Insulin resistance as a predictor of incident asthma‐like symptoms in adults

Background There is accumulating evidence that obesity is associated with an increased risk of asthma. It has been hypothesized that insulin resistance may be involved in obesity‐induced asthma, but till date there is no prospective data on this issue. Objective To investigate the association of obesity and insulin resistance with the incidence of asthma‐like symptoms in adults. Methods Out of a random sample of 12 934 persons from a general population, 6784 (52.5%) were included and participated in a health examination in 1999–2001. After 5 years they were re‐invited and 4516 (66.6%) participated at follow‐up. At baseline three obesity measures were considered: body mass index, waist circumference, and waist‐to‐hip ratio. In addition, fasting glucose and insulin were measured for determination of insulin resistance. Information on asthma‐like symptoms at baseline and follow‐up were obtained by questionnaires. A total of 3441 participants defined as non‐asthmatic at baseline and with complete information on all the considered variables were included in the analyses. Data were controlled for confounding by sex, age, social status, and smoking. Results All obesity measures were associated with incident wheezing and asthma‐like symptoms. In addition, insulin resistance was associated with incident wheezing [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.38–2.54] and asthma‐like symptoms (OR 1.61, 95% CI 1.23–2.10). The effect of insulin resistance was stronger than that of obesity and was independent of sex. Conclusion We found that insulin resistance was associated with an increased risk of developing asthma‐like symptoms. This finding supports the hypothesis that obesity and asthma may be linked through inflammatory pathways also involved in insulin resistance.     

Association of obesity and insulin resistance with asthma and aeroallergen sensitization

Background:  It has been hypothesized that obesity and insulin resistance may play a role in the development of asthma and allergy. The aim of the study was to examine the association of obesity and insulin resistance with asthma and aeroallergen sensitization.
Methods:  Cross-sectional population-based study of 3609 Danish men and women aged 30–60 years. Aeroallergen sensitization was defined as positive levels of specific IgE against a panel of inhalant allergens. Asthma was defined as self-reported physician diagnosed asthma. Allergic asthma was defined as the presence of both asthma and aeroallergen sensitization. The homeostasis model assessment of insulin resistance was used to estimate the degree of insulin resistance. Body mass index, waist-to-hip ratio, and waist circumference were used as measures of obesity. Data were analyzed by multiple logistic regression analyses.
Results:  Obesity was associated with increased risk of aeroallergen sensitization as well as allergic and nonallergic asthma. Insulin resistance was asssociated with aeroallergen sensitization and allergic asthma, but not nonallergic asthma. The associations of obesity with aeroallegen sensitization and allergic asthma became nonsignificant after adjustment for insulin resistance, whereas the association of obesity with nonallergic asthma was unaffected. No sex-differences were observed.
Conclusion:  Obesity may be related to an increased risk of aeroallergen sensitization and allergic asthma through mechanisms also involved in the development of insulin resistance.     

The impact of obesity and insulin resistance on the outcome of IVF or ICSI in women with polycystic ovarian syndrome

The impact of insulin resistance on the outcome of IVF or intracytoplasmic sperm injection (ICSI) in women with polycystic ovarian syndrome (PCOS) was examined. Insulin sensitivity was measured by the continuous infusion of glucose with model assessment (CIGMA) test. Insulin-resistant (n = 26) and non-insulin-resistant women (n = 30) with PCOS underwent a total of 100 cycles of long-term down-regulation with buserelin acetate, stimulation with human recombinant FSH, and IVF or ICSI. Blood samples were taken throughout ovarian stimulation for hormone assays. Insulin-resistant and non-insulin-resistant women had similar concentrations of FSH, LH, testosterone and androstenedione throughout stimulation, but insulin-resistant women had hyperinsulinaemia and lower sex hormone binding globulin concentrations. Insulin-resistant women also had lower oestradiol concentrations during stimulation and required higher FSH doses, but these differences disappeared after controlling for the higher body weight in the group of insulin-resistant women. Groups had similar number of oocytes collected, similar implantation and pregnancy rates, and the incidence of ovarian hyperstimulation syndrome was also similar. Obesity, independent of hyperinsulinaemia, was related to a lower oocyte count and increased FSH requirement. It is concluded that in PCOS women receiving long-term down-regulation and stimulation with recombinant FSH, insulin resistance is neither related to hormone levels nor to IVF outcome. Obesity, independent of insulin resistance, is associated with relative gonadotrophin resistance.     

Newly identified set of obesity-related genotypes and abdominal fat influence the risk of insulin resistance in a Korean population

We aimed to identify obesity-related single-nucleotide polymorphism (SNP) loci in a Korean population and construct an obesity genetic risk score (GRS) to examine the association of the genetic predisposition to obesity with insulin resistance (IR). In total, 9675 subjects were included, and 7666 of these subjects were used for replication. A GRS was constructed using the SNP loci that overlapped in both cohort sets. The subjects showed a trend toward an increase in body mass index, waist circumference, systolic/diastolic blood pressure, homeostatic model assessment (HOMA)-IR, HOMA-B, and levels of insulin, triglyceride, and alanine aminotransferase across the tertiles of obesity GRS, while the adiponectin level showed a trend toward a decrease with increasing GRS. The associations between the obesity GRS and the measures of fasting insulin, HOMA-IR, and adiponectin were significant after adjusting for confounding factors. Moreover, a significant association between obesity GRS and HOMA-IR was observed in subjects with abdominal obesity. The present results indicate that a predisposition to obesity may affect IR in the Korean population and that abdominal fat may alter or modify the genetic effects. Furthermore, the set of obesity-related genotypes and abdominal fat may play interactive roles in determining the risk of IR.     

Effects of glutathione S-transferase M1, T1 and P1 on lung function in asthmatic families

RATIONALE: Previous data have suggested that glutathione-S-transferase (GST) genotypes are important in determining the rate of lung function growth in childhood. This effect was most marked in Caucasian children with asthma. OBJECTIVES: We investigated the association of lung function with GSTM1, GSTP1 and GSTT1 genotypes in Caucasian families with asthma. METHODS: Four hundred and eighteen children and 316 parents from 224 Caucasian families were recruited via a child with asthma, the proband. Associations between lung function and GST genotype were determined using multilevel models. RESULTS: There were no observed associations between lung function and GST genotype in parents. However, in the children, the GSTP1 val(105)/val(105) and GSTM1 null genotypes were associated with significantly higher forced expiratory volume in 1 s (FEV(1)) and FVC values as percentage of predicted. This effect was not statistically significant in the probands but was marked in their siblings in whom GSTP1 val(105)/val(105) was associated with 9.4% higher FEV(1) and 10.7% higher FVC (P=0.005 and 0.001, respectively). The GSTM1 null genotype was associated with a 6.7% higher FEV(1) and 4.1% higher FVC (P=0.003 and 0.063, respectively). These effects remained significant after correcting for the confounders of individual atopic status, tobacco smoke exposure and familial aggregation of lung function values. CONCLUSIONS: GSTM1 and GSTP1 genotypes are important determinants of lung function in childhood. The smaller differences seen in probands are predicted by a simple model in which more rapid decline in lung function is seen in these individuals.     

姜黄素活化肝细胞Nrf2抗氧化系统效应及缓解胰岛素抵抗作用机制研究

目的探讨姜黄素对HepG2细胞Nrf2信号功能的调控作用与其改善胰岛素抵抗的效应关系,并进一步研究高脂饮食诱导小鼠胰岛素抵抗时姜黄素干预对肝脏Nrf2系统功能及糖异生作用的影响。方法在人肝癌细胞HepG2上分别用葡萄糖氧化酶（GO）或长期胰岛素处理,分别制成氧化应激和高胰岛素血症胰岛素抵抗模型;用蛋白印迹方法（WB）检测姜黄素对Nrf2抗氧化系统的作用。另外,对细胞进行短时胰岛素刺激,观察胰岛素信号（PKBSer473磷酸化水平）变化。为研究姜黄素的整体动物药物作用,在高脂诱导的胰岛素抵抗小鼠模型用姜黄素进行干预（雄性C57BL/6J小鼠,给予高脂饲料加上3%的姜黄素）,在第25周进行丙酮酸耐量实验,并于第27周取肝脏组织检测Nrf2系统功能变化。结果姜黄素可明显激活HepG2细胞Nrf2系统,并对抗GO氧化应激所致的PKB磷酸化损害。在高脂饲喂小鼠胰岛素抵抗模型,姜黄素可改善丙酮酸耐量,提示其增强胰岛素作用（抑制肝脏糖异生）,从而缓解肝脏糖代谢异常;姜黄素还明显激活高脂肥胖小鼠肝脏受抑制的Nrf2信号功能。结论姜黄素通过增强内源性Nrf2系统功能对抗氧化应激,是其缓解肝细胞胰岛素抵抗的重要药理机理。     

不同治疗方式对新发2型糖尿病患者胰岛β细胞功能及胰岛素抵抗的影响

目的 比较采用胰岛素治疗(INS)与口服降糖药物治疗(OHA)等不同治疗方式对新发2型糖尿病(T2DM)患者胰岛β细胞功能及胰岛素抵抗的影响,推断新发T2DM的最佳治疗方案.方法 将62例新发T2DM患者随机分为胰岛素治疗组(INS组)和口服降糖药物组(OHA组).OHA组首选磺脲类或二甲双胍,或二者合用,疗效欠佳时增加噻唑烷二酮类,一般为2药或3药合用.两组治疗期均为3个月.每组根据血糖调整剂量,目标为空腹血糖(FBG)＜6.0 mmol/L,餐后2h血糖(2hPG)＜8.0mmol/L.观察两组治疗前后FBG、2h PG、糖化血红蛋白(HbA1C)、空腹胰岛素(FINS)、空腹及餐后2hC肽(FCP、2hCP)水平的变化;用稳态模型(Homa)计算胰岛β细胞功能指数(Homaβ=20×FINS/(FBG-3.5)和胰岛素抵抗指数[HomaIR=(FBG×FINS)/22.5].用治疗后CP、Homaβ、HomaIR等相关指标进行组间比较,以评价胰岛β细胞功能及外周胰岛素抵抗的变化.结果 :(1)治疗后,两组患者FBG、2hPG、HbA1C水平较治疗前均有明显下降(P＜0.01),而在两组间比较差异无统计学意义;(2)治疗后,INS组患者FINS、FCP、2hCP、Homaβ较治疗前升高(P＜0.05),OHA组则无明显变化(P＞0.05),两组间比较差异有统计学意义(P＜0.05);(3)治疗后,INS组患者HomaIR较治疗前有明显下降(P＜0.05),OHA组仅略有下降,两组间比较差异有统计学意义(P＜0.05).结论 早期应用胰岛素治疗可以改善新发T2DM患者胰岛β细胞分泌功能及外周胰岛素抵抗.与OHA相比,INS能更好地保护患者的胰岛B细胞功能.     

Obesity is associated with insulin resistance and components of the metabolic syndrome in Lebanese adolescents

Background: Prevalence of metabolic syndrome (MS) in obese adolescents has been reported to range between 18–42%, depending on country of origin, thus suggesting an ethnic-based association between obesity and MS.

Aim: This study aims to investigate the magnitude of the association between obesity, insulin resistance and components of MS among adolescents in Lebanon.

Subjects and methods: The sample included 263 adolescents at 4^th and 5^th Tanner stages of puberty (104 obese; 78 overweight; 81 normal weight). Anthropometric, biochemical and blood pressure measurements were performed. Body fat was assessed using dual-energy X-ray absorptiometry.

Results: According to International Diabetes Federation criteria, MS was identified in 21.2% of obese, 3.8% of overweight and 1.2% of normal weight subjects. The most common metabolic abnormalities among subjects having MS were elevated waist circumference (96.2%), low HDL (96.2%) and hypertriglyceridemia (73.1%). Insulin resistance was identified in all subjects having MS. Regression analyses showed that percentage body fat, waist circumference and BMI were similar in their ability to predict the MS in this age group.

Conclusions: MS was identified in a substantial proportion of Lebanese obese adolescents, thus highlighting the importance of early screening for obesity-associated metabolic abnormalities and of developing successful multi-component interventions addressing adolescent obesity.     

Weight reduction improves markers of hepatic function and insulin resistance in type-2 diabetic patients with non-alcoholic fatty liver

Objective

The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing dramatically affecting up to 30% of the population worldwide. At present, treatment options are limited and pharmacological management of NAFLD has had disappointing results. Some of the best available evidence to improve NAFLD concerns lifestyle modification.

Objective

To detect the degree of weight reduction needed to improve the markers of hepatic function and insulin resistance in type-2 diabetics with NAFLD.

Methods

One hundred type-2 diabetic male patients with NAFLD were included into this study and divided into two equal groups. Group (A) received aerobic exercise training in addition to diet regimen. Group (B) received no treatment intervention.

Results

There was a 26.99%, 40.8%, 33.81%, 32.73%, 37.8% and 15 % reduction in mean values of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma - Glutamyltransferase (GGT) and Homeostasis Model Assessment-Insulin Resistance-index (HOMA-IR) and BMI respectively in group (A) at the end of the study. While there were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment.

Conclusion

About 15 % reduction in BMI is effective to improve the liver condition and insulin resistance in type-2 diabetics with NAFLD.     

胰岛素抵抗对糖尿病患者心功能的影响

目的:探究分析胰岛素抵抗对糖尿病患者心功能的影响.方法:选择2015年1月至2018年3月在我院内分泌科就诊的156例2型糖尿病患者进行回顾性分析,根据患者胰岛素抵抗指数将所有患者分为胰岛素抵抗组(胰岛素抵抗指数≥2.69,n=82),非胰岛素抵抗组(胰岛素抵抗指数<2.69,n=74),并选取同时期在我院体检的和78...     

Effect of obesity on airway inflammation: a cross-sectional analysis of body mass index and sputum cell counts

BACKGROUND: Several observational studies have demonstrated an association between obesity and asthma. Studies evaluating exhaled nitric oxide levels and obesity have revealed that a higher body mass index (BMI) is associated with elevated exhaled nitric oxide levels. Airway inflammation using sputum cell counts has not been assessed in obese patients with airway diseases. OBJECTIVE: The primary aim of this study was to determine whether obesity (based on BMI) is associated with eosinophilic or neutrophilic bronchitis. METHODS: The results from a database of induced sputum cell counts were compared with BMI and analysed using correlation statistics, regression and parametric and non-parametric analysis. RESULTS: Seven-hundred and twenty-seven adult participants with an equal number of sputum samples were included in the analysis. BMI varied from 14.5 to 55 kg/m(2). Sputum total cell count (mean+/-SD: 12.9 x 10(6) cell/g+/-21.5), eosinophil percent (median; min to max: 0.3%; 0-89.0), and neutrophil percent (mean+/-SD: 63.5+/-26.6%) were within normal limits. Participants with asthma had a higher percentage of sputum eosinophils than those without asthma (P=0.01). However, there was no difference in the total or differential cell counts among the obese and non-obese participants, when the data were analysed according to BMI category, gender, dose of inhaled corticosteroid, and presence or absence of asthma. CONCLUSION: In this large sample of adult asthmatic and non-asthmatic participants, there was no association between BMI and airway inflammation measured by sputum cell counts. Other mechanisms to explain the relationship between obesity and asthma will need to be explored if this association is to be better understood.     

The relationship between anti-Mullerian hormone, androgen and insulin resistance on the number of antral follicles in women with polycystic ovary syndrome

BACKGROUND: Anti-Müllerian hormone (AMH) is a biomarker that predicts the number of antral follicles and is involved in follicle arrest for women with polycystic ovary syndrome (PCOS). We investigated the association between the characteristic hyperandrogenemia, insulin resistance (IR), AMH, and the morphology and size of ovaries for women with PCOS. METHODS: A total of 99 Taiwanese women with PCOS who were willing to undergo vaginal ultrasonography were enrolled in this cross-sectional study. RESULTS: The number of antral follicles and the ovarian volume showed a significant correlation with AMH, total testosterone and the free androgen index, but not with age, body mass index (BMI) or the homeostasis model assessment of insulin resistance (HOMA-IR). AMH had a significant negative association with both BMI and HOMA-IR. Multiple stepwise regression analysis demonstrated that AMH, BMI and total testosterone were independently related to the number of antral follicles. AMH and total testosterone were the main determinants for ovarian volume in a stepwise regression model. CONCLUSIONS: Our results suggest that not only the AMH level, but also obesity, IR and elevated androgen levels may relate to the development of the large size of antral follicle pool and ovarian volume in women with PCOS. Obesity and IR may enhance the follicular excess through the dysregulation of AMH or through the pathway of hyperandrogenemia. These findings might partly explain why adequate body weight management and improvement in IR can improve the ovulatory function for women with PCOS.     

Clinical effects of air filters in homes of asthmatic adults sensitized and exposed to pet allergens

BACKGROUND: Despite medical advice, many pet-allergic asthma sufferers refuse to remove the pet to which they are sensitized from their home. OBJECTIVE: We aimed to assess the clinical effects of air cleaners in the homes of adult asthma patients sensitized and exposed to cats and/or dogs. METHODS: We performed a randomized, parallel-group study of 30 asthmatic adults sensitized to and sharing a home with cats or dogs. The effects of placing air cleaners in the living room and bedroom for 12 months and using high efficiency particulate air filter vacuum cleaners (active group) were compared with using these vacuum cleaners alone (control group). Measures of airway responsiveness, treatment requirement, lung function, peak flow, reservoir and airborne allergen were recorded before, during and after the interventions. A beneficial clinical response was assessed in terms of a 'combined asthma outcome'. This was defined as a two or more doubling dose improvement in bronchial hyper-reactivity to histamine and/or a reduction in treatment requirement of at least one step change on the British Thoracic Society guidelines for asthma treatment. RESULTS: A beneficial clinical response was observed in 10/15 subjects in the active group compared with 3/15 in the control group after 12 months intervention (P = 0.01). No significant differences between the active and control groups were detected for changes in measures of lung function, reservoir pet allergen and airborne pet allergen during the study. CONCLUSION: Whilst the study design has not allowed complete exclusion of a placebo effect, we believe that this pragmatic study of adult asthmatic patients sensitized and exposed to pets resulted in a small, but significant improvement in combined asthma outcome.     

替米沙坦对胰岛素抵抗大鼠肾脏脂联素受体1及其mRNA表达的影响

目的探讨替米沙坦对胰岛素抵抗大鼠肾脏脂联素受体1(AdipoR1)及其mRNA表达的影响。方法采用长期高脂喂养建立胰岛素抵抗大鼠模型,并用正常血糖-高血浆胰岛素钳夹技术评估。光镜下行肾脏形态学检查,RT-PCR检测分析AdipoR1 mRNA表达,免疫组化染色观察AdipoR1蛋白水平变化。结果胰岛素抵抗大鼠肾脏AdipoR1 mRNA及其蛋白质表达明显低于正常对照组(均P<0.05),同时大鼠肾脏出现病理变化;替米沙坦干预后,肾组织AdipoR1 mRNA及其蛋白质表达较胰岛素抵抗组升高(P<0.05),同时肾脏病理变化也得到明显改善。结论替米沙坦保护胰岛素抵抗相关的肾脏损伤的作用可能与其调节肾脏AdipoR1的表达相关。     

抵抗素在肝脏胰岛素抵抗中的作用及其机制

目的： 探讨抵抗素在肝脏胰岛素抵抗中的作用及其可能的机制。方法： 将载有抵抗素基因的重组腺病毒经尾静脉注射构建高抵抗素血症小鼠模型,同时设正常对照组及病毒对照组,取肝脏组织切片行PAS糖原染色半定量观察肝糖代谢的变化;以Western blotting检测肝腺苷酸活化蛋白激酶（AMPK）的磷酸化,以磷酸化AMPK/总AMPK的比值代表AMPK激活程度;以实时 PCR检测肝组织糖异生关键酶葡萄糖6磷酸酶（G6Pase）和磷酸烯醇式丙酮酸羧激酶（PEPCK）mRNA表达水平的变化。结果： 重组腺病毒注射第5 d,获得血中抵抗素高表达构建了高抵抗素血症动物模型,糖原染色示高抵抗素血症小鼠肝糖原含量较正常对照及病毒对照组降低,分别为0.78±0.06 vs 0.93±0.13、0.89±0.05（P<0.05）;高抵抗素血症组肝AMPK磷酸化水平较正常对照及病毒对照组下降, 磷酸化AMPK/总AMPK比值分别为0.78±0.06 vs 0.93±0.13、 0.89±0.05（P<0.05）。高抵抗素血症小鼠G6Pase和PEPCK 的mRNA表达升高,高抵抗素血症组、对照组及空载病毒组G6Pase分别为2.136±0.857 vs 1.353±0.490、 1.250±0.770 （P<0.05）;高抵抗素血症组、对照组及空载病毒组 PEPCK分别为3.54±0.90 vs 2.75±0.78、 2.63±0.67（P<0.05）。结论： 抵抗素可能通过抑制肝脏AMPK活性,增加肝糖异生关键酶的表达而影响机体肝糖代谢,降低肝糖储量,参与肝脏胰岛素抵抗的形成。     

老年支气管哮喘急性发作诱因分析及肺功能变化

目的探讨老年支气管哮喘患者急性发作的诱发因素及肺功能变化。方法筛选2008年1月至2010年12月典型的老年支气管哮喘急性发作患者88例（年龄60～78岁）,采用问卷调查方式,以非条件Logistic回归法分析其诱发因素;常规治疗前后测定肺功能。结果88例老年患者均按要求完成问卷。非条件logistic回归分析显示周围环境空气污染（如使用煤球烹饪等）、吸烟、每日吸烟支数、受教育程度、近期呼吸系统感染与支气管哮喘具有明显相关性（r=0．378～0．489,P〈0．05）。治疗前后第一秒用力呼气容积（FEV1）、FEV1／预计值、肺内气体最大呼出流速（PEF）的比较有显著差异（P〈0．05）。结论诱发老年支气管哮喘急性发作的因素较多,医护人员应对相关人群进行健康教育。老年支气管哮喘急性发作期患者肺功能受损,进行常规治疗,疗效良好。