Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
  • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N2800/00—Detection or diagnosis of diseases
  • G01N2800/04—Endocrine or metabolic disorders
  • G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism

Definitions

• the invention relates to a method for the diagnosis and / or risk stratification of diabetes mellitus, in particular of diabetic secondary diseases, wherein a determination of the marker comprises midregional pro-adrenomedullin (MR-proADM: SEQ ID No. 2) or a partial peptide or fragment thereof or containing in a marker combination ( Panel, cluster) on a patient to be examined. Furthermore, the invention relates to a diagnostic device and a kit for carrying out the method.
• MR-proADM midregional pro-adrenomedullin
• diabetes mellitus The diagnosis of diabetes mellitus is known for adrenomedullin (Garcia-Unzueta MT, Montalban C, Pesquera C, Berrazueta JR, Amado Y. Plasma adrenomedullin levels in type 1 diabetes.) Diabetes Care. 21: 999-1003, 1998 and Turk HM, Buyukberber S, Sevinc A, Ak G, Ates M, Sari R, Savli H, Cigli A. Relationship between plasma adrenomedullin levels and metabolic control, risk factors, and diabetic microangiopathy in patients with type 2 diabetes : 864-7, 2000).
• proAdrenomedullin proADM
• diagnosis EP0622458B1
• sepsis EP1121600B1
• MR proADM SEQ ID No. 2
• AS45-92 of the preproADM in SEQ ID No. 1 Figure I
• MR-proADM SEQ ID No. 2 for the diagnosis of diabetes mellitus, however, is not disclosed.
• the object is achieved by a method for the in-vitro diagnosis and / or risk stratification of diabetes mellitus, wherein a determination of the marker midregional pro-adrenomedullin (MR-proADM: SEQ ID No. 2) or a partial peptide or fragment thereof or containing in one Marker combination (panel, cluster) is performed on a patient to be examined (method according to the invention).
• MR-proADM marker midregional pro-adrenomedullin
• risk stratification encompasses the finding of diabetes patients, in particular those with diabetic secondary diseases, with the worse prognosis, for the purpose of more intensive diagnostics and (follow-up)
• a reliable diagnosis and / or risk stratification can be carried out particularly advantageously by means of the method according to the invention.
• the method according to the invention enables clinical decisions leading to a faster diagnosis, in particular of the diabetic sequelae. Such clinical decisions also include continuing treatment with drugs for the treatment or therapy of diabetes mellitus.
• the diagnosis and / or risk stratification for prognosis, for prophylaxis, for differential diagnostic early detection and detection, for the assessment of the severity grade and the therapy-accompanying course assessment of diabetes mellitus is taken from the patient to be examined, optionally whole blood, serum or available plasma and the diagnosis is made in vitro / ex vivo, ie outside the human or animal body.
• body fluid in particular blood
• MR-proADM SEQ ID No. 2
• partial peptides or fragments thereof or its existing amount or its change in quantity compared to a reference in at least one patient sample, the diagnosis and / or risk stratification can take place.
• diabetes mellitus in particular type II diabetes mellitus (insulin resistance)
• insulin resistance a chronic metabolic disease in which the insulin production in the ⁇ -cells of the islets of Langerhans is disturbed in the pancreas or if insulin is present on its own The result of this disturbed insulin production or effect is increased blood sugar levels (hyperglycemia) .
• prediabetes in which it only reaches its end stage to a laboratory-diagnosed "disturbed glucose tolerance” comes, and the actual manifest diabetes mellitus. At the beginning of the prediabetic
• the invention relates to the diagnosis and / or risk stratification of type II diabetes mellitus and its concomitant diseases, in particular endothelial dysfunctions, hyperlipoproteinemia, hypertensive circulatory dysregulation, diabetic retinopathy, nephropathy, renal insufficiency, neuropathy, diabetic foot syndrome and cardiovascular complications.
• MR-proADM SEQ ID No. 2
• MR-proADM SEQ ID No. 2
• Figure 1 of the preproAdrenomedullins (Kitamura K, Sakata J, Kangawa K, Kojima M, Matsuo H, Eto T. Cloning and characterization of cDNA encoding a precursor for human adrenomedullin Biochem Biophys Res Commun 1993; 194: 720-725) resp Amino acid sequence 1-48 of SEQ ID No. 2 ( Figure 2) Fragment of the proAdenomedullins is called “midregional proAdrenomedullin (MR-proADM)" (EP 1488209Bl) and has particularly advantageous high plasma stability.
• the "midregional pro-adrenomedullin" of the present invention may have modifications such as glycation, lipidification or derivatizations.
• MR-proADM SEQ ID No. 2
• MR-proADM SEQ ID No. 2
• a marker combination panel, cluster
• This embodiment may also be a vascular marker that may indicate diabetes-related endothelial dysfunction of the circulation.
• the invention relates to such an embodiment of the method according to the invention, wherein the determination is additionally carried out with at least one further marker selected from the group of inflammatory markers, vascular markers on a patient to be examined.
• the inflammatory marker may be selected from at least one marker from the group C-reactive protein (CRP), cytokines, such as TNF-alpha, interleukins, such as IL-6, interleukin-lß, procalcitonin (1-116, 3-116), angiotensin II, endothelin-1 and adhesion molecules such as VCAM or ICAM, and the vascular marker from at least one marker from the group creatine kinase, myeloperoxidase, myoglobin , natriuretic protein, in particular ANP (or ANF), proANP, NT-proANP, BNP, proBNP, NT-proBNP or in each case a partial sequence thereof, CRP. Further, these are preferable among them
• pro-gastrin-releasing peptide proGRP
• pro-endothelin-1 pro-leptin
• pro-neuropeptide-Y pro-somatostatin
• pro-neuropeptide-YY pro-opio-melanocortin or each a subsequence of it.
• diabetic markers / factors are especially those such as adiponectin, carbohydrates, fats, such as cholesterols (LDH) and others, Bodymass Index (BMI), age, blood pressure, HOMA-IR (Homeostasis Model Assessment Insulin Resitance Index, cf.
• the method according to the invention can be carried out by means of parallel or simultaneous Determinations of the markers are carried out (eg multi-well plates with 96 and more cavities), wherein the determinations are carried out on at least one patient sample.
• the method according to the invention and its determinations can be carried out on an automatic analyzer, in particular by means of a cryptor (http://www.kryptor.net/).
• the method according to the invention and its determinations can be carried out by means of a rapid test (for example, lateral-flow test), whether in single or multiparameter determination.
• a rapid test for example, lateral-flow test
• the invention relates to the use of midregional proAdrenomedullin (MR-proADM: SEQ ID No. 2) or partial peptides or fragments thereof or contained in one
• Marker combination for the in-vitro diagnosis and / or risk stratification of diabetes mellitus, especially diabetes mellitus type II and its subsequent and
• the marker combination may contain another suitable mark.
• a further object is the provision of a corresponding diagnostic device or the use of such a device for carrying out the methods according to the invention.
• a diagnostic device in particular an array or assay (eg immunoassay, ELISA etc.), in the broadest sense means a device for carrying out the method according to the invention.
• the invention also relates to a kit or the use of such a kit for the in-vitro diagnosis and risk stratification of diabetes mellitus, in particular type II diabetes mellitus and its concomitant diseases, wherein a determination of midregional proAdrenominated Dullin (MR-proADM: SEQ ID No 2) or partial peptides or fragments thereof or contained in a marker combination (panel, cluster) on a patient to be examined, in particular taking into account the above-mentioned embodiments.
• MR-proADM midregional proAdrenominated Dullin
• detection reagents include e.g. Antibodies, etc.
• the MR-proADM assay was performed according to Morgenthaler et al. (Morgenthaler NG, Struck J, Alonso C, Bergmann A. Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay. Clin Chem. 2005 Oct; 51 (10): 1823-9).
• MR-proADM was evaluated in 100 healthy subjects with undisturbed glucose tolerance, 60 patients with impaired glucose tolerance, and 200 patients with manifested type II diabetes mellitus (DM II for short), divided into 100 diabetics without complications and 100 diabetics
• Figure 3 shows a significant increase in MR proADM values with increasing severity of DM II.
• the two groups of DM II patients differed from the healthy controls and the patients with impaired glucose tolerance
• the highest MR-proADM values were found in the DM II patients who already had diabetic complications.
• Table 1 shows the diabetes-relevant parameters such as glucose and HbAlc in the respective groups.
• FIG. 1 shows the SEQ ID no. 1 of the preproADM together with it Partial sequences.
• FIG. 2 shows SEQ ID no. 2 of the MR-proADM
• FIG. 3 shows MR-proADM in healthy subjects, patients with impaired glucose tolerance, patients with diabetes mellitus type II (DM II) without late complications (SK) (syn: secondary diseases) and patients with DM II with late complications (syn: secondary diseases).

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• Investigating Or Analysing Biological Materials (AREA)
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• Peptides Or Proteins (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 2006
  • 2006-11-08 DE DE102006052916A patent/DE102006052916A1/de not_active Withdrawn
• 2007
  • 2007-11-08 EP EP07866202A patent/EP2097748B1/de active Active
  • 2007-11-08 CN CN200780041709.4A patent/CN101568833B/zh active Active
  • 2007-11-08 US US12/514,194 patent/US20100035275A1/en not_active Abandoned
  • 2007-11-08 ES ES07866202T patent/ES2393262T3/es active Active
  • 2007-11-08 JP JP2009535557A patent/JP5275247B2/ja active Active
  • 2007-11-08 CN CN201410442798.5A patent/CN104198735B/zh active Active
  • 2007-11-08 WO PCT/DE2007/002018 patent/WO2008055491A2/de not_active Ceased
• 2012
  • 2012-10-25 JP JP2012235494A patent/JP2013047689A/ja active Pending
• 2016
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