Stranahan on Diabetes Impairs Hippocampal Function

Significance of Diabetes in cognitive impairment

Diabetes mellitus has many adverse effects on the brain apart from the cardiovascular and peripheral nervous system effects. The increasing prevalence of diabetes mellitus due to the sedentary lifestyles and high-calorie diets of the modern world and enhanced longevity is significant in that the risks of depression, dementia and cognitive decline is heightened.

It is known that diabetes influences the hypothalamic-pituitary-adrenal axis. However, the role of this system in diabetes-impaired cognitive decline has not been fully investigated. Stranahan and his team have attempted to study the effects of diabetes on the hippocampus, which is the part of the brain associated with recent memory, perforant path synaptic plasticity, and adult neurogenesis. They also indicated that corticosterone, a glucocorticoid, mediated the effects. The research was done in insulin-deficient rats and insulin-resistant mice.

Studies that echo similar sentiments

Another study has echoed the same idea that increased glucocorticoid levels produced dysfunction in the hippocampus and is associated with spatial learning deficits in rats (Lupien, 1998). The study showed that aging people with high levels of cortisol

showed a lower volume (14% reduction) of the hippocampus and a deficit in hippocampus-dependent memory tasks when compared to people with normal cortisol. Other studies (Issa, 1990) have mentioned that the cumulative effect of the high level of glucocorticoids produces structural and functional effects on the hippocampus. They compromise hippocampal integrity and the cognitive functions dependent on the hippocampus (Issa, 1990). Glucocorticoids are secreted from the adrenal gland after stress (Karst, 2000).

It is mentioned that these hormones affect synaptic plasticity apart from modulating ionic currents, monoaminergic transmission, and cellular viability, mostly in the hippocampus, where corticosteroid receptors are enriched. The study acknowledges the role of glucocorticoid receptors in hippocampal integrity, mental performance in aging, and psychiatric disorders (Karst, 2000). Identification of the signaling pathways of glucocorticoids helps in developing intervention strategies to reduce cognitive impairment.

Summary

Human beings with both Types I and Type II diabetes mellitus showed a greater cognitive decline when compared to similar-aged non-diabetic persons. Rodents who were made diabetic (Type I) by being given streptozocin, a pancreatic beta-cell.

The toxin showed a lesser performance in spatial learning ability. A similar result was seen. in mice with leptin receptor deficiency which had resulting Type II diabetes with Hyperglycemia, obesity and increased circulating corticosterone. Mechanism of cognitive dysfunction was, however, not discovered.

Strong synapses between neurons in the dentate gyrus of the hippocampus and the addition of new neurons are essential for mediating memory and some types of learning. This inference has been made from animal models. Streptozocin-induced diabetes in rats has indicated impairment in the long-term potentiation of synaptic transmission or plasticity of synapses. Adult neurogenesis was also impaired. As both types of diabetes demonstrate impairment in plasticity, it was obviously not due to insulin changes. People with uncontrolled diabetes had high levels of cortisol due to hyperactivity of the HPA axis. Experimental diabetes had also been known to show a high level of glucocorticoids, but the HPA activation appeared to be not directly due to hyperglycemia. Glucocorticoids had been associated with cognitive impairment in psychosocial stress, aging, and Alzheimer’s but not yet with diabetes. These findings were corroborated with animal experiments. Corticosterone and stress have been found to impair neurogenesis and synaptic plasticity in animals. The impression that diabetes also impairs cognitive functions through glucocorticoids is surmised, hence this experiment.

It was found that maintaining the normal physiological corticosterone prevented learning deficits. The sham-operated mice showed impaired cognitive function. Mice that had adrenalectomy and corticosterone replacement showed a preference for a new object or reduced impairment. Insulin deficient diabetic rats had an elevated cortisol level and thereby showed a learning impairment. The diabetic rats with adrenalectomy and cortisone replacement had no impairment.

The synaptic plasticity in mice with normal physiological corticosterone was not impaired. Picrotoxin was used to decrease local inhibition and GABAergic excitation in insulin-resistant mice, which showed a reduced LTP (long-term potentiation). Sham-operated insulin-deficient rats showed lowered LTP. The streptozocin-induced diabetic rats with intact adrenals showed a lowering of LTP. Lowering the corticosterone reversed the diabetic effects on LTP. Normalizing the glucocorticoid level, the synaptic plasticity at the perforant path at the dentate gyrus was measured. The mice and the streptozocin-induced diabetic rats showed reduced LTP in the presence of picrotoxin. The impairment was prevented by adrenalectomy and corticosterone replacement in both mice and rats.

Baseline synaptic transmission was not different in mice and controls. This was lowered in rats.

The suppression of dentate gyrus cell proliferation in diabetic rodents was caused by elevated corticosterone. Sham-operated mice showed a reduction in neuron proliferation. The diabetic mice showed no difference from the non-diabetic ones.

Lowering the corticosterone level in experimental diabetes did not have any impact on the insulin and glucose levels of any of the animals. Two groups of mice were adrenalectomized, and one group was given low dose corticosterone, and the other a high dosage. The second group showed impairment. Object recognition memory was also affected similarly.

The experiments were done with controls to prove the variations possible with two groups of experimental animals, insulin-resistant mice and insulin-deficient rats, which were sham-operated, streptozocin induced diabetic ones, adrenalectomized ones, and those with corticosterone replacement.

The results showed that diabetes-induced impairments in synaptic plasticity, neurogenesis, and cognitive impairments in the dentate gyrus of the hippocampus and that these impairments are mediated through glucocorticoids or corticosterone. The hypothesis has been proved. Maintaining the normal level of corticosterone allowed the restoration of LTP at the synapses at the perforant path-dentate gyrus and normal neurogenesis. Lowering the glucocorticoid improved the normal functions. Insulin had no role in these functions.

Limitations

The question of insulin receptor signaling has not been answered in this experiment. An increased level of corticosterone is known to influence insulin receptor signaling by reducing it. The possibility of corticosterone negatively affecting the hippocampus by reducing insulin signaling has not been studied here. The effect of diabetes on learning-induced changes in hippocampal glucose metabolism has also not been studied yet. The role of the new neuron after degeneration and injury has yet to be studied.

Salient points in critique

The literature review has taken references from reliable and authentic sources, 75 % of which are very recent sources from 2005-2007. It is therefore up-to-date and based mainly on primary sources. We can expect that the latest findings and views of the subject have been reviewed and that the present study has been derived naturally. It must be noted that the argument was well placed and worded explicitly with no superfluous language or information. The hypothesis is not mentioned as such, but the idea is evident in the title of the research paper, which also gives a good idea of the variables being studied. The study has achieved what it started out for. The problems being discussed, the methods, results, and conclusions appear suitable.

The experiments were done on animal models (adult male Sprague-Dawley rats and male mice mutant for leptin receptor), which were secured from 2 laboratories. The US National Institutes of Health guidelines were followed for animal care and experimental procedures, and the experiments were approved by the US National Institute on Aging Animal Care and Use Committee. All the animals had free access to food and water. The procedures in the various sections followed instructions in the “Supplementary methods.” Statistical analysis was done with SPSS version 11.0.

Significance was set at p<0.05. Graphs were generated with Graphpad Prism 4. The behavioral data were analyzed with repeated measures ANOVA and Tukey’s post hoc test.

The limitations have been mentioned, and guidelines for future researches have been added. A positive suggestion worth mentioning is that no study has demonstrated the effect of diabetes on learning-induced changes in hippocampal glucose metabolism. Moreover, studies that have been done on animal models need to be replicated in humans.

References

Issa, A., Gauthier, S. & Meaney, M.J.; (1990), “ Hypothalamic-pituitary-adrenal activity in aged cognitively impaired and cognitively unimpaired aged rats” Journal of Neurosci. 10, 3247–3254 (1990).

Karst, H. Y.; Karten, J. G.; Reichardt, H. M.; de Kloet, E. R.; Schütz, G. and Joëls, M., “Corticosteroid actions in hippocampus require DNA binding of glucocorticoid receptor homodimers”, Nature neuroscience, Vol 3, No.10, 2000, Nature America Inc.

Lupien, Sonia J.; de Leon, Mony; de Santi, Susan; Convit, Antonio; Tarshish, Chaim and Nair, N.P.V. et al, “Cortisol levels during human aging predict hippocampal atrophy and memory deficits”, Nature Neuroscience, Vol 1, No. 1, 1998, Nature America Inc.

Diabetes in Urban Cities of United States

Introduction

Diabetes mellitus (DM) is one of the common metabolic disorders affecting many citizens in the United States and across the globe. This chronic condition is divided into these two categories: type I and type II. DM type I is usually associated with autoimmune destruction of the beta cells in the pancreas, which are responsible for the production of insulin. Those affected by the condition should receive adequate insulin in order to survive.

DM type II occurs when there is insulin deficiency and/or resistance in the body. The purpose of this research study is to examine how and why diabetes has become a major health problem in America’s urban population. Specifically, this paper will examine how many people in metropolitan cities contract this disease, its leading factors and symptoms, and the most appropriate treatment methods. The discussion will also examine the cost of treating diabetes.

How People in Cities Contract Diabetes

The latest findings by the National Institute of Diabetes and Digestive Kidney Diseases (NIH) revealed that over 30 million American citizens were living with diabetes (Zimmet). In 2018, the CDC went further to indicate that around 7.2 million people in different parts of the United States were living with undiagnosed diabetes (Rege). The highest rates of this chronic condition are currently found among individuals from minority racial groups.

The elderly were also observed to record increased cases of this condition. Past studies have mainly focused on the prevalence of diabetes types I and II in underserved populations and rural communities. Recently, analysts and social workers have indicated that diabetes remains one of the leading health challenges in different urban areas across the country. This is the reason why there is a need for all parties and organizations to collaborate and eventually address this health predicament.

The relationship between urban lifestyle and diabetes is an area that is attracting the attention of many health practitioners, dieticians, and social workers. Individuals living in metropolitans are predisposed to numerous health complications, including obesity, diabetes, stroke, and cancer (Zimmet). This means that there are certain aspects or conditions that explain how such individuals contract this chronic condition. In a study by Yang et al., it was revealed that many people living in metropolitan cities led unhealthy lifestyles (228). Such malpractice was making it impossible for them to engage in a number of activities, including exercises.

The majority of them use cars, trains, or buses to meet their transportation needs. They also walk for very short distances, thereby exposing themselves to obesity. These are some of the risk factors for the development of diabetes.

Many urban areas are crowded and characterized by inappropriate surroundings. This means that citizens living in different American cities are exposed to polluted gases and chemicals that increase their chances of developing various health complications. The absence of adequate playing grounds explains why such dwellers are forced to lead sedentary lifestyles (Yang et al. 230). Consequently, the number of people living with diabetes types I and II will continue to rise in different metropolitan cities across the United States.

Many researchers have tackled the issue of diet in an attempt to understand how and why urbanization is currently associated with increased levels of diabetes. For example, Rege realized that many people living in urban areas were consuming large quantities of junk foodstuffs. This means that they eat foods containing fats, sugars, and carbohydrates. Such unhealthy practices predispose more people to obesity and other opportunistic diseases, such as diabetes. Any effort aimed at addressing this health challenge should, therefore, begin by tackling the problem of dietary intake.

Urban areas are characterized by inequalities, congestion, and poor economic outcomes. Individuals from minority or underprivileged backgrounds find it hard to acquire adequate financial resources to meet their needs. Most of the people affected by such predicaments come from families who have histories of diabetes (Rege). Consequently, they develop this condition and eventually lead unhealthy lifestyles.

Another possible explanation for the increasing levels of diabetes in urban areas is the absence of proper mechanisms and programs to empower more people (Zimmet). This challenge is associated with the increasing levels of congestion. Additionally, many urban areas do not benefit from the functions and roles of community health and social workers. Consequently, the affected dwellers lack adequate knowledge and resources that can guide them to tackle the problem of diabetes.

Factors and Symptoms of Diabetes

There are various risk factors for diabetes mellitus that people should always take seriously. This means that the underlying cause of every type of diabetes will vary from person A to B. However, the common aspect of DM is that it eventually results in increased sugar levels in the body. The elevated quantity of glucose in the blood will trigger various health complications. The first risk factor for this condition is overweight or obesity. The cells of people with increased fatty tissue tend to become insulin resistant. This is the reason why physical activities are recommended to individuals who are at risk of developing diabetes (Chong et al. 47). The absence of exercise is another outstanding risk factor for diabetes. People who smoke and drink alcohol are at risk of developing this health condition.

Family history is another risk factor for DM. People whose relatives had DM tend to have increased chances of developing it. The race is also a critical factor since there are specific groups or populations that record increased cases of diabetes, such as African Americans, Hispanics, and Asian Americans (Rege). Age is another factor that analysts and researchers consider when focusing on the diabetes epidemic. Chong et al. indicate that elderly citizens and those above the age of 50 are usually at a higher risk of developing this condition (48). High blood pressure is another potential trigger for this medical condition.

Diabetes presents unique symptoms depending on the percentage of sugar in the blood. Those affected by DM type I tend to experience symptoms much faster. There are specific signs and symptoms observed in individuals who have both types I and type II DM. The common ones include extreme hunger, sudden or unexplained weight loss, frequent urination, increased thirst, irritability, slow-healing sores, blurred vision, and fatigue. The presence of ketones in a person’s urine can be a sign of diabetes. These are byproducts of the breakdown of fats and muscles occurring in the body due to the absence of insulin (Mendenhall 42).

Another important issue people should take into consideration is the nature and development of diabetes. DM type I can develop at any age after birth. However, it is usually recorded during adolescence or childhood (Mendenhall 59). Although DM type II is common in persons about the age of 40, it can still emerge at any given age.

Treatment and Cost

Health practitioners classify DM as one of the chronic diseases that all affected patients should find evidence-based strategies to manage. There are various strategies that people can use to treat or live with this condition for the rest of their lives. Those who have diabetes type I should receive daily injections of insulin to keep the level of blood glucose in check. This hormone is useful since it helps the body absorb and convert consumed food into energy (Chong et al. 47). Patients who fail to get their daily injections will die within a short period.

Those suffering from DM type II can manage the condition without necessarily having to take drugs or insulin. The main objective is to ensure that their blood glucose levels are within a healthy range. One of the evidence-based initiatives people consider to manage this condition is that of losing weight. Additionally, patients should focus on the best approaches to monitor their body mass indexes (BMIs). They should also consider meal plans that can minimize the amount of sugar in the body. Mendenhall goes further to indicate that exercises and weight control measures might be unable to manage their blood glucose levels (92).

This kind of knowledge explains why there are various oral medications and insulin injections available for persons who have this kind of diabetes. It is appropriate for the affected individuals to liaise with their physicians and dieticians if they are to record positive results (Zimmet). With proper treatment procedures and medications, the chances are high that the affected persons will overcome most of the challenges or complications associated with type II diabetes, including eye disease, kidney failure, and heart attack.

The first medication for treating type II DM is called Metformin. The common types include Glumetza and Glucophage. These drugs work by lowering the amount of glucose produced by life. It also boosts the body’s sensitivity to insulin. Sulfonylureas are also useful since they help the body of the affected patient to secrete more insulin. Meglitinides stimulate the human pancreases to release more insulin. Thiazolidinediones are also important because they reduce the chances of gaining weight (Mendenhall 103). However, they trigger various side effects, including anemia and heart failure. SGLT2 inhibitors are also essential because they prevent the kidney from absorbing high quantities of sugar or glucose. Insulin therapy is also recommendable since it provides numerous positive effects.

The cost of treating diabetes per patient is quite high. Yang et al. indicate that people who have this condition have to spend around 13,700 US dollars annually (231). However, around 8,000 US dollars go directly to the treatment and management of diabetes. Such a high cost explains why the government should implement evidence-based strategies and programs to deal with this health predicament and ensure that all patients achieve their potential.

Conclusion

The above research paper has revealed that diabetes mellitus is a terminal condition that continues to affect many American citizens in different urban areas. The discussion has outlined smoking, alcoholism, sedentary lifestyle, and inappropriate diet as some of the leading causes of diabetes. It is, therefore, appropriate for the government to implement appropriate programs, policies, and initiatives to address this health predicament. Urban dwellers at risk of developing this condition should engage in exercises, eat balanced diets, and avoid smoking. Patients should also embrace insulin therapy and take drugs in order to lead high-quality lives.

Works Cited

Chong, Shanley, et al. “Lifestyle Changes After a Diagnosis of Type 2 Diabetes.” Spectrum, vol. 30, no. 1, 2017, pp. 43-50.

Mendenhall, Emily. Syndemic Suffering: Social Distress, Depression, and Diabetes among Mexican Immigrant Women. 2nd ed., Routledge, 2016.

Rege, Alyssa. “ Becker’s Hospital Review, 2017. Web.

Yang, Wenya, et al. “Diabetes Diagnosis and Management Among Insured Adults Across Metropolitan Areas in the U.S.” Preventive Medicine Reports, vol. 10, no. 1, 2018, pp. 227-233.

Zimmet, Paul Z. “ Clinical Diabetes and Endocrinology, vol. 3, no. 1, 2017. Web.

Diabetes: Discussion of the Disease

Introduction

The state in which a person’s body stops properly using or producing insulin is known as diabetes. When insulin is not used or produced properly then the sugar or glucose levels in our body rise, which results in diabetes. Insulin can be described as a hormone that helps sugar, starch and other food material to get converted into energy.

If elevated sugar level is not controlled then it might lead to very serious health conditions like loss of vision, kidney failure, amputation of limbs, stroke, heart attack etc. Diabetes has become a very common disease and hence there is a huge risk of a large number of people getting affected by these complications. There are also millions of people who are suffering of pre diabetes – a condition in which the blood sugar level is higher than normal but not as high as in patients of diabetes. This category of people has immense risk of turning diabetic if they do not bring changes in their lifestyle.

Charateristics of diabetes

Diabetes can be broadly divided into three categories – Type 1, Type 2 and Gestational diabetes. The maximum numbers of people suffer from Type 2 diabetes. According to Smith, “Type 2 diabetes is the most common type, affecting 90 – 95% of persons with diabetes.” (2006, p.3) Type 1 diabetes affects a minimal number of diabetic patients. Around 5-10% of persons with diabetes get affected by it. The majority of them are young adults and children. Whereas, Type 2 diabetic patients are mostly over 40 years of age. In very few instances children develop it. The people who have developed Type 1 diabetes are generally thin or have normal body weight. The patients of Type 2 diabetes are overweight. The rate of onset is quick in Type 1 patients while the rate of onset is slow in Type 2 patients. While there is no family history involved in Type1 diabetes, family history is a cause of Type 2 diabetes. More than one shot of insulin is required per day to control Type 1 diabetes whereas Type 2 diabetes is controlled by increase of body activity and nutritional changes. However, “For some sufferers of Type 2 diabetes treatment with dietary changes and tablets is not entirely effective for diabetes management, and they may then need insulin injections.” (Dr. Sims, 2007. para. 12) It is difficult to control the fluctuative range of blood sugar in Type 1 diabetes while it is easy to control that in Type 2 diabetes. The similarities between these two types of diabetes are that both respond to changes in diet and body activity.

As the name suggests Gestational diabetes is related to pregnant women and is temporary. Gestational diabetes, though harmful for baby and mother, gets cured completely after the birth of the baby. It is a temporary phase, which about 8 % of pregnant women suffer from each year. It is a condition of increased sugar level during pregnancy and puts women in danger of getting Type 2 diabetes in future. Pregnant women develop this disease at the later stage of their pregnancy. Most of the child’s body gets formed by then. Neglecting it is not good because if left untreated it might affect and harm the baby in the mother’s womb. There are high chances of developing this problem again in the consecutive pregnancies.

There are three methods in which diabetes can be diagnosed. These are “a random or casual glucose level of greater or equal to 200 mg / dl, a fasting blood glucose of greater or equal to 126 mg / dl or 2 hours blood glucose greater or equal to 200 mg / dl during an oral glucose tolerance test.” (Smith, 2006, p. 5)

Symptoms of diabetes

Excessive hunger (polyphagia), excessive thirst (polydipsia), frequent urination (polyuria), slow healing of wounds, frequent infections, feeling of tiredness, dry skin, weight loss are the most common symptoms of diabetes.

Physiology of diabetes

In Type 1 diabetes, the pancreatic beta cells undergo cellular-mediated autoimmune destruction. There is difference in the rate of destruction of beta cells in different people. Environmental as well as genetics factor are responsible for this difference. Islet cell autoantibodies, autoantibodies to glutamic acid decarbooxylase, autoantibodies to the tyrosine phosphatases IA – 2 AND IA – 2B and autoantibodies to insulin are the markers of the immune destruction of beta cells. Around 85-90% of diabetic patient suffer from the presence of one or more of these antibodies when there is initial detection of fasting hyperglycemia. In some forms of type 1 diabetes no evidence of autoimmunity is found. These forms of diabetes are known as ‘idiopathic’. In such cases the individuals are prone to ketoacidosis as their body suffer permanent decrease in concentrations of insulin.

In Type 2 diabetes, the cells prevent glucose from entering them as they become resistant to insulin. The level of insulin needed to maintain normal level of blood glucose stops being produced or released by the pancreas as time passes.

When a woman is pregnant her placenta supports the foetus growing in her womb. But sometimes hormones of the placenta start blocking the insulin’s action in the pregnant women’s body. Since her body does not get appropriate amount of insulin she develops gestational diabetes.

Treatment of diabetes

Diabetes can be treated by both pharmacologic and non-pharmacologic ways. Nutrition therapy and physical activities are the non-pharmacologic ways of treatment. Per week a diabetic patient should have at least 150 minutes of moderate to vigorous physical activity. If one is not in the habit of exercising then he should begin with moderate exercises to the more vigorous exercises in order to reach to the desired level of physical activity. There should be a balance of carbohydrates, fats and protein in the diet as part of the nutritional therapy. Type 2 diabetic patients suffer from excess weight so their aim should be to control their increasing weight. They should follow a diet chart, which consists of 50–60 % of calories from carbohydrates, 30 % of calories from fat and 10–20 % of calories from protein. Calories from saturated fat should not increase from more than 10% each day.

Patients should stop smoking and go for regular blood glucose monitoring to check how much more they need to control. There are many options of pharmacologic treatment. These options are insulin, inhaled medication, oral agents and new inhaled injectibles. Insulin is injected through pen needles or syringes. Hip / buttock area, outer thigh, abdomen and back of arm are the areas in which it is injected. The dose depends upon the complications of the case. Inhaled medication is also insulin, but is available in powder form. Insulin should be taken within 10 minutes of a meal. Sulfonylureas, meglitinides, thiazolidinediones, biguanide and alpha glucosidase inhibitors are some of the different classess of oral agents. All these classess have different dosing and side effects. These should be prescribed after studying the complete medical history of the patients. The injectible medications are exenatide (byetta) and pranlintide (smylin). Exenatide can be prescribed only to Type 2 diabetes, while pranlintide can be prescribed to both Type 1 and Type 2 diabetic patients. The doses of both these injectibles are different. Side effects like vomiting, nausea, weight loss, diarhhea etc. can be expected after the administration of these injectibles. They should be administered on the abdomen, thigh or upper arm.

Apart from the above-mentioned non-pharmacologic treatments Type 1 diabetic patients should also go for psychosocial counseling and regular glucose monitoring. Pharmacologic treatments include either continuous subcutaneous insulin infusion with the help of an insulin pump or multiple doses of insulin daily. If the patient is above 18 years of age then he can also take inhaled insulin before meals.

Treatment of gestational diabetes is simple. It requires a good meal plan and a good regimen of physical activity. In some cases it might also require regular blood glucose testing and insulin treatments. “Maternal follow-up, with an oral glucose tolerance test, should be performed 6-8 weeks postpartum, then at least every 2 years, because of the increased risk of developing permanent diabetes.” (Hoffman et.al., 1998, para.9)

Outcomes of diabetes

If the blood glucose level is not controlled then there can be several complications of this disease. The quality of a person’s life gets affected by it.

It impairs large and small blood vessels. These impairments are also known as macrovascular and microvascular impairments respectively. Macrovascular impairments result in coronary heart disease, cerebral vascular disease and peripheral vascular disease. As a result there is high risk of stroke and heart attack. There is also difficulty in proper circulation of limbs.

Microvascular complications result in nephropathy, neuropathy and retinopathy. This results in autoimmune thyroid disease, celiac disease, gum disease, end stage renal disease, decline in kidney function, cataracts, glaucoma and even blindness.

The outcome of gestational diabetes is that there is great risk of caesarean births. Also there are chances of delivering a fat baby. Due to excessive fat on the shoulders the baby can even damage his shoulders during the normal birth procedure. Also there is risk of him growing into an obese child and developing type 2 diabetes at later stage of his life.

Myth about diabetes

There is a very common myth that one should completely avoid fruits and starchy foods like potatoes, rice etc. if he is suffering from diabetes. But this is not true; one should not stop eating fruits and starchy foods completely thinking it to be a part of his treatment. Rather he should consult his physician and eat the recommended portions of these food items. People also completely avoid eating sugar and sweets as a measure to control their diabetes but there is no need to take such a stringent step. According to Funnel, “Sugar and sweets do raise your blood glucose, but people with diabetes can safely eat sugar as part of their meal plan. And just to clear up another myth, you can’t get diabetes from eating too much sugar.” (2008, para.2) Thus there should be a healthy meal plan in which you should manage your food intake for eg. 3 – 4 servings of carbohydrate, which you get from starchy food item, is not harmful.

Conclusion

Diabetes is a common disease in which the blood glucose level in a person is higher than normal. If the glucose level is not controlled then it can give rise to many complications. Fortunately with a well-planned meal, physical activity and medication, a person suffering from diabetes can lead a healthy life, free of any complications. “Many studies now show that good glucose control can significantly reduce or even stop complications. This means keeping the blood sugar level as close to normal as possible.” (Campbell, Song, 2004, para.54)

References

Smith, D.E. (2006). Type 2 Diabetes: 2006 Update. Pharmacy Tech Topics. Vol. 11. Illinois: Illinois Council of Health-System Pharmacists.

Smith, D.E. (2006). Type 2 Diabetes: 2006 Update. Pharmacy Tech Topics. Vol. 12. Illinois: Illinois Council of Health-System Pharmacists.

Campbell, I.W., Song, S. (2004). Web.

Dr. Sims, J. (2007) Type 2 Diabetes Mellitus Symptoms, Control and Management. Web.

Funnel, M.M. (2008). 10 Myths about Diabetes. Web.

Hoffman, L. et.al. (1998). Gestational diabetes mellitus — management guidelines. Web.

Current Dietary for the Treatment of Diabetes

Diabetes patients present with very different management problems and unraveling the specific factors which are contributing to the individual’s difficulty controlling weight and cholesterol and insulin level, and which of these factors it is feasible for the patient to modify, is an important aspect of the assessment process. In recent years, special attention is given to the individualization of dietary patterns and unique approaches to every patient and his disease history. This approach is based on cultural and regional differences, personal preferences, and style of life (Shaw, 2006).

Current dietary patterns suggest that cholesterol levels in food should be less than 300 mg/day. Fat appears to exert its greatest influence on energy balance through its effects on appetite. In studies where people have been allowed to eat as much as they like, the same quantity of food is generally eaten with high fat as with high carbohydrate meals, but because fat gram for gram contains more than twice the number of calories as carbohydrate, considerably more calories are consumed. Patients should reduce intake of trans fatty acids. It is highly recommended to use current fat replacers. also, patients with type II diabetes should consume saccharin, acesulfame potassium (K), aspartame, and sucralose instead of sugar (Clark, 2004). For instance, in their research, Shaw et al (2006) single out a specific diet and general diet for patients with diabetes. These researchers claim that a specific diet is based on self-care management aimed to help patients deal with dietary changes themselves. This diet involves fruits and vegetables, high-fat foods such as red meat, or full-fat dairy products. Doctors admit that an increasing amount of fruits and vegetables help patients to deal with diabetes and maintain a healthy way of life.

Fruits and vegetables are naturally low in fat, high in fiber, and are rich sources of vitamins and minerals, particularly antioxidant nutrients such as vitamin C, beta-carotene, selenium, and others such as lycopene. Epidemiological studies suggest the antioxidant and fiber content of fruit and vegetables protects against disease, particularly cardiovascular disease and cancer. The mechanism behind this protective effect is believed to be the capacity of antioxidants to scavenge free radicals, preventing DNA damage and subsequent mutation and decreasing atherosclerosis. The model divides food into five food groups and the size of the plate divisions represents the balance of foods needed to make up a healthy diet. It emphasizes the large contribution of fruit and vegetables, the need to increase starchy foods, and the importance of limiting, although not removing completely, foods high in sugars and fat. Regular eating is the main tool for diabetes treatment (Shaw, 2006). Researchers suggest eating 4-5 times a day instead of 3 times. Patients may skip meals as a means of controlling weight, turning to ‘grazing’ patterns of eating. To many, it may seem logical that one less meal a day would result in quicker weight loss. However, evidence suggests the reverse; meal skipping leads to increased eating and overcompensation later in the day and commonly to increased snacking on high fat, energy-dense foods. Patients who present with an irregular pattern of eating must initially focus on establishing regular meals and planned snacks.

Clark admits that traditional carbohydrate counting is also used in the treatment of diabetes, but it is based on individualized approaches and counting methods. Carbohydrate is known to have a greater satiating effect than fat and its intake is quite closely regulated by the body. Furthermore, high carbohydrate meals appear to keep hunger suppressed for longer than meals high in fat. Whether the type of carbohydrate influences energy balance has been subject to some debate. The energy density (calories per unit weight) of carbohydrates varies depending on the type of carbohydrate, for example, bread has a lower energy density than sugar. Evidence is beginning to emerge which supports the theory that low energy density carbohydrates tend to result in lower energy intakes than high energy density carbohydrates, so supporting the increased consumption of high fiber starchy carbohydrates rather than simple sugars to replace fats (Clark, 2004).

Bibliography

Clark, M. 2004, Understanding Diabetes. Wiley.

Shaw, B.A., 2006, Assessing Sources of Support for Diabetes Self-Care in Urban and Rural Underserved Communities. Journal of Community Health, 31 (5), 393.

Latent Autoimmune Adult Diabetes

Introduction

Diabetes mellitus (DM) is a group of metabolic diseases characterized by chronic hyperglycemia, which is the result of a violation of insulin secretion, the effects of insulin, or both of these factors. Chronic hyperglycemia in diabetes is accompanied by damage, dysfunction, and insufficiency of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. LADA is latent autoimmune diabetes in adults, the symptoms and initial course of which are consistent with the clinical picture of diabetes 2, but the etiology is closer to diabetes 1. However, a LADA analysis shows that this is a soft edge of the spectrum of manifestations of diabetes 1, because it is autoimmune, high GAD titer, and small doses of insulin can be prescribed.

Characteristics

The patients in adulthood and with long-term diabetes diagnosed with type 2 diabetes, in which the onset of symptoms was not accompanied by ketosis and did not require the use of insulin therapy. During the examination, it was found that patients had a low level of C-peptide in response to stimulation by glucagon, which indicated that they had an absolute deficit in insulin secretion (Buzzetti, Pozzilli, Frederich, Iqbal, & Hirshberg, 2016). Of no small importance was the fact that in the majority of patients with diabetes mellitus with insulin deficiency GAD was detected, which are a marker of autoimmune insulin, and among patients with diabetes without insulin deficiency, these antibodies were found only in rare cases.

Categories

The term latent autoimmune adult diabetes (LADA) was proposed to describe a group of patients who had clinical manifestations of type 2 diabetes, positive antibodies top-cell components, and when the disease manifested, there was no ketoacidosis and weight loss. With LADA, GAD, and antibodies to the β cells of the pancreas are detected. It is estimated that in different populations, from the minimum to half of the patients diagnosed with type 2 diabetes, LADA is actually affected.

LADA can be classified into type 1 and type 2, depending on the GAD titer (Castelblanco et al., 2018). Patients with a high GAD titer having phenotypic similarities to type 1 diabetes, such as ketoacidosis, lower levels of C-peptide, BMI, and insulin resistance, are type 1 LADA. Patients with a lower GAD titer having phenotypic similarities as type 2 diabetes, such as higher levels of C-peptide, BMI, and insulin resistance, are classified as patients with LADA type 2.

Treatment

Currently, one of the main directions of modern research on LADA is the problem of preventing the development of insulin deficiency. Based on the results of many years of research, it was concluded that it is advisable to prescribe insulin injections in small doses to patients with LADA in order to prevent the development of insulin deficiency in them (Wod et al., 2018). Thus, the appointment of an intensified insulin therapy regimen protects ß cells from destruction and prolongs the endogenous secretion of insulin, which facilitates the maintenance of glycemia at the proper level, reduces the risk of hypoglycemia, and prevents the early development of complications of diabetes.

Conclusion

In conclusion, LADA is a disease pathogenetically caused by autoimmune damage to the cells of the islet apparatus of the pancreas, characterized by a slowly progressing course with the final development of insulin deficiency. The presence of an immunological marker for an autoimmune disease, namely GAD, is the main criterion for the diagnosis of LADA. Given the evidence of the presence of LADA type 2, the identification of patients with LADA among patients with type 2 diabetes is necessary for the earlier appointment of insulin therapy in order to prevent the development of insulin deficiency.

References

Buzzetti, R., Pozzilli, P., Frederich, R., Iqbal, N., & Hirshberg, B. (2016). Saxagliptin improves glycaemic control and C‐peptide secretion in latent autoimmune diabetes in adults (LADA). Diabetes Metabolism Research and Reviews, 32(3), 289-296.

Castelblanco, E., Hernandez, M., Castelblanco, A., Gratacos, M., Esquerda, A., Mollo, A., … Mauricio, D. (2018). Low-grade inflammatory marker profile may help to differentiate patients with LADA, classic adult-onset type 1 diabetes, and type 2 diabetes. Diabetes Care, 41(4), 862-868.

Wod, M., Thomsen, R. W., Pedersen, L., Yherstraede, K. B., Beck-Njelsen, H., & Hojlund, K. (2018). Lower mortality and cardiovascular event rates in patients with Latent Autoimmune Diabetes in Adults (LADA) as compared with type 2 diabetes and insulin deficient diabetes: A cohort study of 4368 patients. Diabetes Research and Clinical Practice, 139(2), 107-113.

Artificial Intelligence for Diabetes: Project Experiences

In the field of health care, many interesting and challenging topics have to be regularly investigated. An understanding of recent discoveries and achievements is not enough to successfully take a course and develop a project. Many tasks have to be done before writing an academic paper, during a working process, and when cooperation is over. In this reflective report, attention will be paid to the role of artificial intelligence (AI) in health care and diabetes management, in particular.

This course has specific goals and outcomes, and this paper aims at discussing the peculiarities of the obtained capstone experience, reflecting on the experiences through the course, and describing project management evaluations. Despite the existing challenges and concerns, this course helps to improve my knowledge about AI and its ethical, social, and security implications. At the end of this reflective practice report, I plan to recognize my strengths and weaknesses in terms of team-working on the project about AI in diabetic retinopathy detection (DRD) and want to determine my future expectations from the chosen course.

Capstone Experience

The core issue of this course included the use of AI techniques and cybersecurity in health care. I began my capstone project by giving a definition and researching the idea of AI with its advantages and threats in different spheres of life, including its direct and indirect impacts on people. Then, I had to narrow down a topic and make sure it was connected to AI innovations that could be implemented in health care.

In my last project, I identified that diabetes is a serious public health issue that requires social and financial expenses to be properly diagnosed and treated. Diabetic retinopathy is one of the complications that may be prevented with the help of computerized image assessment, and AI is a solution that may be implemented. I studied several academic works and research projects to clarify what has already been known about the use of AI techniques in DRD practices and create a solid background for my capstone project.

Much time and certain efforts were spent to configure the AI algorithm for DPD and define dataset and pre-processing considerations. Pre- and post-tests had to be done, and definite numbers were available to understand what results must be achieved, and what biases and errors needed to be avoided. In this case, I discovered such challenges as data volume (transmission capacities to work with gigabytes), external interference (poor image handling), and image processing (poor quality and mismatched tags).

Also, my task was to work with possible social, ethical, and security implications linked with AI use. Such concepts as innovation, mechanization, and technology utilization determined the quality of work that had to be done. Some mechanic mistakes cannot be ignored in such projects because AI algorithms have nothing in common with ethics or legal liabilities. Therefore, as an author of the capstone project, I had to promote safety, transparency, equity, and privacy predict and control biases, and cooperate with patients and healthcare workers to make sure this idea worked effectively.

Course Experience

After my work on a capstone project was over, I got an opportunity to look at what I did and compare my results with the goals and expected outcomes of the course. AI is a broad topic that can be applied in different fields for a variety of purposes. This course made students develop their detailed knowledge and critical understanding of human possibilities within AI technologies. Activities were divided into several sections, including the necessity to cover all the technical aspects of AI in DPD practice, discuss ethical issues of the study, investigate the role of the government in AI control, and focus on practical applications of the gained theoretical knowledge.

To succeed in taking this course, I understood that my priorities should not be focused on one or two aspects of AI in health care. I had to combine theoretical and practical knowledge, use various case studies with AI solutions, and pay attention to both successful and failed projects developed in the past. It was not an easy task, and much time was spent surfing the web and visit local libraries. Communication with technical experts helped me to improve my awareness of Python programming and observe how to apply AI in a working environment.

Finally, AI technologies touch upon the achievements in many spheres of life, and the role of the government cannot be neglected. This body plays an important role in establishing regulations and norms to control human behaviors and the impact on technologies in everyday life. Diabetes is a disease that has already changed the lives of millions of people around the world, and the governments of different countries observe the results that have been achieved and must be demonstrated.

This course was a unique opportunity for me to comprehend what I can personally do to contribute to the healthcare system of my country as a technician and a medical worker. I am satisfied with the experience I received and try not to stop in the chosen direction.

Project Management

Another important aspect of this course was the necessity to develop organizational skills and work in a team. Project management turned out to be an integral part of the working process. For an author of a capstone project, such tasks like editing, proofreading, referencing, structuring, and formatting took much time. Although content had to be properly introduced and expanded in the paper, other details were also a part of a rubric and determined a final grade.

Working in a team was not a new assignment for me, but this time it was challenged by the necessity to combine my medical background, communication skills, technical knowledge, and cooperation. My behavior depended on the roles I should perform during the course. When I need to write a section in a project, I tried to be attentive and follow all the given requirements and recommendations.

In a team, I was not a leader, but my creativity and knowledge were useful for other members, and my opinion was respected. Other students shared their experiences and introduced interesting approaches and ideas. AI in DPD was not out the primary topic, but we came to it after thorough research about AI in the fields of medicine and health. Our cooperation and the chosen team dynamics that “better go about than fall into the ditch” took more time, but it made us confident in every decision.

Challenges

One of the major challenges during this for me was the evaluation of the work done by other members of a team and me. Despite our progress and the ability to answer project questions, some students were confused when the time to proofread the work done came. It was hard to identify the errors in my work because I believed that everything was good. Then, one of our co-participants admitted that good was not enough.

We need to achieve perfect results with a perfect idea. Therefore, my new objective was to strengthen my critical abilities, analytical skills, and evaluations. In addition to reading the studies about diabetes and the use of AI for visual impairment control, I found several past projects in our facility and learned the way of how similar projects were organized. As a result, it was possible to assess the work of the rest of the team and find out what they thought about my progress.

Future Expectations

Taking into consideration the already made achievements and the experience in working with a team, I am going to think about my future projects and the skills that have to be enhanced. For example, I understand that my writing depends on how well I can organize my work and cooperate with people. Therefore, such qualities as a positive attitude towards every activity, and independent and group thinking are those I need to develop and improve constantly.

Being an independent researcher and discoverer is not an easy task in modern science, technology, and medicine. Cooperation and AI knowledge play a critical role in any academic work. My mistakes and obstacles during this course were not in vain. I worked hard to achieve perfect results and demonstrate the high quality of this research. Ethics, security, and the protection of personal information are also considerations that contribute to the creation of a good capstone project. I will improve my learning by reading new academic literature and communicating with writing experts.

Conclusion

This course became a good chance for me to observe what I can do with the already obtained knowledge and what I will be able to do if I continue my education. A working process was not easy, but all the challenges made me stronger as a writer and a researcher. My work in a team had certain benefits because it helped me to improve my communication and assessment skills and define a new scope of creativity and enthusiasm. Now I can say that I am ready for new tasks.

Diabetes Care Advice by Food and Drug Administration

Introduction

The achievements in the field of healthcare and medicine cannot be ignored. Many helpful discoveries are being made to advance the possibility of treating such serious health problems and genetic disorders like Down’s syndrome, Huntington’s disease, and diabetes. Representatives of the US Food and Drug Administration (FDA) aim to ensure the safety and effectiveness of drugs marketed for a particular country (U.S Food and Drug Administration, 2018). The Center for Drug Evaluation and Research (CDER) is the primary center for taking responsibility for new pharmaceutical discoveries. Diabetes is a disorder that plagues millions of people around the globe. Though genetics is a central risk factor for developing diabetes, such aspects as the environment and the chosen lifestyle have to be considered. This paper aims to discuss FDA recommendations, the role of money in health care, and the significance of family involvement in diagnosing and treating diabetes along with the laboratory studies and tests currently available and new perspectives that can improve public understanding of the disease.

Discussion of the Guidelines and Reasons Behind the FDA Regulations for Introducing New Pharmaceutical Agents (Policy)

The FDA supports the idea of innovation and progress in the production of new biological products. The CDER tests discoveries for new opportunities for people to be treated, to relieve pain, and to avoid harmful genetic mutations (Lagassé et al., 2017). The process of introducing new drugs consists of several stages. First, it is necessary to classify new molecular entities in terms of FDA goals (administrative or therapeutic). This decision helps determine if a chosen drug is innovative in terms of its chemical composition. Second, the organization checks all moieties as parts of these drugs in terms of their chemical composition and determines if some of them have already been approved (U.S Food and Drug Administration, 2018). To complete this step, it is necessary to evaluate the entire drug development process, starting from laboratory discoveries and ending with safety monitoring. Finally, the Public Health Service Act must be complied with to make sure that all federal standards have been followed. Recently introduced drugs include opdivo to deal with lung and liver problems and glucagon to counter the action of insulin.

Discussion of the Role that Money and Grants Play in Scientific Advances and the Economics of Health Care

The question about the worth of new therapeutic agents and their cost troubles many people. During the last several years, the number of Americans with diabetes has dramatically increased from 25 million to 29 million (Lopez, Macomson, Ektare, Patel, & Botteman, 2015). Mittermayer et al. (2015) state that the total estimated costs of diabetes diagnosis increased up to $245 billion, with $176 billion to be spent on medical costs and $69 billion reflecting reduced productivity. The investigations of Conti and Rosenthal (2016) show that the government can save about $15 billion annually by conducting negotiations with modern pharmaceutical companies. This step would help protect patients’ rights and encourage lawmakers to develop special grant systems to increase the quality and quantity of production. Still, these numbers attest to the role of money in scientific research and the fact that it is difficult to decrease the price due to the expenses of experimental studies, including purchasing of equipment, acquisition, travels, and communication.

Discussion of the Role and Involvement of Family Plays in Health Care Decisions

Every health care decision should be based on several factors. However, the role of family and the possibility of being involved in the treatment and healing processes remain an urgent topic for discussion. First of all, family caregivers can provide patients with the required emotional and practical support (Itzhaki, Hildesheimer, Barnoy, & Katz, 2016). The second important issue regarding family involvement is the possibility to improve decision making and the evaluation of a patient’s condition, available resources, and costs from several points of view. Finally, family members can make judgments about the quality and outcomes of medical treatments about personal values (Itzhaki et al., 2016). Sometimes, patients have to deal with complex medical information and make decisions using their background knowledge and experience. If they do not have enough confidence and awareness, family involvement can become a helpful alternative. Common interests, family history, and past medical problems may be properly described and explained by several people to make sure health care decisions do not harm patients.

Discussion of the Disease, Its Prevalence, and Its Incidence

Diabetes is a well-known disease around the world because even if a person does not have it, he or she has probably heard about it and its effects on the quality of life. It is a heterogeneous disease that may be of two types, 1 – insulin-dependent (T1D) and 2 – non-insulin-dependent (T2D) (Dooley et al., 2016). The exact etiology of T1D and T2D is currently studied because researchers and practitioners cannot state clearly what factors or triggers can directly cause the development of diabetes in persons. It is found that T1D develops as a result of the autoimmune response of a human organism against certain beta cells in the pancreas. As a result of this reaction, pancreatic beta cells cannot contribute to producing insulin. The development of T1D leads to the situation when a person’s pancreas cannot produce the required insulin anymore. This specific hormone is responsible for regulating sugar levels in the organism (Dooley et al., 2016). This form of insulin deficiency can be caused by genetic aspects and such environmental factors as viruses, but actual causes are unknown. Moreover, T1D is mostly diagnosed in childhood.

On the contrary, the development of T2D can be provoked by a person’s lifestyle and such specific factors like overweight and obesity. However, this type of diabetes can also be hereditary in association with a person’s predisposition to this disease referring to the family medical history. This type of diabetes is usually observed in adults, and it means the decrease in the production of insulin in the pancreas because of certain metabolic changes in the organism that are caused by overweight and obesity (Dooley et al., 2016; Nussbaum, McInnes, & Willard, 2007). As a result, insulin resistance develops in this case while leading to more acute metabolic changes and negative alterations in the work of blood vessels, nerves, and kidneys.

T2D includes about 90% of all diabetes cases, and an increased prevalence of this disorder is observed among Native Americans aged between 35 and 40 years (Nussbaum et al., 2007). The reasons for its prevalence remain unknown. Despite numerous attempts to investigate the features of diabetes, its molecular and genetic bases are poorly defined in the current state of research (Nussbaum et al., 2007). Though diabetes may have different causes, two factors play a crucial role in its development. On the one hand, a patient may inherit a predisposition. On the other hand, genes are not enough to trigger this disease. The environment’s effect should also be considered.

The clinical convergence of diabetes needs to be investigated. T1D and T2D patients demonstrate a progressive decline in beta cells (Dooley et al., 2016). A complex genetic landscape is also observed in the chosen group of patients, with several genes of GLIS3 and EIF2AK3 being recognized (Dooley et al., 2016). From this perspective, these genes cause defects in insulin production and result in hyperglycemia and poor protein and fat metabolism. Thus, the pathogenesis and epistemology of diabetes determine its prevalence and incidence, leading to an increased incidence among children and young adults while depending on the type of diabetes.

Discussion of the Possible Laboratory Testing

The diagnosis, screening, and management of diabetes have to be properly developed in a care plan offered to patients. Patients can check their condition using several laboratory tests, including fasting plasma glucose (FPG), hemoglobin A1C, and random plasma glucose (Dooley et al., 2016). For example, the FPG test can be offered to both adult and child patients. The main requirement is to avoid food intake at least eight hours before the test. It indicates the level of glucose in the blood and can determine prediabetic conditions. The A1C test is focused on the level of hemoglobin in the blood and the presence or absence of oxygen-carrying proteins. The unusual feature of this laboratory test is that patients with specific blood problems cannot obtain clear results. Finally, the random plasma glucose test can be taken by people who are already aware of diabetes as their diagnosis or who observe evident symptoms of the disease.

However, the list of laboratory testing options can be enlarged. For example, Dooley et al. (2016) suggest flow cytometry to detect antigens and evaluate platelet membrane activity. This test can be used to identify the most appropriate drugs approved by the FDA. Metformin, sulfonylureas, DPP4 inhibitors like sitagliptin, and thiazolidinediones can be used (Mittermayer et al., 2015). Still, it is difficult to predict all possible agents and choose effective drug classes for all patients without considering their characteristics and outside factors. Therefore, the investigation of diabetes needs to be continued under laboratory conditions to improve the patient’s quality of life.

Conclusion

In general, diabetes is a condition that has been thoroughly investigated by the FDA and other worldwide organizations. A genetic predisposition is not the only risk factor that should be mentioned in this discussion. The role of the environment has to be emphasized. Therefore, such issues as family involvement, including emotional support and effective decision making, and government participation, including grants and funding alternatives, should be improved and promoted in all countries.

References

Conti, R. M., & Rosenthal, M. B. (2016). Pharmaceutical policy reform – Balancing affordability with incentives for innovation. New England Journal of Medicine, 374(8), 703-706.

Dooley, J., Tian, L., Schonefeldt, S., Delghingaro-Augusto, V., Garcia-Perez, J. E., Pasciuto, E.,… Liston, A. (2016). Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes. Nature Genetics, 48(5), 519-527.

Itzhaki, M., Hildesheimer, G., Barnoy, S., & Katz, M. (2016). Family involvement in medical decision-making: Perceptions of nursing and psychology students. Nurse Education Today, 40, 181-187

Lagassé, H. D., Alexaki, A., Simhadri, V. L., Katagiri, N. H., Jankowski, W., Sauna, Z. E., & Kimchi-Sarfaty, C. (2017). Recent advances in (therapeutic protein) drug development. F1000Research, 6, 113-130. Web.

Lopez, J. M., Macomson, B., Ektare, V., Patel, D., & Botteman, M. (2015). Evaluating drug cost per response with SGLT2 inhibitors in patients with type 2 diabetes mellitus. American Health & Drug Benefits, 8(6), 309-318.

Mittermayer, F., Caveney, E., de Oliveira, C., Gourgiotis, L., Puri, M., Tai, L. J., & Turner, J. R. (2015). Addressing unmet medical needs in type 2 diabetes: A narrative review of drugs under development. Current Diabetes Reviews, 11(1), 17-31.

Nussbaum, R. L., McInnes, R. R., & Willard, H.F. (2007). Thompson & Thompson genetics in medicine (6th ed.). Philadelphia, PA: Saunders Elsevier.

U.S Food and Drug Administration. (2018). New drugs at FDA: CDER’s new molecular entities and new therapeutic biological products. Web.

Diabetes Education for African American Women

Diabetes belongs to the most severe health issues prevailing all over the world. In the USA, this disease impacts millions of people annually. A particular risk group for diabetes is formed by African American females. The vulnerability is high among women of African American descent belonging to the age group of 35-50 years. The present paper aims to identify health promotion and disease prevention issues specific to the selected group and develop a plan of teaching for these females.

Health Promotion and Disease Prevention Issues

To define the points related to the health promotion and disease prevention, research was performed in scholarly journals. Although it was impossible to find an article that would cover all three aspects of the selected group (age, sex, and race), several sources covering at least one of these characteristics were located. As a result, it is possible to establish the following issues related to promoting health and preventing diabetes in African American women aged 35-50:

  • obesity is one of the most frequent health risks in middle-aged women that may lead to the development of diabetes (Fisher & Kridli, 2014);
  • education provided by nurses is a crucial factor in promoting healthy behaviors of obese females (Fisher & Kridli, 2014);
  • it is possible to prevent the development of diabetes if dietary challenges are overcome (Murrock, Taylor, & Marino, 2013);
  • there are substantial barriers to African American females’ physical activity (Joseph, Ainsworth, Keller, & Dodgson, 2015);
  • obstacles to physical activity among African American women exist at interpersonal, intrapersonal, or community level (Joseph et al., 2015);
  • a serious complication of diabetes that should also be considered in the disease prevention process is hypertension (Fisher & Kridli, 2014);
  • a self-management approach can eliminate the risks posed by diabetes to African American women (Rosal et al., 2014).

The Teaching Plan

Taking into consideration issues mentioned in the previous section, the plan of teaching for the selected group of patients should be comprehensive and diversified. Thus, the plan will contain a variety of solutions aimed at eliminating the development of diabetes and its complications. Also, the suggested design is expected to help prevent the disease. The following aspects should be included in the plan:

  • teaching the target group how to keep a healthy diet (Fisher & Kridli, 2014; Murrock et al., 2013);
  • creating a program aimed at engaging patients in physical exercising (Joseph et al., 2015);
  • communicating with the target population both face-to-face and virtually to offer support and help (Rosal et al., 2014).

The information found in scholarly sources is not new. Health problems associated with diabetes, as well as risk issues, have been identified by physicians and scholars many years ago. However, the data mentioned in analyzed articles are relevant to the Nursing Interventions Classification (NIC) and Nursing Outcomes Classification (NOC). In NIC, many aspects mentioned in the reviewed articles are included, including health education, exercise promotion, health system guidance, nutrition management, risk identification, and weight management (Bulechek, Butcher, Dochterman, & Wagner, 2013). Self-management strategies on diabetes mentioned in NOC are also associated with activities outlined in the teaching plan, such as the participation in exercising (Moorhead, Swanson, Johnson, & Maas, 2018). Also, NOC emphasizes the significance of maintaining the plan created by the physician or nurse (Moorhed et al., 2018).

Conclusion

Although diabetes is one of the most widely spread diseases in the world, not all patient groups are affected by it equally. The paper has discussed the need for diabetes education for African American women aged 35-50 years. The suggested teaching plan includes activities related to NIC and NOC standards. The implementation of the offered solutions is expected to improve the target group’s health and eliminate the development of complications.

References

Bulechek, G. M., Butcher, H. K., Dochterman, J. M., & Wagner, C. (Eds.). (2013). Nursing interventions classification (NIC) (6th ed.). St. Louis, MO: Elsevier Mosby.

Fisher, K., & Kridli, S. A.-O. (2014). The role of motivation and self-efficacy on the practice of health promotion behaviours in the overweight and obese middle-aged African American women. International Journal of Nursing Practice, 20(3), 327-335.

Joseph, R. P., Ainsworth, B. E., Keller, C., & Dodgson, J. E. (2015). Barriers to physical activity among African American women: An integrative review of the literature. Women & Health, 55(6), 679-699.

Moorhead, S., Swanson, E., Johnson, M., & Maas, M. L. (Eds.). (2018). Nursing outcomes classification (NOC): Measurement of health outcomes (6th ed.). St. Louis, MO: Elsevier.

Murrock, C. J., Taylor, E., & Marino, D. (2013). Dietary challenges of managing type 2 diabetes in African-American women. Women & Health, 53(2), 173-184.

Rosal, M. C., Heyden, R., Mejilla, R., Capelson, R., Chalmers, K. A., Rizzo, M., … Wiecha, J. M. (2014). A virtual world versus face-to-face intervention format to promote diabetes self-management among African American women: A pilot randomized clinical trial. JMIR Research Protocols, 3(4), e54.

Diabetes Mellitus and Health Determinants

Prevalence and Importance of Diabetes Mellitus

Diabetes is among the most important and widespread consequence of such conditions as obesity or general poor life quality. It is common, complex and expensive in treatment, has multiple serious complications, and may reduce life expectancy by eight to ten years (Astrup, 2001). Type 2 diabetes mellitus is becoming the most common non-communicable disease in the European Union and the United States. According to the World Health Organization (2016) report on diabetes, 422 million people (aged 18 and older) were living with diabetes in 2014, and the prevalence of the condition continues to increase. Approximately half of the diabetes cases on a global scale are attributed to the Western Pacific and South-East Asia regions. The complexity of diabetes mellitus lies in the fact that the determinants of the condition are wide, especially given the family history component contributing to the increased risks.

Studying the problem of type 2 diabetes is important because of the range of adverse health effects for the population. While some impacts of diabetes can be managed, there are still such complications as cardiovascular diseases, kidney disease, issues during pregnancy, eye disease, poor oral health, and multiple others. It should also be mentioned that many interventions presented in the research literature are focused on managing the condition once it occurs, and there is a lack of substantial evidence to support the implementation of prevention programs targeted at high-risk populations.

Determinants of the Issue

Type 2 diabetes has a range of determinants, ranging from social to hereditary. From the environmental perspective, the condition can develop on the basis of a person’s geographic location and the availability of resources necessary for keeping health under control (Giles-Corti & Donovan, 2002). For instance, in areas where fresh produce is readily available and accessible to communities, the likelihoods of effective health behaviors increase. However, in developed countries that have an abundant selection of fast food chains, different restaurants, and various methods of transportation, the prevalence of diabetes is higher than in developing countries. From the social perspective, such determinants as education, economic stability, access to medical care, community support, and multiple other factors can determine the likelihood of diabetes occurrence (Clark & Utz, 2014).

Importantly, type II diabetes also has close connections to the history of family health, which means that people whose relatives were diagnosed with the condition were more likely to get diabetes at some point of their lives. Sakurai et al. (2013) concluded that type 2 diabetes was directly associated with the incidence of diabetes among individuals. Also, the risks of getting diabetes were not connected to other risk factors such as poor lifestyle habits or obesity among both men and women. This shows that there is no one determinant that could explain why diabetes develops in some people and not in others. Rather, it is a combination of different risk factors that can include any aspects ranging from environmental to hereditary factors.

Reducing the Prevalence and Incidence by Paying Attention to Determinants

Since the risks of developing type 2 diabetes can range from one individual to another, there are several generalized interventions helping to reduce the prevalence and incidence of the condition. For example, people are usually advised to lose weight and keep it off; it is usually recommended to lose between 5% to 7% of the starting weight in cases when obesity is a problem. It is also recommended to engage in regular physical activity and eat healthy foods because of the overall benefits that come with healthy lifestyle choices. Thus, reducing the prevalence and occurrence of type 2 diabetes by considering its determinants is predominantly linked to the condition. According to the report by Mayo Clinic Staff (2016), improving the diet, boosting physical activity, and balancing mental health by avoiding stressful situations are the most common risk prevention efforts. Thus, there is a gap in studies as to how to address other determinants of type 2 diabetes that do not include poor diet.

When it comes to environmental factors, increased attention should be paid to individuals who do not understand their risks of developing diabetes and thus do not make any changes in order to reduce the impact of their environment on health. Since not only poor diet or sedentary lifestyles increase obesity risks, it has been advised for people to improve their housing environment and the quality and duration of rest. As found by Kolb and Martin (2017), there is “an association between increased exposure to residential traffic, noise, and fine airborne particulate matter and a higher risk of type 2 diabetes diagnosis” (p. 131). Because of this association, people are advised to make changes in their environments by going to rural areas and spending some time in the fresh air. Also, to improve the quality and the duration of sleep and rest, high-risk populations are recommended to reduce their levels of stress and implement holistic behaviors such as meditation or yoga. In cases of symptoms of depression, anxiety, and other personality issues, it is advised to refer to healthcare specialists for reducing the adverse impact on physical health.

Unfortunately, the socioeconomic status can also act as a determinant of type 2 diabetes, with low levels of income being connected to higher risks of developing the condition. Addressing this problem is only possible through the engagement of governmental stakeholders. For instance, providing free consultations and education to high-risk low-income individuals may be a beneficial strategy that accounts for the socioeconomic determinant. Unfortunately, there is no magical cure that will help individuals with a family history of diabetes avoid the diagnosis altogether; however, preventative measures outlined above can also be applied to this population of high-risk individuals.

In summary, it should be mentioned that there is a variety of unfavorable environmental and behavioral conditions ranging from diet to genetics that can contribute to the increased likelihood of type 2 diabetes development. Therefore, it is unlikely that the general lifestyle and environment changes will yield the same results in all high-risk populations. Because of this, assessing individuals’ risks, needs, environments, behaviors, and other determinants of diabetes is necessary for reducing the occurrence of the condition.

Assisting People with Identified Risk Factors

Following healthy lifestyle habits is the most likely method of helping people with high-risk factors to avoid getting diabetes. Lowering risks can mean anything from knowing one’s family health history to quitting smoking. However, in order to help high-risk individuals avoid getting diabetes, community support and patient education are needed. In this section, several methods of assisting people with high-risk factors will be discussed.

Community-based diabetes prevention programs have been widely studied in the research literature and were shown to affect people with high-risk factors positively. As argued by Philis-Tsimikas and Gallo (2014), with the support of health systems, local communities could successfully use community-based programs that could influence health outcomes across a wide spectrum of care settings. Peer education is a crucial component of community-based programs and includes the participation of nurses, psychologists, and dietitians to deliver them successfully. As found by Phillis-Tsimikas and Gallo (2014), community-based programs for addressing such issues as type 2 diabetes allow for the development of other prevention programs within the health care system, especially given that the number of people requiring wider access to programs of diabetes prevention is growing around the world.

While community-based programs are effective on a narrow scale since they target smaller sections of populations, it is also important to consider large-scale diabetes prevention interventions that require the establishment of frameworks that include health information technologies, a collaboration between healthcare facilities, and community support. Such programs were studied by Vojta, Koehler, Longjohn, Lever, and Caputo (2013) who concluded that large-scale prevention programs could be sustainable and effective in preventing diabetes by means of combining the following aspects:

  • Lower-cost, evidence-based interventions and community-based delivery in order to overcome the prevalence of diabetes and reduce the risks of developing the condition;
  • Management of national programs of diabetes prevention for ensuring patients’ adherence to lifestyle changes;
  • Novel structures of payment that support the implementation of the program and incentivize the outcomes of efficiency;
  • Strong efforts for identifying individuals with high risks of developing type 2 diabetes.

Conclusion

The review of available studies on the occurrence and prevention of type 2 diabetes showed that the condition has an array of determinants, not all of which can be taken under the control of high-risk individuals. In most cases, making healthy lifestyle choices concerning the diet and physical activity was recommended to individuals with high risks of developing diabetes, especially when it comes to patients diagnosed with obesity. Stress and the lack of rest could contribute to the condition, which explains the recommendation to reduce the occurrence of stress factors and get the appropriate amount of sleep. Community support and large-scale interventions can be helpful for assisting high-risk individuals in making healthy decisions to reduce the occurrence of the condition. More research on this issue is needed due to the variability of type 2 diabetes risks among the population.

References

Astrup, A. (2001). Health lifestyles in Europe: Prevention of obesity and diabetes by diet and physical activity. Public Health Nutrition, 4(1), 499-515.

Clark, M. L., & Utz, S. W. (2014). Social determinants of type 2 diabetes and health in the United States. World Journal of Diabetes, 5(3), 296-304.

Giles-Corti, B., & Donovan, R. J. (2002). The relative influence of individual, social and physical environment determinants of physical activity. Social Science & Medicine, 54, 1973-1812.

Kolb, H., & Martin, S. (2017). BMC Medicine, 15, 131. Web.

Mayo Clinic Staff. (2016). Web.

Philis-Tsimikas, A., & Gallo, L. C. (2014). Current Diabetes Reports, 14(2), 462. Web.

Sakurai, M., Nakamura, K., Miura, K., Takamura, T., Yoshita, K., Sasaki, S., … Nakagawa, H. (2013). Family history of diabetes, lifestyle factors, and the 7‐year incident risk of type 2 diabetes mellitus in middle‐aged Japanese men and women. Journal of Diabetes Investigation, 4(3), 261–268.

Vojta, D., Koehler, T. B., Longjohn, M., Lever, J. A., & Caputo, N. F. (2013). A coordinated national model for diabetes prevention: Linking health systems to an evidence-based community program. American Journal of Preventive Medicine, 44(4), 301-306.

World Health Organization. (2016). Web.

Diabetes: Encapsulation to Treat a Disease

Introduction

The science of treating disorders has transformed into a rapid problem solving platform with the intervention of Biomedical engineering. This has initiated confidence in the health care providers and patients with the hope that they could overcome the complications of debilitating disorders. The pathological involvement of vital organs has prompted the researchers to investigate on the strategies that aim at replacing or repairing the tissues with functionally advanced counterparts. This would require an understanding of cellular structural frame work.

However, the approach of drug delivery or any agent intended for alleviating the health complications may also need to be considered in addition to tissue engineering.

For this purpose, there was a growing emphasis on the approach of encapsulation to treat a disease. The present description was focused on the utility and validity of encapsulation concerning Diabetes mellitus. This metabolic disorder has emerged as a major health burden in many countries due to its growing indices of prevalence. The function of key hormone, insulin gets altered leading to insulin resistance and abnormal glucose levels. This disorder may have etiologies of genetic, biochemical or immunological origin. This disorder was also believed to be associated with hypertension and cardiovascular defects. Although conventional therapies have contributed to the understanding and management of diabetes, there is also a need to emphasize on the treatment modalities keeping in view of encapsulation.

This could be because this encapsulation technique was believed to be primarily cost efficient and may serve as better strategy to address the issues concerned with the cure of diabetes. Therefore, the objective of this description was to propose a study for treating diabetes with special emphasis on islet cell encapsulation and the related aspects of tissue engineering.

Background and significance

Diabetes mellitus, considered as a disorder of glucose homeostasis was reported to result from the immune-mediated damage of pancreatic beta cells in the islets of Langerhans (type 1 diabetes) or the insulin resistance and obesity syndromes (Giannoukakis & Robbins, 2002designtheyalginate-based The involvement of the pancreas in the etiopathogenesis of diabetes has increased the focus on Islet cells. Hence, transplantation of islet cells to inhibit the immune-mediated graft rejection was considered a better option previously to restore the specific pancreatic function (Giannoukakis & Robbins, 2002).

Further, diabetes mellitus was associated with the risk of coronary heart disease (CHD) which was revealed by the elevated levels of serum C-reactive protein (CRP) (Bahceci et al., 2008). The utility of CRP was found to play a vital role in disorders where inflammation was reported. Hence, it was better regarded as an important inflammatory marker (Bahceci et al., 2008).

Blaha et al. (2008) reported a comprehensive management plan known as the “ABCDE” approach that could better assist physicians to gain insights on the metabolic syndrome that is associated with cardiovascular disease and type 2 diabetes mellitus. Here”A” stands for the assessment of cardiovascular risk and aspirin therapy, “B” for blood pressure control, “C” for cholesterol management, “D” for diabetes prevention and diet therapy, and “E” for exercise therapy.

These approaches may serve the best to provide a satisfactory remedy (Blaha et al., 2008).

However, growing concerns over the incidence of diabetes mellitus have enabled researchers from the other department of Bio-medical science to contribute to the prevention strategies.

This especially stimulated the minds of tissue engineers to work on the novel approach of encapsulation with the objective of providing a better therapy for diabetic patients.

Chang (1964) previously devised a method of developing microcapsules with semipermeable membranes, by setting down polymer around emulsified aqueous droplets using two options as interfacial coacervation and interfacial polycondensation. The researchers of subsequent periods have made this strategy worth fitting for treating disorders like diabetes.

It was reported that islet cells could be better developed by using alginate-poly (L-lysine) alginate membranes (Sun, 1988). They are further described to be biocompatible and viable that would remain impermeable to cells and effector molecules of the immune system.

This could protect the transplanted islet cells against host rejection thus making it a good substitute for immunosuppressive therapy (Sun, 1988). This has strengthened an earlier description of the significance of the bioartificial pancreas. It was described that the transplantation of encapsulated islets could overcome the problems of islet availability and rejection in the treatment of insulin-dependent diabetes with organ replacement (Zekron et al., 1996). The compatibility of the bioartificial pancreas was reported to depend on the reaction of the entrapped islet to the encapsulation technique and material, the reaction of the recipient against the incorporated device ( foreign body reaction), and the reaction of the recipient against the encapsulated islet ( immunology of bioartificial pancreas) (Zekron et al., 1996).

The interactions between a variety of donor and recipient related factors may contribute to certain reactions like inflammation and fibrosis. This study has suggested large experiments on animal models to obtain significant data for the progress in the development of a bioartificial pancreas (Zekron et al., 1996). Encapsulation was believed to allow animal islets or insulin-producing cells to be engineered from stem cells (De Vos, Hamel, & Tatarkiewicz, 2002). As such three major approaches to encapsulation have been focused such as intravascular microcapsules, which are anastomosed to the vascular system as AV shunt and extravascular microcapsules and extravascular microcapsules transplanted in the peritoneal cavity.

Although this intervention was proved to be successful, the extravascular approach was found to be reliable over others since it is associated with fewer complications such as thrombosis and infection (De Vos, Hamel, & Tatarkiewicz, 2002). It was further described that the transplantation of microencapsulated islets close to blood vessels in revascularized solid supports would solve problems concerned with the performance and survival (De Vos, Hamel, & Tatarkiewicz, 2002). Hence, there is a need to implement the strategies found with significant progress for diabetic patients. It was reported that the bioartificial pancreas developed on the basis of encapsulation of islet cells could offer protection to cells from the host’s immune attack. This was mainly for its ability to eliminate the need for immunosuppressive drugs, improved diffusion capacity, and ease of transplantation. Hence, the utility of the Bioartificial pancreas needs to be evaluated.

The material to be used for tissue engineering plays a vital role. Here biodegradable polymers of both natural and synthetic origin were the preferred candidates as they meet the requirements of sutures, scaffolds for tissue regeneration, tissue adhesives, hemostats, and transient barriers for tissue adhesion, as well as drug delivery systems (Nair & Laurencin, 2006). The use of polymers may be largely dependant on the progress achieved in the field of molecular and cellular biology with regard to the development of biotechnological drugs (Nair & Laurencin, 2006). So, there may be a need to take the assistance of a good number of professionals concerned with the relevant field.

Further, the encapsulation technique for treating diabetes may require an evaluation of factors that influence the survival of islet cells. This could in turn rely on the metabolism more probably the internal homeostatic environment that may undergo changes during pathological conditions.

It was described that although encapsulation facilitates the long-term survival of islet grafts in the absence of immunosuppression, it may be confined to only several months due to the effect of nonprogressive pericapsular overgrowth (De Vos et al., 2003). It was revealed that such overgrowth was due to macrophages that produce nitric oxide which, rather than cytokines, may lead to the deleterious effect on the neighboring encapsulated islets. (De Vos et al., 2003). De Groot et al. (2004) reported that the graft function of encapsulated islets may be hindered by a gradual decrease in the glucose-induced insulin response (GIIR), a hyperproliferation of islet cells, and gradual necrosis. This was described to be associated with the increased number of macrophages on the overgrown capsules A concomitant necrosis on the total islet surface was also observed (De Groot et al., 2004intoThe abnormal levels of glucose or the insulin may also indicate an underlying complication that could originate from the cytokines released as a result of altered macrophage function or necrosis.

Although macrophages have an important phagocytic function, their problematic intervention has become a concern in this context. Hence, studies need to be focused on the growth of macrophages that may play a suspicious role during the survival of encapsulated islets.

Further, encapsulated islets may fail to be accepted by the host’s body because of Hypoxia (De Groot et al., 2003). This was revealed when the mRNA expression levels of Bcl-2, Bax, inducible nitric oxide synthase (iNOS), and monocyte chemoattractant protein 1 (MCP-1) were assessed in association with the amount of nitrite and MCP-1 in the culture medium (De Groot et al., 2003). They have described that the increased MCP-1 mRNA levels may serve as an indication that encapsulated islets in vivo contribute to their graft failure by attracting cytokine-producing macrophages (De Groot et al., 2003).

Preventing Hypoxia may significantly ameliorate the function of islet cells and lessen the attraction of macrophages by encapsulated islets (De Groot et al., 2003).

It was reported that the success of islet transplantation would depend on the production of purified alginates of high transplantation-grade quality (Zimmermann et al., 2005).

This would require a designing of immunoisolating alginate-based microcapsules by maintaining the uninterrupted exchange of nutrients, oxygen, and therapeutic factors that are released by the encapsulated cells while simultaneously avoiding swelling and subsequent rupture of the microcapsules (Zimmermann et al., 2005). This strategy would be largely influenced by the implementation of a validated and well-documented technology for cross-linking alginates with divalent cations. As the progress in alginate based therapy was demonstrated by transplantation of encapsulated rat and human islet grafts in diabetic mice models, there may be a scope for diabetic individuals in the near future (Zimmermann et al., 2005). This has indicated the role of encapsulated islet cells that were considered to be immunoisolated. Earlier workers described that immunoioslated islet allo- and xenotransplants, would better have clinical application because of satisfactory findings with alginate microcapsules in both allo- and xenogeneic (porcine) islet transplantation in the spontaneously diabetic dogs and monkeys(Mullen, Maruyama & Smith, 2000). They have also described a reversal of diabetes in mice with cryopreserved, microencapsulated rat islets. Pancreomatized dogs were able to successfully allow the long-term allo- and xenogeneic islet survival of vascularized bioartificial devices (Mullen, Maruyama & Smith, 2000) The limitations of this approach were that a failure of the devices may contribute to thrombosis and the associated problems. This has indicated a partial success of immunoisolated islet transplants in animal experiments. As such, minimizing adverse reactions produced by immunoisolation devices or capsules intended for treating diabetes may ensure the efficacy of technologies concerned with islet encapsulation (Mullen, Maruyama & Smith, 2000)

Recently, it was reported that a new technique known as cell sheet engineering using temperature-responsive culture dishes would facilitate the use of living cells as an immunoisolating membrane (Lee et al., 2008). Since immunisation involves the encapsulation of a graft in a selectively permeable membrane, encapsulation of cellular grafts may protect the graft from immune attack without the need for immunosuppressive agents (Lee et al., 2008). Using the microencapsulation technique, a chondrocyte sheeting immunodelusive immunoisolated bioartificial pancreas (CSI-BAP) was manufactured by means of cell sheet engineering, and an auricular cartilage, which is histologically elastic cartilage from dogs (beagle), was used as a source of immunoisolating membrane. CSI-BAP was able to secrete insulin into the culture medium indicating the efficacy of this approach (Lee et al., 2008). Another recent description has highlighted the importance of a novel composite alginate/poly (lactic-co-glycolic) acid microparticulate system for protein stabilization and delivery using bovine insulin as a model drug (Schoubben et al., 2008). Composite microparticles filled with insulin were reported to show reproducible encapsulation efficiency with a higher soluble insulin content when compared to conventional microparticles(Schoubben et al., 2008). Therefore, it is reasonable to mention that the above strategies may produce significant results if further investigations were made.

Specific Aims

In view of the above information, the main objectives of the proposed study were:

  1. To select a large population of diabetic individuals for testing the efficacy of technology of tissue engineering and encapsulation.
  2. To conduct experiments on animal models.

The rationale for this purpose was that there were poorly available treatment options other than the conventional methods. Pharmacological interventions, gene therapies may accompany the risk of side effects and could not ensure a reliable remedy. In addition, they are not as cost-efficient as the immunization encapsulation technique.

Hence this study was proposed with the anticipation that it could produce better results than might promote a faster drive towards the standard therapeutic establishment of encapsulation.

Research Design and Methods

Specific Aim # 1: To select a large population of diabetic individuals for testing the efficacy of technology of tissue engineering and encapsulation.

Rationale: Reliable treatment of diabetes requires the intervention of novel strategies.

Methods: Online databases would be searched to gather the relevant information. Health authorities would be approached to obtain a permission grant. A survey would be conducted in government and private hospitals to find diabetic patients. Based on the records, a total of 300 patients would be approached and informed about the study. Informed consent would be obtained from patients willing to participate in the study. Those meeting the standard criteria for diabetes classification will be only selected while others are excluded from the study.

Initially, baseline characteristics like age, BMI would be considered. Based on the values obtained, diabetic individuals will be separated into two groups as non-obese and obese.

Fasting blood glucose and CRP levels will be determined. Here, CRP would be used as a concomitant parameter due to the risk of cardiovascular inflammation in diabetic individuals.

Further, islet cell autoantibodies would be determined to detect the defects of islet cells.

Patients who exhibit a markedly decreased pancreatic organ function would be selected for the transplantation experiments. Encapsulated islet cells would be developed by either following the approaches mentioned previously like alginate-poly (L- lysine) alginate membranes, immunoisolated alginate-based microcapsules, or a chondrocyte sheeting immunodelusive immunoisolated bioartificial pancreas (CS-BAP). Encapsulated islet microcapsules would also be obtained commercially to compare the efficacy of the methods developed in the laboratory.

The risk of hypoxia would be monitored by determining the mRNA expression levels of mRNA, Bcl-2, Bax, (iNOS), MCP-1, and nitrite in the culture medium. The risk of macrophage-induced nitric oxide levels and its overgrowth on the neighboring encapsulated islets would be checked by monitoring the cytokine secretions of the macrophage. Human models receiving encapsulated islet cells would be monitored for insulin secretion. These findings would be compared with the strategies implemented for rat models. This is to find the difference in the levels of insulin which might reflect the degree of immune suppression. Obese individuals would also be selected from the 300 diabetic patients for the encapsulation intervention program after conducting preliminary tests on their insulin and glucose levels. Those found with absolutely pancreatic defects would be selected for the surgical removal of the pancreas. Transplantation of encapsulated islet grafts or bioartificial pancreas would be allowed. They would be then monitored for insulin levels. As obese individuals are susceptible to cardiovascular problems, CRP levels would be checked after encapsulated islet cell transplantation. This is to determine whether inflammation would interfere with the survival of islet grafts.

All the subjects will be followed for a period of one year. During this period they could be also evaluated for the negative effects of the host’s immune attack.

Specific Aim # 2: To conduct experiments on animal models.

Rationale: Studies on encapsulation techniques involving animal models are largely needed for confirmation reports.

Methods: An equal number of mice would be selected after obtaining permission from the veterinary authorities. These animal models were initially monitored for their insulin and glucose levels. Those found with a defect in the glucose metabolism would be selected. Those with normal functions would serve as controls.

Pancreas would be surgically removed from the mice and they would be monitored for immune suppression without external treatment. Microencapsulated islet cells obtained previously would be surgically delivered. The mice would be determined for GIIR, the rate of islet cell replication, and islet cell death as described previously (Vos et al., 2004).

The novel approach of CSI-BAP would also be applied. Here, islet cells would be collected and prepared from the rat. CSI-BAP would be cultured for nearly 83 days and the cultured medium would be collected every 24 h to measure the insulin concentrations. The CSI-BAP was examined histologically using hematoxylin and eosin (H&E), and azan dye staining.

Immunohistochemical staining would be additionally performed to demonstrate the insulin production of CSI-BAP. Insulin secretion of CSI-BAP would be observed daily and recorded.

The results obtained on the earlier days would be compared with the later days.

For example, the percentage of insulin secretion obtained on day 10 would be compared with that of day 15. These findings would be later compared with the rats described to be surviving with the defective pancreas. Obese rats would be specially obtained from animal houses of various biomedical research institutions/ laboratories. Their pancreas would be surgically removed and encapsulated islet cells would be transplanted. Immunosuppressive drugs would not be given to human and rat models. The results obtained from the overall experiments would be checked for the approach that has comparatively more significant data.

The treatment option that produced the best results would be further refined by conducting additional studies on both human and animal models. The estimated time period of the proposed project would be fourteen to eighteen months. For the human subjects, six months for the survey and selection, two months for the development and transplantation of encapsulated islet cells, and one-year follow-up. For the animal models, two months for animal selection, two months for the development and transplantation of encapsulated islet cells, and one year follow up.

References

  1. Bahceci, M, Tuzcu, A, Ogun, C, Canoruc, N, Iltimur, K, Aslan, C. “Is serum C-reactive protein concentration correlated with HbA1c and insulin resistance in Type 2 diabetic men with or without coronary heart disease?” J Endocrinol Invest 28.2 (2005):145-50.
  2. Blaha, MJ, Bansal, S, Rouf, R, Golden, SH, Blumenthal, RS, Defilippis, AP. “A practical “ABCDE” approach to the metabolic syndrome.” Mayo Clin Proc 83.8(2008): 932-41.
  3. Chang, TM. “Semipermeable Microcapsules.” Science 146 (1964):524-5.
  4. De Groot, M, Schuurs, TA, Leuvenink, HG, Van Schilfgaarde, R. “Macrophage overgrowth affects neighboring nonovergrown encapsulated islets.” J Surg Res115.2 (2003): 235-41.
  5. De Groot, M, Schuurs, TA, Keizer, PP, Fekken, S, Leuvenink, HG, Van Schilfgaarde, R. “Response of encapsulated rat pancreatic islets to hypoxia.” Cell Transplant 12.8 (2003) 867-75.
  6. De Vos, P, Hamel, AF, Tatarkiewicz, K. “Considerations for successful transplantation of encapsulated pancreatic islets.” Diabetologia 45.2 (2002):159-73.
  7. De Vos, P, De Haan, BJ, De Haan, A, Van Zanten, J, Faas, MM. “Factors influencing functional survival of microencapsulated islet grafts.” Cell Transplant.13.5 (2004):515-24.
  8. Giannoukakis N and Robbins PD. “Gene and cell therapies for diabetes mellitus: strategies and clinical potential.” Bio Drugs 16.3 (2002):149-73.
  9. Lee, JI, Nishimura, R, Sakai, H, Sasaki, N, Kenmochi, T. “A newly developed immunoisolated bioartificial pancreas with cell sheet engineering.” Cell Transplant 17.1-2 (2008):51-9.
  10. Mullen, Y, Maruyama M, Smith, CV. “Current progress and perspectives in immunoisolated islet transplantation.” J Hepatobiliary Pancreat Surg 7.4 (2000):347-57.
  11. Nair, LS and Laurencin, CT. “Polymers as biomaterials for tissue engineering and controlled drug delivery.” Adv Biochem Eng Biotechnol 102(2006):47-90.
  12. Schoubben, A, Blasi, P, Giovagnoli, S, Perioli, L, Rossi, C, Ricci, M. “” Eur J Pharm Sci 2008 [Epub ahead of print] Web.
  13. Sun, AM. ”Microencapsulation of pancreatic islet cells: a bioartificial endocrine pancreas.” Methods Enzymol 137 (1988): 575-80.
  14. Zimmermann, H, Zimmermann, D, Reuss, R, Feilen, PJ, Manz, B, Katsen, A, Weber, M, Ihmig, FR, Ehrhart, F, Gessner, P, Behringer, M, Steinbach, A, Wegner, LH, Sukhorukov, VL, Vásquez, JA, Schneider, S, Weber, MM, Volke, F, Wolf, R, Zimmermann, U. Towards a medically approved technology for alginate-based microcapsules allowing long-term immunoisolated transplantation. J Mater Sci Mater Med 16.6 (2005):491-501.
  15. Zekorn, TD, Horcher, A, Mellert, J, Siebers, U, Altug, T, Emre, A, Hahn, HJ, Federlin, K. “Biocompatibility and immunology in the encapsulation of islets of Langerhans (bioartificial pancreas). ” Int J Artif Organs19.4 (1996):251-7.