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Background: Little is known about the relationship between patients' cultural and linguistic backgrounds and patient activation, especially in people with diabetes and chronic kidney disease (CKD). We examined the association between culturally and linguistically diverse (CALD) background and patient activation and evaluated the impact of a codesigned integrated kidney and diabetes model of care on patient activation by CALD status in people with diabetes and CKD. Methods: This longitudinal study recruited adults with diabetes and CKD (Stage 3a or worse) who attended a new diabetes and kidney disease service at a tertiary hospital. All completed the patient activation measure at baseline and after 12 months and had demographic and clinical data collected. Patients from CALD backgrounds included individuals who spoke a language other than English at home, while those from non‐CALD backgrounds spoke English only as their primary language. Paired t‐tests compared baseline and 12‐month patient activation scores by CALD status. Results: Patients from CALD backgrounds had lower activation scores (52.1 ± 17.6) compared to those from non‐CALD backgrounds (58.5 ± 14.6) at baseline. Within‐group comparisons showed that patient activation scores for patients from CALD backgrounds significantly improved by 7 points from baseline to 12 months follow‐up (52.1 ± 17.6–59.4 ± 14.7), and no significant change was observed for those from non‐CALD backgrounds (58.5 ± 14.6–58.8 ± 13.6). Conclusions: Among patients with diabetes and CKD, those from CALD backgrounds report worse activation scores. Interventions that support people from CALD backgrounds with comorbid diabetes and CKD, such as the integrated kidney and diabetes model of care, may address racial and ethnic disparities that exist in patient activation and thus improve clinical outcomes. Patient or Public Contribution: Patients, caregivers and national consumer advocacy organisations (Diabetes Australia and Kidney Health Australia) codesigned a new model of care in partnership with healthcare professionals and researchers. The development of the model of care was informed by focus groups of patients and healthcare professionals and semi‐structured interviews of caregivers and healthcare professionals. Patients and caregivers also provided a rigorous evaluation of the new model of care, highlighting its strengths and weaknesses. [ABSTRACT FROM AUTHOR]

Accumulation of advanced glycation endproducts (AGEs) is linked to decline in renal function, particularly in patients with diabetes. Major forms of AGEs in serum are protein-bound AGEs and AGE free adducts. In this study, we assessed levels of AGEs in subjects with and without diabetes, with normal renal function and stages 2 to 4 chronic kidney disease (CKD), to identify which AGE has the greatest progressive change with decline in renal function and change in diabetes. We performed a cross-sectional study of patients with stages 2–4 CKD, with and without diabetes, and healthy controls (n = 135). Nine protein-bound and free adduct AGEs were quantified in serum. Most protein-bound AGEs increased moderately through stages 2–4 CKD whereas AGE free adducts increased markedly. Methylglyoxal-derived hydroimidazolone MG-H1 free adduct was the AGE most responsive to CKD status, increasing 8-fold and 30-fold in stage 4 CKD in patients without and with diabetes, respectively. MG-H1 Glomerular filtration flux was increased 5-fold in diabetes, likely reflecting increased methylglyoxal glycation status. We conclude that serum MG-H1 free adduct concentration was strongly related to stage of CKD and increased in diabetes status. Serum MG-H1 free adduct is a candidate AGE risk marker of non-diabetic and diabetic CKD. [ABSTRACT FROM AUTHOR]

Background Current healthcare models are ill-equipped for managing people with diabetes and chronic kidney disease (CKD). We evaluated the impact of a new diabetes and kidney disease service (DKS) on hospitalization, mortality, clinical and patient-relevant outcomes. Methods Longitudinal analyses of adult patients with diabetes and CKD (Stages 3a–5) were performed using outpatient and hospitalization data from January 2015 to October 2018. Data were handled according to whether patients received the DKS intervention (n  = 196) or standard care (n  = 7511). The DKS provided patient-centred, coordinated multidisciplinary assessment and management of patients. Primary analyses examined hospitalization and mortality rates between the two groups. Secondary analyses evaluated the impact of the DKS on clinical target attainment, changes in estimated glomerular filtration rate (eGFR), glycated haemoglobin A1c (HbA1c), self-care and patient activation at 12 months. Results Patients who received the intervention had a higher hospitalization rate {incidence rate ratio [IRR] 1.20 [95% confidence interval (CI) 1.13–1.30]; P < 0.0001}, shorter median length of stay {2 days [interquartile range (IQR) 1–6] versus 4 days [IQR 1–9]; P < 0.0001} and lower all-cause mortality rate [IRR 0.4 (95% CI 0.29–0.64); P < 0.0001] than those who received standard care. Improvements in overall self-care [mean difference 2.26 (95% CI 0.83–3.69); P < 0.001] and in statin use and eye and feet examinations were observed. The mean eGFR did not change significantly after 12 months [mean difference 1.30 mL/min/1.73 m2 (95% CI −4.17–1.67); P = 0.40]. HbA1c levels significantly decreased by 0.40, 0.35, 0.34 and 0.23% at 3, 6, 9 and 12 months of follow-up, respectively. Conclusions A co-designed, person-centred integrated model of care improved all-cause mortality, kidney function, glycaemic control and self-care for patients with diabetes and CKD. [ABSTRACT FROM AUTHOR]

Lower leg ulcers are a serious and long-term complication in patients with diabetes and pose a major health concern because of the increasing number of patients diagnosed with diabetes each year. This study sought to evaluate the clinical benefit of topical activated protein C (APC) on chronic lower leg ulcers in patients with diabetes. Twelve patients were randomly assigned to receive either APC (N =6) or physiological saline (placebo; N =6) in a randomised, placebo-controlled, doubleblind pilot clinical trial. Treatment was administered topically, twice weekly for 6weeks with final follow-up at 20 weeks. Wound area was significantly reduced to 34·8±16·4% of week 0 levels at 20 weeks in APC-treated wounds (p =0·01). At 20 weeks, three APC-treated wounds had completely healed, compared to one salinetreated wound. Full-thickness wound edge skin biopsies showed reduced inflammatory cell infiltration and increased vascular proliferation following APC treatment. Patient stress scores were also significantly reduced following APC treatment (p <0·05), demonstrating improved patient quality of life as assessed by the Cardiff Wound Impact Questionnaire. This pilot trial suggests that APC is a safe topical agent for healing chronic lower leg ulcers in patients with diabetes and provides supporting evidence for a larger clinical trial. [ABSTRACT FROM AUTHOR]

Background: Little is known about how patient reported barriers to health care impact the quality of life (HRQoL) of patients with comorbid disease. We investigated patient reported barriers to health care and low physical and mental well-being among people with diabetes and chronic kidney disease (CKD).Methods: Adults with diabetes and CKD (estimated Glomerular Filtration Rate < 60 ml/min/1.73m2) were recruited and completed a questionnaire on barriers to health care, the 12-Item HRQoL Short Form Survey and clinical assessment. Low physical and mental health status were defined as mean scores < 50. Logistic regression models were used.Results: Three hundred eight participants (mean age 66.9 ± 11 years) were studied. Patient reported 'impact of the disease on family and friends' (OR 2.07; 95% CI 1.14 to 3.78), 'feeling unwell' (OR 4.23; 95% CI 1.45 to 12.3) and 'having other life stressors that make self-care a low priority' (OR 2.59; 95% CI 1.20 to 5.61), were all associated with higher odds of low physical health status. Patient reported 'feeling unwell' (OR 2.92; 95% CI 1.07 to 8.01), 'low mood' (OR 2.82; 95% CI 1.64 to 4.87) and 'unavailability of home help' (OR 1.91; 95% CI 1.57 to 2.33) were all associated with higher odds of low mental health status. The greater the number of patient reported barriers the higher the odds of low mental health but not physical health status.Conclusions: Patient reported barriers to health care were associated with lower physical and mental well-being. Interventions addressing these barriers may improve HRQoL among people with comorbid diabetes and CKD. [ABSTRACT FROM AUTHOR]

Aims: In patients with comorbid diabetes and chronic kidney disease, the extent to which patient-reported barriers to health-care and patient reported outcomes influence the quality of health care is not well established. This study explored the association between patient-reported barriers to health-care, patient activation, quality of life and diabetes self-care, with attainment of glycaemic and blood pressure (BP) targets.Methods: This cross-sectional study recruited adults with diabetes and CKD (eGFR 20 to <60 ml/min/1.73m2) across four hospitals. We combined clinical data with results from a questionnaire comprising measures of patient-identified barriers to care, the Patient Activation Measure (PAM), 12-Item Short Form Survey (SF-12), and the Summary of Diabetes Self-Care Activity (SDSCA).Results: 199 patients, mean age 68.7 (SD 9.6), 70.4% male and 90.0% with type 2 diabetes were studied. Poor glycaemic control was associated with increased odds of patient reported "poor family support" (OR 4.90; 95% CI 1.80 to 13.32, p < 0.002). Poor BP control was associated with increased odds of patient reported, "not having a good primary care physician" (OR 6.01; 2.42 to 14.95, p < 0.001). The number of barriers was not associated with increased odds of poor control (all p > 0.05).Conclusions: Specific patient-reported barriers, lack of patient perceived family and primary care physician support, are associated with increased odds of poor glycaemic and blood pressure control respectively. Interventions addressing these barriers may improve treatment target attainment. [ABSTRACT FROM AUTHOR]

Aims There is insufficient and inconsistent data regarding the association between diabetes self-management, the process of facilitating the knowledge, skill, and ability necessary for diabetes self-care, and health-related quality of life (HRQOL) in people with diabetes and moderate to severe chronic kidney disease (CKD). Methods In a cross sectional study, participation in diabetes self-management assessed by the Summary of Diabetes Self-Care Activities (SDSCA) questionnaire and HRQOL was examined in 308 patients with diabetes and CKD (stages 3 to 5) recruited from outpatient diabetes and renal clinics of 4 public tertiary hospitals. Associations were examined by Pearson correlation coefficients and hierarchical multiple regression after controlling for potential confounders. An examination of trend across the levels of patient participation in self-management was assessed using a non-parametric test for trend. Results The median age and interquartile range (IQR) of patients were 68 and 14.8 years, respectively with 59% of the population being over 65 years old and 69.5% male. The median durations of diabetes and CKD were 18 years (IQR-17) and 5 years (IQR-8) respectively. General diet, exercise and medication taking were positively associated with at least one HRQOL subscale (all p < 0.05) but diabetes specific diet, blood sugar testing and foot checking were not. As levels of participation in self-management activities increased there was a graded increase in mean HRQOL scores across all subscales ( p for trend < 0.05). Conclusions In people with diabetes and moderate to severe CKD, participation in diabetes self-management activities, particularly those focused on general diet, exercise and medication taking, was associated with higher HRQOL. [ABSTRACT FROM AUTHOR]

Activated protein C (aPC) is a natural anticoagulant with strong cyto-protective and anti-inflammatory properties. aPC inhibits pancreatic inflammation and preserves functional islets after intraportal transplantation in mice. Whether aPC prevents the onset or development of type 1 diabetes (T1D) is unknown. In this study, when human recombinant aPC was delivered intraperitoneally, twice weekly for 10 weeks (from week 6 to 15) to non-obese diabetic (NOD) mice, a model for T1D, the incidence of diabetes was reduced from 70% (saline control) to 7.6% by 26 weeks of age. Islets of aPC-treated mice exhibited markedly increased expression of insulin, aPC/protein C, endothelial protein C receptor, and matrix metalloproteinase (MMP)-2 when examined by immunostaining. The insulitis score in aPC-treated mice was 50% less than that in control mice. T regulatory cells (Tregs) in the spleen, pancreatic islets, and pancreatic lymph nodes were increased 37, 53, and 59%, respectively, in NOD mice following aPC treatment. These Tregs had potent suppressor function and, after adoptive transfer, delayed diabetes onset in NOD.severe combined immunodeficiency mice. The culture of NOD mouse spleen cells with aPC reduced the secretion of inflammatory cytokines interleukin (IL)-1β and interferon-γ but increased IL-2 and transforming growth factor-β1, two cytokines required for Treg differentiation. In summary, our results indicate that aPC prevents T1D in the NOD mouse. The aPC mechanism of action is complex, involving induction of Treg differentiation, inhibition of inflammation, and possibly direct cyto-protective effects on β cells. [ABSTRACT FROM AUTHOR]