High protein diet induced reduction of fatty liver is dependent on GIPR SNP s10423928 genotype in type 2 diabetes patients

In the past decade researchers have looked for links between type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). Evidence points out that genetic variation plays an important role modulating the simultaneous occurrence of insulin resistance, adipose tissue distribution and ectopic lipid deposition. In this context glucose-dependent insulinotropic polypeptide receptor (GIPR) is a biologically plausible candidate. In individuals with T2DM, the insulinotropic response to GIP is reduced even though their stimulated GIP secretion appears normal [1]. Previous studies found that the A allele of rs10423928 in GIPR was associated with increased 2-h glucose levels and lower insulinogenic index [2]. Furthermore, GIPR knockout studies show that interruption of the GIP signaling pathway prevents high fat/high sucrose diet–induced obesity [3] and NAFLD [4].

We investigated the effects of GIPR SNP s10423928 in 32 patients with T2DM and NAFLD. Participants were placed on protein rich, isocaloric diets (HPD) (30% protein, 40% carbohydrates, and 30% fat) for six weeks [5].

T homozygous individuals of GIPR SNP s10423928 showed significant greater response to the diets compared with A allele carriers, having an intrahepatic lipid reduction almost twice as large (A: -5.0 ± 3.0 vs. TT:-8.8 ± 6.1, P = 0.036).

This may indicate that HPD induced liver fat reduction in type 2 diabetes patients mellitus is dependent on GIPR genotype.

[1] DOI: 10.1210/jcem-63 – 2-492

[2] DOI: 10.1038/ng.521

[3] PMCID: PMC24735

[4] DOI: 10.1007/s00125 – 014 – 3423 – 5

[5] DOI: 10.1053/j.gastro.2016.10.007