Medicine (Austin & Northern Health) - Research Publications

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    The threat among us: significance and scale of diabetic chronic kidney disease in Australia
    Lecamwasam, A ; Ekinci, EI ; MacIsaac, RJ ; Saffery, R ; Dwyer, KM (WILEY, 2017-12)
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    Relationship between urinary sodium-to-potassium ratio and ambulatory blood pressure in patients with diabetes mellitus
    Libianto, R ; Moran, J ; O'Callaghan, C ; Baqar, S ; Chen, AX ; Baker, ST ; Clarke, M ; MacIsaac, RJ ; Jerums, G ; Ekinci, EI (WILEY, 2018-01)
    Previous studies investigating the relationship between sodium intake and blood pressure have mostly relied on dietary recall and clinic blood pressure measurement. In this cross-sectional study, we aimed to investigate the relationship between 24 hour urinary sodium and potassium excretion, and their ratio, with 24 hour ambulatory blood pressure parameters including nocturnal blood pressure dipping in patients with type 1 and 2 diabetes. We report that in 116 patients with diabetes, systolic blood pressure was significantly predicted by the time of day, age, the interaction between dipping status with time, and 24 hour urinary sodium-to-potassium ratio (R2  = 0.83) with a relative contribution of 53%, 21%, 20% and 6%, respectively. However, there was no interaction between urinary sodium-to-potassium ratio and dipping status.
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    What is new in lipid-lowering therapies in diabetes?
    Cheung, Y-M ; O'Brien, R ; Ekinci, EI (WILEY, 2019-12)
    Diabetes can lead to a myriad of microvascular and macrovascular complications - with the leading cause of mortality in diabetes being cardiovascular disease. Low-density lipoprotein cholesterol, along with non-high-density lipoprotein cholesterol and triglycerides are proven, modifiable risk factors for cardiovascular disease. This article will focus on lipid-lowering agents in individuals with diabetes. It will summarise relevant changes in the latest guidelines for dyslipidaemia and will also review the mechanisms of action of lipid-lowering agents along with the latest cardiovascular outcomes data specific to individuals with diabetes. Older agents such as statins, ezetimibe, fibrates and nicotinic acid will be reviewed with a focus on new diabetes-specific evidence. Similarly, a relatively novel agent proprotein-convertase subtilisin-kexin type 9 will be reviewed and details around the Pharmaceutical Benefits Scheme criteria governing its usage in Australia will be reported. Finally, this review will touch on agents still on the horizon such as icosapent ethyl, high-density lipoprotein mimetics, bempedoic acid, omega-3 free fatty acids, bromodomain and extra-terminal protein inhibitors and inclisiran - a long-acting ribonucleic acid interference agent. In the appropriately selected population of individuals with diabetes, these agents can assist to improve further lipid profile and reduce cardiovascular events.
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    Metformin: time to review its role and safety in chronic kidney disease
    Tanner, C ; Wang, G ; Liu, N ; Andrikopoulos, S ; Zajac, JD ; Ekinci, EI (WILEY, 2019-07)
    ■Metformin is recommended as first-line therapy for type 2 diabetes because of its safety, low cost and potential cardiovascular benefits. ■The use of metformin was previously restricted in people with chronic kidney disease (CKD) - a condition that commonly coexists with diabetes - due to concerns over drug accumulation and metformin-associated lactic acidosis. ■There are limited data from observational studies and small randomised controlled trials to suggest that metformin, independent of its antihyperglycaemic effects, may be associated with lower risk of myocardial infarction, stroke and all-cause mortality in people with type 2 diabetes and CKD. ■Research into the risk of metformin-associated lactic acidosis in CKD has previously been limited and conflicting, resulting in significant variation across international guidelines on the safe prescribing and dosing of metformin at different stages of renal impairment. ■Present-day large scale cohort studies now provide supporting evidence for the safe use of metformin in mild to moderate renal impairment (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73m2 ). However, prescribing metformin in people with severe renal impairment (eGFR < 30 mL/min/1.73m2 ) remains a controversial issue. Due to observed increased risk of lactic acidosis and all-cause mortality in people with type 2 diabetes and severe renal impairment, it is generally recommended that metformin is discontinued if renal function falls below this level or during acute renal deterioration.
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    Hospital-acquired complications in intensive care unit patients with diabetes: A before-and-after study of a conventional versus liberal glucose control protocol
    Luethi, N ; Cioccari, L ; Eastwood, G ; Biesenbach, P ; Morgan, R ; Sprogis, S ; Young, H ; Peck, L ; Chong, CK ; Moore, S ; Moon, K ; Ekinci, EI ; Deane, AM ; Bellomo, R ; Martensson, J (WILEY, 2019-07)
    BACKGROUND: Critically ill patients with diabetes mellitus (DM) are at increased risk of in-hospital complications and the optimal glycemic target for such patients remains unclear. A more liberal approach to glucose control has recently been suggested for patients with DM, but uncertainty remains regarding its impact on complications. METHODS: We aimed to test the hypothesis that complications would be more common with a liberal glycemic target in ICU patients with DM. Thus, we compared hospital-acquired complications in the first 400 critically ill patients with DM included in a sequential before-and-after trial of liberal (glucose target: 10-14 mmol/L) vs conventional (glucose target: 6-10 mmol/L) glucose control. RESULTS: Of the 400 patients studied, 165 (82.5%) patients in the liberal and 177 (88.5%) in the conventional-control group were coded for at least one hospital-acquired complication (P = 0.09). When comparing clinically relevant complications diagnosed between ICU admission and hospital discharge, we found no difference in the odds for infectious (adjusted odds ratio [aOR] for liberal-control: 1.15 [95% CI: 0.68-1.96], P = 0.60), cardiovascular (aOR 1.40 [95% CI: 0.63-3.12], P = 0.41) or neurological complications (aOR: 1.07 [95% CI: 0.61-1.86], P = 0.81), acute kidney injury (aOR 0.83 [95% CI: 0.43-1.58], P = 0.56) or hospital mortality (aOR: 1.09 [95% CI: 0.59-2.02], P = 0.77) between the liberal and the conventional-control group. CONCLUSION: In this prospective before-and-after study, liberal glucose control was not associated with an increased risk of hospital-acquired infectious, cardiovascular, renal or neurological complications in critically ill patients with diabetes.
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    Impact of an integrated diabetes service involving specialist outreach and primary health care on risk factors for micro- and macrovascular diabetes complications in remote Indigenous communities in Australia
    Hotu, C ; Remond, M ; Maguire, G ; Ekinci, E ; Cohen, N (WILEY, 2018-12)
    OBJECTIVE: To determine the impact of an integrated diabetes service involving specialist outreach and primary health care teams on risk factors for micro- and macrovascular diabetes complications in three remote Indigenous Australian communities over a 12-month period. DESIGN: Quantitative, retrospective evaluation. SETTING: Primary health care clinics in remote Indigenous communities in Australia. PARTICIPANTS: One-hundred-and-twenty-four adults (including 123 Indigenous Australians; 76.6% female) with diabetes living in remote communities. MAIN OUTCOME MEASURES: Glycosylated haemoglobin, lipid profile, estimated glomerular filtration rate, urinary albumin : creatinine ratio and blood pressure. RESULTS: Diabetes prevalence in the three communities was high, at 32.8%. A total of 124 patients reviewed by the outreach service had a median consultation rate of 1.0 by an endocrinologist and 0.9 by a diabetes nurse educator over the 12-month period. Diabetes care plans were made in collaboration with local primary health care services, which also provided patients with diabetes care between outreach team visits. A significant reduction was seen in median (interquartile range) glycosylated haemoglobin from baseline to 12 months. Median (interquartile range) total cholesterol was also reduced. The number of patients prescribed glucagon-like peptide-1 analogues and dipeptidyl peptidase-4 inhibitors increased over the 12 months and an increase in the number of patients prescribed insulin trended towards statistical significance. CONCLUSION: A collaborative health care approach to deliver diabetes care to remote Indigenous Australian communities was associated with an improvement in glycosylated haemoglobin and total cholesterol, both important risk factors, respectively, for micro- and macrovascular diabetes complications.
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    Flash glucose monitoring-using technology to improve outcomes for patients with diabetes
    Weiss, J ; Cohen, N ; Zajac, JD ; Ekinci, EI (WILEY, 2018-12)
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    Continuous glucose monitoring: a review of the evidence, opportunities for future use and ongoing challenges
    Wood, A ; O'Neal, D ; Furler, J ; Ekinci, EI (WILEY, 2018-05)
    The advent of devices that can track interstitial glucose levels, which are closely related to blood glucose levels, on a near continuous basis, has facilitated better insights into patterns of glycaemia. Continuous glucose monitoring (CGM) therefore allows for more intensive monitoring of blood glucose levels and potentially improved glycaemic control. In the context of the announcement on 1 April 2017 that the Australian Government will fund CGM monitoring for people with type 1 diabetes under the age of 21 years, this paper provides a review of the evidence for CGM and some of the ongoing challenges. There is evidence that real-time CGM in type 1 diabetes improves HbA1c and hypoglycaemia, while in type 2 diabetes, the evidence is less robust. Initial barriers to widespread implementation of CGM included issues with accuracy and user friendliness; however, as the technology has evolved, these issues have largely improved. Ongoing barriers include cost, and weaker evidence for their benefit in certain populations such as those with type 2 diabetes and less glycaemic variability. CGM has the potential to reduce healthcare costs, although real-world studies, including cost-effectiveness analyses, are needed in this area.
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    Contribution of cardiometabolic risk factors to estimated glomerular filtration rate decline in Indigenous Australians with and without albuminuria - the eGFR Follow-up Study
    Barr, ELM ; Barzi, F ; Hughes, JT ; Jerums, G ; O'Dea, K ; Brown, ADH ; Ekinci, EI ; Jones, GRD ; Lawton, PD ; Sinha, A ; MacIsaac, RJ ; Cass, A ; Maple-Brown, LJ (WILEY, 2018-07)
    AIM: We assessed associations between cardiometabolic risk factors and estimated glomerular filtration rate (eGFR) decline according to baseline albuminuria to identify potential treatment targets in Indigenous Australians. METHODS: The eGFR Follow-up Study is a longitudinal cohort of 520 Indigenous Australians. Linear regression was used to estimate associations between baseline cardiometabolic risk factors and annual Chronic Kidney Disease Epidemiology Collaboration eGFR change (mL/min per 1.73m2 /year), among those classified with baseline normoalbuminuria (urine albumin-to-creatinine ratio (uACR) <3 mg/mmol; n = 297), microalbuminuria (uACR 3-30 mg/mmol; n = 114) and macroalbuminuria (uACR ≥30 mg/mmol; n = 109). RESULTS: After a median of 3 years follow-up, progressive declines of the age- and sex-adjusted mean eGFR were observed across albuminuria categories (-2.0 [-2.6 to -1.4], -2.5 [-3.7 to -1.3] and -6.3 [-7.8 to -4.9] mL/min per 1.72m2 /year). Although a borderline association was observed between greater baseline haemoglobin A1c and eGFR decline in those with macroalbuminuria (P = 0.059), relationships were not significant in those with microalbuminuria (P = 0.187) or normoalbuminuria (P = 0.23). Greater baseline blood pressure, C-reactive protein, waist-to-hip ratio and lower high-density lipoprotein cholesterol showed non-significant trends with greater eGFR decline in the presence of albuminuria. CONCLUSION: Over a 3 year period, marked eGFR decline was observed with greater baseline albuminuria. Cardiometabolic risk factors were not strong predictors for eGFR decline in Indigenous Australians without albuminuria. Longer follow-up may elucidate the role of these predictors and other mechanisms in chronic kidney disease progression in this population.
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    Using Automated HbA1c Testing to Detect Diabetes Mellitus in Orthopedic Inpatients and Its Effect on Outcomes (vol 12, e0168471, 2017)
    Ekinci, EI ; Kong, A ; Churilov, L ; Nanayakkara, N ; Chiu, WL ; Sumithran, P ; Djukiadmodjo, F ; Premaratne, E ; Owen-Jones, E ; Hart, GK ; Robbins, R ; Hardidge, A ; Johnson, D ; Baker, ST ; Zajac, JD (PUBLIC LIBRARY SCIENCE, 2017-02-13)
    [This corrects the article DOI: 10.1371/journal.pone.0168471.].