A codesigned integrated kidney and diabetes model of care improves patient activation among patients from culturally and linguistically diverse backgrounds.

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.

A co-designed integrated kidney and diabetes model of care improves mortality, glycaemic control and self-care.

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.

Facilitators and barriers to behaviour change within a lifestyle program for women with obesity to prevent excess gestational weight gain: a mixed methods evaluation.

BACKGROUND: Maternal obesity is associated with health risks for women and their babies and is exacerbated by excess gestational weight gain. The aim of this study was to describe women's experiences and perspectives in attending a Healthy Pregnancy Service designed to optimise healthy lifestyle and support recommended gestational weight gain for women with obesity. METHODS: An explanatory sequential mixed methods study design utilised two questionnaires (completed in early and late pregnancy) to quantify feelings, motivation and satisfaction with the service, followed by semi-structured interviews that explored barriers and enablers of behaviour change. Data were analysed separately and then interpreted together. RESULTS: Overall, 49 women attending the service completed either questionnaire 1, 2 or both and were included in the analysis. Fourteen women were interviewed. Prior to pregnancy, many women had gained weight and attempted to lose weight independently, and reported they were highly motivated to achieve a healthy lifestyle. During pregnancy, diet changes were reported as easier to make and sustain than exercise changes. Satisfaction with the service was high. Key factors identified in qualitative analysis were: service support enabled change; motivation to change behaviour, social support, barriers to making change (intrinsic, extrinsic and clinic-related), post-partum lifestyle and needs. On integration of data, qualitative and quantitative findings aligned. CONCLUSIONS: The Healthy Pregnancy service was valued by women. Barriers and enablers to the delivery of an integrated model of maternity care that supported healthy lifestyle and recommended gestational weight gain were identified. These findings have informed and improved implementation and further scale up of this successful service model, integrating healthy lifestyle into routine antenatal care of women with obesity. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry (no.12620000985987). Registration date 30/09/2020, retrospectively registered. http://www.anzctr.org.au/.

Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.

BACKGROUND: Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017. OBJECTIVES: To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I2 = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I2 = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I2 = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause). AUTHORS' CONCLUSIONS: The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.

A need-based approach to self-management education for adults with co-morbid diabetes and chronic kidney disease.

BACKGROUND: Self-management education needs have not been assessed in patients with complex co-morbid conditions such as diabetes and chronic kidney disease (CKD). The objectives of this study were to 1) determine the self-management education needs for patients with co-morbid diabetes and CKD and 2) co-develop an educational resource meeting the self-management education needs of patients with co-morbid diabetes and CKD. METHODS: Patients with co-morbid diabetes and CKD attending a co-designed, patient-centred outpatient diabetes and kidney clinic at a tertiary metropolitan hospital were recruited for semi-structured interviews. Maximal variation sampling was used, ensuring adequate representation of different gender, age, diabetes duration and stage of CKD. Data were thematically analysed using grounded theory. RESULTS: Forty-two patients participated. Most were male (67%) and the mean age was 64.8 (11.1) years. The majority of patients preferred an educational resource in the form of a Digital Versatile Disc (DVD) and they thought that current education could be improved. In particular patients wanted further education on 1) management of diabetes and kidney disease (including nutrition and lifestyle, and prevention of the progression of kidney disease) and 2) complications of comorbid diabetes and kidney disease. CONCLUSION: Patients with co-morbid diabetes and kidney disease have education gaps on the management of, and complications of diabetes and kidney disease. Interventions aimed at improving patient education need to be delivered through education resources co-developed by patients and health staff. A targeted education resource in the form of a DVD, addressing these needs, may potentially close these gaps.

Patient reported barriers are associated with low physical and mental well-being in patients with co-morbid diabetes and chronic kidney disease.

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.

Insulin and glucose-lowering agents for treating people with diabetes and chronic kidney disease.

BACKGROUND: Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co-exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose-lowering challenging, increasing the risk of hypoglycaemia. Glucose-lowering agents have been mainly studied in people with near-normal kidney function. It is important to characterise existing knowledge of glucose-lowering agents in CKD to guide treatment. OBJECTIVES: To examine the efficacy and safety of insulin and other pharmacological interventions for lowering glucose levels in people with diabetes and CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs looking at head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in people with diabetes and CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) were eligible. DATA COLLECTION AND ANALYSIS: Four authors independently assessed study eligibility, risk of bias, and quality of data and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: Forty-four studies (128 records, 13,036 participants) were included. Nine studies compared sodium glucose co-transporter-2 (SGLT2) inhibitors to placebo; 13 studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; 2 studies compared glucagon-like peptide-1 (GLP-1) agonists to placebo; 8 studies compared glitazones to no glitazone treatment; 1 study compared glinide to no glinide treatment; and 4 studies compared different types, doses or modes of administration of insulin. In addition, 2 studies compared sitagliptin to glipizide; and 1 study compared each of sitagliptin to insulin, glitazars to pioglitazone, vildagliptin to sitagliptin, linagliptin to voglibose, and albiglutide to sitagliptin. Most studies had a high risk of bias due to funding and attrition bias, and an unclear risk of detection bias.Compared to placebo, SGLT2 inhibitors probably reduce HbA1c (7 studies, 1092 participants: MD -0.29%, -0.38 to -0.19 (-3.2 mmol/mol, -4.2 to -2.2); I2 = 0%), fasting blood glucose (FBG) (5 studies, 855 participants: MD -0.48 mmol/L, -0.78 to -0.19; I2 = 0%), systolic blood pressure (BP) (7 studies, 1198 participants: MD -4.68 mmHg, -6.69 to -2.68; I2 = 40%), diastolic BP (6 studies, 1142 participants: MD -1.72 mmHg, -2.77 to -0.66; I2 = 0%), heart failure (3 studies, 2519 participants: RR 0.59, 0.41 to 0.87; I2 = 0%), and hyperkalaemia (4 studies, 2788 participants: RR 0.58, 0.42 to 0.81; I2 = 0%); but probably increase genital infections (7 studies, 3086 participants: RR 2.50, 1.52 to 4.11; I2 = 0%), and creatinine (4 studies, 848 participants: MD 3.82 µmol/L, 1.45 to 6.19; I2 = 16%) (all effects of moderate certainty evidence). SGLT2 inhibitors may reduce weight (5 studies, 1029 participants: MD -1.41 kg, -1.8 to -1.02; I2 = 28%) and albuminuria (MD -8.14 mg/mmol creatinine, -14.51 to -1.77; I2 = 11%; low certainty evidence). SGLT2 inhibitors may have little or no effect on the risk of cardiovascular death, hypoglycaemia, acute kidney injury (AKI), and urinary tract infection (low certainty evidence). It is uncertain whether SGLT2 inhibitors have any effect on death, end-stage kidney disease (ESKD), hypovolaemia, fractures, diabetic ketoacidosis, or discontinuation due to adverse effects (very low certainty evidence).Compared to placebo, DPP-4 inhibitors may reduce HbA1c (7 studies, 867 participants: MD -0.62%, -0.85 to -0.39 (-6.8 mmol/mol, -9.3 to -4.3); I2 = 59%) but may have little or no effect on FBG (low certainty evidence). DPP-4 inhibitors probably have little or no effect on cardiovascular death (2 studies, 5897 participants: RR 0.93, 0.77 to 1.11; I2 = 0%) and weight (2 studies, 210 participants: MD 0.16 kg, -0.58 to 0.90; I2 = 29%; moderate certainty evidence). Compared to placebo, DPP-4 inhibitors may have little or no effect on heart failure, upper respiratory tract infections, and liver impairment (low certainty evidence). Compared to placebo, it is uncertain whether DPP-4 inhibitors have any effect on eGFR, hypoglycaemia, pancreatitis, pancreatic cancer, or discontinuation due to adverse effects (very low certainty evidence).Compared to placebo, GLP-1 agonists probably reduce HbA1c (7 studies, 867 participants: MD -0.53%, -1.01 to -0.06 (-5.8 mmol/mol, -11.0 to -0.7); I2 = 41%; moderate certainty evidence) and may reduce weight (low certainty evidence). GLP-1 agonists may have little or no effect on eGFR, hypoglycaemia, or discontinuation due to adverse effects (low certainty evidence). It is uncertain whether GLP-1 agonists reduce FBG, increase gastrointestinal symptoms, or affect the risk of pancreatitis (very low certainty evidence).Compared to placebo, it is uncertain whether glitazones have any effect on HbA1c, FBG, death, weight, and risk of hypoglycaemia (very low certainty evidence).Compared to glipizide, sitagliptin probably reduces hypoglycaemia (2 studies, 551 participants: RR 0.40, 0.23 to 0.69; I2 = 0%; moderate certainty evidence). Compared to glipizide, sitagliptin may have had little or no effect on HbA1c, FBG, weight, and eGFR (low certainty evidence). Compared to glipizide, it is uncertain if sitagliptin has any effect on death or discontinuation due to adverse effects (very low certainty).For types, dosages or modes of administration of insulin and other head-to-head comparisons only individual studies were available so no conclusions could be made. AUTHORS' CONCLUSIONS: Evidence concerning the efficacy and safety of glucose-lowering agents in diabetes and CKD is limited. SGLT2 inhibitors and GLP-1 agonists are probably efficacious for glucose-lowering and DPP-4 inhibitors may be efficacious for glucose-lowering. Additionally, SGLT2 inhibitors probably reduce BP, heart failure, and hyperkalaemia but increase genital infections, and slightly increase creatinine. The safety profile for GLP-1 agonists is uncertain. No further conclusions could be made for the other classes of glucose-lowering agents including insulin. More high quality studies are required to help guide therapeutic choice for glucose-lowering in diabetes and CKD.

Models of care for co-morbid diabetes and chronic kidney disease.

Diabetes and chronic kidney disease (CKD) are two of the most prevalent co-morbid chronic diseases in Australia. The increasing complexity of multi-morbidity, and current gaps in health-care delivery for people with co-morbid diabetes and CKD, emphasize the need for better models of care for this population. Previously, proposed published models of care for co-morbid diabetes and CKD have not been co-designed with stake-holders or formally evaluated. Particular components of health-care shown to be effective in this population are interventions that: are structured, intensive and multifaceted (treating diabetes and multiple cardiovascular risk factors); involve multiple medical disciplines; improve self-management by the patient; and upskill primary health-care. Here we present an integrated patient-centred model of health-care delivery incorporating these components and co-designed with key stake-holders including specialist health professionals, general practitioners and Diabetes and Kidney Health Australia. The development of the model of care was informed by focus groups of patients and health-professionals; and semi-structured interviews of care-givers and health professionals. Other distinctives of this model of care are routine screening for psychological morbidity; patient-support through a phone advice line; and focused primary health-care support in the management of diabetes and CKD. Additionally, the model of care integrates with the patient-centred health-care home currently being rolled out by the Australian Department of Health. This model of care will be evaluated after implementation across two tertiary health services and their primary care catchment areas.

Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.

BACKGROUND: Kidney transplantation is the preferred form of kidney replacement therapy for patients with end-stage kidney disease (ESKD) and is often complicated by worsening or new-onset diabetes. Management of hyperglycaemia is important to reduce post-transplant and diabetes-related complications. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. OBJECTIVES: To evaluate the efficacy and safety of pharmacological interventions for lowering glucose levels in patients who have undergone kidney transplantation and have diabetes. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 15 April 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: We included seven studies that involved a total of 399 kidney transplant recipients. All included studies had observed heterogeneity in the patient population, interventions and measured outcomes or missing data (which was unavailable despite correspondence with authors). Many studies had incompletely reported methodology preventing meta-analysis and leading to low confidence in treatment estimates.Three studies with 241 kidney transplant recipients examined the use of more intensive compared to less intensive insulin therapy in kidney transplant recipients with pre-existing type 1 or 2 diabetes. Evidence for the effects of more intensive compared to less intensive insulin therapy on transplant graft survival, HbA1c, fasting blood glucose, all cause mortality and adverse effects including hypoglycaemia was of very low quality. More intensive versus less intensive insulin therapy resulted in no difference in transplant or graft survival over three to five years in one study while another study showed that more intensive versus less intensive insulin therapy resulted in more rejection events over the three year follow-up (11 events in total; 9 in the more intensive group, P = 0.01). One study showed that more intensive insulin therapy resulted in a lower mean HbA1c (10 ± 0.8% versus 13 ± 0.9%) and lower fasting blood glucose (7.22 ± 0.5 mmol/L versus 13.44 ± 1.22 mmol/L) at 13 months compared with standard insulin therapy. Another study showed no difference between more intensive compared to less intensive insulin therapy on all-cause mortality over a five year follow-up period. All studies showed either an increased frequency of hypoglycaemia or severe hypoglycaemia episodes.Three studies with a total of 115 transplant recipients examined the use of DPP4 inhibitors for new-onset diabetes after transplantation. Evidence for the treatment effect of DPP4 inhibitors on transplant or graft survival, HbA1c and fasting blood glucose levels, all cause mortality, and adverse events including hypoglycaemia was of low quality. One study comparing vildagliptin to placebo and another comparing sitagliptin to placebo showed no difference in transplant or graft survival over two to four months of follow-up. One study comparing vildagliptin to placebo showed no significant change in estimated glomerular filtration rate from baseline (1.9 ± 10.3 mL/min/1.73 m2, P = 0.48 and 2.1 ± 6.1 mL/min/1.73 m2, P = 0.22) and no deaths, in either treatment group over three months of follow-up. One study comparing vildagliptin to placebo showed a lower HbA1c level (mean ± SD) (6.3 ± 0.5% versus versus 6.7 ± 0.6%, P = 0.03) and trend towards a greater lowering of fasting blood glucose (-0.91 ± -0.92 mmol/L versus vs -0.19 ± 1.16 mmol/L, P = 0.08) with vildagliptin. One study comparing sitagliptin to insulin glargine showed an equivalent lowering of HbA1c (-0.6 ± 0.5% versus -0.6 ± 0.6%, P = NS) and fasting blood glucose (4.92 ± 1.42 versus 4.76 ± 1.09 mmol/L, P = NS) with sitagliptin. For the outcome of hypoglycaemia, one study comparing vildagliptin to placebo reported no episodes of hypoglycaemia, one study comparing sitagliptin to insulin glargine reported fewer episodes of hypoglycaemia with sitagliptin (3/28 patients; 10.7% versus 5/28; 17.9%) and one cross-over study of sitagliptin and placebo reported two episodes of asymptomatic moderate hypoglycaemia (2 to 3.9 mmol/L) when sitagliptin was administered with glipizide. All three studies reported no drug interactions between DPP4 inhibitors and the immunosuppressive agents taken.Evidence for the treatment effect of pioglitazone for treating pre-existing diabetes was of low quality. One study with 62 transplant recipients compared the use of pioglitazone with insulin to insulin alone for treating pre-existing diabetes. Pioglitazone resulted in a lower HbA1c level (mean ± SD) (-1.21 ± 1.2 versus 0.39 ± 1%, P < 0.001) but had no effects on fasting blood glucose (6.58 ± 2.71 versus 7.28 ± 2.78 mmol/L, P = 0.14 ), and change in creatinine (3.54 ± 15.03 versus 10.61 ± 18.56 mmol/L, P = 0.53) and minimal adverse effects (no episodes of hypoglycaemia, three dropped out due to mild to moderate lower extremity oedema, cyclosporin levels were not affected). AUTHORS' CONCLUSIONS: Evidence concerning the efficacy and safety of glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients is limited. Existing studies examine more intensive versus less intensive insulin therapy, and the use of DPP4 inhibitors and pioglitazone. The safety and efficacy of more intensive compared to less intensive insulin therapy is very uncertain and the safety and efficacy of DPP4 inhibitors and pioglitazone is uncertain, due to data being limited and of poor quality. Additional RCTs are required to clarify the safety and efficacy of current glucose-lowering agents for kidney transplant recipients with diabetes.

The association between patient activation and self-care practices: A cross-sectional study of an Australian population with comorbid diabetes and chronic kidney disease.

OBJECTIVE: This study aimed to examine the association between performance of self-care activities and patient or disease factors as well as patient activation levels in patients with diabetes and chronic kidney disease (CKD) in Australia. METHODS: A cross-sectional study was conducted among adults with diabetes and CKD (eGFR <60 mL/min/1.73m2 ) who were recruited from renal and diabetes clinics of four tertiary hospitals in Australia. Demographic and clinical data were collected, as well as responses to the Patient Activation Measure (PAM) and the Summary of Diabetes Self-Care Activities (SDSCA) scale. Regression analyses were performed to determine the relationship between activation and performance of self-care activities. RESULTS: A total of 317 patients (70% men) with a mean age of 66.9 (SD=11.0) years participated. The mean (SD) PAM and composite SDSCA scores were 57.6 (15.5) % (range 0-100) and 37.3 (11.2) (range 0-70), respectively. Younger age, being male, advanced stages of CKD and shorter duration of diabetes were associated with lower scores in one or more self-care components. Patient activation was positively associated with the composite SDSCA score, and in particular the domains of general diet and blood sugar checking (P<.05), but not specific diet, exercising and foot checking. CONCLUSION: In people with diabetes and CKD, a high level of patient activation was positively associated with a higher overall level of self-care. Our results identify subgroups of people who may benefit from tailored interventions to further improve their health outcomes. Further prospective studies are warranted to confirm present findings.

Identifying health service barriers in the management of co-morbid diabetes and chronic kidney disease in primary care: a mixed-methods exploration.

BACKGROUND: Co-morbid diabetes and chronic kidney disease (CKD) are common in primary care but health care can be suboptimal. OBJECTIVE: In this multi-centre mixed-methods study, we investigated GPs' perspectives on health service barriers in managing diabetes and CKD as an initial step towards health care improvement. METHODS: Four focus groups were conducted among GPs in Australia's two largest cities. Transcripts underwent content analysis to inform development of a survey exploring health service barriers. This survey was then emailed/mailed to 840 GPs. Statistical analyses were performed using STATA v2.1. RESULTS: Responses were received from 13.7% of GPs (n = 115), mean (±SD) age 55.3 (10.1) years and mean duration of practice 26.6 (10.6). The majority (88.4%) reported wanting to manage diabetes and CKD in primary care with specialist assistance. However, 34.8% were unclear about the definition of CKD with 73.2% wanting more education. Access to specialist services was problematic with 39.3% and 28.2% reporting the process of referring patients to diabetes or CKD services, respectively, as hard. Coordination of care was also a problem with 35.6% unclear about each health care provider's role, 50.5% believing patients faced difficulties due to poor coordination across providers and 51.6% reporting duplication of tests. CONCLUSIONS: GPs expressed a clear interest in being the principal health care providers for patients with co-morbid diabetes and CKD. Supporting GPs and health care improvement focusing on overcoming reported barriers such as inadequate knowledge about CKD, access to specialist services and coordination of care may improve outcomes for people with co-morbid diabetes and CKD.

Primary and tertiary health professionals' views on the health-care of patients with co-morbid diabetes and chronic kidney disease - a qualitative study.

BACKGROUND: Health-care for co-morbid diabetes and chronic kidney disease (CKD) is often sub-optimal. To improve health-care, we explored the perspectives of general practitioners (GPs) and tertiary health-care professionals concerning key factors influencing health-care of diabetes and CKD. METHODS: A total of 65 health professionals were purposively sampled from Australia's 2 largest cities to participate in focus groups and semi-structured interviews. Four focus groups were conducted with GPs who referred to 4 tertiary health services in Australia's 2 largest cities, with 6 focus groups conducted with tertiary health-care professionals from the 4 tertiary health services. An additional 8 semi-structured interviews were performed with specialist physicians who were heads of diabetes and renal units. All discussions were facilitated by the same researcher, with discussions digitally recorded and transcribed verbatim. All qualitative data was thematically analysed independently by 2 researchers. RESULTS: Both GPs and tertiary health-care professionals emphasised the importance of primary care and that optimal health-care was an inter-play between patient self-management and primary health-care, with specialist tertiary health-care support. Patient self-management, access to specialty care, coordination of care and a preventive approach were identified as key factors that influence healthcare and require improvement. Both groups suggested that an integrated specialist diabetes-kidney service could improve care. Unit heads emphasised the importance of quality improvement activities. CONCLUSIONS: GPs and tertiary health-care professionals emphasised the importance of patient self-management and primary care involvement in the health-care of diabetes and CKD. Supporting GPs with an accessible, multidisciplinary diabetes-renal health service underpinned by strong communication pathways, a preventive approach and quality improvement activities, may improve health-care and patient outcomes in co-morbid diabetes and CKD.

Multi-State Gene Cluster Switches Determine the Adaptive Mitochondrial And Metabolic Landscape of Breast Cancer.

Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution. Metabolic adaptations represent important therapeutic targets in tumors, highlighting the need to characterize the full spectrum, characteristics, and regulation of the metabolic switches. To investigate the hypothesis that metabolic switches associated with specific metabolic states can be recognized by locating large alternating gene expression patterns, we developed a method to identify interspersed gene sets by massive correlated biclustering (MCbiclust) and to predict their metabolic wiring. Testing the method on breast cancer transcriptome datasets revealed a series of gene sets with switch-like behavior that could be used to predict mitochondrial content, metabolic activity, and central carbon flux in tumors. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labelled substrates. The metabolic switch positions also distinguished between cellular states, correlating with tumor pathology, prognosis, and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states.

Cost-effectiveness of health technologies in adults with type 1 diabetes: a systematic review and narrative synthesis.

BACKGROUND: With the rapid development of technologies for type 1 diabetes, economic evaluations are integral in guiding cost-effective clinical and policy decisions. We therefore aimed to review and synthesise the current economic literature for available diabetes management technologies and outline key determinants of cost-effectiveness. METHODS: A systematic search was conducted in April 2019 that focused on modelling or trial based economic evaluations. Searched databases included Medline, Medline in-process and other non-indexed citations, EMBASE, PubMed, All Evidenced Based Medicine Reviews, EconLit, Cost-effectiveness analysis Registry, Research Papers in Economics, Web of Science, PsycInfo, CINAHL, and PROSPERO from inception. We assessed quality of included studies with the Questionnaire to Assess Relevance and Credibility of Modeling Studies for Informing Health Care Decision Making an ISPOR-AMCP-NPC good practice task force report. Screening of abstracts and full-texts, appraisal, and extraction were performed by two independent researches. RESULTS: We identified 16,772 publications, of which 35 were analysed and included 11 health technologies. Despite a lack of consensus, most studies reported that insulin pumps (56%) or interstitial glucose sensors (62%) were cost-effective, although incremental cost-effectiveness ratios ranged widely ($14,266-$2,997,832 USD). Cost-effectiveness for combined insulin pumps and glucose sensors was less clear. Determinants of cost-effectiveness included treatment effects on glycosylated haemoglobin and hypoglycaemia, costing of technologies and complications, and measures of utility. CONCLUSIONS: Insulin pumps or glucose sensors appeared cost-effective, particularly in populations with higher HbA1c levels and rates of hypoglycaemia. However, cost-effectiveness for combined insulin pumps and glucose sensors was less clear. REGISTRATION: The study was registered with PROSPERO, number CRD42017077221.

Time in Range for Multiple Technologies in Type 1 Diabetes: A Systematic Review and Network Meta-analysis.

BACKGROUND: Time in range is a key glycemic metric, and comparisons of management technologies for this outcome are critical to guide device selection. PURPOSE: We conducted a systematic review and network meta-analysis to compare and rank technologies for time in glycemic ranges. DATA SOURCES: We searched Evidenced-Based Medicine Reviews, CINAHL, Embase, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PROSPERO, PsycInfo, PubMed, and Web of Science until 24 April 2019. STUDY SELECTION: We included randomized controlled trials ≥2 weeks' duration comparing technologies for management of type 1 diabetes in adults (≥18 years of age), excluding pregnant women. DATA EXTRACTION: Data were extracted using a predefined template. Outcomes were percent time with sensor glucose levels 3.9-10.0 mmol/L (70-180 mg/dL), >10.0 mmol/L (180 mg/dL), and <3.9 mmol/L (70 mg/dL). DATA SYNTHESIS: We identified 16,772 publications, of which 14 eligible studies compared eight technologies comprising 1,043 participants. Closed-loop systems led to greater percent time in range than any other management strategy, and mean percent time in range was 17.85 (95% predictive interval 7.56-28.14) longer than with usual care of multiple daily injections with capillary glucose testing. Closed-loop systems ranked best for percent time in range or above range with use of Surface Under the Cumulative RAnking curve (SUCRA) (98.5% and 93.5%, respectively). Closed-loop systems also ranked highly for time below range (SUCRA 62.2%). LIMITATIONS: Overall risk of bias ratings were moderate for all outcomes. Certainty of evidence was very low. CONCLUSIONS: In the first integrated comparison of multiple management strategies considering time in range, we found that the efficacy of closed-loop systems appeared better than all other approaches.

The Efficacy of Technology in Type 1 Diabetes: A Systematic Review, Network Meta-analysis, and Narrative Synthesis.

Background: Existing technologies for type 1 diabetes have not been compared against the full range of alternative devices. Multiple metrics of glycemia and patient-reported outcomes for evaluating technologies also require consideration. We thus conducted a systematic review, network meta-analysis, and narrative synthesis to compare the relative efficacy of available technologies for the management of type 1 diabetes. Methods: We searched MEDLINE, MEDLINE In-Process and other nonindexed citations, EMBASE, PubMed, All Evidence-Based Medicine Reviews, Web of Science, PsycINFO, CINAHL, and PROSPERO (inception-April 24, 2019). We included RCT ≥6 weeks duration comparing technologies for type 1 diabetes management among nonpregnant adults (>18 years of age). Data were extracted using a predefined tool. Primary outcomes were A1c (%), hypoglycemia rates, and quality of life (QoL). We estimated mean difference for A1c and nonsevere hypoglycemia, rate ratio for severe hypoglycemia, and standardized mean difference for QoL in network meta-analysis with random effects. Results: We identified 16,772 publications, of which 52 eligible studies compared 12 diabetes management technologies comprising 3,975 participants in network meta-analysis. Integrated insulin pump and continuous glucose monitoring (CGM) systems with low-glucose suspend or hybrid closed-loop algorithms resulted in A1c levels 0.96% (predictive interval [95% PrI] 0.04-1.89) and 0.87% (95% PrI 0.12-1.63) lower than multiple daily injections with either flash glucose monitoring or capillary glucose testing, respectively. In addition, integrated systems had the best ranking for A1c reduction utilizing the surface under the cumulative ranking curve (SUCRA-96.4). While treatment effects were nonsignificant for many technology comparisons regarding severe hypoglycemia and QoL, simultaneous evaluation of outcomes in cluster analyses as well as narrative synthesis appeared to favor integrated insulin pump and continuous glucose monitors. Overall risk of bias was moderate-high. Certainty of evidence was very low. Conclusions: Integrated insulin pump and CGM systems with low-glucose suspend or hybrid closed-loop capability appeared best for A1c reduction, composite ranking for A1c and severe hypoglycemia, and possibly QoL. Registration: PROSPERO, number CRD42017077221.

Type 2 Diabetes Patients' Perspectives, Experiences, and Barriers Toward Diabetes-Related Self-Care: A Qualitative Study From Pakistan.

Objective: This study aimed to qualitatively explore perspectives, practices, and barriers to self-care practices (eating habits, physical activity, self-monitoring of blood glucose, and medicine intake behavior) in urban Pakistani adults with type 2 diabetes mellitus (T2DM). Methods: Pakistani adults with T2DM were recruited from the outpatient departments of two hospitals in Lahore. Semistructured interviews were conducted and audiorecorded until thematic saturation was reached. Two researchers thematically analyzed the data independently using NVivo® software with differences resolved by a third researcher. Results: Thirty-two Pakistani adults (aged 35-75 years, 62% female) participated in the study. Six themes were identified from qualitative analysis: role of family and friends, role of doctors and healthcare, patients' understanding about diabetes, complication of diabetes and other comorbidities, burden of self care, and life circumstances. A variable experience was observed with education and healthcare. Counseling by healthcare providers, family support, and fear of diabetes-associated complications are the key enablers that encourage study participants to adhere to diabetes-related self-care practices. Major barriers to self care are financial constraints, physical limitations, extreme weather conditions, social gatherings, loving food, forgetfulness, needle phobia, and a hectic job. Conclusion: Respondents identified many barriers to diabetes self care, particularly related to life situations and diabetes knowledge. Family support and education by healthcare providers were key influencers to self-care practices among Pakistani people with diabetes.

Health-related quality of life among patients with comorbid diabetes and kidney disease attending a codesigned integrated model of care: a longitudinal study.

OBJECTIVE: To evaluate the impact of an integrated diabetes and kidney disease model of care on health-related quality of life (HRQOL) of patients with comorbid diabetes and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: A longitudinal study of adult patients (over 18 years) with comorbid diabetes and CKD (stage 3a or worse) who attended a new diabetes kidney disease service was conducted at a tertiary hospital. A questionnaire consisting of demographics, clinical data, and the Kidney Disease Quality of Life (KDQOL-36) was administered at baseline and after 12 months. Paired t-tests were used to compare baseline and 12-month scores. A subgroup analysis examined the effects by patient gender. Multiple regression analysis examined the factors associated with changes in scores. RESULTS: 179 patients, 36% of whom were female, with baseline mean±SD age of 65.9±11.3 years, were studied. Across all subscales, HRQOL did not significantly change over time (p value for all mean differences >0.05). However, on subgroup analysis, symptom problem list and physical composite summary scores increased among women (MD=9.0, 95% CI 1.25 to 16.67; p=0.02 and MD=4.5, 95% CI 0.57 to 8.42; p=0.03 respectively) and physical composite scores decreased among men (MD=-3.35, 95% CI -6.26 to -0.44; p=0.03). CONCLUSION: The HRQOL of patients with comorbid diabetes and CKD attending a new codesigned, integrated diabetes and kidney disease model of care was maintained over 12 months. Given that HRQOL is known to deteriorate over time in this high-risk population, the impact of these findings on clinical outcomes warrants further investigation.

Patient-reported barriers and outcomes associated with poor glycaemic and blood pressure control in co-morbid diabetes and chronic kidney disease.

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.