Skip to main content
SpringerLink
Log in

Genetik des Diabetes mellitus Typ 2 und verwandter Diabetesformen

Genetics of diabetes mellitus and related forms of diabetes

  • Leitthema: Diabetes mellitus Typ 2
  • Published:
Monatsschrift Kinderheilkunde Aims and scope Submit manuscript

Zusammenfassung

Diabetes mellitus Typ 2 hat weltweit epidemische Ausmaße angenommen und gewinnt auch in der Kinderheilkunde zunehmend an Bedeutung. Familienuntersuchungen und Zwillingsstudien belegten, dass die genetische Prädisposition einen erheblichen Einfluss auf seine Entstehung hat. Genomweite Linkageanalysen und Assoziationsstudien konnten einige Kandidatengene identifizieren, die für die Entwicklung eines Typ-2-Diabetes eine Rolle spielen. Polymorphismen z. B. im PPARγ-, KCNJ11- und Insulinrezeptorsubstrat-1-Gen sind mit einem erhöhten Risiko für Diabetes mellitus Typ 2 assoziiert. Zudem liegen in unterschiedlichen Populationen unterschiedliche genetische Prädispositionen vor. Die molekulargenetische Aufklärung monogenetischer Diabetesformen, die mit Insulinresistenz oder gestörter Insulinsekretion einhergehen, hat zum besseren Verständnis der Pathogenese des Typ-2-Diabetes beigetragen.

Abstract

Type 2 diabetes mellitus has reached epidemic proportions worldwide and is also becoming increasingly important in pediatrics. Family studies and twin studies have shown that the genetic predisposition has an important impact on the development of type 2 diabetes. Genome-wide linkage studies and association studies have identified various candidate genes that are thought to be involved in the development of type 2 diabetes. Polymorphisms in the PPARγ gene, the KCNJ11 gene, and the insulin receptor substrate 1 gene and others are associated with an elevated risk of development of type 2 diabetes. In addition, these studies also suggest that the genetic predisposition to type 2 diabetes differs in different populations. Elucidation of the molecular basis of monogenetic forms of diabetes associated with insulin resistance or disturbed insulin secretion has also added to our understanding of the pathogenesis of type 2 diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Wiegand S, Maikowski U, Blankenstein O et al. (2004) Type 2 diabetes and impaired glucose tolerance in European children and adolescents with obesity — a problem that is no longer restricted to minority groups. Eur J Endocrinol 151:199–206

    Article  PubMed  Google Scholar 

  2. Reinehr T, Andler W, Kapellen T et al. (2005) Clinical characteristics of type 2 diabetes mellitus in overweight European Caucasian adolescents. Exp Clin Endocrinol Diabetes 113:167–170

    Article  PubMed  Google Scholar 

  3. King H, Rewers M (1993) Global estimates for prevalences of diabetes mellitus and impaired glucose tolerance in adults. WHO Ad Hoc Diabetes Reporting Group. Diabetes Care 16:157–177

    PubMed  Google Scholar 

  4. Simmons D, Williams RC, Pettitt DJ et al. (1991) The Coventry diabetes study: prevalence of diabetes and impaired glucose tolerance in Europians and Asians. Q J Med 81:1021–1030

    PubMed  Google Scholar 

  5. Stumvoll M, Goldstein BJ, van Haeften TW (2005) Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365:1333–1346

    Article  PubMed  Google Scholar 

  6. Pierce M, Keen H, Bradley C (1995) Risk of diabetes in offspring of parents with non-insulin-dependent diabetes. Diabet Med 12:6

    PubMed  Google Scholar 

  7. Tattersal RB, Fajans SS (1975) Prevalence of diabetes and glucose intolerance in 199 offsprings of thirty-seven conjugal diabetes parents. Diabetes 24:452–462

    PubMed  Google Scholar 

  8. Groop LC, Tuomi T (1997) Non-insulin-dependent diabetes mellitus — a collision between thrifty genes and an affluent society. Ann Med 29:37–53

    PubMed  Google Scholar 

  9. Meigs JB, Cupples LA, Wilson PW (2000) Parental transmission of type 2 diabetes: the Framingham offspring study. Diabetes 49:2201–2207

    PubMed  Google Scholar 

  10. Newman B, Selby JV, King MC et al. (1987) Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins. Diabetologia 30:763–768

    Article  PubMed  Google Scholar 

  11. Barnett AH, Eff C, Leslie RD et al. (1981) Diabetes in identical twins. A study of 200 pairs. Diabetologia 20:87–93

    Article  PubMed  Google Scholar 

  12. Poulsen P, Kyvik KO, Vaag A et al. (1999) Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance — a population-based twin study. Diabetologia 42:139–145

    Article  PubMed  Google Scholar 

  13. Barroso I (2005) Genetics of type 2 diabetes. Diabet Med 22:517–535

    Article  PubMed  Google Scholar 

  14. Medici F, Hawa M, Inari A et al. (1999) Concordance rates for type II diabetes mellitus in monozygotic twins: acturial analysis. Diabetologia 42:146–150

    Article  PubMed  Google Scholar 

  15. McCarthy MI (2003) Growing evidence for diabetes susceptibility genes from genome scan data. Curr Diab Rep 3:159–167

    PubMed  Google Scholar 

  16. Hitman GA, Sudagani J (2004) Searching for genes in diabetes and the metabolic syndrome. Int J Clin Pract 143:3–8

    Article  Google Scholar 

  17. Horikawa Y, Oda N, Cox NJ et al. (2000) Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 13:161–166

    Google Scholar 

  18. Horikawa Y, Oda N, Yu L (2003) Genetic variations in calpain-10 gene are not a major factor in the occurence of type 2 diabetes in Japanese. J Clin Endocrinol Metab 88:244–247

    Article  PubMed  Google Scholar 

  19. Hegele RA, Harris SB, Zinnman B et al. (2001) Absence of association of type 2 diabetes with CAPN10 and PC-1 polymorphisms in Oji-Cree. Diabetes Care 24:1498–1499

    Google Scholar 

  20. Silander K, Mohlke KI, Scott IJ (2004) Genetic variation near the hepatocyte nuclear factor-4-alpha gene predicts susceptibility to type 2 diabetes. Diabetes 53:1141–1149

    PubMed  Google Scholar 

  21. Parikh H, Groop LC (2004) Candidate genes for type 2 diabetes. Rev Endocr Metab Disord 5:151–176

    Article  PubMed  Google Scholar 

  22. Lohmueller KE, Pearce CL, Pike M et al. (2003) Meta-analysis of genetic association studies support a contribution of common variants to susceptibility to common disease. Nat Genet 33:177–182

    Article  PubMed  Google Scholar 

  23. Hani EH, Boutin P, Durand E et al. (1998) Missense mutations in the pancreatic beta cell inwardly rectifying K+ channel gene (Kir6.2/BIR): a meta-analysis suggests a role in the polygenic basis of type II diabetes mellitus in Caucasians. Diabetologia 41:1511–1515

    Article  PubMed  Google Scholar 

  24. Jellema A, Zeegers MP, Feskens EJ et al. (2003) Gly972Arg variant in the insulin receptor substrate-1 gene and association with type 2 diabetes: a meta-analysis of 27 studies. Diabetologia 46:990–995

    Article  PubMed  Google Scholar 

  25. Hegele RA, Cao H, Harris SB et al. (1999) Hepatocyte nuclear factor-1alpha G319A. A private mutation in Oji-Cree associated with type 2 diabetes. Diabetes Care 22:524

    Google Scholar 

  26. Poulton J, Luan J, Macaulay V et al. (2002) Type 2 diabetes is associated with a common mitochondrial variant: evidence from a population-based case control study. Hum Mol Genet 11:1581–1583

    Article  PubMed  Google Scholar 

  27. Ten S, Maclaren N (2004) Insulin resistance syndrome in children. J Clin Endocrinol Metab 89:2526–2539

    Article  PubMed  Google Scholar 

  28. Longo N, Wang Y, Smith SA et al. (2002) Genotype-phenotype correlations in inherited severe insulin resistance. Hum Mol Genet 11:1465–1475

    Article  PubMed  Google Scholar 

  29. Taylor SI, Hedo JA, Underhill LH et al. (1982) Extreme insulin resistance in association with abnormally high binding affinity of insulin receptors from a patient with leprechaunism: evidence for a defect intrinsic to the receptor. J Clin Endocrinol Metab 55:1108–1113

    PubMed  Google Scholar 

  30. Porter JR, Barrett TG (2005) Monogenetic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and β-cell failure. J Med Genet in press

    Google Scholar 

  31. Fajans SS, Bell GI, Polonsky KS (2003) Molecular mechanisms and clinical pathophsiology of maturity-onset diabetes of the yong. N Engl J Med 345:971–980

    Article  Google Scholar 

  32. Glaser B (2003) Dominant SUR1 mutation causing autosomal dominant type 2 diabetes. Lancet 361:272–273

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt:

Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen.

Author information

Authors and Affiliations

  1. Abteilung 1, Universitätsklinik für Kinder- und Jugendmedizin, Heidelberg

    J. Grulich-Henn

  2. Abteilung 1, Universitätsklinik für Kinder- und Jugendmedizin, Im Neuenheimer Feld 150, 69120, Heidelberg

    J. Grulich-Henn

Authors
  1. J. Grulich-Henn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Grulich-Henn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grulich-Henn, J. Genetik des Diabetes mellitus Typ 2 und verwandter Diabetesformen. Monatsschr Kinderheilkd 153, 921–926 (2005). https://doi.org/10.1007/s00112-005-1225-z

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00112-005-1225-z

Schlüsselwörter

Keywords

Search

Navigation