High fibrosis-4 index predicts the new onset of ischaemic heart disease during a 10-year period in a general population.

Aims: The fibrosis-4 (FIB-4) index, calculated using age, platelet count, and levels of aspartate aminotransferase and alanine aminotransferase, is a non-invasive indicator for the detection of liver fibrosis. Advanced hepatic fibrosis is associated with morbidity and mortality in patients with non-alcoholic fatty liver disease. However, the relationship between liver fibrosis and the development of ischaemic heart disease (IHD) has not fully been addressed.

Metabolic dysfunction-associated fatty liver disease predicts new onset of chronic kidney disease better than fatty liver or nonalcoholic fatty liver disease.

Background: Possible associations of chronic kidney disease (CKD) with fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) have recently been focused on. Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as FL with overweight/obesity, type 2 diabetes mellitus or metabolic abnormalities, has been proposed as a new feature of chronic liver disease. However, the relationship between MAFLD and new onset of CKD has not been fully addressed.

High fatty liver index is an independent predictor of ischemic heart disease during a 10-year period in a Japanese population.

Aim: Fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, is a validated surrogate marker of nonalcoholic fatty liver disease. We retrospectively investigated the relationship between FLI and the development of ischemic heart disease (IHD) during a 10-year period.

Methods: Among subjects who received annual health checkups (n = 28 990), a total of 18 851 subjects (men/women: 11 659/7192) were enrolled after exclusion of subjects with missing data and those with IHD at baseline.

Plasma Tsukushi Concentration Is Associated with High Levels of Insulin and FGF21 and Low Level of Total Cholesterol in a General Population without Medication.

Tsukushi (TSK) is a member of the small leucine-rich proteoglycan family that controls developmental processes and organogenesis. TSK was also identified as a new hepatokine, which is mainly expressed in the liver, and is secreted by hepatocytes, to regulate energy and glycolipid metabolism in response to nonalcoholic fatty liver disease. However, the role of plasma TSK, especially its role in the general population, has not been fully addressed.

Circulating level of fatty acid-binding protein 4 is an independent predictor of metabolic dysfunction-associated fatty liver disease in middle-aged and elderly individuals.

Aims/introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as hepatosteatosis with type 2 diabetes mellitus, overweight/obesity or metabolic dysregulation, has been proposed as a new feature of chronic liver disease. Fatty acid-binding protein 4 (FABP4) is expressed in adipose tissue, and secreted FABP4 is associated with the development of insulin resistance and atherosclerosis. However, the relationship between MAFLD and FABP4 has not been fully addressed.

Serum uric acid level is associated with an increase in systolic blood pressure over time in female subjects: Linear mixed-effects model analyses.

Whether hyperuricemia is a true risk factor for elevated blood pressure (BP) is controversial, and the sex-specific effects of serum uric acid (SUA) on BP during a follow-up period remain unclear. We investigated whether the association of SUA level with systolic or diastolic BP during a 10-year period differs by sex in a Japanese general population of individuals who received annual health examinations (n = 28,990). After exclusion of subjects who had no BP or SUA data at baseline, a total of 22,994 subjects (male/female: 14,603/8391, age: 47 ± 11 years) were recruited.

Prediction and validation of nonalcoholic fatty liver disease by fatty liver index in a Japanese population.

Fatty liver index (FLI) calculated by using body mass index (BMI), waist circumference and levels of γ-glutamyl transferase and triglycerides is a non-invasive predictor of nonalcoholic fatty liver disease (NAFLD). The original study in Italy showed that the cutoff level for prediction of NAFLD was FLI ≥60. However, the sex difference in FLI was not taken into consideration, and it is unclear whether the cutoff value can be applied to other races.

Circulating PCSK7 Level is Independently Associated with Obesity, Triglycerides Level and Fatty Liver Index in a General Population without Medication.

Aim: Dyslipidemia and altered iron metabolism are typical features of non-alcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7), a transmembrane-anchored endonuclease, is associated with triglycerides level and processing of transferrin receptor 1. However, the significance of circulating PCSK7 has not been fully addressed, though prosegment PCSK7 is secreted from cells.

Independent Association of Fatty Liver Index With Left Ventricular Diastolic Dysfunction in Subjects Without Medication.

Nonalcoholic fatty liver disease has been reported to be potentially linked to cardiovascular disease. Fatty liver index (FLI) is a noninvasive and simple predictor of nonalcoholic fatty liver disease. However, little is known about the relationship between FLI and cardiac function, especially in a general population.

Distinct Regulation of U-ACE2 and P-ACE2 (Urinary and Plasma Angiotensin-Converting Enzyme 2) in a Japanese General Population.

[Figure: see text].

Elevated Fatty Liver Index Is Independently Associated With New Onset of Hypertension During a 10-Year Period in Both Male and Female Subjects.

Background Fatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. Because of a sex difference in FLI level, we hypothesized that FLI is associated with development of hypertension to a greater extent in men or women. Methods and Results We investigated the relationship between FLI and development of hypertension during a 10-year period in a general population of subjects who received annual health examinations (n=28 990).

Prediction of new onset of diabetes mellitus during a 10-year period by using a combination of levels of alanine aminotransferase and γ-glutamyl transferase.

Levels of alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) have been reported to be associated with increased risk of diabetes mellitus (DM). However, whether a combination of levels of ALT and GGT predicts new onset of DM better than does ALT or GGT alone in both males and females has not fully been addressed. We investigated the relationship between the combination of ALT and GGT and DM development during a 10-year follow-up period in 13,919 subjects (male/female: 8,983/4,936; age 48 ± 10 years) who received health examinations.

High level of fatty liver index predicts new onset of diabetes mellitus during a 10-year period in healthy subjects.

Fatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. This study aimed to evaluate the relationship between FLI and new onset of diabetes mellitus (DM). We investigated the association of FLI with new onset of DM during a 10-year period in subjects who received annual health examinations (n = 28,990).

Independent association of plasma xanthine oxidoreductase activity with hypertension in nondiabetic subjects not using medication.

Xanthine oxidoreductase (XOR), a rate-limiting and catalyzing enzyme of uric acid formation in purine metabolism, is involved in reactive oxygen species generation. Plasma XOR activity has been shown to be a novel metabolic biomarker related to obesity, liver dysfunction, hyperuricemia, dyslipidemia, and insulin resistance. However, the association between plasma XOR activity and hypertension has not been fully elucidated.

Fatty liver index is independently associated with deterioration of renal function during a 10-year period in healthy subjects.

A potential link between chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) has been suggested. We investigated the relationship between fatty liver index (FLI), a noninvasive and simple predictor of NAFLD, and the development of CKD defined as estimated glomerular filtration rate < 60 mL/min/1.73 m or positive for urinary protein during a 10-year follow-up period in subjects who received annual health examinations (n = 28,890).

Antiatherosclerotic Phenotype of Perivascular Adipose Tissue Surrounding the Saphenous Vein in Coronary Artery Bypass Grafting.

Background Perivascular adipose tissue (PVAT) is associated with metabolically driven chronic inflammation called metaflammation, which contributes to vascular function and the pathogenesis of vascular disease. The saphenous vein (SV) is commonly used as an essential conduit in coronary artery bypass grafting, but the long-term patency of SV grafts is a crucial issue. The use of the novel "no-touch" technique of SV harvesting together with its surrounding tissue has been reported to result in good long‑term graft patency of SV grafts.

Elevated circulating FABP4 concentration predicts cardiovascular death in a general population: a 12-year prospective study.

Fatty acid-binding protein 4 (FABP4) is secreted from adipose tissue and acts as an adipokine, and an elevated circulating FABP4 level is associated with metabolic disorders and atherosclerosis. However, little is known about the causal link between circulating FABP4 level and mortality in a general population. We investigated the relationship between FABP4 concentration and mortality including cardiovascular death during a 12-year period in subjects of the Tanno-Sobetsu Study, a population-based cohort (n = 721, male/female: 302/419).

Differential Effects of DPP-4 Inhibitors, Anagliptin and Sitagliptin, on PCSK9 Levels in Patients with Type 2 Diabetes Mellitus who are Receiving Statin Therapy.

Aim: Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Treatment with a statin leads to a compensatory increase in circulating PCSK9 level. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, was shown to decrease LDL cholesterol (LDL-C) levels to a greater extent than that by sitagliptin, another DPP-4 inhibitor, in the Randomized Evaluation of Anagliptin versus Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial.

Significance of urinary fatty acid-binding protein 4 level as a possible biomarker for the identification of minimal change disease in patents with nephrotic-range proteinuria.

Background: Fatty acid-binding protein 4 (FABP4), but not FABP1 (liver-type FABP), is ectopically induced in injured glomerular endothelial cells, and urinary FABP4 (U-FABP4) level is associated with proteinuria and renal dysfunction in a general population.

Methods: The clinical significance of U-FABP4 was investigated in 81 patients (male/female: 43/38, age: 57 ± 17 years) who underwent kidney biopsy.

Results: U-FABP4 was negatively correlated with estimated glomerular filtration rate (eGFR) (r = - 0.

Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus.

Among fatty acid-binding proteins (FABPs), secreted forms of FABP4 and FABP5, which are expressed in adipocytes and macrophages, act as bioactive molecules. We investigated concentrations of FABP4 and FABP5 in patients with type 2 diabetes mellitus. As a sub-analysis study of the Randomized Evaluation of Anagliptin vs.

U-shaped relationship between serum uric acid level and decline in renal function during a 10-year period in female subjects: BOREAS-CKD2.

While hyperuricemia is recognized as a risk factor for chronic kidney disease (CKD), the risk of CKD in subjects with a low level of serum uric acid (UA) remains controversial. Here, we examined whether the association of CKD risk with serum UA level differs depending on the sex and age of subjects in a general population. Of subjects who received annual health checkups, we enrolled 6,779 subjects (male/female: 4,454/2,325; age: 45 ± 9 years) with data from a 10-year follow-up after excluding subjects taking anti-hyperuricemic drugs and those with CKD at baseline.

Treatment with anagliptin, a DPP-4 inhibitor, decreases FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular disease who are receiving statin therapy.

Background: Fatty acid-binding protein 4 (FABP4) acts as a novel adipokine, and elevated FABP4 concentration is associated with obesity, insulin resistance and atherosclerosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a class of antidiabetic drugs, have distinct structures among the drugs, possibly leading to a drug class effect and each drug effect. Sitagliptin, a DPP-4 inhibitor, has been reported to decrease FABP4 concentration in drug-naïve and sulfonylurea-treated patients with type 2 diabetes mellitus.

Low urine pH predicts new onset of diabetes mellitus during a 10-year period in men: BOREAS-DM1 study.

Aims/introduction: A low level of urine pH (U-pH) has been reported to be associated with metabolic disorders. However, the relationship between the incidence of diabetes mellitus and U-pH has not yet been fully addressed.

Materials And Methods: We investigated the relationship between U-pH and the development of diabetes mellitus during a 10-year period in a general population of individuals who received annual health examinations in 2006 (n = 28,990).

Differential regulation of hypoxanthine and xanthine by obesity in a general population.

Aims/introduction: Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans, unlike in rodents, and that hypoxanthine is secreted from human fat tissue.

Annual change in plasma xanthine oxidoreductase activity is associated with changes in liver enzymes and body weight.

Xanthine oxidoreductase (XOR), an enzyme of uric acid formation from hypoxanthine and xanthine, is recognized as a source of oxidative stress. Plasma activity of XOR has been reported to be a biomarker of metabolic disorders associated with obesity, liver dysfunction, insulin resistance, hyperuricemia and adipokines. We investigated longitudinal change in plasma XOR activity, which was determined by using mass spectrometry and liquid chromatography to detect [C, N]-uric acid using [C, N]-xanthine as a substrate, in 511 subjects (male/female: 244/267) of the Tanno-Sobetsu Study in the years 2016 and 2017.