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Diabetes is highly prevalent in India and the proportion of younger patients developing diabetes is on the increase. Apart from the more universally known type 1 diabetes and obesity related type 2 diabetes, monogenic forms of diabetes are also suspected to be prevalent in many young diabetic patients. The identification of the genetic basis of the...
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DNA methylation, a major regulator of epigenetic modifications has been shown to alter the expression of genes that are involved in aspects of glucose metabolism such as glucose intolerance, insulin resistance, β-cell dysfunction and other conditions, and it ultimately leads to the pathogenesis of type 2 diabetes mellitus (T2DM). Current evidence i...
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... Diabetes in young has been classically defined as the onset of DM ≤35 years [4] and with this background, this study was undertaken to study DM in young in the Indian population. ...
Background: Younger people are being afflicted with the pandemic of diabetes mellitus(DM). Although DM is conventionally classified based on insulin requirement at a primary level, there is a large spectrum of DM in young. All subtypes of DM have their exclusive management strategy and ‘one size fits all’ strategy can lead to adverse clinical outcomes. Hence, all efforts should be put to differentiate individual entities of DM subtypes by applying appropriate clinical and laboratory tools.
Materials and Methods: This observational cross‑sectional study
was conducted between December 2020 to March 2022 in 30 patients of age <35 years with established diagnosis of DM as per American
Diabetes Association (ADA) criteria. Their clinical profile, anti‑GAD‑65 Ab, abdominal imaging and genetics tests were used for the classification of DM and studying their clinical peculiarities. Results: The mean age of patients was 30.53 ± 5.6 years and the group was
male predominant, consisting of 22 (73.33%) males and 8 (26.67%)females with a ratio of 2.75:1. The main subtypes of DM detected in this
study after application of the study protocol was as follows type 1 DM (T1DM) in 12 (40%), type 2 DM (T2DM) 11 (36%), pancreatogenic DM 3 (10%), maturity‑onset diabetes of the young (MODY) 1 (3.3%), Cushing’s syndrome 1 (3.3%) out of 30 patients, and 1 (3.3%) patient could not be classified. The most common comorbidity noted was primary hypertension in 3 (10.0%), followed by primary autoimmune
hypothyroidism in 1 (3.3%). All patients having primary hypertension had T2DM, whereas primary autoimmune hypothyroidism was seen in a T1DM patient. T1DM had higher glycosylated hemoglobin (HbA1c) levels (average HbA1c >8.9%) and ketosis 10 (83%) and 6 (50%) out of 12 patients, respectively, as compared to T2DM patients in which lower HbA1c level (average HbA1c <9%) and lower incidence of ketosis seen in 3 (27.2%) and 2 (18.1%) out of 11 patients, respectively.
Conclusion: Various clues in history, clinical examination, and laboratory
evaluation help in classification and establishing diagnosis among young DM patients. Apart from T1DM and T2DM, other subtypes of DM also need to be considered in young DM patients.
... A pesar de que la frecuencia de DM MODY es considerablemente menor en comparación a otras formas de diabetes, de manera habitual el diagnóstico se retrasa o se confunde con las DM tipo 1 o tipo 2. La importancia de identificar casos con DM MODY no sólo es porque el tratamiento se optimiza y se puede predecir el curso de la enfermedad, sino que además ayuda a realizar pruebas predictivas para familiares de primer grado, quienes tienen un riesgo de 50% de heredar la mutación. 2 Un aspecto para destacar es que los subtipos de DM MODY tienen manifestaciones clínicas características, las cuales se describen en la Tabla 2. [8][9][10][11][12][13] Aunque se puede establecer una alta sospecha clínica de DM MODY, para llegar al diagnóstico definitivo se requiere identificar cuál es el gen afectado, ya que la gran heterogeneidad de este grupo de trastornos monogénicos tiene un amplio espectro clínico que se confunde con otras formas de diabetes. Por lo anterior, tras la sospecha clínica, debe realizarse el diagnóstico genético, lo cual inclusive permite la identificación de otros familiares afectados que pudieran ser asintomáticos. 4 En el presente caso no fue posible determinarlo por la falta de disponibilidad de pruebas genéticas en nuestro medio, lo cual ocurre muy frecuentemente en unidades de primer y segundo nivel de atención. ...
Introducción:
La diabetes mellitus tipo MODY (maturity-onset diabetes of the young) comprende un grupo de trastornos genéticos que impiden la función normal de las células beta pancreáticas. Este tipo ocurre entre 1-2% de los casos de diabetes mellitus (DM). El diagnóstico definitivo es por la identificación del gen afectado, sin embargo, por falta de recursos, habitualmente estos pacientes se diagnostican solamente con datos clínicos.
Presentación del caso:
Paciente femenino de 10 años que ingresa a urgencias por infección de vías urinarias, pero dado que se detecta glucemia en 256 mg/dL en ayuno y glucosuria, se realiza el diagnóstico de DM. Meses después la paciente fue tratada como DM MODY debido a antecedentes de diabetes de inicio temprano en familiares de primer grado, así como porque no se detectó resistencia a la insulina, aunado a anticuerpos antiglutamato descarboxilasa (GADA) negativos, reserva pancreática conservada y respuesta adecuada a secretagogos de insulina.
Conclusiones:
La frecuencia de DM MODY probablemente es mayor a la descrita, lo cual se relaciona con la dificultad para disponer de las pruebas genéticas específicas. No obstante, un análisis de los antecedentes familiares, características clínicas y pruebas de laboratorio pueden llevar a un diagnóstico clínico de DM MODY. La detección de este tipo de diabetes permite brindar un tratamiento más adecuado.
... MODY was reported in India in 1985. 7 The number of Type 2 Diabetes Mellitus cases in India is exponentially increasing since the last 30 years. 8-10 percent and 15 percent of the population of India are having Type 2 Diabetes and pre diabetes respectively. ...
... Molecular genetic testing is available in the country for diagnosis of MODY. 7 However, in Asian diabetics, rate of detection of autoantibodies is low and is expensive. 23 ...
... In addition, there is little to no evidence of QoL in the Indian population for gestational diabetes mellitus (GDM) and monogenic forms of diabetes. As five million women have GDM in India [62] and new cases of monogenic diabetes are continually being reported due to advances in the field of molecular genetics, [63][64][65] QoL assessment needs to be urgently addressed in these subtypes of diabetes in order to be able to offer more support to these groups. ...
In recent years, numerous studies have explored the quality of life (QoL) in those with diabetes mellitus. The aim of this scoping review was to explore the current state of knowledge on QoL and its various associated factors among people with diabetes in India. Three databases were searched (PubMed, Scopus, and Medline) and the Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines were followed. A total of 41 articles were included in the review. The included studies were largely conducted in the Southern states and mainly investigated individuals with type 2 diabetes. The World Health Organization Quality of Life (WHOQOL‑BREF) and Short
Form Health Survey (SF‑36) were the instruments used most often. In general, the studies showed that people with diabetes had poorer QoL than those without diabetes, and women with diabetes reported poorer QoL than men, consistent with findings across the world. However, the studies had significant methodological flaws which limit the validity and generalizability of the findings. Therefore, there is an urgent need to conduct high‑quality QoL studies which are representative of all states of India as well as different types of diabetes in India in order to address this gap in the evidence.
... Consequently, reduced β-cell glucose sensing leads to decreased insulin secretion. Other metabolic effects include reduced glycogen synthesis, higher hepatic glucon eogenesis, mild fasting hyperglycaemia (35). Moderate hyperglycaemia occurs mainly in the fasting state and chronic complications are rare. ...
Diabetes is a chronic metabolic disorder with a rapidly growing incidence worldwide. It is currently classified into two main types, type 1 and type 2 diabetes, based on status of the autoantibodies directed at the β-cell. However, it does not reflect the complexity of diabetes and the broad spectrum of the clinical manifestations, particularly in type 2. In this review we present the evolution of the World Health Organization (WHO) classification of diabetes, with a focus on newly introduced categories – hybrid forms of diabetes and unclassified diabetes. We compare the WHO diabetes subgroups with the American Diabetes Association (ADA) approach to this issue. Since the current classification systems do not reflect all the factors leading to hyperglycaemia in type 2 diabetes, we present novel approach to phenotyping diabetes in adults based on six variables (age at diagnosis, body mass index [BMI], C-peptide based homeostasis model assessments of β-cell function and insulin resistance, haemoglobin A1c and glutamic acid decarboxylase antibodies [GADA] status) which allowed to distinguish five replicable groups of patients in Swedish cohort with different clinical presentations. The understanding heterogeneity of diabetes helps to classify the patients more adequately, but none of classifications is optimal. Including combination of genetic, metabolomic and clinical factors into classification schemas will pave the way towards personalized medicine in diabetes and will presumably result in more effective treatment of the patients.
... 16 In addition, the diagnosis of MODY in a patient often results in genetic testing and diagnosis of other family members resulting in earlier treatment of the rest of the family. 17 ...
Maturity onset diabetes of the young (MODY) is the most common form of monogenic diabetes and is currently believed to have 14 subtypes. While much is known about the common subtypes of MODY (MODY-1, 2, 3 and 5) little is known about its rare subtypes (MODY4, 6–14). With the advent of next-generation sequencing (NGS) there are several reports of the rarer subtypes of MODY emerging from across the world. Therefore, a greater understanding on these rarer subtypes is needed. A search strategy was created, and common databases were searched, and 51 articles finally selected. INS-(MODY10) and ABCC8-(MODY12) mutations were reported in relatively large numbers compared to the other rare subtypes. The clinical characteristics of the rare MODY subtypes exhibited heterogeneity between families reported with the same mutation. Obesity and diabetic ketoacidosis (DKA) were also reported among rarer MODY subtypes which presents as a challenge as these are not part of the original description of MODY by Tattersal and Fajans. The treatment modalities of the rarer subtypes included oral drugs, predominantly sulfonylureas, insulin but also diet alone. Newer drugs like DPP-4 and SGLT2 inhibitors have also been tried as new modes of treatment. The microvascular and macrovascular complications among the patients with various MODY subtypes are less commonly reported. Recently, there is a view that not all the 14 forms of ‘MODY’ are true MODY and the very existence of some of these rarer subtypes as MODY has been questioned. This scoping review aims to report on the clinical characteristics, treatment and complications of the rarer MODY subtypes published in the literature.
... 24,60 The standard approach includes sequential screening of the three most common MODY genes: HNF-1˛, GCK, and HNF-4˛. 61,62 However, with the advent of next-generation sequencing (NGS) technology, there has been a significant improvement in the speed and scalability of the genetic sequencing and an extended profile is also currently available. 59,61 After a strong clinical suspicion, the genetic mutation diagnosis must be performed in order to accurately define MODY subtype and lead to the identification of other affected family members. ...
Maturity-onset diabetes of the young (MODY) comprises a heterogeneous group of monogenic disorders characterized by primary defect in pancreatic β-cell function, early onset and autosomal dominant inheritance, accounting for about 1–5% of all diabetes diagnoses. Mutations in 14 genes are responsible for the majority of all MODY cases described so far. The clinical phenotype relies on genetic defects, with important implications in the optimal treatment and prognosis definition. MODY's early diagnosis remains a challenge, since this group of inherited disorders comprises a large clinical spectrum and it usually overlaps with other types of diabetes, requiring a high index of suspicion even if the definitive statement demands a molecular genetic study.
Recent advances on the genetic determinants and pathophysiology of MODY have allowed a better understanding of its underlying molecular mechanisms, providing a proper genetic counseling and early diagnosis. These new management insights will make possible to set up new therapeutic strategies, with drugs able to prevent, correct or at least delay the decline of pancreatic β-cell function, thus affording for a more personalized treatment and, ultimately, for a better patient care.
... 24,60 The standard approach includes sequential screening of the three most common MODY genes: HNF-1˛, GCK, and HNF-4˛. 61,62 However, with the advent of next-generation sequencing (NGS) technology, there has been a significant improvement in the speed and scalability of the genetic sequencing and an extended profile is also currently available. 59,61 After a strong clinical suspicion, the genetic mutation diagnosis must be performed in order to accurately define MODY subtype and lead to the identification of other affected family members. ...
Maturity-onset diabetes of the young (MODY) comprises a heterogeneous group of monogenic disorders characterized by primary defect in pancreatic β-cell function, early onset and autosomal dominant inheritance, accounting for about 1-5% of all diabetes diagnoses. Mutations in 14 genes are responsible for the majority of all MODY cases described so far. The clinical phenotype relies on genetic defects, with important implications in the optimal treatment and prognosis definition. MODY's early diagnosis remains a challenge, since this group of inherited disorders comprises a large clinical spectrum and it usually overlaps with other types of diabetes, requiring a high index of suspicion even if the definitive statement demands a molecular genetic study. Recent advances on the genetic determinants and pathophysiology of MODY have allowed a better understanding of its underlying molecular mechanisms, providing a proper genetic counseling and early diagnosis. These new management insights will make possible to set up new therapeutic strategies, with drugs able to prevent, correct or at least delay the decline of pancreatic β-cell function, thus affording for a more personalized treatment and, ultimately, for a better patient care.
... There are more genes that have been associated with MODY, however they are exceptionally rare having been reported once and detected in very few families [2]. The HNF-1A, which is MODY3, is the most common form of MODY reported in studies from UK and from many European countries [8]. Because of its high penetrance nature 63% of carriers develop diabetes by 25 years of age, and almost all carriers develop diabetes by the age of 55 [5] . ...
... These patients are often misdiagnosed for type 1 diabetes and are placed on insulin therapy. Patients with HNF1A-MODY are sensitive to sulfonylurea therapy, which is recommended as fi rst line treatment [8]. According to an observational study done by Pearson et al., [5], patients with HNF1A-MODY can be switched safely from insulin to a sulfonylurea. ...
p>Diabetes Mellitus is a group of metabolic disorders associated with microvascular and macrovascular complications. The rapidly increasing prevalence and incidence of this disease is causing a major worldwide health problem. Maturity onset diabetes of the young (MODY) is a rare monogenic form of diabetes resulting from mutation in a single gene. There are 13 types of MODY genes identified currently. The two main types of MODY is caused by mutations in the hepatocyte nuclear factor 1A and glycolytic enzyme glucokinase (GCK). Genetic testing is the gold standard for diagnosing MODY. It is essential to identify the MODY subtype to determine the management and treatment options.</p
... Furthermore, this particular form of diabetes is known to have familial clustering due to the autosomal dominant inheritance of genetic mutations responsible for beta cell development and functioning. Nair et al. [13] indicate the chief clinical factors of MODY as: ...
