Rapid development of non-alcoholic steatohepatitis in Psammomys obesus (Israeli sand rat)

Background and Aims: A major impediment to establishing new treatments for non-alcoholic steatohepatitis is the lack of suitable animal models that accurately mimic the biochemical and metabolic characteristics of the disease. The aim of this study was to explore a unique polygenic animal model of metabolic disease as a model of non-alcoholic steatohepatitis by determining the effects of 2% dietary cholesterol supplementation on metabolic and liver endpoints in Psammomys obesus (Israeli sand rat). Methods: P. obesus were provided ad libitum access to either a standard rodent diet (20% kcal/fat) or a standard rodent diet supplemented with 2% cholesterol (w/w) for 4 weeks. Histological sections of liver from animals on both diets were examined for key features of non-alcoholic steatohepatitis. The expression levels of key genes involved in hepatic lipid metabolism were measured by real-time PCR. Results: P. obesus fed a cholesterol-supplemented diet exhibited profound hepatomegaly and steatosis, and higher plasma transaminase levels. Histological analysis identified extensive steatosis, inflammation, hepatocyte injury and fibrosis. Hepatic gene expression profiling revealed decreased expression of genes involved in delivery and uptake of lipids, and fatty acid and triglyceride synthesis, and increased expression of genes involved in very low density lipoprotein cholesterol synthesis, triglyceride and cholesterol export. Conclusions: P. obesus rapidly develop non-alcoholic steatohepatitis when fed a cholesterol-supplemented diet that appears to be histologically and mechanistically similar to patients. © 2014 Spolding et al

All-Cause Mortality Risk in Australian Women with Impaired Fasting Glucose and Diabetes

AIMS: Impaired fasting glucose (IFG) and diabetes are increasing in prevalence worldwide and lead to serious health problems. The aim of this longitudinal study was to investigate the association between impaired fasting glucose or diabetes and mortality over a 10-year period in Australian women. METHODS: This study included 1167 women (ages 20-94 yr) enrolled in the Geelong Osteoporosis Study. Hazard ratios for all-cause mortality in diabetes, IFG, and normoglycaemia were calculated using a Cox proportional hazards model. RESULTS: Women with diabetes were older and had higher measures of adiposity, LDL cholesterol, and triglycerides compared to the IFG and normoglycaemia groups (all p < 0.001). Mortality rate was greater in women with diabetes compared to both the IFG and normoglycaemia groups (HR 1.8; 95% CI 1.3-2.7). Mortality was not different in women with IFG compared to those with normoglycaemia (HR 1.0; 95% CI 0.7-1.4). CONCLUSIONS: This study reports an association between diabetes and all-cause mortality. However, no association was detected between IFG and all-cause mortality. We also showed that mortality in Australian women with diabetes continues to be elevated and women with IFG are a valuable target for prevention of premature mortality associated with diabetes

Trabecular Bone Score in Men and Women with Impaired Fasting Glucose and Diabetes.

Diabetes is associated with increased skeletal fragility, despite higher bone mineral density (BMD). Alternative measures are necessary to more accurately determine fracture risk in individuals with diabetes. Therefore, we aimed to describe the relationship between trabecular bone score (TBS) and normoglycaemia, impaired fasting glucose (IFG) and diabetes and determine whether TBS-adjusted FRAX (Aus) score differed between these groups. This study included 555 men (68.7 ± 12.2 years) and 514 women (62.0 ± 12.0 years), enrolled in the observational Geelong Osteoporosis Study. IFG was considered as fasting plasma glucose (FPG) ≥ 5.5 mmol/L and diabetes as FPG ≥ 7.0 mmol/L, with the use of antihyperglycaemic medication and/or self-report. Using multivariable regression, the relationship between groups and TBS was determined. Men and women (all ages) with diabetes had lower mean TBS compared to those with normoglycaemia, in models adjusted for age, height and weight/waist circumference (all p &lt; 0.05). Men with IFG had lower mean TBS in the age-adjusted models only (all p &lt; 0.05). The addition of TBS to the FRAX score improved the discrimination between glycaemia groups, particularly for younger women (&lt; 65 years). There was no difference in TBS detected between normoglycaemia and IFG; however, those with diabetes had lower TBS. Thus, the increased fracture risk in men and women with diabetes may be a result of BMD-independent bone deterioration. TBS adjustment of FRAX scores may be useful for younger women (&lt; 65 years) with diabetes. This suggests that halting or reversing progression from IFG to diabetes could be important to prevent skeletal fragility in diabetes

Association between area-level socioeconomic status, accessibility and diabetes-related hospitalisations: a cross-sectional analysis of data from Western Victoria, Australia

OBJECTIVE: Hospitalisation rates for many chronic conditions are higher in socioeconomically disadvantaged and less accessible areas. We aimed to map diabetes hospitalisation rates by local government area (LGA) across Western Victoria, Australia, and investigate their association with socioeconomic status (SES) and accessibility/remoteness. DESIGN: Cross-sectional study METHODS: Data were acquired from the Victorian Admitted Episodes Dataset for all hospitalisations (public and private) with a diagnosis of type 1 or type 2 diabetes mellitus during 2011-2014. Crude and age-standardised hospitalisation rates (per 1000 population per year) were calculated by LGA for men, women and combined data. Associations between accessibility (Accessibility/Remoteness Index of Australia, ARIA), SES (Index of Relative Socioeconomic Advantage and Disadvantage, IRSAD) and diabetes hospitalisation were investigated using Poisson regression analyses. RESULTS: Higher LGA-level accessibility and SES were associated with higher rates of type 1 and type 2 diabetes hospitalisation, overall and for each sex. For type 1 diabetes, higher accessibility (ARIA category) was associated with higher hospitalisation rates (men incidence rate ratio [IRR]=2.14, 95% CI 1.64 to 2.80; women IRR=2.45, 95% CI 1.87 to 3.19; combined IRR=2.30, 95% CI 1.69 to 3.13; all p<0.05). Higher socioeconomic advantage (IRSAD decile) was also associated with higher hospitalisation rates (men IRR=1.25, 95% CI 1.09 to 1.43; women IRR=1.32, 95% CI 1.16 to 1.51; combined IRR=1.23, 95% CI 1.07 to 1.42; all p<0.05). Similarly, for type 2 diabetes, higher accessibility (ARIA category) was associated with higher hospitalisation rates (men IRR=2.49, 95% CI 1.81 to 3.43; women IRR=2.34, 95% CI 1.69 to 3.25; combined IRR=2.32, 95% CI 1.66 to 3.25; all p<0.05) and higher socioeconomic advantage (IRSAD decile) was also associated with higher hospitalisation rates (men IRR=1.15, 95% CI 1.02 to 1.30; women IRR=1.14, 95% CI 1.01 to 1.28; combined IRR=1.13, 95% CI 1.00 to 1.27; all p<0.05). CONCLUSION: Our observations could indicate self-motivated treatment seeking, and better specialist and hospital services availability in the advantaged and accessible areas in the study region. The determinants for such variations in hospitalisation rates, however, are multifaceted and warrant further research