There is a deadly association between diabetes and sepsis. To understand this association, this paper will review current literature on this topic. The literature review will give particular attention to the pathophysiology of sepsis and latest advancements in diabetes monitoring. Based on the studies reviewed, this paper will give some major implications for research and healthcare fields.
Sepsis and Diabetes
Jensterle (2017) defines diabetes as a chronic autoimmune condition that significantly impairs how the body uses blood sugar (glucose). Having diabetes implies that one must work throughout his/her life to control the blood sugar level to ensure that it does not get too high or too low. The level of glucose in a person’s body is an important factor. Jensterle (2017) argues that though the human body requires glucose for energy, excess of it destroys body tissues and too little starves the body important nutrients. Jensterle (2017) adds that having diabetes puts a person at a high risk of developing sores and wounds, which do not heal properly. While these wounds are present, they are highly vulnerable to developing infections. Further, Teslova et al. (2017) found that the presence of diabetes can make the infections to become severe quickly to a point that they overwhelm the body. When this happens, the body naturally responds by developing sepsis, which further graduates into septic shock. Simply put, sepsis refers to the body’s damaging response to infections.
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Overview of Sepsis
Wanget al. (2017) defines sepsis as an uncontrolled and exaggerated inflammatory response to an infection or body tissue injury. If left untreated, this could result in septic shock. Increased capillary permeability, reduced vascular resistance and massive vasodilatation in the body characterize septic shock, which cause refractory hypotension. As figure 1 illustrates, the result is irreversible tissue ischaemia, organ failure ultimately and ultimately death.
In figure 1, it demonstrates that the invading pathogens cause local infection in one part of the body. Notably, the bacteria from this infection leaks into the bloodstream allowing the infection to spread to the rest of the body. The body’s immune system is compelled to generate antibodies to fight the infection. When the bacteria already in the body combine meets with the strong immune response, the result is excess inflammation. This inflammation causes multiple organ dysfunctions and interferes with blood flow and ultimately death.
According to Wang et al. (2017), sepsis is responsible for an estimated 6000 deaths annually in the United States alone. This mortality statistic is higher than that of prostate cancer (3,200) and breast cancer (2,800) combined. Despite advancements in modern interventions and heightened awareness of the need for timely identification and treatment, sepsis remains the key cause of death from diabetes across the world. Latest research findings offer evidence that at least 40% of diabetic patients diagnosed with severe sepsis die. As revealed by Rudd et al. (2018), Sepsis contributes heavily in number of death cases witnessed in most middle and low-income nations. According to these scholars, some of the factors hindering the reduction of Sepsis include inadequate awareness, health inequity, poverty, inadequate resources in public health facilities, and acute systems of health delivery. The capacity of some healthcare facilities to handle this condition only worsens the situation.
The Pathophysiology of Sepsis
Fabbian and colleagues (2015) focused on the topic, and as revealed, possible association between Takotsubo cardiomyopathy, sepsis, and diabetes mellitus: a still open question. They discovered that sepsis has a complicated pathophysiology. Popular theories explain that multiple derangements prevail in sepsis that involves various body organs. Fabbian and colleagues (2015) cite that during the onset of sepsis, the reaction that a patient makes is largely biphasic and partly genetic in nature. The Systemic Inflammatory Response Syndrome (SIRS) overwhelms the patient’s immune system, causing the body to release proteins similar to a cytokine storm’ (Fabbian et al. 2015).This eventually leads to a cascade of destruction including Multiple Organ Dysfunction Syndrome (MODS), end organ failure and sudden death. Therefore, prompt diagnosis coupled with efficient and early intervention is paramount for one to survive.
Figure 2 gives a summary of the stages of sepsis. In this diagram, there are four stages of sepsis namely, SIRS, sepsis, severe sepsis and septic shock. The diagram offers a basic overview of how the condition progresses. In this diagram, the body naturally responds to infections through inflammation. Usually, adults are armed with defense tools and mechanisms designed to safeguard against harmful microorganisms. As shown in this diagram, in sepsis, a person loses this early physiological response to invading microorganisms. This culminates into an inappropriate and systematic inflammatory reaction that is both deadly and of overwhelming proportion to the body’s immune system.
Philipp et al. (2011) focused on the topic, Diabetes and Sepsis: Preclinical Findings and Clinical Relevance. In their investigation, they found that the result is SIRS, which trigger monocytes, neutrophils, platelets and macrophages to bind to endothelial cells. According to Philipp et al. (2011), the primary role of endothelial cells is selective permeability to serve as an anticoagulant interface and ensure vaso-regulation. Marked phagocytosis takes place and combines with leucocytes triggering further ejection of cytokines and heightened vasodilatation or vasoconstriction.
Figure 3 illustrates that the invading pathogens or damaged tissues often release a large amount of damage associated molecular patterns (DAMP) that initiates SIRS and when exaggerated, they lead to multiple organ failure and eventually death. In this figure, an activation of the coagulation system follows. Due to these changes, the patient experiences cell damage, mitochondrial disruptions in the cells and develops microthrombi. Moreover, cytokines contribute to liver stimulation and increase the generation of the protein called C-reactive.
Latest Developments and Studies
A series of emerging studies offer adequate proof that diabetic patients are highly susceptible to infections. However, the deadly association between diabetes and heightened susceptibility to infections only became clear recently. Latest clinical research findings offer sensibly solid proof that diabetes patients are highly susceptible to various infections. Additionally, other uncommon infections like emphysematous cholecystitis, rhinocerebralmucormycosis and malignant external otitis tend to exclusively occur in diabetes patients. Liberman and Drobnič (2017) focused on diabetes technology and the human factor. They reveal that diabetes associated complications like neuropathy and microvascular damage are major contributors to skin ulceration that predisposes individuals to secondary skin infections. In a study using patient data from 8000 diabetic patients and demographically matched controlled samples across the United States, Fabbian et al (2015) found that diabetes was a primary risk factor for skin infections such as cellulitis and abscess. Also, Fabbian et al identified other infections like urinary tract infection as prevalent in diabetes patients. In diabetes women, there was a two-fold rise in the risk of UTIs compared to the sex-matched control samples.
At the population level, there is enough evidence for a higher infection rate in diabetes patients unlike non-diabetes subjects. In a large cohort study using American database, Philipp and colleagues (2011) discovered that almost half of the subjects with diabetes reported at least one hospitalization or doctor’s claim for an infection. Compared to the non-diabetes subjects, diabetes subjects have a greater risk ration (RR) for acquiring an infection and developing an infectious disease associated with hospitalization.
Though the studies reviewed offer latest information and developments on diabetes and sepsis, they have been widely criticized for numerous methodological issues. Most studies reviewed lacked detailed patient characterization and the impact of diabetes-associated variables like degree of obesity, type of diabetes, presence of secondary complications and insulin resistance. This makes the independent link between diabetes and patient susceptibility to infections unclear. In addition, most of them are epidemiological studies. Therefore, they suffer the risk of selection bias because the doctors in charge of diabetes patients could have a lower threshold for patient hospitalization. This means the doctor could easily overestimate the risk for infection and subsequent hospitalizations.
Advancements in Diabetes Monitoring
Long time ago, it was impossible for diabetes patient to monitor their blood glucose levels while at home. However, Ala-Kokko et al. (2016) reveal that over the years, there have been great advancements in the tools used to monitor diabetes. Moreover, Ala-Kokkoet (2016) asserts that it has become possible for patients to control the consistency of enzymes contained in the test strips. All these improvements have contributed to increased accuracy in diabetes monitoring. Čokolič et al. (2013) focused on the use of continuous glucose monitoring device to improve long-term management of diabetes mellitus. They found that in recent years, one of the most notable advancement is the advent of continuous glucose monitors (CGM). With these devices, patients can obtain a continuous readout of their blood sugar levels. However, it is unfortunate that these devices only measure blood sugar level in an extremely different manner besides being less accurate. CGM often measures blood sugar levels within the intestinal fluid found between the cells and under the skin instead of measuring the sugar levels in the blood. Here, the disadvantage is that intestinal fluid tends to lag behind blood sugar by roughly 15 minutes (Ala-Kokko, 2016).When there is low fluctuation or for fasting blood sugars, accuracy is paramount. However, given that sugar is falling or surging quickly, these meters could easily lose their accuracy. For this reason, patients using CGM are advised to also use the conventional meter to monitor their glucose levels regularly.
In terms of research, it is almost impossible to predict the future direction. Diabetes patients always know that there exist a myriad of new approaches, hopeful cures, technologies and other potential advancements to assist in the care and management of the condition. Personally, I feel that many of these improvements may not advance to the market. For one, research, development and testing take a very long time. Moreover, most of these advancements may prove to be unstable, impractical or could simply fail to deliver the promise they made initially. Ricklin & Lambris, (2013) explored progress and trends in complement therapeutics. They discovered that one line of inquiry appears to hold some realistic promise within the near future; tattoo blood sugar readers. Battelino et al. (2014) report that for a long time, a group of experts from the Massachusetts Institute of Technology (MIT) has been investigating a new technology which can be used to monitor diabetes. According to Battelino et al. (2014), this technology entail injecting unique ink comprising of glucose-responsive nanotubes immediately underneath the skin and create a patch. Exposure to infrared light would make this patch to change its color and then reflect the patient’s blood sugar. Though this technology sounds promising, I have not heard any recent news or updates from the MIT group of experts about this. Another recent promising advancement is that of Amay Bandodkar and his colleagues (Battelino et al. (2014). They invented a wearable patch, which also uses a glucose responsive ink aimed at giving a continuous readout of blood glucose. Human trials have been conducted to test this device and it has proven to yield results, which are as accurate as those of traditional finger stick tests. However, I must mention that these trials were based on a very limited sample size. According to Battelino et al. (2014), Amay Bandodkar and his colleagues are currently working to create an accompanying meter, which provides a traditional number indication. Eventually, it is likely that the device will equally communicate with patients’ healthcare givers through Bluetooth because we are currently living in a new media era.
Over the past many years, the management of diabetes has undergone some dramatic changes. Although today’s therapeutic options are significantly highly effective, within the next a thousand years, our successors are likely to perceive them as arcane given that the present trajectory in advancements continue. Even so, the current treatments used in diabetes management have dramatically reduced mortality and morbidity rates.
Conclusions
This literature review has some important implications for the research field and the healthcare field. Beginning with the research field, the reviewed studies find that diabetes patients are highly susceptible to obtain infections. But, it is challenging to interpret the clinical and preclinical data. Most of these researchers employed a hyperglycemia model, which involves inducing diabetes into animal samples by destroying their pancreatic b-cells. Such animals are similar to type 1-diabetes patients with recent disease onset. However, these models are only conditionally applicable to type 2 diabetes patients. Some of these researchers have used models with leptin-deficient obese mice to reproduce type 2 diabetes. These models have been criticized for failing to accurately account for long term complications associated with hyperglycemia namely chronic renal failure and arteriosclerosis. Often, the clinical studies are thwarted by their insufficient description of duration and type of diabetes, degree of obesity, secondary complications and insulin resistance. It would be interesting for future studies to consider if genetic polymorphisms are responsible for variations in susceptibility and results as presented for other illnesses. Further, diabetes patients could have a lower threshold for hospitalization; this is likely to cause a selection bias when the researcher is recording susceptibility rates and possible outcomes and risks. Future studies must look at diabetes as a syndrome, considering key cofounding variables like obesity, secondary complications, hyperglycemia, endothelia dysfunction and insulin therapy to better understand the complex relation between sepsis and diabetes in human beings.
Research in this topic seeks to better understand the pathophysiology of sepsis to determine key points, which may be receptive to treatment, and to learn why people with diabetes differ in terms of their sepsis outcome. Identification of markers, which make people vulnerable to severe sepsis and detect early sepsis, would determine when to initiate intervention. To translate this knowledge into cure and treatment of diabetes patients, large controlled clinical trials would be paramount.
For the healthcare field, in future, practitioners must develop initiatives that entail a spectrum of sepsis from early identification to prevention to treatment to management in the outpatient, in the hospital and post-sepsis care. Healthcare organizations can reduce the burden of sepsis by partnering with clinicians and communities to introduce initiatives aimed at preventing infections that trigger sepsis. These initiatives should also seek to promote clinician education regarding recommended early recognition of sepsis and management. Early infection detection and prevention programs, which span the spectrum of integrated inpatient and outpatient system, may prevent the onset of sepsis and cut sepsis-related deaths. Practitioners could introduce antibiotic stewardship programs aimed at reducing unnecessary consumption of antibiotics to reduce the burden of sepsis. Research showcases that the recent exposure to antibiotics heightens the risk of developing sepsis.
Conclusively, sepsis remains a serious health concern in diabetes due to its high morbidity and mortality rate. Early recognition and intervention are critical to deliver timely, proper treatment and increase the patient’s chances of survival. At the moment, practitioners focus on biomarkers to diagnose sepsis. Advancements in this area have been sluggish as most efforts are focused on single markers. However, due to the complex nature of sepsis reaction, practitioners should emphasize a combination of markers for sepsis diagnosis. The adoption of biomarkers in future could help enhance the outcomes by increasing the accuracy of diagnosis, cutting the required time to establish the proper intervention and preventing unnecessary tests and treatments.
Scholars have come out to point out major challenges facing the fight against sepsis, and have proposed strategies that can go a long way to solve it. One of the strategies they believe can help alleviate the situation is through strengthening the public health. In addition, experts believe the acute health care delivery systems can equally be empowered. In their observation, the afore-mentioned move can be orchestrated through confronting wealth inequalities and poverty directly. At the same time, authorities should prevent the acquisition and the spread of infectious diseases. Individuals should be enabled to have access to primary health care of high quality. In the same vein, experts suggest that public transport should be made function, besides ensuring that pre-hospital emergency medical services are made readily available to the people. Referral centers should be should be adequately staffed, and supplied with the appropriate staff, and equipment.
There is a great deal of information focusing on how molecules interplay to cause harmful inflammation in diabetes patients. Various scholars have conducted intense researches, most of which are characterized by key variables of the molecular pathways. These studies agree that sepsis is a serious condition that disables and kills millions hence it warrants early detection and rapid intervention for survival. Sepsis tends often results from an infection in any part of the body like influenza, pneumonia and urinary tract infections. Statistics indicate that, globally, at least one-third of diabetic patients who develop sepsis die. Those who survive suffer life-changing impacts like chronic pain and fatigue; post-traumatic stress disorder (PTSD); organ amputations; and organ dysfunction.
While at it, experts believe that conducting inclusive research will go a long way in ensuring sepsis is dealt with accordingly. This strategy can be achieved by ensuring that science research is heavily implemented, and access of data is open to interested parties. The government in the most affected nations should strive to integrate research done on sepsis with the clinical communities. Increased partnership should be encouraged between pediatric research communities and adults. In essence, advocacy can help a great deal in brokering a solution to deal with sepsis. This can be done through supporting intentional sepsis projects and identifying sepsis as one of threats to public health. Researchers and scholars are heavily in support of establishing data driven management guidelines. According to their suggestion, partnerships should be formed between public health professionals, clinicians, and researchers in a bid to establish appropriate guideline. Focus should be emphasized on cost effective, high yield and interventions that are readily available.
To understand the complex interplay between sepsis and diabetes, this paper reviewed current literature on this topic. The literature reviewed gives particular attention to the pathophysiology of sepsis and latest advancements in diabetes monitoring. Based on the studies reviewed, this paper gives some major implications for research and healthcare fields.
References
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