title: Alanine aminotransferase and mortality in patients with type 2 diabetes (ZODIAC-38).
abstract: BACKGROUND
  Combined data suggest a bimodal association of alanine aminotransferase (ALT) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all-cause, cardiovascular and noncardiovascular mortality in patients with type 2 diabetes.
  
  
  METHODS
  A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. Cox regression analyses were performed to determine the associations of log2 -transformed baseline ALT with all-cause, cardiovascular and noncardiovascular mortality.
  
  
  RESULTS
  In 1187 patients with type 2 diabetes (67 ± 12 years, 45% female), ALT levels were 11 (8-16) U/L. During median follow-up for 11.1 (6.1-14.0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all-cause mortality (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.72-0.92), independently of potential confounders. This was less attributable to cardiovascular mortality (HR 0.87; 95% CI 0.72-1.05), than to noncardiovascular mortality (HR 0.77; 95% CI 0.65-0.90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all-cause mortality was present with increasing risk for levels of ALT above normal (P = 0.003).
  
  
  CONCLUSIONS
  In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all-cause mortality, in particular noncardiovascular mortality, compared to normal levels of ALT, while risk again starts to increase when levels are above normal.
authors.affiliation: Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Petronella E
authors.initials: PE
authors.lastname: Deetman
authors.affiliation: Department of Gastroenterology, Isala Clinics, Zwolle, the Netherlands.
authors.forename: Alaa
authors.initials: A
authors.lastname: Alkhalaf
authors.affiliation: Department of Medicine, Gelre Hospital, Apeldoorn, the Netherlands.|Diabetes Centre, Isala Clinics, Zwolle, the Netherlands.
authors.forename: Gijs W D
authors.initials: GW
authors.lastname: Landman
authors.affiliation: Diabetes Centre, Isala Clinics, Zwolle, the Netherlands.|Department of General Practice, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Klaas H
authors.initials: KH
authors.lastname: Groenier
authors.affiliation: Department of Laboratory Medicine, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Kootstra-Ros
authors.affiliation: Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.affiliation: Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.|Diabetes Centre, Isala Clinics, Zwolle, the Netherlands.
authors.forename: Henk J G
authors.initials: HJ
authors.lastname: Bilo
authors.affiliation: Diabetes Centre, Isala Clinics, Zwolle, the Netherlands.|Langerhans Medical Research Group, Zwolle, the Netherlands.
authors.forename: Nanne
authors.initials: N
authors.lastname: Kleefstra
authors.affiliation: Department of Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology; D050171:Dyslipidemias / Q000097:blood / Q000453:epidemiology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009426:Netherlands / Q000453:epidemiology; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000410:Alanine Transaminase; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D014280:Triglycerides; D005723:gamma-Glutamyltransferase; C517652:hemoglobin A1c protein, human
keywords: Alanine aminotransferase; mortality; nonalcoholic fatty liver disease; type 2 diabetes