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Background: This study compared glucose control with fast-acting insulin aspart (FiAsp) versus insulin aspart following moderate-intensity exercise (MIE) and high-intensity exercise (HIE) using a s...

Background: This prerandomization analysis from the Australian HCL-Adult trial (registration number: ACTRN12617000520336) compared masked continuous glucose monitoring (CGM) metrics among adults using insulin pumps versus multiple daily injections (MDIs), who were all self-monitoring blood glucose (SMBG). Methods: Adults with type 1 diabetes, using an insulin pump or MDIs without real-time CGM (and entering a trial of closed-loop technology), were eligible. MDI users were given an insulin dosage calculator. All participants received diabetes and carbohydrate-counting education, then wore masked CGM sensors for 3 weeks. Ethics Approval: HREC-D 088/16 Results: Adults using MDIs (n = 61) versus pump (n = 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA1c at baseline. After education, median (interquartile range) CGM time in range (TIR) 70-180 mg/dL (3.9-10.0 mmol/L) was 54% (47, 62) for those using MDIs and 56% (48, 66) for those using pump (P = 0.40). All CGM metrics were equivalent for 24 h/day for MDI and pump users. Overnight, those using MDIs (vs. pump) spent more time with glucose

Background: Gestational diabetes mellitus (GDM) management using self-monitoring blood glucose (SMBG) does not normalize pregnancy outcomes. Objective: We aimed to conduct an observational study to...

OBJECTIVE To evaluate exercise-related glucose and counterregulatory responses (CRR) in adults with type 1 diabetes with impaired awareness of hypoglycemia (IAH) using hybrid closed-loop (HCL) insulin delivery to maintain glucose homeostasis. RESEARCH DESIGN AND METHODS Twelve participants undertook 45-min high-intensity intermittent exercise (HIIE) and moderate-intensity exercise (MIE) in random order. The primary outcome was continuous glucose monitoring (CGM) time in range (70–180 mg/dL) for 24-h post–exercise commencement. RESULTS CGM time in range was similar for HIIE and MIE (median 79.5% [interquartile range 73.2, 87.6] vs. 76.1% [70.3, 83.9], P = 0.37), and time with levels CONCLUSIONS IAH adults using HCL undertaking HIIE and MIE exhibit heterogeneity in CRR. Novel findings were a preserved cortisol response and variable catecholamine responses to HIIE.

OBJECTIVE To assess the efficacy and safety of closed-loop insulin delivery compared with sensor-augmented pump therapy among older adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This open-label, randomized (1:1), crossover trial compared 4 months of closed-loop versus sensor-augmented pump therapy. Eligible adults were aged ≥60 years, with type 1 diabetes (duration ≥10 years), using an insulin pump. The primary outcome was continuous glucose monitoring (CGM) time in range (TIR; 3.9–10.0 mmol/L). RESULTS There were 30 participants (mean age 67 [SD 5] years), with median type 1 diabetes duration of 38 years (interquartile range [IQR] 20–47), randomized (n = 15 to each sequence); all completed the trial. The mean TIR was 75.2% (SD 6.3) during the closed-loop stage and 69.0% (9.1) during the sensor-augmented pump stage (difference of 6.2 percentage points [95% CI 4.4 to 8.0]; P < 0.0001). All prespecified CGM metrics favored closed loop over the sensor-augmented pump; benefits were greatest overnight. Closed loop reduced CGM time CONCLUSIONS Closed-loop therapy is an effective treatment option for older adults with long-duration type 1 diabetes, and no safety issues were identified. These older adults had higher TIR accompanied by less time below range during closed loop than during sensor-augmented pump therapy. Of particular clinical importance, closed loop reduced the time spent in hypoglycemic range overnight.

OBJECTIVE To compare glucose control with hybrid closed-loop (HCL) when challenged by high intensity exercise (HIE), moderate intensity exercise (MIE), and resistance exercise (RE) while profiling counterregulatory hormones, lactate, ketones, and kinetic data in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This study was an open-label multisite randomized crossover trial. Adults with type 1 diabetes undertook 40 min of HIE, MIE, and RE in random order while using HCL (Medtronic MiniMed 670G) with a temporary target set 2 h prior to and during exercise and 15 g carbohydrates if pre-exercise glucose was RESULTS Median TIR was 81% (67, 93%), 91% (80, 94%), and 80% (73, 89%) for 0–14 h post–exercise commencement for HIE, MIE, and RE, respectively (n = 30), with no difference between exercise types (MIE vs. HIE; P = 0.11, MIE vs. RE, P = 0.11; and HIE vs. RE, P = 0.90). Time-below-range was 0% for all exercise bouts. For HIE and RE compared with MIE, there were greater increases, respectively, in noradrenaline (P = 0.01 and P = 0.004), cortisol (P < 0.001 and P = 0.001), lactate (P ≤ 0.001 and P ≤ 0.001), and heart rate (P = 0.007 and P = 0.015). During HIE compared with MIE, there were greater increases in growth hormone (P = 0.024). CONCLUSIONS Under controlled conditions, HCL provided satisfactory glucose control with no difference between exercise type. Lactate, counterregulatory hormones, and kinetic data differentiate type and intensity of exercise, and their measurement may help inform insulin needs during exercise. However, their potential utility as modulators of insulin dosing will be limited by the pharmacokinetics of subcutaneous insulin delivery.

Background: Older adults with type 1 diabetes (T1D) have unique health challenges and have not been specifically studied in previous closed-loop (CL) trials. Objective: To assess the efficacy and safety of CL compared with sensor-augmented pump (SAP) therapy in older adults with T1D. Methods: We conducted a two-stage randomized, crossover trial comparing 4 months of CL vs. SAP. Adults aged ≥60 years with T1D ≥10 years and using an insulin pump were eligible. SAP (with continuous glucose monitoring [CGM] alerts and optional insulin delivery suspension on low glucose) and multi-disciplinary education were provided during run-in, then CL and SAP stages were undertaken in random order. The primary outcome was CGM time in range (TIR) 70-180 mg/dL comparing the final 3 months of each stage. Results: Thirty adults (mean±SD age 67±5 years, T1D duration 37±15 years and HbA1c 59±9 mmol/mol [7.6±0.9%]) participated. Ten participants (33%) had impaired awareness of hypoglycemia (Gold score ≥4); all were cognitively healthy, and none met the criteria for frailty. CGM TIR was 75.1±6.3% during CL and 69.0±9.1% during SAP (mean difference 6.2% [95% CI 4.3, 8.0]; p Conclusions: In this trial involving adults with T1D aged ≥60 years, CL increased TIR and reduced time below range compared with SAP, particularly overnight. The therapeutic benefit was evident even with relatively low baseline HbA1c. Further research is needed to understand the long-term clinical benefit. Disclosure S. A. Mcauley: Speaker’s Bureau; Self; Sanofi. N. A. O’regan: None. V. Sundararajan: None. G. M. Ward: None. R. Macisaac: Advisory Panel; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Servier Laboratories, Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk. S. Vogrin: None. S. Trawley: None. P. G. Colman: None. S. Fourlanos: Advisory Panel; Self; Pfizer Foundation, Speaker’s Bureau; Self; AstraZeneca, Eli Lilly and Company. C. Grills: None. M. H. Lee: None. A. Mohammad alipoor: None. D. N. O’neal: Advisory Panel; Self; Abbott Diabetes, Medtronic, Sanofi, Research Support; Self; Dexcom, Inc., GlySens Incorporated, Medtronic, Pacific Diabetes Technologies. Funding JDRF (3-SRA-2018-667-M-R); Diabetes Australia

Background: Experience from first-generation closed-loop (CL) systems informs refinements to enhance glucose control and user acceptance. A next-generation prototype enhanced-hybrid CL (E-...

Closed loop (CL) systems deliver insulin with a rapid onset and offset in action. Although favorable overall, the absence of a long-acting insulin increases the risk of diabetic ketoacidosis (DKA) which can occur with insulin delivery failure, acute illness, low carbohydrate diets, sodium glucose-linked transporter inhibitors, and high intensity exercise. A CL system relying entirely on interstitial glucose measurements may not provide an alert for DKA and many people with type 1 diabetes (T1D) do not carry a blood ketone meter and test-strips. Ketone sensing is theoretically feasible. A multianalyte platform incorporating a ketone sensor could provide an additional CL input without an increase in burden for the person with T1D, warning of impending DKA to allow remedial action to be taken. We outline the clinical case for inclusion of continuous ketone sensing as part of future CL systems.

OBJECTIVETo evaluate glucose control using fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp) delivered by the MiniMed Advanced Hybrid Closed-Loop (AHCL) system in adults with type 1 diabetes.RESEARCH DESIGN AND METHODSIn this randomized, open-label, crossover study, participants were assigned to receive faster aspart or IAsp in random order. Stages 1 and 2 comprised of 6 weeks in closed loop, preceded by 2 weeks in open loop. This was followed by stage 3, whereby participants changed directly back to the insulin formulation used in stage 1 for 1 week in closed loop. Participants chose their own meals except for two standardized meal tests, a missed meal bolus and late meal bolus. The primary outcome was the percentage of time sensor glucose values were from 70 to 180 mg/dL (time in range [TIR]).RESULTSTwenty-five adults (52% male) were recruited; the median (interquartile range) age was 48 (37, 57) years, and the median HbA1c was 7.0% (6.6, 7.2) (53 [49, 55] mmol/mol). Faster aspart demonstrated greater overall TIR compared with IAsp (82.3% [78.5, 83.7] vs. 79.6% [77.0, 83.4], respectively; mean difference 1.9% [0.5, 3.3]; P = 0.007). Four-hour postprandial glucose TIR was higher using faster aspart compared with IAsp for all meals combined (73.6% [69.4, 80.2] vs. 72.1% [64.5, 78.5], respectively; median difference 3.5% [1.0, 7.3]; P = 0.003). There was no ketoacidosis or severe hypoglycemia.CONCLUSIONSFaster aspart safely improved glucose control compared with IAsp in a group of adults with well-controlled type 1 diabetes using AHCL. The modest improvement was mainly related to mealtime glycemia. While the primary outcome demonstrated statistical significance, the clinical impact may be small, given an overall difference in TIR of 1.9%.

OBJECTIVE To investigate glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for most adults with type 1 diabetes). RESEARCH DESIGN AND METHODS Adults with type 1 diabetes using MDI or insulin pump without continuous glucose monitoring (CGM) were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR; 70–180 mg/dL) during the final 3 weeks. RESULTS Participants were randomized to HCL (n = 61) or control (n = 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA1c was 7.4% (0.9%) (57 [10] mmol/mol), 53% were women, and 51% used MDI. HCL TIR increased from (baseline) 55% (13%) to (26 weeks) 70% (10%) with the control group unchanged: (baseline) 55% (12%) and (26 weeks) 55% (13%) (difference 15% [95% CI 11, 19]; P < 0.0001). For HCL, HbA1c was lower (median [95% CI] difference −0.4% [−0.6, −0.2]; −4 mmol/mol [−7, −2]; P < 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95% CI 0.4, 1.9]; P < 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. Seventeen (9 device-related) versus 13 serious adverse events occurred in the HCL and control groups, respectively. CONCLUSIONS In adults with type 1 diabetes, 26 weeks of HCL improved TIR, HbA1c, and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most people living with type 1 diabetes globally, this trial demonstrates that HCL is feasible, acceptable, and advantageous.

Background: Faster-acting insulin aspart (FiAsp) may improve responsiveness of closed-loop (CL) systems and provide better postprandial glucose (PPG) management due to its more rapid onset and offset compared to insulin aspart (Asp). The Medtronic Advanced Hybrid Closed Loop (AHCL) System features auto-basal and auto-bolus functions. Aim: To compare PPG control using FiAsp vs. Asp delivered using AHCL. Methods: Twelve adults with T1D (median HbA1c 7.1% [IQR 6.8, 7.2]; 54mmol/mol [51, 55]) were assigned to FiAsp or Asp (unblinded) in random-order over two-stages (6-weeks duration each) using AHCL. Postprandial periods were defined using set time-blocks for breakfast (06:00-10:00); lunch (11:00-15:00); and dinner (17:00-21:00), based on conventional meal-times and meal distribution. CGM data was analyzed using signed-rank test. Results: With all postprandial time-block data aggregated, FiAsp demonstrated greater overall time-in-range (TIR) (70-180mg/dL) (p=0.028) and less hyperglycaemia (p=0.041) compared with Asp (Table). TIR was greater during lunch (p=0.034) for FiAsp vs. Asp, with no difference during breakfast or dinner. Over the 6-week duration, FiAsp use trended towards greater TIR vs. Asp (82.7% vs. 80.4%, p=0.07). Conclusions: FiAsp appears to confer an advantage compared with Asp for PPG control whilst using AHCL even in subjects with high overall TIR. Disclosure M.H. Lee: Research Support; Self; Medtronic. Speaker’s Bureau; Self; AstraZeneca, Medtronic. S. Vogrin: None. B. Paldus: Research Support; Self; JDRF. Speaker’s Bureau; Self; Australian Diabetes Society, Medtronic. D. Morrison: None. D. Zaharieva: Speaker’s Bureau; Self; Ascensia Diabetes Care, Insulet Corporation, Medtronic. J. Lu: None. H. Jones: None. S.A. Wyatt: Other Relationship; Self; Medtronic, Ypsomed AG. E. Netzer: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. R. MacIsaac: None. B. Grosman: Employee; Self; Medtronic. A. Roy: Employee; Self; Medtronic. N. Kurtz: Employee; Self; Medtronic. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. D.N. ONeal: None.

Background: Continuous Glucose Monitoring (CGM) technology has improved glycemia in people with diabetes. However, user burden including frequent calibration, and reinsertion of short-term devices limits adoption of this technology. Aim: Our objective was to retrospectively analyze CGM data from a fully implanted prototype sensor to assess feasibility of an extended calibration interval. Methods: The Eclipse® ICGM® System was surgically inserted in the lower abdomen, superficial to the rectus muscle sheath (Figure 1) in 6 adults with T1 diabetes, Mean (SD) age 42(12) years; 33% Females, HbA1c 7.1% (1.2)%/54(13) mmol/mol. For 6 months participants self-monitored blood glucose 4 times/day and wore a Dexcom G5 CGM. In addition, monthly clinic visits include meal-tests with frequent sampling YSI plasma glucose for paired analyses. Analyses of investigational device CGM data was retrospective against benchmark measurements. Results: There were no device associated adverse events. Data from three participants demonstrate intervals of 30, 48 and 85 days between calibrations without impacting overall performance. Preliminary measures show clinically relevant accuracy of >95 % within the A+B ranges. Conclusion: Interim data supports extended interval calibration for the fully implanted prototype Eclipse® ICGM® System which holds promise of CGM with fewer device interactions and enhanced patient experience. Disclosure P. Gupta: Employee; Self; GlySens Incorporated. A. Butler: Employee; Self; GlySens Incorporated. K. Bertsch: None. H. Jones: None. M.H. Lee: Research Support; Self; Medtronic. Speaker’s Bureau; Self; AstraZeneca, Medtronic. V.R. Obeyesekere: None. S.L. Martha: None. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. D.N. ONeal: None.

Background: Few long-term RCTs compare Hybrid Closed Loop (HCL) insulin delivery to manual (non-HCL) insulin dosing in type 1 diabetes (T1D). Objective: To examine glycemic and psychosocial outcomes in adults with T1D using HCL vs. manual insulin dosing with self-monitoring of blood glucose (SMBG) for 6 months. Methods: Adults using multiple daily injections or pumps with SMBG were randomized 1:1 after insulin dose optimization to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was time in target range (70-180mg/dL) with masked CGM during the final 3 weeks. Secondary outcomes included other CGM metrics, HbA1c, treatment satisfaction (DTSQs) and diabetes distress (PAID). Intention to treat analysis was performed with ANCOVA or rank sum test. Results: HCL and control groups were well balanced at baseline (Table). At 26 weeks, mean (95% CI) CGM time in range with HCL was greater by 14.8% (11.1, 18.5), with reduced high and low glucose time, and lower HbA1c. There were no between-group differences in treatment satisfaction or diabetes distress (Table). Conclusions: HCL provided a significant and sustained glycemic benefit compared with standard therapy. Results will inform potential users and health professionals and a cost-benefit analysis may facilitate HCL access. Disclosure S.A. McAuley: Advisory Panel; Self; Medtronic. Research Support; Self; Medtronic, Roche Diabetes Care. Speaker’s Bureau; Self; Lilly Diabetes, Roche Diabetes Care. M.H. Lee: Research Support; Self; Medtronic. Speaker’s Bureau; Self; AstraZeneca, Medtronic. B. Paldus: Research Support; Self; JDRF. Speaker’s Bureau; Self; Australian Diabetes Society, Medtronic. S. Vogrin: None. M.B. Abraham: Speaker’s Bureau; Self; Lilly Diabetes. L. Bach: None. M. Burt: None. N. Cohen: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes. Research Support; Self; Ypsomed AG. Speaker’s Bureau; Self; Novo Nordisk A/S. P.G. Colman: None. E.A. Davis: None. C. Hendrieckx: None. M. de Bock: None. J. Holmes-Walker: None. J. Kaye: Advisory Panel; Self; Abbott. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. K. Kumareswaran: None. R. MacIsaac: None. R.W. McCallum: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. J. Speight: Research Support; Self; Abbott, AstraZeneca, Medtronic, Sanofi-Aventis. Speaker’s Bureau; Self; American Diabetes Association, Australian Diabetes Society, Roche Diabetes Care. S. Stranks: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Sanofi-Aventis. S. Trawley: None. V. Sundararajan: None. G. Ward: None. A.C. Keech: Advisory Panel; Self; Amgen, Kowa Research Institute, Inc. Consultant; Self; Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Amgen. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. T. Jones: Other Relationship; Self; Medtronic. D.N. ONeal: None.

We have learned that social distancing measures are vital to reduce the spread of COVID-19 in our communities. The COVID-19 pandemic has >2 million confirmed cases and >145 000 deaths globally, with 6497 cases and 63 deaths in Australia at the time of writing. While underlying factors have yet to be defined and the available data do not distinguish between types of diabetes, people with diabetes who contract COVID-19 have a 7.3% risk of death vs 2.3% for the overall population. The authors work in diabetes services in both public and private outpatient clinics of a major city (Melbourne, Australia) and are also active in diabetes clinical research. Multiple processes have been rapidly implemented in both the clinical and research space to support social distancing. Here, we will summarize key changes and present the responses of both patients and physicians to these changes.

BACKGROUND: Diabetic ketoacidosis (DKA) is an acute life-threatening metabolic complication of diabetes that imposes substantial burden on our healthcare system. There is a paucity of published data in Australia assessing factors influencing time to resolution of DKA and length of stay (LOS). AIMS: To identify factors that predict a slower time to resolution of DKA in adults with diabetes. METHODS: Retrospective audit of patients admitted to St Vincent's Hospital Melbourne between 2010 to 2014 coded with a diagnosis of 'Diabetic Ketoacidosis'. The primary outcome was time to resolution of DKA based on normalisation of biochemical markers. Episodes of DKA within the wider Victorian hospital network were also explored. RESULTS: Seventy-one patients met biochemical criteria for DKA; median age 31 years (26-45 years), 59% were male and 23% had newly diagnosed diabetes. Insulin omission was the most common precipitant (42%). Median time to resolution of DKA was 11 h (6.5-16.5 h). Individual factors associated with slower resolution of DKA were lower admission pH (P < 0.001) and higher admission serum potassium level (P = 0.03). Median LOS was 3 days (2-5 days), compared to a Victorian state-wide LOS of 2 days. Higher comorbidity scores were associated with longer LOS (P < 0.001). CONCLUSIONS: Lower admission pH levels and higher admission serum potassium levels are independent predictors of slower time to resolution of DKA. This may assist to stratify patients with DKA using markers of severity to determine who may benefit from closer monitoring and to predict LOS.

Two women presenting with fragility fractures during lactation had bone mineral density (BMD) reduced more greatly than usually associated with lactation. The first woman was 29 years old with a BMD T-score of - 3.2 SD at the spine and- 2.0 SD at the femoral neck. The second woman was 35 years old with a BMD T-score of - 4.5 SD at the spine and - 2.8 SD at the femoral neck. Both women had increased cortical porosity and reduced trabecular density. Investigation identified an elevated serum tryptase, and marrow biopsy confirmed the diagnosis of mastocytosis. Lactation causes bone loss, but the occurrence of fractures in the setting of severe deficits in BMD and microstructural deterioration signals the need to consider additional causes of bone loss.

Key Clinical Message Despite growing evidence for GLP‐1R molecular‐based imaging, successful localization of insulinomas may require the use of multiple imaging modalities. Not all benign insulinomas express the GLP‐1R as expected. Our case demonstrates that there is a still an important role for traditional methods for the anatomical localization of an insulinoma.

Hybrid closed loop (HCL) insulin delivery with the Medtronic Minimed 670G system is effective and safe in people with type 1 diabetes (T1D). This study compared glucose control, closed loop (CL) exits, and alarm frequency with the standard HCL (s-HCL) versus enhanced HCL (e-HCL) Medtronic system. Pump-experienced T1D adults (n = 11; 9 female; mean [SD] age: 51 years [15 years]; HbA1c 7.5% [1.0%] or 58 mmol/mol [7.7 mmol/mol]) were assigned, in random order, s-HCL or e-HCL for 1 week each in a supervised live-in setting. e-HCL incorporated enhanced bolus reminders and iterative changes, broadening glucose and insulin delivery parameters permitting persistence in CL. For both s-HCL and e-HCL, insulin delivery was by a Medtronic pump with identical interventions (missed bolus, exercise, high-glycemic index, and high-fat meals), insulin action times, and insulin-carbohydrate ratios implemented. The primary outcome was continuous glucose monitoring time in target range. Analysis was by paired t-test for normally distributed data and Wilcoxon-signed rank test otherwise. e-HCL resulted in significantly fewer CL alerts and exits. Time in target and mean glucose favored e-HCL but did not reach statistical significance. No episodes of severe hypoglycemia or ketoacidosis occurred. Relative to s-HCL, e-HCL use significantly decreases CL exits and alerts, and tended to improve glycemia without compromising safety, despite multiple food and exercise challenges during the study. Longer term studies at home are merited.

Aims To compare meal-time glycaemia in adults with type 1 diabetes mellitus (T1D) managed with multiple daily injections (MDI) vs. insulin pump therapy (IPT), using self-monitoring blood glucose (SMBG), following diabetes education. Methods Adults with T1D received carbohydrate-counting education and a bolus calculator: MDI (Roche Aviva Expert) and IPT (pump bolus calculator). All then wore 3-weeks of masked-CGM (Enlite, Medtronic). Meal-times were assessed by two approaches: 1) Set time-blocks (breakfast 06:00–10:00hrs; lunch 11:00–15:00hrs; dinner 17:00–21:00hrs) and 2) Bolus-calculator carbohydrate entries signalling meal commencement. Post-meal masked-CGM time-in-range (TIR) 3.9–10.0 mmol/L was the primary outcome. Results MDI(n = 61) and IPT (n = 59) participants were equivalent in age, sex, diabetes duration and HbA1c. Median (IQR) education time provided did not differ (MDI: 1.1 h (0.75, 1.5) vs. IPT: 1.1 h (1.0, 2.0); p = 0.86). Overall, daytime (06:00–24:00hrs), lunch and dinner TIR did not differ for MDI vs. IPT participants but was greater for breakfast with IPT in both analyses with a mean difference of 12.8%, (95 CI 4.8, 20.9); p = 0.002 (time-block analysis). Conclusion After diabetes education, MDI and IPT use were associated with similar day-time glycemia, though IPT users had significantly greater TIR during the breakfast period. With education, meal-time glucose levels are comparable with use of MDI vs. pumps.

Fibrous dysplasia (FD) is an uncommon benign skeletal disorder, characterized by bone pain, deformities, and the development of pathological fractures. It is caused by osteoblastic lineage differentiation defects, leading to the replacement of normal bone with benign disorganized fibrous connective tissue. Avascular necrosis (AVN) of the femoral head is an insidious condition that can often be challenging to diagnose in its early stages. The pathogenesis of AVN is not well understood; however, it causes femoral head ischemia and collapse, often requiring hip arthroplasty. We report the first case of FD and bilateral AVN of the femoral head in the absence of an antecedent fracture. We postulate several mechanisms to explain how FD may result in AVN; however, further research is required to understand its pathophysiology and thus to guide clinical practice. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Aceruloplasminaemia is an autosomal recessive disorder of iron metabolism which is characterised by diabetes, neurodegeneration and anaemia. It should be considered in the differential diagnosis of adult onset, antibody-negative diabetes associated with persistent mild anaemia and hyperferritinaemia and/or progressive neuropsychiatric impairments.

Background: A missed or late meal insulin bolus can impact glycemia in type 1 diabetes (T1D). Aim: To study glucose control after missed and late meal boluses in T1D adults using a prototype enhanced hybrid closed-loop (E-HCL) system (Medtronic) providing automated basal insulin and correction boluses. Methods: Twelve T1D adults (median HbA1c 6.8% [IQR 6.2-7.2] | 51mmol/mol [44-55] participated. After 1-week run-in at home in Open Loop, E-HCL was activated during 1-week supervised hotel phase followed by 3 weeks free-living at-home. Participants consumed a standardized 40g carbohydrate dinner in the supervised phase. Four hours of post-prandial glucose data following a standard bolus pre-meal in E-HCL at home were compared in a pairwise manner to 1) Pre-meal bolus in Open Loop Run-In; 2) 20minute Late bolus in E-HCL supervised; 3) Missed bolus in E-HCL supervised using Wilcoxon Signed-Rank Test. Results: Late bolus was associated with mild hypoglycemia and higher glucose variability; missed bolus was associated with hyperglycemia (Table). Overall time in CL was 99.98%. E-HCL at home vs. Open Loop (run-in) had greater time-in-70-180mg/dL range (85.3 vs. 75.0%, p=0.003). There was no severe hypoglycemia or ketoacidosis. Conclusions: While glucose excursions were modest, the administration and timing of meal boluses influenced post-meal glycemia in well-controlled T1D adults using E-HCL. Disclosure M.H. Lee: Research Support; Self; Medtronic. Speaker's Bureau; Self; AstraZeneca. S. Vogrin: None. B. Paldus: Other Relationship; Self; Australian Diabetes Society, JDRF, Medtronic. H. Jones: None. V.R. Obeyesekere: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. S.A. Wyatt: Other Relationship; Self; Animas Corporation, Medtronic. G.M. Ward: None. S.A. McAuley: Research Support; Self; JDRF, Medtronic. Speaker's Bureau; Self; Australian Diabetes Society, Eli Lilly and Company. R. MacIsaac: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. Other Relationship; Self; AstraZeneca, Novo Nordisk Inc. B. Krishnamurthy: None. V. Sundararajan: None. A. Jenkins: Advisory Panel; Self; Abbott, Australian Diabetes Society, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Mylan. Speaker's Bureau; Self; Eli Lilly and Company, Novo Nordisk Inc. D.N. O'Neal: None.

To evaluate the safety and efficacy of empagliflozin 10- and 25-mg doses plus a unique lower dose (2.5 mg) as adjunct to intensified insulin in patients with type 1 diabetes (T1D).The EASE (Empagliflozin as Adjunctive to inSulin thErapy) program (The observed largest mean placebo-subtracted glycated hemoglobin reductions were -0.28% (95% CI -0.42, -0.15) for 2.5 mg, -0.54% (-0.65, -0.42) for 10 mg, and -0.53% (-0.65, -0.42) for 25 mg (allEmpagliflozin improved glycemic control and weight in T1D without increasing hypoglycemia. Ketoacidosis rate was comparable between empagliflozin 2.5 mg and placebo but increased with 10 mg and 25 mg. Ketone monitoring for early ketoacidosis detection and intervention and lower empagliflozin doses may help to reduce this risk.

Background. This is an excerpt from chapter 4 of the annual registry report from the Australia and New Zealand islet and pan- creas transplant registry. The full report is available at http://anziptr.org/reports/. Methods. We report data for all allogeneic islet isolation and transplant activity from 2002 to end 2017. Solid organ pancreas transplantation activity is reported separately. New Zealand does not have an islet transplant program. Data analysis was performed using Stata software version 14 (StataCorp, College Station, TX). Results. From 2002 to 2017, a total of 104 allogeneic islet transplants were performed in 62 recipients. Conclusions. The number of islet transplants performed in Australia was slightly lower in 2017 but continues to increase over time.

Aims To explore the challenges in the management of metastatic differentiated thyroid cancer. Introduction Differentiated thyroid cancer (DTC) is the most common form of thyroid cancer. The initial diagnosis of thyroid carcinoma and the distinction between benign and neoplastic disease can be challenging. Radioiodine-refractory metastatic DTC also presents a therapeutic dilemma. Novel targeted agents for advanced radioiodine-refractory metastatic thyroid cancer, such as tyrosine kinase inhibitors (TKIs), are being increasingly used with clinical success, broadening current available therapeutic options. Case report We present the case of a 61-year-old woman with radioiodine-refractory metastatic follicular thyroid carcinoma, which was initially misdiagnosed as benign Hurthle cell adenoma. We focus on the challenges in both the initial diagnosis and the subsequent management of her advanced disease with skeletal dominant metastases. Conclusion The advent of targeted systemic therapies as emerging frontline and salvage therapy is a novel addition to the management of radioiodine-refractory advanced DTC. Further studies to expand the role of sequential and redifferentiation therapy for advanced disease and strategies to reduce skeletalrelated events are still required. How to cite this article Lee MH, Moxey JE, McLachlan S-A, MacIsaac RJ, Sachithanandan N. Dilemmas in Metastatic Differentiated Thyroid Cancer: To irradiate, medicate, or palliate? World J Endoc Surg 2016;8(2):168-171.

Background: Hybrid closed loop (HCL) insulin delivery with the Medtronic MiniMed 670G system is safe and effective in improving glycemia for people with type 1 diabetes (T1D). Aims: To compare glucose control, CL exits and alarm frequency with standard HCL vs. enhanced HCL (eHCL) systems. Methods: Pump experienced adults with T1D (n=11; 9 women; mean[SD] age: 51[15]Y; HbA1c 7.5[1.0]%) were assigned in random order HCL and eHCL for 1 week each in a supervised live-in setting. eHCL incorporated enhanced bolus reminders and iterative changes broadening glucose and insulin delivery parameters permitting persistence in CL. For both HCL and eHCL insulin delivery was by a Medtronic pump with identical interventions (missed bolus, exercise, high GI and high fat meals), insulin action times and insulin-carbohydrate ratios implemented. The primary outcome was CGM time in target range. Results: eHCL resulted in fewer CL alerts and exits. Time in target and mean glucose favored eHCL but did not reach significance (Table). No episodes of severe hypoglycemia or ketoacidosis occurred. Conclusions: Iterative changes to the Medtronic HCL system resulted in trends towards improved glycemia, fewer CL exits and alerts without compromising safety, despite multiple food and exercise challenges during the study periods. Longer term studies at home are required to confirm these findings. Table: All results are Mean (SD); *NS= Not Significant.HCL (n=11)eHCL (n=11)pInsulin DeliveryTotal daily insulin (units/day)44 (18)47 (24)NS*Daily basal (%)55 (8)55 (7)NS*Daily bolus (%)45 (8)45 (7)NS*Daily insulin to carbohydrate ratio9.6 (3.1)9.6 (3.1)NS*Insulin action time (hrs)3.7 (0.6)3.7 (0.6)NS*Glucose Metrics% time in 70-180mg/dL69 (11)74 (10)0.16Mean sensor glucose (mg/dL)160 (13)151 (11)0.091Time 180mg/dL (%)29 (11)24 (9)0.37Time >250mg/dL (%)7.3 (5.6)6.1 (4.7)0.48Algorithm related Alerts and Dropout Alerts (n/week)8.6 (5.8)3.9 (2.8)0.01CL exits (n/week)3.5 (3.1)0 (0)0.004 Disclosure B. Paldus: None. M.H. Lee: None. H. Jones: None. S.A. McAuley: Research Support; Self; JDRF. Speaker's Bureau; Self; Novo Nordisk Inc., Australian Diabetes Society. J.C. Horsburgh: None. K.L. Roem: None. G. Ward: None. R. MacIsaac: None. N. Cohen: None. P.G. Colman: None. A. Jenkins: Research Support; Self; Medtronic, Mylan, Sanofi-Aventis. D.N. O'Neal: Research Support; Self; Medtronic MiniMed, Inc.. Advisory Panel; Self; Medtronic MiniMed, Inc.. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Sanofi.

IntroductionManual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months’ closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes.Methods and analysisThis open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9–10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users.Ethics and disseminationThe study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications.Trial registration numberNCT12617000520336.

The aim was to examine predictors of duration of inpatient hospital stay in people with diabetes mellitus to assist implementation of strategies to reduce hospital stay. This audit prospectively studied patients with diabetes mellitus admitted to a medical unit of an Australian community public hospital. Other outcome measures included glucose treatment optimisation and access to GP and diabetes-specific healthcare professionals. Comparison was made to patients without diabetes mellitus who were admitted concomitantly. Diabetes patients represented 26% of admissions over a 2-month period. In total, 73% had seen a GP within the prior 6 months. Patients with diabetes mellitus (n=79) had a median age of 69 years; 53% were male and median HbA1c was 65mmolmol–1 (8.1%). Diabetes mellitus was associated with a longer inpatient stay (P=0.03), particularly among patients admitted with vascular disease. Age >65 years and seeing

Seventeen subjects with confirmed primary aldosteronism and stable serum potassium (K) levels ≥ 3.5 mmol l-1 underwent saline suppression testing. They were retrospectively evaluated for changes in serum K levels post test. We found that there was a significant decrease in serum K levels post saline suppression test (3.7 ± 0.05 vs 3.5 ± 0.08, P = 0.01). This effect of saline suppression testing on serum K levels is not well described. We conclude that a decrease in serum K is common post-saline suppression test, even in subjects who are normokalemic pretest. The factors which predispose to the decrease in serum K level post saline load remain unclear.