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. During the 10-year period, 617 males (6.9%) and 153 females (3.1%) had new onset of DM. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard ratios (HRs) of DM development increased with higher levels of ALT and GGT at baseline in both sexes after adjustment of confounding factors. When divided into 4 subgroups of high (H-) and low (L-) levels of ALT (male/female: 27/21 U/L) and GGT (male/female: 43/23 U/L) using cutoff values shown by receiver operating characteristic curve analyses, the adjusted HR in the H-ALT/H-GGT group was significantly higher than HR in the L-ALT/L-GGT group as the reference in males (HR [95% confidence interval]: 1.73[1.36-2.20], p < 0.001) but was not significantly higher in females (1.50 [0.97-2.33], p = 0.065). The addition of the combination of H-ALT/H-GGT to traditional risk factors with and without H-ALT or H-GGT alone significantly improved the discriminatory capability for predicting development of DM. In conclusion, the combination of H-ALT/H-GGT efficiently predicts development of DM in male individuals but not significantly in female individuals.

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). After exclusion (44.9%) of subjects with missing data and those with hypertension at baseline, a total of 15 965 subjects (men/women: 9466/6499) were included. FLI level was significantly higher in men than in women. During the 10-year period, 2304 men (24.3%) and 745 women (11.5%) had new onset of hypertension. Multivariable Cox proportional hazard models with a restricted cubic spline showed that the hazard ratios (HRs) for development of hypertension after adjustment of age, systolic blood pressure, estimated glomerular filtration rate, habits of smoking and alcohol drinking, family history of hypertension, and diagnosis of diabetes mellitus and dyslipidemia increased gradually with increase in FLI in men and increased rapidly and then slowly with increase in FLI in women. There was a significant interaction between FLI and sex for the risk of hypertension in all of the subjects (P=0.049). The addition of FLI to traditional risk factors significantly improved the discriminatory capability. Conclusions A high level of FLI predicts the development of hypertension in both men and women, although distribution patterns of HRs were different between sexes.

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). After exclusion of subjects with DM at baseline and those with missing data, a total of 12,290 subjects (male/female: 7925/4365) who received health examinations were recruited. FLI was significantly higher in males than in females. During the 10-year period, DM was developed in 533 males (6.7%) and 128 females (2.9%). Multivariable Cox proportional hazard models with a restricted cubic spline showed that the risk of new onset of DM increased with a higher FLI at baseline in both sexes after adjustment of age, fasting plasma glucose, habits of alcohol drinking and current smoking, family history of DM and diagnosis of hypertension and dyslipidemia at baseline. When the subjects were divided into subgroups according to tertiles of FLI level at baseline (T1-T3) in the absence and presence of impaired fasting glucose (IFG), hazard ratios after adjustment of the confounders gradually increased from T1 to T3 and from the absence to presence of IFG in both male and female subjects. In conclusion, a high level of FLI predicts new onset of DM in a general population of both male and female individuals.

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 m2 or positive for urinary protein during a 10-year follow-up period in subjects who received annual health examinations (n = 28,890). After exclusion of CKD at baseline, a total of 14,163 subjects (male/female: 9077/5086) were recruited. During the 10-year period, 1458 males (16.1%) and 737 females (14.5%) had new onset of CKD. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard ratios (HRs) of CKD development increased with a higher FLI at baseline in both males and females after adjustment of confounders. When divided by tertiles of FLI level at baseline (T1 ~ T3), the adjusted risk of CKD development in the T3 group (HR [95% confidence interval], male/female: 1.33 [1.16-1.54]/1.33 [1.08-1.63]) was significantly higher than that in both sexes in the T1 group as the reference. The addition of FLI into traditional risk factors significantly improved the discriminatory capability for predicting CKD. In conclusion, a high level of FLI predicts the development of CKD in both sexes in a general population.

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. During the follow-up period, 11.4% of the males and 11.7% of the females developed CKD. A significant interaction of sex, but not age, with the effect of baseline UA level on CKD risk was found. A restricted cubic spline analysis showed a U-shaped association of the baseline UA level with the risk of CKD in females. Multivariable Cox proportional hazard analyses for females showed that baseline UA levels in the 5th quintile (Q5, ≥5 mg/dL; HR: 1.68) and the 1st quintile (Q1, ≤3.5 mg/dL; HR: 1.73) were independent risk factors for CKD when compared with UA levels in the 4th quintile (Q4, 4.5-4.9 mg/dL). In males, restricted cubic spline analysis indicated increased CKD risk in subjects with a higher baseline UA level but not in those with a low UA level. In conclusion, a low UA level is a significant risk factor for CKD in females, while an elevated UA level increases the risk of CKD in both sexes.

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). After exclusion of individuals with missing data, and those with diabetes mellitus and/or chronic kidney disease at baseline, a total of 12,476 individuals (men/women: 8,027/4,449) who received health examinations at least once during the period from 2007 to 2016 were recruited. The recruited individuals were divided into four groups according to their U-pH levels: groups of U-pH ≤5.0, 5.5, 6.0 and ≥6.5. RESULTS: During a 10-year period, 521 men (6.5%) and 132 women (3.0%) had new onset of diabetes mellitus. The cumulative incidence of diabetes mellitus was 7.5% (men/women: 9.3%/4.4%) per 100 person-years. The hazard ratios (HRs) in the U-pH ≤5.0 (HR 1.93) and U-pH 5.5 groups (HR 1.46) were significantly higher than that in the U-pH ≥6.5 group as a reference for men, but not for women. After adjustment of age, obesity, fasting glucose, smoking and alcohol drinking habits, family history of diabetes mellitus, and use of drugs for hypertension and dyslipidemia, HR in the U-pH ≤5.0 group (HR 1.39) was significantly higher than that in the U-pH ≥6.5 group for men, but not for women. CONCLUSIONS: Low U-pH predicts new onset of diabetes mellitus in a general population of men.