Key Study Points:
1. Increased plasma bicarbonate is associated with a decreased odds of developing diabetes.
2. Each unit increase in plasma bicarbonate was associated with a 4% decrease in the odds of developing diabetes.
Primer: It is currently thought that metabolic acidosis may play a role in the development of insulin resistance. In fact, multiple studies in animal models have previously demonstrated an association between decreased insulin receptor binding and metabolic acidosis. In addition, metabolic acidosis is a known cause of increased cortisol secretion, which in itself has also been associated with decreased insulin responsiveness in tissues. The aim of this study was to determine whether levels of a specific biomarker for blood pH, plasma bicarbonate, were associated with the development of type II diabetes mellitus (DM) in a subset of nurses.
This [case-control] study: 630 cases and 730 controls were included. All subjects were female nurses without diabetes mellitus type II at the time of enrollment from 1989 to 1990. The authors obtained initial blood samples from each subject and levels of plasma bicarbonate were measured. Cases of type II DM were identified by self-report using questionnaires during 10 years of follow up. The primary endpoint of this study was the development of type II DM during the follow up period. The authors found that in women who subsequently developed diabetes, the mean plasma bicarbonate level was significantly lower than those who never went on to develop diabetes (p = 0.02). In addition, women with plasma bicarbonate levels above the median of 22.4mmol/L were found to have lower odds of incident diabetes (OR 0.77, CI 0.62–0.96) when compared to women at or below the median. Finally, for each unit increase in plasma bicarbonate, there was also found to be an associated 4% decrease in the odds of developing diabetes (OR 0.96, CI 0.92–1.00) after adjustment for matching factors.
In Sum: The authors build upon previous animal studies and demonstrate that increases in plasma bicarbonate in humans are associated with a decrease in the odds of developing diabetes. This association provides more evidence for the current hypothesis that metabolic acidosis may play a role in the development of diabetes. The results of the study provide us with a greater understanding of the underlying pathophysiology behind diabetes, while possibly opening the door for development of new anti-diabetes therapeutics aimed at controlling metabolic acidosis in high-risk patients. Since the trial was only a prospective observational study, additional randomized controlled trials are needed to confirm true causation and further characterize the association.
The study has several limitations including an ambiguous cause-effect relationship between diabetes and bicarbonate levels. In addition, the range of plasma bicarbonate levels in the study was found to be lower than commonly encountered clinically. Further, the authors did not retrieve data on arterial or venous pH for participants, which limited their ability to accurately evaluate the acid-base status of subjects. Finally, only a single bicarbonate measurement was taken which prevented the authors from drawing conclusions as to how changes in bicarbonate over time affects the odds of diabetes.
By MM and AH
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