Hidden chronic metabolic acidosis of diabetes type 2 (CMAD): Clues, causes and consequences

AbstractInterpretation of existing data revealed that chronic metabolic acidosis is a pathognomic feature for type 2 diabetes (T2D), which is described here as “chronic metabolic acidosis of T2D (CMAD)” for the first time. The biochemical clues for the CMAD are summarised in the following; low blood bicarbonate (high anionic gap), low pH of interstitial fluid and urine, and response to acid neutralization, while the causes of extra protons are worked o ut to be; mitochondrial dysfunction, systemic inflammation, gut microbiota (GM), and diabetic lung. Although, the intracellular pH is largely preserved by the buffer system and ion transporters, a persistent systemic mild acidosis leaves molecular signature in cellular metabolism in diabetics. Recip rocally, there are evidences that CMAD contributes to the initiation and progression of T2D by; reducing insulin production, triggering insulin resistance directly or via altered GM, and inclined oxidative stress. The details about the above clues, causes and consequences of CMAD are obtained by sea rching literature spanning between 1955 and 2022. Finally, the molecular bases of CMAD are discussed in details by interpretation of an up-to-date data and aid of well constructed diagrams, with a conclusion unravelling that CMAD is a major player in T2D pathophysiology. To this end, the CMAD disclo sure offers several therapeutic potentials for prevention, delay or attenuation of T2D and its complications.
Source: Reviews in Endocrine and Metabolic Disorders - Category: Endocrinology Source Type: research