Association between Markers of Fatty Liver Disease and Impaired Glucose Regulation in Men and Women from the General Population: The KORA-F4-Study

Objective: To investigate whether the elevated liver enzymes gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT) and alkaline phosphatase (AP) and non-alcoholic fatty liver disease (NAFLD) respectively are independently associated with pre-diabetic states, namely impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or known and newly diagnosed diabetes (NDD), in men and women from the general German population. Methods: The study was based on 3009 subjects (1556 females, 1453 males) aged 32 to 81 years who participated in the KORA-F4-Study in 2006/2008 in Augsburg, Southern Germany. All non-diabetic participants underwent an oral glucose tolerance test to assess disturbances in glucose metabolism. NAFLD was estimated by liver enzyme concentrations and the Bedogni Fatty Liver Index (FLI). Results: 229 participants (7.6%) reported known diabetes, 106 had NDD (3.5%), 107 (3.6%) had IFG, 309 (10.3%) had IGT, 69 (2.3%) were affected with both metabolic disorders (IFG/IGT) and 74 (2.5%) could not be classified. GGT and GPT were significantly elevated in persons with pre-diabetes and diabetes (GGT in diabetic persons OR = 1.76, [1.47-2.09], in IFG OR = 1.79 [1.50-2.13], GPT in diabetic persons OR = 1.51, [1.30-1.74], in NDD OR = 1.77 [1.52-2.06]), GOT and AP only inconsistently in some pre-diabetes groups. The effects were sharpened in models using an increase of two or three out of three enzymes as an estimate of fatty liver and especially in models using the FLI. Overall frequency of NAFLD applying the index was 39.8% (women: 27.3% and men: 53.2%). In participants with fatty liver disease, the OR for NDD adjusted for sex and age was 8.48 [5.13-14.00], 6.70 [3.74-12.01] for combined IFG and IGT and 4.78 [3.47-6.59] for known diabetes respectively. Conclusions: Elevated GGT and GPT-values as well as estimates of fatty liver disease are significantly associated with prediabetes and diabetes and thus very useful first indicators of a disturbed glucose metabolism.