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.
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.
Abstract： Objective To investigate the effect of preoperative oral carbohydrate （CHO） administration on perioperative risks of patients with surgical thoracic oncology，and provide evidence for establishing new scientific preoperative fasting strategy.Methods?In this prospective study， from July to September 2010，32 out of 65 enrolled patients with surgical thoracic oncology in Department 1 of Thoracic Surgery，Cancer Hospital of Peking University， were randomly allocated to preoperative experiment group （fasting overnight and oral 12.5% dextrose 400 ml administration 2 h before anesthesia induction） or control group （fasting overnight and water deprivation from midnight）. Clinical data were collected including subjective evaluation of thirst and hunger measured by visual analogue scale （VAS）， blood glucose level（BGL），serum insulin level， homeostasis model assessment insulin resistance（HOMA-IR），postoperative length of hospital stay （LOS） and complications.Results?Sixteen patients were enrolled in each group. VAS scores of thirst and hunger of the preoperative experiment group at 1 h before anesthesia induction were significantly lower than those of the control group（24 vs. 49，24 vs. 62 ，P=0.000）. BGL（8.59±0.43 mmol/L vs. 5.59±0.43 mmol/L， P=0.000）， serum insulin level （24.33±1.80 mIU/ ml vs. 16.28±1.80 mIU/ml， P=0.004）and HOMA-IR（9.23±0.77 vs. 4.03±0.77，P=0.000）of the preoperative experiment group before anesthesia induction were significantly higher than those of the control group，and these three variables of the preoperative experiment group returned to baseline level soon after surgery. There was no statistical difference in postoperative LOS and complication rate between the two groups （P＞0.05）.Conclusion?Preoperative oral CHO treatment is safe for non-diabetic patients with surgical thoracic oncology， can alleviate their subjective discomfort，decrease insulin resistance， and ameliorate their perioperative stress and metabolism.
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.
Objective To assess the tolerance of preoperative carbohydrate-rich beverage, to determine its effect on postoperative insulin resistance and analyze its potential mechanism. Methods Thirty-two patients undergoing elective colorectal cancer resection were recruited to this randomized controlled study and assigned to two groups at random. Patient in control group was fasted before operation, while patient in study group was given oral water. Homeostasis model assessment (HOMA) indexes, activity of PTK, and mRNA and (or) protein expressions of PKB, PI3K and GluT4 were measured before and (or) immediately after surgery. Furthermore preoperative well-beings of patients were studied. Results Among well-beings, feeling of thirst, hunger and anxiety tended to be better in patients receiving carbohydrate-rich beverages compared with fasted ones (P＜0.05). Whole body insulin sensitivity decreased by 33% in the study group while 38% in the control group (P=0.007 2), and the activity of PTK, expressions of PI3K and PKB in study group were higher than those in control group (P＜0.05， P＜0.01), but no significantly difference was observed about GluT4 in both groups (Pgt;0.05）. Conclusion Preoperative consumption of carbohydrate-containing fluids is safe and effective. Provision of carbohydrate energy source prior to surgery may attenuate immediate postoperative insulin resistance. A carbohydrate-rich drink enhances insulin action at the time of onset of anaesthesia or surgery by activating three kinases named PTK, PI3K, PKB which are key enzymes in pathway of insulin signal transduction. It is likely to explain the effects on postoperative insulin resistance.
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.
ObjectiveTo study effect of expression levels of serum inflammatory factors and insulin receptor substrate(IRS)-1/2 in visceral adipose tissue after Roux-en-Y gastric bypass(RYGB) on type 2 diabetes mellitus(T2DM) rats, and explore possible mechanism in treatment of T2DM. MethodsThe T2DM rats models were established, which were divided into 3 groups by intervention: T2MD-RYGB group(n=14), T2MD-sham operation(T2MD-SO) group(n=10), and T2MD group(n=10), and 10 normal rats were selected as control group. The rats of the T2MD-RYGB group were received the RYGB, and of the T2MD-SO group were received transection and reanastomosis of the gastroin-testinal tract. The fasting plasma glucose(FPG), fasting insulin(FINS), C-reaction protein(CRP), tumor necrosis factor-α(TNF-α), free fatty acid(FFA), homestasis model assessment for insulin resistance(HOMA-IR), adipose tissue insulin resistance(Adipo-IR) were tested respectively before operation and on week 1, 4, 8 after operation(synchronous detec-tion of rats with or without surgical intervention). The IRS-1 and IRS-2 protein contents of the rat epididymal adipose tissue were tested on week 8 after operation. ResultsThe FPG, FINS, CRP, TNF-α, FFA levels, and HOMA-IR, Adipo-IR indexes in the T2DM rats were significantly higher than those in the normal rats(P < 0.05) before operation, the above indicators on week 4, 8 after operation were significantly lower than those before operation in the T2MD-RYGB group(P < 0.05). The differences of changes among the other groups were not statistically significant(P > 0.05). The IRS-1 and IRS-2 protein expressions in the adipose tissue of the rats were significantly increased in the T2MD-RYGB group as compared with these indicators in the T2MD group and T2MD-SO group(P < 0.05), but which were significantly lower than those in the control group(P < 0.05). ConclusionsRYGB could increase IRS-1/2 expression levels in adipose tissue, which could enhance insulin sensitivity, decrease serum inflammatory factors levels, and improve insulin resistance ultimately. This might be one of the mechanisms in treatment of T2DM.
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.
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 review the research progress of the relationship between the insulin resistance, insulin-like growth factor-Ⅰ(IGF-Ⅰ), insulin-like growth factor-Ⅱ(IGF-Ⅱ), and colorectal cancer, and to explore the future research trends. MethodsThe related literatures in recent 5 years from abroad databases (PubMed, Web of Science, and EMBASE)and domestic databases (CNKI, WANFANG, and WEIPU)were collected and reviewed. ResultsThe research on the correlation between the changes and colorectal cancer with insulin resistance and IGF-Ⅰand IGF-Ⅱlevels, epidemiological studies and the mechanism research, indicates that there are complex and close relationship between them. ConclusionsThe research about the relationship between the insulin resistance, IGF-Ⅰ, IGF-Ⅱ, and colorectal cancer is promising.However, many issues need to be further investigated.