Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults:The Kangbuk Samsung Health Study

Aims: Whether changes in serum uric acid (SUA) are associated with resolution of nonalcoholic fatty liver disease (NAFLD) is uncertain. We aimed to determine the association between (i) baseline SUA and (ii) SUA changes over time, and NAFLD resolution. Materials and Methods: A retrospective cohort study, comprising 38,483 subjects aged &lt;40 years with pre-existing NAFLD, were undertaken. The effects of SUA changes over time were studied in 25,266 subjects. Participants underwent a health examination between 2011 and 2019, and had at least one follow-up liver ultrasound until December 2020. Exposures included baseline SUA levels, and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. Results: During a median follow-up of 4 years, low baseline SUA and decreases in SUA over time, were independently associated with NAFLD resolution (p for trend &lt;0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1 mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, the aHRs (95%CIs) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. Conclusions: Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.<br/

Nonalcoholic Fatty Liver Disease without overlapping Metabolic Associated Fatty Liver Disease and the risk of incident type 2 diabetes

Background and aims: re-classifying NAFLD as metabolic-associated fatty liver (MAFLD) has been proposed. While some people fulfil criteria for NAFLD, they do not have MAFLD; and whether NAFLD-only subjects have increased the risk of type 2 diabetes remains unknown. We compared risk of incident T2D in individuals with: (a) NAFLD-only; and (b) MAFLD, to individuals without fatty liver, considering effect modification by sex.Methods: 246 424 Koreans without diabetes or a secondary cause of ultrasound-diagnosed hepatic steatosis were studied. Subjects were stratified into: (a) NAFLD-only status and (b) NAFLD that overlapped with MAFLD (MAFLD). Cox proportional hazards models with incident T2D as the outcome were used to estimate hazard ratios (HRs) for: (a) and (b). Models were adjusted for time-dependent covariates, and effect modification by sex was analysed in subgroups.Results: a total of 5439 participants had NAFLD-only status and 56 839 met MAFLD criteria. During a median follow-up of 5.5 years, 8402 incident cases of T2D occurred. Multivariable-adjusted HRs (95% CI) for incident T2D comparing NAFLD-only and MAFLD to the reference (neither condition) were 2.39 (1.63–3.51) and 5.75 (5.17–6.36) (women), and 1.53 (1.25–1.88) and 2.60 (2.44–2.76) (men), respectively. The increased risk of T2D in the NAFLD-only group was higher in women than in men (p for interaction by sex &lt;0.001) and consistently observed across all subgroups. Risk of T2D was increased in lean participants regardless of metabolic dysregulation (including prediabetes).Conclusions: NAFLD-only participants without metabolic dysregulation and the criteria for MAFLD are at increased risk of developing T2D. This association was consistently stronger in women than in men.<br/

Nonalcoholic fatty liver disease and risk of incident young-onset hypertension:effect modification by sex

Background and aims: although nonalcoholic fatty liver disease (NAFLD) and hypertension are increasingly common among young adults, it is uncertain if NAFLD affects incidence of young-onset hypertension, and if the association is modified by sex. We investigated potential effect modification by sex on the association between NAFLD and incident hypertension in young adults (&lt;40 years).Method and results: this cohort study comprised 85,789 women and 67,553 men aged &lt;40 years without hypertension at baseline. Hepatic steatosis was assessed by liver ultrasound and classified as mild or moderate/severe. Hypertension was defined as blood pressure (BP) ≥130/80 mmHg; self-reported history of physician-diagnosed hypertension; or current use of BP-lowering medications. Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident hypertension by NAFLD status (median follow-up 4.5 years). A total of 25,891 participants developed incident hypertension (incidence rates per 103 person-years: 15.6 for women and 63.5 for men). Multivariable-adjusted HRs (95% CIs) for incident hypertension comparing no NAFLD (reference) with mild or moderate/severe NAFLD were 1.68 (1.56–1.80) and 1.83 (1.60–2.09) for women and 1.21 (1.17–1.25) and 1.23 (1.17–1.30) for men, respectively. Stronger associations were consistently observed between NAFLD and incident hypertension in women, regardless of obesity/central obesity (all p-values for interaction by sex &lt;0.001).Conclusions: NAFLD is a potential risk factor for young-onset hypertension with a relatively greater impact in women and in those with more severe hepatic steatosis

Serum 25-hydroxyvitamin D levels and risk of colorectal cancer:an age-stratified analysis

Background and aims: the role of circulating 25-hydroxyvitamin D (25(OH)D) in prevention of early-onset colorectal cancer (CRC) in young adults under 50 years is uncertain. We evaluated the age-stratified associations (&lt;50 vs. ≥50 years) :circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults.Methods: our cohort study included 236,382 participants (mean [standard deviation] age, 38.0 [9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as follows: &lt;10, 10–20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders.Results: during the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5–7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 105 person-years). Among young individuals aged &lt;50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43–0.86) and 0.41 (0.27–0.63) for 25(OH)D 10-19 and ≥20 ng/mL, respectively, with respect to the reference (&lt;10 ng/mL) (p for trend &lt;0.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared to younger individuals. Conclusions: serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease. <br/

Nonalcoholic fatty liver disease without overlapping metabolic associated fatty liver disease and the risk of incident type 2 diabetes

Background and aims: re-classifying NAFLD as metabolic-associated fatty liver (MAFLD) has been proposed. While some people fulfil criteria for NAFLD, they do not have MAFLD; and whether NAFLD-only subjects have increased the risk of type 2 diabetes remains unknown. We compared risk of incident T2D in individuals with: (a) NAFLD-only; and (b) MAFLD, to individuals without fatty liver, considering effect modification by sex.Methods: 246 424 Koreans without diabetes or a secondary cause of ultrasound-diagnosed hepatic steatosis were studied. Subjects were stratified into: (a) NAFLD-only status and (b) NAFLD that overlapped with MAFLD (MAFLD). Cox proportional hazards models with incident T2D as the outcome were used to estimate hazard ratios (HRs) for: (a) and (b). Models were adjusted for time-dependent covariates, and effect modification by sex was analysed in subgroups.Results: a total of 5439 participants had NAFLD-only status and 56 839 met MAFLD criteria. During a median follow-up of 5.5 years, 8402 incident cases of T2D occurred. Multivariable-adjusted HRs (95% CI) for incident T2D comparing NAFLD-only and MAFLD to the reference (neither condition) were 2.39 (1.63–3.51) and 5.75 (5.17–6.36) (women), and 1.53 (1.25–1.88) and 2.60 (2.44–2.76) (men), respectively. The increased risk of T2D in the NAFLD-only group was higher in women than in men (p for interaction by sex &lt;0.001) and consistently observed across all subgroups. Risk of T2D was increased in lean participants regardless of metabolic dysregulation (including prediabetes).Conclusions: NAFLD-only participants without metabolic dysregulation and the criteria for MAFLD are at increased risk of developing T2D. This association was consistently stronger in women than in men.<br/

Baseline and change in serum uric acid level over time and resolution of NAFLD in young adults: The Kangbuk Samsung Health Study

Aims: whether changes in serum uric acid (SUA) are associated with resolution of nonalcoholic fatty liver disease (NAFLD) is uncertain. We aimed to determine the association between (i) baseline SUA and (ii) SUA changes over time, and NAFLD resolution.Materials and methods: a retrospective cohort study, comprising 38,483 subjects aged Results: during a median follow-up of 4 years, low baseline SUA and decreases in SUA over time, were independently associated with NAFLD resolution (p for trend Conclusions: low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults

Synergistic effect of non-alcoholic fatty liver disease and history of gestational diabetes to increase risk of type 2 diabetes

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