Chronic metabolic acidosis of diabetes (CMAD): clinical features, diagnosis, and therapeutic potentials of pH correction

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Abstract
PH changes are a cardinal feature in metabolic disorders. Based on published literature, chronic metabolic acidosis is a major finding in type 2 diabetes (T2D), which is recently described as CMAD (chronic metabolic acidosis of T2D). Several disorders characterized by overt metabolic acidosis are recognized as T2D co-morbidities or are dual risk factors that pertain to their unique signs and symptoms in T2D. Over time, many terms were used for chronic metabolic acidosis (CMA) in different disorders. However, the lack of a unified term for CMA, delayed the recognition of CMAD as a prime feature of T2D, and the setting of the diagnostic criteria and management protocol for this disorder. Other than the classical diabetic complications, CMAD contributes to non-classical organ-specific local diabetic complications. Here we described the likely clinical features of CMAD in general, such as fatigue, tiredness, cramps, and aches, as well as organ/system-specific symptoms of T2D related to the liver, skeletal muscles, bones and joints, lungs, nervous system, eyes, kidneys and urinary tract, oral cavity and teeth, gastrointestinal tract, immune system, and skin. Diagnostic criteria and confirmatory tests are enlisted together with the laboratory tools used for pH estimation in different body compartments. Finally, a management protocol is proposed, which covers: 1) lifestyle (exercise, stress management); 2) nutrition (drinks, foods, and supplements); and 3) therapeutic pH correction: general proton pump inhibitor (PPI) and alkaline minerals; and organ-specific therapies with different modalities of action. In addition, the therapeutic potentials of nanomedicine and immune and gene therapies for pH correction are raised.

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