Obesity, diabetes and cancer: insight into the relationship from a cohort with growth hormone receptor deficiency

Diabetologia. 2015 Jan;58(1):37-42. doi: 10.1007/s00125-014-3397-3. Epub 2014 Oct 15.


Obesity with insulin-resistant diabetes and increased cancer risk is a global problem. We consider the alterations of metabolism attendant on the underlying pathogenic overnutrition and the role of the growth hormone (GH)-IGF-1 axis in this interaction. Obesity-induced insulin resistance is a determinant of diabetes. Excess glucose, and an elevated concentration of insulin acting through its own receptors along with complex interactions with the IGF-1 system, will add extra fuel and fuel signalling for malignant growth and induce anti-apoptotic activities, permitting proliferation of forbidden clones. In Ecuador there are ~100 living adults with lifelong IGF-1 deficiency caused by a GH receptor (GHR) mutation who, despite a high percentage of body fat, have markedly increased insulin sensitivity compared with age- and BMI-matched control relatives, and no instances of diabetes, which is present in 6% of unaffected relatives. Only 1 of 20 deceased individuals with GHR deficiency died of cancer vs 20% of ~1,500 relatives. Fewer DNA breaks and increased apoptosis occurred in cell cultures exposed to oxidant agents following addition of serum from GHR-deficient individuals vs serum from control relatives. These changes were reversible by adding IGF-1 to the serum from the GHR-deficient individuals. The reduction in central regulators of pro-ageing signalling thus appears to be the result of an absence of GHR function. The complex inter-relationship of obesity, diabetes and cancer risk is related to excess insulin and fuel supply, in the presence of heightened anti-apoptosis and uninhibited DNA damage when GHR function is normal.

Publication types

  • Review

MeSH terms

  • Adult
  • Body Composition
  • Case-Control Studies
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics
  • Ecuador / epidemiology
  • Humans
  • Insulin / physiology
  • Insulin-Like Growth Factor I / physiology
  • Laron Syndrome / complications
  • Laron Syndrome / epidemiology*
  • Laron Syndrome / genetics
  • Neoplasms / complications
  • Neoplasms / epidemiology*
  • Neoplasms / genetics
  • Obesity / complications
  • Obesity / epidemiology*
  • Obesity / genetics


  • Insulin
  • Insulin-Like Growth Factor I