Added citation to a study published in July of which 2009 sheds light on what exactly it is that an allele (gene variant) often found associated with diabetes does. The allele in question is one of TCF7L2 transcription factor gene.
The study involved 81 normal healthy young Danish men whose genes were tested. They were then given a battery of tests to examine their glucose metabolisms. The researchers found that:
Carriers of the T allele were characterised by reduced 24 h insulin concentrations ... and reduced insulin secretion relative to glucose during a mixed meal test ... but not during an IVGTT [intravenous glucose tolerance test].This is an interesting finding, because what damages our bodies is the blood sugar we experience after eating "a mixed meal" but so much research uses the artificial glucose tolerance (GTT) test to assess blood sugar health. This result suggests that the GTT may be missing important signs of early blood sugar dysfunction and that the mixed meal test may be a better diagnostic test than the GTT. I have long believed this to be true, since so many people experience reactive lows when they take the GTT which produces a seemingly "normal reading" though they routinely experience highs after eating meals. These highs are what damage our organs.
Young men with the TCF7L2 allele also responded with weak insulin secretion in response to the incretin hormone GLP-1 and "Despite elevated hepatic [liver] glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations ... suggesting altered alpha cell function."
Here again we see evidence that long before obesity develops, people with this common diabetes gene variant show highly abnormal blood sugar behavior. Abnormal production of glucose by the liver may also contribute to obesity as metformin, a drug that that blocks the liver's production of glucose blocks weight gain and often causes weight loss.
The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men. K. Pilgaard et al. Diabetologia, Issue Volume 52, Number 7 / July, 2009. DOI 10.1007/s00125-009-1307-x