Clinical characteristics of adolescent-onset gout in Chinese: A hospital-based cross-sectional study.

OBJECTIVE: Adolescent-onset gout has a greater impact on the lives and health of patients than adult-onset gout. However, there is a relative lack of clinical information on adolescent-onset gout. Hence, we analyzed a Chinese cohort. METHODS: We studied clinical features of 9,003 Chinese patients. Gout onset age of 12 - 19 years is defined as adolescent-onset group (AG), 20 - 40 years as early-onset group (EG), and 41 - 64 years as late-onset group (LG). Multivariable regression analysis evaluated factors associated with recurrent flares, serum urate (SU) levels, and underexcretion type in AG. RESULTS: Compared with EG and LG, the AG had higher SU levels [AG: 9.5 (2.2) mg/dL, EG: 8.6 (2.1) mg/dL, LG: 7.73 (2.0) mg/dL, P < 0.001], higher percentage of positive family history of gout (AG: 41.8 %, EG: 29.6 %, LG: 24.6 %, P < 0.001), underexcretion type (AG: 62.4 %, EG: 62.5 %, LG: 58.8 %, P = 0.04), recurrent flares (AG: 78.1 %, EG: 70.3 %, LG: 68.9 %, P = 0.01). Urate-lowering therapy (ULT) initiated [OR 6.58 (95 % CI 1.35 - 32.00)] and hypercholesterolemia [OR 4.16 (95 % CI 1.28 - 13.53)] were associated with recurrent flares. eGFR was identified to be a significant variable of increasing SU levels [beta -0.24 (95 % CI -0.04 to -0.01)]. Hypertriglyceridemia [OR 0.35 (95 % CI 0.17 - 0.71)] was related to underexcretion type. CONCLUSION: Adolescent-onset gout patients had clinically distinctive features with higher SU levels, BMI, positive gout family history, underexcretion type and recurrent flares. These specific populations were less likely to achieve ULT target, requiring more clinical attention.

Advancements in NSCLC: From Pathophysiological Insights to Targeted Treatments.

With the global incidence of non-small cell lung cancer (NSCLC) on the rise, the development of innovative treatment strategies is increasingly vital. This review underscores the pivotal role of precision medicine in transforming NSCLC management, particularly through the integration of genomic and epigenomic insights to enhance treatment outcomes for patients. We focus on the identification of key gene mutations and examine the evolution and impact of targeted therapies. These therapies have shown encouraging results in improving survival rates and quality of life. Despite numerous gene mutations being identified in association with NSCLC, targeted treatments are available for only a select few. This paper offers an exhaustive analysis of the pathogenesis of NSCLC and reviews the latest advancements in targeted therapeutic approaches. It emphasizes the ongoing necessity for research and development in this domain. In addition, we discuss the current challenges faced in the clinical application of these therapies and the potential directions for future research, including the identification of novel targets and the development of new treatment modalities.

Relationship between circulating senescence-associated secretory phenotype levels and severity of type 2 diabetes-associated periodontitis: A cross-sectional study.

BACKGROUND: Senescence-associated secretory phenotype (SASP) has recently been found to drive comorbid diabetes and periodontitis by inducing a chronic, low-degree inflammatory state. Here, we sought to explore the relationship between circulating SASP and the severity of type 2 diabetes-associated periodontitis (DP). METHODS: Eighty patients (middle-aged periodontitis, M-P group; aged periodontitis, A-P group; M-DP group; and A-DP group; n = 20) provided gingival epithelium, serum, and periodontal clinical parameters. Circulating levels of 12 DP-related SASP factors were analyzed by immunoassay. Correlation between periodontal clinical parameters and circulating SASP levels was analyzed by Spearman's rank correlation coefficient and back propagation artificial neural network (BPNN). Senescence markers (p16, p21, and HMGB1) in gingiva were determined by immunofluorescence assay. RESULTS: M-DP group had increased serum levels of twelve SASP factors compared with the M-P group (p < 0.5). Serum levels of IL-6, IL-4, and RAGE were higher in the A-DP group than the A-P group (p < 0.5). The circulating concentrations of certain SASP proteins, including IL-1ß, IL-4, MMP-8, OPG, RANKL, and RAGE were correlated with the clinical parameters of DP. BPNN showed that serum SASP levels had considerable predictive value for CAL of DP. Additionally, the DP group had higher expressions of p16, p21, and cytoplasmic-HMGB1 in the gingiva than the P group (p < 0.5). CONCLUSIONS: Significantly enhanced circulating SASP levels and aggravated periodontal destruction were observed in patients with DP. Importantly, a non-negligible association between serum SASP levels and the severity of DP was found.

Molecular diagnosis of adult patients with clinically unexplained hypokalemia without hypertension demonstrated a diagnostic yield of 30.5.

Hypokalemia is a common disorder in clinical settings; however, nonmolecular diagnostic testing cannot explain some causes of hypokalemia. To determine the etiology of clinically unexplained hypokalemia without hypertension (CUHypoNH) and to obtain a diagnostic yield of monogenic hypokalemia without hypertension in adults (MHNHA), we enrolled 82 patients with CUHypoNH for whole-exome sequencing or targeted gene sequencing of genes associated with 4000 monogenic disorders. Through molecular diagnosis, 25 patients were diagnosed with monogenic hypokalemia, and a diagnostic yield of 30.5% was obtained. Among patients with MHNHA, 18 patients (18/82, 22.0% and 72% of MHNHA) with Gitelman syndrome accounted for the largest proportion. Among the 29 diagnostic variants found, eight mutations have not been reported previously; these include three point mutations, one frameshift mutation, and four exon deletions. Based on the clinical presentation of patients with CUHypoNH, the diagnostic yield of monogenic hypokalemia was the highest for chronic asymptomatic hypokalemia (8/11, 72.7%). Twenty-one patients had concomitant hypomagnesemia, when accompanied with hypocalciuria, the molecular diagnostic yield of Gitelman syndrome increased to 88.2%. Overall, this study on hospitalized adult patients explored the etiology of CUHypoNH using high-throughput sequencing. Molecular diagnosis of CUHypoNH is clinically significant in guiding precision treatment and improving disease prognosis.

Evidence From a Systematic Review and Meta-Analysis: Classical Impaired Glucose Tolerance Should Be Divided Into Subgroups of Isolated Impaired Glucose Tolerance and Impaired Glucose Tolerance Combined With Impaired Fasting Glucose, According to the Risk of Progression to Diabetes.

BACKGROUND: The American Diabetes Association (ADA) 2003 diagnostic criteria divide impaired glucose tolerance (IGT) into isolated impaired glucose tolerance with normal fasting glucose (I-IGT, IGT+NFG) and impaired glucose tolerance combined with impaired fasting glucose (IGT+IFG), while the World Health Organization (WHO) 1999 criteria do not. The aim of this meta-analysis was to evaluate whether IGT should be divided into I-IGT (IGT+NFG) or IGT+IFG according to their risk of progression to type 2 diabetes. METHODS: The MEDLINE and EMBASE were searched to identify prospective cohort studies published in English prior to April 18, 2020. Review Manager 5.3 was used to calculate the pooled risk ratios (RRs) and 95% confidence intervals (CIs) as summary statistics for each included study. RESULTS: Sixteen eligible studies (n = 147,006) were included in the analysis. The subsequent incidence of type 2 diabetes was lower in the I-IGT (IGT+NFG) group than in the IGT+IFG group (0.45 [95% CI 0.37, 0.55] according to WHO 1999 criteria and 0.59 [95% CI 0.54, 0.66] according to ADA 2003 criteria). It was higher in the I-IFG, I-IGT (IGT+NFG), and IGT+IFG groups than in the normoglycemic group (95% CI of 5.53 [3.78, 8.08], 5.21 [3.70, 7.34], and 11.87 [7.33, 19.20] according to the WHO 1999 criteria and 95% CI of 2.66 [2.00, 3.54], 3.34 [2.81, 3.97], and 6.10 [4.72, 7.88] according to the ADA 2003 criteria). In general, the incidence of diabetes in the IGT+IFG group was the highest in the prediabetic population. CONCLUSIONS: The present meta-analysis suggested that the established WHO diagnostic criteria for IGT should be revised to separately identify individuals with IGT+NFG or IGT+IFG.

Association between MRI-based visceral adipose tissues and metabolic abnormality in a Chinese population: a cross-sectional study.

BACKGROUND: Previous studies have indicated that the deposition of abdominal adipose tissue was associated with the abnormalities of cardiometabolic components. The aim of this study was to examine the relationship of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and metabolic status and the different effects between males and females. METHODS: The 1388 eligible subjects were recruited in a baseline survey of metabolic syndrome in China, from two communities in Hangzhou and Chengdu. Areas of abdominal VAT and SAT were measured by magnetic resonance imaging (MRI). Serum total triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) were measured by an automated biochemical analyzer. Metabolic abnormality (MA) was defined more than one abnormal metabolic components, which was based on the definition of metabolic syndrome (IDF 2005). Multiple logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (95%CI). Predictive value was assessed by area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI), respectively. RESULTS: Their mean age was 53.8 years (SD: 7.1 years), the mean body mass index (BMI) was 23.7 kg/m2, and 44.8% of the subjects were male. Both male and female with MA had higher VAT levels compared to subjects with normal metabolism (MN), and male had higher SAT levels than female (P < 0.05). Higher VAT was significantly associated with MA with ORs in the fourth quartile (Q4) of 6.537 (95% CI = 3.394-12.591) for male and 3.364 (95% CI = 1.898-5.962) for female (P for trend < 0.05). In female, VAT could increase the risk of metabolic abnormalities, but SAT could increase the risk of MA in the second and fourth quartiles (Q2 and Q4) only at BMI > 24 kg/m2. In male, VAT improved the predictive value of MA compared to BMI and waist circumference (WC), the AUC was 0.727 (95% CI = 0.687-0.767), the NRI was 0.139 (95% CI = 0.070-0.208) and 0.106 (95% CI = 0.038-0.173), and the IDI was 0.074 (95% CI = 0.053-0.095) and 0.046 (95% CI = 0.026-0.066). Similar results were found in female. CONCLUSIONS: In male, VAT and SAT could increase the risk of metabolic abnormalities both at BMI < 24 kg/m2 and at BMI ≥ 24 kg/m2. In female, VAT could increase the risk of metabolic abnormalities but SAT could increase the risk of MA in the second and fourth quartiles (Q2 and Q4) only at BMI > 24 kg/m2. Deposition of abdominal adipose tissue was associated with metabolic abnormalities. VAT improved the predictive power of MA.

Gray Matter and Regional Brain Activity Abnormalities in Subclinical Hypothyroidism.

Background: Subclinical hypothyroidism (SCH) brain structure and resting state of functional activity have remained unexplored. Purpose: To investigate gray matter volume (GMV) and regional brain activity with the fractional amplitude of low-frequency fluctuations (fALFF) in subclinical hypothyroidism (SCH) patients before and after treatment. Material and Methods: We enrolled 54 SCH and 41 age-, sex-, and education-matched controls. GMV and fALFF of SCH were compared with controls and between pre- and post-treatment within SCH group. Correlations of GMV and fALFF in SCH with thyroid function status and mood scales were assessed by multiple linear regression analysis. Results: Compared to controls, GMV in SCH was significantly decreased in Orbital part of inferior frontal, superior frontal, pre-/postcentral, inferior occipital, and temporal pole gyrus. FALFF values in SCH were significantly increased in right angular, left middle frontal, and left superior frontal gyrus. After treatment, there were no significant changes in GMV and the local brain function compared to pre-treatment, however the GMV and fALFF of the defective brain areas were improved. Additionally, decreased values of fALFF in left middle frontal gyrus were correlated with increased mood scales. Conclusion: In this study we found that patients with SCH, the gray matter volume in some brain areas were significantly reduced, and regional brain activity was significantly increased. After treatment, the corresponding structural and functional deficiencies had a tendency for improvement. These changes may reveal the neurological mechanisms of mood disorder in SCH patients.

Tissue-resident macrophage inflammaging aggravates homeostasis dysregulation in age-related diseases.

Organs and tissues contain a large number of tissue-resident macrophages (MΦ-Ts), which are essential for regulating homeostasis and ensuring a rapid response to injury. However, the environmental signals shaping MΦ-Ts phenotypes and the contribution of MΦ-Ts to pathological processes are just starting to be identified. MΦ-Ts isolated from aged animals or patients show alterations in morphology and distribution, defects in phagocytosis and autophagy, and loss of tissue-repair capacity. These variations are closely associated with age-associated disorders, such as inflammaging, which is characterized by cell senescence and a senescence-associated secretory phenotype (SASP) and is frequently observed in patients afflicted with chronic diseases. It seems that the role of these resident populations cannot be avoided in the treatment of aging-related diseases. This review will describe the mechanism by which MΦ-Ts support immune homeostasis and will then discuss how MΦ-Ts facilitate inflammaging and age-related diseases, which will be helpful in the development of new interventions and treatments for chronic diseases of the elderly.

Activated PPARß/δ Protects Pancreatic ß Cells in Type 2 Diabetic Goto-Kakizaki Rats from Lipoapoptosis via GPR40.

GW501516-activated peroxisome proliferator-activated receptor (PPAR) ß/δ and G-protein-coupled receptor (GPR) 40 were shown to protect pancreatic ß cells against lipoapoptosis. Therefore, this study aimed to investigate whether activated PPARß/δ could protect type 2 diabetic rats from lipoapoptosis through regulation of GPR40 and to compare the protective effects of activated PPARß/δ and PPARγ. We made an animal model of type 2 diabetic lipoapoptosis by feeding spontaneously type 2 diabetic Goto-Kakizaki (GK) rats with a high-fat diet (HFD) to evaluate the effects of PPARß/δ on islet ß cell apoptosis. And, treated INS-1 cells with 0.5 mM palmitate (PAM) in the absence/presence of GW501516 (a specific agonist of PPAR ß/δ) and with/without transfection of GPR40 siRNA to explore the underlying molecular mechanism. HFD aggravated GK rats' poorer INSR30, lower mass, greater apoptosis of ß cells, lower mass, and lower expression of GPR40, which were similarly improved by GW501516 at 3 or 6 mg/kg day and pioglitazone. Compared with pioglitazone, GW501516 caused more weight loss and had no effect on insulin resistance. GW501516 protected INS-1 cells from PAM-induced apoptosis by upregulating GPR40 and activating Akt/Bcl-2/caspase-3. Activated extracellular regulated protein kinases (ERK) was relevant to the lipoapoptosis in INS-1 cells, but was not involved in the antilipoapoptotic effect of GW501516. These results showed that the PPARß/δ agonist GW501516 protected ß cells from lipoapoptosis and improved ß cell mass by upregulating GPR40 and activating the Akt/Bcl-2/caspase-3 pathway, but not the ERK-signaling pathway.

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and moderate renal function impairment: A systematic review and meta-analysis.

AIMS: A systematic review and meta-analysis was conducted to evaluate the clinical efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) and moderate renal function impairment. METHODS: Embase, Medline, and Cochrane Central were searched, and randomized controlled trials comparing SGLT2 inhibitors to placebos and other drugs for T2D were collected. RESULTS: Seven RCTs with a total of 3307 participants were included, and the overall bias was low. In the patients with T2D and moderate renal function impairment (30 ml/min/1.73 m2 ≤ estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2) compared with the placebo, SGLT2 inhibitors improved HbA1c significantly (WMD, -0.23%; 95% CI: -0.38 to -0.08), presented a lower incidence of hypoglycemia (30.1% vs. 34.6%; RR, 0.85; 95% CI: 0.76 to 0.96), led to the reduction of eGFR (WMD, -1.74 ml/min/1.73 m2; 95% CI: -3.45 to -0.03), resulted in an obvious reduction in body weight (WMD, -1.45 kg; 95% CI: -2.01 to -0.89), and presented a similar risk of urinary tract infection and genital infection. CONCLUSIONS: SGLT2 inhibitors are safe, but mildly reduce the HbA1c level. The clinical significance of SGLT2 inhibitors in the target population was limited.

Preoperative selective vs non-selective α-blockade in PPGL patients undergoing adrenalectomy.

PURPOSE: Preoperative preparation for adrenalectomy for pheochromocytomas and paragangliomas (PPGL) is universally recognized as necessary, while the optimal strategy remains controversial. Our aims were to increase intraoperative hemodynamic stability, expedite postoperative recovery, decrease side effects and reduce costs for patients with PPGL undergoing adrenalectomy. METHODS: We identified 526 patients undergoing open adrenalectomy for PPGL in the West China Hospital of Sichuan University between May, 2007 and December, 2016. 149 patients received preoperative selective α-blockade with phenoxybenzamine, and 377 patients received non-selective α-blockade with prazosin, doxazosin or terazosin. There were no statistical differences between groups regarding preoperative patient and tumor characteristics. Operations were planned once hypertensive patients were well-controlled with blood pressure ≤130/85 mmHg. Intraoperatively, all patients received arterial blood pressure monitoring, and indwelling urinary catheters to record urine output. We recorded intraoperative hemodynamics, status in the postanesthesia or intensive care unit, postoperative recovery and complications. RESULTS: Patients in the non-selective group showed a more significant decline in postoperative systolic blood pressure than the selective group (P = 0.041). Also, patients in the non-selective group appeared to receive a long-term anti-hypertensive effect, especially for diastolic blood pressure (P = 0.037), which was a novel finding, based on the current literature. CONCLUSIONS: Our results confirmed that non-selective α-blockade produced a more significant anti-hypertensive effect than selective α-blockade. However, we found no significant difference in intraoperative hemodynamic instability, postoperative recovery and postoperative complications between groups.

The association of hypernatremia and hypertonic saline irrigation in hepatic hydatid cysts: A case report and retrospective study.

RATIONALE: Hypernatremia is a rare but fatal complication of hypertonic saline (HS) irrigation in hepatic hydatid disease. It needs careful monitoring and treatment. PATIENT CONCERNS: A 28-year-old woman with hepatic hydatid cysts who received operation treatment developed electrolyte disturbances. We also conducted a retrospective study about influence of HS application on electrolytes in patients with hepatic hydatid disease receiving surgery. DIAGNOSES: Hypernatremia, developed after HS irrigation. INTERVENTIONS: Normal saline, 5% dextrose and other supportive treatment were administered. In the retrospective study, a comparison of electrolyte and glucose fluctuation was made among different HS application groups. OUTCOMES: The patient developed hypernatremia after irrigation with HS and died from severe complications. Although some cases of complications are found, no significant relationship between HS irrigation and hypernatremia was reported according to the retrospective study. LESSONS: Hypernatremia after HS irrigation remains rare but might cause severe complications. Monitoring and appropriate treatment are needed to improve prognosis.

Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: New drugs are urgently needed for the treatment of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). The aim of this meta-analysis was to evaluate the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in NAFLD/NASH. METHODS: We searched the MEDLINE, Embase, and Cochrane Library Central to identify randomized controlled trials (RCTs) and observational studies that compared GLP-1RAs with a control treatment or baseline values with respect to efficacy and safety in patients with NAFLD/NASH. Mean differences (MDs) with 95% confidence intervals (CIs) and odds ratios (ORs) were pooled using a random-effect model. RESULTS: Six studies were eligible and included. Among the 329 NAFLD/NASH patients included in these studies, 277 patients had type 2 diabetes (T2D). GLP-1RA treatment produced significant reductions relative to baseline in liver histology scores for steatosis (MD, 0.80; 95% CI, 0.49 to 1.11), lobular inflammation (MD, 0.22; 95% CI, 0.00 to 0.45), hepatocellular ballooning (MD, 0.41; 95% CI, 0.15 to 0.67) and fibrosis (MD, 0.35; 95% CI, 0.00 to 0.70). Compared with placebo and positive agents, GLP-1RAs significantly reduced gamma-glutamyl transpeptidase (GGT) levels (MD, 13.8 U/L; 95% CI, 7.4 to 20.3; P<0.001). The reported major adverse events associated with GLP-1RA treatment included mild to moderate gastrointestinal discomfort that resolved within a few weeks. CONCLUSIONS: Our study suggests that in NASH patients, particularly patients with diabetes, GLP-1RAs may improve liver histology and reduce aminotransferase levels from baseline. Benefits of GLP-1RAs are considered to outweigh the risks in NAFLD/NASH patients with or without diabetes.

Protective Role of PPARdelta in Lipoapoptosis of Pancreatic ß Cells.

Lipoapoptosis plays an important role in the pathogenesis of type 2 diabetes. Peroxisome proliferator-activated receptor delta (PPARdelta), a vital regulator of glucose and lipid metabolism, may reduce fatty acid-induced pancreatic ß cell lipotoxicity in diabetes. However, the detailed molecular mechanisms underlying this process are not fully understood. In this study, we investigated the effect of activation of PPARdelta on palmitate-induced ß cell apoptosis, and we explored the potential mechanism of the antiapoptotic effect. The cell apoptosis was determined by DNA fragmentation analysis and Hoechst 33342 staining. The expressing of glucagon-like peptide-1 receptor (GLP-1R) in INS-1 cells was assessed by Western blotting, quantification of PCR, and was further confirmed by immunofluorescence staining. The potential of PPARdelta to interact with homologous PPRE in the GLP-1R gene was determined by Chromatin immunoprecipitation (ChIP). Our results showed that exposure of INS-1 cells to palmitate for 24 h caused a significant increase in cell apoptosis, which was inhibited by GW501516. PPARdelta exerted anti-apoptotic effects in pancreatic ß cells via the PI3 K/PKB/FoxO1 signaling pathway. Moreover, PPARdelta upregulated the GLP-1R expression under lipotoxic conditions. The ChIP assay revealed a direct binding of PPARdelta to a noncanonical PPRE motif of the GLP-1R gene in INS-1 cells. Our study suggested that the anti-apoptotic action of PPARdelta may involve its transcriptional regulation of GLP-1R and PI3 K/PKB/FoxO1 signaling. GW501516 and possible other GW-based strategies may confer additional benefit beyond improved glycemic control.

Effects on All-cause Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes by Comparing Insulin With Oral Hypoglycemic Agent Therapy: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: Retrospective, case-control studies and prospective randomized controlled trials (RCTs) on insulin treatment for diabetic patients yielded contradictory mortality and cardiovascular outcomes. We aimed to evaluate the effects of insulin versus oral hypoglycemic agents (OHAs) on all-cause mortality and cardiovascular outcomes in patients with type 2 diabetes (T2D). METHODS: We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Chinese Technical Periodicals, and Wanfang Data, up to July 10, 2015, for RCTs on insulin and OHAs that assessed all-cause mortality and/or cardiovascular death as primary end points. We derived pooled risk ratios (RRs) as summary statistics. RESULTS: Three trials were included in which 7649 patients received insulin and 8322 received OHAs, with mean (SD) diabetes duration of 5.0 (6.2) and 4.4 (5.9) years, respectively. Insulin did not differ from OHAs in all-cause mortality (RR = 1.00; 95% CI, 0.93-1.07), cardiovascular death (RR = 1.00; 95% CI, 0.91-1.09), myocardial infarction (RR = 1.04; 95% CI, 0.93-1.16), angina (RR = 0.97; 95% CI, 0.88-1.06), sudden death (RR = 1.02; 95% CI, 0.66-1.56), or stroke (RR = 1.01; 95% CI, 0.88-1.15). Insulin reduced the risk of heart failure compared with OHAs (RR = 0.87; 95% CI, 0.75-0.99). In the subgroup of secondary prevention of cardiovascular diseases (CVDs) or very high risk of CVDs, insulin did not differ from OHAs in all-cause mortality (RR = 0.99; 95% CI, 0.92-1.07), cardiovascular death (RR = 0.99; 95% CI, 0.90-1.09), myocardial infarction (RR = 1.01; 95% CI, 0.88-1.15), heart failure (RR = 0.69; 95% CI, 0.34-1.40), or stroke (RR = 1.05; 95% CI, 0.90-1.21). IMPLICATIONS: Insulin did not provide a clear benefit over OHAs in all-cause mortality or cardiovascular outcomes in the patients with T2D. Insulin therapy has many shortcomings, including inconvenience (injection, strict blood glucose monitoring), hypoglycemia, and obvious weight gain. Thus, we conclude that no robust evidence supports the active use of insulin for this population at present.

Acarbose Monotherapy and Type 2 Diabetes Prevention in Eastern and Western Prediabetes: An Ethnicity-specific Meta-analysis.

PURPOSE: Acarbose is effective in delaying or preventing the progression of prediabetes to type 2 diabetes mellitus (T2DM). The aim of this study was to assess differences in the preventive effects of acarbose in Eastern and Western populations with prediabetes. METHODS: We performed a systematic search of databases and reference lists of clinical trials conducted through August 2013. Randomized controlled trials of acarbose alone, with a minimum intervention duration of 3 years and which provided data on T2DM incidence, were included for analysis. Analyses were conducted by using Review Manager version 5.1 software. FINDINGS: Eight randomized controlled trials with 2628 participants were included. Acarbose decreased the occurrence of T2DM (number needed to treat [NNT], 6.7). Compared with the control (placebo and/or lifestyle intervention), the incidence of T2DM was significantly lower in the Eastern group (NNT, 5.9) than in the Western group (NNT, 11.1) (P < 0.0001, I(2) = 94.7%). At the end of follow-up, reversal of prediabetes to normal glucose tolerance was more likely in the Eastern group (NNT, 4.3) than in the Western group (NNT, 25) (P = 0.004, I(2) = 92%). Among those remaining prediabetic, there was no significant difference between the subtotal estimates for the subgroups (P = 0.17, I(2) = 46.5%). There was no positive correlation between preventive effect and dose, and no difference in studies with varying follow-up durations within and across either ethnic group. IMPLICATIONS: The preventive effect of acarbose on the development of diabetes seems superior in Eastern populations with prediabetes compared with Western populations.

The association between thyroid autoantibodies in serum and abnormal function and structure of the thyroid.

OBJECTIVES: To evaluate the association between thyroid autoantibodies and abnormalities in thyroid function and structure, and to investigate any risk factors. METHODS: A cross-sectional survey was undertaken in Chengdu residents ≥ 18 years with no previous thyroid disease. The study participants provided demographic and clinical data. Thyroid function and serum concentrations of the thyroid autoantibodies antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) were measured. RESULTS: A total of 1334 subjects were included in this study. The prevalence of TPOAb and TgAb positivity was significantly higher in female than in male subjects. The prevalence of thyroid autoantibodies in those with subclinical hypothyroidism and clinical hyper- and hypothyroidism was significantly greater than in euthyroid subjects. The concentration of TPOAb and TgAb in subjects with both TPOAb and TgAb was significantly higher than in those who exhibited only one type of thyroid autoantibody. Using multivariate logistic regression analysis, female sex, thyroid volume, thyroid hypo- and heteroechogenicity were found to be risk factors for the presence of autoantibodies. CONCLUSIONS: Thyroid autoantibodies were common in the general population. Women with thyroid enlargement, hypoechogenicity and heteroechogenicity might benefit from routine screening for thyroid autoantibodies and thyroid function.

PPARδ Activation Rescues Pancreatic ß-Cell Line INS-1E from Palmitate-Induced Endoplasmic Reticulum Stress through Enhanced Fatty Acid Oxidation.

One of the key factors responsible for the development of type 2 diabetes is the loss of functional pancreatic ß cells. This occurs due to a chronic exposure to a high fatty acid environment. ER stress is caused by an accumulation of irreversible misfold or unfold protein: these trigger the death of functional pancreatic ß cells. PPARδ is an orphan nuclear receptor. It plays a pivotal role in regulating the metabolism of dietary lipids and fats. However, the correlation between PPARδ of fatty acids and ER stress of pancreatic ß cells is not quite clear till date. Here, we show that PPARδ attenuates palmitate-induced ER stress of pancreatic ß cells. On the other hand, PPARδ agonist inhibits both abnormal changes in ER structure and activation of signaling cascade, which is downstream ER stress. Further, we illustrate that PPARδ attenuates palmitate-induced ER stress by promoting fatty acid oxidation through treatment with etomoxir, an inhibitor of fatty acid oxidation. It dramatically abolishes PPARδ-mediated inhibition of ER stress. Finally, we show that PPARδ could protect pancreatic ß cells from palmitate-induced cell death and dysfunction of insulin secretion. Our work elucidates the protective effect of PPARδ on the fatty-acid-induced toxicity of pancreatic ß cells.

Modified high-sucrose diet-induced abdominally obese and normal-weight rats developed high plasma free fatty acid and insulin resistance.

INTRODUCTION: Metabolically obese but normal-weight (MONW) individuals have metabolic features of overt obesity, and abdominal adiposity is common in them. Animal models of MONW individuals are lacking. We aimed to develop an abdominally obese and normal-weight (AONW) rat model. METHODS AND RESULTS: Young male Sprague-Dawley rats were fed chow or a modified high-sucrose (HS) diet for 20 weeks. The HS diet induced increased visceral adipose tissue without increased body weight, reduced glucose disposal rates, and increased hepatic glucose output during the hyperinsulinemic-euglycemic clamp, increased plasma glucose during the intraperitoneal glucose tolerance test, and increased plasma free fatty acids. Hepatic lipidosis and hepatocyte mitochondria swelling were found in HS rats through light microscopy and transmission electron microscopy; similar impairments were not observed in muscle. RT-PCR showed that mRNA expression of uncoupling protein 3 and peroxisome proliferator-activated receptor-gamma coactivator 1α increased in muscle of HS rats, while expression of mitochondrial transcription factor A, glucose transporter type 4, and insulin receptor substrate-1 did not change significantly. CONCLUSION: AONW rats developed metabolic disorders seen in MONW individuals. Steatosis, mitochondrial morphologic changes, and insulin resistance were more serious in liver than in muscle. Genes involved in fatty acid metabolism and mitochondrial function changed in less impaired muscle.