TY - JOUR A1 - Appeltshauser, Luise A1 - Messinger, Julia A1 - Starz, Katharina A1 - Heinrich, David A1 - Brunder, Anna-Michelle A1 - Stengel, Helena A1 - Fiebig, Bianca A1 - Ayzenberg, Ilya A1 - Birklein, Frank A1 - Dresel, Christian A1 - Dorst, Johannes A1 - Dvorak, Florian A1 - Grimm, Alexander A1 - Joerk, Alexander A1 - Leypoldt, Frank A1 - Mäurer, Mathias A1 - Merl, Patrick A1 - Michels, Sebastian A1 - Pitarokoili, Kalliopi A1 - Rosenfeldt, Mathias A1 - Sperfeld, Anne-Dorte A1 - Weihrauch, Marc A1 - Welte, Gabriel Simon A1 - Sommer, Claudia A1 - Doppler, Kathrin T1 - Diabetes Mellitus Is a Possible Risk Factor for Nodo-paranodopathy With Antiparanodal Autoantibodies JF - Neurology: Neuroimmunology & Neuroinflammation N2 - Background and Objectives Nodo-paranodopathies are peripheral neuropathies with dysfunction of the node of Ranvier. Affected patients who are seropositive for antibodies against adhesion molecules like contactin-1 and neurofascin show distinct clinical features and a disruption of the paranodal complex. An axoglial dysjunction is also a characteristic finding of diabetic neuropathy. Here, we aim to investigate a possible association of antibody-mediated nodo-paranodopathy and diabetes mellitus (DM). Methods We retrospectively analyzed clinical data of 227 patients with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome from multiple centers in Germany who had undergone diagnostic testing for antiparanodal antibodies targeting neurofascin-155, pan-neurofascin, contactin-1–associated protein 1, and contactin-1. To study possible direct pathogenic effects of antiparanodal antibodies, we performed immunofluorescence binding assays on human pancreatic tissue sections. Results The frequency of DM was 33.3% in seropositive patients and thus higher compared with seronegative patients (14.1%, OR = 3.04, 95% CI = 1.31–6.80). The relative risk of DM in seropositive patients was 3.4-fold higher compared with the general German population. Seropositive patients with DM most frequently harbored anti–contactin-1 antibodies and had higher antibody titers than seropositive patients without DM. The diagnosis of DM preceded the onset of neuropathy in seropositive patients. No immunoreactivity of antiparanodal antibodies against pancreatic tissue was detected. Discussion We report an association of nodo-paranodopathy and DM. Our results suggest that DM may be a potential risk factor for predisposing to developing nodo-paranodopathy and argue against DM being induced by the autoantibodies. Our findings set the basis for further research investigating underlying immunopathogenetic connections. KW - Diabetes mellitus KW - Nodo-parandopathy KW - Antiparanodal Autoantibodies Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300551 VL - 9 IS - 3 ER - TY - JOUR A1 - Rosenstock, Julio A1 - Perkovic, Vlado A1 - Alexander, John H. A1 - Cooper, Mark E. A1 - Marx, Nikolaus A1 - Pencina, Michael J. A1 - Toto, Robert D. A1 - Wanner, Christoph A1 - Zinman, Bernard A1 - Baanstra, David A1 - Pfarr, Egon A1 - Mattheus, Michaela A1 - Broedl, Uli C. A1 - Woerle, Hans-Jürgen A1 - George, Jyothis T. A1 - von Eynatten, Maximilian A1 - McGuire, Darren K. T1 - Rationale, design, and baseline characteristics of the CArdiovascular safety and Renal Microvascular outcomE study with LINAgliptin - (CARMELINA®): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk JF - Cardiovascular Diabetology N2 - Background: Cardiovascular (CV) outcome trials in type 2 diabetes (T2D) have underrepresented patients with chronic kidney disease (CKD), leading to uncertainty regarding their kidney efficacy and safety. The CARMELINA (R) trial aims to evaluate the effects of linagliptin, a DPP-4 inhibitor, on both CV and kidney outcomes in a study population enriched for cardio-renal risk. Methods: CARMELINA (R) is a randomized, double-blind, placebo-controlled clinical trial conducted in 27 countries in T2D patients at high risk of CV and/or kidney events. Participants with evidence of CKD with or without CV disease and HbA1c 6.5-10.0% (48-86 mmol/mol) were randomized 1:1 to receive linagliptin once daily or matching placebo, added to standard of care adjusted according to local guidelines. The primary outcome is time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke. The key secondary outcome is a composite of time to first sustained occurrence of end-stage kidney disease, >= 40% decrease in estimated glomerular filtration rate (eGFR) from baseline, or renal death. CV and kidney events are prospectively adjudicated by independent, blinded clinical event committees. CARMELINA (R) was designed to continue until at least 611 participants had confirmed primary outcome events. Assuming a hazard ratio of 1.0, this provides 90% power to demonstrate non-inferiority of linagliptin versus placebo within the pre-specified non-inferiority margin of 1.3 at a one-sided a-level of 2.5%. If non-inferiority of linagliptin for the primary outcome is demonstrated, then its superiority for both the primary outcome and the key secondary outcome will be investigated with a sequentially rejective multiple test procedure. Results: Between July 2013 and August 2016, 6980 patients were randomized and took >= 1 dose of study drug (40.6, 33.1, 16.9, and 9.4% from Europe, South America, North America, and Asia, respectively). At baseline, mean +/- SD age was 65.8 +/- 9.1 years, HbA1c 7.9 +/- 1.0%, BMI 31.3 +/- 5.3 kg/m(2), and eGFR 55 +/- 25 mL/min/1.73 m(2). A total of 5148 patients (73.8%) had prevalent kidney disease (defined as eGFR < 60 mL/min/1.73 m(2) or macroalbuminuria [albumin-to-creatinine ratio > 300 mg/g]) and 3990 patients (57.2%) had established CV disease with increased albuminuria; these characteristics were not mutually exclusive. Microalbuminuria (n = 2896 [41.5%]) and macroalbuminuria (n = 2691 [38.6%]) were common. Conclusions: CARMELINA (R) will add important information regarding the CV and kidney disease clinical profile of linagliptin by including an understudied, vulnerable cohort of patients with T2D at highest cardio-renal risk. KW - Diabetes mellitus KW - type 2 KW - Cardiovascular diseases KW - Diabetic nephropathies KW - Dipeptidyl-peptidase IV inhibitors KW - Linagliptin KW - Clinical trial KW - phase IV KW - Research design KW - Treatment outcome Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226996 VL - 17 ER - TY - JOUR A1 - Busch, Martin A1 - Nadal, Jennifer A1 - Schmid, Matthias A1 - Paul, Katharina A1 - Titze, Stephanie A1 - Hübner, Silvia A1 - Köttgen, Anna A1 - Schultheiss, Ulla T. A1 - Baid-Agrawal, Seema A1 - Lorenzen, Johan A1 - Schlieper, Georg A1 - Sommerer, Claudia A1 - Krane, Vera A1 - Hilge, Robert A1 - Kielstein, Jan T. A1 - Kronenberg, Florian A1 - Wanner, Christoph A1 - Eckardt, Kai-Uwe A1 - Wolf, Gunter T1 - Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort JF - BMC Nephrology N2 - Background Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. Methods The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18–74 years with an estimated glomerular filtration rate (eGFR) between 30–60 mL/min/1.73 m2 or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. Results At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25th–75th percentile: 6.8–7.9 %), equalling 53 mmol/mol (51, 63); 24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m2, 95 % CI 1.02–1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04–1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26–7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77–6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. Conclusions Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels. KW - Chronic kidney disease KW - Glycaemic control KW - Hemoglobin A1C KW - Insulin therapy KW - Oral antidiabetic drugs KW - Diabetes mellitus Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164687 VL - 17 IS - 59 ER -