Circulating irisin in nonalcoholic fatty liver disease: an updated meta-analysis

Introduction: Exogenous administration of recombinant irisin may reverse hepatic steatosis and steatohepatitis. However, it remains controversial as to whether nonalcoholic fatty liver disease (NAFLD) shows reduced circulating (serum/plasma) irisin levels. A meta-analysis was conducted to address this issue. Material and methods: A literature search of databases was performed up to June 2021. Observational studies that reported circulating irisin in NAFLD ascertained by any methods (e.g. ultrasonography or magnetic resonance) and compared with any controls were eligible for inclusion. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were obtained using a random-effects meta-analysis model. Results: Eleven studies enrolling 1277 NAFLD cases and 944 non-NAFLD controls were included. The approaches used for NAFLD ascertainment included ultrasonography (4 studies), magnetic resonance (3 studies), and liver biopsy (5 studies). Meta-analysis showed that circulating irisin in NAFLD was comparable to any non-NAFLD controls (10 studies with 11 datasets; SMD –0.09, 95% CI: –0.48 to 0.29), including the body mass index (BMI)-matched and lean controls (both p ≥ 0.80). Restricting studies to NAFLD ascertained by magnetic resonance or liver biopsy rather than ultrasonography showed that serum irisin was reduced in NAFLD (5 studies, SMD –0.63, 95% CI: –1.14 to –0.13). Meta-analysis also suggested that circulating irisin did not differ between mild and moderate-to-severe NAFLD (7 studies; SMD 0.02, 95% CI: –0.25 to 0.30), and this association was not significantly moderated by study location (Europe versus Asia). Conclusions: Circulating irisin in NAFLD did not differ from any non-NAFLD controls and was unlikely to be affected by disease severity or racial-ethnic difference

OCT1-Mediated Metformin Uptake Regulates Pancreatic Stellate Cell Activity

Background/Aims: Metformin treatment is reported to be associated with a lower incidence of and mortality from pancreatic cancer (PC) in type 2 diabetes patients. Activated pancreatic stellate cells (PSCs) are key stroma cells responsible for pancreatic fibrogenesis and PC progression. However, little research is about the influence of metformin on PSCs. Given the potential beneficial effects of metformin on PC, pancreatic tumour stroma is an important target for new therapeutics. We observed the effects of metformin on PSCs. We investigated the effects of metformin on human PSCs proliferation and the production of extracellular matrix (ECM) proteins. Methods: Cells were cultured with different concentrations of metformin (0-10 mmol/L). Cell proliferation was determined by immunofluorescence staining for nuclear Ki67 labelling. ECM production was studied by quantitative real-time polymerase chain reaction, immunoblotting and immunofluorescence microscopy. Adenosine monophosphate–activated protein kinase (AMPK), an important regulatory molecule responsible for metformin action, and the organic cation transporter member 1 (OCT1), which is believed to be the most important transporter for the pharmacological action of metformin, were investigated for their possible involvements in metformin-induced proliferation and ECM production. Results: Our results showed that metformin inhibited PSCs proliferation and decreased the production of ECM proteins by activation of AMPK phosphorylation. Silencing of OCT1 expression resulted in a reduction in the effects of metformin on PSCs activity. Conclusions: Collectively, the data indicate that OCT1 may contribute to uptake metformin and regulate PSCs activity. OCT1 is a target of metformin in regulating PSCs activity

The Prevalence and Risk Factors of Diabetic Retinopathy: Screening and Prophylaxis Project in 6 Provinces of China.

Purpose: To investigate the prevalence and associated factors of diabetic retinopathy (DR) and advanced DR in Chinese adults with diabetes mellitus (DM). Patients and Methods: A cross-sectional study was performed on 4831 diabetic patients from 24 hospitals from April 2018 to July 2020. Non-mydriatic fundus of patients were interpreted by an artificial intelligence (AI) system. Fundus photos that were unsuitable for AI interpretation were interpreted by two ophthalmologists trained by one expert ophthalmologist at Beijing Tongren Hospital. Medical history, height, weight, body mass index (BMI), glycosylated hemoglobin (HbA1c), blood pressure, and laboratory examinations were recorded. Results: A total of 4831 DM patients were included in this study. The prevalence of DR and advanced DR in the diabetic population was 31.8% and 6.6%, respectively. In multiple logistic regression analysis, male (odds ratio [OR], 1.39), duration of diabetes (OR, 1.05), HbA1c (OR, 1.11), farmer (OR, 1.39), insulin treatment (OR, 1.61), region (northern, OR, 1.78; rural, OR, 6.96), and presence of other diabetic complications (OR: 2.03) were associated with increased odds of DR. The factors associated with increased odds of advanced DR included poor glycemic control (HbA1c > 7.0%) (OR, 2.58), insulin treatment (OR, 1.73), longer duration of diabetes (OR, 3.66), rural region (OR, 4.84), and presence of other diabetic complications (OR, 2.36), but overweight (BMI > 25 kg/m2) (OR, 0.61) was associated with reduced odds of advanced DR. Conclusion: This study shows that the prevalence of DR is very high in Chinese adults with DM, highlighting the necessity of early diabetic retinal screening

Muscle strength and prediabetes progression and regression in middle‐aged and older adults: a prospective cohort study

Background: Prediabetes progression is associated with increased mortality while its regression decreases it. It is unclear whether muscle strength is related to prediabetes progression or regression. This study investigated the associations of muscle strength, assessed by grip strength and chair‐rising time, with prediabetes progression and regression based on the China Health and Retirement Longitudinal Study (CHARLS) enrolling middle‐aged and older adults. Methods: We included 2623 participants with prediabetes from CHARLS, who were followed up 4 years later with blood samples collected for measuring fasting plasma glucose and haemoglobin A1c. Grip strength (normalized by body weight) and chair‐rising time were assessed at baseline and categorized into tertiles (low, middle, and high groups). Prediabetes at baseline and follow‐up was defined primarily using the American Diabetes Association (ADA) criteria and secondarily using the World Health Organization (WHO) and International Expert Committee (IEC) criteria. Multinomial logistic regression analysis was applied to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Results: The mean age of included participants was 59.0 ± 8.6 years, and 46.6% of them were males. During follow‐up, 1646 participants remained as prediabetes, 379 progressed to diabetes, and 598 regressed to normoglycaemia based on ADA criteria. Participants who progressed to diabetes had lower normalized grip strength than those who remained as prediabetes (0.49 ± 0.15 vs. 0.53 ± 0.15, P < 0.001), but participants who regressed to normoglycaemia showed the opposite (0.55 ± 0.16 vs. 0.53 ± 0.15, P = 0.003). However, chair‐rising time was comparable across different groups (P overall = 0.17). Compared with participants in low normalized grip strength or high chair‐rising time group, those in high normalized grip strength or low chair‐rising time group had decreased odds of progression to diabetes (OR 0.62, 95% CI 0.44 to 0.87; and OR 0.69, 95% CI 0.51 to 0.93, respectively) after multivariable adjustment. However, both were unrelated to the odds of regression to normoglycaemia (OR 0.94, 95% CI 0.71 to 1.25; and OR 0.84, 95% CI 0.65 to 1.07, respectively). These outcomes remained generally comparable when prediabetes was defined by WHO or IEC criteria. Higher normalized grip strength but not lower chair‐rising time was prospectively associated with lower blood pressure, better glycaemic condition, and lower inflammation (all P ≤ 0.04). Conclusions: High muscle strength is associated with reduced odds of progression to diabetes but does not predict regression to normoglycaemia in prediabetes. Future studies are warranted to assess whether increases in muscle strength promote prediabetes regression

Ruta de la gran pasión Argentina: un recurso turístico para Buenos Aires

Treball Final de Grau en Turisme. Codi: TU0944. Curs acadèmic: 2016-201

Prediabetes Progression and Regression on Objectively- Measured Physical Function: A Prospective Cohort Study

Prediabetes leads to declines in physical function in older adults, but the impact of prediabetes progression or regression on physical function is unknown. This study assessed this longitudinal association, with physical function objectivelymeasured by grip strength, walking speed, and standing balance, based on the Health and Retirement Study enrolling United States adults aged >50 years. Participants with prediabetes were followed-up for 4-year to ascertain prediabetes status alteration (maintained, regressed, or progressed), and another 4-year to assess their impacts on physical function. Weak grip strength was defined as <26 kg for men and <16 kg for women, slow walking speed was as <0.8 m/sec, and poor standing balance was as an uncompleted fulltandem standing testing. Logistic and linear regression analyses were performed. Of the included 1,511 participants with prediabetes, 700 maintained as prediabetes, 306 progressed to diabetes, and 505 regressed to normoglycemia over 4 years. Grip strength and walking speed were declined from baseline during the 4-year followup, regardless of prediabetes status alteration. Compared with prediabetes maintenance, prediabetes progression increased the odds of developing weak grip strength by 89% (95% confidence interval [CI], 0.04 to 2.44) and exhibited larger declines in grip strength by 0.85 kg (95% CI, -1.65 to -0.04). However, prediabetes progression was not related to impairments in walking speed or standing balance. Prediabetes regression also did not affect any measures of physical function. Prediabetes progression accelerates grip strength decline in aging population, while prediabetes regression may not prevent physical function decline due to aging

Efficacy of calcium dobesilate in treating Chinese patients with mild-to-moderate non-proliferative diabetic retinopathy (CALM-DR): protocol for a single-blind, multicentre, 24-armed cluster-randomised, controlled trial.

INTRODUCTION Calcium dobesilate (CaD) has been used in the treatment of diabetic retinopathy (DR) due to its potential in protecting against retinal vascular damage. However, there is limited evidence exploring its efficacy in combating DR progression. This study is aimed at evaluating whether CaD could prevent DR progression into an advanced stage among Chinese patients with mild-to-moderate non-proliferative DR (NPDR). METHODS AND ANALYSIS This study is a single-blind, multicentre, cluster-randomised, controlled superiority trial. A total of 1272 patients with mild-to-moderate NPDR will be enrolled and randomly assigned at a 1:1 ratio into the control group (conventional treatment group) and the intervention group (conventional treatment plus CaD (500 mg three times per day) for 12 months). Patients will be followed at 1, 3, 6 and 12 months after randomisation and receiving treatments, with the severity of DR assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. The primary endpoint is the progression of DR during follow-up, which is defined as an increase of two or more steps in the ETDRS scale. The secondary endpoints include the concomitant changes in visual acuity, presence, number, location and type of retinal lesions, and retinal blood vessel diameter as well as the arteriovenous ratio at different visits. ETHICS AND DISSEMINATION Each local ethics committee (first Vote: Ethical Review Committees of Zhongda Hospital of Southeast University (2019ZDSYLL132-P01)) has approved the study. The results will be published in high impact peer-reviewed scientific journals aimed at the general reader. TRIAL REGISTRATION NUMBERS NCT04283162

Efficacy of Co-administration of Liuwei Dihuang Pills and Ginkgo Biloba Tablets on Albuminuria in Type 2 Diabetes: A 24-Month, Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Purpose: We investigated the effects of Traditional Chinese Medicine (TCM) on the occurrence and progression of albuminuria in patients with type 2 diabetes.Methods: In this randomized, double-blind, multicenter, controlled trial, we enrolled 600 type 2 diabetes without diabetic nephropathy (DN) or with early-stage DN. Patients were randomly assigned (1:1) to receive Liuwei Dihuang Pills (LWDH) (1.5 g daily) and Ginkgo biloba Tablets (24 mg daily) orally or matching placebos for 24 months. The primary endpoint was the change in urinary albumin/creatinine ratio (UACR) from baseline to 24 months.Results: There were 431 patients having UACR data at baseline and 24 months following-up in both groups. Changes of UACR from baseline to follow-up were not affected in both groups: −1.61(−10.24, 7.17) mg/g in the TCM group and −0.73(−7.47, 6.75) mg/g in the control group. For patients with UACR ≥30 mg/g at baseline, LWDH and Ginkgo biloba significantly reduced the UACR value at 24 months [46.21(34.96, 58.96) vs. 20.78(9.62, 38.85), P &lt; 0.05]. Moreover, the change of UACR from baseline to follow-up in the TCM group was significant higher than that in the control group [−25.50(−42.30, −9.56] vs. −20.61(−36.79, 4.31), P &lt; 0.05].Conclusion: LWDH and Ginkgo biloba may attenuate deterioration of albuminuria in type 2 diabetes patients. These results suggest that TCM is a promising option of renoprotective agents for early stage of DN.Trial registration: The study was registered in the Chinese Clinical Trial Registry. (no. ChiCTR-TRC-07000037, chictr.org

Irisin response to exercise training in adults and its effect on the regulation of C2C12 cell proliferation and differentiation

Irisin is now recognized as an exercise-induced hormone that is produced primarily by skeletal muscles and adipose tissue. However, its physiological characteristics in the response to acute or chronic exercise training still remains somewhat controversial. By using serum samples at different time points before and after an acute bout of exercise among trained and untrained healthy adults, this study showed that serum irisin transiently increases in response to acute exercise, which is independent of training status. This study also showed that running could keep irisin at significantly elevated levels for a longer time-period versus cycling; suggesting that irisin response to acute exercise is dependent upon exercise mode. By conducting a meta-analysis, this study provided evidence that chronic exercise training is associated with decreased irisin levels in the randomized controlled trials. This study further showed that differences in study design and failure to control for confounders in non-randomized studies might be the major sources of heterogeneity and bias underlying current inconsistent findings. Moreover, since regular exercise is demonstrated to be a key element in the management of some muscular diseases by preventing skeletal muscle atrophy and enhancing skeletal muscle mass, and given the fact that irisin is responsive to exercise and positively modulates the metabolism in skeletal muscle cells, it seems plausible that irisin might affect the development of skeletal muscle cells. By treating mouse skeletal muscle cells continuously with or without irisin at physiological and pharmacological concentrations during different stages of differentiation, this study showed that irisin promotes mouse skeletal muscle cell proliferation in a dose-dependent manner, while irisin seems to have no significant effects in regulating mouse skeletal muscle cell differentiation

Effects of resveratrol on glucose control and insulin sensitivity in subjects with type 2 diabetes: systematic review and meta-analysis

Abstract Although the regular consumption of resveratrol has been known to improve glucose homeostasis and reverse insulin resistance in type 2 diabetes mellitus (T2DM), the reported results are inconsistent. Thus, we aimed to assess the effects of resveratrol on glycemic control and insulin sensitivity among patients with T2DM. We searched for relevant articles published until June 2017 on PubMed-Medline, Embase, Cochrane Library, and Web of Science. Randomized controlled trials in T2DM patients administered with resveratrol as intervention were included. After study selection, quality assessment and data extraction were performed independently by two authors, and STATA and RevMan software were used for statistical analysis. Nine randomized controlled trials involving 283 participants were included. Meta-analysis showed that resveratrol significantly improved the fasting plasma glucose ( −0.29 mmol/l, 95% CI: −0.51, −0.06, p < 0.01) and insulin levels (−0.64 U/mL, 95% CI: −0.95, −0.32, p < 0.0001). The drug also reduced homeostasis model assessment of insulin resistance (HOMA-IR) index, systolic blood pressure, and diastolic blood pressure among participants with T2DM. The changes in hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were negligible. Subgroup analysis comparing the resveratrol supplementation doses of < 100 mg/d versus ≥ 100 mg/d revealed a significant difference in fasting plasma glucose. In particular, the latter dose presented more favorable results. This meta-analysis provides evidence that supplementation of resveratrol may benefit management of T2DM