title: Large-scale population analysis reveals an extremely low threshold for "non-healthy" alanine aminotransferase that predicts diabetes mellitus.
abstract: OBJECTIVE
  Serum alanine aminotransferase (ALT) is commonly used to detect liver damage. Recent studies indicate that ALT levels at the upper range of normal limits are predictors of adverse outcomes, especially diabetes mellitus (DM) and the metabolic syndrome. The aim of our study was to define the ALT threshold for both men and women that may predict the onset of DM.
  
  
  METHODS
  We analyzed a large Health Maintenance Organization cohort of 157 308 healthy subjects with no evidence of liver disease and with baseline ALT levels ≤ 120 U/L, and identified those who developed DM within 6 years.
  
  
  RESULTS
  Overall, an elevated baseline serum ALT value was significantly associated with the development of DM, with an odds ratio of 3.3 when comparing the higher and the lower quartiles of the whole study population. A subgroup analysis revealed that baseline ALT values higher than 10 U/L among women and 22 U/L among men were already significantly associated with an increased risk for DM for any increment in ALT level. Notably, ALT values higher than ∼55 U/L were associated with increased risk for DM that was relatively constant for any increment in ALT. Higher baseline ALT levels were stronger predictors for DM as compared with age, triglycerides and cholesterol levels.
  
  
  CONCLUSIONS
  Our study implies that ALT values higher than 10 U/L and 22 U/L for women and men, respectively, may predict DM. We suggest redefining ALT values as either 'normal' or 'healthy', with the later reflecting much lower values, above which an individual is at increased risk for DM.
authors.affiliation: Department of Gastroenterology and Liver Disease, Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Israel. amirsh@tasmc.health.gov.il
authors.forename: Amir
authors.initials: A
authors.lastname: Shlomai
authors.forename: Revital
authors.initials: R
authors.lastname: Kariv
authors.forename: Moshe
authors.initials: M
authors.lastname: Leshno
authors.forename: Anat
authors.initials: A
authors.lastname: Beth-or
authors.forename: Bracha
authors.initials: B
authors.lastname: Sheinberg
authors.forename: Zamir
authors.initials: Z
authors.lastname: Halpern
mesh_terms: D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000453:epidemiology / Q000209:etiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008107:Liver Diseases / Q000097:blood* / Q000150:complications; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D000410:Alanine Transaminase