The Play Of Genes And Non
- Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, China
Diabetes has been a disease of public health concern for a number of decades. It was in the 1930s when scientists made an interesting discovery that the disease is actually divided into two types as some patients were insensitive to insulin treatment then. Type 2 Diabetes which happens to be the non-insulin dependent one is the most common form of the disease and is caused by the interaction between genetic and non-genetic factors. Despite conflicting results, numerous studies have identified genetic and non-genetic factors associated with this common type of diabetes. This review has summarized literature on some genes and non-genetic factors which have been identified to be associated with Type 2 diabetes. It has sourced literature from PubMed, Web of Science and Medline without any limitation to regions, publication types, or languages. The paper has started with the introduction, the play of non-genetic factors, the impact of genes in general, and ended with the interaction between some genes and environmental factors.
More On Inheriting Type 2 Diabetes Through Genes
Type 2 diabetes has a greater link to family history and lineage than type 1, and twin studies have revealed that genes significantly influence the development of type 2 diabetes. The race might also be a factor.
If you have a family history of type 2 diabetes, then determining whether your diabetes is caused by lifestyle factors or genetics might be difficult. However, it is a combination of the two. Exercising and losing weight have been shown in researches to help delay or prevent type 2 diabetes. However, some of the causes that may complicate type 2 diabetes are:
Identifying The Genes Responsible For Type 2 Diabetes
Studies of twins suggest that type 2 diabetes might be linked to genetics. These studies were complicated by the environmental influences that also affect type 2 diabetes risk.
To date, numerous mutations have been shown to affect type 2 diabetes risk. The contribution of each gene is generally small. However, each additional mutation you have seems to increase your risk.
In general, mutations in any gene involved in controlling glucose levels can increase your risk for type 2 diabetes. These include genes that control:
- the production of glucose
- the production and regulation of insulin
- how glucose levels are sensed in the body
Genes associated with type 2 diabetes risk include:
- TCF7L2, which affects insulin secretion and glucose production
- ABCC8, which helps regulate insulin
- CAPN10, which is associated with type 2 diabetes risk in Mexican Americans
- GLUT2, which helps move glucose into the pancreas
- GCGR, a glucagon hormone involved in glucose regulation
The interactions between genetics and the environment make it difficult to identify a definite cause of type 2 diabetes. However, that doesnt mean you cant reduce your risk through modifying your habits.
The Diabetes Intervention Accentuating Diet and Enhancing Metabolism study a large, 2020 randomized clinical trial of people with type 2 diabetes, suggests that weight loss and increased physical activity can prevent or reverse early type 2 diabetes.
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Genetic Prediction Of Type 2 Diabetes
Individual genetic variants, too, can predict incident T2D. In the Swedish Malmö Preventive Project, 11 SNPs individually predicted incident T2D in more than 15,000 participants over a median 24.8 years of follow-up, after adjustment for sex and baseline age. The odds ratio per risk allele ranged from 1.07 for the variant near HHEX to 1.30 for that in TCF7L2, compared with 1.67 for having a first-degree family member with diabetes and 1.84 for each standard deviation increase in BMI.
The 28-year cumulative incidence of type 2 diabetes by genotype risk score in 2377 participants in the Framingham Offspring Study. Reprinted with permission from the Massachusetts Medical Society, Copyright© 2008.
Is Type 2 Diabetes Genetic
Its hard to say. On the one hand, there is a very strong link between your familys genetics and the onset of type 2 diabetes. Race can also be a determining factor. We dont know why but type 2 diabetes seems to have a link to race and ethnicity, showing up more often in people of Black African descent, Hispanic populations, Native American, Asian, and Pacific Islanders. Age plays a role as well. If youre 45 or over, youre at a higher risk for type 2 diabetes.
However, its important to look at environmental and cultural factors here as well. Lifestyle choices like what you eat, how often you exercise, and whether you maintain a healthy weight are all part of the bigger picture and these kinds of habits often run in families and cultures.
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Insr And Diabetes: Digest Of Recent Articles
For a more complete list of research articles on INSR and diabetes, .
Mutations in INSR lead to a variety of rare clinical syndromes ranging in severity from , , and .
Resistance to insulin is one of the characteristics of type 2 diabetes. However, most diabetics have a normal sequence of the insulin receptor, indicating that if insulin receptor mutations contribute to the development of type 2 diabetes, they will be present only in a minor fraction of the diabetic population.
Several variants of the insulin receptor have been associated with hyperglycemia and type 2 diabetes . A heterozygous mutation changing Val-985 into methionine has been found to be more common in type 2 diabetics than in controls the relative risk for diabetes was over 4% for Met-985 carriers. The prevalence of the mutation increased with increasing serum glucose levels, suggesting a role for this receptor variant in hyperglycemia.
More Information On Genetics
If you would like to learn more about the genetics of all forms of diabetes, the National Institutes of Health has published The Genetic Landscape of Diabetes. This free online book provides an overview of the current knowledge about the genetics of type 1 and type 2 diabetes, as well other less common forms of diabetes. The book is written for health care professionals and for people with diabetes interested in learning more about the disease.
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Pik3r1 And Diabetes: Digest Of Recent Articles
For a more complete list of research articles on PIK3R1 and diabetes, .
A methionine to isoleucine switch at residue 326 has been observed in Europeans and Japanese . This change occurs just six amino acids from the N-terminal SH2 domain and appears to affect glucose homeostasis. In the Danish population, the variant was common in both diabetics and healthy subjects, with homozygous carriers being less effective at glucose regulation . In the Pima Indians, diabetes was less common in homozygous carriers compared with individuals who were heterozygous or wild type .
The M326I variant may lead to a reduced level of protein being expressed . The enzyme variant may also be less efficient in suporting the development of fat cells and in supporting insulin-stimulated glucose uptake into certain cells .
Overall, the M326I variant may only have a minor impact on the signaling events initiated by the insulin. But if combined with gene variants encoding other signaling proteins or acquired alterations in protein levels, this enzyme variant may contribute to a functional impact on insulin signaling and thus contribute to the events that lead to type 2 diabetes.
Pparg And Diabetes: Digest Of Recent Articles
For a more complete list of research articles on PPARG and diabetes, .
The variant of the PPAR receptor inherited may affect the risk of obesity or developing type 2 diabetes. Of particular interest is position 12 of the coding region. Most people have the amino acid proline here this confers a small risk of developing obesity, about 1.3% . For the individual, this 1.3% increase in risk is a small risk, but because 75% of the population have the proline allele, this translates into a tremendous impact on the number of people developing diabetes .
A common variant of the PPARÎ³2 is a single nucleotide polymorphism that has alanine in the place of proline at position 12 . Individuals who inherit this variant have a degree of protection against insulin resistance and obesity .
One study screened Pima Indians of Arizona for variations in PPARÎ³2. Type 2 diabetes is particularly common among this population. Affected individuals are obese and resistant to the insulin they produce in inadequate amounts. Several new SNPs were identified, many in the promoter region of the gene . It is not yet clear which SNPs are the most important in contributing to diabetes in this and in other populations.
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Genetic Architecture Of T2dm Disease Risk
The detailed genetic architecture of T2D risk has not yet been precisely defined. A relatively small percentage of non-autoimmune diabetes is due to monogenic causes and is classified as monogenic diabetes of the young or MODY . These cases are understood to be caused by single genes of high penetrance, of which mutations in the Hepatocyte nuclear factor-1A and the glucokinase gene are the most common. These forms of diabetes are sometimes misdiagnosed as T2D but clinically they are distinct diseases. They will not be considered further in this review but it should be kept in mind that the boundaries between polygenic and monogenic forms are not always sharply defined at the genetic level. Polymorphisms in genes involved in monogenic forms of diabetes also play a role in polygenic T2D.
Link Roundup For Hnf4a
Location of INS on the human genome. INS maps to chromosome 11, approximately between 2,144 and 2,148 kilobases . Click on the figure or here for a current and interactive view of the location of INS in the human genome. Note: this figure was created
C-peptide is secreted in equal amounts to insulin, but it has long been thought that it has no biological role. However, in diabetic rats C-peptide has been shown to reduce the dysfunction of blood vessels and the nervous system that is common in diabetes . C-peptide contains the greatest variation among species, whereas regions of insulin that bind to the insulin receptor are highly conserved.
Several single nucleotide polymorphisms have been found within the INS gene, none of which cause non-synonymous amino acid changes in the mature protein .
A using the human proinsulin precursor as a query finds proteins in 107 different species, which are all metazoans apart from three plants and one bacterium. However, potential true have thus far been identified only in the mouse and rat.
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Extended Drs For T2d For Secondary Analyses
Although the most consistent associations with T2D have been observed for the food components we included in our DRS, some studies have also indicated that intake of other foods may be associated with risk of T2D. A recent meta-analysis suggested high intake of fruit to be protective , but the latest meta-analysis indicated no additional risk decrease at intakes above two servings per day . Likewise, a non-linear association was seen for vegetable intake , although high intakes of specific types of vegetables, especially green leafy vegetables may be beneficial . Moreover, total intake of fruits and vegetables does not seem to associate with the risk of T2D . Dairy products have been suggested to be protective , especially fermented dairy products such as yoghurt and cheese , but it is unclear whether specific dairy foods or dairy components explain observed associations . Lastly, findings regarding fatty fish are non-conclusive .
For secondary analyses, extended scores were created that additionally included intakes of fruit and vegetables, fermented dairy or high-fat fish. Thus, each extended score is included in total five foods or beverages. The extended scores summed up to low , medium and high DRS. Finally, we constructed an extended risk score simultaneously including intakes of the original components and all three additional components: low , medium and high DRS.
Diabetes Risk Genes As A Predictor Of Diabetes
Various studies have tested whether it can be possible to distinguish between persons with prevalent or incident type 2 diabetes and those without diabetes on the basic of data about gene variants. The usual procedure is the C-statistic . Combinations of SNPs alone lead to C-values < 0.65, which is much closer to 0.5 than to 1.0 . Studies have also tested whether SNP data can improve prediction models based on age, sex, obesity, and clinical, metabolic, and lifestyle factors, and have achieved prediction models with C-values between 0.66 and 0.91 .
Although a few studies have shown statistically significant improvements in the C-statistic, these gains in C-statistics were 0.03 . This small improvement in diabetes prediction accords with the estimate that the known > 60 risk gene variants explain only about 10% to 15% of the heritable component of type 2 diabetes . For this reason, determining gene variants in order to predict individual type 2 diabetes risk is not worthwhile at present. The same holds for the use of genetic data to plan personalized treatment options.
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Risk For Type 2 Diabetes: Epigenetic Causes Or Geneenvironment Interaction
Why, despite so many studies, the major part of the genetic component of type 2 diabetes remains unexplained, remains an open question. However, to date, the only SNPs that have been investigated are those for which the rare variant occurs with a frequency of at least 1% to 5%. It has been speculated that prediction could be improved on the basis of other, rarer forms of genetic variation, which can be detected with new sequencing methods, and of duplications or insertions into the genome . Early data indicate a role for geneenvironment interactions, since small studies have observed a dependence of the metabolic effect of physical activity on certain gene variants .
It is also possible that epigenetic changes such as DNA methylation contribute to the unexplained heritable component . Changes in methylation patterns and impairments of glucose metabolism have been shown in people who were exposed to malnutrition in utero during the Dutch Hunger Winter of 1944/45 . Future studies will show what other environmental factors affect on methylation patterns, and whether these epigenetic changes contribute to diabetes risk.
Genetic Factors Affecting Type 1 Diabetes
Type 1 diabetes is an autoimmune illness. It occurs when the bodys immune system kills healthy cells by mistake. This type most commonly appears during puberty, however, it can develop at any age. Doctors used to believe that type 1 diabetes was entirely hereditary. Not everyone with type 1 diabetes, however, has a family history of the disease.
Scientists have discovered alterations in the genes that create particular proteins in people with type 1 diabetes. These proteins are essential for the immune system to function properly. These genetic characteristics make a person prone to acquire type 1 diabetes, which can trigger a variety of circumstances. When a doctor diagnoses someone with type 1 diabetes, they will have it for the rest of their lives.
Some of the symptoms that develop or shows diabetes are:
- Increased thirst
- Irritability and other mood changes
- Fatigue and weakness
- Blurred vision
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These Are Some Of The Statistics:
- 80-90% of people with Type 2 diabetes have other family members with diabetes.
- 10-15% of children of a diabetic parent will develop diabetes.
- If one identical twin has type 2 diabetes, there is up to a 75% chance that the other will also be diabetic.
- There are many genetic or molecular causes of type 2 diabetes, all of which result in a high blood sugar.
- As yet, there is no single genetic test to determine who is at risk for type 2 diabetes.
- To develop type 2 diabetes, you must be born with the genetic traits for diabetes.
- Because there is a wide range of genetic causes, there is also a wide range in how you will respond to treatment. You may be easily treated with just a change in diet or you may need multiple types of medication.
The hallmark of type 2 diabetes is resistance to the action of insulin and insufficient insulin to overcome that resistance
Create A Balanced Meal Plan
Cooking your own meals is the easiest way to make nutrient-dense choices.
Come up with a weekly meal plan that includes dishes for every meal. Stock up on all of the groceries youll need and do some of the prep work ahead of time.
You can ease yourself into it, too. Start by planning your lunches for the week. Once youre comfortable with that, you can plan out additional meals.
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Genetics Of Type 2 Diabetes Mellitus
Unlike single gene disorders, where expression of the disease is influenced by a mutant allele at one gene locus, in common diseases like type 2 diabetes mellitus the disease expression depends on many gene loci which all have small to moderate effects. Type 2 diabetes mellitus is a so-called multifactorial disease in which the genes not only interact with each other but also with environmental factors. It is probable that both insulin activity and secretion are subject to genetic variance at several loci. According to this multifactorial model, predisposition to the disease could be determined by many different combinations of genetic variants and environmental factors the genetically predisposed subjects will not necessarily develop the overt syndrome unless they are also exposed to particular environmental factors. It is well known that exogenous factors such as age, physical activity, diet, and obesity, play a major role in the disease aetiology of type 2 diabetes mellitus.