Discrepancies Between Blood Glucose and Interstitial Glucose-Technological Artifacts or Physiology: Implications for Selection of the Appropriate Therapeutic Target

J Diabetes Sci Technol. 2017 Jul;11(4):766-772. doi: 10.1177/1932296817699637. Epub 2017 Mar 21.


Background: For decades, the major source of information used to make therapeutic decisions by patients with diabetes has been glucose measurements using capillary blood samples. Knowledge gained from clinical studies, for example, on the impact of metabolic control on diabetes-related complications, is based on such measurements. Different to traditional blood glucose measurement systems, systems for continuous glucose monitoring (CGM) measure glucose in interstitial fluid (ISF). The assumption is that glucose levels in blood and ISF are practically the same and that the information provided can be used interchangeably. Thus, therapeutic decisions, that is, the selection of insulin doses, are based on CGM system results interpreted as though they were blood glucose values.

Methods: We performed a more detailed analysis and interpretation of glucose profiles obtained with CGM in situations with high glucose dynamics to evaluate this potentially misleading assumption.

Results: Considering physical activity, hypoglycemic episodes, and meal-related differences between glucose levels in blood and ISF uncover clinically relevant differences that can make it risky from a therapeutic point of view to use blood glucose for therapeutic decisions.

Conclusions: Further systematic and structured evaluation as to whether the use of ISF glucose is more safe and efficient when it comes to acute therapeutic decisions is necessary. These data might also have a higher prognostic relevance when it comes to long-term metabolic consequences of diabetes. In the long run, it may be reasonable to abandon blood glucose measurements as the basis for diabetes management and switch to using ISF glucose as the appropriate therapeutic target.

Keywords: blood glucose; continuous glucose monitoring; glucose variability; interstitial glucose; physiology of glucose regulation.

MeSH terms

  • Artifacts
  • Blood Glucose / analysis*
  • Diabetes Mellitus / blood*
  • Extracellular Fluid / chemistry*
  • Glucose / analysis*
  • Humans
  • Monitoring, Physiologic / methods*


  • Blood Glucose
  • Glucose