Effects of Lowering Blood Glucose v Standard Treatment in Patients with Diabetes Mellitus - Research Paper Example

?Effects of Lowering Blood Glucose v. Standard Treatment in Patients with Diabetes Mellitus Research shows mixed results for the anticipatedtherapeutic intervention of intensive glucose lowering in patients with Type 2 diabetes, and whether intensive glucose lowering leads to an impact on major macro and microvascular outcomes. In the Action to Control (2008) study, the researchers found that that the intensive glucose lowering increased mortality, nonfatal myocardial infarction, and nonfatal strokes. Cai-Hong (2013) study combined intensive blood glucose lowering with gliclazide MR, AND blood pressure lowering with preterax. The study found that the combination of blood glucose lowering and blood pressure medication slows the progression of microvascular complications. Similarly, the Turnbull (2009) meta-analysis study found that intensive glucose control leads to a reduced risk of major cardiovascular events, showing a reduction of 9% for major cardiovascular events. Advance Collaborative (2008) found that intensive blood glucose lowering with gliclazide and other drugs resulted in a reduced incidence of combined major macrovascular and microvascular events, as well as major microvascular events, because there also was a reduction of nephropathy. Still another study suggests that any kind of benefit attained by intensive lowering of blood glucose is lost after one year. The study conducted by Hollman et al. (2008) found that the patients who were assigned intensive glucose lowering were compared to patients who were assigned the standard treatment of dietary restriction. While the immediate results were that the intensive glucose lowering showed that the patients had a lower risk of microvascular complications then the patients with conventional dietary therapy, after one year, these advantages were lost. Introduction Patients with diabetes suffer from a variety of ailments. Among these ailments are microvascular and macrovascular diseases. Therefore, therapeutic intervention should be investigated to reduce the risks of a diabetic patient suffering from these ailments. One such intervention is aggressively lowering blood glucose levels through drugs such as glicazide. Therefore, this article will examine studies that are focused around the intervention of blood glucose lowering, and will examine whether this is an intervention that is positive for diabetic patients, with regards to lessening the risk of micro and macrovascular ailments. PICO Question In patients with Type II Diabetes Mellitus (P), what is the effect of intensively lowering the blood glucose (I) as compared with standard treatment (C) on the incidence of major macro- and microvascular outcomes (O)? Clinical Question Selection Criteria Inclusion Criteria 1. Journals and studies featuring patients who are who are subjected to either intensive glucose lowering or standard treatment. 2. The participants in these studies had either a microvascular or macrovascular cardiac event. 3. The journals were either randomized trials or meta-analyses. 4. Were published in peer reviewed journals. 5. Were reported in English. Exclusion Criteria 1. Journals that reported on either type I diabetes, juvenile diabetes or gestational diabetes. 2. Qualitative studies. 3. Studies that focused upon patients who were under the age of 18. Search Process The process began by looking for studies that had, as their focus, type II diabetes, intensive glucose lowering therapy verses traditional therapy and micro and macrovascular outcomes. These peer-reviewed journals were ones that were written in English. The data bases that were used were Pubmed, Psychosocial Instruments, British Nursing Index, Cumulative Index to Nursing and Allied Health Library, Psychosocial Instruments, Allied and Alternative Medicine and Sociofile. These databases were searched with the initial terms of type II diabetes, intensive glucose lowering therapy and micro and macrovascular cardiac. The articles were then narrowed down to studies that were randomized or studies which were meta-analysis. Another criteria that was looked at was how the data was obtained. Also of note was how novel the strategy was. Several of the journals had studies which were duplicative of one another, so these duplicative studies were also eliminated. The number of patients was also looked at, as were the characteristics of the patients. The studies that were well-validated were given priority over studies that did not have the same level of validation, and the studies that were complete and thorough were given priority over those that were not as complete and thorough. Another criteria was the control group, and how the control group was selected, and, importantly, whether the control group had significantly different results from the intervention group. These studies were considered to be strong, because the showed that their control groups had appreciably better outcomes than the patients in the intervention groups. Lastly, there were several journals that were selected because they presented a more comprehensive look at other studies, as these articles were helpful in that they allowed for finding different strategies and outcomes that might not have been considered otherwise. Evaluative Comments Critical Appraisal of Collective Evidence The research shows mixed results for the anticipated therapeutic intervention of intensive glucose lowering in patients with Type 2 diabetes, and whether intensive glucose lowering leads to an impact on major macro and microvascular outcomes. In the Action to Control (2008) study, the researchers found that intensive lowering of glucose, when the patient population consisted of patients with established cardiovascular disease or cardiovascular risk factors, 35% of whom had a prior cardiovascular incident, the findings was that the intensive glucose lowering increased mortality, nonfatal myocardial infarction, and nonfatal strokes. During the 1 year follow up period, 257 patients in the intensive therapy group died, compared to 203 patients in the stand therapy group. While the above study would suggest that intensive blood glucose lowering is not advisable to patients with type 2 diabetes, another study contradicts this finding. The Cai-Hong (2013) study combined intensive blood glucose lowering with gliclazide MR, AND blood pressure lowering with preterax. This study found that the patients in the standard group, who received routine medications, had less visual acuity after 5 years of treatment, and the UMA/UCR ratio wasn't obviously changed in the intensive therapy group, but was significantly increased in the standard group. The study also found that the combination of blood glucose lowering and blood pressure medication slows the progression of microvascular complications. Similarly, the Turnbull (2009) meta-analysis study found that intensive glucose control leads to a reduced risk of major cardiovascular events, showing a reduction of 9% for major cardiovascular events. There also was a 15% reduced risk of myocardial infarction. The study indicated that intensive glucose lowering may lead to modestly reduced major macrovascular events. However, it also may lead to increased major hypoglycaemia, which was another finding of this study. Advance Collaborative (2008) found that intensive blood glucose lowering with gliclazide and other drugs resulted in a reduced incidence of combined major macrovascular and microvascular events, as well as major microvascular events, because there also was a reduction of nephropathy. However, there was not a reduction of macrovascular events, nor was there a reduction in death from cardiovascular causes, or death from any cause. Moreover, the study found that severe hypoglycemia was more common in the intensive-control group. Still another study suggests that any kind of benefit attained by intensive lowering of blood glucose is lost after one year. The study that would suggest this is the 10 year follow up study conducted by Hollman et al. (2008). In this study, the patients who were assigned intensive glucose lowering were compared to patients who were assigned the standard treatment of dietary restriction. While the immediate results were that the intensive glucose lowering showed that the patients had a lower risk of microvascular complications then the patients with conventional dietary therapy, after one year, these advantages were lost. Collective Results The results would suggest that intensive glucose lowering, in and of itself, is not effective in lowering the incidence of major macro and microvascular outcomes. The Action to Control (2008) study found that there was more mortality in patients who receive intensive glucose therapy, and no benefit for cardiovascular events. That study has a 95% confidence interval. In the meta-analysis conducted by Turnbull et al. (2009), intensive blood glucose lowering showed only a modest reduction of macrovascular events, but a higher risk of major hypoglycaemia over 4.4 years. Mortality risks were not decreased in this study. That said, there is some indication that combining intensive glucose lowering with other therapies, such as blood pressure lowering and dietary restrictions might be beneficial. The Cai-Hong (2013) study showed that the combination of blood pressure medicine with glucose medicine slowed the progression of microvascular complications, while maintaining stable vision. The P values for the visual acuity was .04, while the P values for the severity of diabetic retinopathy was .0006. The P values for the UMA/UCR ratio, which wasn't changed in the intensive group, but was in the standard group was .00. Meanwhile, the Advance Collaborative (2008) study showed that combining gliclazide with other drugs resulted in reduced combined major macrovascular and microvascular events, as it lowered nephropathy. The P value for the reduction of major macrovascular and microvascular events was .01, and for microvascular events alone, it was .01. Interestingly, in this study, retinopathy was essentially not affected by the intensive blood glucose lowering (P=.50), nor was major macrovascular events in isolation (P=.32). Finally, the Hollman et al. (2008) study suggests that dietary restriction should be combined with intensive blood glucose lowering, as both of these groups essentially had the same risk of micro and macrovascular complications after 10 years, and that metformin should be administered to overweight patients. Further risk reduction were seen in the group using sulfonylurea-insulin, with microvascular disease showing P=.001, and the metformin group showing P=.005 for myocardial infarction. Intervention Decision In this case, the EPB model for implementation is one that is advocated by Johns Hopkins in the United States. This EPB calls for a team that communicates and obtains feedback from appropriate organizational leadership, bedside clinicians and other stakeholders who might be affected by the implementation decision. This interdisciplinary team determines if the change is appropriate and feasible. Then, an action plan is developed, and this action plan is sent to the organizational leadership, bedside clinicians and other stakeholders for evaluation. The action plan, in this case, would be that the patients who are type II diabetics should be prescribed a combination of intensive glucose lowering medicine, dietary restrictions and blood pressure medicine. The next step is to implement the change, which is where the action plan is implemented. This implementation plan will be described further in the next section. The final step is to evaluate the outcomes. This is where the interdisciplinary team that is assembled reviews the outcomes for the patient and decide of the goals for the treatment were met, and if there are unexpected outcomes, the team should examine why the unexpected outcomes occurred. The findings for the action plan are then sent to the decision makers (organizational leadership, etc.), then, if the outcome is favorable, the decision makers may implement the recommended change more broadly (Newhouse et al., 2007). Plan for Implementation In this case, the patients should receive dietary restrictions, gliclazide and blood pressure lowering drugs. They should be monitored carefully through the implementation period. The patients should also be subjected to some kind of behavioural modification program, because making dietary changes might be difficult for the patient to implement without some kind of reinforcement for the patient. The team should make a decision upon the right kind of behavioural modification program to implement with the dietary changes. After the patient has been on the prescribed therapeutic intervention for six weeks, the interdisciplinary team should evaluate the changes that the patient is experiencing regarding the objective vital signs, and, if the patient is not responding or responding negatively, then intervention should be evaluated accordingly. The most important aspect is that the patient must be treated as an individual. Some individuals might do better with this kind of intervention than would others, so the six-week evaluation is important in this case. If the patient improves, then the patient should continue on the prescribed therapy indefinitely, but also must come in for evaluation every 3 months. Conclusion With patients with type II diabetes, macro and microvascular issues is often a concern. Therefore, it is important that there be some kind of intervention that might target this issue. The intervention that was studied in this instance was intensive lowering of the blood glucose through medication. The studies that were found regarding this issue showed mixed results - one study showed that aggressively lowering blood glucose is harmful and could lead to an increased risk of serious ailments and an increased risk of death. Another study found that aggressively lowering blood glucose works well if combined with lowering blood pressure. The other studies weakly favoured lowering blood glucose, finding that it leads to minimal results that do not necessarily persist over time. By far the most promising study is the study conducted by Cai-Hong (2013). This study showed that lowering blood glucose should be combined with lowering blood pressure. Therefore, the best intervention would be to lower both blood glucose and blood pressure at the same time, while also instituting dietary restrictions, as the Hollman et al. (2008) study showed that, over time, dietary restrictions works just as well as aggressively lowering blood glucose through drug intervention. Moreover, dietary restrictions is something that is benign and has benefits and few drawbacks. Therefore, this is the regimen that should be prescribed to patients, on a carefully monitored level, with an interdisciplinary team that would evaluate the process every step of the way. References Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein, H.C., Miller, M.E., Byington, R.P., Goff, D.C., Jr, Bigger, J.T., Buse, J.B., Cushman, W.C., Genuth, S., Ismail-Beigi, F., Grimm, .RH., Jr, Probstfield, J.L., Simons-Morton, D.G., Friedewald, W.T. (2008). Effects of intensive glucose lowering in type 2 diabetes. The New England Journal of Medicine. 358 (24), 2545-2559. doi: 10.1056/NEJMoa0802743. Retrieved from http://europepmc.org/abstract/MED/18539917/reload=0;jsessionid=UKLFSQ0HYwqy56GC2VJT.6 Cai-Hong, Z., Shi-Sheng, Z., Yan, K., Yu-Fang, B., Ling, W., and Qiong, Z. (2013). Effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type II diabetes mellitus. International Journal of Opthalmology. 6 (2), 141–145. doi: 10.3980/j.issn.2222-3959.2013.02.06. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633749/ Holman, R.R., Paul, S. J., Bethel, M.A., Matthews, D.R., Andrew, H., Neil, W. (2008). 10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes. The New England Journal of Medicine. 359, 1577-89. doi:1056/NEJMoa0806470. Retrieved from http://www.nejm.org/doi/pdf/10.1056/NEJMoa0806470 Riva, J.J., Malik, K.M.P., Burnie, S.J., Endicott, A.R., Busse, J.W. (2012). An introduction to the PICOT format to clinicians. The Journal of Canadian Chiropractic Association. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3430448/ The ADVANCE Collaborative Group. (2008). Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes. The New England Journal of Medicine. 359, 1577-89. doi: 10.1056/NEJMoa0802987. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMoa0802987 Turnbull, F.M., Abraira, C., Anderson, R.J., Byington, R.P., Chalmers, J.P., Duckworth, W.D., Evans, G.W., Gerstein, H.C., Holman, R.R., Moritz, T.E., Neal, B.C., Ninomiya, T., Patel, A.A., Paul, S.K., Travert, F., Woodward, M. (2009). Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 52, 2288–2298. doi:10.1007/s00125-009-1470-0. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19655124 Appendix A: Review of Literature Matrix Directions: Complete matrix for each of the studies/publications you have selected as “best evidence” for your PICOT question. PICOT question: In patients with Type II Diabetes Mellitus (P), what is the effect of intensively lowering the blood glucose (I) as compared with standard treatments (C) on the incidence of major macro and microvascular outcomes (O)? Author, Year, Title, Design/Type & Level of Evidence Study Purpose Population investigated Intervention/Comparison & Outcomes (Independent/Dependent Variables) Results Action to Control, 2008. Method: Randomized study. To investigate whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with Type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors. 10,251 patients, with a mean age of 62.2 years, with a median glycatedhemoglobin level of 8.1%. 38% were women and 35% have had a previous cardiovascular event. IV: Intensive therapy to target normal glycated hemoglobin levels. DV: Cardiovascular events in patients with Type 2 diabetes who either had established cardiovascular disease or additional cardiovascular risk factors. At 1 years, the stable median glycated hemoglobin levels were6.4% in the intensive-therapy group, and 7.5% in the standard-therapy group. In the follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, and 371 patients in the standard therapy group. 257 patients in the intensive therapy group died, compared to 203 patients in the standard-therapy group. The intensive therapy group had more frequent occurrences of hypoglycemia that required assistance and weight gain. Cai-Hong Method: Randomized study. To evaluate the effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with Type II diabetes by comparing the therapeutic effects of intensive and standard treatment in patients with Type II diabetes. 107 patients with Type II Diabetes. IV: Intensive treatment using preterax to control blood pressure and gliclazide MR to control blood glucose. DV: Microvascular complications in patients with Type II diabetes. After five years, visual acuity decreased in the standard group, but was stable in the intensive group. Diabetic retinopathy had not progressed in patients in the intensive group, but had deteriorated in the standard group. The ratio of urinary microalbumin to urinary creatine was not obviously changed in patients in the intensive group, but was significantly increased in the standard group. Advance Collaborative, 2008. Method: Randomized study. To determine the effects of intensive glucose control on vascular outcomes. 11,140 patients with Type 2 diabetes. IV: Glucose control. DV: Vascular outcomes. After 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group than in the standard control group. The intensive control reduced the incidence of combined major macrovascular and microvascular events. There was a reduction in the incident of nephropathy in the intervention group. On major macrovascular events, there were no signficant effects on the type of glucose control. Hollman et al., 2008. Method: Randomized study. Determining whether improved glucose control persisted after patients receive intensive glucose therapy, and if this therapy has a long-term effect on macrovascular outcomes. 5,102 patients with newly diagnosed Type 2 diabetes. IV: Glucose control. DV: Long-term vascular outcomes. Between group differences in glycated hemoglobin levels were lose after the first year. In the group receiving sulfonylurea insulin, the relative reductions in risk persisted at 10 years for microvascular disease, myocardial infarction and death from any cause. Appendix B: Critique Template Directions: Complete critique template for each of the research articles that you have selected as “best evidence” for your PICOT question. Provided below are critique templates for systematic reviews, meta-analyses, practice guidelines, quantitative studies, and qualitative studies. Utilize the critique template(s), which correspond with the type(s) of evidence you selected. Meta-Analysis Template Citation (APA) Turnbull, F. et al.(2009) Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia, 52: 2288-2298. Title Intensive glucose control and macrovascular outcomes in type 2 diabetes. Database Source (& ID number) Google Scholar. Type of Evidence Meta-analysis Hierarchical Evidence Rating Level Your Summary of the Study/Publication (use paraphrasing, not quotes) What was the stated research question/objective of the study? What are the effects of more-intensive, compared with less-intensive, glucose control on the risk of major cardiovascular events amongst patients with Type 2 Diabetes? What search strategies were used to locate applicable studies for possible inclusion? Literature search, scrutiny of clinical trial registers and abstracts of proceedings, and equiry among colleagues and industry representatives, in accordance with internationally accepted norms. MEDLINE, controlled clinical trial registers and the Cochrane Database were all searched for articles published in English up until January 2009. Studies were identified through PubMed searches of the MEDLINE database with the headings “blood glucose,” “diabetes mellitus,” “clinical trial,” “glycaemic/glycemic blood glucose control” and “aggressive/tight/intensive.” Reference lists of the retrieved articles were also searched to identify other eligible studies, and information from colleagues was used to identify more recently published articles. What were the stated inclusion/exclusion criteria? Trials were eligible to be included if they were designed to assess directly the impact of achieving lower v. higher levels of glycaemia on cardiovascular outcomes in adult patient with Type 2 diabetes and: had at least 1,000 person-years of follow-up in each treatment arm and a minimum of 2 years median post-radomisation follow-up; were randomised and controlled; were double-blind or blind assessment of endpoint design; had pre-specified cardiovascular outcomes; were analysed using an intention to treat approach; and had follow-up of at least 90% of radomised participants for vital status. Exclusion criteria were trial randomising individuals to comprehensive cardiovascular risk-reduction strategies, unless there was a separate randomisation to different levels of glycaemic control. Trials conducted in patients with type 1 diabetes, with gestational diabetes or in children less than 16 years of age were excluded. Also excluded were trials conducted in acute or critical-care settings. What was the total sample size (e.g., how many studies were included, number of subjects)? A total of 27,049 participants and 2,370 major vascular events. What were the results of the study? At what Level of Significance? A risk of a major cardiovascular event was reduced by 9% in those allocated to more-intensive compared with less-intensive glycaemic control with no evidence of heterogeneity among trials. The cumulative HRs by year of follow-up did not differ appreciably and showed no systematic trend. The risk of non-fatal/fatal myocardial infarction was reduced by 15% in those allocated to more-intensive compared to less-intensive glycaemic control, with a non-significant reduction in the risk of non-fatal/fatal stroke and no difference for hospitalised fatal heart failure. 1,864 patients died. Cause of death was categorised as cardiovascular or non-cardiovascular in all but 18 participants. The estimated HR for cardiovascular death varied among trials but the overall estimate did not differ significantly from unity. What conclusions/implications for practice were drawn by the authors? More intensive therapy resulted in less risk of major cardiac events in patients with Type 2 Diabetes. There was a modest reduction in major macrovascular events with greater glucose lowering in the groups that have more intensive glycaemic control. Your Critical Appraisal of the Study’s Appropriateness for Application to Clinical Practice Is the sample size adequate? Support your response. Yes. The sample size included some 27,000 patients and over 2,300 cardiovascular events. There were a total of four studies that were included. This is a large enough sample to determine the effects of intensive therapy verses standard therapy, because there was a large number of studies that were included. However, the authors did not disclose how many studies were included, but, with the number of participants in this meta-analysis, the conclusion was that the meta-analysis included many studies. Are the research methods used appropriate for the study’s research question/objective? Support your response. Yes. It seemed the the authors had wide inclusion criteria, and they were only interested in trials that had more than 1,000 person years follow-up for the trials with a minimum of 2 years median follow-up. These are solid criteria for inclusion, because the person years follow-up is large, and the authors also were interested in more long-term outcomes. Also, the authors made sure that the studies included followed up on at least 90% of the participants, so the vast majority of the studies had a very large percentage of follow up. Also important was the fact that the studies had to be double-blind, which means that these studies are valid. Their study was also focused, in that it excluded studies that featured other risk reduction strategies, type 1 or gestational diabetes and young adolescents and children. Was the completed search systematic, comprehensive, and without bias? Support your response. Yes. The bias was eliminated through the use of double-blind or blind studies. The search was also systematic and comprehensive, in that the authors searched for the articles by using a wide array of tools, which included journal articles, trial registers and equiry of colleagues. Because there was a wide net cast, this search was systematic and comprehensive. Were selection criteria clearly described? Are they appropriate? Was bias demonstrated in the study’s inclusion/exclusion criteria? Support your responses. The selection criteria was clearly described, and the individual trials were also clearly described in a table that stated the key characteristics of trials and length of follow-up. There was not bias in the inclusion/exclusion criteria, as they specifically only selected double-blind or blind trials. Is the research recent enough to be applied to current clinical practice? Support your response. Three of the trials that were described in this meta-analysis were from 2008, so these are recent enough that they can be applied to clinical practice. One trial was from 1998, which is old, therefore this is a study that would be less likely to be relevant to current practice. Were the study results significant (level of significance)? Support your response. They were significant, in that the risk of cardiovascular events went down by 9% in the group that were subjected to more intensive therapy, and there was a 15% reduction in risk of myocardial infarction. These are significant reductions in these numbers, even if mortality did not increase. Is the study and its findings directly applicable to your EBP question (match all selection criteria)? Support your response. Yes. It involved the patient population of diabetic patient (P), studies on the effect of intensively lowering blood glucose (I) compared to standard treatment (C) on the incidents of microvascular events (O). Read More