New Clues to Genetics of Type 2 Diabetes - Article Example

To what extent and why is type 2 diabetes more extensively found in certain ethnic groups? This article is concerned with Type 2 Diabetes,its consequences, its causes and in particular to what extent and why is it more common among certain people groups than in other groups. It considers various research projects into the condition and possible genetic links. The conclusion is that, while there continues to be a need for more research, education and planning, in most cases the causes are environmental rather than genetic, although more is at present being discovered about various genetic mutations and how they affect the risk of developing the condition. Introduction Type 2 diabetes is also known as adult onset diabetes or non insulin dependent diabetes. It is a chronic condition and in many cases is associated with weight gain in middle life. However this isn’t always so and nor does this explain why it should be more prevalent among certain racial groups than others. The difference between this and type 1 diabetes is that, according to the WebMD page “Type 2 diabetes Overview” in the latter condition no insulin is produced. Diabetes is the most frequent cause of chronic renal failure as well as blindness in adults and the necessity for the amputation of limbs because of circulation problems, and it is also a major risk factor in cardiac disease, strokes, and can cause birth defects. I t is important that the causes, whether genetic or otherwise, are known as this will help with the education of both medical personnel and their patients as to the best way to deal with the condition. The hypoglycemia associated with the condition, when the body’s cells don’t receive enough calories to work properly, results in increased levels of hunger much like that experienced by those with type one diabetes. It can also make the person concerned nervous or shaky. They will perspire more than the non diabetic person and they become dizzy or light headed. Anxiety or weakness may result in difficulty with speech or feelings of restlessness. The diabetic person may become confused and even hallucinate. Because of anxiety, they may have nightmares or produce large amounts of sweat during sleep that their entire bed becomes damp. Often diabetics wake up still tired as well as irritable and perhaps confused. Of those worldwide who have diabetes, whether or not already diagnosed, in about 90% of cases it is the type 2. Rates of type 2 diabetes have been increasing around the globe. The rise is believed to be due to increasingly aging populations in developed countries and increasing obesity levels worldwide, mainly due to the adoption of a more western lifestyle.. In those affected by the condition the body becomes gradually more resistant to the effects of insulin, that is it doesn’t respond normally to the levels of insulin present. Insulin is a pancreatic hormone, produced by the islets of Langerhans, which in normal circumstances regulates the level of sugar in the blood stream and so controls the amount of sugar that enters the cells in order to provide energy. In some cases the problem is that the body fails to produce enough insulin to keep up a normal blood glucose level. In some cases none at all is produced. This lowering of insulin levels or the bodies ability to ignore the levels available results in a number of symptoms and if untreated can be fatal. The condition has no actual cure as yet, but the condition can be both managed and prevented if careful attention is paid to the diet and this is accompanied by exercise, both working towards maintaining a healthy weight level. Causes Theories as to the exact cause of the condition are numerous. It is certainly commoner in those with a family history of the condition and in women who had high blood sugar levels during pregnancy ( Gestational diabetes). One idea is that it is commoner in those who store fat around the abdominal organs rather than under the skin (subcutaneous fat). Abdominal fat may produce adipokines, a group of hormones that impair glucose tolerance. Aging also pays its part as the body mechanisms begin to fail with increased age. The increased incidence of childhood obesity has also led to young people developing the condition. It is surmised that the adoption of a western diet may lead to members of certain ethic groups developing the condition. There is even evidence that the use of certain plastics may lead to the onset of the condition. However research also points out that it is linked to poverty in inner city dwellers and as this often tends to include higher than usual proportions of those from non-Caucasian backgrounds, some of whom are shorter than average, that may be the reason why levels are higher in certain groups i.e. the situations in which their ethnicity tends to place them rather than a direct genetic link. In certain groups the disease has reached what, in an infectious disease, would have been referred to as ‘epidemic proportions.’ Members of one such group are older black American women. Those over 55 years of age have twice the amount of diabetes as is found in white women of a similar age. Not only that, but the condition tends to be generally more serious than in white women. They are one of several groups worldwide where a higher than average incidence of the condition has been studied, and in which, as in many other cases, it is closely associated with obesity and a certain lifestyle. Problems associated with type 2 diabetes Dehydration. The increase in the blood sugar because glucose is not being released into the cells can cause an increase in urination as the body attempts to remove the excess glucose in urine. This requires larger than normal amounts of water to pass through the kidneys and so dehydration may happen. Diabetic Coma. When someone with type 2 diabetes becomes badly dehydrated and does not drink enough fluids to make up for the extra water passed in the urine they may pass into a coma. The American Diabetic Association web page “Type 2 Diabetes” explains how the bodies cells become starved of the energy they need and at the same time continue dhigh levels of blood sugar can damage the eyes, the kidneys, the nerves and the cardiac system. Certain Groups Have a Higher Risk of Developing This Condition The American Diabetic Association lists a number of people groups who have a higher than average chance of developing this condition. These are Afro Americans, Latinos, Native Americans, Asian Americans, Pacific Islanders, as well as older members of society. In the case of the various people groups this is not necessarily related to their body weight according to a Reuters report, ‘Type 2 Diabetes Risk Differs by Ethnic Group’, dated March 20th 2009. The Reuters report says that this suggests to researchers that there is a genetic link. However the study chief, Dr Gertraud Maskarinec, of the Center for the Advancement of Health, noted that the condition is closely linked to being overweight and said "Everyone who is really overweight has a high risk for developing diabetes," but it seems that other factors can also be important. In Hawaii 187,000 adults from 5 different ethnic backgrounds participated in the Multiethnic Cohort Study of Diet and Cancer. Almost 12% were reported as having diabetes. However upon analysis only 6% of white Caucasian Americans had the condition compared with rates of 10% in Japanese – Americans, 15% in Afro-Americans and 16% in both Native Americans and those with a Latin background. The Reuters report quotes from the Journal of Ethnicity and Disease where Maskarinec and her fellows point out that “ The prevalence of diabetes was at least two-fold higher in all ethnic groups than among Caucasians," These differences were noted even in those of normal weight and even the under weight.. In a press statement, also quoted by Reuters, Matt Peterson, representing the American Diabetes Association, said ‘Clearly genes are involved.’ In another report, this time based upon poorer people in inner city Manchester, in North West England, a very racially diverse area, and one ranked in 1998 as the third most impoverished area of the United Kingdom according to the Manchester City Council web page. Riste, Khan and Cruickshank found high levels of diabetes among Europeans. A group of 1,318 individuals were included in the study. Their ages ranged from 25 to 79 years of age.More than 60% had very low incomes. Energy levels and exercise taken were both at low levels. They found higher levels of diabetes than in the American study described above with levels of 20% in Europeans and even higher levels of 22% in Afro Caribberans and 33% among Pakistanis. The study went beyond a vague ‘Genetic cause’ and began to define it - those with a larger waist measurement , lower height, and greater age were independently related to the plasma glucose levels found, and also to physical activity. The conclusion of these researchers was that an individual’s history and their relative poverty, when linked with obesity and physical inactivity, are likely contributing causes. Differences between the sexes was minimal. The reasearchers felt that differences between the groups was linked to waist size, height and activity levels and this made the difference between the various ethnic groups. Body mass was the best indicator of the possiblity of diabetes, that is the relationship between an individual’s height and their weight. The weight in kilograms is divided by the square of the persons height in meters and the result is their body mass. There are also formulas for obtaining similar results using Imperial measures i.e. pounds and ounces. The criteria used to define people as having diabetes by these researchers were those of theWorld Health Organization and of the American Diabetes Organization. This research was hindered by the mobility of these poverty stricken inner city dwellers. Many could not be located at the addresses given – presumably to their local National Health Service general practitioner. When everything had been taken into consideration the city dwellers had in general more than twice the incidence of type 2 diabetes than had been found in Ely, a small town in Cambridgeshire, South East England, with a mainly Anglo Saxon population,many with a relatively higher income than the Mancunian inner city dwellers. Reference is made to several other studies which have shown such things as an increase in the BMI ( body mass index) among people of West African descent when they become urbanised. This could be because of changes in diet and activity levels over time. Amy Adams, M.S. however, on the webpage “Genes Can Cause Type 2 Diabetes” staates that “Researchers have found many genes that can effect your heritable risk for developing Type 2 diabetes.” It depends upon the number of genetic mutations that occur, she says, whether or not Type 2 Diabetes will occur. The higher the number of such deviations then the higher the risk a person has of developing the condition. However it is not as simple as that. Any two patients with Type 2 diabetes may be found to have mutations in different subsets of genes. This makes it difficult for those studying the condition to predict which genetic subsets are likely to cause problems. As has been shown in many studies an individual’s life patterns and their surrounding environment are major factors when it comes to whether or not they fall victim of type 2 diabetes. There may be two people with apparently identical risk levels and even the same subset of gene mutations, but if one of them is able to control their body weight, and they take regular exercise, they may escape the condition. Amy Adams also mentions inherited life style patterns. Bad eating habits and reluctance to exercise are types of learned behavior that children copy from their older relatives. This type of inheritance is not genetic , and relatively hard to research, thus making it even harder for researchers to genuinely identify genetic risks for type 2 diabetes. Amy Adams, in her article, “What is Type 2 Diabetes?” points out how, if an identical twin develops the condition then the other twin has more or less a 100% chance of also having diabetes. She points out however that such a twin will usually have a more or less identical lifestyle. In the case of other siblings, or those who have a parent with the condition, then the risk falls to about 15%. There are however, despite the difficulties described above, some genes such as the Beta3-Adrenergic Receptor Gene that have been definitely implicated. This gene creates within the body’s fat cells a protein that is involved in deciding how many calories a person uses when they are resting. Mutation of this gene slows down the rate at which fat is burned off and so increases the possibility of obesity. A specific mutation within this gene, referred to as TRP64ARG, is more than three times more common in Pima Indians than in Caucasians, and in people of African or Mexican descent it is one and a half times more often. This mutation accounts, at least to some extent, for the higher levels of type 2 diabetes in these population groups. However, as Amy Adams points out in her article “What is type 2 diabetes?” the story of the Pima tribe of Native Americans clearly show the influence of environment. These people live in the Gila River valley near Phoenix. For 2 millennia the Pima Indians irrigated their land for farming. Then their water supply was diverted, and the Pimas were forced to adopt a more Western lifestyle. Obesity increased among tribal members, and the diabetes incidence rate quickly rose from only just over 0 percent to more or less 50 percent. The tribal genetic makeup did not change, but the lifestyle and environment. According to Beverleigh Piepers researchers in Australia have investigated the influence of genes upon type 2 diabetes in more than 2000 teenage twins and their brothers and sisters. The research was concerned with mitochondria. This was because of interest in the association of mitochondrial disorders and the development of type 2 diabetes. She discusses how researchers from the Queensland Institute of Medical Research conclude that diet is more important than genetic makeup. It is a person’s chosen lifestyle that makes the difference between a healthy life and one in which type 2 diabetes develops. There are scientific researchers who believe that in many populations there are genes which aided them in their struggle for survival in difficult times. These are called the ‘thrifty genes’. Those who carried such genes could store food more efficiently. This ensured not only their own survival, but also that they would live long enough to pass on their genes to their offspring. This positive result was maintained as long as traditional lifestyles were the norm, but it is thought that the same genes increased the risk of obesity, and so of type 2 diabetes, when a 21st century Western life style became the norm. There are those who have a double copy of the TRP64ARG mutation have a slower metabolism than people without the mutation. Therefore, they tend to be more obese — even in mutation carriers who do not go on to develop diabetes. They also have a harder time losing weight than the general population. In addition, people with the TRP64ARG mutation develop diabetes at an earlier age than Type 2 diabetics without the mutation. This mutation is not present in all Type 2 diabetics, but it appears to change the course of diabetes in those who carry it. The report of the American Medical Association, “Genetics of Type 2 Diabetes,” quotes vague estimates of between 30%-70% of type 2 diabetes risk is being attributable to genetics, with several genes involved. They say that various combinations of genes play their part in different subsets of the people concerned. They admit that it is still not known either how many genes may be involved or how much each gene controls the gradual development of the condition. The report goes on to cite gene variation TCF7L2, concerned with the development of pancreatic islet tissue, of as being associated with the impaired secretion of insulin secretion and so with increased liver glucose production. This, the writers believe, may in part explain why those with this variation may develop Type 2 Diabetes. Their risk is increased by 1 ½ times. If a double dose of the variation is present the risk goes up to 2.4 % SLC30A8, is a gene which makes zinc available for the formation of insulin. Any mutation of this gene is, according to the American Medical Association report, likely to cause problems with the secretion of insulin. Another possible troublesome gene mentioned is PPARγ as this affects the body’s sensitivity to the presence of insulin. In another report, “ The Genetics of Type 2 Diabetes: A Realistic Appraisal, 2008”. Jose Florez, of the Diabetes Unit and Center for Human Genetic Research at Massachusetts General Hospital, claims there are some 17 genetic connections that have been associated with type 2 diabetes. Many of these he says are to be found among European populations, yet are associated with only low risks. A March 2008 report by the Wellcome Trust is entitled “Scientists offer new clues to genetics of type 2 diabetes”. I t describes how 6 new genes have been implicated in the onset of diabetes by a group of 90 scientists working together internationally in more than 40 centers. According to the writers this brings the total of known genetic factors up to 16. Professor Mark McCarthy of Oxford University is quoted as saying None of the genes we have found was previously on the radar screen of diabetes researchers. Each of these genes therefore provides new clues to the processes that go wrong when diabetes develops, and each provides an opportunity for the generation of new approaches for treating or preventing this condition. The research has been found to back up earlier studies which suggest that an important process in the development of this type of diabetes is the failure to control the amount of pancreatic insulin-producing cells.. JAZF1 is one example of a gene that hadn’t been previously expected to be concerned, although it had already been known to be involved in prostate cancer, a totally different condition. The report’s first author, Dr Eleftheria Zeggini from the University of Oxford, said:- Genetic studies of this kind are revealing new and unsuspected connections between diseases…..This is now the second example of a gene which affects both type 2 diabetes and prostate cancer. We don’t yet know what the connections are, but this has important implications for the future design of drugs for these conditions. It is known that the presence of each of the newly discovered genes only increases the risk of diabetes by a little amount. I t is when an individual has a number of such genes the effects are enhanced. In the same report American professor David Altshuler of the Broad Institute of Harvard and MIT in Cambridge, USA is quoted as saying :- Once we more fully understand the large numbers of genes now implicated in diabetes risk, it might become possible to identify people at particularly high risk before the disease takes root. Conclusion By finding out previously unknown ways in which the body is normally able to keep control of blood glucose levels the various research projects offers new opportunities for the development of new and more effective methods of both treating and preventing this prevalent disease. Whatever its cause type 2 diabetes has increased in prevelence in recent years. BBC News reported in October 2004 that the number of sufferers in the United Kingdom had increased to 1.8 million, an increase of 400,000 in 8 years. Such increases can be seen worldwide as the average age of the population increases, and more people becoem city and town dwellers, and the changes in lifestyle that brings, such as changes in foods eaten and lower levels of exercise taken than those of rural farmers.. Although it does occur in all populations around the globe it is obvious that the incidence of this condition does vary widely among various people groups and also according to environmental and life style differences.. The American Medical Associtation report “Genetics of Type 2 Diabetes” describes it as a multifactorial condition, that is the causes are not straight forward, but are combination of genetic factors and the environment.This presents a complex problem to those who plan and oversee health services. This is especially so as often the disease is undetected until a major problem occurs e.g. diabetic come or damage to the eyesight . It is also an increasing expense. In the United Kingdom for instance it is expected to take up 10% of the National health Service budget by 2011. In 2004 the figure was half that amount. One of the few good things that can be said on the subject is that it has been well studied and the facts are made freely available to the general public. Although not all cases of type 2 diabetes are related to lack of exercise and poor dietary choices, for the majority , whatever their ethnic background, these are however important factors and, to a greater or lesser degree, within an individual’s control. In these early years of the 21st century scientific research has now advanced to the point where the influence of genes, and genetic variations, can be discovered in almost every medical condition. Despite this from the evidence provided by the various studies cited above it seems likely that the problem is not actually genetic in many cases i.e. the condition is not passed on at birth in a person’s genes. Rather these genes predispose certain people to have short stature and larger than average waist measurements and these factors, together with the fact that they often belong to poorer sections of society with a relatively inactive life style, that makes them more susuceptable to the condition. Future Research It is perhaps surprising how much there is still to learn about such a common condition as type 2 diabetes. Because of its worldwide prevelence and importance economically, as well as in health terms, there must be continued research into Type 2 Diabetes. This could be used to predict trends which would make planning easier. This would also make it possible to provide material to educate both medical staff and diabetics, and to teach the public, of whatever genetic makeup, how best to avoid the condition. At the present time a study of the genetics of the condition among the Han Chinese is recruiting participants. One of the objectives of the study to is find out whether genetic variants which are associated with diabetes and which have been found in Europeans also increase the risk of the condition among Han Chinese. The researchers also want to try and replicate studies of variants found in African and European ancestry samples. They also wish to conduct a genome-wide association study in order to identify variants among genetics in the case of Han Chinese which make them more susceptible to the condition. John Timmer in “Genetics and Type 2 Diabetes” describes research into genetic factors in Iceland, a place where the population are almost entirely descended from a very small number of ancestors. The investigation is to link genetics with a high fat diet. It is concerned with variations in gene TCF7L2. Those with only one copy of this variant increase their risk of type 2 diabetes by a high 45%. Having more than one copy of this gene variation makes even bigger increases. These high level are to be expected not only in Iceland, but also to places where Icelanders have emigrated such as the United States of America, Timmer points out that the research will not mean that a cure is possible, but genetic testing will mean that possible sufferers can be identified and may afterwards make positive changes to their life styles. Works Cited Electronic Sources Adams, A. Genes Can Cause Type 2 Diabetes, Genetic Health, 15th September 2000, http://www.genetichealth.com/DBTS_Genetics_of_Type_2_Diabetes.shtml accessed 5th October 2009 Adams, A. What is Type 2 Diabetes?, Genetic Health, 15th September 2000, http://www.genetichealth.com/DBTS_What_Is_Type_2_Diabetes.shtml#Anchor2, accessed 5th October 2009 Florez,.J., The Genetics of type 2 Diabetes: A Realistic Appraisal, 2008, http://jcem.endojournals.org/cgi/content/abstract/jc.2008-1345v1 accessed 5th October 2009 Genetics of Type 2 Diabetes, The American Medical Association, http://www.ama-assn.org/ama1/pub/upload/mm/464/genetics-type-2-diabetes.pdf accessed 5th October 2009 Genetics of Type 2 Diabetes Among Han Chinese, National Institutes of Health Clinical Center, http://clinicaltrials.gov/ct2/show/NCT00837408 accessed 5th October 2009 Manchester City Council, http: //www.manchester.gov.uk. accessed 4th October 2009 Piepers, B., Is Types 2 Diabetes Caused by Genetics?, Ezine, http://ezinearticles.com/?Is-Type-2-Diabetes-Caused-by-Genetics?&id=2937105 accessed 5th October 2009 Riste, L., Khan, F. and Cruickshank, K., High Prevalence of Type 2 Diabetes in All Ethnic Groups, Including Europeans, in a British Inner City Relative poverty, history, inactivity, or 21st century Europe? , http://care.diabetesjournals.org/content/24/8/1377.full accessed 4th October 2009 Sharp Increase in Diabetes Cases, BBC News, 6th October 2004, http://news.bbc.co.uk/1/hi/health/3719490.stm accessed 4th October 2009 Type 2 Diabetes, American Diabetic Association http://www.diabetes.org/type-2-diabetes.jsp accessed 4th October 2009 Type 2 Diabetes Overview, WebMD http://diabetes.webmd.com/guide/type-2-diabetes, accessed 4th October 2009 Type 2 Diabetes Risk Differs by Ethnic Group, Reuters, 20th March 2009, http://www.reuters.com/article/healthNews/idUSTRE52J2UL20090320 accessed 4th October 2009 Wellcome Trust, Scientists Offer New Clues To Genetics of Type 2 Diabetes, Physorg.com, March 3rd 2008, http://www.physorg.com/news126112230.html accessed 5th October 2009 Read More