Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

Abstract

Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous group of monogenic endocrine disorders that is characterised by autosomal dominant inheritance and pancreatic β-cell dysfunction. These patients are commonly misdiagnosed with type 1 or type 2 diabetes, as the clinical symptoms largely overlap. Even though several biomarkers have been tested none of which could be used as single clinical discriminator. The correct diagnosis for individuals with MODY is of utmost importance, as the applied treatment depends on the gene mutation or is subtype-specific. Moreover, in patients with HNF1A-MODY, additional clinical monitoring can be included due to the high incidence of vascular complications observed in these patients. Finally, stratification of MODY patients will enable better and newer treatment options for MODY patients, once the disease pathology for each patient group is better understood. In the current review the clinical characteristics and the known disease-related abnormalities of the most common MODY subtypes are discussed, together with the up-to-date applied diagnostic criteria and treatment options. Additionally, the usage of pluripotent stem cells together with CRISPR/Cas9 gene editing for disease modelling with the possibility to reveal new pathophysiological mechanisms in MODY is discussed.

From Genes to Diagnosis: Examining the Clinical and Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in TCGS

“…This result was accordant with a previous study on Chinese participants which concluded that individuals with KLF11-MODY7 and PAX4-MODY9 were found to have a higher BMI [39]. However, due to their rarity, the characteristics of these MODY subtypes have not been completely elucidated [25]. Regarding GCK-MODY2, these carriers typically exhibit mild hyperglycemia with an OGTT glucose increment of less than 60 mg/dl in European individuals.…”

“…We estimated the prevalence of MODY at 1.77% of diabetes patients. Although in Europe the most prevalent subtypes are HNF1A-MODY3 and GCK-MODY2, in the MENA region, MODY prevalence is mainly unexplored [25,[38][39][40]. According to our ndings, INS-MODY10 was the most common type of MODY accounting for 46.6% of all mutations in Iranian participants.…”

Maturity-onset diabetes of the young type 7 (MODY7) and mutation in the Krüppel-like transcription factor 11 (KLF11) gene

“…MODY is not progressively mild, characterized by persistent fasting hyperglycemia, presence of residual pancreatic function, negative for diabetes-associated antibodies, non-insulin-dependent and involvement across multiple generations within a family. 1 , 2 …”

Hypoglycemic Activity of Plant-Derived Traditional Preparations Associated with Surinamese from African, Hindustani, Javanese, and Chinese Origin: Potential Efficacy in the Management of Diabetes Mellitus

“…An estimated 1-5% of cases of diabetes are caused by conditions other than those mentioned above, including those with a genetic background and those that are non-genetically related. Types of diabetes with a genetic background are neonatal diabetes [14] and maturity-onset diabetes in the young [15], Wolfram syndromerelated (type 1) diabetes [16], and cystic fibrosis-related (type 1) diabetes [17]. Types of diabetes with a non-genetic background are, among others, chronic pancreatitisassociated diabetes, which is usually caused by extensive damage to the exocrine tissue of the pancreas [18], brittle diabetes, which primarily affects patients with type 1 diabetes and manifests as frequent and severe fluctuations in blood glucose levels [19], and Cushing's syndrome-related diabetes [20].…”