Publications by authors named "Elif I Ekinci"

100 Publications

Feasibility trial of metformin XR in people with pre-diabetes and stroke (MIPPS)-randomised open blinded endpoint controlled trial.

J Clin Neurosci 2021 Apr 2;86:103-109. Epub 2021 Feb 2.

Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia. Electronic address:

Aims: Pre-diabetes is a common condition that affects about 16.4% of Australian adults. Hyperglycaemia is a strong risk factor for the development of stroke. Metformin XR is an approved medication to treat type 2 diabetes in Australia but not pre-diabetes. Additionally, whether it is tolerated following a stroke is unclear. In this pilot study, we aimed to assess the feasibility of Metformin XR in people with stroke and pre-diabetes.

Methods: In this PROBE design trial, people who had recent stroke (within 3 months) with pre-diabetes were randomized to either the active arm (n = 13) receiving usual care plus Metformin XR (500 mg daily increased to a total daily dose of 1500 mg) or the control group receiving only usual care (n = 13). At baseline & after four months of intervention, clinical and biomedical characteristics, cardiovascular risk factors and medication data were recorded. At one month and 2.5 months into the study, compliance rateandside effects were determined.

Results: This trial showed that it is feasible to recruit, retain and monitor participants. However, the compliance rate was low. Adherence to metformin XR was 52% (IQR:42% to 61%) based on the remaining tablets in the container after 4 months of intervention. None of the reported side effects were deemed to be related to the study treatment and no significant differences were observed between the metformin XR and the control group.

Conclusion: Treatment with Metformin XR in participants admitted with stroke and with pre-diabetes is feasible and safe. Strategies are needed to improve adherence in future trials.
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http://dx.doi.org/10.1016/j.jocn.2021.01.006DOI Listing
April 2021

Geometric Distortion Correction of Renal Diffusion Tensor Imaging Using the Reversed Gradient Method.

J Comput Assist Tomogr 2021 Mar-Apr 01;45(2):218-223

Department of Radiology, NYU Langone Medical Center, New York, NY.

Abstract: Renal echo planar diffusion tensor imaging (DTI) has clinical potential but suffers from geometric distortion. We evaluated feasibility of reversed gradient distortion correction in 10 diabetic patients and 6 volunteers. Renal area, apparent diffusion coefficient, fractional anisotropy, and tensor eigenvalues were measured on uncorrected and distortion-corrected DTI. Corrected DTI correlated better than uncorrected DTI (r = 0.904 vs 0.840, P = 0.002) with reference anatomic T2-weighted imaging, with no significant difference in DTI metrics.
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http://dx.doi.org/10.1097/RCT.0000000000001124DOI Listing
April 2021

Gut microbiome, prebiotics, intestinal permeability and diabetes complications.

Best Pract Res Clin Endocrinol Metab 2021 Feb 17:101507. Epub 2021 Feb 17.

Department of Diabetes, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia; Baker Heart and Diabetes Institute, Melbourne, Australia.

Diabetes is a metabolic condition. The composition of the gut microbiota is altered in diabetes with reduced levels of short chain fatty acids (SCFA) producers, notably butyrate. Butyrate is associated with a number of beneficial effects including promoting the integrity of the gastrointestinal barrier. Diabetes may lead to an increase in the permeability of the gut barrier, which is thought to contribute to systemic inflammation and worsen the microvascular complications of diabetes. Prebiotics, non-digestible carbohydrates, are fermented by the colonic microbiota leading to the production of a range of metabolites including SCFAs. Thus, prebiotics represent a dietary approach to increase levels of microbially produced SCFAs and improve intestinal permeability in diabetes. Whether prebiotics can lead to a reduction in the risk of developing diabetes complications in individuals with type 2 diabetes needs to be explored.
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http://dx.doi.org/10.1016/j.beem.2021.101507DOI Listing
February 2021

Treatment implications of a delayed diagnosis of maturity-onset diabetes of the young.

Intern Med J 2021 Jan;51(1):116-120

Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia.

Maturity-onset diabetes of the young (MODY) is a rare form of monogeneic diabetes that classically presents as non-insulin requiring diabetes with evidence of autosomal dominant inheritance in individuals who are typically young and lean. However, these criteria do not capture all cases and can also overlap with other types of diabetes. The hepatocyte nuclear factor-1 alpha (HNF1A) mutation is a common cause of MODY and is highly sensitive to sulphonylureas, which should be first-line therapy. Our case represents the diagnostic challenges of HNF1A MODY and the implications of a delayed diagnosis, which can lead to reduced success of sulphonylurea treatment.
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http://dx.doi.org/10.1111/imj.15157DOI Listing
January 2021

Gut Microbiome Composition Remains Stable in Individuals with Diabetes-Related Early to Late Stage Chronic Kidney Disease.

Biomedicines 2020 Dec 29;9(1). Epub 2020 Dec 29.

School of Medicine, Faculty of Health, Deakin University, Geelong Waurn Ponds, VIC 3220, Australia.

(1) Background: Individuals with diabetes and chronic kidney disease display gut dysbiosis when compared to healthy controls. However, it is unknown whether there is a change in dysbiosis across the stages of diabetic chronic kidney disease. We investigated a cross-sectional study of patients with early and late diabetes associated chronic kidney disease to identify possible microbial differences between these two groups and across each of the stages of diabetic chronic kidney disease. (2) Methods: This cross-sectional study recruited 95 adults. DNA extracted from collected stool samples were used for 16S rRNA sequencing to identify the bacterial community in the gut. (3) Results: The phylum Firmicutes was the most abundant and its mean relative abundance was similar in the early and late chronic kidney disease group, 45.99 ± 0.58% and 49.39 ± 0.55%, respectively. The mean relative abundance for family Bacteroidaceae, was also similar in the early and late group, 29.15 ± 2.02% and 29.16 ± 1.70%, respectively. The lower abundance of Prevotellaceae remained similar across both the early 3.87 ± 1.66% and late 3.36 ± 0.98% diabetic chronic kidney disease groups. (4) Conclusions: The data arising from our cohort of individuals with diabetes associated chronic kidney disease show a predominance of phyla Firmicutes and Bacteroidetes. The families Ruminococcaceae and Bacteroidaceae represent the highest abundance, while the beneficial Prevotellaceae family were reduced in abundance. The most interesting observation is that the relative abundance of these gut microbes does not change across the early and late stages of diabetic chronic kidney disease, suggesting that this is an early event in the development of diabetes associated chronic kidney disease. We hypothesise that the dysbiotic microbiome acquired during the early stages of diabetic chronic kidney disease remains relatively stable and is only one of many risk factors that influence progressive kidney dysfunction.
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http://dx.doi.org/10.3390/biomedicines9010019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824346PMC
December 2020

An overview of COVID-19 in people with diabetes: Pathophysiology and considerations in the inpatient setting.

Diabet Med 2021 03 5;38(3):e14509. Epub 2021 Feb 5.

Department of Medicine Austin Health, Melbourne Medical School, The University of Melbourne, Austin Health, Heidelberg, Vic., Australia.

Introduction: The coronavirus disease (COVID-19) pandemic has continued to have a devastating impact on health worldwide. There has been a rapid evolution of evidence, establishing an increased risk of morbidity and mortality associated with diabetes and concurrent COVID-19. The objective of this review is to explore the current evidence for inpatient assessment and management of diabetes during the COVID-19 pandemic and highlight areas requiring further exploration.

Methods: A literature search of databases was conducted to November 2020 using variations on keywords SARS-CoV-2, COVID-19, SARS, MERS and diabetes. Information relating to the impact of diabetes on severity of COVID-19 infection, the impact of COVID-19 infection on diabetes management and diabetes-related complications was integrated to create a narrative review.

Discussion: People with diabetes and COVID-19 are at an increased risk of morbidity and mortality. It is important that people with both known and previously unrecognised diabetes and COVID-19 be promptly identified and assessed during acute illness, with close monitoring for clinical deterioration or complications. People with diabetes may require titration or alteration of their glycaemic management due to the potential for worse outcomes with hyperglycaemia and COVID-19 infection. Comprehensive discharge planning is vital to optimise ongoing glycaemic management.

Conclusion: Further understanding of the risk of adverse outcomes and optimisation of glycaemic management for people with diabetes during COVID-19 is required to improve outcomes. Increased glucose and ketone monitoring, substitution of insulin for some oral anti-hyperglycaemic medications and careful monitoring for complications of diabetes such as diabetic ketoacidosis should be considered.
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http://dx.doi.org/10.1111/dme.14509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883197PMC
March 2021

Sarcopenia Is Associated With Reduced Function on Admission to Rehabilitation in Patients With Diabetes.

J Clin Endocrinol Metab 2021 Jan;106(2):e687-e695

Department of Medicine, Austin Health, Melbourne Medical School, The University of Melbourne, Heidelberg, Victoria, Australia.

Objective: This work aims to estimate the prevalence of sarcopenia and to investigate the association between sarcopenia and functional performance in patients with and without diabetes admitted for inpatient rehabilitation.

Materials And Methods: Consecutive patients admitted to the subacute inpatient rehabilitation unit at St Vincent's Hospital Melbourne, Australia (November 2016 to March 2020) were prospectively recruited into this cross-sectional study. Sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People 2018 algorithm. Participants' functional performance was measured by the total Functional Independence Measure, motor Functional Independence Measure, and the Short Physical Performance Battery. The association between sarcopenia and functional performance was investigated using quantile regression.

Results: Of 300 participants, 49 (16%) had a history of diabetes and 44 (14.7%) were diagnosed with sarcopenia. No significant difference in the prevalence of sarcopenia between patients with or without diabetes was identified (11/49, 22.5% vs 33/251, 13.2%, P = .12). In patients with diabetes, those with sarcopenia had significantly reduced functional performance compared to those without sarcopenia on Functional Independence Measure, motor Functional Independence Measure, and the Short Physical Performance Battery, whereas in patients without diabetes no significant difference between patients with and without sarcopenia were identified for either functional performance measure (all P values for interaction < .005).

Conclusions: The diagnosis of sarcopenia was associated with a reduced functional performance on admission to inpatient rehabilitation in patients with diabetes, but not in those without diabetes. Further investigation is needed into the progress of patients with dual diagnoses of diabetes and sarcopenia in inpatient rehabilitation.
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http://dx.doi.org/10.1210/clinem/dgaa878DOI Listing
January 2021

DNA methylation profiling identifies epigenetic differences between early versus late stages of diabetic chronic kidney disease.

Nephrol Dial Transplant 2020 Nov 4. Epub 2020 Nov 4.

Epigenetics Research, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Background: We investigated a cross-sectional epigenome-wide association study of patients with early and late diabetes-associated chronic kidney disease (CKD) to identify possible epigenetic differences between the two groups as well as changes in methylation across all stages of diabetic CKD. We also evaluated the potential of using a panel of identified 5'-C-phosphate-G-3' (CpG) sites from this cohort to predict the progression of diabetic CKD.

Methods: This cross-sectional study recruited 119 adults. DNA was extracted from blood using the Qiagen QIAampDNA Mini Spin Kit. Genome-wide methylation analysis was performed using Illumina Infinium MethylationEPIC BeadChips (HM850K). Intensity data files were processed and analysed using the minfi and MissMethyl packages for R. We examined the degree of methylation of CpG sites in early versus late diabetic CKD patients for CpG sites with an unadjusted P-value <0.01 and an absolute change in methylation of 5% (n = 239 CpG sites).

Results: Hierarchical clustering of the 239 CpG sites largely separated the two groups. A heat map for all 239 CpG sites demonstrated distinct methylation patterns in the early versus late groups, with CpG sites showing evidence of progressive change. Based on our differentially methylated region (DMR) analysis of the 239 CpG sites, we highlighted two DMRs, namely the cysteine-rich secretory protein 2 (CRISP2) and piwi-like RNA-mediated gene silencing 1 (PIWIL1) genes. The best predictability for the two groups involved a receiver operating characteristics curve of eight CpG sites alone and achieved an area under the curve of 0.976.

Conclusions: We have identified distinct DNA methylation patterns between early and late diabetic CKD patients as well as demonstrated novel findings of potential progressive methylation changes across all stages (1-5) of diabetic CKD at specific CpG sites. We have also identified associated genes CRISP2 and PIWIL1, which may have the potential to act as stage-specific diabetes-associated CKD markers, and showed that the use of a panel of eight identified CpG sites alone helps to increase the predictability for the two groups.
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http://dx.doi.org/10.1093/ndt/gfaa226DOI Listing
November 2020

Performance of 4 Creatinine-based Equations in Assessing Glomerular Filtration Rate in Adults with Diabetes.

J Clin Endocrinol Metab 2021 Jan;106(1):e61-e73

Melbourne Medical School, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.

Aims: To evaluate diagnostic performance of glomerular filtration rate (GFR) estimated by modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI), full age spectrum (FAS), and revised Lund-Malmö (r-LM) equations in adults with diabetes.

Methods: Individuals were included in this cross-sectional study if they had at least 1 measurement of technetium-99m diethylenetriamine-pentaacetic acid (99mTc-DTPA) GFR (mGFR) and serum creatinine (1487 patients with 2703 measures). GFR calculated by estimation equations was compared with mGFR. Diagnostic performance was assessed using concordance correlation coefficient (CCC), bias, precision, accuracy, reduced major axis regression (RMAR), and Bland-Altman plot. Analysis was repeated in subgroups based on sex, diabetes type, Hemoglobin A1C, and GFR level.

Results: Of all patients, 1189 (86%) had type 2 diabetes. Mean mGFR, MDRD, CKD-EPI, FAS, and revised Lund-Malmö eGFR were 66, 72, 74, 71, and 67 mL/min/1.73m2, respectively. Overall, the r-LM had the highest CCC (0.83), lowest bias (-1.4 mL/min/1.73 m2), highest precision (16.2 mL/min/1.73 m2), and highest accuracy (P10 = 39%). The RMAR (slope, intercept) in r-LM, FAS, MDRD, and CKD-EPI was 1.18, -13.35; 0.97, -2.9; 1, -6.4, and 1.04, -11.3, respectively. The Bland-Altman plot showed that r-LM had the lowest mean difference and the narrowest 95% limit of agreement (-1.0, 54.1 mL/min/1.73 m2), while mean difference was more than 5-fold higher in FAS, MDRD, and CKD-EPI (-5.2, -6.3, and -8.2, respectively).

Conclusions: In adults with diabetes the revised Lund-Malmö performs better than MDRD, CKD-EPI, and FAS in calculating point estimates of GFR.
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http://dx.doi.org/10.1210/clinem/dgaa722DOI Listing
January 2021

Potential for Novel Biomarkers in Diabetes-Associated Chronic Kidney Disease: Epigenome, Metabolome, and Gut Microbiome.

Biomedicines 2020 Sep 10;8(9). Epub 2020 Sep 10.

School of Medicine, Faculty of Health, Deakin University, Geelong Waurn Ponds, VIC 3220, Australia.

Diabetes-associated chronic kidney disease is a pandemic issue. Despite the global increase in the number of individuals with this chronic condition together with increasing morbidity and mortality, there are currently only limited therapeutic options to slow disease progression. One of the reasons for this is that the current-day "gold standard" biomarkers lack adequate sensitivity and specificity to detect early diabetic chronic kidney disease (CKD). This review focuses on the rapidly evolving areas of epigenetics, metabolomics, and the gut microbiome as potential sources of novel biomarkers in diabetes-associated CKD and discusses their relevance to clinical practice. However, it also highlights the problems associated with many studies within these three areas-namely, the lack of adequately powered longitudinal studies, and the lack of reproducibility of results which impede biomarker development and clinical validation in this complex and susceptible population.
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http://dx.doi.org/10.3390/biomedicines8090341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7555227PMC
September 2020

Lipoprotein apheresis and PCSK9 inhibitors for severe familial hypercholesterolaemia: Experience from Australia and New Zealand.

J Clin Apher 2021 Feb 10;36(1):48-58. Epub 2020 Sep 10.

School of Medicine, University of Western Australia, Crawley, Western Australia, Australia.

Introduction: Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid-lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time-consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA.

Materials And Methods: We audited the records of 16 patients (eight homozygous, eight heterozygous) treated with LA in Australia and New Zealand, 14 of whom subsequently commenced PCSK9 inhibitor therapy. LA was performed by cascade filtration in all centres.

Results: LDL-cholesterol was acutely lowered by 69 ± 7% in patients with homozygous FH and by 72 ± 9% in those with heterozygous FH, representing time-averaged reductions of 36 ± 12% and 34 ± 5%, respectively. LA was well-tolerated, and patients reported comparable quality of life to population and disease-related norms. After commencement of PCSK9 inhibitors, four of seven patients with homozygous FH had meaningful biochemical responses, with a reduction in the frequency of LA permitted in one patient and complete cessation in another. Four of seven patients with heterozygous FH were able to be managed without LA after commencing PCSK9 inhibitors.

Conclusion: While PCSK9 inhibitors have reduced the need for LA, some patients with severe FH continue to require LA, and will require it for the foreseeable future. However, emerging therapies, including angiopoetin-like 3 inhibitors, may further reduce the need for LA.
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http://dx.doi.org/10.1002/jca.21839DOI Listing
February 2021

Identification of Potential Biomarkers of Chronic Kidney Disease in Individuals with Diabetes: Protocol for a Cross-sectional Observational Study.

JMIR Res Protoc 2020 Jul 31;9(7):e16277. Epub 2020 Jul 31.

Epigenetics Research, Murdoch Children's Research Institute, Victoria, Australia.

Background: The importance of identifying people with diabetes and progressive kidney dysfunction relates to the excess morbidity and mortality of this group. Rates of cardiovascular disease are much higher in people with both diabetes and kidney dysfunction than in those with only one of these conditions. By the time these people are identified in current clinical practice, proteinuria and renal dysfunction are already established, limiting the effectiveness of therapeutic interventions. The identification of an epigenetic or blood metabolite signature or gut microbiome profile may identify those with diabetes at risk of progressive chronic kidney disease, in turn providing targeted intervention to improve patient outcomes.

Objective: This study aims to identify potential biomarkers in people with diabetes and chronic kidney disease (CKD) associated with progressive renal injury and to distinguish between stages of chronic kidney disease. Three sources of biomarkers will be explored, including DNA methylation profiles in blood lymphocytes, the metabolomic profile of blood-derived plasma and urine, and the gut microbiome.

Methods: The cross-sectional study recruited 121 people with diabetes and varying stages (stages 1-5) of chronic kidney disease. Single-point data collection included blood, urine, and fecal samples in addition to clinical data such as anthropometric measurements and biochemical parameters. Additional information obtained from medical records included patient demographics, medical comorbidities, and medications.

Results: Data collection commenced in January 2018 and was completed in June 2018. At the time of submission, 121 patients had been recruited, and 119 samples remained after quality control. There were 83 participants in the early diabetes-associated CKD group with a mean estimated glomerular filtration rate (eGFR) of 61.2 mL/min/1.73 m2 (early CKD group consisting of stage 1, 2, and 3a CKD), and 36 participants in the late diabetic CKD group with a mean eGFR of 23.9 mL/min/1.73 m2 (late CKD group, consisting of stage 3b, 4, and 5), P<.001. We have successfully obtained DNA for methylation and microbiome analyses using the biospecimens collected via this protocol and are currently analyzing these results together with the metabolome of this cohort of individuals with diabetic CKD.

Conclusions: Recent advances have improved our understanding of the epigenome, metabolomics, and the influence of the gut microbiome on the incidence of diseases such as cancers, particularly those related to environmental exposures. However, there is a paucity of literature surrounding these influencers in renal disease. This study will provide insight into the fundamental understanding of the pathophysiology of CKD in individuals with diabetes, especially in novel areas such as epigenetics, metabolomics, and the kidney-gut axis.

International Registered Report Identifier (irrid): DERR1-10.2196/16277.
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http://dx.doi.org/10.2196/16277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428908PMC
July 2020

GripBMI - A fast and simple sarcopenia screening tool in post acute inpatient rehabilitation.

Clin Nutr 2021 Mar 14;40(3):1022-1027. Epub 2020 Jul 14.

Department of Medicine, Austin Health, Melbourne Medical School, The University of Melbourne, Heidelberg, Victoria, Australia; Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.

Background & Aims: Sarcopenia is prevalent in post acute inpatient rehabilitation. An easy to administer screening test may improve identification of sarcopenia in this population, which may promote its early detection and treatment. THE AIMS OF THIS STUDY WERE: a) To investigate clinical utility of SARC-F as a European Working Group on Sarcopenia in Older People2 (EWGSOP2) recommended tool for sarcopenia case finding in post acute inpatient rehabilitation. b) To develop an easy and pragmatic screening test for sarcopenia in healthcare settings with limited ability to measure the patients' muscle mass for confirmation of the sarcopenia diagnosis.

Methods: This cross-sectional study with prospective data collection recruited patients admitted to a general inpatient rehabilitation unit in a metropolitan tertiary referral hospital in Australia. Participant's true sarcopenia status was ascertained, as per EWGSOP2, from their grip strength and muscle mass. Two SARC-F questionnaires were administered, for participants' current and, by recall, premorbid status. To develop GripBMI screening tool, BMI test positivity cut off was established on training sample and validated in conjunction with the established grip strength cut off on validation sample using area under the Receiver Operating Curve (ROC) analysis.

Results: True prevalence of sarcopenia in 277 participants (median age 64 years (IQR 53-72), 52% male) was 14% (95%CI 11%-19%). Screening utility of SARC-F positive status at the time of admission for sarcopenia had ROC of 0.50, and of premorbid SARC-F positive status had ROC of 0.51. Out of 42 participants positive on the GripBMI screen, 33 had sarcopenia, and out of 235 participants negative on the GripBMI screen, 7 participants had sarcopenia, resulting in GripBMI ROC area 0.89, sensitivity 83%, specificity 96%, positive predictive value 79%, negative predictive value 97%, diagnostic odds ratio 119 (95% CI 42-338).

Conclusions: The GripBMI screening tool uses the combination of EWGSOP2 recommended low grip strength cut offs and Body Mass Index of less than 25 as a positive screening test for sarcopenia. It may assist in promoting early detection and management of sarcopenia in post acute inpatient rehabilitation.
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http://dx.doi.org/10.1016/j.clnu.2020.06.034DOI Listing
March 2021

Considerations for people with diabetes during the Coronavirus Disease (COVID-19) pandemic.

Diabetes Res Clin Pract 2020 Aug 3;166:108296. Epub 2020 Jul 3.

Department of Medicine, Austin Health, Melbourne, Victoria, Australia; Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia. Electronic address:

Introduction: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) continues to cause havoc globally, resulting in unprecedented healthcare, societal and economic disruption. People with diabetes have been shown to be at higher risk of complications and death when exposed to pneumonia, influenza and other coronaviruses. Despite pandemic scale infection, there is currently limited understanding on the potential impact of coronavirus disease (COVID-19) on people with diabetes.

Aims: (1) To characterise the outcomes of COVID-19 for people with diabetes and (2) add value to current recommendations for healthcare providers and people with diabetes to encourage optimal management.

Methods: A search of PubMed, Embase and MEDLINE to March 2020 was undertaken, using search terms pertaining to diabetes, coronavirus and acute respiratory distress syndrome (ARDS). We briefly reviewed the epidemiology and pathophysiology of SARS-CoV-2 in the context of diabetes.

Conclusion: People with diabetes are at greater risk of severe infection and death with COVID-19. COVID-19 has significantly impacted the daily lives of individuals living with diabetes through financial implications, food and medication scarcity and its burden on mental health. In Australia, delivery of medical care has been adapted to reduce the risk of transmission, with a particular emphasis on telehealth and remote monitoring.
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http://dx.doi.org/10.1016/j.diabres.2020.108296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332442PMC
August 2020

Exploring the Relationship Between Maternal Circulating Hormones and Gestational Weight Gain in Women Without Obesity: A Cross-Sectional Study.

Int J Womens Health 2020 15;12:455-462. Epub 2020 Jun 15.

University of Melbourne, Department of Medicine (Austin), Melbourne, Australia.

Background: Central homeostatic regulation of fat stores is attenuated during pregnancy, to allow for adequate fat deposition to support fetal development and lactation. What factors particular to pregnancy facilitate fat accumulation, and why gestational weight gain (GWG) is so variable, are not clear. The aim of this cross-sectional study was to examine the associations between GWG and circulating hormones with known effects on appetite and growth.

Methods: Women without obesity (body mass index, BMI <30 kg/m), with a healthy singleton pregnancy, were recruited at the time of delivery by elective Caesarean section at a tertiary obstetric hospital. Women with preterm (<37 weeks) delivery and smokers were excluded. Maternal blood was collected at the time of delivery for measurement of fasting oestradiol, progesterone, prolactin, insulin, leptin, insulin-like growth factor 1 and insulin-like growth factor binding protein 3. Comparisons were made between women who gained weight within the range recommended by Institute of Medicine guidelines for normal weight women (11.5-16 kg; n=34) and those who gained excessive weight (>16 kg; n=35) during pregnancy. Analysis of covariance was carried out using multiple linear regression to test the effect of GWG group on biochemical parameters, accounting for pre-pregnancy BMI.

Results: The 69 participants had a mean age of 34.6 ± 4.3 years, and pre-pregnancy BMI of (23.3 ± 1.8 kg/m), with no significant differences between groups in pre-pregnancy weight, BMI, age, birthweight or parity. Mean GWG was 14.0 ± 1.3 kg in the "recommended" group and 19.6 ± 3.2 kg in the "excessive" group. Leptin was significantly higher (43.4 ± 21.6 vs 33.4 ± 15.0 ng/mL, p=0.03) and prolactin tended to be lower (159.5 ± 66.1 vs 194.0 ± 85.6 ng/mL, p=0.07) at delivery in women with excessive (vs recommended) GWG. No other circulating factors were found to differ between groups. The between-group difference in leptin remained after adjustment for pre-pregnancy BMI in multiple linear regression and quantile regression analyses.

Conclusion: In women without obesity, leptin remains a marker of adiposity during pregnancy. GWG was not associated with other circulating hormones with effects on appetite and growth.
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http://dx.doi.org/10.2147/IJWH.S241785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305340PMC
June 2020

Dietary sodium and potassium intake in people with diabetes: are guidelines being met?

Nutr Diabetes 2020 06 17;10(1):23. Epub 2020 Jun 17.

Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia.

Objective: Despite public health bodies advocating for lowering dietary sodium and increasing potassium intake to improve cardiovascular outcomes, people with diabetes are not meeting these targets. We hypothesize that (i) both at an individual level and within the cohort, there will be a low adherence to the guidelines and (ii) sodium and potassium intake will remain stable over time.

Methods: We conducted this prospective study in a cohort of 904 participants with diabetes who provided 24-h urine collections from 2009 to 2015. Dietary sodium and potassium intake were estimated from 24-h urinary sodium (uNa) and potassium (uK) measurements. Additional data were collected for: 24-h urinary volume (uVol), creatinine (uCr),; serum creatinine, urea, estimated glomerular filtration rate (eGFR), glycated haemoglobin (HbA1c), fasting glucose, lipids); clinical characteristics (age, blood pressure (BP), body mass index (BMI) and duration of diabetes). Adherence to recommended dietary sodium (uNa < 2300 mg/24 h (100mmol/24 h)) and potassium (uK > 4680 mg/24 h(120 mmol/24)) intake were the main outcome measures.

Results: Participants (n = 904) completed 3689 urine collections (average four collections/participant). The mean ± SD (mmol/24 h) for uNa was 181 ± 73 and uK was 76 ± 25. After correcting uNa for uCr, 7% and 5% of participants met dietary sodium and potassium guidelines respectively. Males were less likely to meet sodium guidelines (OR 0.40, p < 0.001) but were more likely to meet potassium guidelines (OR 6.13, p < 0.001). Longer duration of diabetes was associated with higher adherence to sodium and potassium guidelines (OR 1.04, p < 0.001 and OR 0.96, p = 0.006 respectively). Increasing age was significantly associated with adherence to potassium guidelines (OR 0.97, p = 0.007).

Conclusions: People with diabetes do not follow current dietary sodium and potassium guidelines and are less likely to change their dietary intake of sodium and potassium over time.
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http://dx.doi.org/10.1038/s41387-020-0126-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298627PMC
June 2020

The association between maternal renal function and pregnancy outcomes in type 1 and type 2 diabetes.

Diabetes Res Clin Pract 2020 Jul 20;165:108225. Epub 2020 May 20.

Department of Perinatal Medicine, Mercy Health, 163 Studley Road, Heidelberg, VIC 3084, Australia; Department of Endocrinology and Diabetes, Austin Health, 145 Studley Road, Heidelberg, VIC 3084, Australia. Electronic address:

Aims: To investigate the prognostic value of estimated glomerular filtration rate (eGFR) and albuminuria in determining pregnancy outcomes in women with type 1 and type 2 diabetes.

Methods: An observational study of pregnant women with type 1 (n = 92) and type 2 diabetes (n = 106) who delivered between 2004 and 2014 at a single tertiary obstetric centre. Clinical and biochemical characteristics were determined and related to major obstetric outcomes: preeclampsia, preterm birth <32 and <37 weeks, and neonatal intensive care admission. We used univariate analyses and multivariable logistic regression models with eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and albuminuria as covariates.

Results: In the pooled diabetes cohort, multivariable logistic regression with eGFR and albuminuria status demonstrated that the presence of albuminuria (albumin-to-creatinine ratio ≥ 3.5 mg/mmol) (OR, 2.7; 95% CI, 1.42-4.99; P = 0.002) was associated with preeclampsia, whilst an eGFR of < 120 mL/min/1.73 m was associated with preterm birth < 32 weeks (OR, 1.04; 95% CI, 1.00-1.09; P = 0.02).

Conclusions: Despite its recognized limitations in pregnancy, lower eGFR values were associated with increased risk of adverse outcomes. Our exploratory data suggest eGFR, along with albuminuria, can aid in identifying women at high risk of developing adverse obstetric outcomes.
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http://dx.doi.org/10.1016/j.diabres.2020.108225DOI Listing
July 2020

Evolving Evidence of Diabetic Ketoacidosis in Patients Taking Sodium-Glucose Cotransporter 2 Inhibitors.

J Clin Endocrinol Metab 2020 08;105(8)

Department of Medicine, Austin Health, Heidelberg, Victoria, Australia.

Introduction: Sodium glucose cotransporter 2 inhibitors (SGLT2i) have emerged as an important class of blood glucose-lowering medications, due to cardiovascular, metabolic, and renal benefits. However, there is a small but significant risk of diabetic ketoacidosis (DKA) associated with their use.

Methods: A literature search was conducted in Ovid MEDLINE and Embase to July 2019 using variants on the key search terms sodium-glucose cotransporter 2, diabetic ketoacidosis, and type 2 diabetes. A broad spectrum of evidence was incorporated to facilitate a comprehensive narrative review. Further sources were identified through hand searching of reference lists.

Discussion: Although cardiovascular outcome trials demonstrated mixed evidence of SGLT2i associated DKA, increasing evidence from case reports and cohort studies has identified an increased risk. SGLT2i use is associated with a ketotic state caused by an increased glucagon:insulin ratio and stimulated by factors including stress-induced hormonal changes, insufficient insulin, decreased glucose, increased ketone resorption, and hypovolemia. Atypical presentations of DKA with lower-than-expected blood glucose levels are possible with SGLT2i use, so clinical and biochemical monitoring is vital for early identification and management. DKA risk is particularly increased with precipitating factors, therefore optimization of risk factors is vital. Recommendations for perioperative and sick day management of patients taking SGLT2i have been suggested based on available evidence.

Conclusion: SGLT2i are an excellent class of drug in the physician's toolkit for managing type 2 diabetes. However, both clinicians and patients must be aware of the potential for DKA and the need for increased monitoring, both clinically and biochemically, when potential precipitating factors are present. In acutely unwell patients, these medications should be withheld to reduce the risk of DKA.
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http://dx.doi.org/10.1210/clinem/dgaa200DOI Listing
August 2020

Goal attainment scaling outcomes in general inpatient rehabilitation: association with functional independence and perceived goal importance and difficulty.

J Rehabil Med 2020 Apr 29;52(4):jrm00054. Epub 2020 Apr 29.

Rehabilitation Unit, St Vincent's Health, Fitzroy, Australia.

Objective: To investigate the association of goal attainment scaling outcomes with change in the Func-tional Independence Measure, and the association between the perceived importance, difficulty and degree of achievement of individual goals in general inpatient rehabilitation.

Design: Prospective cohort study.

Participants: A total of 208 participants admitted to inpatient rehabilitation in a metropolitan tertiary referral hospital in Melbourne, Australia.

Methods: Participants determined the nature of the goals and their importance, and therapists determined the difficulty of the goals. The associations were investigated using median regression and random effect ordinal regression.

Results: An increase of each point in the goal attainment scaling score was associated with an adjusted median increase of 0.34 points (95% confidence interval (CI): 0.18-0.5, p < 0.001) in Functional Independence Measure change. More important goals of similar difficulty (very important vs a little important: adjusted common odds ratio (cOR) = 1.97, 95% CI: 1.01-3.83, p = 0.045) and less difficult goals of similar importance (moderately difficult vs a little difficult cOR = 0.59, 95% CI: 0.04-0.87, p = 0.007; very difficult vs a little difficult cOR = 0.59, 95% CI 0.37-0.94, p = 0.027) were better achieved.

Conclusion: Rehabilitation progress measured using the goal attainment scaling method is associated with changes in functional outcomes. For goals with similar difficulty, those with higher importance were better achieved, while for goals with similar importance, less difficult goals were better achieved.
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http://dx.doi.org/10.2340/16501977-2675DOI Listing
April 2020

Risk factors for pregnancy outcomes in Type 1 and Type 2 diabetes.

Intern Med J 2021 Jan;51(1):78-86

Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia.

Background: Understanding the risk factors and pregnancy outcomes in women affected by Type 1 and Type 2 diabetes is important for pre-pregnancy counselling.

Aim: To explore differences in pregnancy outcomes between women with Type 1 and Type 2 diabetes, and healthy controls, and to examine the relationships between potential adverse risk factors and pregnancy outcomes in this cohort of women.

Methods: This is a 10-year retrospective study of women with Type 1 diabetes (n = 92), Type 2 diabetes (n = 106) and healthy women without diabetes (controls) (n = 119) from a tertiary obstetric centre. Clinical and biochemical characteristics of women with Type 1 and Type 2 diabetes were determined and related to major obstetric outcomes using univariate analysis.

Results: Women with pre-existing diabetes had higher adverse pregnancy outcomes (preeclampsia, emergency caesarean section, preterm birth <32 and 37 weeks, large for gestational age, neonatal jaundice, Apgar score < 7 at 5 min, neonatal intensive care admission and neonatal hypoglycaemia) compared to controls. A higher birth weight gestational centile (97.4% vs 72.4%, P = 0.001) and large for gestational age rate (63.4% vs 35.8%, P = 0.001) were observed in Type 1 diabetes compared to Type 2 diabetes. There were no differences in other outcomes between women with Type 1 and 2 diabetes.

Conclusion: In this exploratory study, risk factors for maternal adverse outcomes differ between Type 1 and Type 2 diabetes. Maternal and foetal adverse outcomes were higher in pregnancies affected by diabetes compared to healthy women but occurred with similar frequency in women with Type 1 and Type 2 diabetes.
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http://dx.doi.org/10.1111/imj.14840DOI Listing
January 2021

A safety and pharmacodynamics study of temelimab, an antipathogenic human endogenous retrovirus type W envelope monoclonal antibody, in patients with type 1 diabetes.

Diabetes Obes Metab 2020 07 12;22(7):1111-1121. Epub 2020 Mar 12.

Eastern Clinical Research Unit, Eastern Health and Monash University, Box Hill, Victoria, Australia.

Aim: To report the first study of temelimab, a monoclonal antibody neutralizing the pathogenic human endogenous retrovirus type W envelope, in patients with type 1 diabetes (T1D).

Materials And Methods: This double-blind, placebo-controlled, randomized clinical trial recruited adult patients with T1D within 4 years postdiagnosis and remaining C-peptide secretion. Sixty-four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks followed by a 24-week, open-label extension, during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess the pharmacodynamics response such as C-peptide levels, insulin use, HbA1c, hypoglycaemia and autoantibodies.

Results: Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C-peptide, insulin use or HbA1c between treatment groups at weeks 24 and 48. The frequency of hypoglycaemia events was reduced with temelimab (P = 0.0004) at week 24 and the level of anti-insulin antibodies was lower with temelimab (P < 0.01); the other autoantibodies did not differ between groups.

Conclusions: Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti-insulin antibodies) under temelimab were observed. Markers of β-cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset.
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http://dx.doi.org/10.1111/dom.14010DOI Listing
July 2020

Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes.

Med J Aust 2020 02 7;212(3):133-139. Epub 2020 Jan 7.

Melbourne University, Melbourne, VIC.

Treatment options for type 2 diabetes have expanded. While metformin remains the first line treatment in most cases, choices for second line treatment now extend beyond sulfonylureas and include the sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1) receptor agonists, and dipeptidyl peptidase 4 (DPP4) inhibitors. SGLT2 inhibitors are recommended for people with atherosclerotic cardiovascular disease, heart failure or kidney disease. Diabetic ketoacidosis is an uncommon but important side effect; its occurrence can be minimised with appropriate patient education and management, especially during perioperative periods and times of illness. GLP1 receptor agonists are recommended for people with atherosclerotic cardiovascular disease. Gastrointestinal side effects are common but are less prominent with the longer acting agents and can be minimised with slow titration of the shorter acting agents. DPP4 inhibitors are generally well tolerated, but alogliptin and saxagliptin should be used with caution in people with risk factors for heart failure. To optimise the management of type 2 diabetes, clinicians need to be aware of the pharmacological characteristics of each class of blood glucose-lowering medications and of the effect on cardiovascular health and renal function, balanced by potential adverse effects. Medications that have cardiovascular or renal benefits should be prescribed for patients with these comorbidities, and this is reflected in recent international guidelines.
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http://dx.doi.org/10.5694/mja2.50472DOI Listing
February 2020

Effect of Salt Supplementation on Sympathetic Activity and Endothelial Function in Salt-Sensitive Type 2 Diabetes.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Endocrinology, Austin Health, Heidelberg, Victoria, Australia.

Context: Lower sodium intake is paradoxically associated with higher mortality in type 2 diabetes (T2D).

Objective: To determine whether sympathetic nervous system (SNS) activation and endothelial dysfunction contribute to these observations, we examined the effect of salt supplementation on these systems in people with T2D with habitual low sodium. We hypothesized that salt supplementation would lower SNS activity and improve endothelial function compared to placebo.

Design: We conducted a randomized, double-blinded, placebo-controlled crossover trial.

Setting: The study took place in a tertiary referral diabetes outpatient clinic.

Participants: Twenty-two people with T2D with habitual low sodium intake (24-hour urine sodium <150 mmol/24h) were included.

Intervention: Salt supplementation (100 mmol NaCl/24h) or placebo for 3 weeks was administered.

Main Outcome Measures: The primary outcome of SNS activity and endothelial function was assessed as follows: Microneurography assessed muscle sympathetic nerve activity (MSNA), pulse amplitude tonometry assessed endothelial function via reactive hyperemic index (RHI), and arterial stiffness was assessed via augmentation index (AI). Secondary outcomes included cardiac baroreflex, serum aldosterone, ambulatory blood pressure monitoring (ABPM), heart rate variability (HRV), and salt sensitivity.

Results: Compared to placebo, salt supplementation increased MSNA (burst frequency P = .047, burst incidence P = .016); however, RHI (P = .24), AI (P = .201), ABPM (systolic P = .09, diastolic P = .14), and HRV were unaffected. Salt supplementation improved baroreflex (slope P = .026) and lowered aldosterone (P = .004), and in salt-resistant individuals there was a trend toward improved RHI (P = .07).

Conclusions: In people with T2D and low habitual sodium intake, salt supplementation increased SNS activity without altering endothelial function or blood pressure but improved baroreflex function, a predictor of cardiac mortality. Salt-resistant individuals trended toward improved endothelial function with salt supplementation.
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http://dx.doi.org/10.1210/clinem/dgz219DOI Listing
April 2020

A physician-initiated double-blind, randomised, placebo-controlled, phase 2 study evaluating the efficacy and safety of inhibition of NADPH oxidase with the first-in-class Nox-1/4 inhibitor, GKT137831, in adults with type 1 diabetes and persistently elevated urinary albumin excretion: Protocol and statistical considerations.

Contemp Clin Trials 2020 03 16;90:105892. Epub 2019 Nov 16.

Baker Heart and Diabetes Institute, Level 4, Alfred Centre, 99 Commercial Road, Melbourne, VIC 3004, Australia. Electronic address:

Purpose: Kidney disease caused by type 1 diabetes can progress to end stage renal disease and can increase mortality risk. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) plays a major role in producing oxidative stress in the kidney in diabetes, and its activity is attenuated by GKT137831, an oral Nox inhibitor with predominant inhibitory action on Nox-1 and Nox - 4. Previous studies have demonstrated renoprotective effects with GKT137831 in various experimental models of type 1 diabetes-related kidney disease. This study will evaluate the effect of GKT137831 in treating clinical diabetic kidney disease.

Design: This is a multi-center, randomized, placebo-controlled trial, parallel arm study evaluating the effect on albuminuria of treatment with GKT137831 400 mg BID for 48 weeks. The study will randomize 142 participants who have persistent albuminuria and estimated glomerular filtration rate (eGFR) at baseline of at least 40 ml/min/1.73m.

Primary Outcome Measures: Difference between arms in urine albumin to creatinine ratio. Secondary outcome measures include eGFR.

Conclusion: This study is important because it may identify a new way of slowing renal disease progression in people with type 1 diabetes and albuminuria already receiving standard of care treatment.
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http://dx.doi.org/10.1016/j.cct.2019.105892DOI Listing
March 2020

Inflammatory proteins in diabetic kidney disease-potential as biomarkers and therapeutic targets.

Ann Transl Med 2019 Sep;7(Suppl 6):S243

Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.

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http://dx.doi.org/10.21037/atm.2019.08.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789318PMC
September 2019

Complement C5a Induces Renal Injury in Diabetic Kidney Disease by Disrupting Mitochondrial Metabolic Agility.

Diabetes 2020 01 17;69(1):83-98. Epub 2019 Oct 17.

Department of Diabetes, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia

The sequelae of diabetes include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury associated with a disruption in mitochondrial metabolic agility, inflammation, and fibrosis. We explored the role of the innate immune complement component C5a, a potent mediator of inflammation, in the pathogenesis of DKD in clinical and experimental diabetes. Marked systemic elevation in C5a activity was demonstrated in patients with diabetes; conventional renoprotective agents did not therapeutically target this elevation. C5a and its receptor (C5aR1) were upregulated early in the disease process and prior to manifest kidney injury in several diverse rodent models of diabetes. Genetic deletion of C5aR1 in mice conferred protection against diabetes-induced renal injury. Transcriptomic profiling of kidney revealed diabetes-induced downregulation of pathways involved in mitochondrial fatty acid metabolism. Interrogation of the lipidomics signature revealed abnormal cardiolipin remodeling in diabetic kidneys, a cardinal sign of disrupted mitochondrial architecture and bioenergetics. In vivo delivery of an orally active inhibitor of C5aR1 (PMX53) reversed the phenotypic changes and normalized the renal mitochondrial fatty acid profile, cardiolipin remodeling, and citric acid cycle intermediates. In vitro exposure of human renal proximal tubular epithelial cells to C5a led to altered mitochondrial respiratory function and reactive oxygen species generation. These experiments provide evidence for a pivotal role of the C5a/C5aR1 axis in propagating renal injury in the development of DKD by disrupting mitochondrial agility, thereby establishing a new immunometabolic signaling pathway in DKD.
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http://dx.doi.org/10.2337/db19-0043DOI Listing
January 2020

Feasibility of using a transition diabetes team to commence injectable therapies postdischarge from a tertiary hospital: a pilot, randomised controlled trial.

BMJ Open 2019 09 20;9(9):e023583. Epub 2019 Sep 20.

Endocrinology, Austin Health, Heidelberg, Victoria, Australia.

Objectives: This study aimed to investigate if the use of a transition team was feasible for patients with diabetes being discharged from hospital on injectable diabetes therapies.

Design: Pilot, randomised controlled trial.

Setting: The trial was conducted between 2014 and 2016 conjointly by a tertiary referral hospital and a community healthcare provider.

Participants: Hospital inpatients (n=105) on new injectable diabetes therapies were randomised 1:1 to transition team or standard care. The transition team received in-home diabetes education 24-48 hours postdischarge, with endocrinologist review 2-4 weeks and 16 weeks postdischarge.

Main Outcome Measures: The primary outcome was feasibility, defined by percentage of patients successfully receiving the intervention. Secondary outcomes included safety, defined by hospital readmission and emergency department presentations within 16 weeks postrandomisation, and treatment satisfaction, measured using Diabetes Treatment Satisfaction Questionnaire (DTSQ). Exploratory outcomes included length of stay (LOS) and change in haemoglobin A1c (HbA1c) throughout the study.

Results: The intervention was deemed feasible (85% (95% CI 73% to 94%)). No difference in safety between groups was detected. No difference in change in HbA1c between groups was detected (standard care median HbA1c -1.5% (IQR -3.7% to -0.2%) vs transition team median HbA1c -1.9% (IQR -3.8% to -0.2%), p=0.83). There was a trend towards reduced LOS in the transition team group (per protocol, standard care median LOS 8 (IQR 5.5-12); transition team median LOS 6 (IQR 3-12), p=0.06). There was a significant improvement in patient satisfaction in the transition team (standard care median 10.5 (IQR 8.5-16); transition team DTSQ change version median 15 (IQR 10-17.5), p=0.047), although interpretability is limited by missing data.

Conclusion: This study demonstrated that the use of a novel transition diabetes team is a feasible alternative model of care.
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http://dx.doi.org/10.1136/bmjopen-2018-023583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756454PMC
September 2019

Progression of Diabetic Kidney Disease in the Absence of Albuminuria.

Diabetes Care 2019 Oct;42(10):1842-1844

Austin Health and Department of Medicine, University of Melbourne, Melbourne, Australia.

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http://dx.doi.org/10.2337/dci19-0030DOI Listing
October 2019

Effect of angiotensin II receptor blocker and salt supplementation on short-term blood pressure variability in type 2 diabetes.

J Hum Hypertens 2020 02 9;34(2):143-150. Epub 2019 Sep 9.

Department of Endocrinology, Austin Health, Melbourne, VIC, Australia.

High blood pressure variability (BPV) has been associated with increased cardiovascular (CV) risk. The effect of dietary salt and renin-angiotensin-aldosterone system (RAAS) activity on short-term BPV in type 2 diabetes mellitus (T2DM) is not well characterised. We aimed to determine the effect of dietary salt (sodium chloride, NaCl) supplementation on 24-h mean arterial BPV (24hBPV) during angiotensin II receptor blocker (telmisartan) use and to evaluate the effects of age, sex, plasma renin activity (PRA) and serum aldosterone on 24hBPV. In a randomised, double-blind, crossover study, patients with T2DM (n = 28), treated with telmisartan received NaCl (100 mmol/24 h) or placebo capsules during 2 weeks of telmisartan. Following a 6-week washout, the protocol was repeated in reverse. 24hBPV was evaluated as a co-efficient of variation [CV (%) = mean/standard deviation] × 100). Twenty-four hour urinary sodium excretion, ambulatory BP and biochemical tests were performed at each phase. Results were analysed using a linear mixed model to generate predicted values for 24hBPV. Predicted 24hBPV was higher with telmisartan vs baseline (p = 0.01), with a trend towards reduced 24hBPV with salt (p = 0.052). Predicted 24hBPV was lower in females (p = 0.017), increasing age (p = 0.001) and increasing PRA (p = 0.011). In patients with T2DM, predicted 24hBPV increased from baseline with telmisartan, but there was no additional increase in predicted 24hBPV with salt supplementation. This suggests that in the short-term, salt supplementation has no apparent deleterious effects on 24hBPV. Long-term studies are required to evaluate the effect of 24hBPV on CV outcomes in patients with T2DM.
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http://dx.doi.org/10.1038/s41371-019-0238-3DOI Listing
February 2020

Impact of botanical fermented foods on metabolic biomarkers and gut microbiota in adults with metabolic syndrome and type 2 diabetes: a systematic review protocol.

BMJ Open 2019 07 30;9(7):e029242. Epub 2019 Jul 30.

School of Agriculture and Food, University of Melbourne, Melbourne, Victoria, Australia

Introduction: Dysfunctional gut microbiota is a common finding in patients with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). Recent clinical trials have assessed whether botanical fermented foods (BFFs) have beneficial effects on metabolic biomarkers, inflammatory markers and gut microbiota. The aim of this review is to critically evaluate all randomised controlled trials (RCTs) of BFF for evidence of impact on the outcome measures of these disease states.

Methods And Analysis: Four electronic databases (Embase, MEDLINE, CENTRAL and Google Scholar) as well as the grey literature will be searched from inception to present without language or publication status restrictions applied. Eligible RCTs which have enrolled adult participants with T2DM, any MetS components or combinations of these components, treated prophylactically or therapeutically with any botanical fermented food intervention, compared with a control group (no intervention, placebo or active control) will be assessed. Primary outcomes are related to the target conditions, including metabolic biomarkers, inflammatory markers and gut microbiota composition/function. Using Covidence, two independent investigators will conduct title and abstract screening, followed by full-text screening to identify appropriate studies. Methodological quality of the trials will be assessed using the Cochrane risk of bias assessment tool. Findings will be summarised with a narrative synthesis of the differences between included studies. A meta-analysis will be conducted if sufficient data are obtained.

Ethics And Dissemination: Ethical approval is not required as primary data will not be collected. Results will be disseminated through peer-reviewed publication, conference presentations and press.

Prospero Registration Number: CRD42018117766.
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http://dx.doi.org/10.1136/bmjopen-2019-029242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678017PMC
July 2019