Discordance Between Glucose Levels Measured in Interstitial Fluid vs in Venous Plasma After Oral Glucose Administration: A Post-Hoc Analysis From the Randomised Controlled PRE-D Trial.

Kristine Færch,Kim Katrine Bjerring Clemmensen,Adam Hulman,Marit Eika Jørgensen,Martin Bæk Blond,Mathias Ried-Larsen,Dorte Vistisen,Hanan Amadid,Lea Bruhn

doi:10.3389/fendo.2021.753810

Abstract

AimsThe oral glucose tolerance test (OGTT) is together with haemoglobin A1c (HbA1c) gold standard for diagnosing prediabetes and diabetes. The objective of this study was to assess the concordance between glucose values obtained from venous plasma versus interstitial fluid after oral glucose administration in 120 individuals with prediabetes and overweight/obesity.Methods120 adults with prediabetes defined by HbA1c 39-47 mmol/mol and overweight or obesity who participated in the randomised controlled PRE-D trial were included in the study. Venous plasma glucose concentrations were measured at 0, 30, 60 and 120 minutes during a 75 g oral glucose tolerance test (OGTT) performed on three different occasions within a 26 weeks period. During the OGTT, the participants wore a CGM device (IPro2, Medtronic), which assessed glucose concentrations every five minutes.ResultsA total of 306 OGTTs with simultaneous CGM measurements were obtained. Except in fasting, the CGM glucose values were below the OGTT values throughout the OGTT period with mean (SD) differences of 0.2 (0.7) mmol/L at time 0 min, -1.1 (1.3) at 30 min, -1.4 (1.8) at 60 min, and -0.5 (1.1) at 120 min). For measurements at 0 and 120 min, there was a proportional bias with an increasing mean difference between CGM and OGTT values with increasing mean of the two measurements.ConclusionsDue to poor agreement between the OGTT and CGM with wide 95% limits of agreement and proportional bias at 0 and 120 min, the potential for assessing glucose tolerance in prediabetes using CGM is questionable.

Highlights

The oral glucose tolerance test (OGTT) provides important information about fasting and post-challenge glucose metabolism and is together with haemoglobin A1c (HbA1c) gold standard for diagnosing prediabetes and diabetes [1]
For the OGTT values at 60 and 120 min, the best match of continuous glucose monitoring (CGM) measurements was at the same time as the OGTT measurements for approximately half of the participants, but in 33% and 26% of the participants, a 15 min lag-time in CGM measurements at 60 and 120 min, respectively, was present
The potential usefulness of CGMs to guide diagnostic decisions has received less attention. In this analysis of 120 individuals with prediabetes and overweight or obesity, we show that glucose levels obtained by CGMs during an OGTT are on average 12-13% lower at 30 and 60 min and 4% lower at 120 min after oral glucose administration than those measured in venous plasma – even when taking individual timelag in sensor glucose measurements into account

Summary

Introduction

The oral glucose tolerance test (OGTT) provides important information about fasting and post-challenge glucose metabolism and is together with haemoglobin A1c (HbA1c) gold standard for diagnosing prediabetes and diabetes [1]. The use of HbA1c for diagnosing diabetes and especially prediabetes is challenging, as HbA1c levels in the non-diabetic range is affected by several factors not related to glycaemia (e.g. genetics, irondeficiency, anaemia, etc.) [2, 3]. Glucose concentrations measured by a glucose sensor (CGM) placed in the subcutaneous tissue for several days may be more physiologically and clinically relevant for assessing glucose tolerance than a single OGTT. Glycaemic variability assessed by the CGM is associated with the development of diabetic complications even in people with well-controlled HbA1c levels [4], which makes the CGM relevant as a monitor of cardiometabolic risk

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Conclusion