title: Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis.
abstract: OBJECTIVE
  The magnitude of the risk of incident type 2 diabetes (T2D) and metabolic syndrome (MetS) among patients with nonalcoholic fatty liver disease (NAFLD) is poorly known. We gauged the risk of developing T2D and MetS in patients with NAFLD diagnosed by either serum liver enzymes (aminotransferases or gamma-glutamyltransferase [GGT]) or ultrasonography.
  
  
  METHODS
  Pertinent prospective studies were identified through extensive electronic database research, and studies fulfilling enrolment criteria were included in the meta-analysis.
  
  
  RESULTS
  Overall, in a pooled population of 117020 patients (from 20 studies), who were followed-up for a median period of 5 years (range: 3-14.7 years), NAFLD was associated with an increased risk of incident T2D with a pooled relative risk of 1.97 (95% confidence interval [CI], 1.80-2.15) for alanine aminotransferase, 1.58 (95% CI, 1.43-1.74) for aspartate aminotransferase, 1.86 (95% CI, 1.71-2.03) for GGT (last vs first quartile or quintile), and 1.86 (95% CI, 1.76-1.95) for ultrasonography, respectively. Overall, in a pooled population of 81411 patients (from eight studies) who were followed-up for a median period of 4.5 years (range: 3-11 years), NAFLD was associated with an increased risk of incident MetS with a pooled relative risk of 1.80 (95% CI, 1.72-1.89) for alanine aminotransferase (last vs first quartile or quintile), 1.98 (95% CI, 1.89-2.07) for GGT, and 3.22 (95% CI, 3.05-3.41) for ultrasonography, respectively.
  
  
  CONCLUSIONS
  Nonalcoholic fatty liver disease, as diagnosed by either liver enzymes or ultrasonography, significantly increases the risk of incident T2D and MetS over a median 5-year follow-up.
authors.affiliation: Azienda USL, Internal Medicine, Pavullo Hospital, Pavullo, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ballestri
authors.affiliation: University of Modena and Reggio Emilia, Metabolic Clinic, Infectious and Tropical Disease Unit, Policlinico Hospital, Modena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Zona
authors.affiliation: Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Targher
authors.affiliation: Azienda USL, Outpatient Liver Clinic and Internal Medicine, NOCSAE, Modena, Italy.
authors.forename: Dante
authors.initials: D
authors.lastname: Romagnoli
authors.affiliation: Azienda USL, Outpatient Liver Clinic and Internal Medicine, NOCSAE, Modena, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Baldelli
authors.affiliation: Azienda USL, Outpatient Liver Clinic and Internal Medicine, NOCSAE, Modena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Nascimbeni
authors.affiliation: Department of Statistics, University of Bologna, Bologna, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Roverato
authors.affiliation: University of Modena and Reggio Emilia, Metabolic Clinic, Infectious and Tropical Disease Unit, Policlinico Hospital, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guaraldi
authors.affiliation: Azienda USL, Outpatient Liver Clinic and Internal Medicine, NOCSAE, Modena, Italy.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Lonardo
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004796:Clinical Enzyme Tests; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D024821:Metabolic Syndrome / Q000175:diagnosis / Q000453:epidemiology*; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000453:epidemiology*; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014463:Ultrasonography; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015415:Biomarkers; D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: ALT; AST; Diabetes; GGT; Liver enzymes; Metabolic Syndrome; NAFLD; Ultrasonography