Serum bicarbonate, anion gap and insulin resistance in the National Health and Nutrition Examination Survey

Diabet Med. 2008 Jul;25(7):798-804. doi: 10.1111/j.1464-5491.2008.02471.x.


Aims: Metabolic acidosis may contribute to the development of insulin resistance. To date, there have been no population-based studies of acid-base status and insulin resistance. We examined the cross-sectional relations between serum bicarbonate, anion gap, and insulin resistance in a subset of healthy participants in the 1999-2000 and 2001-2002 National Health and Nutrition Examination Surveys.

Methods: We included 1496 adults without diabetes or other chronic diseases. Insulin sensitivity was estimated by an index based on fasting insulin and triglyceride levels (MFFM). Linear regression was used to adjust for age, race, body mass index, albumin and other factors. Sample weights were used to produce weighted regression parameters.

Results: Median values of bicarbonate, anion gap and fasting levels of insulin, triglycerides and glucose were 23 mmol/l, 12.5 mmol/l, 48 pmol/l, 1.08 mmol/l and 5.0 mmol/l, respectively. After multivariable adjustment, bicarbonate was positively associated and anion gap was inversely associated with MFFM (P < 0.01). Participants in the highest quartile of bicarbonate had fasting insulin 12.76 pmol/l lower [95% confidence interval (CI) 5.96, 19.55; P for trend < 0.01] than those in the lowest quartile. Participants in the highest quartile of anion gap had fasting insulin 4.39 pmol/l higher (95% CI 0.47, 8.31; P for trend < 0.01) than those in the lowest quartile.

Conclusions: Lower bicarbonate and higher anion gap are independently associated with insulin resistance. Further research is needed to elucidate the relations between organic acid production, insulin resistance, and the pathogenesis of Type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acid-Base Imbalance / metabolism*
  • Adult
  • Bicarbonates / metabolism*
  • Blood Glucose / metabolism*
  • Fasting
  • Female
  • Humans
  • Insulin Resistance*
  • Male


  • Bicarbonates
  • Blood Glucose