Fatty liver index and progression to type 2 diabetes: a 5-year longitudinal study in Spanish workers with pre-diabetes.

The main aim of the study was to evaluate the association between non-alcoholic fatty liver disease (NAFLD), estimated by fatty liver index (FLI), and the development of type 2 diabetes (T2D) in a large cohort of adult workers with pre-diabetes. Prospective cohort study. Occupational health services from Spain. 16 648 adult workers (aged 20-65 years) with pre-diabetes (fasting plasma glucose (FPG) of 100-125 mg/dL). FLI was calculated based on measurements of triglycerides, body mass index, waist circumference and γ-glutamyltransferase. The population was classified into three categories: FLI<30 (no hepatic steatosis), FLI 30-60 (intermediate status) and FLI>60 (hepatic steatosis). Sociodemographic, anthropometric, dietary habits, physical activity and clinical data were collected from all subjects. The incidence rate of T2D was determined after 5 years of follow-up. After 5 years of follow-up, 3706 of the 16 648 participants (22.2%) were diagnosed with T2D, corresponding to an annual rate of progression of 4.5%. FLI was strongly associated with T2D conversion. The incidence rates of T2D in the FLI<30, FLI 30-60 and FLI>60 groups were significantly different after 5 years of follow-up were 19/6,421 (0.3%), 338/4,318 (7.8%) and 3,349/5,909 (56.7%), respectively. This association remained significant for FLI>60 after adjustment for, age, diet, physical activity, FPG, blood pressure, social class and smoking habits (adjusted HR=6.879; 95% CI 5.873 to 8.057 for men, and HR=5.806; 95% CI 4.863 to 6.932 for women). NAFLD assessed by FLI independently predicted the risk of conversion to T2D among people with pre-diabetes. FLI may be an easily determined and valuable early predictor for T2D in people with pre-diabetes. FLI-based assessment of NAFLD in subjects with pre-diabetes in routine clinical practice could allow the adoption of effective measures to prevent and reduce their progression to T2D.

Busquets-Cortés C ，Bennasar-Veny M ，López-González AA ，Fresneda S ，Aguiló A ，Yanez A ... -  《BMJ Open》

Fatty liver index is a predictor of incident diabetes in patients with prediabetes: The PREDAPS study.

Franch-Nadal J ，Caballeria L ，Mata-Cases M ，Mauricio D ，Giraldez-García C ，Mancera J ，Goday A ，Mundet-Tudurí X ，Regidor E ，PREDAPS Study Group ... -  《PLoS One》

Non-Alcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: Role of Circulating Branched-Chain Amino Acids.

van den Berg EH ，Flores-Guerrero JL ，Gruppen EG ，de Borst MH ，Wolak-Dinsmore J ，Connelly MA ，Bakker SJL ，Dullaart RPF ... -  《Nutrients》

Nonalcoholic fatty liver disease (NAFLD) and associated mortality in individuals with type 2 diabetes, pre-diabetes, metabolically unhealthy, and metabolically healthy individuals in the United States.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is high among subjects with type 2 diabetes (T2D). However, the prevalence and outcomes of NAFLD among individuals with pre-diabetes (PreD) and metabolically healthy and metabolically unhealthy individuals without T2D are not known. Our aim was to assess prevalence and mortality of NAFLD among these four groups. The Third National Health and Nutrition Examination Survey (NHANES) III (1988-1994) with mortality data (follow up to 2019) via linkage to the National Death Index was utilized. NAFLD was defined by ultrasound and absence of other liver diseases and excess alcohol use. Pre-D was defined as fasting plasma glucose values of 100-125 mg/dL and/or HbA1c level between 5.7 %-6.4 % in the absence of established diagnosis of T2D. Metabolically healthy (MH) was defined if all of the following criteria were absent: waist circumference of ≥102 cm (men) or ≥ 88 cm (women) or BMI of ≥30; blood pressure (BP) ≥ 130/85 mmHg or using BP-lowering medication; triglyceride level ≥ 150 mg/dL or using lipid-lowering medication; lipoprotein cholesterol level of <40 mg/dL (men) or < 50 mg/dL (women); homeostasis model assessment of insulin resistance (HOMA-IR) score ≥ 2.5; C-reactive protein (CRP) level of >2 mg/L; Pre-D and T2D. Metabolically unhealthy (MU) individuals were defined as the presence of any component of metabolic syndrome but not having Pre-D and T2D. Competing risk analyses of cause-specific mortality were performed. 11,231 adults (20-74y) were included: mean age 43.4 years; 43.9 % male; 75.4 % white, 10.8 % Black, and 5.4 % Mexican American, 18.9 % NAFLD, 7.8 % T2D; 24.7 % PreD; 44.3 % MU; and 23.3 % in MH individuals. In multivariable adjusted logistic model, as compared to MH individuals, the highest risk of having NAFLD were in T2D individuals (Odd Ratio [OR] = 10.88 [95 % confidence interval: 7.33-16.16]), followed by Pre-D (OR = 4.19 [3.02-5.81]), and MU (OR = 3.36 [2.39-4.71]). During a median follow up of 26.7 years (21.2-28.7 years), 3982 died. NAFLD subjects had significantly higher age-adjusted mortality than non-NAFLD (32.7 % vs. 28.7 %, p < .001). Among subjects with NAFLD, the highest age-standardized cumulative mortality was observed among those with T2D (41.3 %), followed by with Pre-D (35.1 %), MU subjects (30.0 %), and MH subjects (21.9 %) (pairwise p-values<.04 vs. MH). Multivariable adjusted cox models showed that NAFLD with T2D had a higher risk of all-causes and cardiac-specific deaths (Hazard Ratio [HR] = 4.71 [2.23-9.96] and HR = 20.01 [3.00-133.61]), followed by NAFLD with Pre-D (HR = 2.91 [1.41-6.02] and HR = 10.35 [1.57-68.08]) and metabolically unhealthy NAFLD (HR = 2.59 [1.26-5.33] and HR = 6.74 [0.99-46.03]) compared to metabolically healthy NAFLD. In addition to older age, independent predictors of mortality among NAFLD with T2D included high CRP, CVD, CKD, high FIB-4, and active smoking. Similarly, among NAFLD with PreD, high CRP, CKD, CVD, hypertension, and active smoking were associated with mortality. Finally, CVD and active smoking were predictors of mortality among metabolically unhealthy NAFLD, and active smoking was the only mortality risk among metabolically healthy NAFLD subjects. Metabolic abnormality impacts both prevalence and outcomes of subjects with NAFLD.

Golabi P ，Paik JM ，Kumar A ，Al Shabeeb R ，Eberly KE ，Cusi K ，GunduRao N ，Younossi ZM ... -  《-》

Sex and age differences in the association of fatty liver index-defined non-alcoholic fatty liver disease with cardiometabolic risk factors: a cross-sectional study.

Despite the extensive scientific evidence accumulating on the epidemiological risk factors for non-alcoholic fatty liver disease (NAFLD), evidence exploring sex- and age-related differences remains insufficient. The present cross-sectional study aims to investigate possible sex differences in the prevalence of FLI-defined NAFLD as well as in its association with common risk factors across different age groups, in a large sample of Spanish working adults. This cross-sectional study included data from 33,216 Spanish adult workers (18-65 years) randomly selected during voluntary routine occupational medical examinations. Sociodemographic characteristics (age and social class), anthropometric (height, weight, and waist circumference) and clinical parameters (blood pressure and serum parameters) were collected. NAFLD was determined by the validated fatty liver index (FLI) with a cut-off value of ≥ 60. The presence of metabolic syndrome (MetS) was assessed according to the diagnostic criteria of the International Diabetes Federation. Cardiovascular risk was determined using the REGICOR-Framingham equation. The association between FLI-defined NAFLD and risk factors by sex and age was evaluated by multivariate logistic regression. The prevalence of FLI-defined NAFLD (FLI ≥ 60) was 19.1% overall, 27.9% (95% CI 23.3-28.5%) for men and 6.8% (95% CI 6.4-7.3%) for women and increasing across age intervals. As compared to women, men presented worse cardiometabolic and anthropometric profiles. The multivariate analysis model showed that hepatic steatosis assessed by FLI was strongly associated with age, HDL-cholesterol, social class, prediabetes, diabetes, prehypertension, hypertension, and smoking status for both men and women. The association between diabetes and hypertension with FLI-defined NAFLD was stronger in women than in men at both univariate and multivariate analyses. Men presented a higher prevalence of NAFLD than women across all age intervals, as well as a worse cardiometabolic profile and a higher cardiovascular risk. Nevertheless, the association between FLI-defined NAFLD and diabetes or hypertension was significantly stronger in women than in men, possibly indicating that the presence of a dysmetabolic state might affect women more than men with regard to liver outcomes.

Fresneda S ，Abbate M ，Busquets-Cortés C ，López-González A ，Fuster-Parra P ，Bennasar-Veny M ，Yáñez AM ... -  《Biology of Sex Differences》