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Context: In observational studies, low serum 25-hydroxyvitamin D (25-OHD) concentration is associated with an increased risk of type 2 diabetes mellitus (DM). Increasing serum 25-OHD may have beneficial effects on insulin resistance or beta-cell function. Cross-sectional studies utilizing suboptimal methods for assessment of insulin sensitivity and serum 25-OHD concentration provide conflicting results., Objective: This study examined the relationship between serum 25-OHD concentration and insulin resistance in healthy overweight individuals at increased risk of cardiovascular disease, using optimal assessment techniques., Methods: A total of 92 subjects (mean age 56·0, SD 6·0 years), who were healthy but overweight (mean body mass index 30·9, SD 2·3 kg/m(2) ), underwent assessments of insulin sensitivity (two-step euglycaemic hyperinsulinaemic clamp, HOMA2-IR), beta-cell function (HOMA2%B), serum 25-OHD concentration and body composition (DEXA)., Results: Mean total 25-OHD concentration was 32·2, range 21·8-46·6 nmol/l. No association was demonstrated between serum 25-OHD concentration and insulin resistance., Conclusions: In this study using optimal assessment techniques to measure 25-OHD concentration, insulin sensitivity and body composition, there was no association between serum 25-OHD concentration and insulin resistance in healthy, overweight individuals at high risk of developing cardiovascular disease. This study suggests the documented inverse association between serum 25-OHD concentration and risk of type 2 DM is not mediated by a relationship between serum 25-OHD concentration and insulin resistance., (© 2016 John Wiley & Sons Ltd.)

Objectives: The mechanism of hypertension in Cushing's syndrome remains undetermined. Some studies have demonstrated an increased sensitivity to pressor agents but it is not clear if patients with Cushing's syndrome of different aetiologies demonstrate this finding. We have examined pressor sensitivity in a group of patients with Cushing's disease (pituitary dependent hypercortisolism) by measuring blood pressure during incrementally increasing infusions of noradrenaline., Methods: Eight subjects (7 female, 1 male), aged 42.2 +/- 4.5 years (mean +/- SEM) with Cushing's disease were studied. Eight age- and sex-matched control subjects were also studied. Four of the eight controls and five patients with Cushing's disease had elevated blood pressure. All medication for this had been stopped at least seven days prior to the study. After subjects ate a light breakfast, ECG leads and a sphygmomanometer were attached, an intravenous cannula was inserted and all subjects then rested quietly for 60 minutes. Noradrenaline was then infused intravenously for 10-minute periods at concentrations of 0.01, 0.03, 0.07, 0.11 and 0.18 microg/kg/minute., Results: On the day of the study the baseline blood pressures and pulse rates in the patients with Cushing's disease (blood pressure; 138/87 +/- 6/3 mmHg, pulse 76.5 +/- 4.8 beats/minute) and controls (blood pressure; 126/86 +/- 6/6 mmHg, pulse 71.2 +/- 3.7 beats/minute) were not significantly different. The mean change in diastolic blood pressure from baseline at the time of the peak increase or when the test was stopped was 21. 5 +/- 4.7 mmHg in Cushing's disease compared to 7.0 +/- 2.5 mmHg in controls (P = 0.03). The mean change in mean arterial pressure from baseline at the time of the peak increase or when the test was stopped was 22.0 +/- 4.0 mmHg in Cushing's disease compared to 13.0 +/- 2.4 mmHg in controls (P = 0.03). No significant difference in mean change of systolic pressure (26.0 +/- 4.6 vs. 25 +/- 4.0 mmHg) or pulse rates (- 11.1 +/- 1.8 vs. - 4.7 +/- 2.6) was seen in the group with Cushing's disease as compared to the control group., Conclusions: We conclude that patients with pituitary-dependent Cushing's syndrome have enhanced pressor diastolic and mean arterial responses to noradrenaline and this may be an important underlying mechanism for the hypertension seen in this particular group of Cushing's syndrome patients.

We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)