Dr Katie Wynne

Objectives Early detection of cystic fibrosis (CF) related diabetes (CFRD) improves health outcomes and reduces CF-related mortality. The study aims to evaluate the ratio of islet amyloid polypeptide (IAPP) to C-peptide in CF patients with diabetes and without diabetes. Methods Cross-sectional analysis was carried out in a prospective cohort of 33 participants (CF [n=16] and CFRD [n=18]). We examined the association of plasma IAPP:C-peptide ratio with clinical information, including glycated hemoglobin, and lung function markers. Results The median (interquartile range) IAPP:C-peptide ratio was significantly (P=0.004) higher in people with CFRD (4.8 [4.5]) compared with participants without CFRD (12.1 [19.7]). The ratio of IAPP to C-peptide significantly accounted for a 38% variation in the diabetes status in patients with CF (r2=0.399, P < 0.001). Islet amyloid polypeptide is strongly correlated with serum ferritin levels (r=0.683, P=0.005) and forced expiratory volume in CFRD, but not in nondiabetic participants with CF. Conclusions Islet amyloid polypeptide:C-peptide ratio could be a potential marker of CFRD in adults with CF. Further research requires validation of this marker in longitudinal cohort studies to confirm the capability of IAPP:C-peptide to predict CFRD.

Aims: Hyperglycaemia following antenatal corticosteroids is common in women with diabetes in pregnancy, and validated algorithms to maintain pregnancy-specific glucose targets are lacking. The Pregnancy-IVI, an intravenous-insulin (IVI) algorithm, has been validated in gestational diabetes; however, its performance in pre-existing diabetes (Type 1 and Type 2 diabetes) is not known. We hypothesised that Pregnancy-IVI would be superior to a generic Adult-IVI protocol (prior standard of care) following betamethasone in women with pre-existing diabetes. Methods: A retrospective cohort study enrolled all women with pre-existing diabetes at a tertiary centre receiving betamethasone and treated with IVI according to one of two protocols: Adult-IVI (n¿=¿73, 2014¿2017) or Pregnancy-IVI (n¿=¿62, 2017¿2020). The primary outcome was on-IVI glycaemic time-in-range (capillary blood glucose (BGL) 3.8¿7.0¿mmol/L). Secondary outcomes included time with critical hyperglycaemia (BGL¿>¿10¿mmol/L); occurrence of maternal hypoglycaemia (BGL¿<¿3.8¿mmol/l) and incidence of neonatal hypoglycaemia (BGL¿=¿2.5¿mmol/L). Analysis was stratified by diabetes type. Results: Overall, Pregnancy-IVI achieved a higher proportion of on-IVI time-in-range (70%, IQR 56¿78%) compared to Adult-IVI (52%, IQR 41¿69%, p¿<¿0.0001). The duration of critical hyperglycaemia with Pregnancy-IVI was also reduced (2% [IQR 0¿7] vs 8% [IQR 4¿17], p¿<¿0.0001), without an increase in hypoglycaemia. Glycaemic variability was significantly reduced with Pregnancy-IVI. No difference in the rate of neonatal hypoglycaemia was observed. The Pregnancy-IVI was most effective in women with Type 1 diabetes. Conclusion: The Pregnancy-IVI algorithm is safe and effective when used following betamethasone in type 1 diabetes in pregnancy. Further study of women with type 2 diabetes is required.

Diabetic neuropathic pain is a common and devastating complication of type 1 diabetes, but the mechanism by which it develops and persists is yet to be fully elucidated. This study utilised high-dimensional suspension mass cytometry in a pilot cohort to investigate differences in peripheral blood immunophenotypes between type 1 diabetes patients with (n ¿= ¿9) and without (n ¿= ¿9) peripheral neuropathic pain. The abundance and activation of several leukocyte subsets were investigated with unsupervised clustering approaches FlowSOM and SPADE, as well as by manual gating. Major findings included a proportional increase in CD4+ central memory T cells and an absolute increase in classical monocytes, non-classical monocytes, and mature natural killer cells in type 1 diabetes patients with pain compared to those without pain. The expression of CD27, CD127, and CD39 was upregulated on select T cell populations, and the phosphorylated form of pro-inflammatory transcription factor MK2 was upregulated across most populations. These results provide evidence that distinct immunological signatures are associated with painful neuropathy in type 1 diabetes patients. Further research may link these changes to mechanisms by which pain in type 1 diabetes is initiated and maintained, paving the way for much needed targeted treatments.

Transgender individuals who desire medical transition need to access care through their local healthcare system. This is the first study to explore the perceptions of the community and attitudes of healthcare providers towards the delivery of transgender health care in an Australian context. An anonymous survey was conducted of trans and gender-diverse community members; and physicians and trainees in the Hunter New England Local Health District of New South Wales, Australia. Community members were surveyed about their healthcare experiences. Medical students, GPs and hospital physicians were surveyed on their attitudes towards the delivery of transgender health care before and after a 1-h education session that included the lived experience of a community member. Community members expressed a need for increased education for healthcare providers in transgender medicine. Following the intervention, significantly more healthcare providers felt confident to facilitate transgender health care for adults, adolescents and children; and more healthcare providers agreed that medical and surgical treatment should be offered to transgender patients if desired. The positive safety profile of treatment was felt to be the most persuasive factor for the provision of care. Healthcare providers identified a need for health education in transgender medicine; easy access to evidence-based resources; and local referral pathways as key strategies to improving transgender health care.

Epidemiological and interventional studies have linked saturated fatty acids (SFA) with elevated levels of low-density lipoprotein cholesterol (LDL-C) and increased CVD risk. However, the effects of the SFA chain length on postprandial lipemia in humans are not well elucidated. The aim of this study was to investigate the impact of short, medium and long-chain SFA on postprandial blood lipids in healthy volunteers. Sixteen healthy volunteers consumed test biscuits containing 40 g of either butter (BB), coconut oil (CB) or lard (LB) in a single-blinded, randomized crossover design. Blood samples were collected fasting and 2, 3, 4, and 6 hours postprandially and assessed for blood lipids (total cholesterol, TC; high-density lipoprotein cholesterol, HDL-C; LDL-C and triglyceride, TG). The postprandial TG response following CB was 59.8% lower than following BB (p < 0.01) and 58.8% lower than LB (p < 0.01), although no difference was observed between the BB and the LB responses. The net area under the LDL-C concentration curve was significantly larger after consumption of the CB compared to the BB, despite no significant differences in postprandial net area under the TC and HDL-C concentration curves. Consumption of medium-chain SFA as CB resulted in lower postprandial TG excursions compared to short-chain SFA as BB and long-chain SFA as LB, despite their identical fat and caloric content. These results suggest that SFA differ in their potential to elevate postprandial lipid levels, and that coconut oil, a rich source of medium-chain SFA may not be as hyperlipidemic as animal fats rich in long chain SFA. Anzctr identifier: 12617000903381. Clinical trial registry number: The study was registered with the Australia New Zealand Trial registry as ACTRN12617000903381.

Objective: Post-thyroidectomy hypocalcaemia is a significant cause of morbidity and prolonged hospitalization, usually due to transient parathyroid gland damage, treated with calcium and vitamin D supplementation. We present a randomized, double-blinded placebo-controlled trial of preoperative loading with high-dose cholecalciferol (300¿000 IU) to reduce post-thyroidectomy hypocalcaemia. Patients and Measurements: Patients (n¿=¿160) presenting for thyroidectomy at tertiary hospitals were randomized 1:1 to cholecalciferol (300¿000¿IU) or placebo 7¿days prior to thyroidectomy. Ten patients withdrew prior to surgery. The primary outcome was post-operative hypocalcaemia (corrected calcium <2.1¿mmol/L in first 180¿days). Results: The study included 150 patients undergoing thyroidectomy for Graves¿ disease (31%), malignancy (20%) and goitre (49%). Mean pre-enrolment vitamin D was 72¿±¿26¿nmol/L. Postoperative hypocalcaemia occurred in 21/72 (29%) assigned to cholecalciferol and 30/78 (38%) participants assigned to placebo (P¿=¿0.23). There were no differences in secondary end-points between groups. In pre-specified stratification, baseline vitamin D status did not predict hypocalcaemia, although most individuals were vitamin D replete at baseline. Post-hoc stratification by day 1 parathyroid hormone (PTH) (<10¿pg/mL, low vs =10¿pg/mL, normal) was explored due to highly divergent rates of hypocalcaemia in these groups. Using a Cox regression model, the hazard ratio for hypocalcaemia in the cholecalciferol group was 0.56 (95%CI 0.32-0.98, P¿=¿0.04) after stratification for Day 1 PTH. Further clinical benefits were observed in these subgroups. Conclusions: Pre-thyroidectomy treatment with high-dose cholecalciferol did not reduce the overall rate of hypocalcaemia following thyroidectomy. In subgroups stratified by day 1 PTH status, improved clinical outcomes were noted.

Diabetes of the exocrine pancreas (DEP) is a form of diabetes that occurs due to pancreatic disease. It is far more common than has been previously considered, with a recent study showing 1.8% of adults with new-onset diabetes should have been classified as DEP. The majority is misdiagnosed as type 2 diabetes mellitus (T2DM). Patients with DEP exhibit varying degrees of exocrine and endocrine dysfunction. Damage to the islet of Langerhans effects the secretion of hormones from the ß, a, and pancreatic polypeptide cells; the combination of low insulin, glucagon, and pancreatic polypeptide contributes to rapid fluctuations in glucose levels. This form of ¿brittle diabetes¿ may result in the poorer glycemic control observed in patients with DEP, when compared with those with T2DM. Diabetes of the exocrine pancreas has a different natural history to other forms of diabetes; patients are more likely to require early insulin initiation compared with those with T2DM. Therefore, individuals with DEP should be advised about the symptoms of decompensated hyperglycemia, although they are less likely to develop ketoacidosis. Clinicians should screen for DEP in patients with acute or chronic pancreatitis, following pancreatic resection, or with co-existing cystic fibrosis or hemochromatosis. Incident diabetes may herald the onset of pancreatic ductal carcinoma in a small subset of patients. Once identified, patients with DEP can benefit from specific lifestyle advice, pancreatic enzyme replacement therapy, metformin treatment, appropriate insulin dosing, and monitoring. Further research is needed to establish the ideal treatment regimens to provide optimal clinical outcomes for this unique form of diabetes.

Aims: Marked hyperglycaemia is common following betamethasone administration in women with gestational diabetes (GDM), and may contribute to neonatal hypoglycaemia. Validated protocols to deliver glycaemic stability following betamethasone are lacking. We hypothesized that an intravenous insulin (IVI) protocol for pregnancy-specific glycaemic targets (Pregnancy-IVI) would achieve greater at-target glycaemic control than a generic adult intravenous insulin protocol (Adult-IVI), and may reduce neonatal hypoglycaemia. Methods: A retrospective cohort study of the performance Adult-IVI and Pregnancy-IVI following betamethasone in GDM, sequentially implemented at a tertiary hospital, without change in indication for IVI. Cases were identified by electronic record search. Primary outcome was percentage of on-IVI time with at-target glycaemia [blood glucose level (BGL) 3.8¿7¿mmol/l]. Secondary outcomes were time with critical hyperglycaemia (BGL >¿10¿mmol/l), occurrence of maternal hypoglycaemia (BGL <¿3.8¿mmol/l), and incidence of neonatal hypoglycaemia (BGL =¿2.5¿mmol/l) if betamethasone was administered within 48¿h of birth. Results: The cohorts comprised 151 women (Adult-IVI n¿=¿86; Pregnancy-IVI n¿=¿65). The primary outcome was 68% time-at-target [95% confidence interval (CI) 64¿71%) for Pregnancy-IVI compared with 55% (95% CI 50¿60%) for Adult-IVI (P¿=¿0.0002). Critical maternal hyperglycaemia (0% vs. 2%, P¿=¿0.02) and hypoglycaemia (2% vs. 12%, P¿=¿0.02) were both lower with Pregnancy-IVI than Adult-IVI. Neonatal hypoglycaemia was less common after Pregnancy-IVI (29%) than after Adult-IVI (54%, P¿=¿0.03). A multiple logistic regression model adjusting for potential confounders gave an odds ratio for neonatal hypoglycaemia with Pregnancy-IVI of 0.27 (95% CI 0.10¿0.76, P¿=¿0.01). Conclusions: An IVI protocol designed for pregnancy effectively controlled maternal hyperglycaemia following betamethasone administration in GDM. This is the first intervention to show a reduction in betamethasone-associated neonatal hypoglycaemia, linked with optimum maternal glycaemic control.

Background Medium-chain saturated fatty acids (MCFAs) may affect circulating lipids and lipoproteins differently than long-chain saturated fatty acids (LCSFAs), but the results from human intervention trials have been equivocal. Objective The aim of this study was to determine whether MCFAs and LCSFAs have differential impacts on blood lipids and lipoproteins. Design Five databases were searched (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus) until April 2018, and published clinical trials investigating the differential effects of dietary MCFAs and LCSFAs on blood lipids were included. Searches were limited to the English language and to studies with adults aged >18 y. Where possible, studies were pooled for meta-analysis using RevMan 5.2. The principle summary measure was the mean difference between groups calculated using the random-effects model. Results Eleven eligible crossover and 1 parallel trial were identified with a total of 299 participants [weighted mean ± SD age: 38 ± 3 y; weighted mean ± SD body mass index (kg/m 2): 24 ± 2]. All studies were pooled for the meta-analysis. Diets enriched with MCFAs led to significantly higher high-density lipoprotein (HDL) cholesterol concentrations than diets enriched with LCSFAs (0.11 mmol/L; 95% CI: 0.07, 0.15 mmol/L) with no effect on triglyceride, low-density lipoprotein (LDL) cholesterol, and total cholesterol concentrations. Consumption of diets rich in MCFAs significantly increased apolipoprotein A-I (apoA-I) concentrations compared with diets rich in LCSFAs (0.08 g/L; 95% CI: 0.02, 0.14 g/L). There was no evidence of statistical heterogeneity for HDL cholesterol, apoA-I, and triglyceride concentrations; however, significant heterogeneity was observed for the total cholesterol (I 2 = 49%) and LDL cholesterol analysis (I 2 = 58%). Conclusion The findings of this research demonstrate a differential effect of MCFAs and LCSFAs on HDL cholesterol concentrations. Further investigations are warranted to elucidate the mechanism by which the lipid profile is altered. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42017078277.

Aim: There is a high incidence of neonatal hypoglycaemia in neonates born to mothers with pre-existing diabetes. This often necessitates admission to the neonatal intensive care. Guidelines suggest maintaining intrapartum blood glucose levels (BGLs) of 4¿7 mmol/l in women with diabetes to reduce the risk of neonatal hypoglycaemia. This study assessed whether intrapartum BGLs in women with pre-gestational Type 1 and 2 diabetes were predictive of neonatal hypoglycaemia. Methods: A retrospective analysis of 261 births delivered at a tertiary hospital in Australia from 2009 to 2014. Results: There were 122 cases of neonatal hypoglycaemia (glucose = 2.6 mmol/l) in 261 births (47%). The mothers in the neonatal hypoglycaemia group spent less time with BGL in the range 4¿7 mmol/l [55 ± 37% vs. 65 ± 35%, P = 0.02; odds ratio (OR) 0.992, P = 0.03] and more time with BGL in the 7¿10 mmol/l range (31 ± 34% vs. 18 ± 27%, P = 0.003; OR 1.013, P = 0.003) compared with those without neonatal hypoglycaemia. Although statistically significant, receiver operating characteristic (ROC) curve analysis showed that time spent with maternal BGLs in the range 4¿7 mmol/l [area under the curve (AUC) = 0.58] or 7¿10 mmol (AUC = 0.60) was not strong enough to be a useful clinical predictor of neonatal hypoglycaemia. HbA1c in the second trimester of pregnancy (P = 0.02, OR 1.42) and percentage time spent in BGL range of 7¿10 mmol/l (P = 0.001, OR 1.02) were both associated with a risk of neonatal hypoglycaemia in a logistic regression model. HbA1c in the third trimester (P = 0.07, OR 1.28) approached, but did not reach, significance. Conclusions: These data support a BGL range of 4¿7 mmol/l as an intrapartum target. Glycaemic control in the second trimester is associated with neonatal hypoglycaemia. Improvement in ante- and intrapartum glycaemic control may reduce neonatal hypoglycaemia in women with pre-existing diabetes.

Aims To assess the relationship between insulin resistance (IR), retinopathy and maculopathy in young adults with Type 1 diabetes mellitus. Methods A cross-sectional study at a regional Australian tertiary hospital. Retinal pathology, assessed by colour fundus photography, was correlated with two surrogate measures of IR: estimated Glucose Disposal Rate (eGDR) and Insulin Sensitivity Score (ISS), where lower scores reflect greater IR. Results 107 patients were recruited, with mean age 24.7¿years, 53% male, and mean duration of disease 10.8¿years. Mean eGDR scores (5.6¿vs 8.0 p¿<¿0.001) and ISS (4.7¿vs 7.9, p¿<¿0.001) were lower in subjects having at least moderate non-proliferative diabetic retinopathy (NPDR; relative to nil/mild-NPDR). Similarly, mean eGDR (4.2¿vs 6.2, p¿=¿0.001) and ISS (3.8¿vs 6.1, p¿=¿0.003) were lower in patients with maculopathy. Multivariate logistic regression modelling was used to control for confounding. For retinopathy severity, a unit increase in eGDR or ISS (representing lower IR) was associated with a 50% decrease in odds of moderate-NPDR or worse (eGDR OR 0.5, 95%CI 0.32¿0.77, p¿=¿0.002; ISS OR 0.49, 95%CI 0.29¿0.84, p¿=¿0.01). A unit increase in eGDR or ISS was associated with a 46¿56% decrease in odds of maculopathy (eGDR OR 0.54, 95%CI 0.37¿0.81, p¿=¿0.003; ISS OR 0.44, 95%CI 0.22¿0.88, p¿=¿0.02). Conclusions IR correlates with more severe retinopathy in young adults with Type 1¿DM. This is the first description of a correlation between IR and maculopathy in Type 1¿DM, warranting further evaluation. Prospective studies examining whether reducing IR can improve microvascular complications are required.

Diabetes is a chronic, complex condition requiring sound knowledge and self-management skills to optimize glycemic control and health outcomes. Dietary intake and physical activity are key diabetes self-management (DSM) behaviors that require tailored education and support. Electronic health (eHealth) technologies have a demonstrated potential for assisting individuals with DSM behaviors. This review provides examples of technologies used to support nutrition and physical activity behaviors in the context of DSM. Technologies covered include those widely used for DSM, such as web-based programs and mobile phone and smartphone applications. In addition, examples of novel tools such as virtual and augmented reality, video games, computer vision for dietary carbohydrate monitoring, and wearable devices are provided. The challenges to, and facilitators for, the use of eHealth technologies in DSM are discussed. Strategies to support the implementation of eHealth technologies within practice and suggestions for future research to enhance nutrition and physical activity behaviors as a part of broader DSM are provided.