A systematic review of the prevalence and prognosis of posttransplant diabetes mellitus (PTDM) following the transplantation of heart, lung, liver and kidney and a metaanalysis of randomised studies ...of glucose-lowering treatment is reported.
We searched for publications on solid organ transplants and PTDM in relation to the risk and total mortality of PTDM and randomized controlled trials aiming at reducing glucose levels.
PTDM prevalence one year after transplantation was reported to be 9-40%. Ten years after transplantation, 60-85% of people without PTDM and 30-76% of people with PTDM were alive. Following kidney transplantation, we identified six randomized controlled trials on the treatment of PTDM. Intervention ranged from 3 to 12 months. Four studies used intervention with oral glucose-lowering drugs, one used dietician appointments and exercise, and one used insulin treatment. Among the intermediate results reported, a reduction in HbA1c of 2.7 mmol/mol, and an increase in the odds ratio of serious adverse events of 3.0 was significant.
In conclusion, information on the prevalence and effect on survival of PTDM is heterogeneous, and the randomized studies on the effect of treatment available are short and lack information on clinically important endpoints, such as mortality or morbidity.
Post-transplant diabetes mellitus (PTDM) is associated with a higher risk of adverse outcomes. We aimed to describe the proportion of patients with diabetes prior to solid organ transplantation (SOT) ...and post-transplant diabetes mellitus (PTDM) in three time periods (early-likely PTDM: 0-45 days; 46-365 days and >365 days) post-transplant and to estimate possible risk factors associated with PTDM in each time-period. Additionally, we compared the risk of death and causes of death in patients with diabetes prior to transplant, PTDM, and non-diabetes patients. A total of 959 SOT recipients (heart, lung, liver, and kidney) transplanted at University Hospital of Copenhagen between 2010 and 2015 were included. The highest PTDM incidence was observed at 46-365 days after transplant in all SOT recipients. Age and the Charlson Comorbidity Index (CCI Score) in all time periods were the two most important risk factors for PTDM. Compared to non-diabetes patients, SOT recipients with pre-transplant diabetes and PTDM patients had a higher risk of all-cause mortality death (aHR: 1.77, 95% CI: 1.16-2.69 and aHR: 1.89, 95% CI: 1.17-3.06 respectively). Pre-transplant diabetes and PTDM patients had a higher risk of death due to cardiovascular diseases and cancer, respectively, when compared to non-diabetes patients.
Post-transplant diabetes mellitus (PTDM) is a frequent and relevant complication after renal transplantation: it affects 20-30% of renal transplant recipients and increases the risk for ...cardiovascular and infectious events. Thus, understanding pathogenesis of PTDM would help limiting its consequences. In this review, we analyse novel aspects of PTDM, based on studies of the last decade, such as the clinical evolution of PTDM, early and late, the reversibility rate, diagnostic criteria, risk factors, including pre-transplant metabolic syndrome and insulin resistance (IR) and the interaction between these factors and immunosuppressive medications. Also, we discuss novel pathogenic factors, in particular the role of β-cell function in an environment of IR and common pathways between pre-existing cell damage and tacrolimus-induced toxicity. The relevant role of prediabetes in the pathogenesis of PTDM and cardiovascular disease is also addressed. Finally, current evidence on PTDM treatment is discussed.
Nicotinamide adenine dinucleotide (oxidized form, NAD
) is a critical coenzyme, with functions ranging from redox reactions and energy metabolism in mitochondrial respiration and oxidative ...phosphorylation to being a central player in multiple cellular signaling pathways, organ resilience, health, and longevity. Many of its cellular functions are executed via serving as a co-substrate for sirtuins (SIRTs), poly (ADP-ribose) polymerases (PARPs), and CD38. Kidney damage and diseases are common in the general population, especially in elderly persons and diabetic patients. While NAD
is reduced in acute kidney injury (AKI) and chronic kidney disease (CKD), mounting evidence indicates that NAD
augmentation is beneficial to AKI, although conflicting results exist for cases of CKD. Here, we review recent progress in the field of NAD
, mainly focusing on compromised NAD
levels in AKI and its effect on essential cellular pathways, such as mitochondrial dysfunction, compromised autophagy, and low expression of the aging biomarker αKlotho (Klotho) in the kidney. We also review the compromised NAD
levels in renal fibrosis and senescence cells in the case of CKD. As there is an urgent need for more effective treatments for patients with injured kidneys, further studies on NAD
in relation to AKI/CKD may shed light on novel therapeutics.
Abstract
Background
Non-adherence to medication is a common and complex issue faced by individuals undergoing hemodialysis (HD). However, more knowledge is needed about modifiable factors influence ...on non-adherence. This study investigated the prevalence of non-adherence, medication beliefs and symptom burden and severity among patients receiving HD in Denmark. Associations between non-adherence, medications beliefs and symptom burden and severity were also explored.
Method
A cross-sectional questionnaire-based multisite study, including 385 participants. We involved patient research consultants in the study design process and the following instruments were included: Medication Adherence Report Scale, Beliefs about Medication Questionnaire and Dialysis Symptom Index. Logistic regression analysis was performed.
Results
The prevalence of non-adherence was 32% (95% CI 27–37%) using a 23-point-cut-off. Just over one third reported being concerned about medication One third also believed physicians to overprescribe medication, which was associated with 18% increased odds of non-adherence. Symptom burden and severity were high, with the most common symptoms being tiredness/ lack of energy, itching, dry mouth, trouble sleeping and difficulties concentrating. A high symptom burden and/or symptom severity score was associated with an increased odd of non-adherence.
Conclusion
The study found significant associations between non-adherence and, beliefs about overuse, symptom burden and symptom severity. Our results suggest health care professionals (HCP) should prioritize discussion about medication adherence with patients with focus on addressing patient-HCP relationship, and patients’ symptom experience. Future research is recommended to explore the effects of systematically using validated adherence measures in clinical practice on medication adherence, patient-HCP communication and trust. Additionally, studies are warranted to further investigate the relationship between symptom experience and adherence in this population.
Trial registration
NCT03897231.
Cardiovascular mortality and the impact of cardiac risk factors in advanced chronic kidney disease (CKD) remain poorly investigated. We examined the risk of cardiovascular mortality in patients with ...advanced CKD with and without diabetes as well as the impact of albuminuria, plasma hemoglobin, and plasma low-density lipoprotein (LDL) cholesterol levels.
In a Danish nationwide registry-based cohort study, we identified persons aged ≥ 18 years with an estimated glomerular filtration rate < 30 mL/min/1.73m
between 2002 and 2018. Patients with advanced CKD were age- and sex-matched with four individuals from the general Danish population. Cause-specific Cox regression models were used to estimate the 1-year risk of cardiovascular mortality standardized to the distribution of risk factors in the cohort.
We included 138,583 patients with advanced CKD of whom 32,698 had diabetes. The standardized 1-year risk of cardiovascular mortality was 9.8% (95% CI 9.6-10.0) and 7.4% (95% CI 7.3-7.5) for patients with and without diabetes, respectively, versus 3.1% (95% CI 3.1-3.1) in the matched cohort. 1-year cardiovascular mortality risks were 1.1- to 2.8-fold higher for patients with diabetes compared with those without diabetes across the range of advanced CKD stages and age groups. Albuminuria and anemia were associated with increased cardiovascular mortality risk regardless of diabetes status. LDL-cholesterol was inversely associated with cardiovascular mortality risk in patients without diabetes, while there was no clear association in patients with diabetes.
Diabetes, albuminuria, and anemia remained important risk factors of cardiovascular mortality whereas our data suggest a limitation of LDL-cholesterol as a predictor of cardiovascular mortality in advanced CKD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IntroductionPatients receiving haemodialysis are at increased risk of arrhythmias and sudden cardiac death, but data on arrhythmia burden and the pathophysiology remain limited. Among potential risk ...factors, hypoglycaemia is proposed as a possible trigger of lethal arrhythmias. The development of implantable loop recorders (ILR) and continuous glucose monitoring (CGM) enables long-term continuous ECG and glycaemic monitoring. The current article presents the protocol of a study aiming to increase the understanding of arrhythmias and risk factors in patients receiving haemodialysis. The findings will provide a detailed exploration of the burden and nature of arrhythmias in these patients including the potential association between hypoglycaemia and arrhythmias.Methods and analysisThe study is an investigator-initiated, prospective, multicentre cohort study recruiting 70 patients receiving haemodialysis: 35 with diabetes and 35 without diabetes. Participants are monitored with ILRs and CGM for 18 months follow-up. Data collection further includes a monthly collection of predialysis blood samples and dialysis parameters. The primary outcome is the presence of clinically significant arrhythmias defined as a composite of bradycardia, ventricular tachycardia, or ventricular fibrillation. Secondary outcomes include the characterisation of clinically significant arrhythmias and other arrhythmias, glycaemic characteristics, and mortality. The data analyses include an assessment of the association between arrhythmias and hypoglycaemia and hyperglycaemia, baseline clinical variables, and parameters related to kidney failure and the haemodialysis procedure.Ethics and disseminationThe study has been approved by the Ethics Committee of the Capital Region of Denmark (H-20069767). The findings will be presented at national and international congresses as well as in international peer-reviewed scientific journals.Trial registration numberNCT04841304.
Medication nonadherence is common among patients with hemodialysis, leading to poorer patient outcomes. Health care professionals have an important role in assessing risk of nonadherence and ...intervening to support adherence. The aim of this study was to explore physicians' and nurses' current medication adherence practices in hemodialysis settings.
A generic qualitative design with inductive content analysis and focus group methodology. Focus groups with health care professionals were conducted in four Nephrology Centers, representing three different regions of Denmark. An interview guide was developed in collaboration with 3 patient representatives.
Six focus group interviews involving a total of forty-two health care professionals were conducted. Five main categories were identified; Laboratory tests are the "gold standard" for assessing adherence, suggesting that abnormal results motivated investigation of adherence, Varying practices for supporting adherence, alluding to the impact of individual clinician priority and preference on choice of adherence interventions, Unclear allocation of roles and responsibility, specifically referring to uncertainty in the delegation of roles between physicians and nurses, Navigating time and resource limitations, intimating the resources needed to support medication adherence and Suggestions for future strategies.
We suggest implementing systematic use of validated patient-reported outcome measures for assessing adherence and deprescribing tools to support adherence, as these instruments might identify the patients who are in most need of support and promote patient adherence to their prescribed medications. The findings also point to a need for interdisciplinary clarification of roles and responsibilities regarding medication adherence, with the aim of building a strong collaborative partnership between professions.
Hyperreflective dots are a common but highly variable feature of optical coherence tomography (OCT) scans of the retina. We studied the spatial characteristics and perfusion of hyperreflective dots ...using both structural and angiographic OCT B-scans of the macula in 16 eyes in 8 healthy subjects and 8 patients with diabetic retinopathy without macular edema. Hyperreflective dots were manually graded in a 1000 µm parafoveal area by number, diameter, location and perfusion status and traced through adjacent B-scans at 11 µm intervals to determine their length. Thereby, this study defined a procedure to identify granular and elongated hyperreflective elements and differentiate between presumably perfused and occluded capillaries. The latter were only found in the diabetic patients. This classification can potentially be automated to non-invasively identify capillary non-perfusion in vivo.
Exogenous Glucagon-Like Peptide-2 (GLP-2) treatment improves intestinal wet weight absorption in short bowel syndrome (SBS) patients. In healthy subjects, administration of GLP-2 increases small ...intestinal blood flow. The aim of the study was to evaluate the effect of GLP-2 on mesenteric blood flow and dynamic changes in cardiac parameters in SBS patients with jejunostomy and varying length of remnant small intestine.
8 SBS patients with end-jejunostomy and less than 200
cm small intestine were given GLP-2, 1600
μg subcutaneously (SC), or isotonic saline in a double blinded manner. At 0, 30 and 60
min plasma GLP-2 was measured, and from 0 to 90
min, blood flow in the superior mesenteric artery (SMA) and the celiac artery (CA) was measured using Doppler ultrasound (US), and cardiovascular variables were measured by continuous impedance cardiography and finger plethysmography.
Plasma GLP-2 concentrations increased significantly in the GLP-2 group, whereas no changes were seen in the placebo group. Compared to baseline, GLP-2 SC elicited a 19.4% decrease (p
<
0.01) in the resistance index (RI) and a 97.6% increase in time averaged maximal velocity (TAMV) in the SMA (P
<
0.01). In the CA there were no significant changes in RI or TAMV in the GLP-2 or placebo group. Blood flow and length of remaining intestine were correlated (RI: y
=
0.14
+
4.3, R
=
0.83, p
=
0.01 and TAMV: y
=
1.21
+
21.3, R
=
0.63, p
=
0.09).
GLP-2 non significantly increased cardiac output (CO), stroke volume (SV) and significantly increased heart rate (HR) compared to baseline.
Subcutaneous GLP-2 increased SMA blood flow in end-jejunostomy SBS patients with less than 200
cm of remaining small intestine. The increase in blood flow correlated with the length of remaining intestine, suggesting that the increase is coupled to the metabolic actions of GLP-2 on the gut rather than effects on the vasculature.
► Exogenous GLP-2 administration increases mesenteric blood flow in SBS patients. ► Increase in blood flow seems to correlate to the length of remaining small intestine. ► The findings suggest that the increase is coupled to the metabolic actions of GLP-2.
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