ObjectiveTo systematically evaluate the changes in placental protein expressions in gestational diabetes mellitus (GDM) and their correlations with maternal insulin resistance (IR). Methods PubMed, Cochrane Library, Scopus, Web of Science, Embase, China National Knowledge Infrastructure, VIP database, Wanfang Database and CBMdisc were searched for case-control studies published from January 2009 to November 2021, which reported the placental protein expressions in GDM and their correlations with IR. Two researchers independently reviewed the literature, extracted data and evaluated the literature quality. RevMan 5.4 software was used for meta-analysis, and descriptive analysis was performed on data that cannot be combined. ResultsA total of 19 studies were included, comprising 2 012 patients. The results of meta-analysis showed that: the expression level of retinol binding protein 4 (RBP4) [standard mean difference=2.11, 95% confidence interval (CI) (1.64, 2.58), P<0.000 01] and the positive rate of protein tyrosine phosphatase-1B (PTP1B) [relative risk (RR)=1.56, 95%CI (1.29, 1.88), P<0.000 01] were up-regulated, and the positive rate of insulin receptor substrate 1 (IRS-1) [RR=0.69, 95%CI (0.60, 0.78), P<0.000 01] was down-regulated. The protein expression levels of RBP4 (P<0.000 01) and PTP1B (P<0.000 01) were positively correlated with homeostasis model assessment of insulin resistance (HOMA-IR), while the protein expression levels of IRS-1 (P<0.000 01) and APN (P=0.002) were negatively correlated with HOMA-IR, and glucose transporter 4 (GLUT 4) was not correlated with HOMA-IR (P=0.79). Descriptive analysis found that the expression levels or positive rates of adipocytokines (leptin, resistin), oxidative stress markers (xanthione oxidase, malondialdehyde, 8-isoprostaglandin),inflammatory factors (tumor necrosis factor α, Toll-like receptor 4, Galectin-3, Galectin-2, migration inhibitory factor),fetuin-A, forkhead box transcription factor 1, forkhead box transcription factor 3a and estrogen receptor α in GDM placenta were up-regulated and all were positively correlated with HOMA-IR. The expression levels or positive rates of insulin signaling pathway proteins [phosphoinositide 3-kinase (PI3K), protein kinases B (AKT), phospho-protein kinases B (p-AKT), GLUT 4] were down-regulated, PI3K and AKT were negatively correlatedwith HOMA-IR, while p-Akt had no correlation with HOMA-IR. ConclusionsThe dysregulation of placental protein expressions may mediate maternal IR exacerbation, thus promote the occurrence and development of GDM and other pregnancy complications. The causal relationship and regulatory mechanism are still unclear, which need to be further studied.
Objective To investigate the clinical significance of insulin resistance ( IR) in chronic obstructive pulmonary disease ( COPD) .Methods Patients with stable COPD were recruited while healthy volunteers were enrolled as control. The diagnosis and severity assessment were made according to chronic obstructive pulmonary disease diagnosis and treatment guideline ( revised edition 2007) . Fasting serum levels of glucose ( FBG) , insulin ( FIN) , blood lipids, fibrinogen, C-reactive protein ( CRP) , tumor necrosis factor ( TNF-α) , and interleukin-6 ( IL-6) were measured. The degree of IR was calculated by IAI( IAI =1/FBG ×FIN) . The relationship of IR with COPD severity and above parameters was analyzed. Results A total of 121 subjects with COPD were enrolled in which 22 cases of mild COPD, 28 cases of moderate COPD,34 cases of severe COPD, and 37 cases of extremely severe COPD. The levels of FBG and FIN were significantly higher in the COPD group than those in the normal control group ( P lt;0. 05) . ISI in the COPD patients was higher than that in the controls ( - 3. 88 ±0. 54 vs. - 3. 40 ±0. 28, P lt;0. 05) . The levels of CRP, fibrinogen, TNF-α, and IL-6 were significantly higher in the COPD group than those in the control group ( P lt;0. 05) . The levels of CRP, TNF-αand IL-6 increased progressively with the severity of COPD. There was a negative correlation between ISI and the severity of COPD ( r = - 0. 512, P lt; 0. 01) , positive correlations of CRP, fibrinogen, TNF-αand IL-6 levels with COPD severity, respectively( r=0. 710, 0. 600,0. 708,0. 707, all P lt;0. 01) , and negative correlations of ISI with the levels of CRP, fibrinogen, TNF-α and IL-6 ( r = - 0. 384, - 0. 240, - 0. 298, - 0. 396, all P lt; 0. 01) , respectively. Conclusion There is an increase in fasting serum insulin and insulin resistance in patients with COPD compared with healthy subjects, which deteriorates with severity of COPD.
Objective To investigate the changes of CD4 + CD25 + Foxp3 + regulatory T cells( Treg) in peripheral blood of patients with acute exacerbation of COPD( AECOPD) , and analyze the relationship of CD4 + CD25 + Foxp3 + Treg with insulin resistance. Methods A total of 79 patients with AECOPD were divided into four groups according to disease severity( 11 cases in stage Ⅰ,31 cases in stage Ⅱ,28 cases in stage Ⅲ, an 9 cases in stage Ⅳ) .42 healthy volunteers were recruited as control. Fast blood glucose( FBG) and fast insulin( FINS) were measured for calculating the insulin resistance index. The CD4 + CD25 + Foxp3 + Treg were detected by flow cytometry. The relationship between the proportion and number of CD4 + CD25 + Foxp3 + Treg with insulin resistance was statistically analyzed. Results Compared with the healthy control group, the levels of FBG, FINS, and insulin resistance index in the AECOPD patients were significantly higher ( P lt; 0. 01, P lt; 0. 05) . The proportion and number of CD4 + CD25 + Foxp3 + Treg in peripheral blood decreased significantly( P lt; 0. 01, P lt; 0. 05) . The insulin resistance index increased with the severity of AECOPD while the proportion and number of CD4 + CD25 + Foxp3 + Treg in peripheral blood decreased. The insulin resistance index in the AECOPD patients of stage Ⅲ and Ⅳ were higher than those of stage Ⅰ and Ⅱ. The proportion and number of CD4 + CD25 + Foxp3 + Treg in the AECOPD patients of stage Ⅲ and Ⅳ were significantly lower than those of stage Ⅰ and Ⅱ. Both the proportion and number of CD4 + CD25 + Foxp3 + Treg were negatively correlated with insulin resistance ( r = - 0. 633, - 0. 871, P lt; 0. 01) . Conclusions CD4 + CD25 + Foxp3 + Treg cells might may play important role in modulating insulin resistance in AECOPD. The more serious the disease, the lower the CD4 + CD25 + Foxp3 + Treg and the worse insulin resistance.
ObjectiveExploring the potential causal effects and directions of insulin resistance (IR) and chronic airway inflammatory diseases, including asthma and chronic obstructive pulmonary disease (COPD), through two sample Mendelian randomization (MR). MethodsA total of 53 validated single nucleotide polymorphisms (SNPs) associated with IR were selected as instrumental variables. The inverse variance-weighted (IVW) method was used to model the causal association, and sensitivity analyses through leave-one-out analysis and pleiotropy testing were conducted to assess the relationship between IR and asthma and COPD. ResultsMR analysis revealed no significant causal effect of IR on asthma (IVW: OR=1.067, 95%CI 0.871 to 1.306, P=0.531) or COPD (IVW: OR=0.906, 95%CI 0.686 to 1.196, P=0.557). The results were consistent across sensitivity analyses and multiple pleiotropy tests, with no evidence of horizontal pleiotropy detected. ConclusionNo causal association was found between IR and the development of asthma or COPD. The relationship between these conditions may be influenced indirectly through complex interactions between metabolic and inflammatory pathways affecting disease progression.
Objective We investigated the effect of supplementation with alanyl-glutamine dipeptide on insulin resistance and outcome in patients with chronic obstructive pulmonary disease (COPD) and respiratory failure. Methods A prospective, randomized, open and controlled trial was conducted. Patients with COPD and respiratory failure were recruited between Jan 2005 to Feb 2006 and randomly assigned to a trial group (n=14) with glutamine dipeptide supplmented parenteral nutrition and a control group (n=16) with isocaloric, isonitrogenic parenteral nutrition. On the third day and fifth day of nutrition treatment, blood glucose was clamped at level of 4.4 to 6.1 mmol/L by intravenously bumped insulin. Blood gas, blood glucose level, insulin dosage were recorded everyday. The outcomes were mortality, length of stay (LOS) in hospital and in ICU, mechanical ventilation times and the costs of ICU and hospital.Results Thirty patients successfully completed the trial. There was no difference in blood gas between two groups, but PaO2 increased gradually. Compared with control group, blood glucose level had trend to decrease in trial group. The average insul in consumption decreased significantly in trial group on the fifth day. There was no statistical difference between two groups in mortality, length of stay in hospital and the costs of hospital. But compared with control group, length of stay in ICU and mechanical ventilation days had trend to decrease in trial group. Conclusion Alanyl-glutamine dipeptide do not improve pulmonary function of patients with COPD and respiratory failure. However, alanyl-glutamine dipeptide attenuated insul in resistance and stabilized blood glucose. This trial does not confirm alanyl-glutamine di peptide can improve outcome in critically ill patients with COPD and respiratory failure between two groups in mortality at the end of 30 days, length of stay in hospital and the costs of hospital. But the length of stay in ICU and the duration of mechanical ventilation does decrease, but not significantly, in the trial group.
Objective
To explore the association between 25-hydroxyvitamin D (25OHD) level and risk of the onset of metabolic syndrome (MS) in people in Chengdu.
Methods
In total, 474 participants were selected randomly by cluster sampling from one urban district and two rural villages in Longquanyi district of Chengdu. The data of sociodemographic information, lifestyle and family history were collected by questionnaires. Binary logistic regression was performed to assess the relationship between baseline 25OHD level and incident of MS, while multiple linear regression was conducted to analyze the relationship between baseline 25OHD level and insulin resistance.
Results
Four hundred seventy-four people were enrolled in the cohort study, 39 of them developed MS, with the incidences of 20.8 events per 1 000 person years. Among women, low 25OHD status was significantly associated with the risk of developing MS (OR=4.29, 95%CI 1.05 to 29.50, P=0.044) after adjustment for multiple potential confounders. In a multiple linear regression analysis, low 25OHD level of baseline was independently associated with the increased HOMA-IR over a 4-year period among Chengdu individuals (P<0.05) and was independently related to the decreased ISIcomp over a 4-year period in female (P<0.05).
Conclusions
The current prospective study suggests that low 25OHD level may contribute to increase insulin resistance in Chengdu population. Furthermore, low 25OHD level may increase the risk of MS among women in Chengdu.
Objective To evaluate the efficacy and safety of testosterone supplementary treatment for the middle-aged and the senile with insulin resistance (IR). Methods Such databases as PubMed (Jan. 1966 to July 2010), EMbase (Jan. 1984 to July 2010), The Cochrane Library (Issue 3, 2010), CBM (1978 to July 2010), CNKI (Jan. 1994 to July 2010), WanFang Data (1994 to July 2010) and VIP Data (1989 to July 2010) were searched. Randomized controlled trials (RCTs) about testosterone treatment for IR were included. Two reviewers independently extracted the data and evaluated the quality of the included studies. Meta-analyses were performed for the results of homogeneous studies by using RevMan 5.0 software, and other results not suitable for meta-analysis were described with qualitative analyses. Results Nine RCTs involving 573 patients were included. Of them, 308 cases were in the testosterone group and 265 in the placebo group. The baseline data of studies was comparable. The results of meta-analyses showed that, a) Efficacy: testosterone was superior to placebo in decreasing insulin resistance index (HOMA-IR) (WMD= –?0.56, 95%CI –?0.75 to –?0.37) and fasting insulin (FINS) (WMD= –2.4, 95%CI –3.25 to –1.56); and b) Safety: no significant difference was found in prostate specific antigen (PSA) (WMD= –?0.02, 95%CI –?0.22 to 0.18). Conclusion The testosterone supplementary treatment for insulin resistance is superior to the placebo, and there is no significant difference in PSA compared to the placebo. More multicenter double-blind RCTs in large-scale are required to verify this conclusion because of lack of high quality literature with large sample size.
Objective To evaluate the effects of saxagliptin on β cell function of type 2 diabetic patients. Methods The Cochrane Library, PubMed, EMbase, CBM, VIP, and CNKI were searched from their establishment to November, 2011, for relevant randomized controlled trials on the effects of saxagliptin on β cell function in type 2 diabetic patients. Language was limited to Chinese and English only. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and evaluated and cross-checked the methodological quality. Then meta-analysis was conducted using RevMan 5.0 software. Results Five RCTs were included. The results of meta-analysis showed that: HOMA-B was significantly increased in the saxagliptin (or saxagliptin plus routine treatment) 2.5 mg, 5 mg, and 10 mg groups (MD=8.03, 95%CI 4.57 to 11.48, Plt;0.000 01; MD=7.50, 95%CI 4.27 to 10.73, Plt;0.000 01; MD=17.45, 95%CI 13.93 to 20.97, Plt;0.000 01); HOMA-IR was similar between saxagliptin 2.5 or 10 mg group, and control group (MD= –0.05, 95%CI –0.18 to 0.08, P=0.47; MD= –0.18, 95%CI –0.60 to 0.24, P=0.4). Conclusion Current evidence shows that saxagliptin is effective in improving β cell function and insulin resistance. Due to short follow-up and small sample size, this conclusion has to be further proved by more high-quality RCTs.
ObjectiveTo explore the effect of gastric bypass (GBP) on metabolic syndrome (MS) and the related mechanisms. MethodsThe literatures addressed the effect of GBP on glucose metabolism and blood pressure were retrospectively analyzed. ResultsIt showed that GBP achieved durable level of blood glucose, remission of dylipidemia and hypertension, however, which occurred before significant weight loss. The changes of many factors such as food intake, gastrointestinal hormones, adipocytokines, fat distribution might be involved in GBP to improve MS. ConclusionGBP seems to achieve the control of MS as a primary and independent effect, rather than secondary to the treatment of overweight.
ObjectiveTo investigate the relationship between glucose metabolism and endocannabinoid system (ECS) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).MethodsA total of 64 OSAHS patients (18 cases of mild OSAHS, 24 cases of moderate OSAHS, 22 cases of severe OSAHS) and 24 controls were included in the study. Body mass index, waist circumference, fasting blood lipids, fasting blood glucose, fasting blood insulin, homeostasis model of assessment for insulin resistance index (HOMA-IR), polysomnography and endogenous cannabinoid receptor 1 (CB1R) protein expression levels in peripheral blood mononuclear cells (PBMC) were measured in participants.ResultsThe incidence of diabetes and impaired fasting glucose (IFG) in the OSAHS group was significantly higher than that in the control group (28.12% vs. 8.33%). With the increase of apnea hypopnea index (AHI), HOMA-IR and the expression levels of CB1R protein increased gradually (HOMA-IR: 2.40±0.90, 2.34±0.59, 2.94±0.99, 3.46±0.77, respectively; CB1R protein: 0.04±0.01, 0.37±0.09, 0.40±0.07, 0.62±0.14, respectively). Correlation analysis showed that HOMA-IR, AHI and the expression of CB1R protein were significantly positively correlated with each other (P<0.05).ConclusionOSAHS patients are prone to insulin resistance, IFG and diabetes mellitus, which are closely related to the activation of ECS induced by OSAHS.
