Medicine (Austin & Northern Health) - Research Publications
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ItemNo Preview AvailableComparison of white matter hyperintensity abnormalities and cognitive performance in individuals with low and high cardiovascular risk: Data from the Diabetes and Dementia (D2) study(Wiley, 2021-12)Abstract Background Type 2 diabetes Mellitus (T2DM) is recognised as a major contributor to cognitive decline. People with T2DM demonstrate increased white matter hyperintensity (WMH) abnormalities on MRI compared to control individuals. We investigated associations between a validated vascular risk score: The Framingham Risk Score (FRS), WMH volumes and cognitive function in the Diabetes‐and‐Dementia (D2) study, a longitudinal cohort study of community dwelling people with T2DM. Method One hundred and twenty‐three non‐demented participants with T2DM (age 66.7±6.8 years, range 50‐80, 68M/55F) completed neuropsychological assessments, health questionnaires to allow FRS calculation, 24‐hour ambulatory blood pressure monitoring, and a 3T‐MRI scan. WMH were calculated using the functionality "run‐samseg" in FreeSurfer 7. Quality control on the traced lesions was performed using an in‐house semi‐automated MATLAB tool. Periventricular and deep WMH volumes were estimated based on the edited lesion traces. We divided participants into low (n=61) and high (n=62) FRS groups based on the median score (x=48.7). Differences in WMH volumes were compared between the FRS groups after correcting for sex and age. We compared cognitive performance between low/high FRS individuals across five composite cognitive domains: memory, language, visuospatial skills, executive function, and attention‐and‐processing‐speed. The composite score for each domain was the normalised z‐scores average for the respective tests. Result Participants with high FRS (implicating greater vascular risk) were significantly older (age F(1, 122)=14.97; p<0.001), were less likely to be female (sex χ2=16.73, p<0.001), and tend to have less than 12 years of education (χ2= 3.69, p = 0.041). Relative to individuals with low FRS, those with high FRS showed significantly higher WMH volumes (F(1, 121)=6.11; p=0.015). Significant differences were also identified for periventricular (F(1, 121)=6.16; p=0.014) and deep (F(1, 121)=4.25; p=0.042) WMH volumes. When the cognitive data were analysed, the low FRS group performed signifcantly better than the high FRS group only on the attention‐and‐processing‐speed factor (F(1,115)=5.17; p=0.025). Conclusion High cardiovascular risk, defined as a high FRS, in participants with T2DM was associated with greater WMH volume, a marker of white matter dysfunction, and with deficits in processing speed and attention. Subclinical cognitive deficits were common in our community dwelling cohort without known or preceding cognitive dysfunction.
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ItemFeasibility study of a prototype extended-wear insulin infusion set in adults with type 1 diabetes(WILEY, 2022-06)AIM: To assess the feasibility of a prototype insulin infusion set (IIS) for extended wear in adults with type 1 diabetes. MATERIALS AND METHODS: The prototype Capillary Biomedical investigational extended-wear IIS (CBX IIS) incorporates a soft, flexible, reinforced kink-resistant angled nylon-derivative cannula with one distal and three proximal ports to optimize insulin delivery. Twenty adult participants with type 1 diabetes established on insulin pump therapy used the CBX IIS for two 7-day test periods while wearing a Dexcom G5 continuous glucose monitor. RESULTS: Participants were able to wear the CBX IIS for an average of 6.6 ± 1.4 days. Eighty-eight percent (36 of 41) of sets were worn for 7 days. No serious adverse events were reported. Five infusion sets failed prematurely because of: unresolvable hyperglycaemia (three); hyperglycaemia with elevated ketones (one); or infection (one). Median time in range (3.9-10.0 mmol/L) was 62% (54-76). Average glucose levels per day of infusion set wear showed a statistically significant increase over time (p < .001). CONCLUSIONS: Our preliminary observations confirm the tolerability of the prototype CBX IIS for extended wear, albeit with a deterioration in glucose control after the third day.
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ItemThe ambulatory glucose profile and its interpretation(WILEY, 2022-09)
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ItemReview of potential biomarkers of inflammation and kidney injury in diabetic kidney disease(WILEY, 2022-09)Diabetic kidney disease is expected to increase rapidly over the coming decades with rising prevalence of diabetes worldwide. Current measures of kidney function based on albuminuria and estimated glomerular filtration rate do not accurately stratify and predict individuals at risk of declining kidney function in diabetes. As a result, recent attention has turned towards identifying and assessing the utility of biomarkers in diabetic kidney disease. This review explores the current literature on biomarkers of inflammation and kidney injury focussing on studies of single or multiple biomarkers between January 2014 and February 2020. Multiple serum and urine biomarkers of inflammation and kidney injury have demonstrated significant association with the development and progression of diabetic kidney disease. Of the inflammatory biomarkers, tumour necrosis factor receptor-1 and -2 were frequently studied and appear to hold most promise as markers of diabetic kidney disease. With regards to kidney injury biomarkers, studies have largely targeted markers of tubular injury of which kidney injury molecule-1, beta-2-microglobulin and neutrophil gelatinase-associated lipocalin emerged as potential candidates. Finally, the use of a small panel of selective biomarkers appears to perform just as well as a panel of multiple biomarkers for predicting kidney function decline.
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ItemA systematic review: Cost-effectiveness of continuous glucose monitoring compared to self-monitoring of blood glucose in type 1 diabetes(WILEY, 2022-11)Continuous glucose monitoring (CGM) is rapidly becoming a vital tool in the management of type 1 diabetes. Its use has been shown to improve glycaemic management and reduce the risk of hypoglycaemic events. The cost of CGM remains a barrier to its widespread application. We aimed to identify and synthesize evidence about the cost-effectiveness of utilizing CGM in patients with type 1 diabetes. Studies were identified from MEDLINE, Embase and Cochrane Library from January 2010 to February 2022. Those that assessed the cost-effectiveness of CGM compared to self-monitored blood glucose (SMBG) in patients with type 1 diabetes and reported lifetime incremental cost-effectiveness ratio (ICER) were included. Studies on critically ill or pregnant patients were excluded. Nineteen studies were identified. Most studies compared continuous subcutaneous insulin infusion and SMBG to a sensor-augmented pump (SAP). The estimated ICER range was [$18,734-$99,941] and the quality-adjusted life year (QALY) gain range was [0.76-2.99]. Use in patients with suboptimal management or greater hypoglycaemic risk revealed more homogenous results and lower ICERs. Limited studies assessed CGM in the context of multiple daily injections (MDI) (n = 4), MDI and SMBG versus SAP (n = 2) and three studies included hybrid closed-loop systems. Most studies (n = 17) concluded that CGM is a cost-effective tool. This systematic review suggests that CGM appears to be a cost-effective tool for individuals with type 1 diabetes. Cost-effectiveness is driven by reducing short- and long-term complications. Use in patients with suboptimal management or at risk of severe hypoglycaemia is most cost-effective.
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ItemComplications of Diabetes and Metrics of Glycemic Management Derived From Continuous Glucose Monitoring(ENDOCRINE SOC, 2022-05-17)CONTEXT: Although glycated hemoglobin A1c is currently the best parameter used clinically to assess risk for the development of diabetes complications, it does not provide insight into short-term fluctuations in glucose levels. This review summarizes the relationship between continuous glucose monitoring (CGM)-derived metrics of glycemic variability and diabetes-related complications. EVIDENCE ACQUISITION: PubMed and Embase databases were searched from January 1, 2010 to August 22, 2020, using the terms type 1 diabetes, type 2 diabetes, diabetes-related microvascular and macrovascular complications, and measures of glycaemic variability. Exclusion criteria were studies that did not use CGM and studies involving participants who were not diabetic, acutely unwell (post stroke, post surgery), pregnant, or using insulin pumps. EVIDENCE SYNTHESIS: A total of 1636 records were identified, and 1602 were excluded, leaving 34 publications in the final review. Of the 20 852 total participants, 663 had type 1 diabetes (T1D) and 19 909 had type 2 diabetes (T2D). Glycemic variability and low time in range (TIR) showed associations with all studied microvascular and macrovascular complications of diabetes. Notably, higher TIR was associated with reduced risk of albuminuria, retinopathy, cardiovascular disease mortality, all-cause mortality, and abnormal carotid intima-media thickness. Peripheral neuropathy was predominantly associated with standard deviation of blood glucose levels (SD) and mean amplitude of glycemic excursions (MAGE). CONCLUSION: The evidence supports the association between diabetes complications and CGM-derived measures of intraday glycemic variability. TIR emerged as the most consistent measure, supporting its emerging role in clinical practice. More longitudinal studies and trials are required to confirm these associations, particularly for T1D, for which there are limited data.
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ItemBlood Plasma Metabolites in Diabetes-Associated Chronic Kidney Disease: A Focus on Lipid Profiles and Cardiovascular Risk(FRONTIERS MEDIA SA, 2022-02-28)BACKGROUND: We investigated a cross-sectional metabolomic analysis of plasma and urine of patients with early and late stage diabetes associated chronic kidney disease (CKD), inclusive of stages 1-5 CKD, to identify potential metabolomic profiles between the two groups. METHODS: This cross-sectional study recruited 119 adults. Metabolomic biomarkers were quantified in 119 non-fasted plasma and 57 urine samples using a high-throughput proton Nuclear Magnetic Resonance platform. Analyses were conducted using R with the ggforestplot package. Linear regression models were minimally adjusted for age, sex, and body mass index and p-values were adjusted for multiple comparisons using the Benjamini-Hockberg method with a false discovery rate of 0.05. RESULTS: Apolipoprotein A1 concentration (ApoA1) was reduced (adj. p = 0.04) and apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) was increased (adj. p = 0.04) in late CKD compared with early CKD. Low-density lipoprotein triglyceride (LDL-TG) had an increased concentration (adj. p = 0.01), while concentrations of high-density lipoprotein cholesterol (HDL-C) were reduced (adj. p = 0.04) in late CKD compared to early stages of disease. CONCLUSION: Our results highlight the presence of abnormal lipid metabolism namely significant reduction in the protective ApoA1 and significant increase in atherogenic ApoB/ApoA1 ratio. The study also demonstrates significantly elevated levels of triglyceride-rich lipoproteins such as LDL-TG. We illustrate the significant reduction in protective HDL-C in individuals with diabetic CKD. It explores a detailed plasma lipid profile that significantly differentiates between the late and early CKD groups as well as each CKD stage. The study of complex metabolite profiles may provide additional data required to enable more specific cardiovascular risk stratification.
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ItemRole of the adaptive immune system in diabetic kidney disease(WILEY, 2022-02)Diabetic kidney disease (DKD) is a highly prevalent complication of diabetes and the leading cause of end-stage kidney disease. Inflammation is recognized as an important driver of progression of DKD. Activation of the immune response promotes a pro-inflammatory milieu and subsequently renal fibrosis, and a progressive loss of renal function. Although the role of the innate immune system in diabetic renal disease has been well characterized, the potential contribution of the adaptive immune system remains poorly defined. Emerging evidence in experimental models of DKD indicates an increase in the number of T cells in the circulation and in the kidney cortex, that in turn triggers secretion of inflammatory mediators such as interferon-γ and tumor necrosis factor-α, and activation of cells in innate immune response. In human studies, the number of T cells residing in the interstitial region of the kidney correlates with the degree of albuminuria in people with type 2 diabetes. Here, we review the role of the adaptive immune system, and associated cytokines, in the development of DKD. Furthermore, the potential therapeutic benefits of targeting the adaptive immune system as a means of preventing the progression of DKD are discussed.
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ItemThe Association Between Sarcopenia and Functional Improvement in Older and Younger Patients Who Completed Inpatient Rehabilitation: A Prospective Cohort Study(FRONTIERS MEDIA SA, 2021-10-21)Objective: To investigate the association between sarcopenia and functional improvement in patients older and younger than 65 years upon completion of an inpatient rehabilitation program. Design: Prospective cohort study. Participants: Adult consecutive patients who completed the inpatient rehabilitation program at a metropolitan tertiary referral hospital general inpatient rehabilitation unit. Methods: Sarcopenia status was determined using the European Working Group on Sarcopenia in Older People 2 algorithm, using muscle mass measured by BioImpedance Analysis and grip strength. Progress in rehabilitation was measured using change in the Functional Independence Measure and Goal Attainment Scaling score. To investigate the age group by sarcopenia status interaction we used quantile regression models with bootstrapped standard error estimation for functional improvement and linear regression model with robust standard error estimation for GAS score. Results: 257 participants [128 (50%) male, median age 63 years (IQR: 52-72)], 33(13%) with sarcopenia, completed inpatient rehabilitation [median length of stay 16 days (IQR: 11-27.5)]. Participants' median Functional Independence Measure change was 24 (IQR 15-33.5) and mean total Goal Attainment Scaling score was 57.6 (SD 10.2). Adjusting for admission Functional Independence Measure score, the median difference in Functional Independence Measure change between participants with and without sarcopenia was: -4.3 (95% CI: -10.6, 1.9); p = 0.17 in participants 65 years and younger, and 4.6 (95% CI: 1.0, 8.2); p = 0.01 in participants older than 65; age-by-sarcopenia interaction p = 0.02. Conclusions: Unlike younger people, older people with sarcopenia have greater functional improvement in inpatient rehabilitation than those without sarcopenia.