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Aims. To assess morbidity among young people with diabetes presenting to a regional hospital in Northern Australia and compare the risk of complications among those living with type 2 diabetes (T2D) versus type 1 diabetes (T1D). Materials and Methods. A cross‐sectional study of young people with T1D or T2D (diagnosed age 1–25 years) presenting to a regional Northern Australian hospital with any condition from 2015 to 2019. Demographics, cardiometabolic comorbidities, and diabetes‐related complications were collected from individual medical records and compared between those with T1D and T2D. Results. Among 357 young people (192 had T2D, 165 T1D), the mean age was 22 years, the mean duration of diabetes was 6.7 years, 52% were Aboriginal or Torres Strait Islander, and 28% lived remotely. Cardiometabolic comorbidities (obesity, hypertension, and dyslipidaemia) and diabetes‐related complications (microalbuminuria, amputation, and elevated non‐alcoholic fatty liver disease score) were more prevalent in those with T2D compared to T1D, despite shorter disease duration and lower median HbA1c. When adjusted for age, sex, and BMI, the odds ratio (95% CI) for microalbuminuria was 4.8 (1.83–12.8) with T2D compared to T1D. Conclusion. In a cohort of young people with diabetes in Northern Australia, the prevalence of diabetes‐related complications was higher among those with T2D than T1D. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically at‐risk for type 1 diabetes followed from birth who had developed islet autoantibodies ("seroconverted"), by measuring mucosa‐associated cytokines in their sera. Materials and Methods: Sera were collected 3 monthly from birth from children with a first‐degree type 1 diabetes relative, in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Children who seroconverted were matched for sex, age, and sample availability with seronegative children. Luminex xMap technology was used to measure serum cytokines. Results: Of eight children who seroconverted, for whom serum samples were available at least 6 months before and after seroconversion, the serum concentrations of mucosa‐associated cytokines IL‐21, IL‐22, IL‐25, and IL‐10, the Th17‐related cytokines IL‐17F and IL‐23, as well as IL‐33, IFN‐γ, and IL‐4, peaked from a low baseline in seven around the time of seroconversion and in one preceding seroconversion. These changes were not detected in eight sex‐ and age‐matched seronegative controls, or in a separate cohort of 11 unmatched seronegative children. Conclusions: In a cohort of children at risk for type 1 diabetes followed from birth, a transient, systemic increase in mucosa‐associated cytokines around the time of seroconversion lends support to the view that mucosal infection, e.g., by an enteric virus, may drive the development of islet autoimmunity. [ABSTRACT FROM AUTHOR]

Aim: Randomized trials reporting 5‐year outcomes have shown bariatric surgery to induce diabetes remission and improve cardiovascular risk. However, the longer‐term effects of surgery are uncertain, with only one randomized trial reporting 10‐year diabetes outcomes in people with obesity. We aimed to compare 10‐year diabetes outcomes of people who are overweight but not obese, randomly assigned to receive either multidisciplinary diabetes care, or multidisciplinary diabetes care combined with gastric band (GB) surgery. Methods: Between 2009 and 2011, 51 adults were randomized. After 5 years, they were discharged to receive community care and reassessed after 10 years. The primary outcome was diabetes remission, defined as glycated haemoglobin (HbA1c) <6.5% (48 mmol/mol) without glucose‐lowering medication. Results: Forty‐one participants (20 medical and 21 GB) completed the 10‐year assessment. The median (Q1, Q3) weight loss in the GB group was 9.8 (6.7, 16.3)% at 10 years compared with 5.6 (3.4, 7.6)% in the medical group (median difference 4.2%; p =.008). Diabetes remission occurred in five GB participants and no medical participants (relative risk 0.76, 95% CI: 0.55‐0.93, p =.048). GB participants used fewer glucose‐lowering medications at 10 years but HbA1c, fasting glucose, calculated cardiovascular risk, quality‐of‐life and incident diabetes complications did not differ significantly between the groups. Conclusion: When compared with medical care, GB surgery achieved greater weight loss and modestly increased the likelihood of diabetes remission. However, it did not improve HbA1c, cardiovascular risk or quality of life. [ABSTRACT FROM AUTHOR]

Aims: Islet autoantibody screening of infants and young children in the Northern Hemisphere, together with semi‐annual metabolic monitoring, is associated with a lower risk of ketoacidosis (DKA) and improved glucose control after diagnosis of clinical (stage 3) type 1 diabetes (T1D). We aimed to determine if similar benefits applied to older Australians and New Zealanders monitored less rigorously. Methods: DKA occurrence and metabolic control were compared between T1D relatives screened and monitored for T1D and unscreened individuals diagnosed in the general population, ascertained from the Australasian Diabetes Data Network. Results: Between 2005 and 2019, 17,105 relatives (mean (SD) age 15.7 (10.8) years; 52% female) were screened for autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma‐associated protein 2. Of these, 652 screened positive to a single and 306 to multiple autoantibody specificities, of whom 201 and 215, respectively, underwent metabolic monitoring. Of 178 relatives diagnosed with stage 3 T1D, 9 (5%) had DKA, 7 of whom had not undertaken metabolic monitoring. The frequency of DKA in the general population was 31%. After correction for age, sex and T1D family history, the frequency of DKA in screened relatives was >80% lower than in the general population. HbA1c and insulin requirements following diagnosis were also lower in screened relatives, consistent with greater beta cell reserve. Conclusions: T1D autoantibody screening and metabolic monitoring of older children and young adults in Australia and New Zealand, by enabling pre‐clinical diagnosis when beta cell reserve is greater, confers protection from DKA. These clinical benefits support ongoing efforts to increase screening activity in the region and should facilitate the application of emerging immunotherapies. [ABSTRACT FROM AUTHOR]

Aim: We aimed to characterize associations between diet and the gut microbiome and short chain fatty acid (SCFA) products in youth with islet autoimmunity or type 1 diabetes (IA/T1D) in comparison with controls. Research design and methods: Eighty participants (25 diagnosed with T1D, 17 with confirmed IA, 38 sibling or unrelated controls) from the Australian T1D Gut Study cohort were studied (median [IQR] age 11.7 [8.9, 14.0] years, 43% female). A Food Frequency Questionnaire characterized daily macronutrient intake over the preceding 6 months. Plasma and fecal SCFA were measured by gas chromatography; gut microbiome composition and diversity by 16S rRNA gene sequencing. Results: A 10 g increase in daily carbohydrate intake associated with higher plasma acetate in IA/T1D (adjusted estimate +5.2 (95% CI 1.1, 9.2) μmol/L p = 0.01) and controls (adjusted estimate +4.1 [95% CI 1.7, 8.5] μmol/L p = 0.04). A 5 g increase in total fat intake associated with lower plasma acetate in IA/T1D and controls. A 5% increase in noncore (junk) food intake associated with reduced richness (adjusted estimate −4.09 [95%CI –7.83, −0.35] p =.03) and evenness (−1.25 [95% CI –2.00, −0.49] p < 0.01) of the gut microbiome in IA/T1D. Fiber intake associated with community structure of the microbiome in IA/T1D. Conclusions: Modest increments in carbohydrate and fat intake associated with plasma acetate in all youth. Increased junk food intake associated with reduced diversity of the gut microbiome in IA/T1D alone. These associations with the gut microbiome in IA/T1D support future efforts to promote SCFA by using dietary interventions. [ABSTRACT FROM AUTHOR]

Aim: To determine the clinical and biochemical variables associated with change in HbA1c in patients with type 2 diabetes who start sodium‐glucose linked transporter (SGLT) inhibitor therapy. Methods: We performed a prospective cohort study (ACTRN12616000833460) of 48 adults (30 male, 18 female) with type 2 diabetes who attended a tertiary hospital diabetes clinic. Fasting serum and urine samples, collected during clinic visits prior to and at 1, 12 and 24 weeks after commencing SGLT inhibitor treatment, were analysed for HbA1c, electrolytes, urea, creatinine and glucose. Results: After 12 weeks, SGLT inhibitor therapy was associated with respective median (97% CI) decreases in weight, blood pressure, HbA1c and urine albumin/creatinine ratio of 3.0 (1.7–3.4) kg, 8 (2–16)/4 (3–9) mmHg, 6 (3–14) mmol/mol and 0.69 (0.18–1.8) mg/mmol. These effects persisted to 24 weeks. Urinary frequency and genitourinary infection were common adverse effects. Baseline HbA1c and eGFR independently predicted ΔHbA1c at 12 weeks whereas only baseline HbA1c independently predicted ΔHbA1c at 24 weeks. Urinary fractional glucose excretion and change in fasting glucose 1 week after starting SGLT inhibitor did not contribute to prediction of glycaemic response. Conclusions: SGLT inhibitor therapy in a hospital clinic setting was associated with clinical improvements comparable to those observed in clinical trials but with higher incidence of genitourinary side‐effects. Baseline HbA1c and eGFR, but not urine fractional glucose excretion, predicted glycaemic response. [ABSTRACT FROM AUTHOR]

We aimed to describe the glycaemic trajectory and define characteristics associated with suboptimal glycaemic control in the type 2 diabetes clinic. Higher glycosylated haemoglobin (HbA1c) at 1 year was associated with higher baseline HbA1c, concurrent anti‐depressant or antipsychotic medication, higher bodyweight and low treatment adherence. These characteristics may help identify patients unlikely to attain HbA1c treatment targets and be better served by a different model of care. [ABSTRACT FROM AUTHOR]

Backgrounds: We aimed to monitor pancreatic exocrine function longitudinally in relation to the development of islet autoimmunity (IA) and type 1 diabetes (T1D) in at‐risk children with a first‐degree relative with T1D, who were followed prospectively in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Methods: Fecal elastase‐1 (FE‐1) concentration was measured longitudinally in 85 ENDIA children from median age 1.0 (IQR 0.7,1.3) year. Twenty‐eight of 85 children (progressors) developed persistent islet autoantibodies at median age of 1.5 (IQR 1.1,2.5) years, of whom 11 went on to develop clinical diabetes. The other 57 islet autoantibody‐negative children (non‐progressors) followed similarly were age and gender‐matched with the progressors. An adjusted linear mixed model compared FE‐1 concentrations in progressors and non‐progressors. Results: Baseline FE‐1 did not differ between progressors and non‐progressors, or by HLA DR type or proband status. FE‐1 decreased over time in progressors in comparison to non‐progressors (Wald statistic 5.46, P =.02); in some progressors the fall in FE‐1 preceded the onset of IA. Conclusions: Pancreatic exocrine function decreases in the majority of young at‐risk children who progress to IA and T1D. [ABSTRACT FROM AUTHOR]

The methionine aminopeptidase 2 (MetAP2) inhibitor ZGN‐1061 lowered weight and improved glucose in preclinical studies. We sought to determine its efficacy and safety by performing a multicentre, phase 2, randomized controlled trial involving overweight and obese adults with type 2 diabetes and HbA1c between 7% and 11% inclusive. Participants were randomized to receive subcutaneous treatment with placebo or 0.05, 0.3, 0.9 or 1.8 mg ZGN‐1061 every third day for 12 weeks. The primary outcome was change in HbA1c at week 12. Relative to placebo, the 0.9 and 1.8 mg doses induced clinically meaningful reductions in HbA1c of 0.6% (95% CI 0.2% to 0.9%; P = 0.0006) and 1.0% (95% CI 0.6% to 1.4%; P < 0.0001), respectively. The 1.8 mg dose also induced weight loss of 2.2% (95% CI 1.1% to 3.3%; P = 0.0002). The incidence of adverse events was balanced across the treatment groups. We conclude that MetAP2 inhibition with ZGN‐1061 for 12 weeks improved glucose control and aided weight loss in overweight and obese people with type 2 diabetes. However, given safety issues, Zafgen has discontinued MetAP2 inhibitor development. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: To investigate the longitudinal relationship between the gut microbiome, circulating short chain fatty acids (SCFAs) and intestinal permeability in children with islet autoimmunity or type 1 diabetes and controls. Methods: We analyzed the gut bacterial microbiome, plasma SCFAs, small intestinal permeability and dietary intake in 47 children with islet autoimmunity or recent‐onset type 1 diabetes and in 41 unrelated or sibling controls over a median (range) of 13 (2‐34) months follow‐up. Results: Children with multiple islet autoantibodies (≥2 IA) or type 1 diabetes had gut microbiome dysbiosis. Anti‐inflammatory Prevotella and Butyricimonas genera were less abundant and these changes were not explained by differences in diet. Small intestinal permeability measured by blood lactulose:rhamnose ratio was higher in type 1 diabetes. Children with ≥2 IA who progressed to type 1 diabetes (progressors), compared to those who did not progress, had higher intestinal permeability (mean [SE] difference +5.14 [2.0], 95% confidence interval [CI] 1.21, 9.07, P =.006), lower within‐sample (alpha) microbial diversity (31.3 [11.2], 95% CI 9.3, 53.3, P =.005), and lower abundance of SCFA‐producing bacteria. Alpha diversity (observed richness) correlated with plasma acetate levels in all groups combined (regression coefficient [SE] 0.57 [0.21], 95% CI 0.15, 0.99 P =.008). Conclusions/Interpretation: Children with ≥2 IA who progress to diabetes, like those with recent‐onset diabetes, have gut microbiome dysbiosis associated with increased intestinal permeability. Interventions that expand gut microbial diversity, in particular SCFA‐producing bacteria, may have a role to decrease progression to diabetes in children at‐risk. [ABSTRACT FROM AUTHOR]

The introduction of anti- HER2 therapy with trastuzumab has seen an increase in frequency of central nervous system metastasis as the site of first recurrence. Here, we present a rare case of a 63-year-old woman who presented with an isolated breast carcinoma pituitary metastasis 5 years following treatment for a high-risk breast cancer. This report underscores the changing nature of HER2-positive disease in the post-trastuzumab era. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is caused by an autoimmune attack on pancreatic beta cells that leads to insulin deficiency. The incidence of T1D in Australia has doubled over the past 20 years. T1D treatment focuses on physiological insulin replacement, aiming for near-normal blood glucose levels. Hypoglycaemia is a significant cause of morbidity and mortality in T1D. Optimal T1D management is complex, and is enhanced by empowering individuals in all aspects of managing diabetes. New technologies, including insulin pumps, continuous glucose monitors and sensor-augmented pumps, can assist people achieve better glycaemic control and reduce the risk of severe hypoglycaemia. Women with T1D can achieve significantly better outcomes during pregnancy and for their infants by planning for their pregnancy and by intensive glycaemic control. Several trials are underway that seek to identify the determinants of autoimmunity and to develop therapies that prevent T1D in at-risk individuals. Pancreatic and islet cell transplants are proven therapies, but are only offered to individuals with diabetes and renal failure (pancreas) or severe hypoglycaemia unawareness (islet cell transplants). Although T1D is still associated with considerable premature mortality, recent findings show that a significant improvement in life expectancy has occurred. [ABSTRACT FROM AUTHOR]

Background Most pituitary surgery centres prescribe perioperative glucocorticoids to subjects undergoing transsphenoidal pituitary adenomectomy (TSA), despite reports suggesting this may be unnecessary. Evidence-based guidelines for glucocorticoid use in TSA have recently been published but there are no prospective studies of their utility. Objective To implement and assess a protocol for reduced glucocorticoid replacement for subjects undergoing TSA. Design Prospective and retrospective cohort study in an Australian pituitary surgery centre. Patients and measurements Clinical and biochemical data for 56 TSAs performed for non-ACTH-secreting tumours between March 2004 and April 2006 were prospectively collected and compared with data for 47 TSAs performed between October 2001 and November 2003, before implementation of the protocol. In the prospective cohort, a postoperative days 1–3 morning serum cortisol threshold of 250 nmol/l (91 µg/dl) was used to guide long-term glucocorticoid requirement. Results Implementation of the protocol was associated with significant reductions in dose and duration of glucocorticoid treatment post TSA in 44 ‘low-risk’ cases (no preoperative glucocorticoid use or evidence of pituitary apoplexy). In two low-risk cases, long-term glucocorticoid replacement was required despite postoperative cortisol greater than 250 nmol/l. Following the remaining 42 low-risk operations, glucocorticoid was not prescribed on hospital discharge on the basis of morning serum cortisol > 250 nmol/l and no clinical evidence of hypocortisolism. None of these 42 cases required glucocorticoid treatment for hypocortisolism following surgery. Short synacthen tests were performed in 35 of these subjects a minimum of 6 months after surgery and were normal. Use of the protocol was not associated with differences in postoperative complications. Conclusions Reduced glucocorticoid replacement in TSA is safe and reduces patient exposure to glucocorticoids and their potential adverse events. The occurrence of hypocortisolism in two low-risk subjects with serum cortisol > 250 nmol/l highlights the importance of daily clinical assessment when using this protocol. [ABSTRACT FROM AUTHOR]