Glycemic Variability and Vascular Complications in Patients with Type 2 Diabetes Mellitus

Abstract Background: Presence of macro- and microvascular complications in patients with diabetes mellitus (DM) is not only related to chronic hyperglycemia represented by glycated hemoglobin (HbA1c) but also to acute glycemic fluctuations (glycemic variability, GV). The association between GV and DM complications is not completely clear. Aim of our study was to evaluate GV by MAGE index in patients with type 2 DM and to verify association of MAGE index with presence of macro- and microvascular DM complications. Methods: 99 patients with type 2 DM were included in the study. Every patient had done big glycemic profile, from which MAGE index was calculated. Anthropometric measurements, evaluation of HbA1c and fasting plasma glucose (FPG) and assessment for macrovascular (coronary artery disease – CAD; peripheral artery disease – PAD; cerebral stroke – CS) and microvascular (diabetic retinopathy – DR; nephropathy – DN; peripheral neuropathy – DPPN) DM complications were done. Results: Average MAGE index value was 5.15 ± 2.88 mmol/l. We found no significant differences in MAGE index values in subgroups according to presence of neither CAD, CS, PAD nor DR, DN, DPPN. MAGE index value significantly positively correlated with FPG (p < 0.01) and HbA1c (p < 0.001) and negatively with weight (p < 0.05). Conclusion: In our study we failed to show association of MAGE index with presence of macrovascular and microvascular complications in patients with type 2 DM. However, this negative result does not necessarily disprove importance of glycemic variability in pathogenesis of diabetic complications.

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

[2]  I. Hirsch,et al.  Beyond hemoglobin A1c--need for additional markers of risk for diabetic microvascular complications. , 2010, JAMA.

[3]  G. Filippatos,et al.  2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. , 2020, European heart journal.

[4]  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 .

[5]  R. Testa,et al.  Oscillating Glucose Is More Deleterious to Endothelial Function and Oxidative Stress Than Mean Glucose in Normal and Type 2 Diabetic Patients , 2008, Diabetes.

[6]  Z. Li,et al.  Association of glycemic variability and the presence and severity of coronary artery disease in patients with type 2 diabetes , 2011, Cardiovascular diabetology.

[7]  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.

[8]  J. Mastrototaro,et al.  Continuous glucose monitoring used to adjust diabetes therapy improves glycosylated hemoglobin: a pilot study. , 1999, Diabetes research and clinical practice.

[9]  E. Kilpatrick,et al.  Glycemic Variability: Both Sides of the Story , 2013, Diabetes Care.

[10]  L. Norgren,et al.  Inter-society consensus for the management of peripheral arterial disease. , 2007, International angiology : a journal of the International Union of Angiology.

[11]  G. Paolisso,et al.  Reduction of Oxidative Stress and Inflammation by Blunting Daily Acute Glucose Fluctuations in Patients With Type 2 Diabetes , 2012, Diabetes Care.

[12]  M. Muggeo,et al.  Plasma Glucose Levels Throughout the Day and HbA 1 c Interrelationships in Type 2 Diabetes , 2001 .

[13]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[14]  G. Paolisso,et al.  Decreased carotid atherosclerotic process by control of daily acute glucose fluctuations in diabetic patients treated by DPP-IV inhibitors. , 2013, Atherosclerosis.

[15]  L. M. Lou-Arnal,et al.  Fasting plasma glucose variability as a risk factor of retinopathy in Type 2 diabetic patients. , 2003, Journal of diabetes and its complications.

[16]  A. Rigby,et al.  Glucose variability does not contribute to the development of peripheral and autonomic neuropathy in type 1 diabetes: data from the DCCT , 2009, Diabetologia.

[17]  Pratik Choudhary,et al.  Normal reference range for mean tissue glucose and glycemic variability derived from continuous glucose monitoring for subjects without diabetes in different ethnic groups. , 2011, Diabetes technology & therapeutics.

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

[19]  S. Tigan,et al.  Glycemic Variability and Type 2 Diabetes Mellitus , 2013 .

[20]  Jean-Paul Cristol,et al.  Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. , 2006, JAMA.

[21]  D. Owens,et al.  Regulation of oxidative stress by glycaemic control: evidence for an independent inhibitory effect of insulin therapy , 2009, Diabetologia.

[22]  S. Goldstein,et al.  A Miniature Fiberoptic pH Sensor Potentially Suitable for Glucose Measurements , 1982, Diabetes Care.

[23]  E. Kilpatrick.  Arguments for and against the Role of Glucose Variability in the Development of Diabetes Complications , 2009, Journal of diabetes science and technology.

[24]  A. Depierre,et al.  Harry Potter in True Translation: Long Live the Original , 2014 .

[25]  J. DeVries,et al.  A Decrease in Glucose Variability Does Not Reduce Cardiovascular Event Rates in Type 2 Diabetic Patients After Acute Myocardial Infarction , 2011, Diabetes Care.

[26]  Y. Matsuyama,et al.  The effect of fasting plasma glucose variability on the risk of retinopathy in type 2 diabetic patients: retrospective long-term follow-up. , 2010, Diabetes research and clinical practice.

[27]  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.

[28]  R. de Marco,et al.  Long-term instability of fasting plasma glucose, a novel predictor of cardiovascular mortality in elderly patients with non-insulin-dependent diabetes mellitus: the Verona Diabetes Study. , 1997, Circulation.

[29]  P. Sönksen,et al.  A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population , 1993, Diabetologia.

[30]  L. Sestoft.  Fructose and the dietary therapy of diabetes mellitus , 1979, Diabetologia.

[31]  Zhao Li,et al.  Impact of Admission Glycemic Variability, Glucose, and Glycosylated Hemoglobin on Major Adverse Cardiac Events After Acute Myocardial Infarction , 2013, Diabetes Care.

[32]  E. Bonora,et al.  Long-term instability of fasting plasma glucose predicts mortality in elderly NIDDM patients: the Verona Diabetes Study , 1995, Diabetologia.

[33]  B. Kasiske,et al.  KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease Foreword , 2013 .

[34]  L. Monnier,et al.  Glycemic Variability , 2008, Diabetes Care.

[35]  D. Trence,et al.  Glycemic Variability: Looking Beyond the A1C , 2012, Diabetes Spectrum.

[36]  Chia-Ing Li,et al.  Variation of fasting plasma glucose: a predictor of mortality in patients with type 2 diabetes. , 2012, The American journal of medicine.

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

[38]  J. DeVries,et al.  Glucose fluctuations and activation of oxidative stress in patients with type 1 diabetes , 2007, Diabetologia.

[39]  Paola Palazzo,et al.  Impact of Glycemic and Blood Pressure Variability on Surrogate Measures of Cardiovascular Outcomes in Type 2 Diabetic Patients , 2011, Diabetes Care.

[40]  P. Valensi,et al.  Continuous glucose profiles with vildagliptin versus sitagliptin in add-on to metformin: results from the randomized Optima study. , 2012, Diabetes & metabolism.

[41]  Mathias M. Müller,et al.  Consensus Statement on the Worldwide Standardization of the Hemoglobin A1C Measurement , 2007, Diabetes Care.

[42]  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.

[43]  Paul Zimmet,et al.  The metabolic syndrome—a new worldwide definition , 2005, The Lancet.