Glucose variability, HbA1c and microvascular complications

Microvascular complications in diabetes are associated with poor long-term diabetes control as measured by HbA1c levels. Glucose fluctuations are related to oxidative stress, endothelial dysfunction, and inflammation, factors traditionally associated with the pathogenesis of vascular damage. Glucose variability has been associated with macrovascular disease in some studies but any association with microvascular disease remains controversial. This overview summarizes recent findings in the field of glucose variability and its possible relationship with retinopathy, nephropathy and neuropathy. It is concluded that randomized prospective follow-up trials could possibly help estimate whether short-term glucose variability should be considered as an independent risk factor for microvascular complications in diabetes.

[1]  A. Rigby,et al.  A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes , 2008, Diabetes Care.

[2]  M. Orsini Federici,et al.  Assessment of the association between glycemic variability and diabetes-related complications in type 1 and type 2 diabetes. , 2014, Diabetes research and clinical practice.

[3]  B. Jacobs,et al.  Insulin‐induced hypoglycemia decreases single‐unit activity of serotonergic medullary raphe neurons in freely moving cats: relationship to sympathetic and motor output , 2002, The European journal of neuroscience.

[4]  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.

[5]  L. Chuang,et al.  Glycated hemoglobin variability and retinopathy progression in type 1 diabetes: Is month‐to‐moth instability a better predictor? , 2013, Journal of diabetes investigation.

[6]  B. Davis,et al.  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 , 2015, Diabetes Care.

[7]  P. Weston,et al.  The role of continuous subcutaneous insulin infusion therapy in patients with diabetic gastroparesis , 2011, Diabetologia.

[8]  A. Ceriello,et al.  Glucose oscillations, more than constant high glucose, induce p53 activation and a metabolic memory in human endothelial cells , 2011, Diabetologia.

[9]  S. Su,et al.  High glucose induces and activates Toll-like receptor 4 in endothelial cells of diabetic retinopathy , 2015, Diabetology & Metabolic Syndrome.

[10]  E. Ortega,et al.  Vitamin C Further Improves the Protective Effect of Glucagon-Like Peptide-1 on Acute Hypoglycemia-Induced Oxidative Stress, Inflammation, and Endothelial Dysfunction in Type 1 Diabetes , 2013, Diabetes Care.

[11]  J. Zhao,et al.  Relationship between blood glucose fluctuation and macrovascular endothelial dysfunction in type 2 diabetic patients with coronary heart disease. , 2014, European review for medical and pharmacological sciences.

[12]  M. Rutter,et al.  Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis , 2015, Diabetes Care.

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

[14]  Lei Gong,et al.  Fluctuation between Fasting and 2-H Postload Glucose State Is Associated with Glomerular Hyperfiltration in Newly Diagnosed Diabetes Patients with HbA1c < 7% , 2014, PloS one.

[15]  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.

[16]  Kyungdo Han,et al.  Association between hemoglobin A1c variability and subclinical coronary atherosclerosis in subjects with type 2 diabetes. , 2015, Journal of diabetes and its complications.

[17]  J. Škrha,et al.  Glycemic variability is higher in type 1 diabetes patients with microvascular complications irrespective of glycemic control. , 2014, Diabetes technology & therapeutics.

[18]  R. Bergenstal Glycemic Variability and Diabetes Complications: Does It Matter? Simply Put, There Are Better Glycemic Markers! , 2015, Diabetes Care.

[19]  R. Pop-Busui,et al.  Association Between Impaired Cardiovascular Autonomic Function and Hypoglycemia in Patients With Type 1 Diabetes , 2014, Diabetes Care.

[20]  P. Oskarsson,et al.  Can glycaemic variability, as calculated from blood glucose self-monitoring, predict the development of complications in type 1 diabetes over a decade? , 2008, Diabetes & metabolism.

[21]  R. Klein,et al.  Association of 1,5-anhydroglucitol with diabetes and microvascular conditions. , 2014, Clinical chemistry.

[22]  Niansong Wang,et al.  HbA1C Variability and the Risk of Renal Status Progression in Diabetes Mellitus: A Meta-Analysis , 2014, PloS one.

[23]  R. Roeder,et al.  Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia , 2008, The Journal of Experimental Medicine.

[24]  K. Dharmashankar,et al.  Acute Exposure to Low Glucose Rapidly Induces Endothelial Dysfunction and Mitochondrial Oxidative Stress: Role for AMP Kinase , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[25]  Cherng-Ru Hsu,et al.  Glycemic variability and diabetes retinopathy: a missing link. , 2015, Journal of diabetes and its complications.

[26]  A. Kowluru,et al.  Lipotoxicity augments glucotoxicity-induced mitochondrial damage in the development of diabetic retinopathy. , 2015, Investigative ophthalmology & visual science.

[27]  A. Nakhaee,et al.  Insulin-induced hypoglycemia and stress oxidative state in healthy people , 2012, Acta Diabetologica.

[28]  R. Testa,et al.  Short-term high glucose exposure impairs insulin signaling in endothelial cells , 2015, Cardiovascular Diabetology.

[29]  Akihisa Imagawa,et al.  Coefficient of variation of R-R interval closely correlates with glycemic variability assessed by continuous glucose monitoring in insulin-depleted patients with type 1 diabetes. , 2015, Diabetes research and clinical practice.

[30]  L. Niskanen,et al.  Fasting plasma glucose variability as a marker of nocturnal hypoglycemia in diabetes: evidence from the PREDICTIVE study. , 2009, Diabetes research and clinical practice.

[31]  W. Fendler,et al.  Metabolic control and its variability are major risk factors for microalbuminuria in children with type 1 diabetes. , 2014, Endokrynologia Polska.

[32]  S. Shin,et al.  HbA1c variability is associated with microalbuminuria development in type 2 diabetes: a 7-year prospective cohort study , 2012, Diabetologia.

[33]  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.

[34]  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.

[35]  H. Itoh,et al.  Relationships among different glycemic variability indices obtained by continuous glucose monitoring. , 2015, Primary care diabetes.

[36]  Giovanni Sparacino,et al.  Glucose variability indices in type 1 diabetes: parsimonious set of indices revealed by sparse principal component analysis. , 2014, Diabetes technology & therapeutics.

[37]  M. Samsom,et al.  Gastrointestinal motor mechanisms in hyperglycaemia induced delayed gastric emptying in type I diabetes mellitus. , 1997, Gut.

[38]  Michael Brownlee,et al.  The Effect of Glucose Variability on the Risk of Microvascular Complications in Type 1 Diabetes , 2007, Diabetes Care.

[39]  Michael Brownlee,et al.  The pathobiology of diabetic complications: a unifying mechanism. , 2005, Diabetes.

[40]  Eckhard Salzsieder,et al.  Utility of different glycemic control metrics for optimizing management of diabetes. , 2015, World journal of diabetes.

[41]  J. Joung,et al.  Association between the extent of urinary albumin excretion and glycaemic variability indices measured by continuous glucose monitoring , 2015, Diabetic medicine : a journal of the British Diabetic Association.

[42]  D. Giugliano,et al.  Premature ejaculation is associated with glycemic control in Type 1 diabetes. , 2015, The journal of sexual medicine.

[43]  L. Kessler,et al.  Glucose Variability , 2016, Journal of diabetes science and technology.

[44]  Kyu Yeon Hur,et al.  The association between glycemic variability and diabetic cardiovascular autonomic neuropathy in patients with type 2 diabetes , 2015, Cardiovascular Diabetology.

[45]  M. Woodward,et al.  Impact of Visit-to-Visit Glycemic Variability on the Risks of Macrovascular and Microvascular Events and All-Cause Mortality in Type 2 Diabetes: The ADVANCE Trial , 2014, Diabetes Care.

[46]  R. Testa,et al.  Hyperglycemia following recovery from hypoglycemia worsens endothelial damage and thrombosis activation in type 1 diabetes and in healthy controls. , 2014, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[47]  Xiao-hua Wang,et al.  The relationship between glycemic variability and diabetic peripheral neuropathy in type 2 diabetes with well-controlled HbA1c , 2014, Diabetology & Metabolic Syndrome.

[48]  D. Rodbard Evaluating Quality of Glycemic Control , 2014, Journal of diabetes science and technology.

[49]  P. Cryer Severe Hypoglycemia Predicts Mortality in Diabetes , 2012, Diabetes Care.

[50]  A. Zuger A piece of my mind. Both sides of the story. , 1991 .

[51]  C. Forsblom,et al.  HbA1c variability is associated with an increased risk of retinopathy requiring laser treatment in type 1 diabetes , 2013, Diabetologia.

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

[53]  Giuseppe Pugliese,et al.  HbA1c Variability as an Independent Correlate of Nephropathy, but Not Retinopathy, in Patients With Type 2 Diabetes , 2013, Diabetes Care.

[54]  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.

[55]  H. Hammes,et al.  HbA1c Variability as an Independent Risk Factor for Diabetic Retinopathy in Type 1 Diabetes: A German/Austrian Multicenter Analysis on 35,891 Patients , 2014, PloS one.

[56]  U. Bronas,et al.  Reactive Oxygen and Nitrogen Species: Impact on Endothelial Dysfunction , 2015, Nursing research.

[57]  P. Cryer Hypoglycemia: still the limiting factor in the glycemic management of diabetes. , 2008, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[58]  P. Baghurst,et al.  Hypoglycemia, but not glucose variability, relates to vascular function in children with type 1 diabetes. , 2012, Diabetes technology & therapeutics.

[59]  I. Hirsch Glycemic Variability and Diabetes Complications: Does It Matter? Of Course It Does! , 2015, Diabetes Care.

[60]  D. Nathan,et al.  Relationship of Glycated Albumin to Blood Glucose and HbA1c Values and to Retinopathy, Nephropathy, and Cardiovascular Outcomes in the DCCT/EDIC Study , 2013, Diabetes.

[61]  Y. Saisho Glycemic Variability and Oxidative Stress: A Link between Diabetes and Cardiovascular Disease? , 2014, International journal of molecular sciences.

[62]  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.