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1.
Aims
To compare the risk of vascular disease, HbA1c and weight change, between first prescribed insulins in people with type 2 diabetes.Methods
People included in THIN United Kingdom primary care record database who began insulin (2000–2007) after poor control on oral glucose-lowering agents (OGLD) were grouped by the number of OGLDs in their treatment regimen immediately before starting insulin (n = 3,485). Within OGLD group, Cox regression compared macrovascular (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and microvascular disease (peripheral neuropathy, nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A1c (HbA1c) and weight change.Results
Mean follow-up was 3.6 years. Rates of incident macrovascular events were similar when basal insulin was compared to pre-mix or NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH 1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32, 1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus basal after 3 OGLDs, adjusted hazard ratio1.87 (1.04, 3.36), was not seen after two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs, weight increase was less with basal compared with pre-mix. After three OGLDs, mean HbA1c had reduced less in basal versus pre-mix or NPH at 6–8 and at 9–11 months, and versus pre-mix at 12–14 months.Conclusion
We found no difference in the risk of macrovascular events between first insulins in the medium term when started during poor glycaemia control. The increased risk of microvascular events with NPH warrants further study. In certain groups, first use of basal insulin was associated with less gain in weight and decrease in HbA1c compared to other insulins. 相似文献2.
Soo Lim Katherine G. Stember Wei He Porneala C. Bianca Carine Yelibi Alison Marquis Til Stürmer John B. Buse James B. Meigs 《PloS one》2014,9(10)
Background
Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years.Methods and Findings
From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR). From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2) and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2) who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36–1.19).Conclusions
Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data. 相似文献3.
Sumeet R. Singh Fida Ahmad Avtar Lal Changhua Yu Zemin Bai Heather Bennett 《CMAJ》2009,180(4):385-397
Background
Although insulin analogues are commonly prescribed for the management of diabetes mellitus, there is uncertainty regarding their optimal use. We conducted meta-analyses to compare the outcomes of insulin analogues with conventional insulins in the treatment of type 1, type 2 and gestational diabetes.Methods
We updated 2 earlier systematic reviews of the efficacy and safety of rapid-and long-acting insulin analogues. We searched electronic databases, conference proceedings and “grey literature” up to April 2007 to identify randomized controlled trials that compared insulin analogues with conventional insulins. Study populations of interest were people with type 1 and type 2 diabetes (adult and pediatric) and women with gestational diabetes.Results
We included 68 randomized controlled trials in the analysis of rapid-acting insulin analogues and 49 in the analysis of long-acting insulin analogues. Most of the studies were of short to medium duration and of low quality. In terms of hemoglobin A1c, we found minimal differences between rapid-acting insulin analogues and regular human insulin in adults with type 1 diabetes (weighted mean difference for insulin lispro: –0.09%, 95% confidence interval [CI] –0.16% to –0.02%; for insulin aspart: –0.13%, 95% CI –0.20% to –0.07%). We observed similar outcomes among patients with type 2 diabetes (weighted mean difference for insulin lispro: –0.03%, 95% CI –0.12% to –0.06%; for insulin aspart: –0.09%, 95% CI –0.21% to 0.04%). Differences between long-acting insulin analogues and neutral protamine Hagedorn insulin in terms of hemoglobin A1c were marginal among adults with type 1 diabetes (weighted mean difference for insulin glargine: –0.11%, 95% CI –0.21% to –0.02%; for insulin detemir: –0.06%, 95% CI –0.13% to 0.02%) and among adults with type 2 diabetes (weighted mean difference for insulin glargine: –0.05%, 95% CI –0.13% to 0.04%; for insulin detemir: 0.13%, 95% CI 0.03% to 0.22%). Benefits in terms of reduced hypoglycemia were inconsistent. There were insufficient data to determine whether insulin analogues are better than conventional insulins in reducing long-term diabetes-related complications or death.Interpretation
Rapid-and long-acting insulin analogues offer little benefit relative to conventional insulins in terms of glycemic control or reduced hypoglycemia. Long-term, high-quality studies are needed to determine whether insulin analogues reduce the risk of long-term complications of diabetes.Diabetes mellitus is associated with serious long-term complications and premature death.1 Data from the Health Canada National Diabetes Surveillance System indicate that, in 2004/05, diabetes was diagnosed in about 5.5% (1.8 million) of Canadians aged 20 years and older.2 Because the disease goes undetected in many cases, the true prevalence may approach 1.9 million.3Tight glycemic control, to maintain a hemoglobin A1c concentration of 7.0% or less, is recommended for all patients with diabetes to reduce the risk of long-term complications such as cardiovascular-related death, retinopathy and nephropathy.4 Insulin is indicated for all patients with type 1 diabetes and for patients with type 2 diabetes if adequate glycemic control cannot be achieved through exercise, diet or oral antidiabetic therapy.4Conventional insulins include regular human insulin and intermediate-acting neutral protamine Hagedorn insulin. However, these agents do not replicate the pattern of basal and postprandial endogenous secretion of insulin. Insulin analogues are modified human insulins developed to address this limitation.5 The rapid-acting insulin analogues insulin lispro, insulin aspart and insulin glulisine are marketed in Canada as bolus insulins; the long-acting agents insulin glargine and insulin detemir are marketed as basal insulins.6Systematic reviews of the insulin analogues have been published previously.7–10 However, through our comprehensive search of the literature, we did not identify any reviews of long-acting insulin analogues in the management of type 1 diabetes or gestational diabetes. In this article, we provide an up-to-date, comprehensive systematic review and meta-analysis of outcomes associated with the use of rapid-and long-acting insulin analogues in type 1 and type 2 diabetes (adult and pediatric patients) and gestational diabetes. Detailed methods and complete results are reported elsewhere.11,12 相似文献4.
Larissa W. van Golen Dick J. Veltman Richard G. IJzerman Jan Berend Deijen Annemieke C. Heijboer Frederik Barkhof Madeleine L. Drent Michaela Diamant 《PloS one》2014,9(4)
Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli.
Trial Registration
ClinicalTrials.gov NCT00626080. 相似文献5.
Background
Insulin analogues may be associated with fewer episodes of hypoglycemia than conventional insulins. However, they are costly alternatives. We compared the cost-effectiveness of insulin analogues and conventional insulins used to treat type 1 and type 2 diabetes mellitus in adults.Methods
We conducted a cost-effectiveness evaluation of insulin analogues versus conventional insulins using the Center for Outcomes Research Diabetes Model. We compared rapid-acting analogues (insulin aspart and insulin lispro) with regular human insulin, and long-acting analogues (insulin glargine and insulin detemir) with neutral protamine Hagedorn insulin. We derived clinical information for the comparisons from meta-analyses of randomized controlled trials. We obtained cost and utility estimates from published sources. We performed sensitivity analyses to test the robustness of our results.Results
For type 1 diabetes, insulin aspart was more effective and less costly than regular human insulin. Insulin lispro was associated with an incremental cost of Can$28 996 per quality-adjusted life-year. The incremental cost per quality-adjusted life-year was Can$87 932 for insulin glargine and Can$387 729 for insulin detemir, compared with neutral protamine Hagedorn insulin. For type 2 diabetes, insulin aspart was associated with an incremental cost of Can$22 488 per quality-adjusted life-year compared with regular human insulin. For insulin lispro, the incremental cost was Can$130 865. Compared with neutral protamine Hagedorn insulin, insulin detemir was less effective and more costly. Insulin glargine was associated with an incremental cost of Can$642 994 per quality-adjusted life-year. The model was sensitive to changes in the effect size of hemoglobin A1c and to decrements applied to utility scores when fear of hypoglycemia was included as a factor.Interpretation
The cost-effectiveness of insulin analogues depends on the type of insulin analogue and whether the patient receiving the treatment has type 1 or type 2 diabetes. With the exception of rapid-acting insulin analogues in type 1 diabetes, routine use of insulin analogues, especially long-acting analogues in type 2 diabetes, is unlikely to represent an efficient use of finite health care resources.Insulin agents available for the treatment of diabetes mellitus include conventional insulins and insulin analogues. Insulin analogues were developed to mimic more closely the separate bolus and basal components of insulin secretion.1 Rapid-acting (bolus or mealtime) and long-acting (basal or background) analogue formulations are available. This new class of drugs has been promoted as providing more flexible treatment schedules and a reduced risk of hypoglycemia relative to conventional insulins.1The cost of insulin analogues exceeds that of conventional insulins.2,3 More than US$7.3 billion was spent globally on the purchase of insulin products in 2005 — an increase of 19% over the previous year.4 It has been suggested that the increased expenditure was due to both the increasing prevalence of diabetes and the increased use of insulin analogues.5We performed an analysis of the cost-effectiveness of insulin analogues compared with conventional insulins in the management of type 1 or type 2 diabetes in adults. 相似文献6.
Tzuo-Yun Lan Ya-Fang Zeng Gau-Jun Tang Hui-Chuan Kao Hsien-Jane Chiu Lan Tsuo-Hung Hsiao-Feng Ho 《PloS one》2015,10(12)
Background
Sleep disorders, especially chronic insomnia, have become major health problem worldwide and, as a result, the use of hypnotics is steadily increasing. However, few studies with a large sample size and long-term observation have been conducted to investigate the relationship between specific hypnotics and mortality.Methods
We conducted this retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. Information from claims data including basic characteristics, the use of hypnotics, and survival from 2000 to 2009 for 1,320,322 individuals were included. The use of hypnotics was divided into groups using the defined daily dose and the cumulative length of use. Hazard ratios (HRs) were calculated from a Cox proportional hazards model, with two different matching techniques to examine the associations.Results
Compared to the non-users, both users of benzodiazepines (HR = 1.81; 95% confidence interval [CI] = 1.78–1.85) and mixed users (HR = 1.44; 95% CI = 1.42–1.47) had a higher risk of death, whereas the users of other non-benzodiazepines users showed no differences. Zolpidem users (HR = 0.73; 95% CI = 0.71–0.75) exhibited a lower risk of mortality in the adjusted models. This pattern remained similar in both matching techniques. Secondary analysis indicated that zolpidem users had a reduced risk of major cause-specific mortality except cancer, and that this protective effect was dose-responsive, with those using for more than 1 year having the lowest risk.Conclusions
The effects of different types of hypnotics on mortality were diverse in this large cohort with long-term follow-up based on representative claims data in Taiwan. The use of zolpidem was associated with a reduced risk of mortality. 相似文献7.
Chen-Yi Wu Hsiao-Yun Hu Lok-Hi Chow Yiing-Jenq Chou Nicole Huang Pei-Ning Wang Chung-Pin Li 《PloS one》2015,10(6)
Background
Few studies have examined the contribution of treatment on the mortality of dementia based on a population-based study.Objective
To investigate the effects of anti-dementia and nootropic treatments on the mortality of dementia using a population-based cohort study.Methods
12,193 incident dementia patients were found from 2000 to 2010. Their data were compared with 12,193 age- and sex-matched non-dementia controls that were randomly selected from the same database. Dementia was classified into vascular (VaD) and degenerative dementia. Mortality incidence and hazard ratios (HRs) were calculated.Results
The median survival time was 3.39 years (95% confidence interval [CI]: 2.88–3.79) for VaD without medication, 6.62 years (95% CI: 6.24–7.21) for VaD with nootropics, 3.01 years (95% CI: 2.85–3.21) for degenerative dementia without medication, 8.11 years (95% CI: 6.30–8.55) for degenerative dementia with anti-dementia medication, 6.00 years (95% CI: 5.73–6.17) for degenerative dementia with nootropics, and 9.03 years (95% CI: 8.02–9.87) for degenerative dementia with both anti-dementia and nootropic medications. Compared to the non-dementia group, the HRs among individuals with degenerative dementia were 2.69 (95% CI: 2.55–2.83) without medication, 1.46 (95% CI: 1.39–1.54) with nootropics, 1.05 (95% CI: 0.82–1.34) with anti-dementia medication, and 0.92 (95% CI: 0.80–1.05) with both nootropic and anti-dementia medications. VaD with nootropics had a lower mortality (HR: 1.25, 95% CI: 1.15–1.37) than VaD without medication (HR: 2.46, 95% CI: 2.22–2.72).Conclusion
Pharmacological treatments have beneficial effects for patients with dementia in prolonging their survival. 相似文献8.
Aim
The role of insulin glargine as a risk factor for cancer is controversial in human studies. The aim of this meta-analysis was to evaluate the relationship between insulin glargine and cancer incidence.Methods
All observational studies and randomized controlled trials evaluating the relationship of insulin glargine and cancer risk were identified in PubMed, Embase, Web of Science, Cochrane Library and the Chinese Biomedical Medical Literature Database, through March 2012. Odds ratios (ORs) with corresponding 95% confidence interval (CI) were calculated with a random-effects model. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.Results
A total of 11 studies including 448,928 study subjects and 19,128 cancer patients were finally identified for the meta-analysis. Insulin glargine use was associated with a lower odds of cancer compared with non-glargine insulin use (OR 0.81, 95% CI 0.68 to 0.98, P = 0.03; very low-quality evidence). Glargine did not increase the odds of breast cancer (OR 0.99, 95% CI 0.68 to 1.46, P = 0.966; very low-quality evidence). Compared with non-glargine insulin, no significant association was found between insulin glargine and prostate cancer, pancreatic cancer and respiratory tract cancer. Insulin glargine use was associated with lower odds of other site-specific cancer.Conclusions
Results from the meta-analysis don''t support the link between insulin glargine and an increased risk of cancer and the confidence in the estimates of the effects is very low. Further studies are needed to examine the relation between insulin glargine and cancer risk, especially breast cancer. 相似文献9.
Shuichiro Yamamoto Yumi Matsushita Toru Nakagawa Toru Honda Takeshi Hayashi Mitsuhiko Noda Tetsuya Mizoue 《PloS one》2016,11(2)
Objective
To investigate visceral fat accumulation and markers of insulin resistance in relation to elevated depressive symptoms (EDS).Methods
Participants were 4,333 male employees (mean age, 49.3 years) who underwent abdominal computed tomography scanning, measured fasting insulin, and did not self-report diabetes and mental disorders under treatment and history of cancer, myocardial infarction, and stroke. Multivariable logistic regression was used to assess the association of EDS with abdominal fat deposition and markers of insulin resistance.Results
Visceral fat area (VFA) and fasting insulin were significantly, positively associated with EDS. Multivariable-adjusted odds ratios (95% confidence interval) of high VFA for the lowest through highest quartile of depression score were 1 (reference), 1.18 (0.97–1.42), 1.25 (1.02–1.54), 1.23 (1.01–1.51), respectively, and corresponding figures for high fasting insulin were 1 (reference), 0.98 (0.80–1.19), 1.12 (0.91–1.38), and 1.29 (1.06–1.57), respectively. Subcutaneous fat area was not associated with EDS.Conclusions
Results suggest that EDS is related to visceral, but not subcutaneous, fat accumulation and insulin resistance in middle-aged Japanese men. 相似文献10.
Yunjuan Gu Chunfang Wang Ying Zheng Xuhong Hou Yifei Mo Weihui Yu Lei Zhang Cheng Hu Hairong Nan Lei Chen Jie Li Yuxiang Liu Zhezhou Huang Ming Han Yuqian Bao Weijian Zhong Weiping Jia 《PloS one》2013,8(1)
Aim
The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes.Methods
We recruited 8,774 insulin-naïve diabetes patients from the Shanghai Diabetes Registry (SDR). The follow-up rate was 85.4%. All subjects were divided into the insulin use cohort (n = 3,639) and the non-insulin use cohort (n = 5,135). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. Cox proportional hazards model was used to estimate the relative risk (RR) of cancer and mortality.Results
We observed 98 cancer events in the insulin use cohort and 170 in the non-insulin use cohort. Cancer incidence rates were 78.6 and 74.3 per 10,000 patients per year in the insulin users and the non-insulin users, respectively. No significant difference in cancer risk was observed between the two cohorts (adjusted RR = 1.20, 95% CI 0.89–1.62, P = 0.228). Regarding site-specific cancers, only the risk of liver cancer was significantly higher in the insulin users compared to that in the non-insulin users (adjusted RR = 2.84, 95% CI 1.12–7.17, P = 0.028). The risks of overall mortality (adjusted RR = 1.89, 95% CI 1.47–2.43, P<0.0001) and death from cancer (adjusted RR = 2.16, 95% CI 1.39–3.35, P = 0.001) were all significantly higher in the insulin users than in the non-insulin users.Conclusion
There was no excess risk of overall cancer in patients with type 2 diabetes who were treated with human insulin. However, a significantly higher risk of liver cancer was found in these patients. Moreover, insulin users showed higher risks of overall and cancer mortality. Considering that individuals treated with insulin were more likely to be advanced diabetic patients, caution should be used in interpreting these results. 相似文献11.
César Garriga Patricia García de Olalla Josep M. Miró Inma Oca?a Hernando Knobel Maria Jesús Barberá Victoria Humet Pere Domingo Josep M. Gatell Esteve Ribera Mercè Gurguí Andrés Marco Joan A. Caylà 《PloS one》2015,10(12)
Introduction
Antiretroviral therapy has led to a decrease in HIV-related mortality and to the emergence of non-AIDS defining diseases as competing causes of death. This study estimates the HIV mortality rate and their risk factors with regard to different causes in a large city from January 2001 to June 2013.Materials and Methods
We followed-up 3137 newly diagnosed HIV non-AIDS cases. Causes of death were classified as HIV-related, non-HIV-related and external. We examined the effect of risk factors on survival using mortality rates, Kaplan-Meier plots and Cox models. Finally, we estimated survival for each main cause of death groups through Fine and Gray models.Mortality Results
182 deaths were found [14.0/1000 person-years of follow-up (py); 95% confidence interval (CI):12.0–16.1/1000 py], 81.3% of them had a known cause of death. Mortality rate by HIV-related causes and non-HIV-related causes was the same (4.9/1000 py; CI:3.7–6.1/1000 py), external was lower [1.7/1000 py; (1.0–2.4/1000 py)].Survival Results
Kaplan-Meier estimate showed worse survival in intravenous drug user (IDU) and heterosexuals than in men having sex with men (MSM). Factors associated with HIV-related causes of death include: IDU male (subHazard Ratio (sHR):3.2; CI:1.5–7.0) and <200 CD4 at diagnosis (sHR:2.7; CI:1.3–5.7) versus ≥500 CD4. Factors associated with non-HIV-related causes of death include: ageing (sHR:1.5; CI:1.4–1.7) and heterosexual female (sHR:2.8; CI:1.1–7.3) versus MSM. Factors associated with external causes of death were IDU male (sHR:28.7; CI:6.7–123.2) and heterosexual male (sHR:11.8; CI:2.5–56.4) versus MSM.Conclusion and Recommendation
There are important differences in survival among transmission groups. Improved treatment is especially necessary in IDUs and heterosexual males. 相似文献12.
Jiun-Chi Huang Hugo You-Hsien Lin Lee-Moay Lim Szu-Chia Chen Jer-Ming Chang Shang-Jyh Hwang Jer-Chia Tsai Chi-Chih Hung Hung-Chun Chen 《PloS one》2015,10(5)
Background and Aim
A higher body mass index (BMI) appears to be reversely associated with mortality in dialysis patients. Moreover, although women have better survival in chronic kidney disease (CKD), this survival advantage is cancelled in dialysis. The association between BMI and mortality and the gender difference remain controversial in advanced CKD.Methods
This study enrolled 3,320 patients (1,938 men and 1,382 women) from southern Taiwan who had CKD stages 3–5 with a BMI of 15.0–35.0 kg/m2.Results
During a median 2.9-year follow-up, there were 328 (16.9%) all-cause mortality and 319 (16.5%) cardiovascular (CV) events and death in male patients, 213 (15.4%) all-cause mortality and 224 (16.2%) CV events and death in female patients. Compared with the reference BMI of 27.6–30.0 kg/m2 in an adjusted Cox model, lower-BMI groups in men, BMI 15.0–20.0 kg/m2 and 20.1–22.5 kg/m2, were associated with higher risks of all-cause mortality: hazard ratios (HRs) 3.19 (95% confidence interval [CI], 1.97–5.18) and 2.01 (95% CI, 1.29–3.14), respectively. Higher-BMI group in men, BMI 30.1–35.0 kg/m2, was associated with a higher risk of all-cause mortality: HR 1.72 (95% CI, 1.02–2.96). Likewise, lower- and higher-BMI groups in men were associated with a higher risk of CV events and death. In women, these associations between BMI and poor outcomes were not observed.Conclusions
In advanced CKD, there was a reverse J-shaped association between BMI and all-cause mortality, and a U-shaped association between BMI and CV outcomes in men. Neutral associations between BMI and poor outcomes were detected in women. Gender could modify the effect of BMI on mortality in patients with CKD. 相似文献13.
14.
Ding Ding Dongfang Su Xinrui Li Zhongxia Li Yujie Wang Jian Qiu Puqing Lin Yuan Zhang Pi Guo Min Xia Dan Li Yan Yang Gang Hu Wenhua Ling 《PloS one》2015,10(3)
Background
Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors.Methods
MCP-1 was measured at baseline in 1411 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk.Results
During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89–2.58), 1.00, and 2.11 (95% CI 1.31–3.40) for all-cause mortality, and 1.50 (95% CI 0.80–2.81), 1.00, and 2.21 (95% CI 1.27–3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method.Conclusions
Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance. 相似文献15.
Purpose
Hydrazine is carcinogenic in animals, but there is inadequate evidence to determine if it is carcinogenic in humans. This study aimed to evaluate the association between hydrazine exposure and the risk of lung cancer.Methods
The cause specific mortality rates of a cohort of 427 men who were employed at an English factory that produced hydrazine between 1945 and 1971 were compared with national mortality rates.Results
By the end of December 2012 205 deaths had occurred. For men in the highest exposure category with greater than two years exposure and after more than ten years since first exposure the relative risks compared with national rates were: 0.85 (95% CI: 0.18–2.48) for lung cancer, 0.61 (95% CI: 0.07–2.21) for cancers of the digestive system, and 0.44 (95% CI: 0.05–1.57) for other cancers.Conclusions
After 50 years of follow up, the results provide no evidence of an increased risk of death from lung cancer or death from any other cause. 相似文献16.
Background
An association between education level and survival after esophageal cancer has recently been indicated, but remains uncertain. We conducted a large study with long follow-up to address this issue.Methods
This population-based cohort study included all patients operated for esophageal cancer in Sweden between 1987 and 2010 with follow-up until 2012. Level of education was categorized as compulsory (≤9 years), intermediate (10–12 years), or high (≥13 years). The main outcome measure was overall 5-year mortality after esophagectomy. Cox regression was used to estimate associations between education level and mortality, expressed as hazard ratios (HRs) with 95% confidence intervals (CIs), with adjustment for sex, age, co-morbidity, tumor stage, tumor histology, and assessing the impact of education level over time.Results
Compared to patients with high education, the adjusted HR for mortality was 1.29 (95% CI 1.07–1.57) in the intermediate educated group and 1.42 (95% CI 1.17–1.71) in the compulsory educated group. The largest differences were found in early tumor stages (T-stage 0–1), with HRs of 1.73 (95% CI 1.00–2.99) and 2.58 (95% CI 1.51–4.42) for intermediate and compulsory educated patients respectively; and for squamous cell carcinoma, with corresponding HRs of 1.38 (95% CI 1.07–1.79) and 1.52 (95% CI 1.19–1.95) respectively.Conclusions
This Swedish population-based study showed an association between higher education level and improved survival after esophageal cancer surgery, independent of established prognostic factors. The associations were stronger in patients of an early tumor stage and squamous cell carcinoma. 相似文献17.
Mark R. Sommerfeld Günter Müller Georg Tschank Gerhard Seipke Paul Habermann Roland Kurrle Norbert Tennagels 《PloS one》2010,5(3)
Background
Insulin glargine (Lantus®) is a long-acting basal insulin analog that demonstrates effective day-long glycemic control and a lower incidence of hypoglycemia than NPH insulin. After subcutaneous injection insulin glargine is partly converted into the two main metabolites M1 ([GlyA21]insulin) and M2 ([GlyA21,des-ThrB30]insulin). The aim of this study was to characterize the glargine metabolites in vitro with regard to their insulin receptor (IR) and IGF-1 receptor (IGF1R) binding and signaling properties as well as their metabolic and mitogenic activities.Methods
The affinity of human insulin, insulin glargine and its metabolites to the IR isoforms A and B or IGF1R was analyzed in a competitive binding assay using SPA technology. Receptor autophosphorylation activities were studied via In-Cell Western in CHO and MEF cells overexpressing human IR-A and IR-B or IGF1R, respectively. The metabolic response of the insulins was studied as stimulation of lipid synthesis using primary rat adipocytes. Thymidine incorporation in Saos-2 cells was used to characterize the mitogenic activity.Conclusions
The binding of insulin glargine and its metabolites M1 and M2 to the IR were similar and correlated well with their corresponding autophosphorylation and metabolic activities in vitro. No differences were found towards the two IR isoforms A or B. Insulin glargine showed a higher affinity for IGF1R than insulin, resulting in a lower EC50 value for autophosphorylation of the receptor and a more potent stimulation of thymidine incorporation in Saos-2 cells. In contrast, the metabolites M1 and M2 were significantly less active in binding to and activation of the IGF1R and their mitogenicity in Saos-2 cells was equal to human insulin. These findings strongly support the idea that insulin glargine metabolites contribute with the same potency as insulin glargine to blood glucose control but lead to significantly reduced growth-promoting activity. 相似文献18.
Background
Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies. Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression.Methods
Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts. A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients. Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. Odds ratios (ORs) were pooled by random effects models.Results
Fourteen observational studies were eligible for the study. Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29–3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16–7.82), severe airway obstruction (1.31, 95% CI, 1.09–1.58) and mortality (1.96, 95% CI, 1.04–3.70).Conclusions
The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. 相似文献19.
Ding Ding Min Wang Dongfang Su Changjiang Hong Xinrui Li Yunou Yang Yuan Zhang Gang Hu Wenhua Ling 《PloS one》2015,10(8)
Background
To investigate single and joint associations of body mass index (BMI) and serum high-sensitivity C-reactive protein (hsCRP) with death.Methods
The study included 1871 coronary artery disease (CAD) patients aged 40–85 year-old recruited from 2008 to 2011. Cox regression models were used to estimate the association of BMI and hsCRP with mortality. The data was analyzed in 2014.Results
During 3.1 years follow-up, 141 deaths were recorded, 110 died of cardiovascular disease (CVD). After adjustment of major CVD risk factors, there was a J-shaped association between BMI and all-cause and CVD mortality, and a positive association between hsCRP and mortality. The J-shaped association of BMI with mortality was present among patients who never smoked or with elevated hsCRP (≥3.0 mg/L). Compared with overweight (BMI 24–27.9 kg/m2) patients with normal hsCRP (<3.0 mg/L), obese patients (BMI≥28 kg/m2) with elevated hsCRP had a 3.41-fold risk of all-cause mortality (95% CI 1.49–7.80) and a 3.50-fold risk of CVD mortality (1.40–8.75), lean patients (BMI<24 kg/m2) with elevated hsCRP concentration had a 2.54-fold risk of all-cause mortality (1.36–4.74) and a 2.36-fold risk of CVD mortality (1.19–4.70).Conclusions
The association pattern between baseline BMI and mortality changed among different baseline hsCRP concentrations, indicating that low-grade inflammation may be related to BMI and secondary prognosis of CAD. 相似文献20.
Togoobaatar Ganchimeg Chie Nagata Joshua P. Vogel Naho Morisaki Cynthia Pileggi-Castro Eduardo Ortiz-Panozo Kapila Jayaratne Suneeta Mittal Erika Ota Jo?o Paulo Souza Rintaro Mori WHO Multicountry Survey on Maternal Newborn Health Research Network 《PloS one》2016,11(2)