Metabolism open最新文献

Background

Insulin icodec is a novel, long-acting, once-weekly basal insulin analog. Its comparative efficacy and safety with basal once-daily insulins in type 2 diabetes mellittus is uncertain.

Objective

Evaluate potential efficacy, benefits and risks associated with icodec compared to once-daily basal insulin analogs (degludec or glargine).

Methods

We systematically searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) published until June 2023 comparing icodec versus long-acting insulin analogs (degludec and glargine) in type 2 diabetes mellitus (T2DM) with at least 12 weeks of follow-up. Binary endpoints were assessed with risk ratios (RRs) and continuous endpoints were compared using mean differences (MDs), with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023452468).

Results

A total of seven RCTs and 3286 patients with T2DM were included, of whom 1509 (60.6%) received icodec treatment. The follow-up period ranged from 16 to 78 weeks. Compared with once-daily basal insulin analogs, icodec led to a greater improvement in HbA1c (MD -0.15%; 95% CI -0.21, −0.10; p < 0.0001; I² = 0%) and time in range (TIR) (MD 2.83%; 95%CI 0.94; 4.71; p = 0.003; I² = 22%). Body weight was increased with icodec treatment (MD 0.78 Kg; 95%CI 0.42, 1.15; p < 0.01; I² = 86%). There was also a higher rate of injection site reactions (RR 1.89; 95%CI 1.12, 3.18; p = 0.016; I² = 0%) and nasopharyngitis (RR 1.94; 95%CI 1.11, 3.38; p = 0.020; I² = 0%) in the icodec group, compared with once-daily regimens. There was no significant difference between groups in fasting plasma glucose.

Conclusions

In this meta-analysis of RCTs, insulin icodec led to better control of HbA1c and TIR as compared with once-daily insulin regimens, albeit with increased weight gain and a higher rate of injection site reaction in the Icodec group.

Background

The leaves of Dovyalis Abyssinica have been used traditionally for the management of diabetes mellitus. Thus, this study aimed to evaluate the Antioxidant and Antihyperglycemic Effects of Dovyalis Abyssinica leaves crude extract in streptozotocin-induced diabetic mice.

Methods

To Evaluate the Antihyperglycemic, and Antioxidant Effects of Dovyalis Abyssinica Leaves Extract in Streptozotocin-Induced Diabetic Mice. Male Swiss albino mice were induced into diabetes using 100 mg/kg of streptozotocin. Mice were allocated randomly into six groups, six mice per group. The body weight and FBG measurements were done on days 0, 7th, 14th and 21st of treatment. Additionally, in vitro Antioxidant Activity of the Extract was determined using a DPPH assay. The data were entered into Epi-Data version 4.6, exported to SPSS version 26.0, and analysed by using a one-way ANOVA followed by a Tukey post hoc test, and P < 0.05 was considered statistically significant.

Results

Dovyalis Abyssinica leaves crude extract showed significant (P < 0.05-P< 0.001) blood-glucose-lowering activity. Moreover, the crude extract of D. abyssinica reduced the fasting blood glucose level by 45.13 %, 52.51 %, 54.85 %, and 56.38 %, respectively, for DA 100, DA 200, DA 400, and GLC 5 mg/kg on the 21st day of treatment. After diabetic mice were treated with Dovyalis Abyssinica (100, 200, and 400 mg/kg) for 21 days, there was a significant increase in body weight as compared to diabetic control. Antioxidant activities of the leaf extract was found to be comparable to ascorbic acid with an IC50 of 140.04 μg/ml.

Conclusion

The present findings revealed that D. abyssinica leaves could be useful for the management of diabetes mellitus and other abnormalities related to this metabolic disorder. Thus, the present study may support the traditional use of D. abyssinica for diabetes mellitus treatment.

The complex and multidimensional landscape of type 2 diabetes mellitus (T2D) is a major global concern. Despite several years of extensive research, the precise underlying causes of T2D remain elusive, but evidence suggests that it is influenced by a myriad of interconnected risk factors such as epigenetics, genetics, gut microbiome, environmental factors, organelle stress, and dietary habits. The number of factors influencing the pathogenesis is increasing day by day which worsens the scenario; meanwhile, the interconnections shoot up the frame. By gaining deeper insights into the contributing factors, we may pave the way for the development of personalized medicine, which could unlock more precise and impactful treatment pathways for individuals with T2D. This review summarizes the state of knowledge about T2D pathogenesis, focusing on the interplay between various risk factors and their implications for future therapeutic strategies. Understanding these factors could lead to tailored treatments targeting specific risk factors and inform prevention efforts on a population level, ultimately improving outcomes for individuals with T2D and reducing its burden globally.

Background

Advancements in type 2 diabetes mellitus (T2DM) therapy, notably with weekly agents like glucagon-like peptide-1 receptor agonists (GLP-RAs) such as dulaglutide, offer promising outcomes in clinical practice. The emergence of once-weekly insulin adds to this therapeutic arsenal. This research aims to explore and compare the efficacy and safety profiles of these agents in diabetes management, facilitating informed decision-making for optimizing their utilization in clinical practice.

Methods

A systematic search of PubMed, Scopus, Cochrane, and Web of Science databases was conducted. The research protocol was registered at OSF registries (https://osf.io/gd67x). The primary outcome of interest was the change in hemoglobin A1C (HbA1c), with secondary outcomes including the change in fasting plasma glucose, body weight, prevalence of hypoglycemia, and treatment discontinuation due to adverse events. The evaluation of bias risk was conducted utilizing the RoB2 tool developed by the Cochrane Collaboration. Statistical analysis was performed using RStudio version 4.3.2 with the meta package version 7.0–0 and the netmeta package version 2.9–0. Confidence in network meta-analysis estimates was evaluated using the CINeMA (Confidence In Network Meta-Analysis). Heterogeneity was assessed by comparing the magnitude of the common between-study variance (τ2) for each outcome with empirical distributions of heterogeneity variances.

Results

Dulaglutide 1.5 mg (mg) weekly demonstrated superior reduction in hemoglobin A1C (HbA1c) compared to insulin, with a mean difference (MD) of −0.35 (95 % CI: −0.51 to −0.19). Additionally, Dulaglutide 1.5 mg exhibited greater weight loss, with an MD of −3.12 (95 % CI: −3.55 to −2.68). However, it also showed a higher rate of adverse events, with an odds ratio (OR) of 1.40 (95 % CI: 1.12 to 1.75) compared to insulin. Both doses of Dulaglutide (1.5 mg and 0.75 mg) had lower prevalence of hypoglycemia compared to insulin, with ORs of 0.60 (95 % CI: 0.41 to 0.87) and 0.59 (95 % CI: 0.41 to 0.86), respectively. There was no significant difference in treatment discontinuation among the treatment groups.

Conclusion

Dulaglutide, particularly at higher doses, demonstrates superior efficacy in lowering hemoglobin A1C and reducing hypoglycemia risk compared to Icodec insulin in type 2 diabetes management. However, its use is also associated with a higher incidence of adverse events. Clinicians should carefully consider these factors when selecting optimal treatment strategies for patients with type 2 diabetes mellitus.

Aim

Emerging anti-obesity pharmacotherapy provides an option to correct maladaptive physiological and hormonal changes associated with obesity. One of the widely used medications in this context is glucagon-like peptide 1 (GLP-1) agonists. However, the misuse of these medications without any guidance and monitoring of lifestyle modifications can lead to unfavorable outcomes. The study aims to evaluate the effectiveness of a hybrid care model, incorporating GLP-1 and GLP-1/GIP agonist therapies, in managing obese patients with/without pre-diabetes. This study showcases the midway results of a 6-month program, which includes a multidisciplinary care team and digital technology for continuous engagement and monitoring of patients, both in-clinic and remotely.

Methods

In a retrospective observational study, 115 participants were treated with GLP-1s (semaglutide, tirzepatide, and liraglutide). Physicians, dietitians, and coaches worked together to support behavioral changes using a dedicated app provided to patients. At the care team end, an integrated portal enabled continuous data flow allowing for the care team to provide personalized care via chat at regular intervals. Data collected included food logs, continuous glucose monitoring (CGM), and digital biomarkers such as sleep and activity.

Results

At the midpoint of the program, participants exhibited statistically significant improvements in various metabolic parameters. Mean weight reduction was 8 %, with significant reductions in BMI, fat mass, and cholesterol levels. 24 (20.9 %) of patients lost ≥5 % of body weight, 55 (47.8 %) patients lost ≥10 % weight, and 36 (31.3 %) patients lost ≥15 % weight. Sub-analysis of pre-diabetic patients (n=36) demonstrated substantial improvements, including control of pre-diabetes in 80.6 % of cases and reduced HbA1c levels back to normoglycemia (5.39 ± 0.27).

Conclusion

The Zone.Health's program, which combines pharmacotherapy with continuous engagement and monitoring to enable sustainable lifestyle modifications, demonstrated significant improvements in weight, body composition, and metabolic markers. Pre-diabetes was also effectively addressed. It is necessary to conduct further research to assess the long-term sustainability and optimal adoption of such care models into clinical practice.

Aim

To assess the differences in glucose readings between the continuous glucose monitoring calibration-free interstitial sensors versus capillary blood glucose monitoring by glucometer.

Study design

Two healthy non-pregnant volunteers participated in the study, and wore simultaneously both the calibration-free Freestyle Libre and the Dexcom G6 sensor. Glucose values were recorded before and after meals during breakfast, lunch, and dinner on three separate days by either scanning the Freestyle Libre CGM sensor with a smartphone, or obtaining glucose readings real-time through the Dexcom G6 CLARITY mobile application. Blood glucose values were recorded using the Accu-Chek Active glucose meter. The Wilcoxon signed-rank test was used for paired non-parametric data to compare glucose readings between groups.

Results

The average glucose values obtained from the Dexcom G6 CGM consistently registered higher (6.54 ± 0.80 mmol/L) and those from the Freestyle Libre (5.49 ± 0.65 mmol/L) consistently lower, from the glucometer (6.17 ± 0.55 mmol/L), with p-value <0.05 between groups. In the three-way comparison, the Dexcom G6 CGM sensor yielded the highest values, followed by the glucose meter, and finally the Freestyle Libre CGM sensor

Conclusion

Both CGM systems exhibited discrepancies from blood glucose (BG) measurements, and variations were observed among the different CGM systems themselves.

Background

Metabolic syndrome (MetS), characterized by elevated blood pressure, high blood glucose, excess abdominal fat, and abnormal cholesterol or triglyceride levels, significantly increases the risk of various non-communicable diseases. This study focuses on understanding the sex-specific association between Apolipoprotein E (APOE) polymorphism and MetS among middle-aged and older adults in rural southern India.

Methods

This cross-sectional study utilized data from the Centre for Brain Research-Srinivaspura Aging, Neuro Senescence, and COGnition (CBR-SANSCOG) study. Participants (n = 3741) underwent comprehensive clinical assessments and blood investigations, including APOE genotyping. MetS was defined using the National Cholesterol Education Program – Adult Treatment Panel III (NCEP ATP III) and the Consensus criteria. Statistical analyses, including chi-square tests, ANCOVA, and logistic regression, were conducted to explore the association of APOE genotype with MetS and its components, stratified by sex.

Results

Females carrying the APOE E4 allele had 1.31-fold increased odds of MetS (95 % CI: 1.02,1.69, p = 0.035) according to the NCEP ATP III criteria but not when the Consensus criteria were applied. The study also noted sex-specific differences in the association of APOE with various MetS components, including lipid levels and waist circumference.

Discussion

Our findings reveal a sex-specific association between the APOE E4 allele and MetS, with only females having an increased risk. This study contributes to the understanding of the genetic underpinnings of MetS and highlights the importance of considering sex-specific differences in MetS research and its prevention strategies. This study underscores the complexity of MetS etiology and emphasizes the need for further research to elucidate the role of genetic, environmental, and lifestyle factors in its progression, particularly in sex-specific contexts.

Background

The circadian rhythm involves numerous metabolic processes, including sleep/awakening, body temperature regulation, hormone secretion, hepatic function, cellular plasticity, and cytokine release (inflammation), that appear to have a dynamic relationship with all the processes above. Studies have linked various cytokines to the chronic state of low-grade inflammation and oxidative stress in obesity. Dawn-to-dusk dry fasting (DDDF) could alleviate the adverse effects of obesity by decreasing inflammation. This study examined the effects of DDDF on circulating inflammatory cytokines in subjects with increased body mass index (BMI).

Methods

The current observational prospective study included adult subjects with a BMI equal to or greater than 25 kg/m² who practiced the annual religious 30-day DDDF. Individuals with significant underlying medical conditions were excluded to limit confounding factors. All subjects were evaluated within two weeks before 30-day DDDF, within the fourth week of 30-day DDDF, and within two weeks after 30-day DDDF. Multiple cytokines and clinical health indicators were measured at each evaluation.

Results

Thirteen subjects (10 men and three women) with a mean age of 32.9 years (SD = 9.7 years) and a mean BMI of 32 kg/m2 (SD = 4.6 kg/m²) were included. An overall associated decrease in the levels of multiple cytokines with DDDF was observed. A significant decrease in the mean interleukin 1 beta level was observed within the fourth week of 30-day DDDF (P = 0.045), which persisted even after the fasting period (P = 0.024). There was also a significant decrease in the mean levels of interleukin 15 (IL-15) (P = 0.014), interleukin 1 receptor antagonist (P = 0.041), macrophage-derived chemokine (MDC) (P = 0.013), and monokine induced by interferon gamma/chemokine (C-X-C motif) ligand 9 (P = 0.027) within the fourth week of 30-day DDDF and in the mean levels of fibroblast growth factor 2 (P = 0.010), interleukin 12 p40 subunit (P = 0.038), interleukin 22 (P = 0.025) and tumor necrosis factor alpha (P = 0.046) within two weeks after 30-DDDF. In terms of anthropometric parameters, there was a decrease in mean body weight (P = 0.032), BMI (P = 0.028), and hip circumference (P = 0.007) within the fourth week of 30-day DDDF and a decrease in mean weight (P = 0.026), BMI (P = 0.033) and hip circumference (P = 0.016) within two weeks after 30-day DDDF compared with the levels measured within two weeks before 30-day DDDF. Although there was no significant correlation between changes in weight and changes in circulating inflammatory cytokines, there was a significant positive correlation between changes in waist circumference and changes in specific inflammatory cytokines (e.g., IL-15, MDC, platelet-derived growth factor, soluble CD40L, vascular endothelial growth factor A) within the fourth week of 30-day DDDF and/or two weeks after 30-day DD