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Published Online: 24 August 2011

Normal Reference Range for Mean Tissue Glucose and Glycemic Variability Derived from Continuous Glucose Monitoring for Subjects Without Diabetes in Different Ethnic Groups

Publication: Diabetes Technology & Therapeutics
Volume 13, Issue Number 9

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.

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References

1.
Goldstein DELittle RRWiedmeyer HMEngland JDMcKenzie EM. Glycated hemoglobin: methodologies and clinical applicationsClin Chem198632B64-B70. 1. Goldstein DE, Little RR, Wiedmeyer HM, England JD, McKenzie EM: Glycated hemoglobin: methodologies and clinical applications. Clin Chem 1986;32:B64–B70.
2.
The effect of intensive treatment of diabetes on development and progression of long-term complications in insulin-dependent diabetes melitus. The Diabetes Control and Complications Trial Research GroupN Engl J Med1993329977-986. 2. The effect of intensive treatment of diabetes on development and progression of long-term complications in insulin-dependent diabetes melitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977–986.
3.
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) GroupLancet1998352837-854Erratum in: Lancet 1998;352:1558. 3. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837–854. Erratum in: Lancet 1998;352:1558.
4.
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UPKPS) GroupLancet1998352854-865Erratum in: Lancet 1999;354:602. 4. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UPKPS) Group. Lancet 1998;352:854–865. Erratum in: Lancet 1999;354:602.
5.
Nathan DMCleary PABacklund JYGenuth SMLachin JMOrchard TJRaskin PZinman B. Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group: Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetesN Engl J Med20053532643-2653. 5. Nathan DM, Cleary PA, Backlund JY, Genuth SM, Lachin JM, Orchard TJ, Raskin P, Zinman B; Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group: Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353:2643–2653.
6.
American Diabetes Association: Standards of medical care in diabetesDiabetes Care200528Suppl 1S4-S36. 6. American Diabetes Association: Standards of medical care in diabetes. Diabetes Care 2005;28(Suppl 1):S4–S36.
7.
The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications TrialDiabetes199544968-983. 7. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995;44:968–983.
8.
Lachin JMGenuth SNathan DMZinman BRutledge BN. Effect of glycemic exposure on the risk of microvascular complications in the Diabetes Control and Complications Trial—revisitedDiabetes200857995-1001. 8. Lachin JM, Genuth S, Nathan DM, Zinman B, Rutledge BN: Effect of glycemic exposure on the risk of microvascular complications in the Diabetes Control and Complications Trial—revisited. Diabetes 2008;57:995–1001.
9.
Kilpatrick ESRigby ASAtkin SL. The effect of glucose variability on the risk of microvascular complications in type 1 diabetesDiabetes Care2006291486-1490. 9. Kilpatrick ES, Rigby AS, Atkin SL: The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care 2006;29:1486–1490.
10.
Kilpatrick ESRigby ASGoode KAtkin SL. Relating mean blood glucose and glucose variability to the risk of multiple episodes of hypoglycaemia in type 1 diabetesDiabetologia2007502553-2561. 10. Kilpatrick ES, Rigby AS, Goode K, Atkin SL: Relating mean blood glucose and glucose variability to the risk of multiple episodes of hypoglycaemia in type 1 diabetes. Diabetologia 2007;50:2553–2561.
11.
Risso AMercuri FQuagliaro LDamante GCeriello A. Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in cultureAm J Physiol Endocrinol Metab2001281E924-E930. 11. Risso A, Mercuri F, Quagliaro L, Damante G, Ceriello A: Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol Endocrinol Metab 2001;281:E924–E930.
12.
Quagliaro LPiconi LAssaloni RMartinelli LMotz ECeriello A. Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activationDiabetes2003522795-2804. 12. Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A: Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes 2003;52:2795–2804.
13.
Piconi LQuagliaro LDa Ros RAssaloni RGiugliano DEsposito KSzabó CCeriello A. Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymeraseJ Thromb Haemost200421453-1459. 13. Piconi L, Quagliaro L, Da Ros R, Assaloni R, Giugliano D, Esposito K, Szabó C, Ceriello A: Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymerase. J Thromb Haemost 2004;2:1453–1459.
14.
Schiekofer SAndrassy MChen JRudofsky GSchneider JWendt TStefan NHumpert PFritsche AStumvoll MSchleicher EHäring HUNawroth PPBierhaus A. Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK, and nuclear factor kappaB in PBMCsDiabetes200352621-633. 14. Schiekofer S, Andrassy M, Chen J, Rudofsky G, Schneider J, Wendt T, Stefan N, Humpert P, Fritsche A, Stumvoll M, Schleicher E, Häring HU, Nawroth PP, Bierhaus A: Acute hyperglycemia causes intracellular formation of CML and activation of ras, p42/44 MAPK, and nuclear factor kappaB in PBMCs. Diabetes 2003;52:621–633.
15.
Monnier LMas EGinet CMichel FVillon LCristol JPColette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetesJAMA20062951681-1687. 15. Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C: Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 2006;295:1681–1687.
16.
Wentholt IMKulik WMichels RPHoekstra JBDeVries JH. Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetesDiabetologia200851183-190. 16. Wentholt IM, Kulik W, Michels RP, Hoekstra JB, DeVries JH: Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes. Diabetologia 2008;51:183–190.
17.
Matthews DR. Time series analysis in endocrinologyActa Paediatr Scand Suppl198834755-62. 17. Matthews DR: Time series analysis in endocrinology. Acta Paediatr Scand Suppl 1988;347:55–62.
18.
Schlichtkrull JMunck OJersild M. The M-valve, an index of blood-sugar control in diabeticsActa Med Scand196517795-102. 18. Schlichtkrull J, Munck O, Jersild M: The M-valve, an index of blood-sugar control in diabetics. Acta Med Scand 1965;177:95–102.
19.
Service FJMolnar GDRosevear JWAckerman EGatewood LCTaylor WF. Mean amplitude of glycemic excursions, a measure of diabetic instabilityDiabetes197019644-655. 19. Service FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF: Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 1970;19:644–655.
20.
Kovatchev BPOtto ECox DGonder-Frederick LClarke W. Evaluation of a new measure of blood glucose variability in diabetesDiabetes Care2006292433-2438. 20. Kovatchev BP, Otto E, Cox D, Gonder-Frederick L, Clarke W: Evaluation of a new measure of blood glucose variability in diabetes. Diabetes Care 2006;29:2433–2438.
21.
Ryan EAShandro TGreen KPaty BWSenior PABigam DShapiro AMVantyghem MC. Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantationDiabetes200453955-962. 21. Ryan EA, Shandro T, Green K, Paty BW, Senior PA, Bigam D, Shapiro AM, Vantyghem MC: Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes 2004;53:955–962.
22.
Wojcicki JM. “J”-index. A new proposition of the assessment of current glucose control in diabetic patientsHorm Metab Res19952741-42. 22. Wojcicki JM: “J”-index. A new proposition of the assessment of current glucose control in diabetic patients. Horm Metab Res 1995;27:41–42.
23.
Kovatchev BPCox DJKumar AGonder-Frederick LClarke WL. Algorithmic evaluation of metabolic control and risk of severe hypoglycemia in type 1 and type 2 diabetes using self-monitoring blood glucose dataDiabetes Technol Ther20035817-828. 23. Kovatchev BP, Cox DJ, Kumar A, Gonder-Frederick L, Clarke WL: Algorithmic evaluation of metabolic control and risk of severe hypoglycemia in type 1 and type 2 diabetes using self-monitoring blood glucose data. Diabetes Technol Ther 2003;5:817–828.
24.
McDonnell CMDonath SMVidmar SIWerther GACameron FJ. A novel approach to continuous glucose analysis utilizing glycemic variationDiabetes Technol Ther20057253-263. 24. McDonnell CM, Donath SM, Vidmar SI, Werther GA, Cameron FJ: A novel approach to continuous glucose analysis utilizing glycemic variation. Diabetes Technol Ther 2005;7:253–263.
25.
Molnar GDTaylor WFHo MM. Day-to-day variation of continuously monitored glycaemia: a further measure of diabetic instabilityDiabetologia19728342-348. 25. Molnar GD, Taylor WF, Ho MM: Day-to-day variation of continuously monitored glycaemia: a further measure of diabetic instability. Diabetologia 1972;8:342–348.
26.
Hill NRHindmarsh PCStevens RJStratton IMLevy JCMatthews DR. A method for assessing quality of control from glucose profilesDiabet Med200724753-758. 26. Hill NR, Hindmarsh PC, Stevens RJ, Stratton IM, Levy JC, Matthews DR: A method for assessing quality of control from glucose profiles. Diabet Med 2007;24:753–758.
27.
Mazze RSStrock EWesley DBorgman SMorgan BBergenstal RCuddihy R. Characterizing glucose exposure for individuals with normal glucose tolerance using continuous glucose monitoring and ambulatory glucose profile analysisDiabetes Technol Ther200810149-159. 27. Mazze RS, Strock E, Wesley D, Borgman S, Morgan B, Bergenstal R, Cuddihy R: Characterizing glucose exposure for individuals with normal glucose tolerance using continuous glucose monitoring and ambulatory glucose profile analysis. Diabetes Technol Ther 2008;10:149–159.
28.
Munir AChoudhary PHarrison BHeller SNewell-Price J. Continuous glucose monitoring in patients with insulinomaClin Endocrinol (Oxf)200868912-918. 28. Munir A, Choudhary P, Harrison B, Heller S, Newell-Price J: Continuous glucose monitoring in patients with insulinoma. Clin Endocrinol (Oxf) 2008;68:912–918.
29.
O'Riordan SMHindmarsh PHill NRMatthews DRGeorge SGreally PCanny GSlattery DMurphy NRoche ECostigan CHoey H. Validation of continuous glucose monitoring in children and adolescents with cystic fibrosis: a prospective cohort studyDiabetes Care2009321020-1022. 29. O'Riordan SM, Hindmarsh P, Hill NR, Matthews DR, George S, Greally P, Canny G, Slattery D, Murphy N, Roche E, Costigan C, Hoey H: Validation of continuous glucose monitoring in children and adolescents with cystic fibrosis: a prospective cohort study. Diabetes Care 2009;32:1020–1022.
30.
Marfella RBarbieri MRuggiero RRizzo MRGrella RMozzillo ALDocimo LPaolisso G. Bariatric surgery reduces oxidative stress by blunting 24-h acute glucose fluctuations in type 2 diabetic obese patientsDiabetes Care201033287-289. 30. Marfella R, Barbieri M, Ruggiero R, Rizzo MR, Grella R, Mozzillo AL, Docimo L, Paolisso G: Bariatric surgery reduces oxidative stress by blunting 24-h acute glucose fluctuations in type 2 diabetic obese patients. Diabetes Care 2010;33:287–289.
31.
Hermanides JVriesendorp TMBosman RJZandstra DFHoekstra JBDevries JH. Glucose variability is associated with intensive care unit mortalityCrit Care Med201038838-842. 31. Hermanides J, Vriesendorp TM, Bosman RJ, Zandstra DF, Hoekstra JB, Devries JH: Glucose variability is associated with intensive care unit mortality. Crit Care Med 2010;38:838–842.
32.
Wentholt IMHart AAHoekstra JBDevries JH. Relationship between interstitial and blood glucose in type 1 diabetes patients: delay and the push–pull phenomenon revisitedDiabetes Technol Ther20079169-175. 32. Wentholt IM, Hart AA, Hoekstra JB, Devries JH: Relationship between interstitial and blood glucose in type 1 diabetes patients: delay and the push–pull phenomenon revisited. Diabetes Technol Ther 2007;9:169–175.
33.
Altman DGPratical Statistics for Medical ResearchLondonChapman & Hall1991. 33. Altman DG: Pratical Statistics for Medical Research. London: Chapman & Hall, 1991.
34.
Zhou JLi HRan XYang WLi QPeng YLi YGao XLuan XWang WJia W. Establishment of normal reference ranges for glycemic variability in Chinese subjects using continuous glucose monitoringMed Sci Monit201117CR9-CR13. 34. Zhou J, Li H, Ran X, Yang W, Li Q, Peng Y, Li Y, Gao X, Luan X, Wang W, Jia W: Establishment of normal reference ranges for glycemic variability in Chinese subjects using continuous glucose monitoring. Med Sci Monit 2011;17:CR9–CR13.

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cover image Diabetes Technology & Therapeutics
Diabetes Technology & Therapeutics
Volume 13Issue Number 9September 2011
Pages: 921 - 928
PubMed: 21714681

History

Published in print: September 2011
Published online: 24 August 2011
Published ahead of print: 29 June 2011

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Nathan R. Hill, DPhil
*
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, United Kingdom.
Tse Medical Academy, Harris Manchester College, University of Oxford, Oxford, United Kingdom.
Nick S. Oliver, MRCP*
Faculty of Medicine, Imperial College, London, United Kingdom.
Pratik Choudhary, M.D.
Kings College London, London, United Kingdom.
Jonathan C. Levy, M.D.
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, United Kingdom.
Peter Hindmarsh, M.D.
Developmental Endocrinology Research Group, Institute of Child Health, University College London, London, United Kingdom.
David R. Matthews, DPhil, M.D.
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, United Kingdom.
Tse Medical Academy, Harris Manchester College, University of Oxford, Oxford, United Kingdom.

Notes

Address correspondence to:Nathan R. Hill, DPhilOxford Centre for Diabetes, Endocrinology and MetabolismChurchill HospitalOld RoadHeadington, Oxford,UK, OX3 7LJ
E-mail: [email protected]

Author Disclosure Statement

No competing financial interest exists for any of the authors.

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