Endocrinology

The laws governing treatment consent in gender dysphoria have rapidly evolved in the past two decades, with the uncertainty, and at times confusion, regarding the law resulting in volatility in clinical practice

Calina Ouliaris

A 67-year-old man presented to his rural GP with left facial pain

Timothy R Holmes · Jenny L Hepschke · Ian Jacobson · Anthony Maloof

A 31-year-old Caucasian woman presented to the emergency department with a 1-day history of vomiting and lethargy, but no other symptoms

Nardeen S Habashy · Hwang Tan · Emily J Hibbert

A 62-year-old man presented with left eye swelling and 3 weeks of intermittent epiphora without visual disturbance

Douglas Dunn · Sebastian Brown · Sartaj Sandhu · Domit Azar

Annual audits of practice, national guidelines, specialist diabetes care teams, and increased patient participation are all needed

Jeffrey D Zajac · Sofianos Andrikopoulos

In Australia, there is a paucity of coordinated strategies for preventing, detecting, and managing NAFLD

Lucy Gracen · Elizabeth E Powell

Intensive metabolic control reduces the incidence and progression of diabetes‐related micro‐ and macrovascular complications.1,2 Nevertheless, the risk of developing cardiovascular disease is higher for people with diabetes,3 although cardiovascular disease incidence rates are generally declining more rapidly for people with diabetes than for other people.4,5 We analysed hospital discharge data from the Victorian Admitted Episode Dataset6 for 1 January 1999 – 31 December 2016. We identified incident cases of three cardiovascular disease complications (acute myocardial infarction [AMI], stroke, and heart failure) by International Statistical Classification of Diseases, tenth revision, Australian modification (ICD‐10‐AM) codes. Data for 1999‒2003 were examined to ensure that admissions during the observation period (2004‒2016) were index admissions for the specific complication, but were not included in our main analysis. Admission rates were separately calculated for people with type 1 or type 2 diabetes (numbers of people with diagnosed diabetes, by year, were obtained from the National Diabetes Services Scheme, which captures 80–90% of diabetes diagnoses7) and for people without diabetes (derived from Australian Bureau of Statistics census data8). We analysed changes in admission rates by Joinpoint regression (https://surveillance.cancer.gov/joinpoint); points at which changes in the direction or magnitude of linear trends were statistically significant (P < 0.05) were determined with permutation tests. Each trend segment was described by an annual percentage change (APC), and the change for the entire study period as the mean APC (further details: online Supporting Information). The study was approved by the St Vincent’s Hospital Melbourne Human Research Ethics Committee (HREC/18/SVHM/146). A total of 382 107 patients were admitted to Victorian hospitals during 2004–2016 with cardiovascular complications: 278 991 without diabetes (73%), 3645 with type 1 diabetes (1%), and 99 471 with type 2 diabetes (26%). AMI admission rates declined during this period for people with type 1 (mean APC, –7.7%; 95% confidence interval [CI], –13.4% to –1.5%) or type 2 diabetes (mean APC, –11.4%; 95% CI, –13.0% to –9.9%), as well as for people without diabetes (mean APC, –5.0%; 95% CI, –6.7% to –3.4%) (Box 1, Box 2). Stroke admission rates declined significantly during 2004–2016 for people with type 1 diabetes (mean APC, –7.2%; 95% CI, –12.2% to –1.9%); for people with type 2 diabetes, rates declined during 2005–2011 and 2014–2016, but not during 2011–2014 (overall change: –11.9%; 95% CI, –17.0% to –6.5%). For patients without diabetes, the decline during 2005–2014 was significant (mean APC, –4.1%; 95% CI, –5.8% to –2.3%), but not during 2015–2016 (Box 1, Box 2). Admissions for heart failure declined during 2004–2016 for people with type 1 diabetes (mean APC, –10.3%; 95% CI, –14.1% to –6.4%) or type 2 diabetes (mean APC, –9.2%; 95% CI, –11.0% to –7.3%), and also for people without diabetes (mean APC, –2.8%; 95% CI, –4.1% to –1.5%) (Box 1, Box 2). As hospital discharge coding data do not provide information on metabolic control or medication use, we could not assess whether cardiovascular risk factor modification and use of specific medications were associated with changes in admission rates. We also lacked information on disease duration for patients with hospital‐coded diabetes. Further, we have counted admissions of any patients who had presented with complications before 1998 (ie, outside our 5‐year clearance period) as incident admissions; these patients would be at very high risk of further admissions, and their inclusion may have inflated the admission rates we report for the observation period of our study. Few recent studies have assessed outcomes for all three cardiovascular complications in a single investigation. Cardiovascular complication‐related admissions to Victorian hospitals declined during 2004–2016 more rapidly for people with diabetes than for those without diabetes. The relatively greater absolute decline in the numbers of admissions of people with diabetes may be related to the fact that they are considered to be at high risk for cardiovascular disease and are therefore treated more aggressively; the scope for reducing risk with multifactorial target‐driven interventions is greater in these patients. Nevertheless, admission rates for cardiovascular complications of people with diabetes remain relatively high. Box 1 – Age‐ and sex‐adjusted admission rates for cardiovascular complications (with 95% confidence intervals), Victoria, 2004–2016, by diabetes status of patients Box 2 – Annual percentage change (APC) in admissions for cardiovascular complications, Victoria, 2004–2016, by diabetes status Change in event rate, 2004–2016* Change in event rate, by period* Cardiovascular complication and diabetes status Admissions Overall change (95% CI) Mean APC (95% CI%) Mean APC (95% CI) Acute myocardial infarction No diabetes 114 965 –24.8% (–24.9% to –24.7%) –5.0% (–6.7% to –3.4%) — Type 1 diabetes 1272 –7.7% (–8.8% to –6.7%) –7.7% (–13.4% to –1.5%) 1. 2005–2009: +7.0% (–9.7% to +22.8%) 2. 2009–2016: –15.1% (–21.3% to –8.7%) Type 2 diabetes 15 278 –69.0% (–69.0% to –68.8%) –11.4% (–13.0% to –9.9%) — Stroke No diabetes 52 320 –10.9% (–13.6% to –10.6%) –1.7% (–4.9% to +1.5%) 1. 2005–2014: –4.1% (–5.8% to –2.3%) 2. 2014–2016: +9.6% (–10.2% to +33.8%) Type 1 diabetes 504 –44.4% (–50.0% to –41.4%) –7.2% (–12.2% to –1.9%) — Type 2 diabetes 17 440 –68.0% (–68.0% to –67.9%) –11.9% (–17.0% to –6.5%) 1. 2005–2011: –14.7% (–17.6% to –11.7%) 2. 2011–2014: +5.8% (–19.0% to +38.2%) 3. 2014–2016: –26.1% (–39.8% to –9.2%) Heart failure No diabetes 135 524 –22.2% (–22.3% to –22.2%) –2.8% (–4.1% to –1.5%) — Type 1 diabetes 1393 –55.1% (–58.6% to –52.4%) –10.3% (–14.1% to –6.4%) — Type 2 diabetes 52 831 –67.3% (–67.4% to –67.3%) –9.2% (–11.0% to –7.3%) — * Adjusted for age and sex. Event rates for 2004 and 2016 are included in the expanded version of this table in the online Supporting Information.

Katerina V Kiburg · Andrew I MacIsaac · Andrew Wilson · Vijaya Sundararajan · Richard J MacIsaac

Introduction: Type 1 diabetes presents significant challenges for optimal management. Despite intensive glycaemic control being the standard of care for several decades, glycaemic targets are infrequently achieved and the burden of complications remains high. Therefore, the advancement of diabetes management technologies has a major role in reducing the clinical and economic impact of the disease on people living with type 1 diabetes and on health care systems. However, a national framework is needed to ensure equitable and sustainable implementation of these technologies as part of holistic care. Main recommendations: This consensus statement considers technologies for insulin delivery, glucose sensing and insulin dose advice that are commercially available in Australia. While international position statements have provided recommendations for technology implementation, the ADS/ADEA/APEG/ADIPS Working Group believes that focus needs to shift from strict trial‐based glycaemic criteria towards engagement and individualised management goals that consider the broad spectrum of benefits offered by technologies. Changes in management as result of this statement: This Australian consensus statement from peak national bodies for the management of diabetes across the lifespan outlines a national framework for the optimal implementation of technologies for people with type 1 diabetes. The Working Group highlights issues regarding equity of access to technologies and services, scope of clinical practice, credentialling and accreditation requirements, regulatory issues with “do‐it‐yourself” technology, national benchmarking, safety reporting, and ongoing patient advocacy.

Anthony J Pease · Sofianos Andrikopoulos · Mary B Abraham · Maria E Craig · Brett Fenton · Jane Overland · Sarah Price · David Simmons · Glynis P Ross

A 56-year-old man presented with cough, dyspnoea and urinary symptoms

Michael A Cilento · Christopher M Hocking

Objectives: To assess the quality of care for patients with diabetes in Queensland hospitals, including blood glucose control, rates of hospital‐acquired harm, the incidence of insulin prescription and management errors, and appropriate foot and peri‐operative care. Design, setting: Cross‐sectional audit of 27 public hospitals in Queensland: four of five tertiary/quaternary referral centres, four of seven large regional or outer metropolitan hospitals, seven of 13 smaller outer metropolitan or small regional hospitals, and 12 of 88 hospitals in rural or remote locations. Participants: 850 adult inpatients with diabetes mellitus in medical, surgical, mental health, high dependency, or intensive care wards. Results: Twenty‐seven of 115 public hospitals that admit acute inpatients participated in the audit, including 4175 of 6652 eligible acute hospital beds in Queensland. A total of 1003 patients had diabetes (24%), and data were collected for 850 (85%). Their mean age was 65.9 years (SD, 15.1 years), 357 were women (42%), and their mean HbA1c level was 66 mmol/mol (SD, 26 mmol/mol). Rates of good diabetes days (appropriate monitoring, no more than one blood glucose measurement greater than 10 mmol/L, and none below 5 mmol/L) were low in patients with type 1 diabetes (22.1 per 100 patient‐days) or type 2 diabetes treated with insulin (40.1 per 100 patient‐days); hypoglycaemia rates were high for patients with type 1 diabetes mellitus (24.1 episodes per 100 patient‐days). One or more medication errors were identified for 201 patients (32%), including insulin prescribing errors for 127 patients (39%). Four patients with type 1 diabetes experienced diabetic ketoacidosis in hospital (8%); 121 patients (14%) met the criteria for review by a specialist diabetes team but were not reviewed by any diabetes specialist (medical, nursing, allied health). Conclusions: We identified several deficits in inpatient diabetes management in Queensland, including high rates of medication error and hospital‐acquired harm and low rates of appropriate glycaemic control, particularly for patients treated with insulin. These deficits require attention, and ongoing evaluation of outcomes is necessary.

Peter Donovan · Jade Eccles-Smith · Nicola Hinton · Clare Cutmore · Kerry Porter · Jennifer Abel · Lee Allam · Alexis Dermedgoglou · Gaurav Puri

To the Editor: The Coroners Court of Victoria made several recommendations in 2020 after a 38‐year‐old man died alone at home.1 The cause of death was determined to be sepsis in the setting of an adrenal crisis. The key coronial recommendations1 were to emphasise to the general medical community the non‐specific nature of symptoms of impending adrenal crisis (eg, fatigue, nausea, loss of appetite, vomiting),2 to record the diagnosis of adrenal insufficiency prominently as an alert in medical records,3 and to encourage endocrinologists to provide sick day or steroid stress dosing letters to patients, general practitioners, and family members and carers. The Endocrine Society of Australia (ESA) endorses these recommendations. A standard patient letter has been developed and is now available on the ESA’s Hormones Australia website.4 We strongly support medical record alerts for the diagnosis of cortisol deficiency due to Addison disease or hypopituitarism. It is crucial for doctors to have a high index of suspicion for the possibility of impending adrenal crisis in a patient with known adrenal insufficiency. The clinical syndrome evolves from acute adrenal insufficiency with symptoms of malaise, nausea and lethargy — all of which are non‐specific and may be considered part of another pathological process — to adrenal crisis, which is associated with hypotension initially manifest by postural blood pressure falls greater than 20 mmHg.2,3 Prevention involves advice on stress dosing:1 triple glucocorticoid dosing for 3 days (ie, the 3 × 3 rule),2 parenteral hydrocortisone at home (SOLU‐CORTEF Act‐O‐Vial, Pfizer) when unable to take tablets,3 and the availability of personal alerts (eg, a MedicAlert bracelet [MedicAlert Foundation], a steroid card) when the person is delirious or very unwell (Box). The incidence of adrenal crises is increasing in Australia.3 Missed cases or failure to treat them because of overestimation of the risks of glucocorticoid therapy are unfortunately too common. Box – Practical steps to reduce the risk of adrenal crisis Ensure that others are aware of the diagnosis of established adrenal insufficiency Prominent medical alert in GP and hospital medical records Patient carries either a steroid card, which lists diagnosis and glucocorticoid therapy, or uses a MedicAlert bracelet (MedicAlert Foundation) A sick day or steroid stress dosing letter should be provided by the endocrinologist to the patient with adrenal insufficiency, with a copy to their GP Encourage the patient with adrenal insufficiency to provide copies of the letter to their next of kin, close relatives or carer Have a high index of suspicion for an impending adrenal crisis Beware of non-specific symptoms of nausea, vomiting or lethargy in a patient with established adrenal insufficiency Prevent an adrenal crisis in patients with established adrenal insufficiency When unwell, follow the 3 × 3 rule (ie, three times the usual glucocorticoid dose for 3 days) and seek urgent medical attention if not improving Promptly treat an impending adrenal crisis The patient and/or carer should be trained to administer 100 mg SOLU‐CORTEF Act‐O‐Vial (Pfizer) intramuscularly* if vomiting occurs or the patient is unable to swallow tablets GP = general practitioner. * Some authorities recommend the off‐label use of a subcutaneous injection as this is easier for patient and/or carer to administer.

Peter S Hamblin · Bu B Yeap · David J Torpy

To the Editor: Siru and colleagues have raised potential concerns about the strategy recommended by the Australian Diabetes Society (ADS) and other peak bodies to diagnose gestational diabetes (GDM) during the coronavirus disease 2019 (COVID‐19) pandemic.1 In their study, 46% of subjects diagnosed with GDM had a fasting blood glucose level (BGL) < 4.7 mmol/L but elevated post‐load blood glucose levels, and would be missed by the ADS‐recommended strategy. The authors suggested that this exposes women and their newborns to significant risks with the potential for significant harm. No outcome data were provided to justify these assertions. Evidence from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study suggests that such women do not have increased rates of pregnancy‐associated complications.2,3,4,5 The subgroups with the highest odds ratios for newborns who were large for gestational age had an elevated fasting BGL and any elevation of post‐load BGL (odds ratio > 3), whereas subgroups having only elevated fasting or post‐load BGL had a considerably lower odds ratio, equivalent to the diagnostic threshold for GDM of 1.75.2 Further, women with a fasting BGL < 4.5 mmol/L had low rates of some complications irrespective of their post‐load BGL.3 A subsequent analysis of 6128 patients from five centres involved in the HAPO study did not observe any increase in pregnancy‐associated complications in women with a fasting BGL below the 75th centile (4.6 mmol/L).4 A recent analysis of 5974 women in the HAPO study assessed the ADS‐recommended COVID‐19 GDM strategy and reported no increase in any complication.5 There were fewer cases of pregnancy‐associated hypertension and caesarean delivery, with similar rates of large‐for‐gestational‐age newborns and neonatal hypoglycaemia. These data provide reassurance. There is no evidence of harm. When this strategy is used, women with a fasting BGL < 4.7 mmol/L are spared being labelled with GDM and do not require education, monitoring, more frequent follow‐up or transfer to specialist services, freeing up valuable health care resources. Importantly, they will not be advised to inappropriately restrict their dietary intake or commence therapy with insulin or metformin with the potential for harm. An initial fasting BGL test would eliminate the need for a pregnancy oral glucose tolerance test in the majority of women, identifying a smaller group of women at risk of pregnancy‐associated complications where management can be more appropriately targeted.

Michael C d'Emden · Jacobus PJ Ungerer · Susan J Jersey

To the Editor: This retrospective population‐based study aimed to determine the incidence of type 2 diabetes from 2012 to 2019 in Western Australian youth aged under 16 years, and to examine temporal trends between 2000 and 2019, using data from the Western Australian Children’s Diabetes Database (WACDD).1 The data extracted for eligible patients diagnosed with type 2 diabetes, according to standard criteria,2 included diagnosis year, age, sex and self‐reported Aboriginal or Torres Strait Islander status. Poisson regression was used to determine incidence rates and trends by calendar year, sex, and Aboriginal or Torres Strait Islander status. This study received ethics approval from the Western Australian Child and Adolescent Health Service Human Research Ethics Committee (RGS0000002386). To ensure the validity of our findings, a secondary aim was to estimate completeness of the WACDD for type 2 diabetes diagnosed in patients aged under 16 years from 1999 to 2016. For this purpose, we used the capture–recapture method with two independent sources: the primary source was WACDD, and the secondary source was the National Diabetes Services Scheme (NDSS) database.3 We identified 224 eligible cases from WACDD (2000–2019), of which 129 (58%) were girls and 128 (57%) were Aboriginal or Torres Strait Islander children. The mean age at diagnosis of type 2 diabetes was 13.2 years (standard deviation, 2.0 years), with no differences observed by sex or Aboriginal or Torres Strait Islander status. The overall mean incidence was 2.3/100 000 (95% CI, 2.1–2.7), with an average annual increase of 5.2% (95% CI, 2.8–7.8%). No differences were observed in the mean incidence or incidence rate trends between boys and girls. The mean incidence in Aboriginal or Torres Strait Islander children was 18‐fold higher (incidence rate ratio, 18.31; 95% CI, 14.05–23.86) than in non‐Aboriginal or Torres Strait Islander children (Box). In addition, the incidence increased by an annual average of 6.2% (95% CI, 2.8–9.6%) in Aboriginal or Torres Strait Islander children compared with 3.9% (95% CI, 0.3–7.6%) in non‐Aboriginal or Torres Strait Islander children (Box). Of the 170 eligible cases identified in the WACDD, 107 were ascertained from both WACDD and NDSS, 40 from NDSS only, and 63 from WACDD only. Using the capture–recapture method,3 the WACDD was estimated as 73% complete. This study provides further evidence for the growing incidence of type 2 diabetes in Australian children and highlights the urgent need for community, public health providers, and government to address this disease and its significant burden in young people.4,5 Box – Case numbers, person years of observation, mean incidence (95% CI) and average annual increase in incidence (95% CI) by Aboriginal or Torres Strait Islander status for youth aged under 16 years diagnosed with type 2 diabetes in Western Australia (2000–2019) Non‐Aboriginal or Torres Strait Islander Aboriginal or Torres Strait Islander Combined Cases 96 (43%) 128 (57%) 224 (100%) Sex, female 54 (56%) 75 (59%) 139 (58%) Mean age at diagnosis (SD), years 13.6 (1.8) 13.0 (2.1) 13.2 (1.9) Age range at diagnosis, years 6.9–15.9 6.8–15.9 6.8–15.9 Total person years 8 884 383 644 157 9 528 540 Mean annual incidence (95% CI) per 100 000 person years 1.1 (0.9–1.3) 19.9 (16.6–23.6) 2.3 (2.1–2.7) Average annual increase in incidence (95% CI) 3.9% (0.3–7.6%) 6.2% (2.8–9.6%) 5.2% (2.8–7.8%) CI = confidence interval; SD = standard deviation.

Aveni Haynes · Jacqueline A Curran · Elizabeth A Davis

Technology is changing the way that people with type 1 diabetes are monitoring and managing their blood glucose levels Diabetes technologies have transformed management options in type 1 diabetes. The most notable innovations include the commercialisation of insulin pumps, advancements in glucose monitoring and the capacity for these technologies to interact. New technologies offer enhanced flexibility in insulin delivery and opportunities to improve glucose levels and enhance quality of life. Recognising these benefits, the uptake of advanced technologies in Australians with type 1 diabetes has increased. In 2018–2019, 41% of children and 26% of adults attending hospital diabetes clinics managed their type 1 diabetes with insulin pumps, and 55% of children and 13% of adults newly commenced continuous glucose monitoring (CGM).1 In this article, we provide a guide to current diabetes technologies available in Australia, describe their benefits and discuss important factors in assessing an individual’s suitability. Continuous glucose monitoring Accurate and accessible glucose monitoring is key to effective diabetes management. Finger‐prick testing of capillary blood for self‐monitoring of blood glucose (SMBG) became commercially available in the 1980s, and CGM since 1999. CGM is distinguished from SMBG by the measurement of glucose concentration within interstitial fluid by a small subcutaneous glucose‐sensing electrode. Data are transmitted to a receiving device (eg, insulin pump or smartphone) and converted into a continuous graphic display. Interstitial glucose concentrations correlate with plasma glucose, albeit with an average 7–8 minute time lag for equilibration of glucose between blood and the interstitial compartment. This delay is exaggerated at times of rapidly changing glucose. CGM systems come in different forms, with the main distinguishing features being the capacity to alert users and/or carers to high and/or low blood glucose levels set to individual preference. Various systems are available (Box 1).2,3 Product selection depends on the desirability of alarm functions, ease of sensor application, need for finger‐prick calibration, cost, and connectivity of the device to existing technologies (insulin pumps, Apple v Android systems). Modern CGM systems are reliable. Their performance is assessed by the mean absolute relative difference, an accuracy metric expressed as the percentage difference relative to a reference glucose concentration. CGM devices with a mean absolute relative difference < 10% are appropriate for treatment decisions.2,4 To optimise sensor performance, SMBG testing is still required to calibrate a number of real‐time CGM devices, yet devices are increasingly reliable such that newer factory calibrated devices no longer require user calibrations5 — a welcome feature for convenience and reduced finger‐prick burden. CGM offers several benefits to users, including on‐demand glucose testing, trend arrows, alarm functions and easy detection of out‐of‐range glucose levels. For clinicians, CGM offers additional data beyond glycated haemoglobin (HbA1c) measurements. HbA1c measurements are point estimates of haemoglobin glycation over 3 months, whereas CGM displays day‐to‐day glucose variability that often challenges people with type 1 diabetes. Consensus statements have attempted to harmonise the various commercially available CGM systems into a common reporting method to aid comparison between devices and also provide clinicians and users with more clinically meaningful data and targets (Box 2).2,6,7 Clinical trials provide evidence that CGM use may improve glycaemia in type 1 diabetes. A recent meta‐analysis of 15 randomised controlled trials comparing CGM with standard care (usually SMBG) in people with either type 1 or type 2 diabetes over 12–36 weeks found that CGM was associated with a slight reduction in HbA1c levels (weighted mean difference, − 0.17%), and increased time in range (TIR; 71 minutes/day).8 Added up over a year the benefit equates to an additional 18 days of TIR. The effect on TIR was independent of diabetes type, or method of insulin delivery (insulin pump v needle injections). Overall, studies favour CGM to improve glucose variability (optimal coefficient of variation in diabetes management, 34%; coefficient of variation reduced by 3.0–6.7%) and reduce hypoglycaemia (0.4–1.2 hours reduction in time spent with glucose levels < 3.9 mmol/L) compared with SMBG.2 The benefits of CGM and flash glucose monitoring for type 1 diabetes management have been recognised by the Australian Government, which first pledged $54 million in 2016 to fully subsidise CGM in people under 21 years of age. In 2019, a further $100 million in subsidies was added. Eligibility criteria were again expanded in March 2020 (Box 3).9 Insulin pumps An insulin pump delivers short‐acting insulin continuously via a cannula self‐inserted into subcutaneous tissue. In the 1970s, the first insulin pumps were large and bulky and delivered a single basal rate of insulin. Modern pumps are more discrete, the size of a pager. An insulin pump set‐up includes two major components (Box 4): Insulin pump — case with display, battery and an insulin reservoir connected to a plunger that controls the passage of insulin into the line tubing. The insulin pump is programmed to deliver continuous quick‐acting insulin in equal aliquots (0.01–0.025 mL) across an hour depending on the pre‐set rate to replicate basal insulin. Programmed rates can be customised to vary across a 24‐hour period, distinguishing delivery from long‐acting insulin delivered at an inflexible basal rate. The user must initiate bolus doses for meals or for correction of an elevated glucose reading, but pre‐programmed settings provide dose calculations (insulin‐to-carbohydrate ratio for meals, and insulin sensitivity factor for correction doses). Line tubing and infusion set — up to 60 cm of thin plastic tubing connects the insulin reservoir to a subcutaneous teflon cannula (tubeless insulin patch pumps with variable hourly rates are not currently available in Australia). Potential benefits of insulin pumps include: ► Flexibility in dosing — useful for extreme insulin sensitivity, erratic schedules, more convenient and frequent bolusing, to accommodate exercise, or to manage the dawn phenomenon (increased insulin requirements in the early morning period due to counter‐regulatory hormone secretion). ► Bolus calculation capacity. ► Less frequent insertion events (about every 3 days) — favourable for individuals with needle phobia. ► Insulin delivery and glucose data can be generated electronically and remotely for review. As only quick‐acting insulin is used in insulin pumps, insulin deficiency (leading to possible diabetic ketoacidosis) may occur within 2–3 hours of discontinuation of the insulin pump, or in the event of set occlusion. Set occlusion is one of the leading causes of ketoacidosis in insulin pump‐treated individuals but is rapidly corrected with recommencement of insulin in the absence of intercurrent infection (Box 5). However, insulin pump use has not resulted in the increased diabetic ketoacidosis events anticipated when first introduced, aided by appropriate education.10 There are out‐of‐pocket costs, especially for individuals without private health insurance, and running costs are higher than with insulin injection. Wearing an externally attached device to the body 24 hours a day is a deterrent to some, but a convenience for others who dislike carrying needle tips and insulin pens. Insulin pumps can be used either as a stand‐alone device or in conjunction with CGM sensors (Box 6). Sensor‐augmented insulin pumps have the added benefits of suspended insulin delivery for predicted low glucose (predictive low glucose suspend), or at the threshold of hypoglycaemia (low glucose suspend) to reduce the frequency and duration of hypoglycaemia. In a study of individuals with documented nocturnal hypoglycaemia, those randomised to insulin pumps with low glucose suspend function for 3 months had 32% less frequent hypoglycaemia than without suspend function.11 Other trials have also demonstrated reduced time in hypoglycaemia without increase in time in hyperglycaemia.12 The latest insulin pump systems (hybrid closed loop; HCL) can provide a further degree of automation of insulin delivery. HCL pumps provide real‐time adjustment of insulin delivery in response to ambient glucose levels detected by a CGM sensor, via an inbuilt control algorithm. The user is still required to manually deliver boluses for meals or adjust insulin for exercise. A recent study comparing HCL to sensor‐augmented insulin pump therapy reported improved TIR during daytime hours as well as overnight, and a small reduction in time in hypoglycaemia over 6 months.13 There is currently only one registered HCL insulin pump in Australia. Future technologies may provide further integration of CGM and insulin pump devices via phone‐based applications. Tailoring treatments to individual needs The optimal approach for the management of type 1 diabetes depends on individual and practical considerations. Initiation of insulin pump therapy requires extended consultation to discuss device selection and cannula insertion technique, and review carbohydrate counting and troubleshooting (including diabetic ketoacidosis risk mitigation). It also requires a multidisciplinary approach involving an endocrinologist, credentialled diabetes educator and dietitian.14 In concert with the individual with diabetes, factors to discuss include: the need for alerts and alarms: presence of hypoglycaemia unawareness and susceptibility to alarm fatigue; affordability and eligibility for CGM supplied under the National Diabetes Services Scheme (Box 3); access to training and education; customisation of glucose targets for pregnancy, age and comorbidities; ability to use software to upload data and share reports with health professionals; and allergies to cannula or CGM site adhesives. Conclusion Diabetes technologies are being increasingly adopted by people with type 1 diabetes, and clinicians should familiarise themselves with the spectrum of devices. These advancements offer potential benefits for people with diabetes, although prescribing these devices requires evaluation of cost and benefit for the individual. Human factors are the main determinant of success and satisfaction, highlighting the importance of consideration of the needs of the individual. Box 1 – Types of continuous glucose monitoring (CGM) systems2,3 Professional (retrospective): professional CGMs were the first CGM systems approved by the United States Food and Drug Administration in 1999. They provide blinded glucose data for review by a health care provider. The iPro (Medtronic) and Freestyle Libre Pro (Abbott) are currently available systems in Australia. Real‐time CGM: patient‐inserted systems include Guardian (Medtronic), Guardian Connect (Medtronic) and G6 (Dexcom). The Eversense (Senseonics) CGM implantable system is inserted subcutaneously by a physician and worn for 90–180 days with a transmitter adherent to the overlying skin with alert capacity (not currently available in Australia). Intermittently viewed CGM or flash glucose monitoring: Freestyle Libre for continuous glucose measurements shown retrospectively at the time of physical scanning of the sensor does not have alert capacity. Freestyle Libre 2 will have optional alerts but is not yet available in Australia. Box 2 – Internationally accepted continuous glucose monitoring (CGM) metrics for clinical use and comparison between devices (adapted from guidelines)2,6,7 Percentage sensor wear and data captured — to gauge completeness of data capture (optimal wear time assessed as > 70% capture across a 14‐day time period) Mean glucose — the sum of all glucose levels, divided by number of measurements; a surrogate of overall glucose control, with reasonable correlation with glycated haemoglobin Glucose variability — standard deviation of glucose/mean glucose × 100 = coefficient of variation (CV); goal is CV < 36% in type 1 diabetes Time in range (3.9–10.0 mmol/L) — aim > 70%; the ranges can be tailored to the individual depending on their age and comorbidities (eg, older individuals or pregnancy) and provide an estimate of level of current glycaemic control otherwise not reflected in a glycated haemoglobin measurement Time in hypoglycaemia: ► < 3.9 mmol/L — goal < 4% (includes proportion values < 3.0 mmol/L) ► < 3.0 mmol/L — goal < 1% ► number of CGM events < 3.0 mmol/L for 15 minutes or more in previous 2 weeks — focuses on the importance of moderate hypoglycaemia Time in hyperglycaemia: ► 10 mmol/L — goal < 25% (including time > 13.9 mmol/L) ► 13.9 mmol/L — goal < 5%. Other reportable data (from insulin pump downloads): ► total daily insulin, % basal — a summary of current total insulin delivery, split into dose delivered as basal and bolus insulin; this allows for comparison between visits Standardisation of CGM reporting improves comparisons between devices and treatments and enhances decisions in diabetes care for both clinicians and people with diabetes Box 3 – Access to subsidised continuous glucose monitoring (CGM) through the National Diabetes Services Scheme (NDSS)*9 The following groups can access CGM or flash glucose monitoring through the NDSS: Children and young people under 21 years of age with type 1 diabetes Children and young people with conditions very similar to type 1 diabetes, such as cystic fibrosis‐related diabetes or forms of genetic diabetes (including maturity onset diabetes of the young), who require insulin Women with type 1 diabetes who are actively planning pregnancy (up to 12 months before conception), pregnant or immediately post‐pregnancy (pregnancy plus 3 months from expected date of confinement) People with type 1 diabetes aged 21 years or older who have concessional status Applications can be made through the patient’s credentialled diabetes educator or endocrinologist *Criteria valid from 1 March 2020. Box 4 – Major components of insulin pump and continuous glucose monitoring (CGM) set‐up Box 5 – Steps in managing ketosis caused by insulin pump line occlusion (in the absence of vomiting) Insulin pen injection using pump‐advised correction dose for high blood glucose Replace insulin pump cannula set Run increased basal insulin rates (200%) temporarily for 2 hours to restore subcutaneous insulin reservoir and missed insulin At 2 hours, deliver correction insulin dose with insulin pump Monitor blood ketones every 3–4 hours using a ketone meter to ensure ketone levels < 1.5 mmol/L Box 6 – Options for insulin delivery and glucose monitoring CGM = continuous glucose monitoring; HCL = hybrid closed loop; MDI = multiple daily injections; PLGS = predictive low glucose suspend; SMBG = self‐monitoring of blood glucose.

Jennifer R Snaith · D Jane Holmes‐Walker

To the Editor: We would like to highlight some points arising from the discussion by Hamblin and colleagues regarding euglycaemic diabetic ketoacidosis associated with sodium–glucose cotransporter type 2 (SGLT2) inhibitors.1 First, clinicians should be aware that this condition occurs not only in the perioperative context but also in systemically unwell patients with medical problems. Apart from the periprocedural insult, four categories of precipitating factors are recognised: intercurrent illness; dietary modifications (eg, prolonged fasting, very low calorie diet); medication changes (especially reducing or stopping insulin); and health system factors (eg, use in misdiagnosed type 2 rather than type 1 diabetes, and lack of patient education on the handling of SGLT2 inhibitors perioperatively).2,3,4 Second, diabetic ketoacidosis is more frequently reported with major surgery; for example, cardiothoracic, bariatric and abdominal surgery (postoperative ileus contributing). Third, clinicians should be aware that the current recommendations5 are based on low quality evidence and are potentially subjective. For example, the use of glycated haemoglobin levels < 75 mmol/mol (9%) as one factor to stratify lower patient risk, while intuitive, is not an unequivocal finding in the literature.4 We are in agreement that one should not overreact to capillary ketone levels in the perioperative period; these should be interpreted in conjunction with other acidosis markers (pH, bicarbonate and base excess). We differ regarding the authors’ statement that blood ketone testing is warranted only in unwell or symptomatic patients. In our clinical experience, we have encountered asymptomatic presentations with ketone levels > 2.0 mmol/L and acidosis before colonoscopy, despite the cessation of SGLT2 inhibitors on the day of the scheduled colonoscopy, necessitating deferral and inpatient treatment.6 Bowel preparation, diet modification and changes in diabetes medications are possible contributory factors for a minor procedure such as colonoscopy. Further, not all patients attend a pre‐assessment clinic and on the day of their procedure may be unable to recollect their diabetic medications. For these reasons, as recommended by the Australian Diabetes Society, it is prudent to check capillary ketones (using a single glucose strip) on admission for all patients with type 2 diabetes regardless of symptoms in the periprocedural period.5 Finally, in patients who have not held their SGLT2 inhibitors sufficiently or who have ketosis, the decision to proceed should depend on a nuanced appraisal integrating the complexity of the procedure, precipitating factors, and degree of acidosis.

Emily J Meyer · Venkatesan Thiruvenkatarajan · David Jesudason

To the Editor: One evening in February 1974, my fellow endocrinologist Don Gutteridge phoned me to tell me about an ABC television program that I had missed. It had featured an interview in Perth with Sir Richard Kirby, recently retired as Australia’s chief judge in industrial relations. He was showing typical signs of advanced thyroid deficiency. He had slow, coarse speech, periorbital oedema, sparse scalp hair, and was “not as sharp as a chief judge should be”. Don had phoned him at his hotel to discuss the diagnosis. The judge’s response was that he did indeed have symptoms including marked cold intolerance and he had coronary artery disease. Don firmly advised him to have his thyroid tested as soon as possible and in addition he wrote to Sir Richard’s Melbourne physician pointing out that caution was needed when starting thyroxine therapy if the patient had heart disease. Later a Christmas card arrived: “Sincere thanks for a timely telephone call and advice to an old stager who was in need and did not know it … I’m on the treatment and ever since have been a younger, newer and better man.” The before‐and‐after photographs in Blanche d’Alpuget’s biography of Sir Richard1 show a marked improvement in his appearance (Box). He had been unwell for years. Two cardiologists had advised him to retire in 1969. By 1971, he was spending most of his time at his home in Berrara, NSW, feeling ill and sluggish despite a rigorous diet, no cigarettes and almost no alcohol. The story did not end there. In 1979, Don was invited to Sydney to appear on Channel 7’s This is your life television program featuring Sir Richard (https://www.fwc.gov.au>file>your‐life‐sir‐richard‐kirby). “I always saw you with a halo” enthused Sir Richard, sizing up the tall and rangy dark‐haired young doctor, “but I thought you must be an old bloke like me.” Others on the show included Bob Hawke, then President of the ACTU, past Prime Minister Gough Whitlam, and many legal colleagues. Kirby served on three Royal Commissions. He assisted in the mediation of Indonesian Independence from Dutch rule for the United Nations, and he negotiated equal pay for Aboriginal stockmen. His passion to achieve equal pay for women could have been his greatest legacy had bad health not intervened. An undiscovered thyroid deficiency may well have altered the course of Australian industrial relations. Within a month of being treated with thyroxine, Kirby looked and felt better than for almost a decade. He died 27 years later in 2001 at the age of 97. The insidious and subtle onset of hypothyroidism can easily be overlooked by patients, relatives and doctors. Screening for thyroid‐stimulating hormone levels will ensure that an important diagnosis is not missed. Any suspicious symptoms should lead to a careful examination to identify the end‐organ signs of thyroid deficiency, including the slow relaxation phase of tendon reflexes, coarse dry skin, cool extremities and a hoarse voice.2 Box – Sir Richard Kirby before (A) and after (B) treatment for hypothyroidism

Timothy A Welborn

High cumulative doses are often unnecessary and can have major adverse effects

Christine F McDonald · Christopher J Worsnop

To the Editor: In Australia, gestational diabetes mellitus is diagnosed by 75 g oral glucose tolerance test (OGTT). The diagnostic criteria are fasting plasma glucose (FPG) ≥ 5.1 mmol/L, one‐hour glucose level ≥ 10.0 mmol/L, and/or 2‐hour glucose level ≥ 8.5 mmol/L.1,2 International consensus favours OGTT over single measures of glucose because, in the pivotal Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) study, hyperglycaemia at each time point was independently associated with adverse outcomes, individual measures were not well correlated with one another, and no single measure was clearly superior in predicting adverse outcomes, such as birthweight above the 90th percentile, shoulder dystocia and pre‐eclampsia.2,3 To reduce contact time at pathology collection centres during the coronavirus disease 2019 (COVID‐19) pandemic, measurement of FPG alone has been advocated.4,5 One guideline advised that a result below 4.7 mmol/L may not merit a follow‐up OGTT.4 Another advised diagnosing gestational diabetes mellitus by stand‐alone FPG greater than 5.1 mmol/L.5 To determine the proportion and characteristics of gestational diabetes mellitus cases that would be missed by using alternative criteria, we extracted the results of all obstetrician‐referred OGTTs performed by our private community‐based laboratory between January 2017 and April 2020. The analysis, including determination of Wilson score confidence intervals (CIs), was performed with SAS 9.4 (SAS Institute). Of 16 169 patients, 1790 (11.1%) were diagnosed with gestational diabetes mellitus by OGTT. A rule‐out threshold of FPG below 5.1 mmol/L would have resulted in 1202 cases (67%; 95% CI, 65–69%) being missed, and a threshold below 4.7 mmol/L would have resulted in 831 cases (46%; 95% CI, 44–49%) being missed (Box). Women with gestational diabetes mellitus and normal fasting glucose did not have significantly lower one‐ or 2‐hour concentrations than those with increased fasting glucose (data not shown). Missing the diagnosis of gestational diabetes mellitus exposes women and their newborns to significant risks, including birth weight above the 90th percentile, primary caesarean delivery, neonatal hypoglycaemia, premature delivery, shoulder dystocia or birth injury, intensive neonatal care, hyperbilirubinaemia and pre‐eclampsia. Use of fasting glucose to screen for gestational diabetes mellitus would miss a large proportion of cases, with the potential for significant harm to mothers and their offspring. Clinicians must recognise the substantial limitations of stand‐alone FPG so that pregnant women can be adequately counselled and, if opting out of OGTT, considered for careful monitoring for consequences of undiagnosed gestational diabetes mellitus, such as accelerated growth or polyhydramnios. In regions without significant community spread of COVID‐19, modifying sample collection procedures to ensure strict physical distancing and having dedicated collection centres for vulnerable populations may be better than using deficient diagnostic criteria. Box – Distribution of fasting glucose results at 24–28 weeks’ gestation in patients with (n = 1790) and without (n = 14 379) gestational diabetes mellitus* (GDM) The vertical grey lines denote thresholds below which new guidelines propose that oral glucose tolerance testing is not required during the coronavirus disease 2019 (COVID‐19) pandemic. * Diagnosed using oral glucose tolerance test.

Ranita Siru · Johan H Conradie · Melissa J Gillett · Emily Gianatti · Michael M Page

A 51-year-old post-menopausal woman presented with a 6- week history of headaches, nausea and vomiting, and mild lower limb oedema

Ravind Pandher · Anita Puvanendran · Terrence H Diamond

To the Editor: The issue of cancer overdiagnosis highlighted by Glasziou and colleagues1 is not new. The problem lies in how clinicians translate caution into the care of individual patients. In August 2019, non‐clinician epidemiologists, via the media, alarmed and confused many post‐menopausal women by reminding us that menopausal hormone therapy (MHT) mildly increases breast cancer risk.2 This was already known; breast cancer is common in post‐menopausal women, with or without a history of MHT use. Women taking MHT understandably comply with government‐recommended and funded screening mammography.3 Thyroid cancer overdiagnosis has been recognised for many years and is addressed in international evidence‐based management guidelines.4,5 The Royal Australasian College of Physicians has the EVOLVE program, endorsed by the Endocrine Society of Australia, to guide clinicians to order fewer thyroid ultrasounds.6 The adoption of thyroid ultrasound reporting systems such as TIRADS has already reduced the number of thyroid fine needle biopsies.7 Furthermore, active surveillance, rather than surgical intervention, is now advocated and supported by evidence for the management of small low risk thyroid cancers.5 Data from overseas show that older patients may accept surveillance over surgery, but younger patients demand intervention due to uncertainty about tumour behaviour. Active surveillance becomes expensive with time.8 Clinicians face anxious patients seeking guidance over mixed messages from the popular press. Genomics and better personalised medicine may eventually allow prognostication. For now, addressing clinical and family histories, physical examination, and appropriate investigations are done on a case‐by‐case basis. Thyroid cancer guidelines have already been adjusted and expanded to outline an individualised approach.

Diana L Learoyd