Polymorphisms associated with type 2 diabetes in familial longevity: Sthe Leiden Longevity Study

Simon P. Mooijaart, Diana Van Heemst, Raymond Noordam, Maarten P. Rozing, Carolien A. Wijsman, Anton J.M. De Craen, Rudi G.J. Westendorp, Marian Beekman, P. Eline Slagboom

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Human longevity is in part genetically determined, and the insulin/IGF-1 signal transduction (IIS) pathway has consistently been implicated. In humans, type 2 diabetes is a frequent disease that results from loss of glucose homeostasis and for which new candidate polymorphisms now rapidly emerge from genome wide association studies. In the Leiden Longevity Study (n=2415), the offspring of long lived siblings ("offspring") who are genetically enriched for longevity were shown to have a more beneficial metabolic profile compared to their environmentally matched partners ("controls"), including better glucose tolerance. We tested whether the "offspring" carry a lower burden of diabetes risk alleles. Fifteen polymorphisms derived from genome wide association (GWA) scans in type 2 diabetes were tested for association with parameters of glucose metabolism in offspring and controls, and burden of risk alleles was compared between offspring and controls. Among all participants, a higher number of type 2 diabetes risk alleles associated with a higher prevalence of diabetes (P=0.011) and higher serum concentration of glucose (P<0.016) but not insulin (P=0.450). None of the polymorphisms differed in frequency between the offspring and controls (all P>0.05), nor did the mean total number of risk alleles (P=0.977). The association between polymorphisms and glucose levels did not differ between controls and offspring (Pinteraction=0.523). The better glucose tolerance of the "offspring" is not explained by a lower burden of type 2 diabetes risk alleles, suggesting that specific mechanisms determining longevity exist.

Original languageEnglish
Pages (from-to)55-62
Number of pages8
Issue number1
StatePublished - Jan 2011
Externally publishedYes


  • Diabetes mellitus
  • Glucose
  • Insulin
  • Longevity
  • Polymorphism
  • Snp


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