Molecular mechanisms of β-cell dysfunction and death in monogenic forms of diabetes

Area of Science:

• Genetics
• Endocrinology
• Molecular Biology

Background:

• Monogenetic diabetes accounts for 1%-5% of all diabetes cases, stemming from single-gene mutations affecting pancreatic beta-cell function or insulin regulation.
• These mutations can be inherited or de novo, dominant or recessive, leading to diverse clinical presentations and often misdiagnosis as type 1 or type 2 diabetes.
• Symptoms vary based on mutation type, affected gene, and genetic/environmental modifiers, sometimes including syndromic features and a wide age of onset.

Purpose of the Study:

• To describe mutations causing monogenetic diabetes linked to pancreatic development issues or impaired beta-cell function.
• To discuss the molecular mechanisms underlying beta-cell demise in monogenetic diabetes.
• To highlight the importance of accurate diagnosis for effective patient management.

Main Methods:

• Review of genetic mutations associated with monogenetic diabetes.
• Analysis of molecular mechanisms in pancreatic beta-cell dysfunction.
• Clinical case review focusing on diagnosis and treatment variability.

Main Results:

• Identified mutations affecting pancreatic beta-cell development, function, and survival as causes of monogenetic diabetes.
• Detailed diverse clinical presentations, from neonatal to adulthood onset, with or without syndromic features.
• Highlighted the need for individualized treatment strategies, including diet, exercise, insulin, sulfonylureas, or GLP-1 analogs.

Conclusions:

• Accurate diagnosis of monogenetic diabetes is essential for appropriate management and treatment.
• Understanding the molecular basis of beta-cell demise is key to developing targeted therapies.
• Awareness of monogenetic diabetes subtypes is critical for healthcare providers to avoid misdiagnosis and optimize patient care.