Genetics and Diabetes

Diabetes
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Table of Contents
Abstract........................................................................................................................3
Introduction………………………………………………………………………….4
Literature Review ……………………………………………………………………6
Age Factor and Diabetes ……………………………………………………11
Genetics and Diabetes ……………………………………………………….12
Substance Abuse and Diabetes ………………………………………………16
Treatment of Diabetes ……………………………………………………….21
Complications Related to Diabetes ………………………………………….23
Basis of Research ……………………………………………………………………27
Research Methodology……………………………………………………………….33
Results ……………………………………………………………………………….36
Analysis of Results ………………………………………………………………….38
Discussion ……………………………………………………………………………39
Areas of Further Research…………………………………………………………….43
Conclusion…………………………………………………………………………….44
References…………………………….............................................................................49
Abstract
According to input provided by the World Health Organization in 2001, about one hundred and fifty one million people were suffering from diabetes worldwide. The organization as well as stakeholders in various sectors of health argued that the incidence of diabetes would double within the next two decades. Given that diabetes has now become a worldwide pandemic, it can be said that the World Health Organization got their prediction right. It is regrettable that most of the cases of diabetes that have been reported in a recent past could have been avoided. The only problem is that we backed the wrong horse. For the better part of the past period, we have always left the role of controlling diabetes to the healthcare professionals, not knowing that the patients, dieticians, psychologists and the society at large have a role to play in the fight against diabetes. This research paper aims to provide more insight on the factors that cause diabetes as well as some of the mechanisms that we can put in place to accomplish the dream of having a diabetes free population. In a like manner, this research paper looks at some of the emerging trends concerning diabetes that are yet to be researched on.
Introduction
Before getting into the accomplished details of the research, it is far-reaching to have a detailed analysis of diabetes. Diabetes refers to the health condition where the patients who suffer from it have an abnormal quantity of sugar. The normal glucose level within a human body is 140mg/dl, a person is said to be suffering from diabetes when the concentration of glucose within the blood is 200mg/dl. Diabetes is characterized by frequent urination, frequent hunger as well as frequent thirst. In the recent past, though, it has been witnessed that those who suffer from diabetes tend to lose some considerable pounds of weight. There are different forms of diabetes ranging from type 1, type 2 and the forms that come about due to the genetic composition of the individual. Type 1 diabetes comes about by virtue of the failure of the pancreas to produce insulin. It is for this logic that those who suffer from type 1 diabetes are told to wear pumps of insulin wherever they go or are injected with shots of insulin on a regular basis. Type 2 diabetes, on the other hand, comes about due to the failure of the body to fully utilize the insulin that is produced by the pancreas. Congenital diabetes, monogenic diabetes and diabetes related to cystic fibrosis are the forms that come about due to the difference in genetic composition of the body. Moreover, it has been noted that the most occurring type of diabetes is type 2 while the forms of diabetes that come about due to the difference in the genetic composition of the patient such as that associated with cystic fibrosis are rare to come by.
Apart from the frequency of occurrence, there exits several trends that have been witnessed between type 1 and type 2 diabetes. For starters, type 1 diabetes majorly affects the children while type 2 affects those who have attained some considerable age. Similarly, it has been noted that type 1 diabetes is always a sudden occurrence while type 2 tends to occur gradually. In terms of body size, it has been observed that those who suffer from type 1 diabetes are normal in size whereas a plump body is witnessed among those who suffer from type 2 diabetes. The case of the two types of diabetes; type 1 and type 2 diabetes are further made interesting by the difference in rates of occurrence among coincidental twins. It has been ascertained for example; that the chances of coincidental twins suffering from type 1 diabetes is 50% while that of them suffering from type 2 diabetes is 90%. Overally, the incidence rate of type 1 diabetes stands at about 10% while that of type 2 diabetes is 90% this has been attributed partly to the difference in those who are affected by the two types of diabetes.
In the past, the treatment of diabetes mellitus could be carried out by administration of insulin. The health sector has, however, witnessed duration of treatment advances ranging from the transplantation of the islets of langerhans, transplantation of the pancreas all the way to insulin analogues and their contribution to diabetes treatment. In situations where the diagnosis and treatment have not been carried out in time, the patient is likely to develop several complications. These complications majorly affect the cardiovascular system, the eye, as well as the kidney. The prospect of this research paper is to establish the relationship between the lifestyle that we lead and the chances of us falling victims of diabetes.
Literature Review
Over the previous thirty years, the world has been witnessing the recurrence of the communicable diseases such as tuberculosis, Ebola as well as that of non-communicable conditions such as obesity, cardiovascular diseases and type 2 diabetes. The first extreme incidence of diabetes was recognized back in 1970’s among the Pima Indians and the Micronesian Naurans who lived along the Pacific Island. Forty years since the first extreme case of diabetes was registered, diabetes has changed from being a mild ailment to one of the major causes of mortality and morbidity among children, adolescents and adults. The statistics are more worrying among the developed nations where it is one of the top causes of conditions such as blindness, renal failure and lower limb amputation. Moreover, one point of great concern is the event that eighty percent of adults who suffer from diabetes always end up with a cardiovascular disease (Brill, 2012).
Based on the data released by the World Health Organization, the incidence of those who had diabetes increased from 151 million in 2000 to 221 million in 2010. The same organization has predicted that the number will further rise to 300 million by 2025 in all countries. Over the previous decade, the proportion of those who suffer from diabetes has increased from 11.4% to 14.5% in the United States. According to statistics from China, the nation has registered an increase of 3.1% of diabetes incidence (Brill, 2012). The same rate of increase has been registered in Australia where the current morbidity rate stands at 7.4% as compared to 3.4%, which was the situation ten years ago. Among African nations, the morbidity and incidence rate of diabetes has been on the rise with the Mauritius recording a morbidity rate of 14%. One region that stands out, and whose population records a slow incidence rate of diabetes is the Mediterranean region. This is because the rate at which diabetes occurs within the nations of the Mediterranean is quite low compared to data from other continents.
The maximum rates of diabetes are seen in Native Americans as well as Pacific Islanders, followed by Hispanics or the Mexican Americans. The rate at which, diabetes occurs among the African Americans and Africans is rather equivalent. In as much as the Mediterranean region has on several occasions registered several instances of diabetes, a section of their population has more often registered a high incidence rate of diabetes. This has been blamed on them not following the Mediterranean diet. Apart from those who reside in the Mediterranean diet, the only other section of the population to whom diabetes remains indigenous is the people who live a complete traditional lifestyle (Gough et.al, 2011).
As mentioned in the section above, the World Health Organization estimates that, in the next ten years, the number of those who shall be suffering from diabetes shall rise from 221 million to 300 million individuals worldwide. The projections of proliferating figures of people with diabetes are driven majorly by the predictable world population growth, notably amongst the middle-aged and elderly. Indeed, the concerns that have been raised to the effect that the estimates are conservative are true. This is because they have failed to account for the increases in the prevalence of diabetes within the respective age groups. Such age specifications though have been incorporated into the projections of the United States of America, as released by the American Diabetes Association.
The spectacular increase in the increase, in frequency of diabetes, is being parallel by a similarly alarming increase in obesity. Obesity is one of the considerable risk factors of diabetes, and because these two conditions are closely linked, stakeholders in different areas have coined the term diabesity.
The rising burden of diabetes, as well as other non-communicable diseases, has come at a time when modernization is also on the rise. Due to the aspect of modernization, the concept of epidemiological transition can help us understand the high incidence of diabetes. Over the past century, improved nutrition, better hygiene and the control of many communicable diseases has resulted in dramatically improved longevity. These benefits have, however, unmasked many age related non-communicable diseases including diabetes and the cardiovascular diseases. The non-communicable diseases that were uncommon have replaced many communicable diseases and are now major contributors to ill health and death. This phenomenon of shifting disease patterns is referred to us epidemiological transition.
Epidemiological transition, which was initially witnessed within the developed nations has spread intensely and is currently affecting the populations within the developing nations, as well. According to Gough et.al (2011), the impact of the Western nations on the developing nations is referred to us Coca colonization. He goes ahead to say that though the purpose of the western nations intruding on the lives of those living in the developing nations was to help them in achieving stability, one devastating results of the intrusion is the fact that those who live in the developing nations left their traditional lives and embraced the lifestyle of the developed nations. This has in effect led to those who suffer from developing nations to suffer from the non-communicable diseases.
Many once idyllic atolls in the Pacific region now show the disastrous results of epidemiological transition (Brown, 2008). During the nineteenth century, early voyagers brought infectious diseases such as measles, whooping cough, tuberculosis, influenza and venereal diseases to the Pacific Island region. In the nineteenth century, nearly all the pacific islands suffered a drastic reduction in population as a result of these imported diseases. The transition has seen diabetes catapulting from a rare disease at the beginning of the twentieth century to its present position as one of the major epidemics of the twenty-first century and a major global contributor to disability and death.
While the threat of communicable diseases has reduced, rapid socio-economic development as well as coca-colonization has resulted in a lifestyle transition from traditional to modern. In essentially all populations, greater fat diets and diminished physical activity have come along with the benefits of modernization. Exercising has been engineered out of our daily lives both in work place and in leisure (Shore, 2007). These lifestyle changes are well documented in Canadian and Native American communities, Pacific and Indian Ocean Islands populations as well as Australian Aboriginal communities, and when combined with increasing longevity, form the basis of the dynamic diabetes epidemic that we are witnessing today.
The explosion of diabetes in Native American and Pacific Island populations points the finger squarely at the environmental conditions albeit in populations with high genetic sensitivity to type 2 diabetes. The advancement has taken place too quickly to be due to altered gene frequencies. On the other hand, the high differences in prevalence between ethnic groups when exposed to similar environments also implicate a significant genetic contribution. Overtime, it has been argued that the lifestyle related diabetes epidemic in Native Americans and Pacific Islanders seemingly results from the impact of our ancient hunter-gatherer genes with the new twentieth century way of life. The Western lifestyle must have uncovered the effects of genes that had pre-existed because the insistent result has been diabetes in a period of a few decades. The former dependency on hunting and gathering in these societies and later subsistence agriculture was replaced by with a modern pattern characterized by a sedentary lifestyle together with a diet of energy-dense processed foods, high in saturated fat. These were usually imported from neighboring and perhaps well-meaning developed nations. In the Pacific region, nations such as Australia and New Zealand still export large quantities of consumable products rich in animal fats, e.g. canned meats and fatty joints, to the Pacific Islands. These are foodstuffs that their own populations would be loath to eat.
Another way to explain the epidemic is through Noel’s thrifty genotype hypothesis, which proposes that the genes selected over the past millennia to enable survival during periods of famine by efficiently keeping all available energy during periods of feast, are the very genes that lead to obesity and diabetes when exposed to constant high energy (Thomas, 2013). In recent years, an observation of the association between low birth weight and abnormal glucose tolerance has led to a competing hypothesis of the thrifty phenotype. Studies have shown that middle-aged people with abnormal glucose tolerance were, on average, lighter at birth than the healthy controls. The same studies reveal that those who suffer from both hypertension and cardiovascular diseases were also lighter at birth as compared to the healthy controls. It has been suggested that intra-uterine malnutrition slows fetal growth, causing low birth weight, insulin resistance and defects in insulin secretory function. When these metabolic abnormalities combine with advancing age and obesity, abnormal glucose tolerance develops. Therefore, environmental influences affecting the intra-uterine environment are suggested to be more important than genetic factors causing diabetes. It seems more probable that a combination of genetic factors and environment affects the intra-uterine environment and the fetal response to it. Furthermore, low birth weight does not account for more than 35% of cases of diabetes in any population studied. Thrifty phenotype and genotype may not be competing hypotheses at all, but may both contribute to what is clearly a multifactorial problem.
The Age Factor and Its Relationship to Diabetes
Several decades ago, diabetes was typically regarded as a disease of the middle aged and the elderly. While it is still true that this age group maintains a higher relative risk in relation to younger adults, there is accumulating and disturbing evidence that the onset in the 20-30 year age group is increasingly seen. Even children are now being caught up in the epidemic of diabetes. Although type 1 diabetes is still the main form of the diseases in children worldwide, it is more probable that type 2 diabetes will be the most common form in the next decade in many ethnic groups and potentially in the Europid groups, having already been reported in children from Japan, the USA, Pacific Islands, Hong Kong, Australia and the U.K. This new hypothesis brings a serious new aspect to the diabetes epidemic and advises on an emerging public health problem of serious proportions. Among children in Japan for example, there are more children who suffer from type 2 diabetes as compared to those who suffer from type 1 diabetes. Accounting for eighty percent of childhood diabetes, the incidence almost doubled between 1976-1980 and 1991-1995. The advancing prevalence of obesity as well as type 2 diabetes in children is no doubt one of the symptoms that show the negative effects of globalization and industrialization affecting all societies, with sedentary lifestyle and obesity the predominant factor involved (Thomas, 2013).
This fall in the age that type 2 diabetes begins in children is one of the far-reaching factors that influence the future burden of the diseases. Onset in childhood heralds many years of disease, and the accumulation of the full range of both micro and macro vascular complication. The American Diabetes Association, an institution that is tasked with the responsibility of reducing the incidence of diabetes, together with the American Academy of Pediatrics has recently issued a consensus statement on the problem. The report addresses the issue of compliance in diet and tablet and insulin therapies (Schaffer, 2006). Recently, a number of pharmaceutical companies have embarked on clinical trials of oral hypoglycemic agents to check their safety and efficacy in this age group as they may face up to 40 to 50 years of therapy.
Genetics and Diabetes
Type 1 diabetes mellitus also known as Insulin-Dependent diabetes Mellitus, is a chronic condition of insulin deficiency resulting from the autoimmune distraction of pancreatic beta cells. The disease is most common in childhood as well as among adolescents, though it can occur at any age showing significant heterogeneity in its clinical presentation and evolution. A large proportion of patients with type 1 diabetes mellitus lack a positive family history for the disease, but first degree relatives most commonly siblings or twins have a higher risk of developing type 1 diabetes mellitus than the general population. Within families, individual susceptibility depends on the level of genetic identity with the proband. Similarly, it is of significance to note that the possibility of diabetes in families has a non-linear relationship with the number of alleles shared with the proband.
The highest risk is, therefore, observed in monozygotic twins whose probability index of 100%. The first-degree relatives follow the monozygotic twins with a probability of 50%. The second-degree relatives have a probability of 25% whereas the third degree relatives have a probability of 12.5%. It is far-reaching to recognize that identical twins have a concordance rate for type 1 diabetes mellitus development ranging between 30% and 50% with rates of 70% reported in studies with the longest follow-up. The average prevalence of type 1 diabetes mellitus stands at 6% in siblings compared to 0.4% witnessed among the Caucasian population found in the United States. The familial clustering can of course be achieved by working out the ratio of the risk to siblings weighed to the prevalence of the disease in the general population. It has been estimated that for type 1 diabetes mellitus, the familial clustering has lambda values of 15. From the epidemiological illustrations above, it has been illustrated that genetic factors play a role in the multifactorial origin of this complex disease. Over the years, numerous studies have accumulated a large body of evidence indicating that genetic factors influence both susceptibility as well as the resistance of an individual to type 1 diabetes mellitus. There appears to be several categories of genetic factors or mechanisms that modulate the susceptibility of an individual to diabetes mellitus. Some of the factors that fall in these categories include inherited gene polymorphisms, epigenetic mechanisms regulating the transmission and expression of inherited genes, and post transcriptional regulatory mechanisms.
The genetic composition of an individual also determines whether the individual is likely to suffer from type 2 diabetes mellitus. The first evidence alluding to the possibility of a genetic component in the inter-generation of type 2 diabetes mellitus was derived from the demonstration of familial correlation in a number of diverse ethnic groups. In particular, families with a type 2 diabetes proband have an increased prevalence of disease in their siblings, parents and offspring compared to the population (Stipek, 2004). Similarly, there is an increased prevalence of diabetes in offspring depending on the parental family history of diabetes. Observations among Pima Indians suggested that an even greater risk to disease was conferred to offspring if the parental diabetic history was maternal in origin, or if either parent had an early onset of disease. Based on findings from the San Antonio family study, it was deduced that there is a varying degree of risk within families, and this was dependent on relative kinship with the diabetic proband. First-degree relatives were found to have almost doubled the population risk. Epidemiological studies in twin studies have also been exploited to support the paradigm. That type 2 diabetes mellitus has a genetic component (Bernett, 2009). Twin studies theoretically allow for the separation of the genetic component of variance, since monozygotic twins share 100% of their genes, whilst non-identical dizygotic twins only share half on average. Hence, discordance in the rates of diabetes between monozygotic twins as well as dizygotic twins, with monozygotic twins having greater concordance rates consistently, can be interpreted as evidence that the disease has a genetic basis, under the assumption that they have been subjected to the same shared environment. Concordance rate in European populations has been recorded between 28.6%-34% and 14.3%-16% in monozygotic and dizygotic twins respectively. Studies incorporating follow-ups of 10 and 15 years found the concordance rates elevating to 58% and 76%. Two recent studies in Danish and British subjects found that, in addition to discordance between monozygotic and dizygotic, the concordance rate within twins was higher was higher when measurements of glucose tolerance were considered rather than overt diabetes. Based on these findings, the researchers postulated that a genetic predisposition was more important for the development of abnormal glucose tolerance, whereas non genetic factors predominate in controlling whether a genetically predisposed individual progresses to overt type 2 diabetes mellitus. However, evidence for a genetic component from these epidemiological studies is mainly conjecture. A true unbiased estimate of both additive and non- additive heritability could only be achieved if the monozygotic twins are reared separately, and studies of this kind are rare. Moreover, the inferred genetic components of some of these studies could be inflated due to non-additive genetic effects with also the possibility that a non-genetic mode of disease transmission underlies some if not all the differences in concordance rates.
Further support for a genetic mode of transmission is drawn from the substantial differences in disease prevalence often present in distinct ethnic groups under similar environmental burdens. This is particularly evident in the different racial groups within the USA, with progressive admixture into communities through migration affecting relative risk to disease (Peacock, 2000). Admixed population comprising of two ethnic groups, one at high risk to Type 2 Diabetes Mellitus, such as Native American Indians and another at relatively low disease risk such as Caucasians, can generate an intermediate disease rate status. Under these circumstances, it is hypothesized that the high-risk ethnic group have a higher frequency of disease susceptibility genes and the rate of disease in admixed population is proportional to the percentage of the gene pool derived from this ethnic population. For instance, in full-blooded Nauruan of Micronesia the prevalence of diabetes after the age of sixty years is 83%, whereas it is only 17 % in those inhabitants who have a Caucasian gene admixture. The heterogeneity of the type 2 diabetes mellitus both at phenotypic and pathophysiological levels almost certainly indicates that the genetic components is likely to be heterogenous with no single locus accounting for the disease. However, the manifestation of the common idiopathic type 2 diabetes mellitus phenotype is likely to be the result of the interaction of diverse environmental factors on this background of heterogenous genetic predisposition. The complexity and mechanisms involved in the gene environment interaction and the mode of inheritance of type 2 diabetes mellitus is largely unknown.
The ultimate rationale for studying a disease is to manage, treat and eventually prevent any disorders that are related to the disease. One factor that we agree on, though, is the event that the identification of susceptibility genes that are responsible for the genetic component of type 2 diabetes mellitus could greatly assist in the analysis of the underlying pathophysiological mechanisms leading to the disease and is of significance to the development of more efficient, preventive and therapeutic strategies for this condition.
Substance Abuse and Diabetes
Human beings have several materials that can be used to enhance pleasure and in no way with negative feelings or emotions. Topping the list of substances that humans use for purposes of pleasure is alcohol, followed by tobacco. In as much as different cultures worldwide have a variety of opinions regarding alcohol use, the fact that it is legally available has made it a common product that can be consumed by many. There is a wide body of literature that talks about the role of alcohol in the etiology of diabetes, on glycemic control, as well as on the incidence of complications. It has been ascertained that the effects of alcohol on diabetes are complex and that they depend on dosage. For starters, alc...