Background: Heart rate recovery ( HRR ) is a noninvasive assessment of autonomic dysfunction and has been implicated with risk of cardiovascular events and all‐cause mortality. However, evidence has not been systematically assessed. We performed a meta‐analysis of prospective cohort studies to quantify these associations in the general population. Methods and Results: A literature search using 3 databases up to August 2016 was conducted for studies that reported hazard ratios with 95% CI s for the association between baseline HRR and outcomes of interest. The overall hazard ratios were calculated using a random‐effects model. There were 9 eligible studies in total, with 5 for cardiovascular events enrolling 1061 cases from 34 267 participants, and 9 for all‐cause mortality enrolling 2082 cases from 41 600 participants. The pooled hazard ratios associated with attenuated HRR versus fast HRR that served as the referent were 1.69 (95% CI 1.05–2.71) for cardiovascular events and 1.68 (95% CI 1.51–1.88) for all‐cause mortality. For every 10 beats per minute decrements in HRR , the hazard ratios were 1.13 (95% CI 1.05–1.21) and 1.09 (95% CI 1.01–1.19), respectively. Further analyses suggested that the associations observed between attenuated HRR and risk of fatal cardiovascular events and all‐cause mortality were independent of traditional metabolic factors for cardiovascular disease (all P <0.05). Conclusions: Attenuated HRR is associated with increased risk of cardiovascular events and all‐cause mortality, which supports the recommendation of recording HRR for risk assessment in clinical practice as a routine.

Background and aims: Exercise training is considered a cornerstone in the management of type 2 diabetes, which is associated with impaired endothelial function. However, the association of exercise training with endothelial function in type 2 diabetes patients has not been fully understood. This meta-analysis aimed to investigate their associations with focus on exercise types. Methods: Databases were searched up to January 2018 for studies evaluating the influences of exercise training with durations ≥ 8 weeks on endothelial function assessed by flow-mediated dilation (FMD) among type 2 diabetes patients or between type 2 diabetics and non-diabetics. Data were pooled using random-effects models to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results: Sixteen databases were included. Exercise training resulted in an overall improvement in FMD by 1.77% (95% CI 0.94–2.59%) in type 2 diabetes patients. Specifically, both aerobic and combined aerobic and resistance exercise increased FMD by 1.21% (95% CI 0.23–2.19%) and 2.49% (95% CI 1.17–3.81%), respectively; but resistance exercise only showed a trend. High-intensity interval aerobic exercise did not significantly improve FMD over moderate-intensity continuous exercise. Notably, the improvement in FMD among type 2 diabetes patients was smaller compared with non-diabetics in response to exercise training (WMD − 0.72%, 95% CI − 1.36 to − 0.08%) or specifically to aerobic exercise (WMD − 0.65%, 95% CI − 1.31 to 0.01%). Conclusions: Exercise training, in particular aerobic and combined exercise, improves endothelial function in type 2 diabetes patients, but such an improvement appears to be weakened compared with non-diabetics. Trial registration PROSPERO CRD42018087376

Walking is the most popular and most preferred exercise among type 2 diabetes patients, yet compelling evidence regarding its beneficial effects on cardiovascular risk factors is still lacking. The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the association between walking and glycemic control and other cardiovascular risk factors in type 2 diabetes patients. Three databases were searched up to August 2014. English-language RCTs were eligible for inclusion if they had assessed the walking effects (duration ≥8 weeks) on glycemic control or other cardiovascular risk factors among type 2 diabetes patients. Data were pooled using a random-effects model. Subgroup analyses based on supervision status and meta-regression analyses of variables regarding characteristics of participants and walking were performed to investigate their association with glycemic control. Eighteen studies involving 20 RCTs (866 participants) were included. Walking significantly decreased glycosylated haemoglobin A1c (HbA1c) by 0.50% (95% confidence intervals [CI]: −0.78% to −0.21%). Supervised walking was associated with a pronounced decrease in HbA1c (WMD −0.58%, 95% CI: −0.93% to −0.23%), whereas non-supervised walking was not. Further subgroup analysis suggested non-supervised walking using motivational strategies is also effective in decreasing HbA1c (WMD −0.53%, 95% CI: −1.05% to −0.02%). Effects of covariates on HbA1c change were generally unclear. For other cardiovascular risk factors, walking significantly reduced body mass index (BMI) and lowered diastolic blood pressure (DBP), but non-significantly lowered systolic blood pressure (SBP), or changed high-density or low-density lipoprotein cholesterol levels. This meta-analysis supports that walking decreases HbA1c among type 2 diabetes patients. Supervision or the use of motivational strategies should be suggested when prescribed walking to ensure optimal glycemic control. Walking also reduces BMI and lowers DBP, however, it remains insufficient regarding the association of walking with lowered SBP or improved lipoprotein profiles. PROSPERO CRD42014009515

Background: Diabetes mellitus is considered a common comorbidity of COVID-19, which has a wide spectrum of clinical manifestations ranging from asymptomatic infection to severe respiratory symptoms and even death. However, the impact of COVID-19 on blood glucose has not been fully understood. This meta-analysis aimed to summarize available data on the association between glycemic parameters and severity of COVID-19. Methods: PubMed, EMBASE, and Cochrane Library were searched from December 1, 2019 to May 15, 2020. Observational studies investigating blood glucose or glycated hemoglobin A1c (HbA1c) according to the severity of COVID-19 were considered for inclusion. Two independent researchers extracted data from eligible studies using a standardized data extraction sheet and then proceeded to cross check the results. Data were pooled using a fixed- or random-effects model to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results: Three studies reported blood glucose and HbA1c according to the severity of COVID-19 and were included in this meta-analysis. The combined results showed that severe COVID-19 was associated with higher blood glucose (WMD 2.21, 95% CI: 1.30–3.13, P < 0.001). In addition, HbA1c was slightly higher in patients with severe COVID-19 than those with mild COVID-19, yet this difference did not reach significance (WMD 0.29, 95% CI: −0.59 to 1.16, P = 0.52). Conclusions: This meta-analysis provides evidence that severe COVID-19 is associated with increased blood glucose. This highlights the need to effectively monitor blood glucose to improve prognosis in patients infected with COVID-19.

Advanced glycation end products (AGEs) are pathogenic factors of diabetic nephropathy (DN), causing renal damage in various ways. The aim of this study is to investigate the ectopic lipid accumulation caused by AGEs in human renal tubular epithelial cell line (HK-2) cells and the kidney of type 2 diabetic rats. In vivo study, diabetes was induced in male Sprague–Dawley rats through intraperitoneal injection of high-fat/high-sucrose diet and low-dose streptozocin (STZ). Two weeks after STZ injection, the diabetic rats were randomly divided into two groups, namely, untreated diabetic and Aminoguanidine Hydrochloride (AG, an AGEs formation inhibitor)-treated (100 mg/Kg/day, i.g., for 8 weeks) group. In vitro study, according to the different treatments, HK-2 were divided into 6 groups. Intracellular cholesterol content was assessed by Oil Red O staining and cholesterol enzymatic assay. Expression of mRNA and protein of molecules controlling cholesterol homeostasis in the treated cells was examined by real-time quantitative PCR and western blotting, respectively. SREBP cleavage-activating protein (SCAP) translocation was detected by confocal microscopy. Here we found Nε-(carboxymethyl) lysine (CML, a member of the AGEs family) increased Oil Red O staining and intracellular cholesterol ester (CE) in HK-2 cells; Anti-RAGE (AGEs receptor) reduced lipid droplets and the CE level. A strong staining of Oil Red O was also found in the renal tubules of the diabetic rats, which could be alleviated by AG. CML upregulated both mRNA and protein expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), LDL receptor (LDLr), sterol regulatory element binding protein-2 (SREBP-2) and SCAP, which were inhibited by anti-RAGE. The upregulation of these molecules in the kidney of the diabetic rats was also ameliorated by AG. Furthermore, AG reduced serum and renal CML deposition, and improved urine protein and u-NGAL in type 2 diabetic rats. Overall, these results suggest that CML caused DN might be via disturbing the intracellular feedback regulation of cholesterol. Inhibition of CML-induced lipid accumulation might be a potential renoprotective role in the progression of DN.

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.