The effect of body acid-base state and manipulations on body glucose regulation in human.

Long-term exposure to high dietary acid load has been associated with insulin resistance and type 2 diabetes in epidemiological studies. However, it remains unclear whether the acid load of the diet translates to mild metabolic acidosis and whether it is responsible for the impairment in glucose regulation in humans. Previously, in a cross-sectional study we have reported that dietary acid load was not different between healthy individuals with normal weight and those with overweight/obesity, irrespective of insulin sensitivity. However, 4-week high acid load diet increased plasma lactate (a small component of the anion gap) and increased insulin resistance in healthy participants. The change in plasma lactate correlated significantly with the change in insulin resistance. Because cause-and-effect could not be evaluated in these settings, we sought to directly test the effect of an alkalizing treatment preload on postprandial glucose regulation. In a randomized placebo-controlled study with a crossover design, we administered sodium bicarbonate (NaHCO3, 1.68 g) prior to high acid load meal to healthy individuals. We found that while the bicarbonate preload attenuated the post meal decrease in pH observed with placebo, no effect on postprandial glucose regulation (glucose, insulin, and C-peptide) was observed. Following 3-month treatment of nondiabetic individuals with bicarbonate, others have reported no change in insulin resistance markers, consistent with our findings. Together, studies in human suggest that insulin resistance associated with longstanding obesogenic diet may be mediated by mild metabolic acidosis. However, buffering the Western diet with bicarbonate and increasing body pH does not change glucose homeostasis in nondiabetic individuals. Further studies are required to shed light on the role of body acid–base balance and glucose homeostasis in health and disease.