scholarly journals Emerging roles of rare and low-frequency genetic variants in type 1 diabetes mellitus

2021 ◽  
Vol 58 (5) ◽  
pp. 289-296
Author(s):  
Haipeng Pang ◽  
Ying Xia ◽  
Shuoming Luo ◽  
Gan Huang ◽  
Xia Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Current Knowledge ◽  
Association Studies ◽  
Low Frequency ◽  
Effect Sizes ◽  
Genome Wide Association Studies ◽  
Common Variants

Type 1 diabetes mellitus (T1DM) is defined as an autoimmune disorder and has enormous complexity and heterogeneity. Although its precise pathogenic mechanisms are obscure, this disease is widely acknowledged to be precipitated by environmental factors in individuals with genetic susceptibility. To date, the known susceptibility loci, which have mostly been identified by genome-wide association studies, can explain 80%–85% of the heritability of T1DM. Researchers believe that at least a part of its missing genetic component is caused by undetected rare and low-frequency variants. Most common variants have only small to modest effect sizes, which increases the difficulty of dissecting their functions and restricts their potential clinical application. Intriguingly, many studies have indicated that rare and low-frequency variants have larger effect sizes and play more significant roles in susceptibility to common diseases, including T1DM, than common variants do. Therefore, better recognition of rare and low-frequency variants is beneficial for revealing the genetic architecture of T1DM and for providing new and potent therapeutic targets for this disease. Here, we will discuss existing challenges as well as the great significance of this field and review current knowledge of the contributions of rare and low-frequency variants to T1DM.

scholarly journals Autoimmune thyroid disease and type 1 diabetes mellitus: same pathogenesis; new perspective?

2020 ◽  
Vol 11 ◽  
pp. 204201882095832
Author(s):  
Liyan Li ◽  
Shudong Liu ◽  
Junxia Yu
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Type 1 Diabetes Mellitus ◽  
Thyroid Disease ◽  
Autoimmune Thyroid Disease ◽  
Current Knowledge ◽  
Tyrosine Phosphatase ◽  
Autoimmune Thyroid

Autoimmune thyroid disease (AITD) and type 1 diabetes mellitus (T1DM) are two common autoimmune diseases that can occur concomitantly. In general, patients with diabetes have a high risk of AITD. It has been proposed that a complex genetic basis together with multiple nongenetic factors make a variable contribution to the pathogenesis of T1DM and AITD. In this paper, we summarize current knowledge in the field regarding potential pathogenic factors of T1DM and AITD, including human leukocyte antigen, autoimmune regulator, lymphoid protein tyrosine phosphatase, forkhead box protein P3, cytotoxic T lymphocyte-associated antigen, infection, vitamin D deficiency, and chemokine (C-X-C motif) ligand. These findings offer an insight into future immunotherapy for autoimmune diseases.

scholarly journals Slowly Progressive Type 1 Diabetes Mellitus: Current Knowledge And Future Perspectives

2019 ◽  
Vol Volume 12 ◽  
pp. 2461-2477 ◽  
Author(s):  
Akihiro Nishimura ◽  
Kimio Matsumura ◽  
Shota Kikuno ◽  
Kaoru Nagasawa ◽  
Minoru Okubo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Current Knowledge ◽  
Future Perspectives ◽  
Progressive Type

scholarly journals Association studies between the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2), type 1 diabetes mellitus and diabetic nephropathy

2002 ◽  
pp. 553-558 ◽  
Author(s):  
GG Lavery ◽  
CL McTernan ◽  
SC Bain ◽  
TA Chowdhury ◽  
M Hewison ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Type 1 Diabetes Mellitus ◽  
Association Studies ◽  
Hydroxysteroid Dehydrogenase ◽  
Salt Sensitivity ◽  
Gene Encoding

OBJECTIVE: Mutations in the HSD11B2 gene (encoding human 11beta-hydroxysteroid dehydrogenase type 2) explain the syndrome of apparent mineralocorticoid excess where cortisol acts as a mineralocorticoid. A microsatellite marker within the HSD11B2 gene associates with salt sensitivity and hypertension--phenotypes characterising diabetic nephropathy. Here, we evaluate the HSD11B2 gene as a susceptibility locus for diabetic nephropathy. DESIGN: 150 patients with type 1 diabetes and nephropathy (DN), 145 patients with type 1 diabetes with a long duration of non-nephropathy (LDNN) and 151 normal controls were studied. METHODS: We determined allele frequencies for the (CA)n repeat marker within intron I of the HSD11B2 gene. Duration of type 1 diabetes, diabetic status and renal function were recorded. RESULTS: 11 alleles (138-158) for the marker were observed. Allele 152 was significantly increased in controls compared with LDNN (70.5% vs 57.6%, P(c)<0.05 where P(c) is the P value corrected for multiple comparisons) but no difference was observed between DN and LDNN subjects. Allele 154 was significantly increased in the LDNN compared with the DN subjects (15.9% vs 7.0%, P(c)<0.01) but no difference was observed between DN and controls. A greater proportion of subjects carried at least 1 allele <152 in DN compared with control subjects (47.3% vs 28.5%, P(c)<0.01), but no difference was observed in LDNN compared with control and DN subjects. CONCLUSIONS: Weak associations are reported between the HSD11B2 gene, type 1 diabetes mellitus and nephropathy. The increased frequency of HSD11B2 short alleles in the diabetic groups may reflect reduced renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity and may, in part, explain the enhanced salt sensitivity observed in patients with type 1 diabetes.

scholarly journals Immunological predictors of type 1 diabetes mellitus (literature review)

2021 ◽  
Vol 24 (2) ◽  
pp. 167-174
Author(s):  
K. G. Korneva ◽  
L. G. Strongin ◽  
V. E. Zagainov
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Current Knowledge ◽  
Diagnostic Value ◽  
Individual Variability ◽  
Current Data ◽  
Dynamic Changes ◽  
Chronic Autoimmune Disease

Background: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by insulin deficiency due β-cell destruction and following hyperglycaemia. Specific markers of T1DM are pancreatic islet-targeting autoantibodies that are found months to years before symptom onset, and can be used to identify individuals who are at risk of developing T1DM.Aim: The study is aimed at the review of current knowledge of diabetes-related autoantibodies as biomarkers of T1DM.Materials and methods: Foreign and national clinical studies on this topic were included. PubMed, Medline and ­eLibrary were searched.Results: Modern ideas about known diabetes-specific autoantibodies as markers of autoimmune inflammation of β-cells of the pancreas were discussed. The analysis of their independent diagnostic value in predicting the occurrence of T1DM were carried out.Conclusion: There is no unified concept in the literature on this issue. Current data on autoantibodies in T1DM show a ­significant individual variability in the timing, dynamic changes and autoantibody composition in T1DM progression.

scholarly journals Genetic susceptibility to type 1 diabetes mellitus in humans

2007 ◽  
pp. 255-266
Author(s):  
D Kantárová ◽  
M Buc
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Current Knowledge ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Immune Mediated ◽  
Insulin Dependent ◽  
Genetically Determined

Type 1 diabetes mellitus (DM 1A) is an autoimmune disease belonging to the most frequent chronic diseases of the childhood and young adults. DM 1A results from immune-mediated destruction of the insulin-producing beta cells of the pancreas. It is a genetically determined disease and many genes or genetic regions were found to be associated with its induction. In addition to the insulin-dependent diabetes mellitus 1 (IDDM1) gene, which marks the HLA region, and IDDM2 which marks the insulin gene, significant associations of DM 1A to other IDMM genes or genetic regions we reported. We shortly review recent achievements in the field, and the state of current knowledge.

scholarly journals Cardiovascular Disease in Type 1 Diabetes Mellitus: Epidemiology and Management of Cardiovascular Risk

2021 ◽  
Vol 10 (8) ◽  
pp. 1798
Author(s):  
Cristina Colom ◽  
Anna Rull ◽  
José Luis Sanchez-Quesada ◽  
Antonio Pérez
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Type 1 Diabetes ◽  
Cardiovascular Risk ◽  
Type 1 Diabetes Mellitus ◽  
Current Knowledge ◽  
Chronic Hyperglycemia ◽  
Potential Risk Factors

Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes mellitus (T1DM) patients, and cardiovascular risk (CVR) remains high even in T1DM patients with good metabolic control. The underlying mechanisms remain poorly understood and known risk factors seem to operate differently in T1DM and type 2 diabetes mellitus (T2DM) patients. However, evidence of cardiovascular risk assessment and management in T1DM patients often is extrapolated from studies on T2DM patients or the general population. In this review, we examine the existing literature about the prevalence of clinical and subclinical CVD, as well as current knowledge about potential risk factors involved in the development and progression of atherosclerosis in T1DM patients. We also discuss current approaches to the stratification and therapeutic management of CVR in T1DM patients. Chronic hyperglycemia plays an important role, but it is likely that other potential factors are involved in increased atherosclerosis and CVD in T1DM patients. Evidence on the estimation of 10-year and lifetime risk of CVD, as well as the efficiency and age at which current cardiovascular medications should be initiated in young T1DM patients, is very limited and clearly insufficient to establish evidence-based therapeutic approaches to CVD management.

scholarly journals Epigenetic Regulation in Etiology of Type 1 Diabetes Mellitus

2019 ◽  
Vol 21 (1) ◽  
pp. 36 ◽  
Author(s):  
Marie Cerna
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Current Knowledge ◽  
Autoimmune Diabetes ◽  
Genetic Changes ◽  
Autoimmune Destruction ◽  
Past Half Century ◽  
Short Time

Type 1 diabetes mellitus (T1DM) is caused by an autoimmune destruction of the pancreatic β-cells, a process in which autoreactive T cells play a pivotal role, and it is characterized by islet autoantibodies. Consequent hyperglycemia is requiring lifelong insulin replacement therapy. T1DM is caused by the interaction of multiple environmental and genetic factors. The integrations of environments and genes occur via epigenetic regulations of the genome, which allow adaptation of organism to changing life conditions by alternation of gene expression. T1DM has increased several-fold over the past half century. Such a short time indicates involvement of environment factors and excludes genetic changes. This review summarizes the most current knowledge of epigenetic changes in that process leading to autoimmune diabetes mellitus.

scholarly journals Micro-RNA Implications in Type-1 Diabetes Mellitus: A Review of Literature

2021 ◽  
Vol 22 (22) ◽  
pp. 12165
Author(s):  
Kosmas Margaritis ◽  
Georgia Margioula-Siarkou ◽  
Styliani Giza ◽  
Eleni P. Kotanidou ◽  
Vasiliki Regina Tsinopoulou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Messenger Rna ◽  
Cell Function ◽  
Current Knowledge ◽  
Diagnostic Value ◽  
Micro Rna ◽  
Micro Rnas

Type-1 diabetes mellitus (T1DM) is one of the most well-defined and complex metabolic disorders, characterized by hyperglycemia, with a constantly increasing incidence in children and adolescents. While current knowledge regarding the molecules related to the pathogenesis and diagnosis of T1DM is vast, the discovery of new molecules, such as micro ribonucleic acids (micro-RNAs, miRNAs), as well as their interactions with T1DM, has spurred novel prospects in the diagnosis of the disease. This review aims at summarizing current knowledge regarding miRNAs’ biosynthesis and action pathways and their role as gene expression regulators in T1DM. MiRNAs follow a complex biosynthesis pathway, including cleaving and transport from nucleus to cytoplasm. After assembly of their final form, they inhibit translation or cause messenger RNA (mRNA) degradation, resulting in the obstruction of protein synthesis. Many studies have reported miRNA involvement in T1DM pathogenesis, mainly through interference with pancreatic b-cell function, insulin production and secretion. They are also found to contribute to β-cell destruction, as they aid in the production of autoreactive agents. Due to their elevated accumulation in various biological specimens, as well as their involvement in T1DM pathogenesis, their role as biomarkers in early preclinical T1DM diagnosis is widely hypothesized, with future studies concerning their diagnostic value deemed a necessity.

scholarly journals Heart Rate Variability Analysis: Higuchi and Katz’s Fractal Dimensions in Subjects with Type 1 Diabetes Mellitus

2018 ◽  
Vol 25 (3) ◽  
pp. 289-295 ◽  
Author(s):  
David M. Garner ◽  
Naiara Maria de Souza ◽  
Luiz Carlos M. Vanderlei
Keyword(s):  
Diabetes Mellitus ◽  
Heart Rate ◽  
Type 1 Diabetes ◽  
Fractal Dimension ◽  
Type 1 Diabetes Mellitus ◽  
Fractal Dimensions ◽  
Effect Sizes ◽  
Cohen’S D ◽  
Cohen's D

Abstract Background and aims: Statistical markers are valuable when assessing physiological status over periods of time and in certain disease states. We assess if type 1 diabetes mellitus promote modification in the autonomic nervous system using the main two types of algorithms to estimate a Fractal Dimension: Higuchi and Katz. Material and methods: 46 adults were divided into two equal groups. The autonomic evaluation consisted of recording heart rate variability (HRV) for 30 minutes in supine position in absence of any other stimuli. Fractal dimensions ought then able to determine which series of interbeat intervals are derived from diabetics’ or not. We then equated results to observe which assessment gave the greatest significance by One-way analysis of variance (ANOVA1), Kruskal-Wallis technique and Cohen’s d effect sizes. Results: Katz’s fractal dimension is the most robust algorithm when assisted by a cubic spline interpolation (6 Hz) to increase the number of samples in the dataset. This was categorical after two tests for normality; then, ANOVA1, Kruskal-Wallis and Cohen’s d effect sizes (p≈0.01 and Cohen’s d=0.814143 –medium effect size). Conclusion: Diabetes significantly reduced the chaotic response as measured by Katz’s fractal dimension. Katz’s fractal dimension is a viable statistical marker for subjects with type 1 diabetes mellitus.

The role of bariatric surgery in patients with type 1 diabetes mellitus

2021 ◽  
Vol 75 (6) ◽  
pp. 524-528
Author(s):  
Dita Pichlerová
Keyword(s):  
Diabetes Mellitus ◽  
Bariatric Surgery ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Retrospective Studies ◽  
Current Knowledge ◽  
Case Reports

Bariatric surgery procedures are recognized as the most successful method of treating diabetes in obese patients with type 2 diabetes mellitus. Despite the fact that the number of obese type 1 diabetics has been constantly increasing in the last decade, bariatric surgery in these patients is still waiting to be widely used and standardized. Bariatric surgery has been proposed as an effective treatment for these patients, although data are scarce, based on case reports and retrospective studies. The article summarizes the current knowledge about the use of bariatric surgery in type 1 diabetics with obesity an cites some of the previous studies. Bariatric surgery is not yet routinely recommended in patients with type 1 diabetes mellitus.

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