Development and course of diabetes according to genetic factors and diabetes treatment among patients with nonalcoholic fatty liver disease

Nutrition. 2021 Mar;83:111080. doi: 10.1016/j.nut.2020.111080. Epub 2020 Nov 19.

Abstract

Objectives: Many patients with nonalcoholic fatty liver disease (NAFLD) also have diabetes. However, the genetic factors associated with diabetes in NAFLD are unclear. In this study, we investigated the clinical course and risk factors of diabetes development.

Methods: A total of 544 patients (275 men; 50.6%) with a median age of 53 y and biopsy-confirmed NAFLD enrolled in the study. Patatin-like phospholipase 3 and voltage-gated potassium channel KQT-like subfamily member 1 (KCNQ1) single nucleotide polymorphisms were identified in 287 cases. There were 272 patients without diabetes, and 64, 141, and 67 patients with diabetes not treated with an oral hypoglycemic agent, treated with an oral hypoglycemic agent, and treated with insulin, respectively. Changes in biochemical parameters and body weight over a 1-y period were determined in patients treated with incretin agents (n = 91), a sodium glucose cotransporter 2 inhibitor (n = 19), or both (n = 33). The prevalence and risk factors for diabetes development among patients with NAFLD were determined in nondiabetic patients.

Results: Among patients with NAFLD, half of the patients had diabetes and the incidence was high in those with advanced fibrosis. Reduction in body weight was higher after sodium glucose cotransporter 2 inhibitor treatment (P = .050) and in KCNQ1 CC genotype patients (P < .05). Reduction in hemoglobin A1c level was significantly lower in patatin-like phospholipase 3 GG subjects (P < .05). De novo diabetes developed in 44 patients (10-y incidence: 17.9%), especially in obese (P = .046) and KCNQ1 CC genotype patients (P < .01).

Conclusions: Patient genetic background affected treatment response and incidence of diabetes in patients with NAFLD.

Keywords: Diabetes; KCNQ1; NAFLD; Nonalcoholic fatty liver disease; PNPLA3; SGLT-2; Sodium glucose cotransporter 2 inhibitor; patatin-like phospholipase 3; voltage-gated potassium channel KQT-like subfamily member 1.

MeSH terms

  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / genetics
  • Genetic Predisposition to Disease
  • Humans
  • Lipase
  • Male
  • Membrane Proteins
  • Non-alcoholic Fatty Liver Disease* / epidemiology
  • Non-alcoholic Fatty Liver Disease* / genetics
  • Polymorphism, Single Nucleotide
  • Sodium-Glucose Transporter 2 Inhibitors*

Substances

  • Membrane Proteins
  • Sodium-Glucose Transporter 2 Inhibitors
  • Lipase