Maturity-onset diabetes of the young (MODY): an update

2015 ◽  
Vol 28 (3-4) ◽  
Author(s):  
Ahmet Anık ◽  
Gönül Çatlı ◽  
Ayhan Abacı ◽  
Ece Böber
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Young Adults ◽  
Maturity Onset Diabetes ◽  
Monogenic Disorders ◽  
Onset Diabetes ◽  
Dependent Form ◽  
Insulin Dependent

AbstractMaturity-onset diabetes of the young (MODY) is a group of monogenic disorders characterized by autosomal dominantly inherited non-insulin dependent form of diabetes classically presenting in adolescence or young adults before the age of 25 years. MODY is a rare cause of diabetes (1% of all cases) and is frequently misdiagnosed as Type 1 diabetes (T1DM) or Type 2 diabetes (T2DM). A precise molecular diagnosis is essential because it leads to optimal treatment of the patients and allows early diagnosis for their asymptomatic family members. Mutations in the glucokinase (

scholarly journals Maturity-onset diabetes of the young: difficult differential diagnosis

2020 ◽  
Vol 4 (6) ◽  
pp. 372-376
Author(s):  
K.G. Lobanova ◽  
◽  
V.V. Titova ◽  
K.S. Dolgova ◽  
◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Differential Diagnosis ◽  
Genetic Testing ◽  
Molecular Genetic ◽  
Maturity Onset Diabetes ◽  
Molecular Genetic Testing ◽  
Onset Diabetes

Maturity-onset diabetes of the young (MODY) is a monogenic variant of diabetes characterized by the primary dysfunctions of pancreatic β-cells. MODY accounts for 1–2% of all variants of diabetes. MODY is generally associated with HNF1A gene mutation. The hallmarks of MODY are an autosomal dominant inheritance pattern, the onset of the disease in the young age, stable C-peptide level over a long period, the lack of the autoantibodies considered as the markers of diabetes, and the lack of ketoacidosis at disease onset. Considering that MODY manifests in children and young individuals, these patients are commonly diagnosed with type 1 diabetes. However, due to the atypical clinical signs of type 1 diabetes and the similarity of this disease to type 2 diabetes, these patients are often misdiagnosed with type 2 diabetes. This case report illustrates the differential diagnosis of diabetes in a patient with unusual disease course. The attention is focused on the features of MODY course. The indications to molecular genetic testing to verify the diagnosis are addressed.KEYWORDS: diabetes, maturity-onset diabetes of the young, monogenic diabetes, sulfonylureas, molecular genetic testing, LADA, pancreatogenic diabetes.FOR CITATION: Lobanova K.G., Titova V.V., Dolgova K.S. Maturity-onset diabetes of the young: difficult differential diagnosis. Russian Medical Inquiry. 2020;4(6):372–376. DOI: 10.32364/2587-6821-2020-4-6-372-376.

scholarly journals Susceptible and Protective Human Leukocyte Antigen Class II Alleles and Haplotypes in Bahraini Type 2 (Non-Insulin-Dependent) Diabetes Mellitus Patients

2005 ◽  
Vol 12 (1) ◽  
pp. 213-217 ◽  
Author(s):  
Ayesha A. Motala ◽  
Marc Busson ◽  
Einas M. Al-Harbi ◽  
Manal A. A. Khuzam ◽  
Emtiaz M. D. Al-Omari ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Leukocyte Antigen ◽  
Insulin Dependent

ABSTRACT Whereas the genetic risk for type 1 diabetes is linked to human leukocyte antigen (HLA) class II genes, the HLA association in type 2 (non-insulin-dependent) diabetes is less clear. The association between HLA class II genotypes and type 2 diabetes was examined in adult Bahrainis, an Arab population with a high prevalence of type 2 diabetes. HLA-DRB1* and -DQB1* genotyping of 86 unrelated type 2 diabetes patients (age, 51.6 ± 8.2 years; mean duration of diabetes, 7.7 ± 7.1 years) who had a strong family history of diabetes (52 of 72 versus 0 of 89 for controls, P < 0.001) and 89 healthy subjects was done by PCR-sequence-specific priming. DRB1*040101 (0.1221 versus 0.0562, P = 0.019) and DRB1*070101 (0.2151 versus 0.0843, P < 0.001) were positively associated, while DRB1*110101 (0.0698 versus 0.1461, P = 0.014) and DRB1*160101 (0.0640 versus 0.1236, P = 0.038) were negatively associated with type 2 diabetes. DRB1*040101-DQB1*0302 (0.069 versus 0.0007; P = 0.004), DRB1*070101-DQB1*0201 (0.178 versus 0.0761, P = 0.007), DRB1*070101-DQB1*050101 (0.125 versus 0.0310, P = 0.002), and DRB1*150101-DQB1*060101 (0.0756 versus 0.0281, P = 0.008) were more prevalent among patients, while DRB1*160101-DQB1*050101 (0.0702 versus 0.0349, P = 0.05) was more prevalent among controls, conferring disease susceptibility or protection, respectively. In Bahrainis with type 2 diabetes, there is a significant association with select HLA class II genotypes, which were distinct from those in type 1 diabetes.

Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing

2016 ◽  
Vol 29 (4) ◽  
Author(s):  
Sebahat Yılmaz Ağladıoğlu ◽  
Zehra Aycan ◽  
Semra Çetinkaya ◽  
Veysel Nijat Baş ◽  
Aşan Önder ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Next Generation Sequencing ◽  
Point Mutations ◽  
Maturity Onset Diabetes ◽  
Turkish Children ◽  
Onset Diabetes ◽  
Molecular Studies ◽  
Generation Sequencing

AbstractMaturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11A panel of 11We identified 28 (65%) point mutations among 43 patients. Eighteen patients haveThis is the first study including molecular studies of 11

scholarly journals Improving clinical utility of GAD65 autoantibodies by electrochemiluminescence assay and clinical phenotype when identifying autoimmune adult-onset diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Yong Gu ◽  
Xiaofan Jia ◽  
Tanwi Vartak ◽  
Dongmei Miao ◽  
Fran Dong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Clinical Utility ◽  
Insulin Treatment ◽  
Clinical Phenotype ◽  
Adult Onset ◽  
Onset Diabetes ◽  
Adult Onset Diabetes

Abstract Aims/hypothesis It is important to differentiate the two major phenotypes of adult-onset diabetes, autoimmune type 1 diabetes and non-autoimmune type 2 diabetes, especially as type 1 diabetes presents in adulthood. Serum GAD65 autoantibodies (GADA) are the most sensitive biomarker for adult-onset autoimmune type 1 diabetes, but the clinical value of GADA by current standard radiobinding assays (RBA) remains questionable. The present study focused on the clinical utility of GADA differentiated by a new electrochemiluminescence (ECL) assay in patients with adult-onset diabetes. Methods Two cohorts were analysed including 771 diabetic participants, 30–70 years old, from the Action LADA study (n = 6156), and 2063 diabetic participants, 20–45 years old, from the Diabetes in Young Adults (DiYA) study. Clinical characteristics of participants, including requirement of early insulin treatment, BMI and development of multiple islet autoantibodies, were analysed according to the status of RBA-GADA and ECL-GADA, respectively, and compared between these two assays. Results GADA was the most prevalent and predominant autoantibody, >90% in both cohorts. GADA positivity by either RBA or ECL assay significantly discriminated clinical type 1 from type 2 diabetes. However, in both cohorts, participants with ECL-GADA positivity were more likely to require early insulin treatment, have multiple islet autoantibodies, and be less overweight (for all p < 0.0001). However, clinical phenotype, age at diagnosis and BMI independently improved positive predictive value (PPV) for the requirement of insulin treatment, even augmenting ECL-GADA. Participants with GADA detectable by RBA, but not confirmed by ECL, had a phenotype more similar to type 2 diabetes. These RBA-GADA positive individuals had lower affinity GADA compared with participants in which GADA was confirmed by ECL assay. Conclusions/interpretation Detection of GADA by ECL assay, given technical advantages over RBA-GADA, identified adult-onset diabetes patients at higher risk of requiring early insulin treatment, as did clinical phenotype, together allowing for more accurate clinical diagnosis and management. Graphical abstract

scholarly journals Immune checkpoint inhibitors: an emerging cause of insulin-dependent diabetes

2019 ◽  
Vol 7 (1) ◽  
pp. e000591 ◽  
Author(s):  
Anupam Kotwal ◽  
Candace Haddox ◽  
Matthew Block ◽  
Yogish C Kudva
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Immune Checkpoint ◽  
Insulin Dependent Diabetes ◽  
Insulin Deficiency ◽  
Immune Mediated ◽  
Insulin Dependent ◽  
New Onset

ObjectiveInsulin-dependent diabetes can occur with immune checkpoint inhibitor (ICI) therapy. We aimed to characterize the frequency, natural history and potential predictors of ICI-induced diabetes.Research design and methodsWe reviewed 1444 patients treated with ICIs over 6 years at our cancer center, and from the 1163 patients who received programmed cell death protein 1 (PD-1) inhibitors, we identified 21 such cases, 12 of which developed new-onset insulin-dependent diabetes and 9 experienced worsening of pre-existing type 2 diabetes.ResultsICI-induced diabetes occurred most frequently with pembrolizumab (2.2%) compared with nivolumab (1%) and ipilimumab (0%). The median age was 61 years, and body mass index was 31 kg/m2, which are both higher than expected for spontaneous type 1 diabetes. Other immune-related adverse events occurred in 62%, the most common being immune mediated thyroid disease. New-onset insulin-dependent diabetes developed after a median of four cycles or 5 months; 67% presented with diabetic ketoacidosis and 83% with low or undetectable C-peptide. Autoantibodies were elevated in 5/7 (71%) at the time of new-onset diabetes. Diabetes did not resolve during a median follow-up of 1 year.ConclusionsPD-1 inhibitors can lead to insulin deficiency presenting as new-onset diabetes or worsening of pre-existing type 2 diabetes, with a frequency of 1.8 %. The underlying mechanism appears similar to spontaneous type 1 diabetes but there is a faster progression to severe insulin deficiency. Better characterization of ICI-induced diabetes will improve patient care and enhance our understanding of immune-mediated diabetes.

Altered energetic properties in skeletal muscle of men with well-controlled insulin-dependent (type 1) diabetes

2003 ◽  
Vol 284 (4) ◽  
pp. E655-E662 ◽  
Author(s):  
Gregory J. Crowther ◽  
Jerrold M. Milstein ◽  
Sharon A. Jubrias ◽  
Martin J. Kushmerick ◽  
Rodney K. Gronka ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Glycolytic Flux ◽  
Resonance Spectroscopy ◽  
Diabetic Patients ◽  
Control Subjects ◽  
Energetic Properties ◽  
Insulin Dependent

This study asked whether the energetic properties of muscles are changed by insulin-dependent diabetes mellitus (or type 1 diabetes), as occurs in obesity and type 2 diabetes. We used 31P magnetic resonance spectroscopy to measure glycolytic flux, oxidative flux, and contractile cost in the ankle dorsiflexor muscles of 10 men with well-managed type 1 diabetes and 10 age- and activity-matched control subjects. Each subject performed sustained isometric muscle contractions lasting 30 and 120 s while attempting to maintain 70–75% of maximal voluntary contraction force. An altered glycolytic flux in type 1 diabetic subjects relative to control subjects was apparent from significant differences in pH in muscle at rest and at the end of the 120-s bout. Glycolytic flux during exercise began earlier and reached a higher peak rate in diabetic patients than in control subjects. A reduced oxidative capacity in the diabetic patients' muscles was evident from a significantly slower phosphocreatine recovery from a 30-s exercise bout. Our findings represent the first characterization of the energetic properties of muscle from type 1 diabetic patients. The observed changes in glycolytic and oxidative fluxes suggest a diabetes-induced shift in the metabolic profile of muscle, consistent with studies of obesity and type 2 diabetes that point to common muscle adaptations in these diseases.

scholarly journals A Type 1 Diabetes Genetic Risk Score Can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults

Diabetes Care ◽  
2015 ◽  
Vol 39 (3) ◽  
pp. 337-344 ◽  
Author(s):  
Richard A. Oram ◽  
Kashyap Patel ◽  
Anita Hill ◽  
Beverley Shields ◽  
Timothy J. McDonald ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Young Adults ◽  
Risk Score ◽  
Genetic Risk ◽  
Genetic Risk Score

scholarly journals Pregnancy Complicated by Maternal MODY 3 and Paternal MODY 2 Diabetes and Subsequent Rapidly Falling Insulin Requirement

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Anastasia Mikuscheva ◽  
Adel Mekhail ◽  
Benjamin J. Wheeler
Keyword(s):  
Type 2 Diabetes ◽  
Pregnant Woman ◽  
Preterm Labour ◽  
Insulin Requirement ◽  
Monogenic Diabetes ◽  
Maturity Onset Diabetes ◽  
Insulin Requirements ◽  
Onset Diabetes

Background. ‘Maturity-Onset Diabetes of the Young’ (MODY) or monogenic diabetes accounts for approximately 1–2% of diabetes and is frequently misdiagnosed as type 1 or type 2 diabetes. Here we report a case of a 19-year-old pregnant woman with a MODY 3 diabetes expecting a child to a father with MODY 2 diabetes. Possible inheritance scenarios are described and the implications of these scenarios on the pregnancy and infant are discussed. In addition, the pregnancy was complicated by drastically falling insulin requirements in the mother in the 3rd trimester as well as preterm labour and delivery at 33+4 weeks of gestation.

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