Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of type 2 diabetes (DM), therefore, early diagnosis of NAFLD is important to prevent incident DM. FIB-4 index, a biomarker, often used to evaluate severity of NAFLD, may be useful to evaluate risk for incident DM in ordinary clinical setting. Here, we determined the association of FIB-4 index with changes in indices representing glucose metabolism with aging in a non-diabetic population. From among the participants of the population-based Iwaki study of Japanese people conducted during 2014–2017, 1,268 non-diabetic individuals with complete data sets (age: 51.4 ± 15.9 years; men/women: 485/773) were enrolled in a cross-sectional study. In addition, of the participants, 439 who attended consecutive appointments between 2014 and 2017 were enrolled in a longitudinal study that aimed to evaluate the changes in insulin secretion and resistance with aging (age: 53.1 ± 13.7 years; men/women: 178/261). The cross-sectional study showed significant correlations of FIB-4 index with homeostasis model of assessment (HOMA) indices, even after adjustment for multiple factors (HOMA-β: β = − 0.254, p < 0.001; HOMA-R: β = − 0.247, p < 0.001). The longitudinal study showed a significant association between FIB-4 index and the change in HOMA-β (p < 0.001) but not HOMA-R (p = 0.639) during the 3-year study period. Use of the optimal cut-off value of the FIB-4 index for the prediction of decreased insulin secretion (HOMA-β < 30), determined using receiver operating characteristic analysis (1.592), showed that individuals at risk had a hazard ratio of 2.22 (confidence interval 1.17−4.06) for decreased insulin secretion, after adjustment for confounders. FIB-4 index may represent a useful predictor of a subsequent decrease in insulin secretion, at least in a non-diabetic Japanese population.
Highlights
Type 2 diabetes (DM) increases the risks of serious physical and mental health problems, and, the prevalence of DM is increasing w orldwide[1,2]
Evaluation of the relationship between FIB-4 index and changes in glucose metabolism in the general subjects may provide evidence of the mechanisms whereby non-alcoholic fatty liver disease (NAFLD) predisposes toward DM, which is generally though to be via an increase in insulin resistance[5,6,7]
In addition to many clinical characteristics, such as age, gender, body mass index (BMI), fat (%), blood pressures, HbA1c, and serum lipid, uric acid, and urea nitrogen concentrations, FIB-4 index correlated with homeostasis model of assessment (HOMA) indices, and the strongest correlation among these was for HOMA of β-cell function (HOMA-β) (β = − 0.445) (Supplemental Fig. 1)
Summary
Type 2 diabetes (DM) increases the risks of serious physical and mental health problems, and, the prevalence of DM is increasing w orldwide[1,2]. Finding individuals at risk to develop abnormality of glucose metabolism or DM seems to be an important issue to prevent an increase of DM. For such purpose, biological markers seem to be useful in ordinary clinical settings, whether their associations are cause or consequence, or merely association. The influence of the progression of NAFLD or simple steatosis to non-alcoholic steatohepatitis (NASH) on the association with DM or glucose metabolism has not been thoroughly studied, previous studies have shown close associations between decreased glucose tolerance and the presence and severity of liver fibrosis, rather than the degree of steatosis[7,10]. In the present study, we evaluated the relationships between FIB-4 index and changes in indices of glucose metabolism, or insulin secretion and resistance over a 3-year period, as well as evaluating the cross-sectional relationship between FIB-4 index and insulin secretion and resistance, in a non-diabetic Japanese population, which, like other Asian populations, demonstrates lower insulin secretion and resistance than other e thnicities[13]
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