Nanette C Schloot

Publications (65) View all

• Article: Serum adipokines as biomarkers of beta-cell function in patients with type 1 diabetes: positive association with leptin and resistin and negative association with adiponectin.

  Minh Nguyet Pham, Hubert Kolb, Thomas Mandrup-Poulsen, Tadej Battelino, Johnny Ludvigsson, Paolo Pozzilli, Michael Roden, Nanette C Schloot, European C-Peptide Trial
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: We investigated the adipokines adiponectin, leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes. METHODS: 118 patients with type 1 diabetes (20.3 ± 7.5 years) diagnosed <5 years underwent standardized mixed meal test (MMTT) for 2 hours. Systemic concentrations of C-peptide, adiponectin, leptin, and resistin obtained during MMTT were measured and compared between patient groups by multiple regression analysis. RESULTS: Patients were divided by their adipokine levels in subgroups above or below the median level ("high versus low"). High adiponectin levels (>10.6 µg/ml) were associated with lower C-peptide compared to the low adiponectin subgroup (p < 0.03). Increased leptin or resistin concentrations associated positively with beta-cell function even after adjustment for metabolic confounders (p < 0.04). The described associations between adipokines and C-peptide concentrations persisted in Spearman correlation tests (p < 0.05). Serum adipokines fell during MMTT (p < 0.05). CONCLUSIONS: Serum adipokine levels differentially correlate with beta-cell function in type 1 diabetes independently of BMI or metabolic control. Serum adipokines should be investigated as biomarkers of beta-cell function in prospective studies and intervention trials in type 1 diabetes. Copyright © 2012 John Wiley & Sons, Ltd.
  Diabetes/Metabolism Research and Reviews 11/2012; · 3.37 Impact Factor
• Article: Cellular interferon-γ and interleukin-13 immune reactivity in type 1, type 2 and latent autoimmune diabetes: action LADA 6.

  Alexander Strom, Barbara Menart, Marie-Christine Simon, Minh Nguyet Pham, Hubert Kolb, Michael Roden, Paolo Pozzilli, R David G Leslie, Nanette C Schloot
  [show abstract] [hide abstract]
  ABSTRACT: Type 1 diabetes and latent autoimmune diabetes in adults (LADA) are thought to result from immune-mediated β-cell destruction. It remains unclear why LADA is clinically less severe compared to type 1 diabetes. This study aimed to compare the pro-inflammatory (interferon-γ, IFN-γ) and anti-inflammatory (interleukin-13, IL-13) T-cell responses in humans with LADA and type 1 diabetes. IFN-γ and IL-13 T-cell responses to a panel of 16 (auto)-antigens were tested using an enzyme linked immune-spot technique and peripheral T-cells from 35 patients with type 1 diabetes, 59 patients with type 2 diabetes, 23 LADA patients, and 42 control subjects. LADA and type 1 diabetes patients did not display any statistically significant differences in the frequency of IFN-γ or IL-13 responses to auto-antigenic stimuli, positive control or mitogen. Overall very low T cell reactivity to autoantigens was detected in all groups. IL-13 responses but not IFN-γ responses to recall antigen tetanus toxoid were higher in healthy control subjects compared to patients with type 1 or type 2 diabetes or LADA (P<0.05). Diabetes, independent of type, was associated with weaker response to recall antigen tetanus toxoid. LADA patients are indistinguishable from type 1 diabetes patients for cellular IFN-γ and IL-13 responses upon mitogen and recall antigen stimulation. These results extend previous findings showing that systemic cytokine/chemokine and humoral responses in type 1 diabetes and LADA are similar.
  Cytokine 02/2012; 58(2):148-51. · 3.02 Impact Factor
• Article: Biomarker und Typ 1 Diabetes

  Marie-Christine Simon, Minh N. Pham, Nanette C. Schloot
  [show abstract] [hide abstract]
  ABSTRACT: The prevalence of immune-mediated type 1 diabetes is approximately 10% of all cases of diabetes. The disease is the consequence of selective β-cell destruction and subsequent insulin deficiency. Diagnosis of type 1 diabetes is based on clinical symptoms and evaluation of metabolic and immunologic biomarkers including blood glucose, HbA1c and autoantibodies. An increased risk for developing type 1 diabetes is positively associated with increased numbers of islet autoantibodies (GADA, ICA, IAA, IA-2A and ZnT8A), therefore, evaluation of islet autoantibodies is also used for risk prediction. Currently, the immune status of patients with type 1 diabetes can be determined using cellular immunoassays for antigen-specific T cells and soluble immune mediators including cytokines, chemokines and adhesion molecules. Endogenous ß-cell capacity is measured by the C-peptide concentration. In the present review a general overview of current biomarkers and their potential applications for prediction, diagnosis, clinical classification and monitoring of the disease progression of type 1 diabetes is given.
  Der Diabetologe 01/2012; 8(1-DOI 10.1007/s11428-011-0780-2):11-17. · 0.25 Impact Factor
• Source

  Available from: Alexander Strom

  Article: Improved preservation of residual beta cell function by atorvastatin in patients with recent onset type 1 diabetes and high CRP levels (DIATOR trial).

  Alexander Strom, Hubert Kolb, Stephan Martin, Christian Herder, Marie-Christine Simon, Wolfgang Koenig, Tim Heise, Lutz Heinemann, Michael Roden, Nanette C Schloot
  [show abstract] [hide abstract]
  ABSTRACT: A recent randomized placebo-controlled trial of the effect of atorvastatin treatment on the progression of newly diagnosed type 1 diabetes suggested a slower decline of residual beta cell function with statin treatment. Aim of this secondary analysis was to identify patient subgroups which differ in the decline of beta cell function during treatment with atorvastatin. The randomized placebo-controlled Diabetes and Atorvastatin (DIATOR) Trial included 89 patients with newly diagnosed type 1 diabetes and detectable islet autoantibodies (mean age 30 years, 40% females), in 12 centers in Germany. Patients received placebo or 80 mg/d atorvastatin for 18 months. As primary outcome stimulated serum C-peptide levels were determined 90 min after a standardized liquid mixed meal. For this secondary analysis patients were stratified by single baseline characteristics which were considered to possibly be modified by atorvastatin treatment. Subgroups defined by age, sex or by baseline metabolic parameters like body mass index (BMI), total serum cholesterol or fasting C-peptide did not differ in C-peptide outcome after atorvastatin treatment. However, the subgroup defined by high (above median) baseline C-reactive protein (CRP) concentrations exhibited higher stimulated C-peptide secretion after statin treatment (p = 0.044). Individual baseline CRP levels correlated with C-peptide outcome in the statin group (r(2) = 0.3079, p<0.004). The subgroup with baseline CRP concentrations above median differed from the corresponding subgroup with lower CRP levels by higher median values of BMI, IL-6, IL-1RA, sICAM-1 and E-selectin. Atorvastatin treatment may be effective in slowing the decline of beta cell function in a patient subgroup defined by above median levels of CRP and other inflammation associated immune mediators. ClinicalTrials.gov NCT00974740.
  PLoS ONE 01/2012; 7(3):e33108. · 4.09 Impact Factor
• Article: Circulating cytokines are associated with human islet graft function in type 1 diabetes.

  Christian Pfleger, Nanette C Schloot, Mathias D Brendel, Volker Burkart, Viktor Hogenkamp, Reinhard G Bretzel, Clemens Jaeger, Michael Eckhard
  [show abstract] [hide abstract]
  ABSTRACT: Islet cell transplantation has considerable potential as a cure for type 1 diabetes, but recurrent autoimmunity and allograft rejection in which both cytokines play an important role are major obstacles. Using a new approach considering confounders by regression analysis, we investigated circulating cytokines and their association with graft function in type 1 diabetes patients who underwent either simultaneous islet kidney (SIK) or islet after kidney (IAK) transplantation. After transplantation, interleukin (IL)-10 was lower in SIK recipients with subsequent loss of graft function in comparison to recipients maintaining graft function. Before transplantation, high IL-13 and IL-18 concentrations were prospectively associated for subsequent loss of graft function in IAK recipients, whereas in SIK recipients, high macrophage migration inhibitory factor (MIF) concentrations were associated with subsequent loss of graft function. Circulating cytokines are associated with islet graft function in patients with long-standing type 1 diabetes when considering confounders.
  Clinical Immunology 02/2011; 138(2):154-61. · 4.05 Impact Factor