Download PDF
Diabetes aktuell 2014; 12(4): 164-170
DOI: 10.1055/s-0034-1387172
Schwerpunkt
© Georg Thieme Verlag Stuttgart · New York

Personalisierte Diabetestherapie – Wo stehen wir heute?

Personalized diabetes therapy – state of the art
Katharina Susanne Weber
1   Institut für Klinische Diabetologie, Deutsches Diabetes-Zentrum an der Heinrich-Heine-Universität, Leibniz Institut für Diabetesforschung, Düsseldorf
2   Deutsches Zentrum für Diabetesforschung, Partner Düsseldorf
,
Michael Roden
*   Direktor und wissenschaftlicher Geschäftsführer des Deutschen Diabetes-Zentrums; Ärztlicher Direktor der Klinik für Endokrinologie und Diabetologie, Universitätsklinikum Düsseldorf
1   Institut für Klinische Diabetologie, Deutsches Diabetes-Zentrum an der Heinrich-Heine-Universität, Leibniz Institut für Diabetesforschung, Düsseldorf
2   Deutsches Zentrum für Diabetesforschung, Partner Düsseldorf
3   Klinik für Endokrinologie und Diabetologie, Universitätsklinikum, Düsseldorf
,
Karsten Müssig
1   Institut für Klinische Diabetologie, Deutsches Diabetes-Zentrum an der Heinrich-Heine-Universität, Leibniz Institut für Diabetesforschung, Düsseldorf
2   Deutsches Zentrum für Diabetesforschung, Partner Düsseldorf
3   Klinik für Endokrinologie und Diabetologie, Universitätsklinikum, Düsseldorf
› Author Affiliations
Further Information

Publication History

Publication Date:
29 July 2014 (online)

Also available at
    Permissions and Reprints

Die personalisierte Medizin verfolgt das Ziel, individuelle Präventions- und Behandlungsstrategien anzuwenden, die speziell auf einen Patienten zugeschnitten sind. Grundlage dieses Konzepts ist die Identifikation von Genen und Biomarkern, die die Auswahl einer individualisierten Therapie ermöglichen. Der Typ-2-Diabetes mellitus ist eine sehr heterogene Erkrankung mit steigender Prävalenz. Sowohl für das Ansprechen auf eine Lebensstilintervention zur Prävention des Typ-2-Diabetes als auch für den Erfolg einer Therapie des Typ-2-Diabetes konnten Assoziationen mit genetischen Faktoren identifiziert werden. Genpolymorphismen, die einen Einfluss auf den Therapieerfolg haben, wurden beispielsweise bereits für die Behandlung mit Sulfonylharnstoffen, Biguaniden, Thiazolidinedionen und ACE (angiotensin converting enzyme)-Hemmern beschrieben. Um das langfristige Ziel der personalisierten Medizin, die Inzidenz des Typ-2-Diabetes durch erfolgreiche Prävention zu senken und die Patienten mit Typ-2-Diabetes optimal zu therapieren, erreichen zu können, ist jedoch noch eine intensive Grundlagen- und klinische Forschung notwendig. Auch müssen infrastrukturelle, personelle, ethische und finanzielle Barrieren überwunden werden, um eine individualisierte Medizin erfolgreich umzusetzen. Erste Erkenntnisse weisen darauf hin, dass eine Personalisierung einen großen Stellenwert in der Prävention und der Therapie des Typ-2-Diabetes erhalten könnte.

Personalized medicine aims to individualize prevention and treatment options. The concept is based on the identification of genes and biomarkers which allow choosing an individualized therapy. Type 2 diabetes mellitus (T2DM) is a very heterogeneous disease with an increasing prevalence. Associations were identified between genetic factors and the response to lifestyle interventions that aim to prevent T2DM as well as between genetic factors and the response to drug treatment. Gene polymorphisms that influence the treatment response were found for example for the treatment with sulfonylurea, biguanides, thiazolidinediones, and ACE (angiotensin converting enzyme)-inhibitors. Intense basic and clinical research is needed in order to reach the longitudinal aim of personalized medicine that comprises a reduction of the incidence of T2DM by successful diabetes prevention as well as an optimal therapy of the disease. In addition, personal, infrastructural, ethical and financial barriers need to be overcome for an implementation of an individualized medicine. Based on the initial findings, a personalization of the prevention and the therapy of T2DM could become increasingly important.

Key words

Type 2 diabetes mellitus - individualized therapy - gene polymorphism - lifestyle intervention
 

  • Literatur

  • 1 Malandrino N, Smith RJ. Personalized medicine in diabetes. Clin Chem 2011; 57: 231-240
    CrossrefGoogle Scholar
  • 2 Rathmann W, Strassburger K, Heier M et al. Incidence of Type 2 diabetes in the elderly German population and the effect of clinical and lifestyle risk factors: KORA S4/F4 cohort study. Diabet Med 2009; 26: 1212-1219
    CrossrefGoogle Scholar
  • 3 Diagnosis and classification of diabetes mellitus. Diabetes Care 2014; 37 (Suppl. 01)
    Google Scholar
  • 4 Herder C, Roden M. Genetics of type 2 diabetes: pathophysiologic and clinical relevance. Eur J Clin Invest 2011; 41: 679-692
    CrossrefGoogle Scholar
  • 5 Klonoff DC. Personalized medicine for diabetes. J Diabetes Sci Technol 2008; 2: 335-341
    Google Scholar
  • 6 Rathmann W, Scheidt-Nave C, Roden M, Herder C. Type 2 diabetes: prevalence and relevance of genetic and acquired factors for its prediction. Dtsch Arztebl Int 2013; 110: 331-337
    CrossrefPubMedGoogle Scholar
  • 7 Müssig K, Staiger H, Machicao F, Häring HU, Fritsche A. Genetic variants affecting incretin sensitivity and incretin secretion. Diabetologia 2010; 53: 2289-2297
    CrossrefGoogle Scholar
  • 8 Sathananthan A, Vella A. Personalized pharmacotherapy for Type 2 diabetes mellitus. Per Med 2009; 6: 417-422
    CrossrefGoogle Scholar
  • 9 Hamming KS, Soliman D, Matemisz LC et al. Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel. Diabetes 2009; 58: 2419-2424
    CrossrefGoogle Scholar
  • 10 Sesti G, Laratta E, Cardellini M et al. The E23K variant of KCNJ11 encoding the pancreatic beta-cell adenosine 5'-triphosphate-sensitive potassium channel subunit Kir6.2 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes. J Clin Endocrinol Metab 2006; 91: 2334-2339
    CrossrefGoogle Scholar
  • 11 Pearson ER, Donnelly LA, Kimber C et al. Variation in TCF7L2 influences therapeutic response to sulfonylureas: a GoDARTs study. Diabetes 2007; 56: 2178-2182
    CrossrefGoogle Scholar
  • 12 Sesti G, Marini MA, Cardellini M et al. The Arg972 variant in insulin receptor substrate-1 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes. Diabetes Care 2004; 27: 1394-1398
    CrossrefGoogle Scholar
  • 13 Becker ML, Visser LE, Trienekens PH et al. Cytochrome P450 2C9 *2 and *3 polymorphisms and the dose and effect of sulfonylurea in type II diabetes mellitus. Clin Pharmacol Ther 2008; 83: 288-292
    CrossrefGoogle Scholar
  • 14 Shu Y, Sheardown SA, Brown C et al. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest 2007; 117: 1422-1431
    CrossrefGoogle Scholar
  • 15 Becker ML, Visser LE, vanSchaik RH et al. Genetic variation in the multidrug and toxin extrusion 1 transporter protein influences the glucose-lowering effect of metformin in patients with diabetes: a preliminary study. Diabetes 2009; 58: 745-749
    CrossrefGoogle Scholar
  • 16 Wang G, Wang X, Zhang Q, Ma Z. Response to pioglitazone treatment is associated with the lipoprotein lipase S447X variant in subjects with type 2 diabetes mellitus. Int J Clin Pract 2007; 61: 552-557
    CrossrefGoogle Scholar
  • 17 Ruggenenti P, Bettinaglio P, Pinares F, Remuzzi G. Angiotensin converting enzyme insertion/deletion polymorphism and renoprotection in diabetic and nondiabetic nephropathies. Clin J Am Soc Nephrol 2008; 3: 1511-1525
    CrossrefGoogle Scholar
  • 18 Moore AF, Jablonski KA, McAteer JB et al. Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program. Diabetes 2008; 57: 2503-2510
    CrossrefGoogle Scholar
  • 19 Müssig K, Heni M, Thamer C et al. The ENPP1 K121Q polymorphism determines individual susceptibility to the insulin-sensitising effect of lifestyle intervention. Diabetologia 2010; 53: 504-509
    CrossrefGoogle Scholar
  • 20 Brito EC, Lyssenko V, Renstrom F et al. Previously associated type 2 diabetes variants may interact with physical activity to modify the risk of impaired glucose regulation and type 2 diabetes: a study of 16,003 Swedish adults. Diabetes 2009; 58: 1411-1418
    CrossrefGoogle Scholar
  • 21 Kacerovsky-Bielesz G, Kacerovsky M, Chmelik M et al. A single nucleotide polymorphism associates with the response of muscle ATP synthesis to long-term exercise training in relatives of type 2 diabetic humans. Diabetes Care 2012; 35: 350-357
    CrossrefGoogle Scholar
  • 22 Stefan N, Thamer C, Staiger H et al. Genetic variations in PPARD and PPARGC1A determine mitochondrial function and change in aerobic physical fitness and insulin sensitivity during lifestyle intervention. J Clin Endocrinol Metab 2007; 92: 1827-1833
    CrossrefGoogle Scholar
  • 23 Weyrich P, Machicao F, Reinhardt J et al. SIRT1 genetic variants associate with the metabolic response of Caucasians to a controlled lifestyle intervention – the TULIP Study. BMC Med Genet 2008; 9: 100-100
    CrossrefGoogle Scholar
  • 24 Thamer C, Haap M, Heller E et al. Beta cell function, insulin resistance and plasma adiponectin concentrations are predictors for the change of postprandial glucose in non-diabetic subjects at risk for type 2 diabetes. Horm Metab Res 2006; 38: 178-182
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Kantartzis K, Thamer C, Peter A et al. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut 2009; 58: 1281-1288
    CrossrefGoogle Scholar
  • 26 Thamer C, Machann J, Stefan N et al. High visceral fat mass and high liver fat are associated with resistance to lifestyle intervention. Obesity (Silver Spring) 2007; 15: 531-538
    CrossrefGoogle Scholar
  • 27 Tuomilehto J, Lindstrom J, Eriksson JG et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343-1350
    CrossrefPubMedGoogle Scholar
  • 28 Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 2009; 373: 1773-1779
    CrossrefGoogle Scholar
  • 29 Schulze MB, Hoffmann K, Boeing H et al. An accurate risk score based on anthropometric, dietary, and lifestyle factors to predict the development of type 2 diabetes. Diabetes Care 2007; 30: 510-515
    CrossrefPubMedGoogle Scholar
  • 30 Kang ES, Park SY, Kim HJ et al. Effects of Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma2 gene on rosiglitazone response in type 2 diabetes. Clin Pharmacol Ther 2005; 78: 202-208
    CrossrefGoogle Scholar
  • 31 Wolford JK, Yeatts KA, Dhanjal SK et al. Sequence variation in PPARG may underlie differential response to troglitazone. Diabetes 2005; 54: 3319-3325
    CrossrefGoogle Scholar