Normal reference range for mean tissue glucose and glycemic variability derived from continuous glucose monitoring for subjects without diabetes in different ethnic groups

Abstract

Background: Glycemic variability has been proposed as a contributing factor in the development of diabetes complications. Multiple measures exist to calculate the magnitude of glycemic variability, but normative ranges for subjects without diabetes have not been described. For treatment targets and clinical research we present normative ranges for published measures of glycemic variability.

Methods: Seventy-eight subjects without diabetes having a fasting plasma glucose of <120 mg/dL (6.7 mmol/L) underwent up to 72 h of continuous glucose monitoring (CGM) with a Medtronic Minimed (Northridge, CA) CGMS(®) Gold device. Glycemic variability was calculated using EasyGV(©) software (available free for non-commercial use at www.easygv.co.uk ), a custom program that calculates the SD, M-value, mean amplitude of glycemic excursions (MAGE), average daily risk ratio (ADRR), Lability Index (LI), J-Index, Low Blood Glucose Index (LBGI), High Blood Glucose Index (HBGI), continuous overlapping net glycemic action (CONGA), mean of daily differences (MODD), Glycemic Risk Assessment in Diabetes Equation (GRADE), and mean absolute glucose (MAG).

Results: Eight CGM traces were excluded because there were inadequate data. From the remaining 70 traces, normative reference ranges (mean±2 SD) for glycemic variability were calculated: SD, 0-3.0; CONGA, 3.6-5.5; LI, 0.0-4.7; J-Index, 4.7-23.6; LBGI, 0.0-6.9; HBGI, 0.0-7.7; GRADE, 0.0-4.7; MODD, 0.0-3.5; MAGE-CGM, 0.0-2.8; ADDR, 0.0-8.7; M-value, 0.0-12.5; and MAG, 0.5-2.2.

Conclusions: We present normative ranges for measures of glycemic variability in adult subjects without diabetes for use in clinical care and academic research.

Figures

FIG. 1.

Graphical illustration of how each of the 10 methods of glycemic variability assessment are calculated from a continuous glucose monitoring trace: average daily risk ratio (ADRR), continuous overlapping net glycemic action (CONGA), Glycemic Risk Assessment in Diabetes Equation (GRADE), High Blood Glucose Index (HBGI), Low Blood Glucose Index (LBGI), J-Index, Lability Index (LI), mean absolute glucose (MAG), mean amplitude of glucose excursions (MAGE), and mean of daily differences (MODD). In practice each method would independently assess the entire trace.