Mortality in Cushing's syndrome: systematic analysis of a large series with prolonged follow-up.

OBJECTIVE: In this study, we aim to assess the long-term survival and causes of death in a retrospective cohort study on patients with all aetiologies of endogenous Cushing's syndrome (CS) (except adrenal cancer), presenting to two large tertiary endocrine referral centres, and to identify variables predicting mortality. SUBJECTS AND METHODS: The records of all patients presenting with endogenous CS in the Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, UK and the Department of Endocrinology, 'Evangelismos' General Hospital, Athens, Greece between 1967-2009 (Oxford series) and 1962-2009 (Athens series) were reviewed. The standardised mortality ratio (SMR) was calculated for the Oxford series. RESULTS: In total, 418 subjects were identified (311 with Cushing's disease (CD), 74 with adrenal Cushing's (AC) and 33 with ectopic Cushing's (EC)). In CD, the probability of 10-year survival was 95.3% with 71.4% of the deaths attributed to cardiovascular causes or infection/sepsis. SMRs were significantly high overall (SMR 9.3; 95% CI, 6.2-13.4, P<0.001), as well as in all subgroups of patients irrespective of their remission status. In AC, the probability of 10-year survival was 95.5% and the SMR was 5.3 (95% CI, 0.3-26.0) with P=0.2. Patients with EC had the worst outcome with 77.6% probability of 5-year survival. CONCLUSIONS: In this large series of patients with CS and long-term follow-up, we report that in CD the mortality is significantly affected, even after apparently successful treatment. The SMR of patients with AC was high, but this was not statistically significant. The implicated pathophysiological mechanisms for these findings need to be further elucidated aiming to improve the long-term outcome.

Erythrocyte fatty acid composition and insulin sensitivity in daughters of Type 2 diabetic patients and women with no family history of diabetes.

BACKGROUND: There is evidence that the impact of environmental factors on insulin sensitivity is modified by the presence of family history of diabetes. AIM: To compare the association between the erythrocyte phospholipid fatty acid composition (a biomarker of dietary fatty acids) and insulin sensitivity in daughters of Type 2 diabetic patients with the corresponding association in women without family history of diabetes. MATERIAL/SUBJECTS AND METHODS: Eighteen offspring of Type 2 diabetic patients [age 30+/-6.5 yr; body mass index (BMI) 22.2+/-2.5 kg/m2; body fat 31.8+/-5.1%] and 18 matched women (age 30.1+/-6.8 yr; BMI 22.2+/-1.8 kg/m2; body fat 32.2+/-6.0%) participated in the study. RESULTS: Insulin Sensitivity Index (ISI)-Matsuda tended to be lower (p=0.06) in the Offspring than the control group. Weight proportions of erythrocyte phospholipid saturated (SFA), polyunsaturated (PUFA), and monounsaturated fatty acids (MUFA) were similar between the two groups. In the offspring, erythrocyte total SFA were negatively correlated with ISI-Matsuda [r=-0.47, p<0.05), ISI(gly)-Belfiore (r=-0.52, p<0.05) and ISI(ffa)-Belfiore (r=-0.53, p<0.05)], whereas total PUFA were positively correlated with insulin sensitivity [ISI-Matsuda, r=0.46, p<0.05; ISI(gly)-Belfiore, r=0.53, p<0.05; ISI(ffa)-Belfiore, r=0.54, p<0.05]. No significant correlations were observed in the control group. CONCLUSIONS: The associations between erythrocyte fatty acid composition and insulin sensitivity are distinct between daughters of Type 2 diabetic patients and women without family history of diabetes.

Elevated fasting plasma C-peptide occurs in non-diabetic individuals with fatty liver, irrespective of insulin resistance.

AIMS: Studies have pointed to insulin resistance as a pathogenic factor in fatty liver. Although pancreatic B-cell function is believed to be involved, its role is unclear. This study was undertaken to test whether fasting C-peptide, an index of fasting B-cell function, was related to intra-hepatic fat (IHF) content in non-diabetic humans. METHODS: We assessed, retrospectively, fasting plasma C-peptide concentration in 31 patients with fatty liver and 62 individuals without fatty liver. The IHF content was measured by proton magnetic resonance spectroscopy ((1)H-MRS), while insulin sensitivity was estimated based on fasting plasma glucose and insulin with the homestasis model assessment (HOMA) 2 method. RESULTS: Age, sex and body mass index (BMI) were not different between groups. Patients with fatty liver had higher fasting insulin (P < 0.01), C-peptide (P < 0.005) and lower insulin sensitivity (HOMA2-%S). Fasting insulin alone explained 14% of the IHF content variability (P < 0.001); inclusion of fasting C-peptide in multivariate regression explained up to 32% (P < 0.001). A subgroup analysis was performed by matching 1 : 1 for HOMA2-%S. These data were analysed by conditional logistic regression which showed that, when HOMA2-%S was matched between groups, fasting C-peptide remained the only significant predictor of fatty liver. CONCLUSIONS: Non-diabetic individuals with fatty liver are characterized by increased fasting plasma C-peptide concentration, irrespective of their insulin resistant state.