Metabolism open最新文献

Aim

To assess the effects of once-weekly subcutaneous retatrutide on weight and metabolic markers and the occurrence of side effects in patients with overweight, obesity and/or type 2 diabetes (T2D).

Methods

PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were systematically searched for placebo-controlled, randomized clinical trials (RCTs) published up until February 23, 2024. Weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) for binary endpoints were computed, with 95 % confidence intervals (CIs).

Results

A total of three studies were included, comprising 640 patients, of whom 510 were prescribed retatrutide. Compared with placebo, retatrutide significantly reduced body weight (WMD -10.66 kg; 95 % CI -17.63, −3.69), body mass index (WMD -4.53 kg/m²; 95 % CI -7.51, −1.55), and waist circumference (WMD -6.61 cm; 95 % CI -13.17, −0.05). In addition, retatrutide significantly increased the proportion of patients who achieved a weight reduction of ≥5 % (RR 2.92; 95 % CI 2.17–3.93), ≥10 % (RR 9.32; 95 % CI 4.56–19.06), ≥15 % (RR 18.40; 95 % CI 6.00–56.42), and ≥20 % (RR 16.61; 95 % CI 4.17–66.12).

Conclusions

In this meta-analysis, the use of once-weekly subcutaneous retatrutide was associated with a significant reduction in body weight and improvement of metabolic markers in patients with overweight, obesity and/or T2D, compared with placebo, with an increase in non-severe gastrointestinal and hypersensitivity adverse events. Phase 3 RCTs are expected to shed further light on the efficacy and safety of once-weekly subcutaneous retatrutide over the long term.

Aim/introduction

Early therapeutic interventions are necessary to reduce cardiovascular and renal composite endpoints in individuals with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Clinical trials have shown that finerenone suppresses cardiovascular and renal composite endpoints by reducing the urinary albumin-to-creatinine ratio (UACR) and suppressing the decline in the Estimated Glomerular Filtration Rate (eGFR). However, the efficacy and safety of finerenone in real-world clinical practice remain unclear. This study aimed to evaluate the reduction in the UACR as an efficacy endpoint as well as changes in eGFR and serum potassium levels as safety endpoints before and after finerenone administration.

Materials and methods

This retrospective observational study collected data from outpatients with T2DM and DKD upon initiation of finerenone treatment and 3 months after treatment. The primary efficacy endpoint was the change in the UACR from the start of finerenone treatment to after 3 months, while the primary safety endpoints were the changes in serum potassium levels and eGFR over the same period.

Results

The mean UACR significantly decreased from 668.6 mg/gCr at the start of finerenone treatment to 367.8 mg/gCr after 3 months (p < 0.001). Contrastingly, serum potassium levels, eGFRs, systolic and diastolic blood pressures, body mass indices, and HbA1c levels showed no significant changes between treatment initiation and 3 months post-treatment (all p > 0.05).

Conclusions

In individuals with T2DM and DKD, finerenone treatment significantly reduced the UACR, with no post-treatment changes in potassium levels or eGFRs.

Trial registration

This trial was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN000054821).

Background

Diabetes mellitus is becoming major health challenge with continually increasing burden. High costs of conventional medicines and numerous side effects associated with them, on the other hand, easy availability and accessibility of traditional herbal medicines calls upon experimental investigations to validate their effect on lowering blood glucose level.

Methods

The dried fruit of Rosa abyssinica was macerated with 70 % ethanol and the extract's in vitro antidiabetic activity was investigated using dinitrosalisylic acid method for alpha amylase inhibitory activity. Furthermore, the in vivo hypoglycemic and Antihyperglycemic effects of various doses of the extract (100, 200 and 400 mg/kg) was determined on normoglycemic, glucose loaded (1500 mg/kg) and Streptozotocine (180 mg/kg)-induced diabetic mice models.

Results

The acute oral toxicity study revealed the plant showed no toxic effect on swiss albino mice at 2000 mg/kg. The in vitro alpha amylase inhibitory activity study showed that the extract has comparable IC50 value of 21.37 ± 4.252 μg/ml with the standard drug acarbose (IC50 value of 26.72 ± 3.59 μg/ml). On the other hand, in normal mice, none of the dose levels except at 400 mg/kg significantly reduces blood glucose level. This is in contrast to the oral glucose tolerance test, which the extract produced significant reduction at 60, 90 and 120 min following glucose challenge. The 70 % ethanolic fruit extracts of Rosa abyssinica also experienced profound antidiabetic activity in streptozotocin-induced diabetic model. In the single-dose study, both RAFE200 and RAFE400 demonstrated a significant (P˂0.05) reduction in blood glucose levels at 1, 2, 3, and 4 h. Similarly, in the repeated-dose study, RAFE200 and RAFE400 not only significantly reduced blood glucose levels but also produced a notable improvement in animal body weight.

Conclusion

The 70 % ethanolic fruit extracts of Rosa abyssinica have shown significant in vitro alpha amylase inhibition effect and an in vivo blood glucose level lowering effects in diabetic mice.

Therefore, this study supports the traditional use of Rosa abyssinica in the management of diabetes mellitus.

Obesity management can effectively reduce the risks and complications associated with obesity and improve the quality of life of patients. After assessing the advantages and limitations of various obesity management approaches, self-management has been strongly recommended due to the advantages of minimal side effects and lower costs compared to treatment via drugs and surgery. However, successfully implementing lifestyle intervention strategies requires scientific guidance and strong determination. With the development of electronic and information technology, lifestyle intervention has transformed considerably. A new concept, called Gamified Digital Therapeutics (GDTx), represents a gaming format with Digital Therapeutics (DTx). It can effectively enhance patient compliance and accessibility to chronic disease management. Here, we review recent studies on the application of GDTx for the self-management of obesity and discuss three aspects surrounding its completion rates, satisfaction levels, and effectiveness. In contrast to traditional approaches to obesity self-management, implementing GDTx effectively corrects unhealthy dietary and lifestyle habits, markedly enhancing the dissemination of nutritional and exercise-related health knowledge. Of particular significance is the evident improvement in the adherence of obese patients to weight loss programs. Despite numerous studies indicating that GDTx may offer an effective solution for obesity self-management, there are still several limitations in the medicalization of GDTx for self-management of obesity. This review aimed to provide a reference for subsequent studies and promote the widespread application of GDTx in obesity self-management to help reduce the obesity rate and alleviate the burden on obese patients.

Background

Diabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The ‘Gold standard’ for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease.

Methods

Thirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD).

Results

Fifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p < 0.001), who had also significantly less interstitial fibrosis (p = 0.02). Finally, the presence of DR, higher levels of interstitial fibrosis and longer T2DM duration were recognized as factors, which were positively associated with DKD.

Conclusion

This study advocates the usefulness of kidney biopsy in patients with T2DM and nephrotic range levels of proteinuria, especially when DR is absent and shorter disease duration is observed.

Introduction

Approximately 25 % of diabetic patients develop diabetic foot ulcers (DFUs), significantly increasing morbidity, mortality, and healthcare costs. Effective control and prevention are crucial.

Objective

This study aims to identify easily measurable parameters for predicting DFU risk by assessing the correlation between Phase Angle (PA) and the Triglyceride-Glucose (TyG) index with DFU risk.

Materials and methods

A comparative case-control study was conducted at the General Hospital of Elche from March to June 2023 with 70 participants (33 with diabetes, 37 without). Cases had diabetes for over five years and a diabetic foot risk grade of 0, 1, or 2 (IWGDF 2019). Exclusion criteria included inability to walk, prior use of orthoses, and severe complications like edema or wounds. Predictive variables were PA, TyG index, body composition, and biochemical markers. Statistical analyses included Pearson/Spearman tests for correlations, Student's t-test/Mann-Whitney test for group comparisons, and ANOVA/Kruskal-Wallis tests for normally and non-normally distributed variables.

Results

PAand TyG index were strongly linked to diabetic foot risk, supporting their potential as biomarkers. Significant relationships with other relevant biomarkers were also confirmed.

Conclusion

PA and TyG index are valuable, easily measurable biomarkers for assessing diabetic foot risk, and can be monitored in primary care settings. Implementing these biomarkers in routine practice could enhance the management of diabetic complications, particularly in resource-limited settings, by enabling early detection and intervention, thus improving patient outcomes and reducing the burden of advanced complications.

The worldwide surge in obesity and associated metabolic disorders is emerging as a significant public health issue for societies and healthcare systems. Available evidence has shown that alterations in the gut microbiota could be implicated in the pathogenesis of obesity and associated disorders. A healthy gut microbiome is characterized by richness and high microbial diversity. Gut microbiota affect how the host responds to diet, and conversely, the host may modify the gut microbiota through changes in dietary habits. Diet can impact and alter the composition, diversity, and species richness of the gut microbiota over time. An unhealthy diet, high in fat and sugar, may lead to decreased microbial diversity, reduced synthesis of metabolites that maintain gut permeability, damage to the mucus layer, increased bacterial translocation and lipopolyssacharide which can trigger endotoxemia, chronic subclinical inflammation and metabolic disorders. Currently, the impact of diet on gut microbial composition and its involvement in the pathogenic mechanisms underlying metabolic disorders is one of the most promising areas of research in nutrition. This special issue has gathered original research articles in topics related to diet patterns, gut microbiota, obesity and associated metabolic disorders as well as brief reports, reviews and perspectives in the wider field of translational and clinical metabolic research. In particular, the aim of this Special Issue was to present evidence connecting gut microbiota with metabolic disorders, explore the underlying mechanisms of this association, and examine how diet patterns may influence this relationship.

Diabetic Nephropathy (DN) has become the leading cause of end-stage renal disease worldwide. Studies have indicated that Transforming Growth Factor beta1 (TGFβ1) is the most potent factor contributing to renal fibrosis, and understanding the exact pathogenic mechanism of renal fibrosis is crucial for alleviating the condition. Previous research has identified Yin Yang 1 (YY1) as an effective inhibitor of TGF-β1. Our study, through dual-luciferase reporter gene assays and Western blot experiments, screened and obtained the small molecule compound PdⅡ. Subsequently, validation in a high-glucose-induced renal mesangial cell injury model showed that PdⅡ treatment significantly increased the expression of YY1 protein and mRNA, while correspondingly reducing the expression of TGFβ1 protein and mRNA. Dual-luciferase reporter gene assay results revealed that, compared to the control group, the luciferase transcription activity of YY1 molecules increased in the PdⅡ treatment group, and the luciferase transcription activity of TGFβ1 decreased. By further designing mutations in the binding sites between TGFβ1 and YY1 on the promoter, transfecting fluorescent enzyme reporter gene plasmids with TGFβ1 mutant promoter into mesangial cells damaged by high glucose, and then treating the cells with PdⅡ, it was observed that the luciferase transcription activity of TGFβ1 did not decrease. Therefore, these results suggest that PdⅡ may inhibit TGFβ1 transcriptional activity by activating YY1, thereby slowing down the progression of diabetic nephropathy.