[Molecular pathophysiology of late complications diabetes mellitus--hyperglycemia-induced changes]

Area of Science:

• Endocrinology and Metabolism
• Molecular Biology

Context:

• Diabetes mellitus, particularly Type 2 Diabetes Mellitus (T2DM), is a growing global health concern with increasing incidence and a trend towards younger age groups.
• Late diabetic complications arise from chronic hyperglycemia, affecting both vascular and extravascular systems, with disease duration and therapeutic control being significant factors.

Purpose:

• To review recent findings on the pathogenesis of late diabetic complications, focusing on hyperglycemia-induced molecular alterations.
• To elucidate the common pathogenic mechanisms, including glycolysis inhibition and cellular damage, that contribute to organ-specific manifestations of diabetes.

Summary:

• Chronic hyperglycemia in diabetes mellitus triggers proximal molecular events, notably inhibiting glycolysis at the Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) level via an increased NADH/NAD+ ratio.
• This inhibition, coupled with increased superoxide generation and intracellular dicarbonyl accumulation, activates gene expression leading to tissue remodeling and characteristic organ damage.
• Secondary prevention and minimizing late complications are achievable goals, necessitating a deeper understanding of diabetes pathogenesis and identification of high-risk individuals.

Impact:

• Improved understanding of diabetes pathogenesis can lead to enhanced therapeutic strategies and better patient prognoses.
• Identifying high-risk individuals for diabetic complications will allow for targeted interventions and personalized medicine approaches.
• This review provides a foundation for future research into the genetic susceptibility of developing late diabetic complications.