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BACKGROUND: Insulinomas are rare tumours of the pancreas and the most common cause of hypoglycaemia in non-diabetic adults. They can be cured by surgery but require precise localization. The aim of this study was to assess the utility of the selective intra-arterial calcium stimulation test (SIACST) in patients with an insulinoma to correctly localize the tumour. METHOD(S): Medical records of patients with a diagnosis of insulinoma or who underwent an SIACST were retrospectively reviewed. Localization of lesions by SIACST was compared to endoscopic ultrasound and radionuclide imaging studies and verified against findings at surgery. RESULT(S): A total of 24 patients (mean age 58years, 16 females, 20 with insulinoma) underwent SIACST. The SIACST correctly localized the insulinoma in 17 of 20 patients (85%). Localization rate for computed tomography was 55% and 75% for endoscopic ultrasound and glucagon-like peptide-1 receptor scan. CONCLUSION(S): SIACST provided incremental diagnostic information in patients with insulinoma who had equivocal non-invasive imaging preoperatively. This technique remains an essential diagnostic tool when a lesion is not localized by other methods.Copyright © 2020 Royal Australasian College of Surgeons.

BACKGROUND: Adrenal vein sampling (AVS) is crucial for accurate lateralization of aldosterone excess but it is technically challenging due to the difficulty of adrenal vein cannulation. The use of adrenocorticotropic hormone (ACTH) to improve cannulation success is controversial and can lead to discordant lateralization outcomes. OBJECTIVE(S): To evaluate the utility of ACTH in two centres with different levels of AVS expertise and formulate a strategy for interpreting discordant results. DESIGN: A retrospective cross-sectional analysis of AVS results and post-operative patient outcomes. SETTING: Two large tertiary hospitals with harmonized AVS protocols where adrenal venous samples are collected both before and after ACTH stimulation. MEASUREMENTS: Cannulation success (measured by selectivity index, SI), lateralization (measured by lateralization index, LI) and post-operative biochemical cure. RESULT(S): Number of AVS procedures judged to have successful bilateral adrenal vein cannulation increased from 53% pre- to 73% post-ACTH. The increase in cannulation success was significantly higher in centre where AVS was performed by multiple radiologists with a lower basal success rate. In both centres, the proportion of cases deemed to display lateralization significantly decreased with the use of ACTH (70% pre- to 52% post-ACTH). Based on post-operative outcomes of patients with discordant results who underwent unilateral adrenalectomy, the combination of LI > 3 pre-ACTH and LI > 2 post-ACTH was predictive of a biochemical cure. CONCLUSION(S): ACTH can increase the rate of cannulation success during AVS at the expense of reduced lateralization. The criteria for lateralization should be carefully determined based on local data when ACTH is used.Copyright This article is protected by copyright. All rights reserved.

Background: Adrenal vein sampling (AVS) is crucial for accurate lateralization of aldosterone excess but it is technically challenging due to the difficulty of adrenal vein cannulation. The use of adrenocorticotropic hormone (ACTH) to improve cannulation success is controversial and can lead to discordant lateralization outcomes. Objective(s): To evaluate the utility of ACTH in two centres with different levels of AVS expertise and formulate a strategy for interpreting discordant results. Design(s): A retrospective cross-sectional analysis of AVS results and postoperative patient outcomes. Setting(s): Two large tertiary hospitals with harmonized AVS protocols where adrenal venous samples are collected both before and after ACTH stimulation. Measurements: Cannulation success (measured by selectivity index, SI), lateralization (measured by lateralization index, LI) and postoperative biochemical cure. Result(s): Number of AVS procedures judged to have successful bilateral adrenal vein cannulation increased from 53% pre- to 73% post-ACTH. The increase in cannulation success was significantly higher in centre where AVS was performed by multiple radiologists with a lower basal success rate. In both centres, the proportion of cases deemed to display lateralization significantly decreased with the use of ACTH (70% pre- to 52% post-ACTH). Based on postoperative outcomes of patients with discordant results who underwent unilateral adrenalectomy, the combination of LI '3 pre-ACTH and LI '2 post-ACTH was predictive of a biochemical cure. Conclusion(s): Adrenocorticotropic hormone can increase the rate of cannulation success during AVS at the expense of reduced lateralization. The criteria for lateralization should be carefully determined based on local data when ACTH is used.Copyright © 2020 John Wiley & Sons Ltd

Mesangial metrics reflect glomerular filtration surface area in diabetes. The point-sampled intercept (PSI) method is the conventional method to calculate these parameters. However, this is time consuming and subject to underestimation. We introduce a novel three-dimensional (3D) reconstruction method applicable to light microscopy to measure mesangial metrics. Transmission electron microscopy (TEM), PSI and our new 3D imaging methods were used to quantify mesangial metrics from 22 patients with type 2 diabetes, normo-, micro- and macroalbuminuria and an estimated glomerular filtration rate of <60mL/min/1.73m2. Repeated-measures ANOVA test was used to test the equality of the measurement means from the three methods and the degree of inter method variability. Repeated-measures and post-estimation ANOVA tests together with correlation coefficient measurements were used to compare the methods with TEM as reference. There was a statistically significant difference in mesangial volume measurements (F(2, 16)=15.53, p=0.0002). The PSI method underestimated measurements compared to TEM and 3D methods by 30% (p=0.001) and 15%, respectively (p<0.001). 3D and TEM measurements did not differ significantly. 3D reconstruction is a reliable and time efficient method for calculating mesangial metrics. It may prove to be a useful tool in clinical and experimental diabetic kidney disease.

Purpose: Kidney disease caused by type 1 diabetes can progress to end stage renal disease and can increase mortality risk. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) plays a major role in producing oxidative stress in the kidney in diabetes, and its activity is attenuated by GKT137831, an oral Nox inhibitor with predominant inhibitory action on Nox-1 and Nox - 4. Previous studies have demonstrated renoprotective effects with GKT137831 in various experimental models of type 1 diabetes-related kidney disease. This study will evaluate the effect of GKT137831 in treating clinical diabetic kidney disease. Design(s): This is a multi-center, randomized, placebo-controlled trial, parallel arm study evaluating the effect on albuminuria of treatment with GKT137831 400 mg BID for 48 weeks. The study will randomize 142 participants who have persistent albuminuria and estimated glomerular filtration rate (eGFR) at baseline of at least 40 ml/min/1.73m2. Primary outcome measures: Difference between arms in urine albumin to creatinine ratio. Secondary outcome measures include eGFR. Conclusion(s): This study is important because it may identify a new way of slowing renal disease progression in people with type 1 diabetes and albuminuria already receiving standard of care treatment.Copyright © 2019

Context Diabetic ketoacidosis (DKA) has been associated with the use of sodium glucose cotransporter 2 inhibitors (SGLT2is). Objective To determine the incidence, characteristics, and outcomes of DKA in SGLT2i users vs nonusers with type 2 diabetes. Design Retrospective, multicenter, controlled cohort study. Setting All public hospitals in Melbourne and Geelong (combined population of 5 million), Australia, from 1 September 2015 to 31 October 2017. Patients Consecutive cases of DKA that developed in the community, or during the course of hospital admission, in patients with type 2 diabetes Main Outcome Measures In SGLT2i users vs nonusers: (i) OR of DKA developing during hospital admission, and (ii) incidence of DKA. Results There were 162 cases of DKA (37 SGLT2i users and 125 non-SGLT2i users) with a physician-adjudicated diagnosis of type 2 diabetes. Of these, DKA developed during the course of inpatient admission in 14 (38%) SGLT2i users vs 2 (2%) non-SGLT2i users (OR, 37.4; 95% CI, 8.0 to 175.9; P < 0.0001). The incidence of DKA was 1.02 per 1000 (95% CI, 0.74 to 1.41 per 1000) in SGLT2i users vs 0.69 per 1000 (95% CI, 0.58 to 0.82 per 1000) in non-SGLT2i users (OR, 1.48; 95% CI, 1.02 to 2.15; P = 0.037). Fifteen SGLT2i users (41%) had peak blood glucose <250 mg/dL (14 mmol/L) compared with one (0.8%) non-SGLT2i user (P < 0.001). Conclusions SGLT2i users were more likely to develop DKA as an inpatient compared with non-SGLT2i users. SGLT2i use was associated with a small but significant increased risk of DKA.Copyright © 2019 Endocrine Society.

The metabolic abnormalities affecting bone in the setting of chronic kidney disease (CKD) are complex with overlapping and interacting aetiologies and have challenging diagnostic and management strategies. Disturbances in calcium, phosphate, fibroblast growth factor 23, parathyroid hormone concentrations and vitamin D deficiency are commonly encountered and contribute to the clinical syndromes of bone disorders in CKD, including hyperparathyroidism, osteomalacia, osteoporosis and adynamic bone disease. Mineral and bone abnormalities may also persist or arise de novo post-renal transplantation. The Kidney Disease Improving Global Outcomes organisation describes these mineral metabolism derangements and skeletal abnormalities as 'CKD Mineral and Bone Disorder'. Patients with this disorder have an increased risk of fracture, cardiovascular events and overall increased mortality. In light of the recently updated 2017 guidelines from the Kidney Disease Improving Global Outcomes, we present a clinical case-based discussion to highlight the complexities of investigating and managing the bone health of patients with CKD with a focus on these updates.Copyright © 2018 Royal Australasian College of Physicians

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). Hypothesis: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. Method(s): A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c >= 6.5% or >= 48 mmol/mol. Anaemia was defined as Hb < 130 g/L or < 120 g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed. Result(s): Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR > 3 mg/mmol and 18.2% with eGFR < 60 mL/min/1.73m2. Median bilirubin concentration was lower in females than males (6 v 8 mumol/L, p < 0.001) and in Aboriginal than TSI participants (6 v 9.5 mumol/L, p < 0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). Conclusion(s): Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed.Copyright © 2017 The Canadian Society of Clinical Chemists

Objective: Adrenal vein sampling (AVS) is crucial for differentiating between unilateral and bilateral causes of primary aldosteronism (PA). However, there is a lack of uniform agreement regarding the use of adrenocorticotropic hormone (ACTH) stimulation during AVS. This study compares basal and post-ACTH aldosterone and cortisol values to evaluate the role of ACTH stimulation in AVS. Method(s): An audit was conducted of 127 AVS procedures performed at Austin Health (Jan 2001-Dec 2015) and Monash Health (Jan 2010-Dec 2015). Both centres performed AVS pre- and post-ACTH using sequential catheterization. Patient demographics, screening aldosterone and renin concentrations, AVS aldosterone and cortisol levels pre- and post- ACTH stimulation, adrenal imaging and surgical outcomes including adrenal histology were retrieved. Successful cannulation and lateralization were defined by the selectivity index (SI) and the lateralization index (LI) respectively. Result(s): ACTH significantly increased the rate of successful cannulation (SI > 2 pre- or > 3 post-ACTH), from 70% to 95% on the left (P < 0.001), and from 54% to 68% on the right (P = 0.03). However ACTH stimulation significantly lowered the LI (P = 0.03). Using LI> 3 pre-ACTH and LI > 4 post-ACTH as thresholds for lateralization, the number of unilateral cases decreased from 70% pre-ACTH to 56% post- ACTH. 17 cases would have been re-classified as bilateral despite basal lateralization. Eight of these patients elected to undergo unilateral adrenalectomy, six of whom were found to have adenomas on histology and had a biochemical cure together with normalization or improvement in blood pressure. All six patients had post-ACTH LI > 2. Conclusion(s): ACTH stimulation increased the rate of successful cannulation in AVS but masked lateralization in six cases of proven adenoma. Basal LI appears to be the more reliable indicator of lateralization although a post-ACTH LI using a lower threshold of >2 also supports the diagnosi

Objective: To determine the prevalence of diabetes in inpatients in Melbourne hospitals. Design(s): Point prevalence survey of all inpatients in each hospital on a single day between 30 November 2010 and 22 November 2012. Setting(s): 11 hospitals in metropolitan Melbourne including community, secondary and tertiary hospitals and one aged care and rehabilitation centre. Participant(s): 2308 adult inpatients in all wards apart from intensive care, emergency, obstetrics and psychiatry. Main Outcome Measure(s): Point prevalence of self-reported diabetes, details of current medication, self-reported frequency of complications. Result(s): Diabetes status was obtained in 2273 of 2308 inpatients (98.5%). Of these, 562 (24.7%) had diabetes (95% CI, 22.9%-26.5%). Diabetes prevalence ranged from 15.7% to 35.1% in diff erent hospitals (P < 0.001). Patients with diabetes were older, heavier and more likely to be taking lipidlowering, antihypertensive and blood-thinning medications. Of 388 patients with complete medication information, 270 (69.6%) were taking oral hypoglycaemic agents alone or in combination with insulin, 158 (40.7%) were treated with insulin (67 [17.3%] with insulin alone) and 51 (13.1%) were not taking medication for diabetes. The frequency of diabetes complications was very high: 207/290 (71.4%) for any microvascular complication, 275/527 (52.2%) for any macrovascular complication and 227/276 (82.2%) for any complication. Conclusion(s): The high burden of diabetes in Melbourne hospital inpatients has major implications for patient health and health care expenditure. Optimising care of these high-risk patients has the potential to decrease inpatient morbidity and length of stay as well as preventing or delaying future complications. A formal Australian national audit of inpatient diabetes would determine its true prevalence and consequences, allowing rational planning to deal with shortcomings in its management.Copyright © MJA 2014, All rights reserved.

To determine the prevalence of diabetes in inpatients in Melbourne hospitals. Point prevalence survey of all inpatients in each hospital on a single day between 30 November 2010 and 22 November 2012. 11 hospitals in metropolitan Melbourne including community, secondary and tertiary hospitals and one aged care and rehabilitation centre. 2308 adult inpatients in all wards apart from intensive care, emergency, obstetrics and psychiatry. Point prevalence of self-reported diabetes, details of current medication, self-reported frequency of complications. Diabetes status was obtained in 2273 of 2308 inpatients (98.5%). Of these, 562 (24.7%) had diabetes (95% CI, 22.9%-26.5%). Diabetes prevalence ranged from 15.7% to 35.1% in different hospitals (P < 0.001). Patients with diabetes were older, heavier and more likely to be taking lipid-lowering, antihypertensive and blood-thinning medications. Of 388 patients with complete medication information, 270 (69.6%) were taking oral hypoglycaemic agents alone or in combination with insulin, 158 (40.7%) were treated with insulin (67 [17.3%] with insulin alone) and 51 (13.1%) were not taking medication for diabetes. The frequency of diabetes complications was very high: 207/290 (71.4%) for any microvascular complication, 275/527 (52.2%) for any macrovascular complication and 227/276 (82.2%) for any complication. The high burden of diabetes in Melbourne hospital inpatients has major implications for patient health and health care expenditure. Optimising care of these high-risk patients has the potential to decrease inpatient morbidity and length of stay as well as preventing or delaying future complications. A formal Australian national audit of inpatient diabetes would determine its true prevalence and consequences, allowing rational planning to deal with shortcomings in its management.

OBJECTIVE-The structural basis of normoalbuminuric renal insufficiency in patients with type 2 diabetes remains to be elucidated. We compared renal biopsy findings in patients with type 2 diabetes and estimated glomerular filtration rate (eGFR) and measured GFR of <60 mL/min/1.73 m2, associated with either normo-, micro-, or macroalbuminuria. RESEARCH DESIGN AND METHODS-In patients with normo- (n = 8) ormicroalbuminuria (n = 6), renal biopsies were performed according to a research protocol. In patients with macroalbuminuria (n = 17), biopsies were performed according to clinical indication. Findings were categorized according to the Fioretto classification: category 1 (C1), normal/near normal; category 2 (C2), typical diabetic nephropathy (DN)with predominantly glomerular changes; and category 3 (C3), atypical with disproportionately severe interstitial/tubular/vascular damage and with no/mild diabetic glomerular changes. RESULTS-In our study population (mean eGFR 35 mL/min/1.73 m2), typical glomerular changes (C2) of DN were observed in 22 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 subjects with normoalbuminuria (P = 0.002). By contrast, predominantly interstitial or vascular changes (C3) were seen in only 1 of 23 subjects with micro- or macroalbuminuria compared with 3 of 8 normoalbuminuric subjects (P = 0.08). Mesangial area increased progressively fromnormal controls to patients with type 2 diabetes and normo-, micro-, and macroalbuminuria. Varying degrees of arteriosclerosis, although not necessarily the predominant pattern, were seen in seven of eight subjects with normoalbuminuria. CONCLUSIONS-Typical renal structural changes of DN were observed in patients with type 2 diabetes and elevated albuminuria. By contrast, in normoalbuminuric renal insufficiency, these changes were seen less frequently, likely reflecting greater contributions from aging, hypertension, and arteriosclerosis. © 2013 by the American Diabetes Association.