Introduction
Diabetes is a health condition affecting the bodily use of food for energy. The body converts most of the consumed food into sucrose or glucose. It is then released into the bloodstream. Young people with maturity-onset Diabetes are a less common disease with a significant hereditary component (MODY). Diabetes is caused by a gene mutation passed from parent to child. In this case, a person’s genes rather than their environment may have an enormous significance in developing this chronic illness. Daily insulin injections are required for diabetic children to maintain natural glucose levels. In this annotated bibliography, they study the genetic factors of Diabetes in children. Each academic resource is summarized, and issues about Diabetes in children have been reflected scientifically.
Annotated Bibliography
Chang, T.-J., Wang, W.-C., Hsiung, C. A., He, C.-T., Lin, M.-W., Sheu, W. H.-H., Chang, Y.-C., Quertermous, T., Chen, Y.-D. I., Rotter, J. I., & Chuang, L.-M. (2018). Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of Diabetes: A SAPPHIRe Cohort Study. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-28891-z
Summary
This Study’s goal was to assess the results of a previous experiment and discover whether particular genetic polymorphisms are connected to markers of glucose homeostasis. The study used the methodology technique of examining the incidence of Diabetes and age onset. Insulin resistance and anomalies in pancreatic beta cells’ insulin secretion, necessary to maintain homeostasis, were the primary pathogenesis in developing type-2 Diabetes. Additionally, inherited and environmental factors are causative agents. Genetic factors, therefore, have a fundamental impact in combination with environmental variability.
Reflection
The Study found that SORBS1 is associated with diabetes prevalence, age onset of the illness, and other aspects of glycemic control. The findings are consistent with previous research in several ethnicities and point to a function for the gene in the pathophysiology and clinical symptoms of Diabetes. Asian ethnicities tend to develop Diabetes at a relatively young age than those in Europe. Along with impacts from lifestyle and the environment, inherited factors may also play a role in this phenomenon. Consequently, this calls on the health industry and the public to collaborate globally. Hence, it will help enhance measures intended to limit the type 2 diabetes epidemic’s rapid development, wreaking havoc on the younger population.
Li, J., Sun, S., Wang, X., Li, Y., Zhu, H., Zhang, H., & Deng, A. (2020). A Missense Mutation in IRS1 is Associated with Early-Onset Type 2 Diabetes Development. International Journal of Endocrinology, 2020, 1–8. https://doi.org/10.1155/2020/9569126
Summary
This Study included a home with possible MODY. The differences in the proband were investigated using whole-exome sequencing (WES). The variants’ frequency, location, functional ramifications, and bioinformatics software were screened. The researchers concluded that WES might be used as a starting point for genetic testing in persons with early-onset Diabetes. IRS1 p. His713Tyr has been proposed as a possible harmful mutation in monogenic Diabetes. However, to determine the specific chemical process behind IRS1 p’s influence, similar studies in the future may be required. More prospective trials are needed to determine the effect of His713Tyr on the onset of Diabetes. Experts are creating methods for estimating a person’s risk of developing Diabetes. For instance, most white people with type 1 diabetes carry the immunological genetic disease genes HLA-DR3 or HLA-DR4 (CDC, 2021).
Reflection
It is essential to understand that inheritance is the fundamental reason for the disease’s increased prevalence worldwide, even though other factors may also impact Diabetes in children. A patient is more likely to develop early-onset Diabetes if their family has a history of the disease. However, a positive parental history of Diabetes and monogenic Diabetes linked to specific disease types may be related to early-onset diabetes mellitus among people diagnosed before age 30. According to studies, young people with maturity-onset Diabetes are the most common kind of monogenic diabetes mellitus (MODY). As a result, MODY is probably the cause of early-onset diabetes mellitus. As a result, the risk to the child is raised if both parents are white and carry these genes. Type 2 diabetes may be passed down through families, and environmental variables are all connected to heredity.
Candler, T. P., Mahmoud, O., Lynn, R. M., Majbar, A. A., Barrett, T. G., & Shield, J. P. H. (2018). The continuing rise of Type 2 diabetes in children and young people in the UK. Diabetic Medicine, 35(6), 737–744. https://doi.org/10.1111/dme.13609
Summary
The Study sought to estimate the prevalence of Type 2 diabetes in patients below 17 in the United Kingdom and Ireland. Also, it outlines its characteristics and clinical symptoms. The Study’s methodology was based on the British Paediatric Surveillance Unit reporting structure. The results were then compared to relevant past studies. There was a trend toward increasing incidence between 2005 and 2015, but it was not found to be statistically significant. However, there is statistical support for the rising frequency among South Asian women and children when comparing the 2005 and 2015 surveys.
Reflection
The economy and society are negatively impacted by type 2 diabetes in young people’s health. The disease is strongly correlated with obesity, non-white ethnicity, family history, and female gender. Growing kid obesity rates, more diabetes screenings, maternal obesity, diabetes exposure in utero, and other variables are all significant in the rising prevalence of type 2. As a result, the significant rise in the prevalence of DM incidence in the UK is primarily due to the dramatic rise in obesity rates. To address the obesity pandemic, physical activity promotion in schools and other critical social institutions is necessary.
Piko, P., Werissa, N. A., Fiatal, S., Sandor, J., & Adany, R. (2021). Impact of Genetic Factors on the Age of Onset for Type 2 Diabetes Mellitus in Addition to the Conventional Risk Factors. Journal of Personalized Medicine, 11(1), 6. https://doi.org/10.3390/jpm11010006
Summary
In this study, 1415 of the general Hungarian population were sampled, and 881 T2DM patients served as the Case Population. In the case group, 23 SNPs were investigated for their connections to the early onset of T2DM. Twelve SNPs with a verified impact on T2DM age onset were chosen for optimum genetic risk score. A complex interplay of environmental, genetic, and behavioural influences leads to diabetes mellitus development. This Study evaluates the impact of SNPs associated with T2DM and the age at which T2DM first manifests in the population.
Reflection
It is proven that early diagnosis of type 2 diabetes is vital for reducing morbidities, infections, and early mortality (T2DM). The data suggest a strong genetic predisposition to T2DM development in childhood and existing risk factors. GRS is used to calculate the risk of early T2DM development and stratify those at risk to create preventative treatments. Therefore, a mix of risk factors such as the environment and lifestyle majorly causes diabetes-mellitus. However, genetics play the most significant causative factor. The body’s procedure mishandles insulin. This makes maintaining normal blood glucose levels challenging. 90% to 85% of all instances of Diabetes are caused by type II diabetes (CDC, 2021). Since it takes a while to develop in humans, it is usually discovered in adults.
Mars, N., Koskela, J. T., Ripatti, P., Kiiskinen, T. T. J., Havulinna, A. S., Lindbohm, J. V., Ahola-Olli, A., Kurki, M., Karjalainen, J., Palta, P., Neale, B. M., Daly, M., Salomaa, V., Palotie, A., Widén, E., & Ripatti, S. (2020). Polygenic and clinical risk scores impact age at onset and prediction of cardiometabolic diseases and common cancers. Nature Medicine, 26(4), 549–557. https://doi.org/10.1038/s41591-020-0800-0
Summary
The findings suggest the additional importance of Polygenic risk scores (PRSs) in clinical disease prediction. PRSs displayed promising ability in predicting disease susceptibility. Using large-scale biobank data from the FINRISK project, the researchers looked at the extra value of genomic sequence PRSs for type 2 diabetes. When paired with clinical risk scores, it investigated the impact on illness onset and prediction of genetic vulnerability at various PRS levels. A high PRS raised lifetime risk by 21% to 38% and hastened illness onset by 4 to 9 years compared to a regular PRS. Polygenic risk ratings have a lot to teach researchers. For example, they serve as prognostic indicators for a certain chronic illness. Additionally, it could create risk groupings among populations.
Reflection
(Genetics of Diabetes | ADA, n.d.) 80% of people with Diabetes are ignorant of their condition. Both adults and children may be affected, and it is reversible. However, it may be managed with medication, more exercise, a nutritious diet, and other lifestyle modifications. The Centers for Disease Control and Prevention estimate that more than 34 million Americans have Diabetes (CDC). Up to 95% of all instances of Diabetes are type 2 cases. Also, in a similar study, 122,780 children and teenagers under the age of 40 have type 2 diabetes, with 1,560 (or roughly 1.3 per cent) of them under the age of 19. All this is due to nutritional factors, obesity rates, and inadequate physical activity levels. It is becoming increasingly common in children and teens. On the other hand, type 2 diabetes in children may be treated and the signs and symptoms reduced by a healthy diet, regular exercise, and other lifestyle modifications. Therefore, achieving a healthy weight and reducing blood sugar spikes helps stop the progression of Type 2 diabetes in children.
Yamada, Y., Kato, K., Oguri, M., Horibe, H., Fujimaki, T., Yasukochi, Y., Takeuchi, I., & Sakuma, J. (2018). Identify four genes as novel susceptibility loci for early-onset type 2 diabetes mellitus, metabolic syndrome, or hyperuricemia. Biomedical Reports. https://doi.org/10.3892/br.2018.1105
Summary
Yamada et al. used human transcriptome accumulator sequencing techniques to conduct exome-wide correlation analyses to find genetic variations that increase a patient’s risk of developing early-onset T2DM in Japanese patients. Early-onset patients were looked at to boost the statistical power of EWASs. The Study assesses the genetic marker of type 2 Diabetes and how proteinuria may benefit by knowing the genotypes for the SNPs in these genes. Elevated proteins in the urine are known as proteinuria, commonly referred to as hyperuricemia. It is a sign of some kidney conditions rather than a disease. A higher chance of death from cardiac diseases may be associated with proteinuria. However, patients can have Hemodialysis and have typical quantities of protein in their urine. Therefore, proteinuria is an early indicator of chronic kidney disease (CKD).
Reflection
Assessment of the genetic predisposition for Type 2 diabetes mellitus among Japanese people may be aided by knowing the genotypes for the SNPs in these genes. The findings show the newly discovered genes that contribute to vulnerability to early-onset T2DM. Due to the high incidence of these illnesses and their role as risk factors for more severe disorders like cancer or type 2 diabetes is a significant public health issue. Twin studies have demonstrated that DNA greatly affects type 2 diabetes development. It has a stronger relation to family background and ancestry than t2dm. An additional factor is race. Nevertheless, environmental variables also influence the outcome. Identifying genetic variations that increase T2DM susceptibility is essential for the therapeutic prevention of these disorders.
Hamet, P., Haloui, M., Harvey, F., Marois-Blanchet, F.-C., Sylvestre, M.-P., Tahir, M.-R., Simon, P. H. G., Kanzki, B. S., Raelson, J., Long, C., Chalmers, J., Woodward, M., Marre, M., Harrap, S., & Tremblay, J. (2017). PROX1 gene CC genotype as a major determinant of early onset of type 2 diabetes in Slavic study participants from Action in Diabetes and Vascular Disease. Journal of Hypertension, 35, S24–S32. https://doi.org/10.1097/hjh.0000000000001241
Summary
The objective of this research was to analyze the variability among Caucasians. The results of this study demonstrated that distinct genetic topologies among Caucasian ethnic groups might have clinical consequences. One of these is the PROX1 gene, which differs according to nationality and is a frontrunner for hyperglycemia with early symptoms. A controller unit protein for lymphovascular invasion in the earliest stages of embryonic growth is PROX1. It is crucial in regulating the features and course of vascular endothelium. Additionally, it serves as a biomarker for these cells. Furthermore, gender-fluid interaction is a key activator for myogenic differentiation.
Reflection
Genetic research considers the seriousness of the geo-ethnic factors, including Caucasians, as shown in the T2D core features. The results demonstrate that understanding distinctive genomic architectures is essential for assessing treatment utility. This Study supports the notion that separating environmental from genetic factors can be accomplished by looking at migration within a particular group before mixing. The findings demonstrate the existence of unique genetic structures among Caucasian ethnic groups. Possibly, it has medical value. The PROX1 gene is a suitable causative agent for the premature development of Diabetes with ethnic differences.
Barkai, L., Kiss, Z., Rokszin, G., Abonyi-Tóth, Z., Jermendy, G., Wittmann, I., & Kempler, P. (2020). Changes in the incidence and prevalence of type 1 and type 2 diabetes among 2 million children and adolescents in Hungary between 2001 and 2016 – a nationwide population-based study. Archives of Medical Science, 16(1), 34–41. https://doi.org/10.5114/aoms.2019.88406
Summary
The objective was to examine changes in the prevalence and frequency of type 1 and type 2 diabetes between 2001 and 2016. It offers nationwide demographic and epidemiological information on Diabetes in children and teenagers under 18. The prevalence of T2DM remained steady overall. The ratio of men to women among those with newly diagnosed T2DM fell noticeably during the trial. Insulin is not generated enough in people with type 1 diabetes. This kind of Diabetes accounts for 5% to 10% of all cases.
Nevertheless, type 2 diabetes affects 90 to 95 per cent of them. Although type 2 diabetes is more prevalent in those over 45, it is also becoming prevalent in children, teens, and young adults. It explains a number of the causes. In conclusion, what is effective for one sort is ineffective for another.
Reflection
Males are more likely to get the most frequent kind of T1DM than females. T2DM is a common disease that affects more women than men, although the number of patients seeking medical care is not increasing.
More research is needed to understand the drop in the male-to-female ratio in T2DM patients with a recent diagnosis. Males are affected by type 2 diabetes almost twice as often as females. Both males and females experience obesity at equal rates in the US. Blood sugar basal levels are lower in females than in males. However, women have higher plasma levels of HDL cholesterol than males, whereas men have higher plasma concentrations of TG and Hdl cholesterol. Therefore, the relationship between sex, weight, and Diabetes may be more nuanced.
Werissa, N. A., Piko, P., Fiatal, S., Kosa, Z., Sandor, J., & Adany, R. (2019). SNP-Based Genetic Risk Score Modeling Suggests No Increased Genetic Susceptibility of the Roma Population to Type 2 Diabetes Mellitus. Genes, 10(11), 942. https://doi.org/10.3390/genes10110942
Summary
The objective was to compare and evaluate an allele load’s susceptibility throughout the larger population. Using GRS modelling on 16 variants associated with T2DM, the Study investigated whether genetic factors cause greater incidence among the Roman population. The findings can be used to pinpoint the people on which diabetes prevention programs in both populations should be concentrated. The majority of Hungarians have a greater inherited risk of getting Type 2 diabetes mellitus. Roma tends to have a frequency band of high T2DM that is more closely correlated with their environmental factors than their better genetic makeup. Prevention efforts should concentrate on the hazardous environmental exposures linked to their unhealthy way of living.
Reflection
The incidence of T2DM in both groups can be reduced more effectively by identifying those more sensitive to the condition. In the general population, the cumulative impact of these genetic changes on the onset of T2DM was greater. However, with Roma, external ethnicity-related factors like lifestyle outweighed the influence of inheritable characteristics. In contrast to their more significant genetic load, Roma tend to have a higher frequency of elevated T2DM, which appears more directly related to their environmental features. Preventive therapies for Roma T2DM should focus on the harmful environmental exposures associated with their standard way of life. The study was the first to examine whether there was a genetic component to the increased prevalence of Diabetes in the community.
Llanaj, E., Pikó, P., Nagy, K., Rácz, G., János, S., Kósa, Z., Fiatal, S., & Ádány, R. (2020). Applicability of Obesity-Related SNPs and Their Effect Size Measures Defined on Populations with European Ancestry for Genetic Risk Estimation among Roma. Genes, 11(5), 516. https://doi.org/10.3390/genes11050516
Summary
This study aimed to examine how hereditary factors contribute to the emergence of obesity. Most genetic variants from European populations have been found through genetic association studies. The findings suggest that Roma-enhanced vulnerability may be estimated using genetic susceptibility variables based on counting Alleles with noticeably greater outcome measurements in persons of European heritage. More Study is required to ascertain the role of SNP(s) with protective effects. Seldom does obesity run in families with a definite inheritance pattern brought about by alterations in a transgene. The MC4R produces receptor binding. A small proportion of 5% of obese persons across many ethnic groups have mutations to MC4R that impair its function.
Reflection
Taking a better, more targeted strategy for preventing obesity is necessary. Also, diabetes consequences in demographic groups biologically. Understanding the variation in genetic vulnerability among diverse populations of varied ancestries can help accomplish it. The reactions of the adult HG and HR populations to an important obesity-related gene polymorphism were characterized. The degree to which these connections are linked to rising overall and abdominal obesity was identified while considering waist circumference and body mass index using different phenotyping criteria. Managing overweight lowers the likelihood of various related illnesses such as Diabetes and heart disease. Obesity may be minimized by adopting a healthy lifestyle that includes regular exercise, nutritious food, and enough sleep.
References
Barkai, L., Kiss, Z., Rokszin, G., Abonyi-Tóth, Z., Jermendy, G., Wittmann, I., & Kempler, P. (2020). Changes in the incidence and prevalence of type 1 and type 2 diabetes among 2 million children and adolescents in Hungary between 2001 and 2016 – a nationwide population-based study. Archives of Medical Science, 16(1), 34–41. https://doi.org/10.5114/aoms.2019.88406
Candler, T. P., Mahmoud, O., Lynn, R. M., Majbar, A. A., Barrett, T. G., & Shield, J. P. H. (2018). The continuing rise of Type 2 diabetes in children and young people in the UK. Diabetic Medicine, 35(6), 737–744. https://doi.org/10.1111/dme.13609
Chang, T.-J., Wang, W.-C., Hsiung, C. A., He, C.-T., Lin, M.-W., Sheu, W. H.-H., Chang, Y.-C., Quertermous, T., Chen, Y.-D. I., Rotter, J. I., & Chuang, L.-M. (2018). Genetic variation of SORBS1 gene is associated with glucose homeostasis and age at onset of Diabetes: A SAPPHIRe Cohort Study. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-28891-z
Hamet, P., Haloui, M., Harvey, F., Marois-Blanchet, F.-C., Sylvestre, M.-P., Tahir, M.-R., Simon, P. H. G., Kanzki, B. S., Raelson, J., Long, C., Chalmers, J., Woodward, M., Marre, M., Harrap, S., & Tremblay, J. (2017). PROX1 gene CC genotype as a major determinant of early onset of type 2 diabetes in Slavic study participants from Action in Diabetes and Vascular Disease. Journal of Hypertension, 35, S24–S32. https://doi.org/10.1097/hjh.0000000000001241
Li, J., Sun, S., Wang, X., Li, Y., Zhu, H., Zhang, H., & Deng, A. (2020). A Missense Mutation in IRS1 is Associated with Early-Onset Type 2 Diabetes Development. International Journal of Endocrinology, 2020, 1–8. https://doi.org/10.1155/2020/9569126
Llanaj, E., Pikó, P., Nagy, K., Rácz, G., János, S., Kósa, Z., Fiatal, S., & Ádány, R. (2020). Applicability of Obesity-Related SNPs and Their Effect Size Measures Defined on Populations with European Ancestry for Genetic Risk Estimation among Roma. Genes, 11(5), 516. https://doi.org/10.3390/genes11050516
Mars, N., Koskela, J. T., Ripatti, P., Kiiskinen, T. T. J., Havulinna, A. S., Lindbohm, J. V., Ahola-Olli, A., Kurki, M., Karjalainen, J., Palta, P., Neale, B. M., Daly, M., Salomaa, V., Palotie, A., Widén, E., & Ripatti, S. (2020). Polygenic and clinical risk scores impact age at onset and prediction of cardiometabolic diseases and common cancers. Nature Medicine, 26(4), 549–557. https://doi.org/10.1038/s41591-020-0800-0
Piko, P., Werissa, N. A., Fiatal, S., Sandor, J., & Adany, R. (2021). Impact of Genetic Factors on the Age of Onset for Type 2 Diabetes Mellitus in Addition to the Conventional Risk Factors. Journal of Personalized Medicine, 11(1), 6. https://doi.org/10.3390/jpm11010006
Werissa, N. A., Piko, P., Fiatal, S., Kosa, Z., Sandor, J., & Adany, R. (2019). SNP-Based Genetic Risk Score Modeling Suggests No Increased Genetic Susceptibility of the Roma Population to Type 2 Diabetes Mellitus. Genes, 10(11), 942. https://doi.org/10.3390/genes10110942
Yamada, Y., Kato, K., Oguri, M., Horibe, H., Fujimaki, T., Yasukochi, Y., Takeuchi, I., & Sakuma, J. (2018). Identify four genes as novel susceptibility loci for early-onset type 2 diabetes mellitus, metabolic syndrome, or hyperuricemia. Biomedical Reports. https://doi.org/10.3892/br.2018.1105
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