Relationship Between Interstitial and Blood Glucose During Hypoglycemia in Subjects with Type 2 Diabetes

Background: Continuous glucose monitoring devices measure interstitial glucose and are commonly used to investigate hypoglycemia. The relationship between interstitial glucose and blood glucose is not completely understood, particularly at low blood glucose concentrations. Interstitial glucose during hypoglycemia is generally lower than blood glucose in young subjects without diabetes and those with type 1 diabetes, but the effect of insulin resistance and obesity in type 2 diabetes on this relationship has not been examined previously. We studied the relationship between blood and interstitial glucose during experimental hypoglycemia in subjects with type 2 diabetes treated with insulin or sulfonylureas and matched controls without diabetes. Methods: Twenty subjects with type 2 diabetes (10 sulfonylurea-treated and 10 insulin-treated) and 10 controls without diabetes of similar age and weight underwent stepped hyperinsulinemic hypoglycemic clamps. We compared blood and interstitial glucose at different levels of hypoglycemia using random effects modeling. Results: Interstitial glucose was significantly higher than blood glucose at all levels of hypoglycemia (P < 0.001), and this difference increased as glucose fell. For every 1 mmol/L drop in blood glucose, the difference increased by 0.32 mmol/L (P < 0.001). This difference was not affected by presence of type 2 diabetes or by modality of treatment (P = 0.10). Conclusions: In older subjects with or without type 2 diabetes, interstitial glucose is significantly higher than blood glucose, and this difference increases with increasing severity of hypoglycemia. Continuous glucose monitors may underestimate hypoglycemia in this group, and this should be taken into account when interpreting results obtained using this technology.