Changes in body composition and low blood urea nitrogen level related to an increase in the prevalence of fatty liver over 20 years: A cross-sectional study.

AIM: Qualitative body composition (BC) change, characterized by the combination of visceral fat gain and muscle loss, is drawing attention as a risk factor for fatty liver (FL). The present study aimed to describe trends in BC change and its association with FL in the Japanese population. METHODS: Data from medical checkups carried out on 56 639 Japanese participants every 5 years from 1997 to 2017 were analyzed. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated using body mass index and body fat percentage. Subjects were divided into two groups according to deviations from the correlation line of FMI and FFMI as the reference: FMI-predominant BC and FFM-dominant BC. Fatty liver was determined using abdominal ultrasonography. RESULTS: The prevalence of FL significantly increased from 27.3% to 42.7% in men and from 18.0% to 25.5% in women. The prevalence of FMI predominance significantly increased from 33.6% to 43.9% in men and from 29.1% to 47.0% in women. Fat mass index predominance was independently associated with FL in men and women (odds ratio: 1.96 and 1.94, respectively). Serum blood urea nitrogen level was inversely associated with FL in men and women (0.958 and 0.961, respectively) and significantly decreased from 15.8 to 14.9 mg/dl in men and from 15.1 to 14.0 mg/dl in women. CONCLUSIONS: Increasing FMI-predominant BC and decreasing serum blood urea nitrogen level could account for the increase in the prevalence of FL over 20 years. We believe that these factors stem from current lifestyle habits in Japan.

Metformin dose increase versus added linagliptin in non-alcoholic fatty liver disease and type 2 diabetes: An analysis of the J-LINK study.

We validated the effect of linagliptin, an oral dipeptidyl peptidase-4 inhibitor, on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). A total of 50 patients with NAFLD and T2DM treated with metformin were randomized (1:1) to metformin plus add-on linagliptin (linagliptin group) or to an increased dose of metformin (metformin group) for 52 weeks. The primary endpoint was change in hepatic steatosis from baseline to week 52 as quantified by unenhanced computed tomography imaging. Secondary endpoints included changes in the levels of anthropometric, biochemical and adipokinetic markers. The linagliptin group showed no statistically significant reduction in hepatic steatosis as compared to the metformin group (P = 0.97), although changes in hepatic steatosis were significantly correlated with decreased liver enzymes in both groups. Body weight was significantly reduced in the metformin group but not in the linagliptin group (P = 0.002). Serum leptin levels were significantly increased in the linagliptin group compared to the metformin group (P = 0.003), and were correlated with the changes body weight in whole samples. Adverse events were not different between the two groups (P = 0.78). Add-on linagliptin demonstrated a safe profile but was not superior to increased metformin in reducing hepatic steatosis.

Increasing prevalence of diabetes mellitus in association with fatty liver in a Japanese population.

BACKGROUND: The prevalence of diabetes mellitus (DM) has been increasing. The present study was carried out to examine the relationship between this increase and fatty liver. METHODS: Japanese participants who underwent regular health examinations in 1991, 1996, 2001, 2006, and 2011 were enrolled. Fatty liver was diagnosed using ultrasonography. DM was defined as requiring the use of medication for DM, having a fasting blood glucose level ≥ 126 mg/dl, or hemoglobin A1c level ≥ 6.5 %. RESULTS: Logistic regression analysis on data from 11,235 participants (6,882 men and 4,271 women) in 2011 revealed that the association between fatty liver and DM was independent of age, body composition, and other confounders [odds ratio (OR) 1.97, 95 % confidence interval (95 % CI) 1.66-2.32 in men, and OR, 3.12; 95 % CI, 2.29-4.26 in women]. In 2006, 5,318 participants did not have DM and were able to be followed up in 2011. Fatty liver in 2006 was an independent predictor of DM in 2011 [OR 1.73 (95 % CI 1.20-2.50) in men, 4.13 (2.16-8.10) in women]. The prevalence of DM increased significantly during the 20-year period examined among both men (6.0, 8.9, 10.0, 10.8, 12.0 %, P < 0.001) and women (3.3, 4.5, 4.2, 4.1, 5.1 %, P = 0.004), accompanied with an increased prevalence of fatty liver among both men (10.8, 26.3, 33.8, 36.7, and 38.0 %, P < 0.001) and women (6.5, 16.7, 22.2, 21.3, and 20.8 %, P < 0.001). CONCLUSION: Fatty liver independently predicts both present and future DM. Fatty liver may play an important role in the recent increases in the prevalence of DM.

Fatty liver in men is associated with high serum levels of small, dense low-density lipoprotein cholesterol.

AIMS: Our study addressed potential associations between fatty liver and small, dense low-density lipoprotein cholesterol (sd-LDL-C) levels using a cross-sectional analysis. METHODS: We enrolled 476 male subjects. Serum sd-LDL-C concentrations were determined using precipitation assays. RESULTS: Subjects were divided into four groups based on triglyceride (TG) and LDL-C levels: A, TG < 150 mg/dl and LDL-C < 140 mg/dl; B, TG < 150 mg/dl and LDL-C ≥ 140 mg/dl; C, TG ≥ 150 mg/dl and LDL-C < 140 mg/dl; and D, TG ≥ 150 mg/dl and LDL-C ≥ 140 mg/dl. sd-LDL-C levels and the prevalence of fatty liver were significantly higher in groups B, C, and D than in group A. Subjects were also categorized into four groups based on serum sd-LDL-C levels; the prevalence of fatty liver significantly increased with increasing sd-LDL-C levels. Additionally, logistic regression analysis revealed an independent association between sd-LDL-C concentrations and fatty liver using such potential confounders as obesity and hyperglycemia as variables independent of elevated TG or LDL-C levels. CONCLUSIONS: Fatty liver is a significant determinant of serum sd-LDL-C levels independent of the presence of obesity or hyperglycemia. Fatty liver may alter hepatic metabolism of TG and LDL-C, resulting in increased sd-LDL-C levels.

Alcohol drinking patterns and the risk of fatty liver in Japanese men.

BACKGROUND: Alcohol is considered to be a major cause of fatty liver (FL). In contrast, however, recent investigations have suggested that moderate alcohol consumption is protective against FL. To clarify the role of alcohol consumption in FL development, we examined the association between drinking patterns and FL prevalence. METHODS: We enrolled 9,886 male participants at regular medical health checks. Each subject's history of alcohol consumption was determined by questionnaire. The subjects were classified according to alcohol consumption as non-, light, moderate, and heavy drinkers (0, <20, 20-59, and ≥60 g/day, respectively). FL was defined by ultrasonography. Independent predictors of FL were determined by logistic regression analysis. RESULTS: The prevalence of FL displayed a "U-shaped curve" across the categories of daily alcohol consumption (non-, 44.7%; light, 39.3%; moderate, 35.9%; heavy drinkers, 40.1%; P < 0.001). The prevalence of FL was associated positively with body mass index and other obesity-related diseases and inversely with alcohol consumption (light, odds ratio [OR] 0.71, 95% confidence interval [CI] 0.59-0.86; moderate, OR 0.55, CI 0.45-0.67; heavy, OR 0.44, CI 0.32-0.62) as determined by multivariate analysis after adjusting for potential confounding variables. In addition, examination of drinking patterns (frequency and volume) revealed that the prevalence of FL was inversely associated with the frequency of alcohol consumption (≥21 days/month) (OR 0.62, CI 0.53-0.71) but not with the volume of alcohol consumed. CONCLUSIONS: Our observations suggest that alcohol consumption plays a protective role against FL in men, and consistent alcohol consumption may contribute to this favorable effect.

Association between changes in body composition and the increasing prevalence of fatty liver in Japanese men.

AIM: Prevalence of fatty liver is increasing. In this study, to elucidate the factor that contributes most to recent increases in prevalence of fatty liver, we determined the independent predictors for the onset of fatty liver and compared these predictors between 2000 and 2005. METHODS: Japanese persons, aged 30-74 years, who participated in regular health checks at Kagoshima Kouseiren Medical Health Care Center (10 336 persons in 2000 and 11 011 persons in 2005) were enrolled in the study. Diagnosis of fatty liver was performed by ultrasonography. Body fat percentage (BFP) was determined using a bipedal bioimpedance instrument. RESULTS: The prevalence of fatty liver has increased between 2000 and 2005 in men (33.3 vs 38.5% in 2000 vs 2005, respectively, P < 0.0001), but not in women (21.3 vs 21.0%, P = 0.8101). Logistic regression analysis revealed that both body mass index (BMI) and BFP are independent predictors of fatty liver in both men and women. BMI did not change in either men (23.4 +/- 2.9 vs 23.8 +/- 3.0 kg/m(2), P = 0.0528) or women (22.8 +/- 3.1 vs 22.8 +/- 3.3 kg/m(2), P = 0.9862) during the survey period. In contrast, BFP increased in men (20.6 +/- 4.7 vs 22.3 +/- 5.0 kg/m(2), P = 0.0003), but not in women (27.4 +/- 5.5 vs 28.4 +/- 5.9 kg/m(2), P = 0.3993). There was no significant change in triglycerides and glucose levels. CONCLUSION: These results suggest that altered body composition, particularly increased BFP without an increase in BMI, has developed in men and is strongly associated with the increasing prevalence of fatty live amongst Japanese men.