Plasma Insulin Levels and Hypoglycemia Affect Subcutaneous Interstitial Glucose Concentration.

Abstract

Continuous glucose monitoring (CGM) accuracy during hypoglycemia is suboptimal. This might be partly explained by insulin or hypoglycemia-induced changes in the plasma interstitial subcutaneous (SC) fluid glucose gradient. The aim of the present study was to assess the role of plasma insulin (PI) and hypoglycemia itself in the plasma and interstitial SC fluid glucose concentration in patients with type 1 diabetes mellitus. Eleven subjects with type 1 diabetes (age 36.5 ± 9.1 years, HbA1c 7.9 ± 0.4% [62.8 ± 2.02 mmol/mol]; mean ± standard deviation) were evaluated under hyperinsulinemic euglycemia and hypoglycemia. Each subject underwent two randomized crossover clamps with either a primed 0.3 (low insulin) or 1 mU/(kg·min) (high insulin) insulin infusion. The raw CGM signal was normalized with median preclamp values to obtain a standardized measure of the interstitial glucose (IG) concentration before statistical analysis. The mean PI concentration was greater in high insulin studies (HISs) versus low insulin studies (LISs) (412.89 ± 13.63 vs. 177.22 ± 10.05 pmol/L). During hypoglycemia, glucagon, adrenaline, free fatty acids, glycerol, and beta-OH-butyrate were higher in the LIS (P < 0.0001). Likewise, the IG concentration was significantly different (P < 0.0001). This was due to lower IG concentration than plasma glucose (PG) concentration during the euglycemic hyperinsulinemic phases in the HIS. In contrast, no difference was observed during hypoglycemia. This was the result of an unchanged PG/IG gradient during the entire LIS, while in the HIS, this gradient increased during the hyperinsulinemic euglycemia phase. Both PI levels and hypoglycemia affect the relationship between IG and PG concentration. ClinicalTrials.gov Identifier: NCT01714895.