Background: Obesity is common in patients with coronavirus disease 2019 (COVID-19). The effects of obesity on clinical outcomes of COVID-19 warrant systematical investigation. Objective: This study explores the effects of obesity with the risk of severe disease among patients with COVID-19. Methods: Body mass index (BMI) and degree of visceral adipose tissue (VAT) accumulation were used as indicators for obesity status. Publication databases including preprints were searched up to August 10, 2020. Clinical outcomes of severe COVID-19 included hospitalization, a requirement for treatment in an intensive care unit (ICU), invasive mechanical ventilation (IMV), and mortality. Risks for severe COVID-19 outcomes are presented as odds ratios (OR) and 95% confidence interval (95%CI) for cohort studies with BMI-defined obesity, and standardized mean difference (SMD) and 95%CI for controlled studies with VAT-defined excessive adiposity. Results: A total of 45, 650 participants from 30 studies with BMI-defined obesity and 3 controlled studies with VAT-defined adiposity were included for assessing the risk of severe COVID-19. Univariate analyses showed significantly higher ORs of severe COVID

OBJECTIVEInsulin has mitogenic effects, although hyperglycemia may be a risk factor for cancer in type 2 diabetes. It remains uncertain whether use of insulin increases cancer risk because of its effect on cell growth and proliferation or decreases cancer risk because of its glucose-lowering effect.RESEARCH DESIGN AND METHODSA 1:2-matched new insulin user cohort on age (±3 years), smoking status, and likelihood of initiating insulin therapy (±0.05) was selected from a cohort of 4,623 Chinese patients with type 2 diabetes, free of cancer, and naive to insulin at enrollment. Stratified Cox regression analysis on the matched pairs was used to obtain hazard ratios (HRs) of insulin therapy and A1C for cancer risk. A structured adjustment scheme was used to adjust for covariates.RESULTSOf 973 new insulin users, 971 had matched nonusers (n = 1935). The cancer incidence in insulin nonusers was much higher than that in insulin users (49.2 vs. 10.2, per 1,000 person-years, P < 0.0001). After further adjustment for all other covariates with a P value less than 0.3 and nonlinear associations with cancer, A1C was associated with an increased cancer risk (HR per percentage 1.26, 95% CI 1.03–1.55), whereas use of insulin was associated with a decreased cancer risk (HR of insulin users vs. nonusers: 0.17, 0.09–0.32). Consistent results were found in analyses including all 973 insulin users and 3,650 nonusers.CONCLUSIONSIn Chinese patients with type 2 diabetes, hyperglycemia predicts cancer, whereas insulin usage was associated with a reduced cancer risk.

Background-Doxorubicin (DOX) is an important antineoplastic agent. However, the associated cardiotoxicity, possibly mediated by the production of reactive oxygen species, has remained a significant and dose-limiting clinical problem. Our hypothesis is that the hematopoietic/megakaryocytopoietic growth factor thrombopoietin (TPO) protects against DOX-induced cardiotoxicity and might involve antiapoptotic mechanism exerted on cardiomyocytes. Methods and Results-In vitro investigations on H9C2 cell line and spontaneously beating cells of primary, neonatal rat ventricle, as well as an in vivo study in a mouse model of DOX-induced acute cardiomyopathy, were performed. Our results showed that pretreatment with TPO significantly increased viability of DOX-injured H9C2 cells and beating rates of neonatal myocytes, with effects similar to those of dexrazoxane, a clinically approved cardiac protective agent. TPO ameliorated DOX-induced apoptosis of H9C2 cells as demonstrated by assays of annexin V, active caspase-3, and mitochondrial membrane potential. In the mouse model, administration of TPO (12.5 g/kg IP for 3 alternate days) significantly reduced DOX-induced (20 mg/kg) cardiotoxicity, including low blood cell count, cardiomyocyte lesions (apoptosis, vacuolization, and myofibrillar loss), and animal mortality. Using Doppler echocardiography, we observed increased heart rate, fractional shortening, and cardiac output in animals pretreated with TPO compared with those receiving DOX alone. Conclusions-These data have provided the first evidence that TPO is a protective agent against DOX-induced cardiac injury. We propose to further explore an integrated program, incorporating TPO with other protocols, for treatment of DOX-induced cardiotoxicity and other forms of cardiomyopathy.

Obesity is a major health hazard and despite lifestyle modification, many patients frequently regain any lost body weight. The use of western anti-obesity drugs has been limited by side effects including mood changes, suicidal thoughts, and gastrointestinal or cardiovascular complications. The effectiveness and safety of traditional Chinese medicine including Chinese herbal medicine (CHM) and acupuncture provide an alternative established therapy for this medical challenge. In this systematic review, we used standard methodologies to search, review, analyse and synthesize published data on the efficacy, safety and relapse of weight regain associated with use of CHM and acupuncture. We also examined the rationale, mechanisms and potential utility of these therapies. A total of 12 electronic databases, including Chinese, English, Korean and Japanese, were searched up to 28 February 2010. Randomized controlled trials (RCTs) for CHM and/or acupuncture with comparative controls were considered. We used the Jadad scale to assess methodological qualities, the random effect model in the pooled analysis of therapeutic efficacy to adjust for heterogeneity and funnel plots to explore publication bias. After screening 2,545 potential articles from the electronic databases, we identified 96 RCTs; comprising of 49 trials on CHM treatment, 44 trials on acupuncture treatment and 3 trials on combined therapy for appraisal. There were 4,861 subjects in the treatment groups and 3,821 in the control groups, with treatment duration ranging from 2 weeks to 4 months. Of the 77 publications written in Chinese, 75 had a Jadad score <3, while 16 of the 19 English publications had a Jadad score of >3. Efficacy was defined as body weight reduction ≥ 2 kg or body mass index (BMI) reduction ≥ 0.5 kg/m(2) . Compared with placebo or lifestyle modification, CHM and acupuncture exhibited respective 'risk ratio' (RR) of 1.84 (95% CI: 1.37-2.46) and 2.14 (95% CI: 1.58-2.90) in favour of body weight reduction, with a mean difference in body weight reduction of 4.03 kg (95% CI: 2.22-5.85) and 2.76 kg (95% CI: 1.61-3.83) and a mean difference in BMI reduction of 1.32 kg m(-2) (95% CI: 0.78-1.85) and 2.02 kg m(-2) (95% CI: 0.94-3.10), respectively. Compared with the pharmacological treatments of sibutramine, fenfluramine or orlistat, CHM and acupuncture exhibited an RR of 1.11 (95% CI: 0.96-1.28) and 1.14 (95% CI: 1.03-1.25) in body weight reduction, mean difference in body weight reduction of 0.08 kg (95% CI: -0.58 to 0.74) and 0.65 kg (95% CI: -0.61 to 1.91), and mean difference in BMI reduction of 0.18 kg m(-2) (95% CI: -0.39 to 0.75) and 0.83 kg m(-2) (95% CI: 0.29-1.37), respectively. There were fewer reports of adverse effects and relapses of weight regain in CHM intervention studies conducted in China than studies conducted outside China. CHM and acupuncture were more effective than placebo or lifestyle modification in reducing body weight. They had a similar efficacy as the Western anti-obesity drugs but with fewer reported adverse effects. How...

Islet amyloid has been suggested to be an important link between insulin resistance and ␤-cell dysfunction in type 2 diabetes. To investigate the prevalence and clinicopathological characteristics of islet amyloid, we examined consecutive autopsies of 235 Chinese patients with type 2 diabetes and 533 nondiabetic subjects. Islet amyloid deposits were identified using Congo red staining and quantitated by image analysis. We found that 3.0% of the nondiabetic subjects versus 39.6% of the diabetic patients displayed islet amyloid (P < 0.001). In diabetic patients, the amyloid deposits occupied a mean islet area of 36.2%, which was positively associated with BMI, blood pressure, and glycemic control. Pancreatic fibrosis and fat infiltration were more frequently found in diabetic patients with islet amyloid than those without islet amyloid, whereas pancreatic arteriosclerosis was identified in all diabetic patients. These findings suggest that islet amyloid deposits reflect greater insulin resistance and islet failure in a subgroup of type 2 diabetic patients. Islet failure may also have been exacerbated by fat infiltration, fibrosis, and arteriosclerosis. Optimal blood pressure and metabolic control may reduce these pathological changes and help preserve islet cell mass. Diabetes 52: 2759 -2766, 2003

Dyslipidemia complicates renal function leading to disturbances of major homeostatic organs in the body. Here we examined the effect of chronic renal dysfunction induced by uninephrectomy on fat redistribution and lipid peroxidation in rats treated with an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) for up to 10 months. Uninephrectomized rats developed fat redistribution and hypercholesterolemia typical of chronic renal failure when compared with sham-operated rats or lisinopril-treated uninephrectomized rats. The weight of the peri-renal fat was significantly less in the untreated compared to the lisinopril-treated uninephrectomized rats or those rats with a sham operation. We also found that there was a shift of heat-protecting unilocular adipocytes to heat-producing multilocular fat cells in the untreated uninephrectomized rats. Similarly in these rats we found a shift of subcutaneous and visceral fat to ectopic fat with excessive lipid accumulation and lipofuscin pigmentation. Lisinopril treatment prevented fat redistribution or transformation and lipid peroxidation. This study shows that ACE inhibition may prevent the fat anomalies associated with chronic renal dysfunction.

Objective. The aim of this study was to investigate the changes of regulatory T cells (Treg), interleukin-6 (IL-6), IL-10, transforming growth factor-β (TGF-β), and tumor necrosis factor-alpha (TNF-α) in patients with type 2 diabetes mellitus (T2DM). Methods. We performed a comprehensive search up to July 2016 for all clinical studies about the changes of Treg, IL-6, IL-10, IL-17, TGF-β, and TNF-α in T2DM patients versus healthy controls. Results. A total of 91 articles (5642 cases and 7378 controls) were included for this meta-analysis. Compared with the controls (all p < 0.001), the patients had increased serum levels of IL-6, TGF-β, and TNF-α but decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and serum IL-10 level. Furthermore, the percentage of peripheral CD4+CD25+Foxp3+Treg (p < 0.001) and serum IL-10 level (p = 0.033) were significantly lower in the patients with complication and in the patients without complication, respectively. No significant changes about the percentage of CD4+CD25+Treg (p = 0.360) and serum IL-17 level (p = 0.459) were found in T2DM patients. Conclusions. T2DM patients have decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and levels of serum IL-10 but elevated serum levels of IL-6, TGF-β, and TNF-α. Presence of diabetic complications further lowers the peripheral CD4+CD25+Foxp3+Treg number.

Up-regulated microRNA-375 is associated with type 2 diabetes and pancreatic islet amyloid formation and beta-cell deficit. microRNA-375 may serve as a biomarker for known and novel pathways in the pathogenesis of type 2 diabetes related to islet amyloid deposition and beta-cell dysfunction.