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Aims/hypothesis We tested the hypothesis that NEFA concentrations are higher in obese subjects with fatty liver than in obese subjects without fatty liver. Materials and methods We recruited 22 obese (BMI>30 kg/m²) men aged 42-64 years, in whom liver fat was assessed by ultrasound and classified into categories of no, mild to moderate and severe fatty liver by two independent radiologists. Regional and visceral abdominal fat were assessed by dual-energy X-ray absorptiometry and magnetic resonance imaging, and endogenous glucose production, whole-body glucose disposal during an insulin clamp, and NEFA concentrations were measured, along with NEFA suppression (percent (%) suppression and insulin sensitivity index for NEFA during an OGTT). Results Seven subjects had no evidence of fatty liver, nine had mild or moderate fatty liver and six had severe fatty liver. The amount of visceral fat was not associated with the degree of fatty liver. Whole-body glucose disposal was inversely associated with fatty liver (38.4, 26.5 and 23.9 μmol kg-¹ min-¹ for the groups with no fatty liver, mild to moderate fatty liver and severe fatty liver, respectively, p=0.004). NEFA suppression during the OGTT was decreased (62.5, 50.8 and 41%, p=0.03, for no, mild to moderate, and severe fatty liver, respectively) and the insulin sensitivity index for NEFA was decreased (0.80, 0.40 and 0.34, p<0.0001). Regression modelling suggested that NEFA concentrations were associated with fatty liver independently of whole-body glucose production and disposal measurements. Conclusions/interpretation In obese men, NEFA concentrations during an OGTT are associated with fatty liver independently of classic measures of insulin sensitivity determined by the hyperinsulinaemic clamp. The contribution to this association by factors regulating NEFA concentrations requires further study.

Aims/hypothesis The relative contributions of fitness (maximal oxygen uptake), physical activity energy expenditure (PAEE) and fatness to whole-body, liver and fat insulin sensitivity is uncertain. The aim of this study was to determine whether fitness and PAEE are associated with whole-body, liver and fat insulin sensitivity independently of body fat. Materials and methods We recruited 25 men (mean [SD] age 53 [6] years). Whole-body (M value) and liver (percentage suppression of endogenous glucose output) insulin sensitivity were estimated using a hyperinsulinaemic-euglycaemic clamp. Insulin sensitivity in fat (insulin sensitivity index for NEFA) was estimated during an OGTT. Total and truncal fat were measured by dual-energy X-ray absorptiometry, fitness by treadmill, and PAEE (n = 21) by 3 day heart rate monitoring and Baecke questionnaire. Results In univariate analyses, fatness was strongly associated with insulin sensitivity (whole-body, liver and fat). Fitness was associated with whole-body (r = 0.53, p < 0.007) and liver (0.42, p = 0.04) insulin sensitivity, while PAEE was associated with liver insulin sensitivity (r = 0.55, p = 0.01). Regression models were established to describe associations between fatness, fitness and physical activity and measures of insulin sensitivity (whole-body, fat and liver) as outcomes. Only fatness was independently associated with whole-body insulin sensitivity (B coefficient -0.01, p = 0.001). Fitness was not associated with any outcome. Only PAEE was independently associated with liver insulin sensitivity (B coefficient 13.5, p = 0.02). Conclusions/interpretation Fatness explains most of the variance in whole-body insulin sensitivity. In contrast, PAEE explains most of the variance in liver insulin sensitivity.

The regulation of cortisol metabolism in vivo is not well understood. We evaluated the relationship between cortisol metabolism and insulin sensitivity, adjusting for total and regional fat content and for non-alcoholic fatty liver disease. Twenty-nine middle-aged healthy men with a wide range of BMI were recruited. We measured fat content by dual-energy X-ray absorptiometry and magnetic resonance imaging (MRI), liver fat by ultrasound and MRI, the hypothalamic-pituitary-adrenal axis by adrenal response to ACTH(1-24), unconjugated urinary cortisol excretion, corticosteroid-binding globulin, and cortisol clearance by MS. We assessed insulin sensitivity by hyperinsulinaemic-euglycaemic clamp and by OGTT. Cortisol clearance was strongly inversely correlated with insulin sensitivity (M value) (r = -0.61, p = 0.002). Cortisol clearance was increased in people with fatty liver compared with those without (mean+/-SD: 243 +/- 10 vs 158 +/- 36 ml/min; p = 0.014). Multiple regression modelling showed that the relationship between cortisol clearance and insulin sensitivity was independent of body fat. The relationship between fatty liver and insulin sensitivity was significantly influenced by body fat and cortisol clearance. Cortisol clearance is strongly associated with insulin sensitivity, independently of the amount of body fat. The relationship between fatty liver and insulin sensitivity is mediated in part by both fatness and cortisol clearance.

This report describes the case of a 28 year old woman with virilisation occurring in two successive pregnancies. Recurrent maternal virilisation is rare (seven previous reports) and this case is unique in its severity. Differential diagnoses include ovarian disease and fetal aromatase deficiency. New techniques to exclude a fetal cause were used in this case. This patient presented during the third trimester of her first pregnancy with rapid onset of hirsuitism, increased musculature, and deepening voice. A blood hormone profile revealed significant hyperandrogenism (testosterone, 72.4 nmol/litre; normal range, 0.5–3.0). She delivered a normal boy and maternal androgen concentrations returned rapidly to normal (testosterone, 0.8 nmol/litre). She presented two years later, during her second pregnancy, with similar symptoms and biochemistry (testosterone, 47.5 nmol/litre). Again, she delivered a healthy normal boy and androgens returned immediately to normal (serum testosterone, 2.0 nmol/litre). Ultrasonography revealed no evidence of ovarian (or adrenal) masses in either pregnancy. Umbilical cord venous blood sampling and placental assays revealed no evidence of fetal aromatase deficiency. Recurrent hyperandrogenism during pregnancy is rare. Ovarian luteoma rarely recurs and hyperreactio luteinalis does not lead to such pronounced androgen concentrations. Therefore, this patient has a unique ovarian condition that could be harmful to offspring and mother.

Archaeologists recently have been focusing increased attention on Native American concerns and archaeology. However, some serious issues of Native American attitudes toward the activities of archaeology have so far been overlooked. For example, in the San Juan Basin of northwestern New Mexico, archaeological activities that have been spurred by energy development violate certain tenets of the Navajo Way of living, with possible adverse effects. Suggestions for the mitigation of these effects are presented as a way of expanding the dialogue between archaeologists and Native American communities, in order to identify and resolve such ethical dilemmas.