Association between glucose variability as assessed by continuous glucose monitoring (CGM) and diabetic retinopathy in type 1 and type 2 diabetes

There is a growing debate in the literature on whether glucose variability contributes, as well as high HbA1c levels and longstanding diabetes, to the onset and progression of diabetic retinopathy (DR) in patients with diabetes types 1 (DM1) and 2 (DM2). Few data, obtained only by self-monitoring of blood glucose, support this hypothesis. We used continuous glucose monitoring (CGM) to investigate the association between DR and glucose variability parameters (SD, CONGA 2, MAGE), acute hyperglycemia (HBGI) and chronic exposure to glucose (AG and AUC tot). We studied 68 patients from 19 to 69 years old, 35 with DM1 and 33 with DM2. The prevalence of retinopathy was 43 % in DM 1 patients and 39 % in DM 2 patients. The values of all indicators were obtained by CGM for 72 h. DR was diagnosed on direct or indirect ophthalmoscopic examination, after inducing mydriasis with tropicamide. HbA1c was measured at the baseline and 6 weeks after CGM to test the stability of the patients’ glycemic control. Univariate analysis showed a close association between DR and duration of diabetes (OR 1.11; 1.04–1.19), intensive insulin therapy (OR 5.6, CI 1.14–27.30), SD (OR 1.03; CI 1.01–1.06) and CONGA 2 (OR 1.02; CI 1.00–1.04)—both indicators of variability and HBGI (OR 1.1, CI 1.01–1.18)—a parameter reflecting acute hyperglycemia. There was no significant correlation with HbA1c (p = 0.070). Multivariate regression analysis showed that disease duration is the parameter most significantly correlating with DR (OR 1.05; 1.01–1.15). These results reinforce the evidence that longstanding disease is the factor most closely associated with DR. Our data also suggest, however, that glucose variability—regardless of HbA1c—may also have a role as a risk factor for DR, particularly in the case of acute fluctuations (as represented by CONGA 2 and SD) and acute hyperglycemia (as represented by HBGI).

[1]  A. Rigby,et al.  Effect of Glucose Variability on the Long-Term Risk of Microvascular Complications in Type 1 Diabetes , 2009, Diabetes Care.

[2]  B. Zinman,et al.  Effect of Glycemic Exposure on the Risk of Microvascular Complications in the Diabetes Control and Complications Trial—Revisited , 2008, Diabetes.

[3]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[4]  M. Ihnat,et al.  Clinical review 2: The "metabolic memory": is more than just tight glucose control necessary to prevent diabetic complications? , 2009, The Journal of clinical endocrinology and metabolism.

[5]  David R. Owens,et al.  Glycemic Variability: The Third Component of the Dysglycemia in Diabetes. Is it Important? How to Measure it? , 2008, Journal of diabetes science and technology.

[6]  M. Ihnat,et al.  ‘Glycaemic variability’: a new therapeutic challenge in diabetes and the critical care setting , 2010, Diabetic medicine : a journal of the British Diabetic Association.

[7]  A. Vazeou Continuous blood glucose monitoring in diabetes treatment. , 2011, Diabetes research and clinical practice.

[8]  P. Lucidi,et al.  Optimizing the replacement of basal insulin in type 1 diabetes mellitus: no longer an elusive goal in the post-NPH era. , 2011, Diabetes technology & therapeutics.

[9]  W. F. Taylor,et al.  Mean Amplitude of Glycemic Excursions, a Measure of Diabetic Instability , 1970, Diabetes.

[10]  B. Klein,et al.  Overview of epidemiologic studies of diabetic retinopathy. , 2007, Ophthalmic epidemiology.

[11]  R. Holman,et al.  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. , 1998 .

[12]  Matthew D. Davis,et al.  Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. , 2003, Ophthalmology.

[13]  E. Chew Epidemiology of diabetic retinopathy. , 2003, Hospital medicine.

[14]  R. Klein,et al.  The Epidemiology of Diabetic Retinopathy , 2008 .

[15]  D. Klonoff Continuous glucose monitoring: roadmap for 21st century diabetes therapy. , 2005, Diabetes care.

[16]  L. V. Van Gaal,et al.  A Review of Current Evidence with Continuous Glucose Monitoring in Patients with Diabetes , 2008, Journal of diabetes science and technology.

[17]  David Rodbard,et al.  New and improved methods to characterize glycemic variability using continuous glucose monitoring. , 2009, Diabetes technology & therapeutics.

[18]  G. Krishnarajah,et al.  Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature , 2010, Diabetes, obesity & metabolism.

[19]  Frits Holleman,et al.  Glucose variability; does it matter? , 2010, Endocrine reviews.

[20]  Ferdinando Giacco,et al.  Oxidative stress and diabetic complications. , 2010, Circulation research.

[21]  D. Owens,et al.  The glycemic triumvirate and diabetic complications: is the whole greater than the sum of its component parts? , 2012, Diabetes Research and Clinical Practice.

[22]  E. Bonora,et al.  Is fasting glucose variability a risk factor for retinopathy in people with type 2 diabetes? , 2009, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[23]  C. Hsieh,et al.  Acute and chronic fluctuations in blood glucose levels can increase oxidative stress in type 2 diabetes mellitus , 2012, Acta Diabetologica.

[24]  D. Schoenfeld,et al.  Translating the A1C Assay Into Estimated Average Glucose Values , 2008, Diabetes Care.

[25]  R. Hovorka,et al.  Glycemic Variability Correlates Strongly With Postprandialβ-Cell Dysfunction in a Segment of Type 2 Diabetic Patients Using Oral Hypoglycemic Agents , 2009, Diabetes Care.

[26]  I. Benzie,et al.  Relationships among Diabetic Retinopathy, Antioxidants, and Glycemic Control , 2011, Optometry and vision science : official publication of the American Academy of Optometry.

[27]  D. Owens,et al.  International Forum for the Advancement of Diabetes Research and Care, April 29-30, 2011, Athens, Greece. , 2011, Diabetes technology & therapeutics.

[28]  Tien Yin Wong,et al.  Diabetic retinopathy , 2010, The Lancet.

[29]  M. C. Leske,et al.  The prevalence of diabetic retinopathy among adults in the United States. , 2004, Archives of ophthalmology.

[30]  S. Powers,et al.  A comparison of average daily risk range scores for young children with type 1 diabetes mellitus using continuous glucose monitoring and self-monitoring data. , 2012, Diabetes technology & therapeutics.

[31]  Y. Matsuyama,et al.  The effects of fasting plasma glucose variability and time-dependent glycemic control on the long-term risk of retinopathy in type 2 diabetic patients. , 2011, Diabetes research and clinical practice.

[32]  C. McDonnell,et al.  A novel approach to continuous glucose analysis utilizing glycemic variation. , 2005, Diabetes technology & therapeutics.

[33]  M. Stolar Glycemic control and complications in type 2 diabetes mellitus. , 2010, The American journal of medicine.

[34]  H. Hammes,et al.  Diabetic retinopathy in type 1 diabetes—a contemporary analysis of 8,784 patients , 2011, Diabetologia.

[35]  Andrea Mosca,et al.  The importance of HbA1c and glucose variability in patients with type 1 and type 2 diabetes: outcome of continuous glucose monitoring (CGM) , 2012, Acta Diabetologica.

[36]  Grading diabetic retinopathy from stereoscopic color fundus photographs--an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. , 1991, Ophthalmology.