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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 < 0.05). Men with IFG had lower mean TBS in the age-adjusted models only (all p < 0.05). The addition of TBS to the FRAX score improved the discrimination between glycaemia groups, particularly for younger women (< 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 (< 65 years) with diabetes. This suggests that halting or reversing progression from IFG to diabetes could be important to prevent skeletal fragility in diabetes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Diabetes is associated with higher fracture risk despite higher bone mineral density (BMD), with FRAX® underestimating risk. This study aimed to investigate FRAX score with and without BMD for women with normoglycaemia, impaired fasting glucose (IFG) and diabetes., Methods: Among 566 women, aged 40-90 years, enrolled in the Geelong Osteoporosis Study, IFG was defined as fasting plasma glucose (FPG) ≥5.5 mmol/L and diabetes as FPG ≥ 7.0 mmol/L, use of antihyperglycaemic medication and/or self-report. FRAX (Australia) 10-year probabilities of major osteoporotic (MOF) and hip fracture were calculated, with and without BMD, producing four FRAX scores per participant. Kruskal-Wallis test for non-parametric data was used to examine differences between the three glycaemia groups. Fractures over 10 years were ascertained using radiological reports. The number of fractures predicted by FRAX was compared with the number of fractures observed using Chi-square tests., Results: For MOF FRAX calculated without BMD, women with diabetes ( n  = 67) tended to have a higher median score 7.1 (IQR 2.7-12.0) than normoglycaemia ( n  = 252) (4.3 (IQR 1.9-9.9) and IFG ( n  = 247) (5.1 (IQR 2.2-9.6)). For hip FRAX without BMD, diabetes tended to have a higher score (2.5 (IQR 06-4.3)) than normoglycaemia (1.2 (IQR 0.3-4.1)) and IFG (1.3 (IQR 0.3-4.1)). In the normoglycaemia and IFG groups, MOFs were underestimated; 15 predicted vs 28 observed, p  = 0.038; and 16 predicted vs 31 observed, p  = 0.021, respectively. Fractures were accurately estimated in all other groups.When including BMD, the association with diabetes was non-significant for both MOF FRAX (normoglycaemia 3.7 (IQR 1.9-8.0), IFG 4.3 (IQR 2.2-8.1) and diabetes 5.3 (IQR 2.7-9.4)) and hip FRAX scores (normoglycaemia 0.6 (IQR 0.2-2.5), IFG 0.8 (IQR 0.2-2.7) and diabetes 1.0 (IQR 0.3-3.0)). For normoglycaemia and IFG, MOFs were underestimated (normoglycaemia: 13 predicted vs 28 observed and IFG: 13 vs 31). For diabetes, both MOFs and hip fractures tended to be underestimated by FRAX with BMD (MOF: 4 predicted vs 11 observed, p  = 0.055, hip: 1 predicted vs 6 observed, p  = 0.052). Hip fractures were accurately estimated in the normoglycaemia and IFG groups., Conclusions: Compared with women who had normoglycaemia or IFG, women with diabetes tended to have a higher FRAX score for both MOF and hip fractures when BMD was not included. When BMD was included, there was no difference. Fractures in diabetes tended to be underestimated by FRAX with BMD. This suggests that FRAX calculations including BMD may not be accurate for estimating fractures in those with diabetes.