Lower Extremity Amputation Rates in People With Diabetes Mellitus: A Retrospective Population Based Cohort Study in Zwolle Region, The Netherlands.

OBJECTIVE: Lower extremity amputations are a major complication of diabetes mellitus (DM). In a previous Dutch study, the incident rate of major amputations was 89.2 per 100 000 person years. The primary aim of this study was to describe the lower extremity amputation rates in people with DM in the Zwolle region, where preventive and curative footcare is organised according to the guidelines of the International Working Group of the Diabetic Foot (IWGDF). The secondary aim was to evaluate outcomes and underlying characteristics of these people. METHODS: This was a retrospective regional population based cohort study. Data from all people with DM treated in primary and secondary care, living in the region Zwolle were collected. All amputations in the period 2017 to 2019 were analysed. Comparisons were made between those with and without an amputation. RESULTS: In the analysis 5 915 people with DM were included, with a mean age of 67.8 (IQR 57.9, 75.9) years. Of those people, 47% were women and the median HbA1c was 53 (IQR 47, 62) mmol/mol. Over the three year study period 68 amputations were performed in 59 people: 46 minor, 22 major. This translated into an average annual crude amputation incidence rate of non-traumatic major and minor amputations of 41.5 and 86.9 per 100 000 person years among people with diabetes. Compared with those not undergoing amputations, those who underwent an amputation were more often men, older, mainly had T2DM, were treated in secondary care, had higher diastolic blood pressure, worse diabetic footcare profile, longer DM duration and higher HbA1c. At the end of the follow up, 111 people died: 96 (1.6%) without and 15 (25.4%) with amputations (p < .001). CONCLUSIONS: This retrospective study provides detailed insight into the rate of amputations in Dutch people with diabetes in the region Zwolle. Compared with previous Dutch estimates, these data suggest a considerable decrease in the major amputation incidence rate.

Physicians and nurses view on their roles in communication and collaboration with families: A qualitative study.

BACKGROUND: Families are introduced as new partners in interprofessional communication and collaboration during hospitalisation of an adult patient. Their introduction into the healthcare team has consequences for the roles and responsibilities of all healthcare professionals. Role clarification is thus needed to create optimal communication and collaboration with families. AIM: To gain insight into how physicians and nurses view their own roles and each other's roles in communication and collaboration with families in the care of adult patients. METHODS: A qualitative interpretive interview design was used. Fourteen semi-structured interviews, with seven physicians and seven nurses, were conducted. Data were analysed according to the steps of thematic analysis. For the study design and analysis of the results, the guidelines of the consolidated criteria for reporting qualitative studies (COREQ) were followed. The ethical committee of the University Medical Center Groningen approved the study protocol (research number 202100640). FINDINGS: Thematic analysis resulted in three themes, each consisting of two or three code groups. Two themes "building a relationship" and "sharing information" were described as roles that both nurses and physicians share regarding communication and collaboration with families. The role expectations differed between physicians and nurses, but these differences were not discussed with each other. The theme "providing support to family" was regarded a nurse-specific role by both professions. CONCLUSION: Physicians and nurses see a role for themselves and each other in communication and collaboration with families. However, the division of roles and expectations thereof are different, overlapping, and unclear. To optimise the role and position of family during hospital care, clarification and division of the roles between physicians and nurses in this partnership is necessary.

An urgent call to raise the bar in oncology.

Important breakthroughs in medical treatments have improved outcomes for patients suffering from several types of cancer. However, many oncological treatments approved by regulatory agencies are of low value and do not contribute significantly to cancer mortality reduction, but lead to unrealistic patient expectations and push even affluent societies to unsustainable health care costs. Several factors that contribute to approvals of low-value oncology treatments are addressed, including issues with clinical trials, bias in reporting, regulatory agency shortcomings and drug pricing. With the COVID-19 pandemic enforcing the elimination of low-value interventions in all fields of medicine, efforts should urgently be made by all involved in cancer care to select only high-value and sustainable interventions. Transformation of medical education, improvement in clinical trial design, quality, conduct and reporting, strict adherence to scientific norms by regulatory agencies and use of value-based scales can all contribute to raising the bar for oncology drug approvals and influence drug pricing and availability.

Urinary liver-type fatty acid-binding protein is independently associated with graft failure in outpatient kidney transplant recipients.

Urinary liver-type fatty acid-binding protein (uL-FABP) is a biomarker of kidney hypoxia and ischemia, and thus offers a novel approach to identify early kidney insults associated with increased risk of graft failure in outpatient kidney transplant recipients (KTR). We investigated whether uL-FABP is associated with graft failure and whether it improves risk prediction. We studied a cohort of 638 outpatient KTR with a functional graft ≥1-year. During a median follow-up of 5.3 years, 80 KTR developed graft failure. uL-FABP (median 2.11, interquartile range 0.93-7.37 µg/24"/>h) was prospectively associated with the risk of graft failure (hazard ratio 1.75; 95% confidence interval 1.27-2.41 per 1-SD increment; P = .001), independent of potential confounders including estimated glomerular filtration rate and proteinuria. uL-FABP showed excellent discrimination ability for graft failure (c-statistic of 0.83) and its addition to a prediction model composed by established clinical predictors of graft failure significantly improved the c-statistic to 0.89 (P for F-test <.001). These results were robust to several sensitivity analyses. Further validation studies are warranted to evaluate the potential use of a risk-prediction model including uL-FABP to improve identification of outpatient KTR at high risk of graft failure in clinical care.

The association between use of proton-pump inhibitors and excess mortality after kidney transplantation: A cohort study.

BACKGROUND: Chronic use of proton-pump inhibitors (PPIs) is common in kidney transplant recipients (KTRs). However, concerns are emerging about the potential long-term complications of PPI therapy. We aimed to investigate whether PPI use is associated with excess mortality risk in KTRs. METHODS AND FINDINGS: We investigated the association of PPI use with mortality risk using multivariable Cox proportional hazard regression analyses in a single-center prospective cohort of 703 stable outpatient KTRs, who visited the outpatient clinic of the University Medical Center Groningen (UMCG) between November 2008 and March 2011 (ClinicalTrials.gov Identifier NCT02811835). Independent replication of the results was performed in a prospective cohort of 656 KTRs from the University Hospitals Leuven (NCT01331668). Mean age was 53 ± 13 years, 57% were male, and 56.6% used PPIs. During median follow-up of 8.2 (4.7-9.0) years, 194 KTRs died. In univariable Cox regression analyses, PPI use was associated with an almost 2 times higher mortality risk (hazard ratio [HR] 1.86, 95% CI 1.38-2.52, P < 0.001) compared with no use. After adjustment for potential confounders, PPI use remained independently associated with mortality (HR 1.68, 95% CI 1.21-2.33, P = 0.002). Moreover, the HR for mortality risk in KTRs taking a high PPI dose (>20 mg omeprazole equivalents/day) compared with patients taking no PPIs (HR 2.14, 95% CI 1.48-3.09, P < 0.001) was higher than in KTRs taking a low PPI dose (HR 1.72, 95% CI 1.23-2.39, P = 0.001). These findings were replicated in the Leuven Renal Transplant Cohort. The main limitation of this study is its observational design, which precludes conclusions about causation. CONCLUSIONS: We demonstrated that PPI use is associated with an increased mortality risk in KTRs, independent of potential confounders. Moreover, our data suggest that this risk is highest among KTRs taking high PPI dosages. Because of the observational nature of our data, our results require further corroboration before it can be recommended to avoid the long-term use of PPIs in KTRs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02811835, NCT01331668.

Relationship between serum B12 concentrations and mortality: experience in NHANES.

BACKGROUND: There is conflicting evidence in the literature on the association between (elevated) serum B12 concentrations and subsequent disease or mortality. We evaluated in the NHANES general population the association of serum B12 concentrations as well as vitamin B12 supplement intake with all-cause, cardiovascular, and cancer-related mortality, while taking into account demographic and lifestyle factors and significant other diseases which are known to be associated with poorer outcome. METHODS: The main outcomes of our study were all-cause mortality, cardiovascular mortality, and cancer-related mortality. Mortality status and cause of death were determined by NHANES-linked National Death Index public access files through December 31, 2015. The association of serum B12 concentrations and vitamin B12 supplement intake with mortality was assessed with Cox proportional hazard (PH) models, with adjustment for a number of relevant demographic and lifestyle factors and comorbidity. RESULTS: The final study population of 24,262 participants had a mean age of 48 (SD 19) years; 50.1% were males. The median follow-up duration was 109 months (range 1-201 months). On the census day of December 31, 2015, 3023 participants were determined as deceased (12.5%). The fully adjusted Cox PH model indicated that low serum B12 concentrations < 140 pmol/l were associated with a small increase in all-cause (hazard ratio, HR 1.39, 95% CI 1.08-1.78, p = 0.011) and cardiovascular (HR 1.64, 95% CI 1.08-2.47, p = 0.020) mortality. Similarly, high serum B12 concentrations > 700 pmol/l were associated with an increase in cardiovascular mortality only (HR 1.45, 95% CI 1.01-2.06, p = 0.042). Participants with a diagnosis of hypertension, dyslipidemia, CVD, and cancer more frequently used vitamin B12-containing supplements than those without these diagnoses. We could not demonstrate an association between vitamin B12 supplement intake and mortality, when adjusted for comorbidity. CONCLUSIONS: In the general population of NHANES, low serum B12 concentrations were associated with a moderate increase in all-cause mortality. There was a small but significant increase in cardiovascular mortality in the groups with low or high serum B12. High intake of vitamin B12 in the form of supplements was not associated with any adverse effect on mortality and therefore can be regarded as safe.

Post-transplantation plasma malondialdehyde is associated with cardiovascular mortality in renal transplant recipients: a prospective cohort study.

BACKGROUND: In renal transplant recipients (RTRs), cardiovascular mortality is the most common cause of long-term renal graft loss. Oxidative stress (OS) has been associated with cardiovascular disease and is known to be enhanced in RTRs. We aimed to prospectively investigate whether the concentration of the OS biomarker malondialdehyde (MDA) is associated with long-term risk of cardiovascular mortality in a large cohort of RTRs. METHODS: The plasma MDA concentration was measured using the thiobarbituric acid reaction assay in 604 extensively phenotyped RTRs with a functioning allograft for ≥1 year. The association between MDA and cardiovascular mortality was assessed using Cox proportional hazard regression analyses in the overall cohort and within subgroups according to significant effect modifiers. RESULTS: Median circulating MDA concentration at baseline was 5.38 [interquartile range (IQR) 4.31-6.45] µmol/L. During a follow-up period of 6.4 (IQR 5.6-6.8) years, 110 (18%) RTRs died, with 40% of deaths due to cardiovascular causes. MDA concentration was significantly associated with the risk for cardiovascular mortality {hazard ratio [HR] 1.31 [95% confidence interval (CI) 1.03-1.67] per 1-SD increment}, independent of adjustment for potential confounders, including renal function, immunosuppressive therapy, smoking status and blood pressure. The association between MDA concentration and the risk for cardiovascular mortality was stronger in RTRs with relatively lower plasma ascorbic acid concentrations [≤42.5 µmol/L; HR 1.79 (95% CI 1.30-2.48) per 1-SD increment] or relatively lower estimated glomerular filtration rates [≤45 mL/min/1.73 m2; HR 2.09 (95% CI 1.45-3.00) per 1-SD increment]. CONCLUSIONS: Circulating MDA concentration is independently associated with long-term risk for cardiovascular mortality, particularly in RTRs with relatively lower ascorbic acid concentrations or renal function. Further studies are warranted to elucidate whether OS-targeted interventions could decrease cardiovascular mortality in RTRs.

Consumption of fruits and vegetables and cardiovascular mortality in renal transplant recipients: a prospective cohort study.

BACKGROUND: It currently remains understudied whether low consumption of fruits and vegetables after kidney transplantation may be a modifiable cardiovascular risk factor. We aimed to investigate the associations between consumption of fruits and vegetables and cardiovascular mortality in renal transplant recipients (RTRs). METHODS: Consumption of fruits and vegetables was assessed in an extensively phenotyping cohort of RTRs. Multivariable-adjusted Cox proportional hazards regression analyses were performed to assess the risk of cardiovascular mortality. RESULTS: We included 400 RTRs (age 52 ± 12 years, 54% males). At a median follow-up of 7.2 years, 23% of RTRs died (53% were due to cardiovascular causes). Overall, fruit consumption was not associated with cardiovascular mortality {hazard ratio [HR] 0.82 [95% confidence interval (CI) 0.60-1.14]; P = 0.24}, whereas vegetable consumption was inversely associated with cardiovascular mortality [HR 0.49 (95% CI 0.34-0.71); P < 0.001]. This association remained independent of adjustment for several potential confounders. The association of fruit consumption with cardiovascular mortality was significantly modified by estimated glomerular filtration rate (eGFR; Pinteraction = 0.01) and proteinuria (Pinteraction = 0.01), with significant inverse associations in patients with eGFR > 45 mL/min/1.73 m2 [HR 0.56 (95% CI 0.35-0.92); P = 0.02] or the absence of proteinuria [HR 0.62 (95% CI 0.41-0.92); P = 0.02]. CONCLUSIONS: In RTRs, a relatively higher vegetable consumption is independently and strongly associated with lower cardiovascular mortality. A relatively higher fruit consumption is also associated with lower cardiovascular mortality, although particularly in RTRs with eGFR > 45 mL/min/1.73 m2 or an absence of proteinuria. Further studies seem warranted to investigate whether increasing consumption of fruits and vegetables may open opportunities for potential interventional pathways to decrease the burden of cardiovascular mortality in RTRs.

Dietary Approach to Stop Hypertension (DASH) diet and risk of renal function decline and all-cause mortality in renal transplant recipients.

Renal transplant recipients (RTR) are at risk of decline of graft function and premature mortality, with high blood pressure as an important risk factor for both. To study the association of the Dietary Approach to Stop Hypertension (DASH) diet with these adverse events, we conducted a prospective cohort study of adult RTR. Dietary data were collected using a validated 177-item food frequency questionnaire and an overall DASH-score was obtained. We included 632 stable RTR (mean ± standard deviation age 53.0 ± 12.7 years, 57% men). Mean DASH score was 23.8 ± 4.7. During median follow-up of 5.3 (interquartile range, 4.1-6.0) years, 119 (18.8%) RTR had renal function decline, defined as a combined endpoint of doubling of serum creatinine and death-censored graft failure, and 128 (20.3%) died. In Cox-regression analyses, RTR in the highest tertile of the DASH score had lower risk of both renal function decline (hazard ratio [HR] = 0.57; 95% confidence interval [CI], 0.33-0.96, P = .03) and all-cause mortality (HR = 0.52; 95%CI, 0.32-0.83, P = .006) compared to the lowest tertile, independent of potential confounders. Adherence to a DASH-style diet is associated with lower risk of both renal function decline and all-cause mortality. These results suggest that a healthful diet might benefit long-term outcome in RTR.

Serum paraoxonase-1 activity is inversely related to free thyroxine in euthyroid subjects: The PREVEND Cohort Study.

BACKGROUND: Low-normal thyroid function within the euthyroid range has been suggested to enhance atherosclerosis susceptibility. Paraoxonase-1 (PON-1) may protect against atherosclerotic cardiovascular disease development by attenuating oxidative stress. We evaluated relationships of PON-1 with thyroid stimulating hormone (TSH), free T4 , free T3 , lipids and apolipoprotein (apo)A-I in euthyroid subjects, and assessed whether such relationships are modified in the context of the metabolic syndrome (MetS). MATERIALS AND METHODS: Serum PON-1 activity (arylesterase activity), TSH, free T4 , free T3 , lipids and apoA-I was measured in 2206 euthyroid subjects (aged 28-75 years; 1138 men (age 49 ± 13 years) and 1068 women (age 46 ± 12 years), recruited from the general population (PREVEND cohort). RESULTS: In age- and sex-adjusted analysis, PON-1 activity (divided into tertiles) was positively related to TSH (ß = -0.045, P = .036) and inversely to free T4 (ß = -0.042, P = .050) but not to free T3 (ß = -0.027, P = .20). PON-1 activity was positively related to total cholesterol, non-HDL cholesterol and triglycerides, as well as to HDL cholesterol and apoA-I (P < .01 to <.001). The inverse relationship of PON-1 activity with free T4 remained present after adjustment for lipids and other potential confounders (ß = -0.066, P = .002), but the positive relationship with TSH lost significance (ß = 0.034, P = .11). The inverse relationship of PON-1 activity with free T4 was not different in subjects with vs without MetS (P = .94), nor modified by the presence of its individual components (P ≥ .22 for each). CONCLUSIONS: Serum PON-1 activity is inversely associated with free T4 in euthyroid subjects, suggesting that low-normal thyroid function may affect PON-1 regulation.

Plasma N-terminal Prosomatostatin and Risk of Incident Cardiovascular Disease and All-Cause Mortality in a Prospective Observational Cohort: the PREVEND Study.

BACKGROUND: Somatostatin is a component of the well-known insulin-like growth factor-1/growth hormone (GH) longevity axis. There is observational evidence that increased GH is associated with an increased risk of cardiovascular disease (CVD). We aimed to investigate the potential association of plasma N-terminal fragment prosomatostatin (NT-proSST) with incident CVD and all-cause mortality in apparently healthy adults. METHODS: We studied 8134 participants without history of CVD (aged 28-75 years; women, 52.6%) from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study in Groningen, the Netherlands. Plasma NT-proSST was measured in baseline samples. Outcomes were incidence of CVD and all-cause mortality. RESULTS: In cross-sectional analyses, NT-proSST [mean (SD), 384.0 (169.3) pmol/L] was positively associated with male sex and age (both P < 0.001). During a median follow-up of 10.5 (Q1-Q3: 9.9-10.8) years, 708 (8.7%) participants developed CVD and 517 (6.4%) participants died. In univariable analyses, NT-proSST was associated with an increased risk of incident CVD and all-cause mortality (both P < 0.001). In multivariable analyses, these associations were independent of the Framingham risk factors, with hazard ratios (95% CI) per doubling of NT-proSST of 1.17 (1.03-1.34; P = 0.02) for incident CVD and of 1.28 (1.09-1.49; P = 0.002) for all-cause mortality. Addition of NT-proSST to the updated Framingham Risk Score improved reclassification (integrated discrimination improvement (P < 0.001); net reclassification improvement was 2.5% (P = 0.04)). CONCLUSIONS: Plasma NT-proSST is positively associated with increased risk of future CVD and all-cause mortality, partly independent of traditional CVD risk factors. Further research is needed to address the nature of associations.

Integrated and implicit: how residents learn CanMEDS roles by participating in practice.

CONTEXT: Learning outcomes for residency training are defined in competency frameworks such as the CanMEDS framework, which ultimately aim to better prepare residents for their future tasks. Although residents' training relies heavily on learning through participation in the workplace under the supervision of a specialist, it remains unclear how the CanMEDS framework informs practice-based learning and daily interactions between residents and supervisors. OBJECTIVES: This study aimed to explore how the CanMEDS framework informs residents' practice-based training and interactions with supervisors. METHODS: Constructivist grounded theory guided iterative data collection and analyses. Data were collected by direct observations of residents and supervisors, combined with formal and field interviews. We progressively arrived at an explanatory theory by coding and interpreting the data, building provisional theories and through continuous conversations. Data analysis drew on sensitising insights from communities of practice theory, which provided this study with a social learning perspective. RESULTS: CanMEDS roles occurred in an integrated fashion and usually remained implicit during interactions. The language of CanMEDS was not adopted in clinical practice, which seemed to impede explicit learning interactions. The CanMEDS framework seemed only one of many factors of influence in practice-based training: patient records and other documents were highly influential in daily activities and did not always correspond with CanMEDS roles. Additionally, the position of residents seemed too peripheral to allow them to learn certain aspects of the Health Advocate and Leader roles. CONCLUSIONS: The CanMEDS framework did not really guide supervisors' and residents' practice or interactions. It was not explicitly used as a common language in which to talk about resident performance and roles. Therefore, the extent to which CanMEDS actually helps improve residents' learning trajectories and conversations between residents and supervisors about residents' progress remains questionable. This study highlights the fact that the reification of competency frameworks into the complexity of practice-based learning is not a straightforward exercise.

Intake of n-3 fatty acids and long-term outcome in renal transplant recipients: a post hoc analysis of a prospective cohort study.

Supplementation with n-3 fatty acids may improve long-term outcomes of renal transplant recipients (RTR). Recent evidence suggests that EPA and DHA have different outcomes compared with α-linolenic acid (ALA). We examined the prospective associations of EPA-DHA and ALA intakes with graft failure and all-cause mortality in 637 RTR. During 3·1 years (interquartile range 2·7, 3·8) of follow-up, forty-one developed graft failure and sixty-seven died. In age- and sex-adjusted analyses, EPA-DHA and ALA intakes were not associated with graft failure. EPA-DHA intake was not significantly associated with mortality (hazard ratio (HR) 0·79; 95% CI 0·54, 1·15 per 0·1 energy% difference). ALA intake was significantly associated with mortality (HR 1·17; 95% CI 1·04, 1·31 per 0·1 energy% difference). This association remained following adjustments for BMI, proteinuria and intakes of fat, carbohydrate and protein. RTR in the highest tertile of ALA intake exhibited about 2-fold higher mortality risk (HR 2·21; 95% CI 1·23, 3·97) compared with the lowest tertile. In conclusion, ALA intake may be associated with increased mortality in RTR. Future RCT are needed to confirm these results.

What supervisors say in their feedback: construction of CanMEDS roles in workplace settings.

The CanMEDS framework has been widely adopted in residency education and feedback processes are guided by it. It is, however, only one of many influences on what is actually discussed in feedback. The sociohistorical culture of medicine and individual supervisors' contexts, experiences and beliefs are also influential. Our aim was to find how CanMEDS roles are constructed in feedback in a postgraduate curriculum-in-action. We applied a set of discourse analytic tools to written feedback from 591 feedback forms from 7 hospitals, including 3150 feedback comments in which 126 supervisors provided feedback to 120 residents after observing their performance in authentic settings. The role of Collaborator was constructed in two different ways: a cooperative discourse of equality with other workers and patients; and a discourse, which gave residents positions of power-delegating, asserting and 'taking a firm stance'. Efficiency-being fast and to the point emerged as an important attribute of physicians. Patients were seldom part of the discourses and, when they were, they were constructed as objects of communication and collaboration rather than partners. Although some of the discourses are in line with what might be expected, others were in striking contrast to the spirit of CanMEDS. This study's findings suggest that it takes more than a competency framework, evaluation instruments, and supervisor training to change the culture of workplaces. The impact on residents of training in such demanding, efficiency-focused clinical environments is an important topic for future research.

A feedback system in residency to evaluate CanMEDS roles and provide high-quality feedback: Exploring its application.

INTRODUCTION: Residents benefit from regular, high quality feedback on all CanMEDS roles during their training. However, feedback mostly concerns Medical Expert, leaving the other roles behind. A feedback system was developed to guide supervisors in providing feedback on CanMEDS roles. We analyzed whether feedback was provided on the intended roles and explored differences in quality of written feedback. METHODS: In the feedback system, CanMEDS roles were assigned to five authentic situations: Patient Encounter, Morning Report, On-call, CAT, and Oral Presentation. Quality of feedback was operationalized as specificity and inclusion of strengths and improvement points. Differences in specificity between roles were tested with Mann-Whitney U tests with a Bonferroni correction (α = 0.003). RESULTS: Supervisors (n = 126) provided residents (n = 120) with feedback (591 times). Feedback was provided on the intended roles, most frequently on Scholar (78%) and Communicator (71%); least on Manager (47%), and Collaborator (56%). Strengths (78%) were mentioned more frequently than improvement points (52%), which were lacking in 40% of the feedback on Manager, Professional, and Collaborator. Feedback on Scholar was more frequently (p = 0.000) and on Reflective Professional was less frequently (p = 0.003) specific. DISCUSSION AND CONCLUSION: Assigning roles to authentic situations guides supervisors in providing feedback on different CanMEDS roles. We recommend additional supervisor training on how to observe and evaluate the roles.

Causal path analyses of the association of protein intake with risk of mortality and graft failure in renal transplant recipients.

The effect of a low protein intake on survival in renal transplant recipients (RTR) is unknown. A low protein intake may increase risks of malnutrition, low muscle mass, and death. We aimed to study associations of protein intake with mortality and graft failure and to identify potential intermediate factors. Protein intake was estimated from 24-h urinary urea excretion (24-h UUE). Graft failure was defined as return to dialysis or retransplantation. We used Cox regression analyses to analyze associations with outcome and potential intermediate factors in the causal path. In 604 RTR, mean ± SD 24-h UUE was 380 ± 114 mmol/24-h. During median follow-up for 7.0 yr (interquartile range: 6.2-7.5 yr), 133 RTR died and 53 developed graft failure. In univariate analyses, 24-h UUE was associated with lower risk of mortality (HR [95% CI] = 0.80 [0.69-0.94]) and graft failure (HR [95% CI] = 0.72 [0.56-0.92]). These associations were independent of potential confounders. In causal path analyses, the association of 24-h UUE with mortality disappeared after adjustment for muscle mass. Low protein intake is associated with increased risk of mortality and graft failure in RTR. Causal path analyses reveal that the association with mortality is explained by low muscle mass. These findings suggest that protein intake restriction should not be advised to RTR.

Circulating peroxiredoxin 4 and type 2 diabetes risk: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study.

AIMS/HYPOTHESIS: Oxidative stress plays a key role in the development of type 2 diabetes mellitus. We previously showed that the circulating antioxidant peroxiredoxin 4 (Prx4) is associated with cardiometabolic risk factors. We aimed to evaluate the association of Prx4 with type 2 diabetes risk in the general population. METHODS: We analysed data on 7,972 individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (49% men, aged 28-75 years) with no diabetes at baseline. Logistic regression models adjusted for age, sex, smoking, waist circumference, hypertension and family history of diabetes were used to estimate the ORs for type 2 diabetes. RESULTS: During a median follow up of 7.7 years, 496 individuals (288 men; 58%) developed type 2 diabetes. The median (Q1-Q3) Prx4 level was 0.84 (0.53-1.40) U/l in individuals who developed type 2 diabetes and 0.68 (0.43-1.08) U/l in individuals who did not develop type 2 diabetes. For every doubling of Prx4 levels, the adjusted OR (95% CI) for type 2 diabetes was 1.16 (1.05-1.29) in the whole population; by sex, it was 1.31 (1.14-1.50) for men and 1.03 (0.87-1.21) for women. Further adjustment for other clinical measures did not materially change the results. The addition of Prx4 to a validated diabetes risk score significantly improved the prediction of type 2 diabetes in men (p = 0.002 for reclassification improvement). CONCLUSIONS/INTERPRETATION: Our findings suggest that elevated serum Prx4 levels are associated with a higher risk of incident type 2 diabetes. For men, taking Prx4 into consideration can improve type 2 diabetes prediction over a validated diabetes risk score; in contrast, there is no improvement in risk prediction for women.

Continuous intraperitoneal insulin infusion in type 1 diabetes: a 6-year post-trial follow-up.

BACKGROUND: Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a treatment option for patients with type 1 diabetes mellitus (T1DM). Aim of the present study was to describe the long-term course of glycaemic control, complications, health related quality of life (HRQOL) and treatment satisfaction among T1DM patients treated with CIPII. METHODS: Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) therapy in 2006 were followed until 2012. Laboratory, continuous glucose monitoring, HRQOL and treatment satisfaction measurements were performed at the start of the study, the end of the SC-, the end of the CIPII treatment phase in 2006 and during CIPII therapy in 2012. Linear mixed models were used to calculate estimated values and to test differences between the moments in time. RESULTS: In 2012, more time was spent in hyperglycaemia than after the CIPII treatment phase in 2006: 37% (95% CI 29, 44) vs. 55% (95% CI 48, 63), mean difference 19.8% (95% CI 3.0, 36.6). HbA1c was 65 mmol/mol (95% CI 60, 71) at the end of the SC treatment phase in 2006, 58 mmol/mol (95% CI 53, 64) at the end of the CIPII treatment phase and 65 mmol/mol (95% CI 60, 71) in 2012, respectively (p > 0.05). In 2012, the median number of grade 2 hypoglycaemic events per week (1 (95% CI 0, 2)) was still significantly lower than during prior SC therapy (3 (95% CI 2, 4)): mean change -1.8 (95% CI -3.4, -0.4). Treatment satisfaction with CIPII was better than with SC insulin therapy and HRQOL remained stable. Pump or catheter dysfunction of the necessitated re-operation in 7 patients. No mortality was reported. CONCLUSIONS: After 6 years of CIPII treatment, glycaemic regulation is stable and the number of hypoglycaemic events decreased compared to SC insulin therapy. Treatment satisfaction with CIPII is superior to SC insulin therapy, HRQOL is stable and complications are scarce. CIPII is a safe and effective treatment option for selected patients with T1DM, also on longer term.