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Current Diabetes Reviews


ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Review Article

Glycemic Variability, Oxidative Stress, and Impact on Complications Related to Type 2 Diabetes Mellitus

Author(s): Tatiana Valente* and Alberto K. Arbex

Volume 17, Issue 7, 2021

Published on: 16 July, 2020

Article ID: e071620183816 Pages: 11

DOI: 10.2174/1573399816666200716201550

Price: $65


Chronic hyperglycemia is an established risk factor for the development of complications in both type 1 and type 2 diabetes, but glycemic variability has emerged as a possible independent risk factor for diabetes complications, possibly through oxidative stress. In this review, methods to access glycemic variability and oxidative stress, as well as their correlations, are discussed. Non-pharmacological and pharmacological strategies are also debated to achieve better glycemic control, not only by HbA1c target but also with reduced glycemic fluctuations, possibly minimizing the risk of diabetes complications.

Keywords: Glycemic variability, oxidative stress, type 2 diabetes, complications, hyperglycemia, type 1 diabetes.

Avignon A, Radauceanu A, Monnier L. Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. Diabetes Care 1997; 20(12): 1822-6.
[] [PMID: 9405900]
Nathan DM, Genuth S, Lachin J, et al. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977-86.
[] [PMID: 8366922]
Epidemiology of Diabetes Interventions and Complications (EDIC). Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care 1999; 22(1): 99-111.
[] [PMID: 10333910]
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352(9131): 837-53.
[] [PMID: 9742976]
Sacks DB, Bruns DE, Goldstein DE, Mac Laren NK, Mc Donald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (Position Statement). Diabetes Care 2002; 25: 750-86.
[] [PMID: 21617111]
Gorus F, Mathieu C, Gerlo E. How should HbA1c measurements be reported? Diabetologia 2006; 49(1): 7-10.
[] [PMID: 16378164]
American Diabetes Association. Standards of medical care in diabetes--2010. Diabetes Care 2010; 33(Suppl. 1): S11-61.
[] [PMID: 20042772]
Monnier L, Colette C. Glycemic variability: should we and can we prevent it? Diabetes Care 2008; 31(Suppl. 2): S150-4.
[] [PMID: 18227477]
Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA 2006; 295(14): 1707-8.
[] [PMID: 16609094]
Ceriello A, Ihnat MA. ‘Glycaemic variability’: a new therapeutic challenge in diabetes and the critical care setting. Diabet Med 2010; 27(8): 862-7.
[] [PMID: 20653741]
Ceriello A, Monnier L, Owens D. Glycaemic variability in diabetes: clinical and therapeutic implications. Lancet Diabetes Endocrinol 2018; S2213-8587(18): 30136-30130.
Danne T, Nimri R, Battelino T, et al. International consensus on use of continuous glucose monitoring. Diabetes Care 2017; 40(12): 1631-40.
[] [PMID: 29162583]
Fleischer J, Cichosz SL, Hansen TK. Comment on Lachin, et al. Association of glycemic variability in type 1 diabetes with progression of microvascular outcomes in the Diabetes Control and Complications. Diabetes Care 2017; 40(11): e164.
[] [PMID: 29061593]
Siegelaar SE, Holleman F, Hoekstra JB, DeVries JH. Glucose variability; does it matter? Endocr Rev 2010; 31(2): 171-82.
[] [PMID: 19966012]
Smith-Palmer J, Brändle M, Trevisan R, Orsini Federici M, Liabat S, Valentine W. Assessment of the association between glycemic variability and diabetes-related complications in type 1 and type 2 diabetes. Diabetes Res Clin Pract 2014; 105(3): 273-84.
[] [PMID: 25023992]
Puñales MK, Geremia C, Mondadori P, Pickler M, Fornari A, Tschiedel B. [How the continuous glucose monitoring system can contribute to HbA1c interpretation in type 1 diabetes mellitus?]. Arq Bras Endocrinol Metabol 2008; 52(2): 299-306.
[PMID: 18438540]
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(2): 253-63.
[] [PMID: 15857227]
Monnier L, Colette C, Owens DR. The application of simple metrics in the assessment of glycaemic variability. Diabetes Metab 2018; 44(4): 313-9.
[] [PMID: 29602622]
Siegelaar SE, Holleman F, Hoekstra JB, DeVries JH. Glucose Variability: Does it matter? Endocrine Reviews, April 2010, 31: 171-182. Rodbard D: Interpretation of continuous glucose monitoring data: glycemic variability and quality of glycemic control. Diabetes Technol Ther 2009; 11(Suppl. 1): S-55-67. [Glycaemic Variability in diabetes?].
Shima K, Tanaka R, Morishita S, Tarui S, Kumahara Y. Studies on the etiology of “brittle diabetes”. Relationship between diabetic instability and insulinogenic reserve. Diabetes 1977; 26(8): 717-25.
[] [PMID: 885295]
Petrie JR, Peters AL, Bergenstal RM, Holl RW, Fleming GA, Heinemann L. Improving the Clinical Value and Utility of CGM Systems: Issues and Recommendations: A Joint Statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group. Diabetes Care 2017; 40(12): 1614-21.
[] [PMID: 29070577]
Hirsch IB, Sherr JL, Hood KK. Connecting the Dots. Diabetes Care 2019; 42(3): 345-8.
[] [PMID: 30787056]
Gorst C, Kwok CS, Aslam S, et al. Long-term glycemic variability and risk of adverse outcomes: a systematic review and meta-analysis. Diabetes Care 2015; 38(12): 2354-69.
[] [PMID: 26604281]
Nusca A, et al. Glycemic variability in the development of cardiovascular complications in diabetes.
Monnier L, Mas E, Ginet C, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 2006; 295(14): 1681-7.
[] [PMID: 16609090]
Hisch IB, Browlee M. The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care 2007; 30: 186-7.
Rösen P, Nawroth PP, King G, Möller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 2001; 17(3): 189-212.
[] [PMID: 11424232]
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414(6865): 813-20.
[] [PMID: 11742414]
Roberts LJ, Morrow JD. Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 2000; 28(4): 505-13.
[] [PMID: 10719231]
Basu S. Metabolism of 8-iso-prostaglandin F2α. FEBS Lett 1998; 428(1-2): 32-6.
[] [PMID: 9645469]
Johnson EL. Glycemic variability: too often overlooked in Type 2 diabetes? JFamPrac 2010; 59(8): E1-8.
Siegelaar SE, Barwari T, Kulik W, Hoekstra JB, DeVries JH. No relevant relationship between glucose variability and oxidative stress in well-regulated type 2 diabetes patients. J Diabetes Sci Technol 2011; 5(1): 86-92.
[] [PMID: 21303629]
Dandona P, Chaudhuri A, Ghanim H, Mohanty P. Insulin as an anti-inflammatory and antiatherogenic modulator. J Am Coll Cardiol 2009; 53(5)(Suppl.): S14-20.
[] [PMID: 19179212]
Zheng F, Lu W, Jia C, Li H, Wang Z, Jia W. Relationships between glucose excursion and the activation of oxidative stress in patients with newly diagnosed type 2 diabetes or impaired glucose regulation. Endocrine 2010; 37(1): 201-8.
[] [PMID: 20963571]
Ohara M, Fukui T, Ouchi M, et al. Relationship between daily and day-to-day glycemic variability and increased oxidative stress in type 2 diabetes. Diabetes Res Clin Pract 2016; 122: 62-70.
[] [PMID: 27810687]
Ohara M, Kohata Y, Nagaike H, et al. Association of glucose and blood pressure variability on oxidative stress in patients with type 2 diabetes mellitus and hypertension: a cross-sectional study. Diabetol Metab Syndr 2019; 11: 29.
[] [PMID: 31044019]
Chang CM, Hsieh CJ, Huang JC, Huang IC. Acute and chronic fluctuations in blood glucose levels can increase oxidative stress in type 2 diabetes mellitus. Acta Diabetol 2012; 49(Suppl. 1): S171-7.
[] [PMID: 22547264]
Ikebuchi M, Nishio Y, Maegawa H, Kashiwagi A. Effects of hyperglycemia on oxidative stress and antioxidant potential in patients with type 2 diabetes. Diabetol Int 2010; 1: 72-7.
Ceriello A, Esposito K, Piconi L, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 2008; 57(5): 1349-54.
[] [PMID: 18299315]
Zaccardi F, Stefano PD, Busetto E, et al. Group of signs: a new method to evaluate glycemic variability. J Diabetes Sci Technol 2008; 2(6): 1061-5.
[] [PMID: 19885294]
Liu Y, He Y. Effect of blood glucose excursions on the risk of diabetic retinopathy in type 2 diabetes. Diabetes Conference: 71st scientific sessions of the American Diabetes Association San Diego.
Liu Y, Li Y, Cai H, Zhang X. The relationship between glycemic variability and macrovascular and microvascular complications in type 2 diabetes. DiabetesConference: 71st scientific sessions of the American Diabetes Association San Diego. [abstract]
Lu J, Ma X, Zhou J, Zhang L, et al. Association of Time in Range, as Assessed by Continuous GlucoseMonitoring, With Diabetic Retinopathy in Type 2 Diabetes. Diabetes Care 2018; 41: 2370-6.
Lu J, Ma X, Zhang L, et al. Glycemic variability assessed by continuous glucose monitoring and the risk of diabetic retinopathy in latent autoimmune diabetes of the adult and type 2 diabetes Diabetes Investig 2019 May; Vol. 10(3): 753-9.
Sartore G, Chilelli NC, Burlina S, Lapolla A. Association between glucose variability as assessed by continuous glucose monitoring (CGM) and diabetic retinopathy in type 1 and type 2 diabetes. Acta Diabetol 2013; 50(3): 437-42.
[] [PMID: 23417155]
Mo Y, Zhou J, Li M, et al. Glycemic variability is associated with subclinical atherosclerosis in Chinese type 2 diabetic patients. Cardiovasc Diabetol 2013; 12: 15.
[] [PMID: 23316958]
Tsuyoshi Ito1, Taku Ichihashi1, Hiroshi Fujita1, et al. The impact of intraday glucose variability on coronary artery spasm in patients with dysglycemia Heart and Vessels 2019; 34(8): 1250-7.
Su G, Mi S, Tao H, et al. Association of glycemic variability and the presence and severity of coronary artery disease in patients with type 2 diabetes. Cardiovasc Diabetol 2011; 10: 19.
[] [PMID: 21349201]
Su G, Mi SH, Li Z, Tao H, Yang HX, Zheng H. Prognostic value of early in-hospital glycemic excursion in elderly patients with acute myocardial infarction. Cardiovasc Diabetol 2013; 12: 33.
[] [PMID: 23399749]
Gerbaud E, Darier R, et al. Glycemic variability is a powerful independent predictive factor of midterm major adverse cardiac events in patients with diabetes with acute coronary syndrome. Diabetes Care 2019; 42(4): 674-81.
Pochinka I, Strongin L, Struchkova J. Glycaemic variability and ventricular cardiac arrhythmias in type 2 diabetic patients with chronic heart failure. 48th annual meeting of the European Association for the Study of Diabetes. [abstract]
Siegelaar SE, Kerr L, Jacober SJ, Devries JH. A decrease in glucose variability does not reduce cardiovascular event rates in type 2 diabetic patients after acute myocardial infarction: a reanalysis of the HEART2D study. Diabetes Care 2011; 34(4): 855-7.
[] [PMID: 21447661]
Mellbin LG, Malmberg K, Rydén L, Wedel H, Vestberg D, Lind M. The relationship between glycaemic variability and cardiovascular complications in patients with acute myocardial infarction and type 2 diabetes: a report from the DIGAMI 2 trial. Eur Heart J 2013; 34(5): 374-9.
[] [PMID: 23144046]
Zoungas S, Patel A, Chalmers J, et al. ADVANCE Collaborative Group. Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010; 363(15): 1410-8.
[] [PMID: 20925543]
Seaquist ER, Miller ME, Bonds DE, et al. ACCORD Investigators. The impact of frequent and unrecognized hypoglycemia on mortality in the ACCORD study. Diabetes Care 2012; 35(2): 409-14.
[] [PMID: 22179956]
Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010; 340: b4909.
[] [PMID: 20061358]
Cavalot F. Diabetes, Obesity and Metabolism. ©2013 John Wiley & Sons Ltd 2013; 15: pp. (Suppl. 2)3-8. review article
Hsu CC, Chang HY, Huang MC, et al. HbA1c variability is associated with microalbuminuria development in type 2 diabetes: a 7-year prospective cohort study. Diabetologia 2012; 55(12): 3163-72.
[] [PMID: 22923064]
Lin CC, Chen CC, Chen FN, Li CI, Liu CS. Risks of diabetic nephropathy with variation in hemoglobin A1c and fasting plasma glucose. Am J Med 2013; 126(11): 1017 e1-10.
Sugawara A, Kawai K, Motohashi S, et al. HbA(1c) variability and the development of microalbuminuria in type 2 diabetes: Tsukuba Kawai Diabetes Registry 2. Diabetologia 2012; 55(8): 2128-31.
[] [PMID: 22580991]
Hindaw BioMed Research International 2020; Volume 20207462158: 8.
Wei F, Sun X, Zhao Y, Zhang H, Diao Y, Liu Z. Excessive visit-to-visit glycemic variability independently deteriorates the progression of endothelial and renal dysfunction in patients with type 2 diabetes mellitus. BMC Nephrol 2016; 17(1): 67.
[] [PMID: 27386849]
Penno G, Solini A, Bonora E, et al. Renal Insufficiency And Cardiovascular Events Study Group. HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study. Diabetes Care 2013; 36(8): 2301-10.
[] [PMID: 23491522]
Lee M-Y, Hsiao P-J, Huang Y-T, Huang J-C, Hsu W-H, Chen S-C, et al. Greater HbA1cvariability is associated with increased cardiovascular events in type 2 diabetes patients with preserved renal function, but not in moderate to advanced chronic kidney disease. PLoS One 2017; 12(6)
Muggeo M, Verlato G, Bonora E, et al. Long-term instability of fasting plasma glucose predicts mortality in elderly NIDDM patients: the Verona Diabetes Study. Diabetologia 1995; 38(6): 672-9.
[] [PMID: 7672488]
Slieker RC, van der Heijden AAWH, Nijpels G, Elders PJM, ’t Hart LM, Beulens JWJ. Visit-to-visit variability of glycemia and vascular complications: the Hoorn Diabetes Care System cohort. Cardiovasc Diabetol 2019; 18(1): 170.
[] [PMID: 31830993]
Hsieh YT, Hsieh MG. Fasting plasma glucose variability is an independent risk factor for diabetic retinopathy and diabetic macular oedema in type 2 diabetes: An eight-year prospective cohort study. Clin Sci (Lond) 2019; (September):
[] [PMID: 32065699]
Kildegaard J, Christensen TF, Hejlesen Ok. Sources of Glycemic variability- what type of thecnology is needed? J Diabetes Sci Technol 2009; 3(4): 986-991.
Farabi SS, Carley DW, Smith D, Quinn L. Impact of exercise on diurnal and nocturnal markers of glycaemic variability and oxidative stress in obese individuals with type 2 diabetes or impaired glucose tolerance. Diab Vasc Dis Res 2015; 12(5): 381-5.
[] [PMID: 25994591]
Valdes CT, Elkind-Hirsch KE. Intravenous glucose tolerance test-derived insulin sensitivity changes during the menstrual cycle. J Clin Endocrinol Metab 1991; 72(3): 642-6.
[] [PMID: 1997519]
Rodbard D. Continuous glucose monitoring: a review of recent studies demonstrating improved glycemic outcomes. Diabetes Technol Ther 2017; 19(S3)(Suppl. 3): S25-37.
[] [PMID: 28585879]
Secrest MH, Udell JA, Filion KB. The cardiovascular safety trials of DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors. Trends Cardiovasc Med 2017; 27(3): 194-202.
[] [PMID: 28291655]
Lund A, Knop FK, Vilsbøll T. Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes: differences and similarities. Eur J Intern Med 2014; 25(5): 407-14.
[] [PMID: 24694879]
Busch RS, Kane MP. Combination SGLT2 inhibitor and GLP-1 receptor agonist therapy: a complementary approach to the treatment of type 2 diabetes. Postgrad Med 2017; 129(7): 686-97.
[] [PMID: 28657399]
Barnett AH. Complementing insulin therapy to achieve glycemic control. Adv Ther 2013; 30(6): 557-76.
[] [PMID: 23797471]
Cryer PE. Severe hypoglycemia predicts mortality in diabetes. Diabetes Care 2012; 35(9): 1814-6.
[] [PMID: 22923682]
Ahrén B. Avoiding hypoglycemia: a key to success for glucose-lowering therapy in type 2 diabetes. Vasc Health Risk Manag 2013; 9: 155-63.
[] [PMID: 23637538]
The DCCT Research Group. Reliability and validity of a diabetes quality-of-life measure for the diabetes control and complications trial (DCCT). Diabetes Care 1988; 11(9): 725-32.
[] [PMID: 3066604]
Bergenstal RM. Glycemic Variability and Diabetes Complications: Does It Matter? Simply Put, There Are Better Glycemic Markers! Diabetes Care 2015; 38: 1615-21.
Shimabukuro M, Higa N, Chinen I, Yamakawa K, Takasu N. Effects of a single administration of acarbose on postprandial glucose excursion and endothelial dysfunction in type 2 diabetic patients: a randomized crossover study. J Clin Endocrinol Metab 2006; 91(3): 837-42.
[] [PMID: 16368744]
Müller G, Satoh Y, Geisen K. Extrapancreatic effects of sulfonylureas--a comparison between glimepiride and conventional sulfonylureas. Diabetes Res Clin Pract 1995; 28(Suppl.): S115-37.
[] [PMID: 8529504]
Dandona P. Minimizing Glycemic fluctuations in patients with type 2 diabetes: Approaches and importance. Diabetes Technol Ther 2017; 19(9): 498-506.
[] [PMID: 28771387]
Lee S, Lee H, Kim H, Kim Y, Kim E. Effect of DPP-IV Inhibitors on Glycemic Variability in Patients with T2DM: A Systematic Review and Meta- Analysis. 2019; 9: 13296.
Monnier L, Colette C, Dejager S, Owens DR. “Mild dysglycemia” in type 2 diabetes: to be neglected or not? J Diabetes Complications 2015; 29(3): 451-8.
[] [PMID: 25572605]
Kim HS, Shin JA, Lee SH, et al. A comparative study of the effects of a dipeptidyl peptidase-IV inhibitor and sulfonylurea on glucose variability in patients with type 2 diabetes with inadequate glycemic control on metformin. Diabetes Technol Ther 2013; 15(10): 810-6.
[] [PMID: 24050737]
Vianna AGD, Lacerda CS, Pechmann LM, Polesel MG, Marino EC, Faria-Neto JR. A randomized controlled trial to compare the effects of sulphonylurea gliclazide MR (modified release) and the DPP-4 inhibitor vildagliptin on glycemic variability and control measured by continuous glucose monitoring (CGM) in Brazilian women with type 2 diabetes. Diabetes Res Clin Pract 2018; 139: 357-65.
[] [PMID: 29596951]
Marfella R, Barbieri M, Grella R, Rizzo MR, Nicoletti GF, Paolisso G. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J Diabetes Complications 2010; 24(2): 79-83.
[] [PMID: 19261490]
Guerci B, Monnier L, Serusclat P, et al. Continuous glucose profiles with vildagliptin versus sitagliptin in add-on to metformin: results from the randomized optima study. Diabetes Metab 2012; 38(4): 359-66.
[] [PMID: 22809630]
Green JB, Bethel MA, Armstrong PW, et al. TECOS study group. effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015; 373(3): 232-42.
[] [PMID: 26052984]
Henry RR, Strange P, Zhou R, et al. Effects of dapagliflozin on 24-hour glycemic control in patients with type 2 diabetes: a randomized controlled trial. Diabetes Technol Ther 2018; 20(11): 715-24.
[] [PMID: 30222367]
Vianna AGD, Lacerda CS, Pechmann LM, et al. Improved glycemic variability and time in range with dapagliflozin versus gliclazide modified release among adults with type 2 diabetes evaluated by continuous glucose monitoring: A 12-week randomized controlled trial. Diabetes Obes Metab 2020; 22(4): 501-11.
[] [PMID: 31709738]
Nomoto H, Miyoshi H, Sugawara H, et al. A randomized controlled trial comparing the effects of dapagliflozin and DPP-4 inhibitors on glucose variability and metabolic parameters in patients with type 2 diabetes mellitus on insulin. Diabetol Metab Syndr 2017; 9: 54.
[] [PMID: 28725273]
Abdul-Ghani M, Del Prato S, Chilton R, DeFronzo R. SGLT2 inhibitors and cardiovascular risk: Lessons learned from the EMPA- REG OUTCOME. StudyDiabetes Care 2016; 39: 717-25.
Wiviott SD, Raz I, Bonaca MP, et al. DECLARE–TIMI 58 investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380(4): 347-57.
[] [PMID: 30415602]
Perkovic V, de Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol 2018; 6(9): 691-704.
[] [PMID: 29937267]
FLAT-SUGAR Trial Investigators. Design of FLAT-SUGAR: randomized trial of prandial insulin versus prandial GLP-1 receptor agonist together with basal insulin and metformin for high-risk type 2 diabetes. Diabetes care the FLAT-SUGAR trial investigators* glucose variability in a 26-week randomized comparison of mealtime treatment with rapid-acting insulin VersusGLP-1 agonist in participants with type 2 diabetes at high cardiovascular risk. Diabetes Care 2015; 38(8): 1558-1566.
Jendle J, Testa MA, Martin S, Jiang H, Milicevic Z. Continuous glucose monitoring in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonist dulaglutide in combination with prandial insulin lispro: an AWARD-4 substudy. Diabetes Obes Metab 2016; 18(10): 999-1005.
[] [PMID: 27279266]
Li L, Yao M, Ma J, Xue P, Li Y. Continuous subcutaneous insulin infusion combined with liraglutide reduced glycemic variability and oxidative stress in type 2 diabetes mellitus: A study based on the flash glucose monitoring system Endocrino Journal 2019; 66(10): 871-880.
Del Olmo García MI, Merino-Torres JF. GLP 1 receptor agonists, glycemic variability, oxidative stress and acute coronary syndrome. Med Hypotheses 2020; 136109504.
[] [PMID: 31794876]
Uemura F, Okada Y, Torimoto K, Tanaka Y. Relation between hypoglycemia and glycemic variability in type 2 diabetes patients with insulin therapy: A study based on continuous glucose monitoring. Diabetes Technol Ther 2018; 20(2): 140-6.
[] [PMID: 29293363]
Johnson EL. Glycemic variability: too often overlooked in Type 2 diabetes? JFamPrac 2010; 59(8): E1-8.
Ferrari MTM, Neto AM. Efficacy, safety and clinical use of newer basal insulins analogs. Endocrinol Metab Int J 2018; 6(3): 215-21.
Lingvay I, Pérez Manghi F, García-Hernández P, et al. DUAL V Investigators. Effect of insulin glargine up-titration vs. insulin degludec/liraglutide on glycated hemoglobin levels in patients with uncontrolled type 2 diabetes: The DUAL V randomized clinical trial. JAMA 2016; 315(9): 898-907.
[] [PMID: 26934259]
Aroda VR, Rosenstock J, Wysham C, et al. LixiLan-L trial investigators. Efficacy and safety of LixiLan, a titratable fixed-ratio combination of insulin glargine plus lixisenatide in type 2 diabetes inadequately controlled on basal insulin and metformin: The LixiLan-L randomized trial. Diabetes Care 2016; 39(11): 1972-80.
[] [PMID: 27650977]
Gimenez M, Tannen AJ, Reddy M, Moscardo V, Conget I, Oliver N. Revisiting the relationships between measures of glycemic control and hypoglycemia in continuous glucose monitoring data sets. Diabetes Care 2018; 41(2): 326-32.
[] [PMID: 29191845]
Monnier L, Colette C, Owens DR. Glycemic variability: the third component of the dysglycemia in diabetes. Is it important? How to measure it? J Diabetes Sci Technol 2008; 2(6): 1094-100.
[] [PMID: 19885298]
Inzucchi SE, DiGenio A, Zhou R, Umpierrez G. The impact of glucose variability on achievement of glycaemic control and risk of hypoglycaemia in patients with type 2 diabetes. Diabetologia Conference: 47th annual meeting of the European Association for the Study of Diabetes, EASD.
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(12): 2553-61.
[] [PMID: 17882397]
Monnier L, Wojtusciszyn A, Colette C, Owens D. The contribution of glucose variability to asymptomatic hypoglycemia in persons with type 2 diabetes. Diabetes Technol Ther 2011; 13(8): 813-8.
[] [PMID: 21561372]
Lipska KJ, Kosiborod M. Hypoglycemia and adverse outcomes: marker or mediator? Rev Cardiovasc Med 2011; 12(3): 132-5.
[PMID: 22080923]
Cryer PE. Glycemic goals in diabetes: trade-off between glycemic control and iatrogenic hypoglycemia. Diabetes 2014; 63(7): 2188-95.
[] [PMID: 24962915]
Wagner JA, Abbott G, Lett S. Age related differences in individual quality of life domains in youth with type 1 diabetes. Health Qual Life Outcomes 2004; 2: 54.
[] [PMID: 15385049]
Diabetes UK. Minding the gap: the provision of psychological support and care for people with diabetes in the UK. A report from Diabetes UK 2008 December; Available at:
Speight J, Reaney MD, Barnard KD. Not all roads lead to Rome-a review of quality of life measurement in adults with diabetes. Diabet Med 2009; 26(4): 315-27.
[] [PMID: 19388959]
Imayama I, Plotnikoff RC, Courneya KS, Johnson JA. Determinants of quality of life in adults with type 1 and type 2 diabetes. Health Qual Life Outcomes 2011; 9: 115.
[] [PMID: 22182307]
Rosenthal MJ, Fajardo M, Gilmore S, Morley JE, Naliboff BD. Hospitalization and mortality of diabetes in older adults. A 3-year prospective study. Diabetes Care 1998; 21(2): 231-5.
[] [PMID: 9539987]
Hoey H, Aanstoot HJ, Chiarelli F, et al. Good metabolic control is associated with better quality of life in 2,101 adolescents with type 1 diabetes. Diabetes Care 2001; 24(11): 1923-8.
[] [PMID: 11679458]
Cox DJ, McCall A, Kovatchev B, Sarwat S, Ilag LL, Tan MH. Effects of blood glucose rate of changes on perceived mood and cognitive symptoms in insulin-treated type 2 diabetes. Diabetes Care 2007; 30(8): 2001-2.
[] [PMID: 17473060]
Penckofer S, Quinn L, Byrn M, Ferrans C, Miller M, Strange P. Does glycemic variability impact mood and quality of life? Diabetes Technol Ther 2012; 14(4): 303-10.
[] [PMID: 22324383]
de Ranitz-Greven W, Beulens J, Biesma D, et al. Is higher glycemic variability in type 2 diabetes patients associated with reduced quality of life? Endocr Rev 2015; 36(Suppl. 2): 2015.
Genovese S, Tedeschi D. Effects of vildagliptin/metformin therapy on patient-reported outcomes: work productivity, patient satisfaction, and resource utilization. Adv Ther 2013; 30(2): 152-64.
[] [PMID: 23430354]
Vigersky RA. The benefits, limitations, and cost-effectiveness of advanced technologies in the management of patients with diabetes mellitus. J Diabetes Sci Technol 2015; 9(2): 320-30.
[] [PMID: 25555391]
Klonoff DC, Buckingham B, Christiansen JS, et al. Endocrine Society. Continuous glucose monitoring: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011; 96(10): 2968-79.
[] [PMID: 21976745]
Giannetti VJ, Kamal KM. Adherence with therapeutic regimens: Behavioral and pharmacoeconomic perspectives. J Pharm Pract 2016; 29(2): 138-43.
[] [PMID: 25292442]
Khairna R, Kamal KM, Giannetti V, Dwibedi N, McConaha J. Barriers and facilitators to diabetes self-management in a primary care setting – Patient perspectives. Res Social Adm Pharm 2018.
[] [PMID: 29776663]
Jung HS. Clinical implications of glucose variability: chronic complications of diabetes. Endocrinol Metab (Seoul) 2015; 30(2): 167-74.
[] [PMID: 26194076]
Ramzi A. Ajjan. How can we realize the clinical benefit of continuous glucose monitoring? Diabetes Technol Ther 2017; 19(Suppl. 2).
Bartelme A, Bridger P. The role of reimbursement in the adoption of continuous glucose monitors. J Diabetes Sci Technol 2009; 3(4): 992-5.
[] [PMID: 20144351]
Heinemann L, DeVries JH. Reimbursement for continuous glucose monitoring. Diabetes Technol Ther 2016; 18(Suppl. 2): S248-52.
[] [PMID: 26784130]
Fonda SJ, Graham C, Munakata J, Powers JM, Price D, Vigersky RA. The cost-effectiveness of real Time continuous glucose monitoring (RT-CGM) in Type 2 diabetes. J Diabetes Sci Technol 2016; 10(4): 898-904.
[] [PMID: 26843480]
Fonseca VA, Grunberger G, Anhalt H, et al. Consensus Conference Writing Committee. Continuous glucose monitoring: a consensus conference of The American Association of Clinical Endocrinologists and American College of Endocrinology. Endocr Pract 2016; 22(8): 1008-21.
[] [PMID: 27214060]
Rodbard D. Continuous Glucose Monitoring: A Review of Successes, Challenges, and Opportunities. Diabetes Technol Ther 2016; 18(Suppl. 2): S3-S13.
[] [PMID: 26784127]

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