable: p &lt; 0.05; free: p &lt; 0.01), lower concentrations of VDBP at V3 (p &lt; 0.05), and elevated ratios of 1,25(OH)2D/VDBP (V2, V3: p &lt; 0.01) and 1,25(OH)2D/25(OH)D (V3, p &lt; 0.05) were all associated with PE, and significance persisted in multivariate analyses. In summary, in women with T1DM, concentrations of 1,25(OH)2D were higher, and VDBP lower, in the second and third trimesters in women who later developed PE than in those who did not. 1,25(OH)2D may serve as a new marker for PE risk and could be implicated in pathogenesis.

• Kelly, Clare B.; Yu, Jeremy Y.; Jenkins, Alica J.; Nankervis, Alison J.; Hanssen, Kristian Folkvord & Garg, Satish K. [Show all 11 contributors for this article] (2019). Haptoglobin Phenotype Modulates Lipoprotein-Associated Risk for Preeclampsia in Women With Type 1 Diabetes. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 104(10), p. 4743–4755. doi: 10.1210/jc.2019-00723. Full text in Research Archive
• Holte, Kristine Bech; Svanteson, Mona; Hanssen, Kristian Folkvord; Haig, Ylva; Solheim, Svein & Berg, Tore Julsrud (2019). Undiagnosed coronary artery disease in long-term type 1 diabetes. The Dialong study. Journal of Diabetes and its Complications (JDC). ISSN 1056-8727. 33(5), p. 383–389. doi: 10.1016/j.jdiacomp.2019.01.006. Full text in Research Archive Show summary

  Aims We studied the total prevalence of obstructive coronary artery disease (CAD), undiagnosed CAD and absent CAD in persons with ≥45-year duration of type 1 diabetes (T1D) versus controls, and associations with mean HbA1c, LDL-cholesterol and blood pressure over 2–3 decades. Methods We included 76% (n = 103) of all persons with T1D diagnosed ≤1970 attending a diabetes center and 63 controls without diabetes. We collected 20–30 years of HbA1c, LDL-cholesterol and blood pressure measurements. Participants without previously diagnosed coronary heart disease (CHD) underwent Computed Tomography Coronary Angiography (CTCA). Undiagnosed obstructive CAD was defined as any coronary stenosis >50% on CTCA, absent CAD as no detected plaque, and total obstructive CAD as either obstructive CAD on CTCA or previous CHD diagnosis. Results The prevalence of undiagnosed, absent and obstructive CAD was 24% (21/88), 16% (14/88) and 35% (36/103) in T1D versus 10% (6/60), 50% (30/60) and 14% (9/63) in controls (all p < 0.05). Mean HbA1c was associated with undiagnosed obstructive CAD (OR 2.30 95% C.I. 1.13–4.69), while mean LDL-cholesterol was inversely associated with absent CAD (0.12, 0.04–0.43). Conclusions The prevalence of undiagnosed obstructive CAD was high (24%) in this cohort of long-term survivors with T1D. Mean LDL-cholesterol and HbA1c were associated with CAD.

• Kuric, Enida; Krogvold, Lars; Hanssen, Kristian Folkvord; Dahl-Jørgensen, Knut; Skog, Oskar & Korsgren, Olle (2018). No evidence for presence of mucosal-associated invariant T cells in the insulitic lesions in patients recently diagnosed with Type 1 diabetes. American Journal of Pathology. ISSN 0002-9440. 188(8), p. 1744–1748. doi: 10.1016/j.ajpath.2018.04.009. Full text in Research Archive
• Holm, Laurits J.; Krogvold, Lars; Hasselby, Jane P.; Kaur, Simranjeet; Claessens, Laura A. & Russell, Mark A. [Show all 15 contributors for this article] (2018). Abnormal islet sphingolipid metabolism in type 1 diabetes. Diabetologia. ISSN 0012-186X. 61(7), p. 1650–1661. doi: 10.1007/s00125-018-4614-2. Full text in Research Archive Show summary

  Aims/hypothesis Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice. Methods We examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy. Transcriptional analysis was used to evaluate expression of sphingolipid-related genes in isolated human islets. Genome-wide association studies (GWAS) and a T cell proliferation assay were used to identify type 1 diabetes related polymorphisms and test how these affect cellular islet autoimmunity. Finally, we treated NOD mice with fenofibrate, a known activator of sulfatide biosynthesis, to evaluate the effect on experimental autoimmune diabetes development. Results We found reduced amounts of sulfatide, 23% of the levels in control participants, in pancreatic islets of individuals with newly diagnosed type 1 diabetes, which were associated with reduced expression of enzymes involved in sphingolipid metabolism. Next, we discovered eight gene polymorphisms (ORMDL3, SPHK2, B4GALNT1, SLC1A5, GALC, PPARD, PPARG and B4GALT1) involved in sphingolipid metabolism that contribute to the genetic predisposition to type 1 diabetes. These gene polymorphisms correlated with the degree of cellular islet autoimmunity in a cohort of individuals with type 1 diabetes. Finally, using fenofibrate, which activates sulfatide biosynthesis, we completely prevented diabetes in NOD mice and even reversed the disease in half of otherwise diabetic animals. Conclusions/interpretation These results indicate that islet sphingolipid metabolism is abnormal in type 1 diabetes and suggest that modulation may represent a novel therapeutic approach.

• Heier, Martin; Stensæth, Knut Haakon; Brunborg, Cathrine; Seljeflot, Ingebjørg; Margeirsdottir, Hanna Dis & Hanssen, Kristian Folkvord [Show all 7 contributors for this article] (2018). Increased arterial stiffness in childhood onset diabetes: A cardiovascular magnetic resonance study. European Heart Journal-Cardiovascular Imaging. ISSN 2047-2404. 19(6), p. 694–700. doi: 10.1093/ehjci/jex178. Full text in Research Archive
• Kelly, Clare B.; Hookham, Michelle B.; Yu, Jeremy Y.; Jenkins, Alica J.; Nankervis, Alison J. & Hanssen, Kristian Folkvord [Show all 12 contributors for this article] (2018). Subclinical first trimester renal abnormalities are associated with preeclampsia in normoalbuminuric women with type 1 diabetes. Diabetes Care. ISSN 0149-5992. 41(1), p. 120–127. doi: 10.2337/dc17-1635. Full text in Research Archive
• Heier, Martin; Nygaard, Cathrine Skorpen; Brunborg, Cathrine; Seljeflot, Ingebjørg; MARGEIRSDOTTIR, HANNA DIS & Hanssen, Kristian Folkvord [Show all 8 contributors for this article] (2018). Preserved endothelial function in young adults with type 1 diabetes. PLOS ONE. 13:e0206523(10), p. 1–8. doi: 10.1371/journal.pone.0206523. Full text in Research Archive Show summary

  Background and aim Endothelial dysfunction is involved in the pathogenesis of atherosclerosis and is typically present in older adults with type 1 diabetes (T1D). In young adults, we aimed to assess the impact of T1D on endothelial function as detected by digital peripheral arterial tonometry (PAT) and its relationship with cardiovascular risk factors and long term glycemic control. Materials and methods Reactive hyperemia index (RHI) as a measure of endothelial function was assessed by PAT in 46 T1D patients and 32 healthy controls. All were participants in the "Atherosclerosis and Childhood Diabetes" study, with baseline values registered five years previously. Annual measurements of HbA1c for assessment of glycemic burden were provided by the Norwegian Childhood Diabetes Registry. Results The diabetes patients had a mean age of 20.8 years, a median duration of diabetes of 10.0 years and a mean HbA1c of 8.7%. RHI was not significantly decreased in the diabetes group, mean 2.00 (SD = 0.59) vs. 2.21 (SD = 0.56), p = .116. There was no gender difference or any associations with traditional risk factors. Furthermore, there was no significant association between RHI and either HbA1c or long term glycemic burden. Conclusions RHI as a measure of endothelial function was preserved in young adults with T1D compared with healthy controls.

• Kelly, Clare B.; Hookham, Michelle B.; Yu, Jeremy Y.; Lockhart, Samuel M.; Du, Mei & Jenkins, Alica J. [Show all 15 contributors for this article] (2017). Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes. Diabetologia. ISSN 0012-186X. 60(12), p. 2514–2524. doi: 10.1007/s00125-017-4415-z. Full text in Research Archive
• Kuric, Enida; Seiron, Peter; Krogvold, Lars; Edwin, Bjørn; Buanes, Trond & Hanssen, Kristian Folkvord [Show all 9 contributors for this article] (2017). Demonstration of tissue resident memory CD8 T cells in insulitic lesions in adult patients with recent-onset type 1 diabetes. American Journal of Pathology. ISSN 0002-9440. 187(3), p. 581–588. doi: 10.1016/j.ajpath.2016.11.002. Full text in Research Archive
• Heier, Martin; Borja, Mark S.; Brunborg, Cathrine; Seljeflot, Ingebjørg; MARGEIRSDOTTIR, HANNA DIS & Hanssen, Kristian Folkvord [Show all 8 contributors for this article] (2017). Reduced HDL function in children and young adults with type 1 diabetes. Cardiovascular Diabetology. 16:85, p. 1–8. doi: 10.1186/s12933-017-0570-2. Full text in Research Archive Show summary

  Background Patients with type 1 diabetes (T1D) are at increased risk of cardiovascular disease (CVD). Measures of high-density lipoprotein (HDL) function provide a better risk estimate for future CVD events than serum levels of HDL cholesterol. The objective of this study was to evaluate HDL function in T1D patients shortly after disease onset compared with healthy control subjects. Methods Participants in the atherosclerosis and childhood diabetes study were examined at baseline and after 5 years. At baseline, the cohort included 293 T1D patients with a mean age of 13.7 years and mean HbA1c of 8.4%, along with 111 healthy control subjects. Their HDL function, quantified by HDL-apoA-I exchange (HAE), was assessed at both time points. HAE is a measure of HDL’s dynamic property, specifically its ability to release lipid-poor apolipoprotein A-I (apoA-I), an essential step in reverse cholesterol transport. Results The HAE-apoA-I ratio, reflecting the HDL function per concentration unit apoA-I, was significantly lower in the diabetes group both at baseline, 0.33 (SD = 0.06) versus 0.36 (SD = 0.06) %HAE/mg/dL, p < 0.001 and at follow-up, 0.34 (SD = 0.06) versus 0.36 (SD = 0.06)  %HAE/mg/dL, p = 0.003. HAE-apoA-I ratio was significantly and inversely correlated with HbA1c in the diabetes group. Over the 5 years of the study, the mean HAE-apoA-I ratio remained consistent in both groups. Individual changes were less than 15% for half of the study participants. Conclusions This study shows reduced HDL function, quantified as HAE-apoA-I ratio, in children and young adults with T1D compared with healthy control subjects. The differences in HDL function appeared shortly after disease onset and persisted over time.

• Holte, Kristine Bech; Juel, Niels Gunnar; Brox, Jens Ivar; Hanssen, Kristian Folkvord; Fosmark, Dag Sigurd & Sell, David R. [Show all 8 contributors for this article] (2017). Hand, shoulder and back stiffness in long-term type 1 diabetes; cross-sectional association with skin collagen advanced glycation end-products. The Dialong study. Journal of Diabetes and its Complications (JDC). ISSN 1056-8727. 31(9), p. 1408–1414. doi: 10.1016/j.jdiacomp.2017.06.007. Full text in Research Archive
• Brunvand, Leif; Heier, Martin; Brunborg, Cathrine; Hanssen, Kristian Folkvord; Fugelseth, Drude & STENSÆTH, KNUT HAAKON [Show all 8 contributors for this article] (2017). Advanced glycation end products in children with type 1 diabetes and early reduced diastolic heart function. BMC Cardiovascular Disorders. 17(133). doi: 10.1186/s12872-017-0551-0. Full text in Research Archive Show summary

  Background Reduced diastolic function is an early sign of diabetes cardiomyopathy in adults and is associated with elevated levels of HbA1c and advanced glycation end products (AGEs). Objective To assess the associations between early reduced diastolic function and elevated levels of HbA1c and AGEs in children and adolescents with type 1 diabetes (T1D). Methods One hundred fourty six T1D patients (age 8–18 years) without known diabetic complications were examined with tissue Doppler imaging and stratified into two groups according to diastolic function. A clinical examination and ultrasound of the common carotid arteries were performed. Methylglyoxal-derived hydroimidazolone-1 (MG-H1) was measured by immunoassay. Results At inclusion, 36 (25%) participants were stratified into a low diastolic function group (E’/A’-ratio < 2.0). Compared to the rest of the T1D children, these participants had higher body mass index (BMI), 22.8 (SD = 4.0) vs. 20.1 (SD = 3.4) kg/m2, p < 0.001, higher systolic blood pressure 104.2 (SD = 8.7) vs. 99.7 (SD = 9.3) mmHg, p = 0.010, and higher diastolic blood pressure, 63.6 (SD = 8.3) vs. 59.9 (SD = 7.9) mmHg, p = 0.016. The distensibility coefficient was lower, 0.035 (SD = 0.010) vs. 0.042 (SD = 0.02) kPa−1, p = 0.013, Young’s modulus higher, 429 (SD = 106) vs. 365 (SD = 143), p = 0.009, and MG-H1 higher, 163.9 (SD = 39.2) vs. 150.3 (SD = 33.4) U/ml, p = 0.046. There was no difference in carotid intima-media thickness between the groups. There were no associations between reduced diastolic function and years from diagnosis, HBA1c, mean HBA1c, CRP or calculated glycemic burden. Logistic regression analysis showed that BMI was an independent risk factor for E’/A’-ratio as well as a non-significant, but relatively large effect size for MG-H1, indicating a possible role for AGEs. Conclusions Early signs of reduced diastolic function in children and adolescents with T1D had higher BMI, but not higher HbA1c. They also had elevated serum levels of the advanced glycation end product MG-H1, higher blood pressure and increased stiffness of the common carotid artery, but these associations did not reach statistical significance when tested in a logistic regression model.

• Heier, Martin; MARGEIRSDOTTIR, HANNA DIS; Torjesen, Peter A; Seljeflot, Ingebjørg; STENSÆTH, KNUT-HAAKON & Gaarder, Mario [Show all 9 contributors for this article] (2015). The advanced glycation end product methylglyoxal-derived hydroimidazolone-1 and early signs of atherosclerosis in childhood diabetes. Diabetes & vascular disease research. ISSN 1479-1641. 12(2), p. 139–145. doi: 10.1177/1479164114560910. Full text in Research Archive
• Heier, Martin; MARGEIRSDOTTIR, HANNA DIS; Brunborg, Cathrine; Hanssen, Kristian Folkvord; Dahl-Jørgensen, Knut & Seljeflot, Ingebjørg (2015). Inflammation in childhood type-1 diabetes; influence of glycemic control. Atherosclerosis. ISSN 0021-9150. 238, p. 33–37. doi: 10.1016/j.atherosclerosis.2014.11.018. Full text in Research Archive
• Heier, Martin; MARGEIRSDOTTIR, HANNA DIS; Gaarder, Mario; STENSÆTH, KNUT-HAAKON; Brunborg, Cathrine & Torjesen, Peter A [Show all 9 contributors for this article] (2015). Soluble RAGE and atherosclerosis in youth with type 1 diabetes: A 5-year follow-up study. Cardiovascular Diabetology. 14(126). doi: 10.1186/s12933-015-0292-2. Full text in Research Archive Show summary

  Background: Advanced glycation end products (AGEs) play a role in the development of late complications and ath‑ erosclerosis in diabetes by engaging the receptor for advanced glycation end products, RAGE. Receptor binding leads to activation of the vascular endothelium and increased inflammation in the vessel wall. The soluble variants of the receptor, endogenous secretory RAGE (esRAGE) and the cleaved cell ‑ surface part of RAGE, which together comprise soluble RAGE (sRAGE), are suggested to have a protective effect acting as decoys for RAGE. We aimed to test whether high levels of soluble variants of RAGE could be protective against atherosclerosis development. Methods: Participants in the prospective atherosclerosis and childhood diabetes study were examined at baseline (aged 8–18) and at follow ‑ up after 5 years. Both sRAGE and esRAGE were measured by immunoassay in 299 patients with type 1 diabetes and 112 healthy controls at baseline and 241 patients and 128 controls at follow ‑ up. The AGEs methylglyoxal ‑ derived hydroimidazolone ‑ 1 (MG ‑ H1) and carboxymethyllysine (CML) were measured by immunoas‑ say. The surrogate markers of atherosclerosis assessed were carotid intima ‑ media thickness (cIMT ), C ‑ reactive protein (CRP) and Young’s modulus, measures of arterial wall thickness, inflammation and arterial stiffness, respectively. Results: Levels of sRAGE and esRAGE correlated strongly both at baseline and at follow ‑ up in both diabetes patients and controls. With increasing age, mean values of both variants declined, independent of gender, diabetes or pubertal stage. In the diabetes group, multiple regression analysis showed a positive association between both variants of solu ‑ ble RAGE and cIMT. There was no significant relationship with Young’s modulus, but a negative association between sRAGE at baseline and CRP at follow ‑ up. The ratios between the AGEs and the variants of soluble RAGE were increased in diabetes patients compared to controls. Conclusions: The results show a possible protective effect of high levels of sRAGE at baseline against inflammation 5 years later, but not on arterial stiffness or wall thickness, in this cohort of adolescents and young adults with T1D. Keywords: Advanced glycation end products, Receptor for advanced glycation end products, sRAGE, esRAGE, Atherosclerosis, Type 1 diabetes, CRP.

• Krogvold, Lars; Skog, Oskar; Sundström, Görel; Edwin, Bjørn; Buanes, Trond & Hanssen, Kristian Folkvord [Show all 10 contributors for this article] (2015). Function of isolated pancreatic islets from patients at onset of type 1 diabetes: Insulin secretion can be restored after some days in a nondiabetogenic environment in vitro results from the divid study. Diabetes. ISSN 0012-1797. 64(7), p. 2506–2512. doi: 10.2337/db14-1911. Full text in Research Archive
• Basu, Arpita; Yu, Jeremy Y.; Jenkins, Alica J.; Nankervis, Alison J.; Hanssen, Kristian Folkvord & Henriksen, Tore [Show all 13 contributors for this article] (2015). Trace elements as predictors of preeclampsia in type 1 diabetic pregnancy. Nutrition Research. ISSN 0271-5317. 35(5), p. 421–430. doi: 10.1016/j.nutres.2015.04.004. Full text in Research Archive
• Sveen, Kari Anne; Dahl-Jørgensen, Knut; STENSÆTH, KNUT-HAAKON; Angel, Kristin; Seljeflot, Ingebjørg & Sell, David R [Show all 8 contributors for this article] (2015). Glucosepane and oxidative markers in skin collagen correlate with intima media thickness and arterial stiffness in long-term type 1 diabetes. Journal of Diabetes and its Complications (JDC). ISSN 1056-8727. 29(3), p. 407–412. doi: 10.1016/j.jdiacomp.2014.12.011. Full text in Research Archive
• Krogvold, Lars; Wiberg, Anna; Edwin, Bjørn; Buanes, Trond; Jahnsen, Frode Lars & Hanssen, Kristian Folkvord [Show all 10 contributors for this article] (2015). Insulitis and characterisation of infiltrating T cells in surgical pancreatic tail resections from patients at onset of type 1 diabetes. Diabetologia. ISSN 0012-186X. 59(3), p. 492–501. doi: 10.1007/s00125-015-3820-4. Full text in Research Archive Show summary

  Aims/hypothesis It is thought that T cells play a major role in the immune-mediated destruction of beta cells in type 1 diabetes, causing inflammation of the islets of Langerhans (insulitis). The significance of insulitis at the onset of type 1 diabetes is debated, and the role of the T cells poorly understood. Methods In the Diabetes Virus Detection (DiViD) study, pancreatic tissue from six living patients with recent-onset type 1 diabetes was collected. The insulitis was characterised quantitatively by counting CD3+ T cells, and qualitatively by transcriptome analysis targeting 84 T and B lymphocyte genes of laser-captured microdissected islets. The findings were compared with gene expression in T cells collected from kidney biopsies from allografts with ongoing cellular rejection. Cytokine and chemokine release from isolated islets was characterised and compared with that from islets from nondiabetic organ donors. Results All six patients fulfilled the criteria for insulitis (5–58% of the insulin-containing islets in the six patients had ≥15 T cells/islet). Of all the islets, 36% contained insulin, with several resembling completely normal islets. The majority (61– 83%) of T cells were found as peri-insulitis rather than within the islet parenchyma. The expression pattern of T cell genes was found to be markedly different in islets compared with the rejected kidneys. The islet-infiltrating T cells showed only background levels of cytokine/chemokine release in vitro. Conclusions/interpretation Insulitis and a significant reserve reservoir for insulin production were present in all six cases of recent-onset type 1 diabetes. Furthermore, the expression patterns and levels of cytokines argue for a different role of the T cells in type 1 diabetes when compared with allograft rejection.

• Krogvold, Lars; Edwin, Bjørn; Buanes, Trond; Frisk, Gun; Skog, Oskar & Anagandula, Mahesh [Show all 19 contributors for this article] (2015). Detection of a low-grade enteroviral infection in the islets of langerhans of living patients newly diagnosed with type 1 diabetes. Diabetes. ISSN 0012-1797. 64(5), p. 1682–1687. doi: 10.2337/db14-1370. Full text in Research Archive Show summary

  The Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3-9 weeks after onset of type 1 diabetes in six adult patients (age 24-35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh-frozen whole pancreatic tissue using PCR and sequencing. Nondiabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetic patients (two of nine controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (one of nine controls). Enterovirus-specific RNA sequences were detected in four of six patients (zero of six controls). The results were confirmed in various laboratories. Only 1.7% of the islets contained VP1(+) cells, and the amount of enterovirus RNA was low. The results provide evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, which is consistent with the possibility that a low-grade enteroviral infection in the pancreatic islets contributes to disease progression in humans.

• Eidem, Ingvild; Vangen, Siri; Henriksen, Tore; Vollset, Stein Emil; Hanssen, Kristian Folkvord & Joner, Geir [Show all 7 contributors for this article] (2014). Discrepancy in term calculation from second trimester ultrasound scan versus last menstrual period in women with type 1 diabetes. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 93(8), p. 809–816. doi: 10.1111/aogs.12422. Full text in Research Archive
• Krogvold, Lars; Edwin, Bjørn; Buanes, Trond; Ludvigsson, Johnny; Korsgren, Olle & Hyöty, Heikki [Show all 9 contributors for this article] (2014). Pancreatic biopsy by minimal tail resection in live adult patients at the onset of type 1 diabetes: experiences from the DiViD study. Diabetologia. ISSN 0012-186X. 57(4), p. 841–843. doi: 10.1007/s00125-013-3155-y. Full text in Research Archive
• Sveen, Kari Anne; Nerdrum, Tone; Hanssen, Kristian Folkvord; Brekke, Magne; Torjesen, Peter A & Strauch, Christopher M [Show all 10 contributors for this article] (2014). Impaired left ventricular function and myocardial blood flow reserve in patients with long-term type 1 diabetes and no significant coronary artery disease: Associations with protein glycation. Diabetes & vascular disease research. ISSN 1479-1641. 11(2), p. 84–91. doi: 10.1177/1479164113518805. Full text in Research Archive
• Sveen, Kari Anne; Karimé, Bassam; Jørum, Ellen; Mellgren, Svein Ivar; Fagerland, Morten & Monnier, Vincent [Show all 8 contributors for this article] (2013). Small- and large-fiber neuropathy after 40 years of type 1 diabetes associations with glycemic control and advanced protein glycation: the Oslo Study. Diabetes Care. ISSN 0149-5992. 36(11), p. 3712–3717. doi: 10.2337/dc13-0788. Full text in Research Archive Show summary

  OBJECTIVE To study large- and small-nerve fiber function in type 1 diabetes of long duration and associations with HbA_1c and the advanced glycation end products (AGEs) N-&#949-(carboxymethyl)lysine (CML) and methylglyoxal-derived hydroimidazolone.<p> <p>RESEARCH DESIGN AND METHODS In a long-term follow-up study, 27 persons with type 1 diabetes of 40 &#177 3 years duration underwent large-nerve fiber examinations, with nerve conduction studies at baseline and years 8, 17, and 27. Small-fiber functions were assessed by quantitative sensory thresholds (QST) and intraepidermal nerve fiber density (IENFD) at year 27. HbA_1cwas measured prospectively through 27 years. Serum CML was measured at year 17 by immunoassay. Serum hydroimidazolone was measured at year 27 with liquid chromatography– mass spectrometry. <p>RESULTS Sixteen patients (59%) had large-fiber neuropathy. Twenty-two (81%) had smallfiber dysfunction by QST. Heat pain thresholds in the foot were associated with hydroimidazolone and HbA_1c. IENFD was abnormal in 19 (70%) and significantly lower in diabetic patients than in age-matched control subjects (4.3 &#177 2.3 vs. 11.2 &#177 3.5 mm, P , 0.001). IENFD correlated negatively with HbA_1c over 27 years (r = 20.4, P = 0.04) and CML (r = 20.5, P = 0.01). After adjustment for age, height, and BMI in a multiple linear regression model, CML was still independently associated with IENFD. <p>CONCLUSIONS Small-fiber sensory neuropathy is a major manifestation in type 1 diabetes of 40 years duration and more prevalent than large-fiber neuropathy. HbA1c and the AGEs CML and hydroimidazolone are important risk factors in the development of large- and small-fiber dysfunction in long-term type 1 diabetes.

• Du, Mei; Basu, Arpita; Fu, Dongxu; Wu, Mingyuan; Centola, Michael & Jenkins, Alica J. [Show all 12 contributors for this article] (2013). Serum Inflammatory Markers and Preeclampsia in Type 1 Diabetes A prospective study. Diabetes Care. ISSN 0149-5992. 36(7), p. 2054–2061. doi: 10.2337/dc12-1934. Full text in Research Archive
• Fraser, David; Diep, Lien My; Hynås, Inger Anette; Nilsen, Kristian Bernhard; Sveen, Kari Anne & Seljeflot, Ingebjørg [Show all 7 contributors for this article] (2012). The Effects of Long-Term Oral Benfotiamine Supplementation on Peripheral Nerve Function and Inflammatory Markers in Patients With Type 1 Diabetes A 24-month, double-blind, randomized, placebo-controlled trial. Diabetes Care. ISSN 0149-5992. 35(5), p. 1095–1097. doi: 10.2337/dc11-1895. Full text in Research Archive
• Basu, Arpita; Alaupovic, Petar; Wu, Mingyuan; Jenkins, Alica J.; Yu, Yongxin & Nankervis, Alison J. [Show all 19 contributors for this article] (2012). Plasma Lipoproteins and Preeclampsia in Women with Type 1 Diabetes: A Prospective Study. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 97(5), p. 1752–1762. doi: 10.1210/jc.2011-3255. Full text in Research Archive
• Yu, Y; Hanssen, Kristian Folkvord; Kalyanaraman, V; Chirindel, A; Jenkins, AJ & Nankervis, AJ [Show all 19 contributors for this article] (2012). Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes. BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. 119(12), p. 1512–1520. doi: 10.1111/j.1471-0528.2012.03463.x. Full text in Research Archive
• Fraser, David; Hessvik, Nina Pettersen; Nikolic, Natasa; Aas, Vigdis; Hanssen, Kristian Folkvord & Bøhn, Siv Kjølsrud [Show all 8 contributors for this article] (2011). Benfotiamine increases glucose oxidation and downregulates NADPH oxidase 4 expression in cultured human myotubes exposed to both normal and high glucose concentrations. Genes & Nutrition. ISSN 1555-8932. doi: 10.1007/s12263-011-0252-8. Full text in Research Archive Show summary

  The aim of the present work was to study the effects of benfotiamine (S-benzoylthiamine O-monophosphate) on glucose and lipid metabolism and gene expression in differentiated human skeletal muscle cells (myotubes) incubated for 4 days under normal (5.5 mM glucose) and hyperglycemic (20 mM glucose) conditions. Myotubes established from lean, healthy volunteers were treated with benfotiamine for 4 days. Glucose and lipid metabolism were studied with labeled precursors. Gene expression was measured using real-time polymerase chain reaction (qPCR) and microarray technology. Benfotiamine significantly increased glucose oxidation under normoglycemic (35 and 49% increase at 100 and 200 μM benfotiamine, respectively) as well as hyperglycemic conditions (70% increase at 200 μM benfotiamine). Benfotiamine also increased glucose uptake. In comparison, thiamine (200 μM) increased overall glucose metabolism but did not change glucose oxidation. In contrast to glucose, mitochondrial lipid oxidation and overall lipid metabolism were unchanged by benfotiamine. The expression of NADPH oxidase 4 (NOX4) was significantly downregulated by benfotiamine treatment under both normo- and hyperglycemic conditions. Gene set enrichment analysis (GSEA) showed that befotiamine increased peroxisomal lipid oxidation and organelle (mitochondrial) membrane function. In conclusion, benfotiamine increases mitochondrial glucose oxidation in myotubes and downregulates NOX4 expression. These findings may be of relevance to type 2 diabetes where reversal of reduced glucose oxidation and mitochondrial capacity is a desirable goal.

• Lund, Terje; Svindland, Aud; Pepaj, Milaim; Jensen, Aase-Brith Ellefsen; Berg, Jens Petter & Kilhovd, Bente [Show all 7 contributors for this article] (2011). Fibrin(ogen) may be an important target for methylglyoxal-derived AGE modification in elastic arteries of humans. Diabetes & vascular disease research. ISSN 1479-1641. 8(4), p. 284–294. doi: 10.1177/1479164111416831. Full text in Research Archive
• Berg, Jens Petter; Hanssen, Kristian Folkvord; Bjerve, Kristian S; Claudi, Tor; Dahl-Jørgensen, Knut & Rustad, Pål [Show all 8 contributors for this article] (2011). Standardisert hemoglobin A1C til diagnostisk bruk? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 131(6), p. 565–6. doi: 10.4045/tidsskr.10.1160. Full text in Research Archive
• Hanssen, Kristian Folkvord (2011). standardisert HbA1c. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.10.1160. Full text in Research Archive
• Eidem, Ingvild; Vangen, Siri; Hanssen, Kristian Folkvord; Vollset, Stein Emil; Henriksen, Tore & Joner, Geir [Show all 7 contributors for this article] (2011). Perinatal and infant mortality in term and preterm births among women with type 1 diabetes. Diabetologia. ISSN 0012-186X. 54(11), p. 2771–2778. doi: 10.1007/s00125-011-2281-7. Full text in Research Archive
• Azar, Madona; Basu, Arpita; Jenkins, Alica J.; Nankervis, Alison J.; Hanssen, Kristian Folkvord & Scholz, Hanne Bjørnson [Show all 12 contributors for this article] (2011). Serum Carotenoids and Fat-Soluble Vitamins in Women With Type 1 Diabetes and Preeclampsia A longitudinal study. Diabetes Care. ISSN 0149-5992. 34(6), p. 1258–1264. doi: 10.2337/dc10-2145. Full text in Research Archive
• Eidem, Ingvild; Stene, Lars Christian; Henriksen, Tore; Hanssen, Kristian Folkvord; Vangen, Siri & Vollset, Stein Emil [Show all 7 contributors for this article] (2010). Congenital anomalies in newborns of women with type 1 diabetes: nationwide population-based study in Norway, 1999-2004. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 89(11), p. 1403–1411. doi: 10.3109/00016349.2010.518594. Full text in Research Archive
• Bangstad, Hans J; Seljeflot, Ingebjørg; Berg, Tore Julsrud & Hanssen, Kristian Folkvord (2009). Renal tubulointerstitial expansion is associated with endothelial dysfunction and inflammation in type-1 diabetes. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 69(1), p. 138–144. doi: 10.1080/00365510802444080. Full text in Research Archive
• Kilhovd, BK; Juutilainen, A; Lehto, S; Ronnemaa, T; Torjesen, PA & Hanssen, Kristian Folkvord [Show all 7 contributors for this article] (2009). Increased serum levels of methylglyoxal-derived hydroimidazolone-AGE are associated with increased cardiovascular disease mortality in nondiabetic women. Atherosclerosis. ISSN 0021-9150. 205(2), p. 590–594. doi: 10.1016/j.atherosclerosis.2008.12.041. Full text in Research Archive
• Yu, Y; Jenkins, AJ; Nankervis, AJ; Hanssen, Kristian Folkvord; Scholz, Hanne Bjørnson & Henriksen, Tore [Show all 21 contributors for this article] (2009). Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women. Diabetologia. ISSN 0012-186X. 52(1), p. 160–168. doi: 10.1007/s00125-008-1182-x. Full text in Research Archive
• Fosmark, Dag Sigurd; Berg, Jens Petter; Jensen, Aase-Brith Ellefsen; Sandvik, Leiv; Agardh, Elisabet & Agardh, Carl-David [Show all 7 contributors for this article] (2009). Increased retinopathy occurrence in type 1 diabetes patients with increased serum levels of the advanced glycation endproduct hydroimidazolone. Acta Ophthalmologica. ISSN 1755-375X. 87(5), p. 498–500. doi: 10.1111/j.1755-3768.2008.01300.x. Full text in Research Archive
• Thorsby, Per Medbøe; Midthjell, Kristian; Gjerlaugsen, Nina; Holmen, Jostein; Hanssen, Kristian F & Birkeland, Kåre I [Show all 7 contributors for this article] (2009). Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population-based study - the HUNT study. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 69(2), p. 282–287. doi: 10.1080/00365510802538188. Full text in Research Archive
• Aas, Anne-Marie; Hanssen, Kristian Folkvord; Berg, Jens Petter; Thorsby, Per Medbøe & Birkeland, Kåre I. (2009). Insulin-Stimulated Increase in Serum Leptin Levels Precedes and Correlates with Weight Gain during Insulin Therapy in Type 2 Diabetes. Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 94(8), p. 2900–2906. doi: 10.1210/jc.2008-1005. Full text in Research Archive
• Hanssen, Kristian Folkvord (2008). Pregnancy in diabetes among Asian, African and norwegian women. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 128, p. 1289–1292. Full text in Research Archive
• Hanssen, Kristian Folkvord (2008). Advanced glycation end products in pregnancies. Hypertension in Pregnancy. ISSN 1064-1955. 27(4), p. 374–386. Full text in Research Archive
• Hanssen, Kristian Folkvord (2008). increased retinopathy occurence in type 1 diabetes patients with increased serum levels of the advanced glycation endproduct hydroimidazolone. Acta Ophthalmologica. ISSN 1755-375X. Full text in Research Archive
• Bangstad, Hans J; Seljeflot, Ingebjørg; Berg, Tore Julsrud & Hanssen, Kristian Folkvord (2008). Renal tubulointerstitial expansion is associated with endothelial dysfunction and inflammation in type 1 diabetes. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. 10, p. 1–7. doi: 10.1080/00365510802444080. Full text in Research Archive
• Harsem, Nina Kittelsen; Brække, Kristin; Torjussen, Tale Mæhre; Hanssen, Kristian Folkvord & Staff, Anne Cathrine (2008). Advanced Glycation End Products in Pregnancies Complicated with Diabetes Mellitus or Preeclampsia. Hypertension in Pregnancy. ISSN 1064-1955. 27(4), p. 374–386. doi: 10.1080/10641950802000968. Full text in Research Archive
• Holan, Synne; Vangen, Siri; Hanssen, Kristian & Stray-Pedersen, Babill (2008). Diabetes hos gravide født i Asia, Afrika og Norge. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 128(11), p. 1289–1292. Full text in Research Archive
• Kilhovd, Bente; Juutilainen, A; Lehto, S; Ronnemaa, T; Torjesen, Peter A & Hanssen, Kristian Folkvord [Show all 7 contributors for this article] (2007). Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study. Diabetologia. ISSN 0012-186X. 50, p. 1409–1417. doi: 10.1007/s00125-007-0687-z. Full text in Research Archive
• Fosmark, Dag Sigurd; Bragadottir, Ragnheidur; Stene-Johansen, Ingar; Berg, Jens Petter; Lund, Terje & Sandvik, Leiv [Show all 7 contributors for this article] (2007). Increased vitreous levels of hydroimidazolone in type 2 diabetes patients are associated with retinopathy: a case-control study. Acta Ophthalmologica Scandinavica. ISSN 1395-3907. 85, p. 618–622. Full text in Research Archive
• Chawla, Jeevan Shikha; Amundsen, Ågot Lia; Hanssen, Kristian F. & Iversen, Per Ole (2006). Svangerskapsdiabetes hos kvinner fra Sør-Asia. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 126(8), p. 1041–1043. Full text in Research Archive
• Skrivarhaug, Torild; Bangstad, Hans-Jacob; Stene, Lars Christian; Sandvik, Leiv; Hanssen, Kristian F. & Joner, Geir (2006). Low risk of overt nephropathy after 24 yr of childhood-onset type 1 diabetes mellitus (T1DM) in Norway. Pediatric Diabetes. ISSN 1399-543X. 7(5), p. 239–246. doi: 10.1111/j.1399-5448.2006.00204.x. Full text in Research Archive Show summary

  AIM: To estimate the risk of diabetic nephropathy and associated risk factors in a nationwide cohort of childhood-onset type 1 diabetes mellitus (T1DM) and 19-30 yr of diabetes duration. METHODS: Patients diagnosed with childhood-onset T1DM (<15 yr) from 1973 through 1982, who previously (1989-1990) participated in a clinical examination to assess diabetic complications, were invited for a new examination in 2002-2003. Of 355 eligible patients, 299 participated (84.2%), and complete urine samples for evaluation of albuminuria were obtained from 295 patients, with a mean age of 33 yr (range 20.9-44.0) and mean diabetes duration of 24 yr (range 19.3-29.9). Persistent microalbuminuria and overt nephropathy [albumin excretion rate (AER) 15-200 microg/min and AER > 200 microg/min, respectively] in at least two out of three consecutive overnight urine samples were defined as diabetic nephropathy. RESULTS: Overt nephropathy was found in 7.8% [95% confidence interval (CI) 4.7-10.9] and persistent microalbuminuria in 14.9% (95% CI 10.8-19.0) of the subjects. Hemoglobin A1c (HbA1c) (p = 0.001), systolic blood pressure (BP) (p = 0.002), total cholesterol (p = 0.019), and C-reactive protein (CRP) (p = 0.019) were associated with diabetic nephropathy. Significant predictors in 1989-1990 for the development of diabetic nephropathy in 2002-2003 were HbA1c (p < 0.001), AER (p = 0.007), and cholesterol (p = 0.022). CONCLUSIONS: In a subgroup of patients diagnosed with childhood-onset T1DM in 1973-1982, 7.8% had overt nephropathy after 19-30 yr of diabetes duration, which is low compared with studies from other countries. HbA1c, systolic BP, total cholesterol, and CRP were each independently associated with diabetic nephropathy.

• Birkeland, Kåre I.; Skeie, Svein & Hanssen, Kristian Folkvord (2006). Biomarkører ved diabetes. Norsk Epidemiologi. ISSN 0803-2491. 16(1), p. 15–21. Full text in Research Archive
• Skrivarhaug, T.; Fosmark, D.S.; Stene, Lars Christian; Bangstad, H.-J.; Sandvik, L. & Hanssen, K.F. [Show all 7 contributors for this article] (2006). Low cumulative incidence of proliferative retinopathy in childhood-onset type 1 diabetes: a 24-year follow-up study. Diabetologia. ISSN 0012-186X. 49(10), p. 2281–2290. doi: 10.1007/s00125-006-0364-7. Full text in Research Archive Show summary

  AIMS/HYPOTHESIS: We estimated cumulative incidence of proliferative diabetic retinopathy (PDR) and risk factors for developing diabetic retinopathy (DR) in childhood-onset type 1 diabetes. MATERIALS AND METHODS: A sample of 294 patients with childhood-onset type 1 diabetes (<15 years) diagnosed in Norway between 1973 and 1982 was examined for retinopathy at baseline between 1989 and 1990 and at follow-up from 2002 to 2003. At follow-up, mean age was 33 years (range: 21-44), mean diabetes duration 24 years (19-30) and total person-time contributed 7,152 person-years. Retinal photographs were taken at baseline and follow-up. Associations between baseline factors and PDR were estimated using Cox regression models. RESULTS: Overall, 262 of 294 (89.1%) developed DR from diabetes onset, of whom 31 developed PDR. The 25-year cumulative incidence of PDR was 10.9% (95% CI 7.3-14.5). Among 194 without retinopathy at baseline, 163 (84%) developed DR and nine (5%) progressed to PDR. Among 97 patients with non-proliferative DR at baseline, 19 (20%) progressed to PDR. Significant predictors for developing PDR were retinopathy at baseline (relative risk [RR]=3.71, 95% CI 1.59-8.68), HbA(1c) (RR=2.05, 1.44-2.93), and triglycerides (RR=1.55, 1.06-1.95). CONCLUSIONS/INTERPRETATION: Nine out of every ten patients diagnosed with type 1 diabetes developed DR, but only one out of ten developed PDR within their first 25 years of diabetes duration. The cumulative incidence of PDR is lower than previously reported from other countries. Potentially modifiable risk factors predict the development of DR and PDR.

• Skrivarhaug, T; Bangstad, HJ; Stene, Lars Christian; Sandvik, L; Hanssen, KF & Joner, G (2006). Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway. Diabetologia. ISSN 0012-186X. 49(2), p. 298–305. doi: 10.1007/s00125-005-0082-6. Full text in Research Archive
• Larsen, Jakob; Brekke, M; Bergengen, L; Sandvik, L; Arnesen, Harald & Hanssen, Kristian Folkvord [Show all 7 contributors for this article] (2005). Mean HbA1c over 18 years predicts carotid intima media thickness in women with type 1 diabetes. Diabetologia. ISSN 0012-186X. 48(4), p. 776–779. Full text in Research Archive
• Kilhovd, Bente K.; Juutilainen, A.; Lehto, S.; Rönnemaa, T.; Torjesen, Peter A. & Birkeland, Kåre I. [Show all 9 contributors for this article] (2005). High Serum Levels of Advanced Glycation End Products Predict Increased Coronary Heart Disease Mortality in Nondiabetic Women but not in Nondiabetic Men. A population-Based 18- Year Follow-Up Study. Arteriosclerosis, Thrombosis and Vascular Biology. ISSN 1079-5642. 25(4), p. 815–20. Full text in Research Archive
• Skrivarhaug, T; Bangstad, Hans J; Stene, LC; Sandvik, L.; Hanssen, Kristian Folkvord & Joner, G (2005). Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway. Diabetologia. ISSN 0012-186X. 20, p. 1–8. Full text in Research Archive
• Dahl-Jørgensen, Knut; Larsen, Jakob & Hanssen, Kristian Folkvord (2005). Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment? Diabetologia. ISSN 0012-186X. 48. Full text in Research Archive
• Hanssen, Kristian Folkvord (2004). Type 2 Diabetes er flere sykdommer. In Vaaler, Stein (Eds.), Diabeteshåndboken. Gyldendal Akademisk. p. 36–41. Full text in Research Archive
• Hanssen, Kristian Folkvord (2004). Diabetisk ketoacidose og non-ketotisk ukontrollert diabetes. In Vaaler, Stein (Eds.), Diabeteshåndboken. Gyldendal Akademisk. p. 182–185. Full text in Research Archive
• Hanssen, Kristian Folkvord (2004). Graviditet og diabetes - en viktig terapeutisk utfordring. In Vaaler, Stein (Eds.), Diabeteshåndboken. Gyldendal Akademisk. p. 284–288. Full text in Research Archive
• Larsen, Jakob; Sjøholm, Hans; Berg, Tore Julsrud; Sandvik, Leiv; Brekke, Magne & Hanssen, Kristian Folkvord [Show all 7 contributors for this article] (2004). Eighteen Years of Fair Glycemic Control Preserves Cardiac Autonomic Function in Type 1 Diabetes. Diabetes Care. ISSN 0149-5992. 27(4), p. 963–6. Full text in Research Archive
• Hanssen, Kristian Folkvord (2004). Offloading in patients with diabetic foot ulceration. International Diabetes Monitor. ISSN 0924-3623. 16, p. 237–239. Full text in Research Archive
• Kilhovd, Bente K.; Giardino, I.; Torjesen, Peter A.; Birkeland, Kåre I.; Berg, Tore Julsrud & Thornalley, P.J. [Show all 8 contributors for this article] (2003). Increased serum levels of the specific AGE-compound methylglyoxal derived hydroimidazolone in patients with type 2 diabetes. Metabolism: Clinical and Experimental. ISSN 0026-0495. 52(2), p. 163–7. Full text in Research Archive
• Birkeland, Kåre I.; Kilhovd, Bente K.; Thorsby, Per; Torjesen, Peter A.; Ganss, R. & Vaaler, Stein [Show all 7 contributors for this article] (2003). Heterogeneity of non-insulin dependent diabetes expressed as variability in insulin sensivity, beta cell function and cardiovascular risk profile. Diabetic Medicine. ISSN 0742-3071. 20(1), p. 37–45. Full text in Research Archive
• Larsen, Jakob R.; Sjøholm, H.; Hanssen, Kristian Folkvord; Sandvik, Leiv; Berg, T Julsrud & Dahl-Jørgensen, Knut (2003). Optimal blood glucose control during 18 years preserves peripheral nerve function in patients with 30 years' duration of type 1 diabetes. Diabetes Care. ISSN 0149-5992. 26(8), p. 2400–4. Full text in Research Archive
• Hanssen, Kristian Folkvord (2003). Melkesyreacidose som bivirkning av metformin. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 123(18), p. 2583–84. Full text in Research Archive
• Bangstad, Hans-Jacob; Østerby, Ruth; Rudberg, Susanne; Hartmann, Anders; Brabrand, Knut & Hanssen, Kristian Folkvord (2002). Kidney function and glomerulopathy over 8 years in young patients with Type 1 diabetes mellitus and microalbuminuria. Diabetologia. ISSN 0012-186X. 45, p. 253–261. Full text in Research Archive
• Larsen, Jakob R.; Brekke, Mette; Sandvik, Leiv; Arnesen, Harald; Hanssen, Kristian Folkvord & Dahl-Jørgensen, Knut (2002). Silent Coronary Artheromatosis in type 1 Diabetic patients and its relation to long-term glycemic control. Diabetes. ISSN 0012-1797. 51, p. 2637–41. Full text in Research Archive
• Bangstad, Hans-Jacob; Osterby, R.; Rudberg, Susanne; Hartmann, Anders; Brabrand, Knut & Hanssen, Kristian Folkvord (2002). Kidney function and glomerulopathy over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria. Diabetologia. ISSN 0012-186X. 45, p. 253–61. Full text in Research Archive

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• Christophersen, Y. & Hanssen, Kristian Folkvord (2004). Diabetes for livet: aldri fred å få? Eget forlag. ISBN 9788299687003. 224 p. Full text in Research Archive

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• Henriksen, Tore; Jenum, Anne Karen; Thordarson, Hrafnkell B; Holm, Helene Oeding; Gudim, Hilde Beate & Hanssen, Kristian Folkvord (2018). Backes sammensurium av retningslinjer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. Full text in Research Archive
• Henriksen, Tore; Jenum, Anne Karen; Thordarson, Hrafnkell B; Holm, Helene Oeding; Gudim, Hilde Beate & Hanssen, Kristian Folkvord (2018). Backe's budskap til norske kolleger: Glem svangerskapsdiabetes. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. Full text in Research Archive
• Henriksen, Tore; Jenum, Anne Karen; Thordarson, Hrafnkell B; Holm, Helene Oeding; Gudim, Hilde Beate & Hanssen, Kristian Folkvord (2018). Lite nytt i kritikk av retningslinjene for svangerskapsdiabetes. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(10), p. 894–894. doi: 10.4045/tidsskr.18.0430. Full text in Research Archive
• Hanssen, Kristian Folkvord; Jenum, Anne Karen; Henriksen, Tore; Bjerkan, Kirsti; Gudim, Hilde Beate & Holm, Helene Oeding [Show all 7 contributors for this article] (2017). Svangerskapsomsorg på rett vei. Aftenposten (morgenutg. : trykt utg.). ISSN 0804-3116. Full text in Research Archive
• Sveen, Kari Anne; Ørstavik, Kristin; Fosmark, Dag Sigurd; Dahl-Jørgensen, Knut & Hanssen, Kristian Folkvord (2013). Retinal nerve fibre layer thickness is associated with measures of small fibre neuropathy in long-term type 1 diabetes. Diabetologia. ISSN 0012-186X. 56, p. S499–S500. Full text in Research Archive
• Fraser, David; Diep, Lien My; Hynås, Inger Anette; Nilsen, Kristian Bernhard; Sveen, Kari Anne & Seljeflot, Ingebjørg [Show all 7 contributors for this article] (2012). Response to Comment on: Fraser et al. The Effects of Long-Term Oral Benfotiamine Supplementation on Peripheral Nerve Function and Inflammatory Markers in Patients With Type 1 Diabetes: A 24-Month, Double-Blind, Randomized, Placebo-Controlled Trial. Diabetes Care 2012;35:1095-1097. Diabetes Care. ISSN 0149-5992. 35(11), p. E80–E80. doi: 10.2337/dc12-1124. Full text in Research Archive
• Fraser, David; Diep, Lien My; Hynås, Inger Anette; Nilsen, Kristian Bernhard; Sveen, Kari Anne & Seljeflot, Ingebjørg [Show all 7 contributors for this article] (2012). The effects of oral benfotiamine on peripheral nerve function and inflammatory markers in type-1 diabetes: a 24-month, double-blind, randomised, placebo-controlled trial. European Journal of Neurology. ISSN 1351-5101. 19, p. 416–416. Full text in Research Archive
• Hanssen, Kristian Folkvord (2012). Legene og legemiddelindustrien. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 132, p. 386–387. Full text in Research Archive
• Eidem, Ingvild; Vangen, Siri; Hanssen, Kristian Folkvord; Vollset, Stein Emil; Henriksen, Tore & Joner, Geir [Show all 7 contributors for this article] (2012). Perinatal and Infant Mortality in Term and Preterm Births Among Women With Type 1 Diabetes EDITORIAL COMMENT. Obstetrical and Gynecological Survey. ISSN 0029-7828. 67(3), p. 139–141. doi: 10.1097/OGX.0b013e31824b6f5f. Full text in Research Archive
• Wu, M.; Du, M; Jenkins, A.; Nankervis, AJ; Hanssen, Kristian Folkvord & Scholz, Hanne Bjørnson [Show all 18 contributors for this article] (2010). CIRCULATING CYTOKINES PREDICT PRE-ECLAMPSIA IN TYPE 1 DIABETES MELLITUS. Journal of Investigative Medicine. ISSN 1081-5589. 58(2), p. 392–392. Full text in Research Archive
• Skrivarhaug, T; Fosmark, D; Bangstad, HJ; Stene, Lars Christian; Sandvik, L & Hanssen, KF [Show all 7 contributors for this article] (2008). Appearance of retinopathy and progression to proliferative retinopathy in childhood-onset type 1 diabetes: a long-term follow-up study. Acta Ophthalmologica. ISSN 1755-375X. 86, p. 43–43. Full text in Research Archive
• Thorsby, Per M; Midthjell, Kristian; Gjerlaugsen, N; Krüger, Øystein; Holmen, Jostein & Hanssen, Kristian [Show all 8 contributors for this article] (2006). Analyses of two major candidate genes for type 2 diabetes - does it provide additional information to traditional risk factors in prediction of diabetes: the HUNT study? Diabetic Medicine. ISSN 0742-3071. 23, p. 463–463. Full text in Research Archive
• Skrivarhaug, Torild; Bangstad, Hans J; Sandvik, Leiv; Hanssen, Kristian Folkvord & Joner, Geir (2004). Low prevalence of clinical nephropathy after 24 years of Type 1 diabetes; a Norwegian population based cohort study. Full text in Research Archive
• Skrivarhaug, Torild; Bangstad, Hans J; Sandvik, L; Hanssen, Kristian Folkvord & Joner, Geir (2004). Cholesterol, HbA1c and AER are predictors of diabetic kidney disease in type 1 diabetes. Full text in Research Archive
• Skrivarhaug, Torild; Bangstad, Hans J; Sandvik, Leiv; Hanssen, Kristian Folkvord & Joner, Geir (2004). Predictors of microalbuminuria and overt nephropathy in patients with type 1 diabetes: a population-based, longitudinal survey. Pediatric Diabetes. ISSN 1399-543X. 5, p. 092–092. Full text in Research Archive
• Larsen, J; Bergengen, L.; Sandvik, Leiv; Arnesen, Harald; Hanssen, Kristian Folkvord & Dahl-Jørgensen, Knut (2003). Mean HbA1c during 18 years predicts common carotide artery intima-media thickness in women with type-1 diabetes. Full text in Research Archive
• Hanssen, Kristian Folkvord (2003). Betacellen kan vekkes? Diabetes (Oslo). ISSN 1502-1424. p. 59–59. Full text in Research Archive
• Hanssen, Kristian Folkvord (2003). Kombinasjonsbehandling ved type 2 Diabetes. Diabetes (Oslo). ISSN 1502-1424. p. 42–42. Full text in Research Archive
• Hanssen, Kristian Folkvord (2003). GLP-1 - den nye vidundermedisinen? Diabetes (Oslo). ISSN 1502-1424. p. 40–40. Full text in Research Archive
• Hanssen, Kristian Folkvord (2003). Over 30 % risiko for å få diabetes i USA! Diabetes (Oslo). ISSN 1502-1424. p. 17–17. Full text in Research Archive
• Hanssen, Kristian Folkvord (2003). Vitaminer mot senkomplikasjoner? Diabetes (Oslo). ISSN 1502-1424. p. 17–17. Full text in Research Archive
• Hanssen, Kristian Folkvord (2003). Behandling med kombinasjon av insulin og perorale antidiabetika med type 2 Diabetes. Diabetes avisen. ISSN 0803-8260. p. 8–9. Full text in Research Archive
• Hanssen, Kristian Folkvord (2003). Type 1 Diabetes gjennom 80 år. Diabetes (Oslo). ISSN 1502-1424. p. 39–39. Full text in Research Archive

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