Hypogonadism in men: how to evaluate and when to treat

Low testosterone levels may be due to underlying disease or lifestyle factors and these need to be addressed before testosterone supplementation is considered.Anjana Radhakutty and Gary Witterthttp://www.medicinetoday.com.au/home/article/view/111

The Performance of Freestyle Libre Pro Flash Continuous Glucose Monitoring in Hospitalized Patients Treated with an Intravenous Insulin Infusion for Acute Prednisolone-Induced Hyperglycemia

Few studies have evaluated the performance of flash glucose monitoring in hospitalized patients requiring intravenous insulin therapy. In this prospective study, an intravenous insulin infusion was adjusted hourly using flash glucose monitoring in hospitalized adults with prednisolone-associated hyperglycemia. The difference in paired point of care (POC) and flash glucose measurements and risk of severe hyper- or hypoglycemia (assessed by Clarke error grid analysis) were assessed. Glucose concentration measured by flash glucose monitoring was lower than POC glucose (mean difference 1.5 mmol/L [27 mg/dL], p < 0.001); however, mean POC glucose was within the target range (9.1 ± 4.1 mmol/L [164 ± 72 mg/dL]) and 97.8% of glucose measurements were within Zone A and B on error grid analysis. Flash glucose monitoring could be used in combination with POC glucose monitoring to minimize the frequency of finger prick blood glucose levels in hospitalized patients prescribed an intravenous insulin infusion.Angela X. Chen, Anjana Radhakutty, Anthony Zimmermann, Stephen N. Stranks, Campbell H. Thompson, and Morton G. Bur

Cardiovascular risk markers in adults with adrenal incidentaloma and mild autonomous cortisol secretion

Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). While MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined. To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma. Cross-sectional study. 20 adults with adrenal adenoma and MACS and 20 controls with non-functioning adrenal adenoma (NFAT). Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure (24h AMBP) monitoring was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal. The primary outcome was the difference in RHI between participants with MACS vs. NFAT. The average cortisol after 1 mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [IQR 1.6-2.4] vs. 2.0 [IQR 1.7-2.2, p = 0.72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs. 1.8 [1.5-2.2], p = 0.04). 24h AMBP and Matsuda Index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS. Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion and this may underlie the association between MACS and increased cardiovascular mortality.Angela X. Chen, Anjana Radhakutty, Sophie M. Drake, Andrew Kiu, Campbell H. Thompson, and Morton G Bur

Clinical determinants of insulin requirements during treatment of prednisolone-induced hyperglycaemia

Aims: The optimal treatment of prednisolone-associated hyperglycaemia is unclear, but guidelines recommend using a body weight-based daily insulin dose. This study evaluated how clinical variables were associated with insulin requirements in hospitalised patients with prednisolone-associated hyperglycaemia. Methods: In this prospective study, fifty adult inpatients who were taking prednisolone ≥20 mg/day and experienced hyperglycaemia were prescribed a 24-h intravenous insulin infusion. The daily insulin dose required to attain a mean glucose of 8 mmol/L was calculated. The associations between daily insulin dose and clinical variables were assessed. Results: The participants age was 69 ± 10 years, daily prednisolone dose was 34 ± 10 mg, HbA1c was 7.7 ± 2.0 % (61 ± 10 mmol/mol), 77 % had known type 2 diabetes and 30 % were female. In univariate analysis, weight was associated with daily insulin dose (r2 = 0.11, p = 0.024). A multivariate model comprising sex, HbA1c, a prior diagnosis of diabetes, diabetes treatment and weight explained nearly-two thirds of the variability in daily insulin dose (r2 = 0.65, p < 0.001). Conclusions: In patients with prednisolone-associated hyperglycaemia, calculating insulin doses based on sex, HbA1c, diabetes status and regular diabetes treatment and weight may improve glycaemic control compared to weight-based dosing.Angela X. Chen, Anjana Radhakutty, Anthony Zimmermann, Stephen N. Stranks, Campbell H. Thompson, Morton G. Bur

Opposing effects of rheumatoid arthritis and low dose prednisolone on arginine metabolomics

Available online 6 October 2017Abstract not availableAnjana Radhakutty, Brenda L. Mangelsdorf, Sophie M. Drake, Andrew Rowland, Malcolm D. Smith, Arduino A. Mangoni, Campbell H. Thompson, Morton G. Bur

Treatment of prednisolone-induced hyperglycaemia in hospitalized patients: Insights from a randomized, controlled study

Aim: Prednisolone causes hyperglycaemia predominantly between midday and midnight. Consequently, glargine-based basal-bolus insulin regimens may under treat daytime hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen is safer and more effective than a glargine-based regimen in hospitalized patients. Materials and methods: Fifty inpatients prescribed ≥20 mg/day prednisolone acutely with (1) finger prick blood glucose level (BGL) ≥15 mmol/L or (2) BGLs ≥10 mmol/L within the previous 24 hours were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg bodyweight or 130% of the current daily insulin dose. Glycaemic control was assessed using a continuous glucose monitoring system. Results: On Day 1, there were no significant differences in percentage of time outside a target glucose range of 4 to 10 mmol/L (41.3% ± 5.5% vs 50.0% ± 5.7%, P  = .28), mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/L, P  = .57) or glucose <4 mmol/L (2.2% ± 1.1% vs 2.0% ± 1.3%, P  = .92) in patients randomized to isophane and glargine. In patients treated for 3 days, the prednisolone dose was reduced ( P  = .02) and the insulin dose was increased over time ( P  = .02), but the percentage of time outside the 4 to 10 mmol/L glucose range did not differ over time ( P  = .45) or between groups ( P  = .24). Conclusions: There were no differences in the efficacy or safety of the isophane and glargine-based insulin regimens. We recommend an initial daily insulin dose of 0.5 units/kg bodyweight if not on insulin, a greater than 30% increase in pre-prednisolone insulin dose and larger insulin dose adjustments in patients with prednisolone-induced hyperglycaemia.Anjana Radhakutty, Jessica L. Stranks, Brenda L. Mangelsdorf, Sophie M. Drake, Gregory W. Roberts, Anthony T. Zimmermann, Stephen N. Stranks, Campbell H. Thompson, Morton G. Bur

Effect of acute and chronic glucocorticoid therapy on insulin sensitivity and postprandial vascular function

Objective: Postprandial hyperglycaemia is associated with increased arterial stiffness and cardiovascular events. Low-dose prednisolone causes insulin resistance that typically manifests as postprandial hyperglycaemia. We investigated whether prednisolone causes postprandial vascular dysfunction in a cohort of patients with rheumatoid arthritis. Design: An open interventional and cross-sectional study was undertaken. Patients and measurements: Eighteen subjects with rheumatoid arthritis who had not taken oral glucocorticoids for ≥6 months were studied before and after prednisolone 6 mg/day for 7 days to determine the acute effects of prednisolone. Pre-prednisolone data were compared to 18 subjects with rheumatoid arthritis taking long-term (>6 months) prednisolone (6·5 ± 1·8 mg/day) to assess the chronic effects of prednisolone. Augmentation index (by applanation tonometry) and reactive hyperaemia index (by peripheral artery tonometry) were measured before and after a mixed-meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). Insulin sensitivity was estimated by the Matsuda index and sympathetic nervous system activity from urinary noradrenaline excretion. Results: Matsuda index was lower after acute (2·0 ± 1·0 vs 3·6 ± 1·1, P = 0·01) and chronic (1·9 ± 1·0 vs 3·6 ± 1·1, P = 0·04) prednisolone. Postprandial augmentation index was lower after acute prednisolone (2551 ± 197 vs 2690 ± 272%*min, P ≤ 0·001), but not chronic prednisolone. There were no significant differences in reactive hyperaemia index with acute or chronic prednisolone. Noradrenaline excretion was lower after acute (54 ± 8 vs 93 ± 23 nmol/6 h, P = 0·02), but not chronic, prednisolone. Conclusions: Prednisolone-induced insulin resistance is not associated with postprandial vascular dysfunction in patients with rheumatoid arthritis. Reduced sympathetic activity may contribute to the reduction in postprandial arterial stiffness with acute prednisolone.Anjana Radhakutty, Brenda L. Mangelsdorf, Sophie M. Drake, Dorit Samocha-Bonet, Arthur B. Jenkins, Leonie K. Heilbronn, Malcolm D. Smith, Campbell H. Thompson and Morton G. Bur

Effects of prednisolone on energy and fat metabolism in patients with rheumatoid arthritis: tissue-specific insulin resistance with commonly used prednisolone doses

Objective: Glucocorticoids can cause postprandial hyperglycaemia, but the effects on postprandial energy and fat metabolism are uncertain. We investigated the effects of acute and chronic low-dose prednisolone on fasting and postprandial energy expenditure and substrate metabolism. Design: An open interventional and cross-sectional study was undertaken. Patients and measurements: Eighteen patients who had not taken oral glucocorticoids for ≥6 months were studied before and after 7 days prednisolone (6 mg/day) to assess the acute effects of prednisolone. Baseline data from patients, not on glucocorticoids, were compared with 18 patients on long-term prednisolone (6·5 ± 1·8 mg/day for >6 months) to assess the chronic effects. Energy expenditure and substrate oxidation were measured using indirect calorimetry before and after a mixed meal. Adipocyte insulin resistance index and insulin-mediated suppression of NEFA were calculated from fasting and postprandial insulin and NEFA concentrations. Results: There were no significant differences in resting energy expenditure or diet-induced thermogenesis with prednisolone. Acute (-2·1 ± 6·2 vs -16·3 ± 4·8 mg/min, P = 0·01) and chronic (-1·4 ± 2·8 vs -16·3 ± 4·8 mg/min, P = 0·01) prednisolone attenuated postprandial suppression of fat oxidation. Chronic (31·6 ± 3·8 vs 17·0 ± 3·3, P = 0·007), but not acute, prednisolone increased adipocyte insulin resistance index. However, insulin-mediated suppression of NEFA was not significantly different after acute or chronic prednisolone. Conclusions: Prednisolone does not alter energy expenditure. However, even at low doses, prednisolone exerts adverse effects on fat metabolism, which could exacerbate insulin resistance and increase cardiovascular risk. Attenuated postprandial suppression of fat oxidation, but not lipolysis, suggests that prednisolone causes greater insulin resistance in skeletal muscle than in adipocytes.Anjana Radhakutty, Brenda L. Mangelsdorf, Sophie M. Drake, Dorit Samocha-Bonet, Leonie K. Heilbronn, Malcolm D. Smith, Campbell H. Thompson and Morton G. Bur