High Plasma Bicarbonate Levels Tied to Lower Diabetes Risk

According to Ernest I. Mandel, MD, of Harvard Medical School in Boston, and colleagues, those whose plasma bicarbonate exceeded the median level of 22.4 mmol/L at baseline were less likely to develop diabetes over a period of 10 years (OR 0.77, 95% CI 0.62 to 0.96, P=0.02),

After adjustment for hypertension, body mass index (BMI), and plasma creatinine, there was a 4% decrease in the likelihood for developing diabetes with each unit increase in bicarbonate (OR 0.96, 95% CI 0.92 to 1.00, P=0.05), the researchers reported online in CMAJ.

Epidemiologic studies have linked biomarkers of metabolic acidosis with insulin resistance and type 2 diabetes, but it has not been clear whether the acidosis plays a causative role in the development of diabetes.

To examine this prospectively, Mandel and colleagues compared plasma bicarbonate levels among participants in the Nurses' Health Study who had blood drawn in 1989-1990.

Between 1990 and 2000, 630 women developed type 2 diabetes. When they were compared with controls, those who developed diabetes had higher baseline BMI (30 versus 26), more hypertension (52% versus 31%) and dyslipidemia (49% versus 39%), and more often had a family history of diabetes (48% versus 23%). All were significant at P<0.01.

Baseline bicarbonate levels were significantly lower in cases than controls (22 versus 22.4 mmol/L, P=0.02). Women who developed diabetes also had higher baseline values for C-reactive protein, fasting insulin, and hemoglobin A1c.

In an adjusted model, risk of diabetes was lower in the two highest quartiles of bicarbonate level (P=0.04 for the linear trend):

• Quartile 3 -- 22.4 mmol/L to 23.9 mmol/L, OR 0.70 (95% CI 0.51 to 0.97)
• Quartile 4 -- >23.9 mmol/L, OR 0.75 (95% CI 0.54 to 1.05)

Further adjustments for cholesterol level, smoking, physical activity, and menopausal status had little effect. In addition, they adjusted for baseline C-reactive protein level and again found no differences in odds ratios.

"The association between lower plasma bicarbonate and development of diabetes may be explained by metabolic acidosis promoting insulin resistance, and this association may be independent of systemic inflammation, given the similar results observed even after we adjusted for C-reactive protein," Mandel and colleagues observed.

They suggested that the association between bicarbonate and diabetes also may be independent of levels of dietary acid, because they adjusted for factors that influence this, such as intake of animal protein and fruits and vegetables.

Further research is needed "to confirm this finding in other populations, to elucidate the mechanism by which this occurs, and to explore increased dietary or supplemental alkali intake as a novel strategy for prevention of type 2 diabetes mellitus," they concluded.

• Those developing diabetes also had higher baseline BMI, more hypertension and dyslipidemia, and were more likely to have a family history of diabetes.
• This substudy of the Nurses' Health Study found that higher plasma bicarbonate levels were associated with a decreased risk of developing type 2 diabetes over a 10-year period.

Mandel E, et al "Plasma bicarbonate and risk of type 2 diabetes mellitus" CMAJ 2012; doi:10.1503/cmaj.120438.