Background and Aims
Trimethylamine‐N‐oxide (TMAO), a gut microbiota‐liver metabolite, has been associated with cardiometabolic disease. However, whether TMAO is associated with nonalcoholic fatty ...liver disease (NAFLD) and NAFLD‐related health outcomes remains unclear. We aimed to investigate the association of TMAO with NAFLD and to assess the extent to which the association of TMAO with all‐cause mortality is dependent on the presence of NAFLD in the general population.
Methods
We included 5292 participants enrolled in the Prevention of Renal and Vascular End‐stage Disease (PREVEND) cohort study. Cox proportional‐hazards regression analyses were performed to study the association of TMAO with all‐cause mortality in subjects with and without a fatty liver index (FLI) ≥60, which was used as a proxy of NAFLD.
Results
During a median follow‐up of 8.2 years, 307 subjects died, of whom 133 were classified with NAFLD. TMAO was positively and independently associated with baseline FLI (Std β 0.08, 95% CI 0.05, 0.11, P < .001). Higher TMAO was associated with increased risk of all‐cause mortality in subjects with NAFLD, in crude analysis (hazard ratio HR per 1 SD, 2.55, 95% CI 1.60, 4.05, P < .001) and after full adjustment (adjHR 1.90, 95% CI 1.18, 3.04, P = .008). Such an association was not present in subjects without NAFLD (crude HR 1.14, 95% CI 0.81, 1.71, P = .39; adjHR 0.95, 95% CI 0.65, 1.39, P = .78).
Conclusion
This prospective study revealed that plasma concentrations of TMAO were associated with all‐cause mortality in subjects with NAFLD, independently of traditional risk factors.
Recently published Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend limiting the use of immunosuppressive drugs in idiopathic membranous nephropathy to patients at the highest ...risk of kidney failure. However, recommendations are based on natural history rather than direct assessment of a restrictive treatment strategy. Here, we describe the long-term outcomes of treating a large cohort of patients with idiopathic membranous nephropathy according to a restrictive treatment policy. We analyzed data for 254 patients who visited our outpatient clinic between 1995 and 2009. All patients were treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Immunosuppressive therapy was recommended in cases of deteriorating renal function or untreatable nephrotic syndrome. Primary outcomes for the present study were renal replacement therapy and death. Secondary outcomes included adverse events during follow-up and remission of proteinuria. In total, 124 patients (49%) received immunosuppressive therapy, which predominantly consisted of cyclophosphamide combined with steroids. Ten-year cumulative incidence rates were 3% for renal replacement therapy and 10% for death. Partial remission rates were 39%, 70%, and 83% after 1, 3, and 5 years, respectively; complete remission rates were 5%, 24%, and 38% at 1, 3, and 5 years, respectively. A serious adverse event occurred in 23% of all patients. The most notable complications were infections (17%), leukopenia (18%), cardiovascular events (13%), and malignancies (8%). In conclusion, the use of a restrictive treatment strategy in this cohort of patients with idiopathic membranous nephropathy yielded favorable outcomes while limiting the number of patients exposed to toxic drugs. These results support current KDIGO guidelines.
Background and aims
Individuals with type 2 diabetes (T2D) have a higher risk of cardiovascular disease, compared with those without T2D. The serum T50 test captures the transformation time of ...calciprotein particles in serum. We aimed to assess whether serum T50 predicts cardiovascular mortality in T2D patients, independent of traditional risk factors.
Methods
We analyzed 621 individuals with T2D in this prospective cohort study. Cox regression models were performed to test the association between serum T50 and cardiovascular and all‐cause mortality. Causes of death were categorized according to ICD‐10 codes. Risk prediction improvement was assessed by comparing Harrell's C for models without and with T50.
Results
The mean age was 64.2 ± 9.8 years, and 61% were male. The average serum T50 time was 323 ± 63 min. Higher age, alcohol use, high‐sensitive C‐reactive protein, and plasma phosphate were associated with lower serum T50 levels. Higher plasma triglycerides, venous bicarbonate, sodium, magnesium, and alanine aminotransferase were associated with higher serum T50 levels. After a follow‐up of 7.55.4–10.7 years, each 60 min decrease in serum T50 was associated with an increased risk of cardiovascular (fully adjusted HR 1.32, 95% CI 1.08–1.50, and p = 0.01) and all‐cause mortality (HR 1.15, 95%CI 1.00–1.38, and p = 0.04). Results were consistent in sensitivity analyses after exclusion of individuals with estimated glomerular filtration rate <45 or <60 mL/min/1.73 m2 and higher plasma phosphate levels.
Conclusions
Serum T50 improves prediction of cardiovascular and all‐cause mortality risk in individuals with T2D. Serum T50 may be useful for risk stratification and to guide therapeutic strategies aiming to reduce cardiovascular mortality in T2D.
Although gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H
2
S) receive a bad connotation; in low concentrations these play a major governing role in local and systemic ...blood flow, stomach acid release, smooth muscles relaxations, anti-inflammatory behavior, protective effect and more. Many of these physiological processes are upstream regulated by gut peptides, for instance gastrin, cholecystokinin, secretin, motilin, ghrelin, glucagon-like peptide 1 and 2. The relationship between gasotransmitters and gut hormones is poorly understood. In this review, we discuss the role of NO, CO and H
2
S on gut peptide release and functioning, and whether manipulation by gasotransmitter substrates or specific blockers leads to physiological alterations.
Purpose
GlycA, a pro-inflammatory glycoprotein biomarker, associates with newly developed type 2 diabetes (T2D). We determined the association of plasma GlycA with the development of microvascular ...complications in patients with established T2D.
Methods
Plasma GlycA was measured by nuclear magnetic resonance spectrometry in T2D patients without microvascular complications at baseline (
n
= 145) participating in a longitudinal cohort study of primary care-treated T2D patients (Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study). Associations of GlycA with incident microvascular complications including nephropathy, retinopathy, and neuropathy, were determined by Cox proportional hazards regression analyses.
Results
After a median follow-up of 3.2 (interquartile range IQR: 2.9–3.4) years, 49 patients (33.8%) developed one or more microvascular complications. Median GlycA levels were 453.5 (IQR: 402.0–512.8) μmol/l. GlycA was associated with incident microvascular complications (hazard ratio HR per 1-SD increment: 1.28 95% confidence interval CI:1.00–1.63,
P
= 0.048), even after adjustment for potential confounders and high-sensitive C-reactive protein (hs-CRP), HR 1.79 95%CI:1.25–2.57,
P
= 0.001). In contrast, hs-CRP levels were not significantly associated with the risk of developing microvascular complications (
P
= 0.792).
Conclusion
Higher plasma GlycA is associated with an increased risk of developing microvascular complications in T2D patients. Altered
N
-glycan branching associated with acute-phase reactive proteins may represent a preferred biomarker of systemic low-grade inflammation in predicting diabetic complications.
Gliclazide has been associated with a low risk of hypoglycemic episodes and beneficial long-term cardiovascular safety in observational cohorts. The aim of this study was to assess in a systematic ...review and meta-analysis of randomized controlled trials the safety and efficacy of gliclazide compared to other oral glucose-lowering agents (PROSPERO2013:CRD42013004156).
Medline, EMBASE, Clinicaltrials.gov, Trialregister.nl, Clinicaltrialsregister.eu and the Cochrane database.
Included were randomized studies of at least 12 weeks duration with the following outcomes: HbA1c change, incidence of severe hypoglycemia, weight change, cardiovascular events and/or mortality when comparing gliclazide with other oral blood glucose lowering drugs. Bias was assessed with the Cochrane risk of bias tool. The inverse variance random effects model was used.
Nineteen trials were included; 3,083 patients treated with gliclazide and 3,155 patients treated with other oral blood glucose lowering drugs. There was a considerable amount of heterogeneity between and bias in studies. Compared to other glucose lowering agents except metformin, gliclazide was slightly more effective (-0.13% (95%CI: -0.25, -0.02, I(2) 55%)). One out of 2,387 gliclazide users experienced a severe hypoglycemic event, whilst also using insulin. There were 25 confirmed non-severe hypoglycemic events (2.2%) in 1,152 gliclazide users and 22 events (1.8%) in 1,163 patients in the comparator group (risk ratio 1.09 (95% CI: 0.20, 5.78, I² 77%)). Few studies reported differences in weight and none were designed to evaluate cardiovascular outcomes.
The methodological quality of randomized trials comparing gliclazide to other oral glucose lowering agents was poor and effect estimates on weight were limited by publication bias. The number of severe hypoglycemic episodes was extremely low, and gliclazide appears at least equally effective compared to other glucose lowering agents. None of the trials were designed for evaluating cardiovascular outcomes, which warrants attention in future randomized trials.
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.
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.
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).
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.
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