Non-Alcoholic Fatty Liver Disease in Long-Term Type 2 Diabetes: Role of rs738409 PNPLA3 and rs499765 FGF21 Polymorphisms and Serum Biomarkers

Abstract

Fibroblast growth factor 21 (FGF21) signaling and genetic factors are involved in non-alcoholic fatty liver disease (NAFLD) pathogenesis. However, these factors have rarely been studied in type 2 diabetes mellitus (T2D) patients from admixed populations such as in those of Brazil. Therefore, we aimed to evaluate rs738409 patanin-like phospholipase domain-containing protein (PNPLA3) and rs499765 FGF21 polymorphisms in T2D, and their association with NAFLD, liver fibrosis, and serum biomarkers (FGF21 and cytokeratin 18 levels). A total of 158 patients were included, and the frequency of NAFLD was 88.6%, which was independently associated with elevated body mass index. Significant liver fibrosis (≥F2) was detected by transient elastography (TE) in 26.8% of NAFLD patients, and was independently associated with obesity, low density lipoprotein, and gamma-glutamyl transferase (GGT). PNPLA3 GG genotype and GGT were independently associated with cirrhosis. PNPLA3 GG genotype patients had higher GGT and AST levels; PNPLA3 GG carriers had higher TE values than CG patients, and FGF21 CG genotype patients showed lower gamma-GT values than CC patients. No differences were found in serum values of FGF21 and CK18 in relation to the presence of NAFLD or liver fibrosis. The proportion of NAFLD patients with liver fibrosis was relevant in the present admixed T2D population, and was associated with PNPLA3 polymorphisms.

Plasma Cytokeratin-18 Fragment Level Reflects the Metabolic Phenotype in Obesity

“…On the other hand, a shorter (4-week) exercise training intervention did not reduce either ALT or CK-18 despite decreasing postprandial insulin [ 58 ]. Similarly, in a study involving diabetic type 2 patients, serum levels of both FGF-21 and CK-18 were not evidently associated with the presence of NAFLD or liver fibrosis [ 59 ].…”

Pnpla3 Gene Polymorphism and Red Meat Consumption Increased Fibrosis Risk in Nash Biopsy-Proven Patients Under Medical Follow-Up in a Tertiary Center in Southwest Brazil

“…Single nucleotide polymorphisms (SNPs) in genes are potentially involved in oxidative stress, lipogenesis de novo, and IR have an important role in the development and progression of NAFLD (11,12) . Polymorphism in the Patatin-like phospholipase domain containing 3 (PNPLA3) gene has an important impact on the susceptibility of NAFLD.…”

Evaluation of the clinical value of shear wave elastography for early detection and diagnosis of diabetic peripheral neuropathy: a controlled preliminary prospective clinical study

“…Moreover, this buccal problem can be transmitted vertically from pregnant women to newborns by influencing the establishment of the buccal microbiome of newborns [ 4 ]. Mauy Frujuello Mana’s [ 5 ] has found that the prevalence of non-alcoholic fatty liver disease in type 2 diabetic patients was as high as 88.6%, of which more than 1/4 of patients had significant liver fibrosis. Hyperglycemia induces the accumulation of sorbitol, causing increased moisture in nerve cells, diffuse swelling of nerves, obscuration of the perineural structures of nerve fascicles, reduced elasticity, increased hardness, leading to a series of peripheral nerve diseases [ 6 ] .…”