This interventional single-center prospective open-label study aims to evaluate the effects of a vegan diet, compared to a vegetarian and omnivorous diet, on metabolic parameters, insulin sensitivity, and liver and kidney steatosis in healthy adults. The study included 53 omnivorous participants aged 18-40 years, body-mass index 18-30 kg/m2, without any chronic disease, chronic medication use, active smoking, or significant alcohol consumption. All participants were omnivorous at baseline and selected to continue an omnivorous diet or transition to a vegetarian or vegan diet, with follow-up over six months.
View Article and Find Full Text PDFMitochondria are essential for cellular energy production and are implicated in numerous diseases, including diabetic kidney disease (DKD). Current evidence indicates that mitochondrial dysfunction results in alterations in several metabolic pathways within kidney cells, thereby contributing to the progression of DKD. Furthermore, mitochondrial dysfunction can engender an inflammatory milieu, leading to the activation and recruitment of immune cells to the kidney tissue, potentially perturbing intrarenal metabolism.
View Article and Find Full Text PDFSexual dimorphism plays an important role in the pathogenesis and progression of CKD. Men with CKD often exhibit faster kidney function decline, leading to higher rates of kidney failure and mortality compared with women. Studies suggest that sex hormones may influence this apparent dimorphism, although the mechanisms underlying these influences remain poorly understood.
View Article and Find Full Text PDFAims/hypothesis: Our aim was to assess sex differences in the efficacy of angiotensin receptor blockers (i.e. losartan and irbesartan) on kidney and cardiovascular outcomes in individuals with type 2 diabetes and diabetic kidney disease.
View Article and Find Full Text PDFImidazole Propionate (ImP), a gut-derived metabolite from histidine, affects insulin signaling in mice and is elevated in type 2 diabetes (T2D). However, the source of histidine and the role of the gut microbiota remain unclear. We conducted an intervention study in mice and humans, comparing ImP kinetics in mice on a high-fat diet with varying histidine levels and antibiotics, and assessed ImP levels in healthy and T2D subjects with histidine supplementation.
View Article and Find Full Text PDFBACKGROUNDIn type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism.METHODSYoung adults with T1D (n = 30) and healthy controls (HCs) (n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA-Seq, and spatial metabolomics to assess this relationship.RESULTSParticipants with T1D had significantly higher glomerular basement membrane (GBM) thickness compared with HCs.
View Article and Find Full Text PDFKey Points: Proteomics analyses identified seven proteins predictive of time to development of albuminuria among youth with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth cohort, 118 proteins predictive of time to development of hyperfiltration, and three proteins predictive of time to rapid eGFR decline. Seven proteins were predictive of all three outcomes (SEM4A, PSB3, dihydroxyphenylalanine decarboxylase, C1RL1, T132A, pyruvate carboxylase, and C1-esterase inhibitor) and have been implicated in immune regulatory mechanisms, metabolic dysregulation, proteostasis, and cellular signaling pathways. Elastic net Cox proportional hazards model identified distinct multiprotein signatures (38–68 proteins) of time to albuminuria, hyperfiltration, and rapid eGFR decline with concordance for models with clinical covariates and selected proteins between 0.
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July 2024
Background: Older patients with type 2 diabetes mellitus (T2D) have an increased risk of hypoglycaemic episodes when using sulphonylureas or insulin. In the Netherlands, guidelines exist for reducing glucose-lowering medication in older patients. However, evidence is lacking that a medication reduction in older patients can be safely pursued.
View Article and Find Full Text PDFBackground: People with type 2 diabetes mellitus treated with sodium-glucose transporter-2 inhibitors (SGLT2i) have lower rates of acute kidney injury (AKI). Sepsis is responsible for the majority of AKI in critically ill patients. This study investigated whether SGLT2i is renoprotective in an ovine model of Gram-negative septic AKI.
View Article and Find Full Text PDFObjectives: The objectives of the current research were to evaluate the accuracy and reliability of continuous glucose monitoring (CGM) in patients undergoing cardiac surgery and assess the impact of preoperative liraglutide administration on perioperative glucose control as captured by CGM.
Design: This was a prospective, single-center, prespecified analysis of the GLOBE trial, a randomized controlled trial comparing preoperative liraglutide treatment to placebo in patients undergoing cardiac surgery.
Setting: The work took place at a single-center academic hospital in the Netherlands.
Aims/hypothesis: The aim of this work was to investigate the association between macronutrient intakes and continuous glucose monitoring (CGM) metrics in individuals with type 1 diabetes.
Methods: In 470 individuals with type 1 diabetes of the GUTDM1 cohort (65% female, median age 40 [IQR 28-53] years, median diabetes duration 15 [IQR 6-29] years), we used logistic regression to establish associations between macronutrient intakes and the CGM metrics time in range (TIR, time spent between 3.9-10.
Context/objective: In order to better understand which metabolic differences are related to insulin resistance in metabolic syndrome (MetSyn), we used hyperinsulinemic-euglycemic (HE) clamps in individuals with MetSyn and related peripheral insulin resistance to circulating biomarkers.
Design/methods: In this cross-sectional study, HE-clamps were performed in treatment-naive men (n = 97) with MetSyn. Subjects were defined as insulin-resistant based on the rate of disappearance (Rd).
Aims/hypothesis: Use of genetic risk scores (GRS) may help to distinguish between type 1 diabetes and type 2 diabetes, but less is known about whether GRS are associated with disease severity or progression after diagnosis. Therefore, we tested whether GRS are associated with residual beta cell function and glycaemic control in individuals with type 1 diabetes.
Methods: Immunochip arrays and TOPMed were used to genotype a cross-sectional cohort (n=479, age 41.
When sodium-glucose cotransporter-2 (SGLT2) inhibitors were primarily prescribed for treatment of diabetes mellitus, guidelines recommended withholding SGLT2 inhibitors before surgery to mitigate the associated risk of ketoacidosis. However, currently, SGLT2 inhibitors are an established therapy for patients with heart failure, and there is evidence that withholding SGLT2 inhibitors can worsen these patients' cardiovascular risk profile. We present an updated risk-benefit analysis of withholding SGLT2 inhibitors before surgery, focusing on patients with heart failure and addressing the risk of ketoacidosis and its treatment in these patients.
View Article and Find Full Text PDFAims/hypothesis: The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes and assessed which clinical features are most important in predicting MASLD severity.
Methods: A total of 453 individuals with type 1 diabetes (41.
Rationale & Objective: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden.
Study Design: Cross-sectional study.
Setting & Participants: Twenty adults with ADPKD (age, 31±6 years; 65% women; body mass index [BMI], 26.
Diabetic kidney disease (DKD), defined as co-existing diabetes and chronic kidney disease in the absence of other clear causes of kidney injury, occurs in approximately 20-40% of patients with diabetes mellitus. As the global prevalence of diabetes has increased, DKD has become highly prevalent and a leading cause of kidney failure, accelerated cardiovascular disease, premature mortality and global health care expenditure. Multiple pathophysiological mechanisms contribute to DKD, and single lifestyle or pharmacological interventions have shown limited efficacy at preserving kidney function.
View Article and Find Full Text PDFObjectives: Glycoprotein acetyls (GlycA's) are biomarkers of systemic inflammation and cardiovascular disease, yet little is known about their role in type 1 diabetes (T1D). In this study we examined the associations among GlycA's, central adiposity, insulin resistance, and early kidney injury in youth with T1D.
Methods: Glomerular filtration rate and renal plasma flow by iohexol and p-aminohippurate clearance, urine albumin-to-creatinine ratio (UACR), central adiposity by dual-energy x-ray absorptiometry, and estimated insulin sensitivity were assessed in 50 youth with T1D (16±3.