METHODS: 1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients.
FINDINGS: One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p
MATERIALS/METHODS: Twelve- to fourteen-week-old CAV-1 knockout (KO) and genetically matched wild-type (WT) male mice were randomized by genotype to one of two dietary regimens: ad libitum (ad lib) food intake or 40% CR for 4 weeks. Three weeks following the onset of dietary restriction, all groups were assessed for insulin sensitivity. At the end of the study, all groups were assessed for fasting glucose, insulin, HOMA-IR, lipids, corticosterone levels and blood pressure (BP). Aldosterone secretion was determined from acutely isolated Zona Glomerulosa cells.
RESULTS: We confirmed that the CAV-1 KO mice on the ad lib diet display a phenotype consistent with the cardiometabolic syndrome, as shown by higher systolic BP (SBP), plasma glucose, HOMA-IR and aldosterone levels despite lower body weight compared with WT mice on the ad lib diet. CAV-1 KO mice maintained their body weight on the ad lib diet, but had substantially greater weight loss with CR, as compared to caloric restricted WT mice. CR-mediated changes in weight were associated with dramatic improvements in glucose and insulin tolerance in both genotypes. These responses to CR, however, were more robust in CAV-1KO vs. WT mice and were accompanied by reductions in plasma glucose, insulin and HOMA-IR in CAV-1KO but not WT mice. Surprisingly, in the CAV-1 KO, but not in WT mice, CR was associated with increased SBP and aldosterone levels, suggesting that in CAV-1 KO mice CR induced an increase in some CV risk factors.
CONCLUSIONS: CR improved the metabolic phenotype in CAV-1 KO mice by increasing insulin sensitivity; nevertheless, this intervention also increased CV risk by inappropriate adaptive responses in the RAAS and BP.
METHODS: We estimated global and regional temporal trends in the burden of cancer attributable to high BMI, and the contributions of various cancer types using the framework of the Global Burden of Disease Study.
RESULTS: From 2010 to 2019, there was a 35 % increase in deaths and a 34 % increase in disability-adjusted life-years from cancers attributable to high BMI. The age-standardized death rates for cancer attributable to high BMI increased over the study period (annual percentage change [APC] +0.48 %, 95 % CI 0.22 to 0.74 %). The greatest number of deaths from cancer attributable to high BMI occurred in Europe, but the fastest-growing age-standardized death rates and disability-adjusted life-years occurred in Southeast Asia. Liver cancer was the fastest-growing cause of cancer mortality (APC: 1.37 %, 95 % CI 1.25 to 1.49 %) attributable to high BMI.
CONCLUSION: The global burden of cancer-related deaths attributable to high BMI has increased substantially from 2010 to 2019. The greatest increase in age-standardized death rates occurred in Southeast Asia, and liver cancer is the fastest-growing cause of cancer mortality attributable to high BMI. Urgent and sustained measures are required at a global and regional level to reverse these trends and slow the growing burden of cancer attributed to high BMI.