The assessment of glycemic variability and its impact on diabetes-related complications: an overview.

There is a growing body of evidence that the sole use of hemoglobin A1c is insufficient to adequately reflect the metabolic situation of patients with diabetes mellitus. The risk of developing diabetes-related complications apparently not only depends on the long-term stability of glucose values, but also on the presence or occurrence of short-term glycemic peaks and nadirs lasting for minutes or hours during a day. This leads to the phenomenon of glycemic variability. This article reviews the existing evidence for the clinical relevance of short-term glucose variations and the currently available different means of measuring glycemic variability.

[1]  William L Clarke,et al.  Quantifying temporal glucose variability in diabetes via continuous glucose monitoring: mathematical methods and clinical application. , 2005, Diabetes technology & therapeutics.

[2]  M. Hanefeld,et al.  Post‐challenge hyperglycaemia relates more strongly than fasting hyperglycaemia with carotid intima‐media thickness: the RIAD Study , 2000, Diabetic medicine : a journal of the British Diabetic Association.

[3]  P. Wilson,et al.  Effects of Prandial Versus Fasting Glycemia on Cardiovascular Outcomes in Type 2 Diabetes: The HEART2D trial , 2009, Diabetes Care.

[4]  Markolf Hanefeld,et al.  Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. , 2003, JAMA.

[5]  A. Ceriello The possible role of postprandial hyperglycaemia in the pathogenesis of diabetic complications , 2003, Diabetologia.

[6]  J. Pugh,et al.  Minority advantage in diabetic end-stage renal disease survival on hemodialysis: due to different proportions of diabetic type? , 1996, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[7]  R. Landgraf The relationship of postprandial glucose to HbA1c , 2004, Diabetes/metabolism research and reviews.

[8]  B. Zinman,et al.  Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. , 2005, The New England journal of medicine.

[9]  A Sekikawa,et al.  Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. , 1999, Diabetes care.

[10]  J. Tuomilehto,et al.  Two-hour glucose is a better risk predictor for incident coronary heart disease and cardiovascular mortality than fasting glucose. , 2002, European heart journal.

[11]  P. Home,et al.  The effect of improved post-prandial blood glucose control on post-prandial metabolism and markers of vascular risk in people with Type 2 diabetes. , 2005, Diabetes research and clinical practice.

[12]  S. Yusuf,et al.  The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. , 1999, Diabetes care.

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

[14]  R. Holman,et al.  UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes. , 2002, Diabetes care.

[15]  D. Singer,et al.  The clinical information value of the glycosylated hemoglobin assay. , 1984, The New England journal of medicine.

[16]  D. Singer,et al.  Tests of glycemia in diabetes mellitus. Their use in establishing a diagnosis and in treatment. , 1989, Annals of internal medicine.

[17]  M Sculpher,et al.  A randomised controlled trial to compare minimally invasive glucose monitoring devices with conventional monitoring in the management of insulin-treated diabetes mellitus (MITRE). , 2009, Health technology assessment.

[18]  G. Gill,et al.  Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes—the ‘dead in bed’ syndrome revisited , 2008, Diabetologia.

[19]  T. Nakagami,et al.  Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin , 2004, Diabetologia.

[20]  Takeo Kato,et al.  Impaired glucose tolerance is a risk factor for stroke in a Japanese sample--the Funagata study. , 2008, Metabolism: clinical and experimental.

[21]  A. Dyer,et al.  One-hour postload plasma glucose and risks of fatal coronary heart disease and stroke among nondiabetic men and women: the Chicago Heart Association Detection Project in Industry (CHA) Study. , 1997, Journal of clinical epidemiology.

[22]  Benjamin Cheong,et al.  Association of hypoglycemia and cardiac ischemia: a study based on continuous monitoring. , 2002, Diabetes care.

[23]  H. van Lenthe,et al.  A randomized clinical trial comparing the effect of basal insulin and inhaled mealtime insulin on glucose variability and oxidative stress , 2009, Diabetes, obesity & metabolism.

[24]  B. Guerci La variabilité glycémique asymptomatique: comment l'évaluer et quelle est son incidence clinique ? , 2003 .

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

[26]  M. Emoto,et al.  Impact of Glycemic Control on Survival of Diabetic Patients on Chronic Regular Hemodialysis , 2006, Diabetes Care.

[27]  Lawrence A Leiter,et al.  Postprandial glucose regulation: new data and new implications. , 2005, Clinical therapeutics.

[28]  R. DeFronzo,et al.  Stimulation of Counterregulatory Hormonal Responses in Diabetic Man by a Fall in Glucose Concentration , 1980, Diabetes.

[29]  R. Kronmal,et al.  Fasting and 2-hour postchallenge serum glucose measures and risk of incident cardiovascular events in the elderly: the Cardiovascular Health Study. , 2002, Archives of internal medicine.

[30]  E. Araki,et al.  Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. , 1995, Diabetes research and clinical practice.

[31]  Bruce Buckingham,et al.  Real-time continuous glucose monitoring , 2007, Current opinion in endocrinology, diabetes, and obesity.

[32]  K. Shima,et al.  Kinetics of HbA1c, Glycated Albumin, and Fructosamine and Analysis of Their Weight Functions Against Preceding Plasma Glucose Level , 1995, Diabetes Care.

[33]  H. Woerle,et al.  Diagnostic and therapeutic implications of relationships between fasting, 2-hour postchallenge plasma glucose and hemoglobin a1c values. , 2004, Archives of internal medicine.

[34]  G Anfossi,et al.  Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. , 2006, The Journal of clinical endocrinology and metabolism.

[35]  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.

[36]  Hanqing Cao,et al.  Blood Glucose Variability is Associated with Mortality in the Surgical Intensive Care Unit , 2008, The American surgeon.

[37]  M. Hanefeld,et al.  Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up , 1996, Diabetologia.

[38]  J. A. Hunt,et al.  Variation of Postprandial Plasma Glucose, Palatability, and Symptoms Associated With a Standardized Mixed Test Meal Versus 75 g Oral Glucose , 1998, Diabetes Care.

[39]  H. Kaneto,et al.  Postprandial hyperglycemia is a better predictor of the progression of diabetic retinopathy than HbA1c in Japanese type 2 diabetic patients. , 2005, Diabetes care.

[40]  M. Hanefeld,et al.  Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. , 2004, European heart journal.

[41]  R J Jarrett,et al.  Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study. , 1983, British medical journal.

[42]  Mai-Szu Wu,et al.  Poor pre-dialysis glycaemic control is a predictor of mortality in type II diabetic patients on maintenance haemodialysis. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[43]  C. Saudek,et al.  Is HbA(1c) affected by glycemic instability? , 2003, Diabetes care.

[44]  Martin J Shipley,et al.  Relation between blood glucose and coronary mortality over 33 years in the Whitehall Study. , 2006, Diabetes care.

[45]  J. Shaw,et al.  Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality , 1999, Diabetologia.

[46]  I. Holme,et al.  Nonfasting serum glucose and the risk of fatal stroke in diabetic and nondiabetic subjects. 18-year follow-up of the Oslo Study. , 1995, Stroke.

[47]  J. Stamler,et al.  Relationship of Postload Plasma Glucose to Mortality With 19-Yr Follow-Up. Comparison of one versus two plasma glucose measurements in the Chicago Peoples Gas Company Study , 1992, Diabetes Care.

[48]  H Hanaire-Broutin,et al.  Value and limitations of the Continuous Glucose Monitoring System in the management of type 1 diabetes. , 2006, Diabetes & metabolism.

[49]  Darren K Mcguire,et al.  Association between hyper- and hypoglycaemia and 2 year all-cause mortality risk in diabetic patients with acute coronary events. , 2005, European heart journal.

[50]  Daniel J Cox,et al.  Algorithmic evaluation of metabolic control and risk of severe hypoglycemia in type 1 and type 2 diabetes using self-monitoring blood glucose data. , 2003, Diabetes technology & therapeutics.

[51]  L. Bouter,et al.  Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study , 1999, Diabetologia.

[52]  A. Shapiro,et al.  Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. , 2004, Diabetes.

[53]  S. Wannamethee,et al.  Nonfasting serum glucose and insulin concentrations and the risk of stroke. , 1999, Stroke.

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

[55]  H. Lapinski,et al.  Continuous glucose monitoring in patients with type 2 diabetes: Why? When? Whom? , 2007, Diabetes & metabolism.

[56]  Grant D. Huang,et al.  Glucose control and vascular complications in veterans with type 2 diabetes. , 2009, The New England journal of medicine.

[57]  E. Barrett-Connor,et al.  Isolated Postchallenge Hyperglycemia and the Risk of Fatal Cardiovascular Disease in Older Women and Men: The Rancho Bernardo Study , 1998, Diabetes Care.

[58]  Michael E. Miller,et al.  Effects of intensive glucose lowering in type 2 diabetes. , 2008, The New England journal of medicine.

[59]  I. Hirsch,et al.  Should minimal blood glucose variability become the gold standard of glycemic control? , 2005, Journal of diabetes and its complications.

[60]  M. Brownlee Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[61]  J. Schlichtkrull,et al.  [M-VALUE, AN INDEX FOR BLOOD SUGAR CONTROL IN DIABETICS]. , 1964, Ugeskrift for laeger.

[62]  Diederick Grobbee,et al.  Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. , 2008, The New England journal of medicine.

[63]  N. Chaturvedi,et al.  Risk factors, ethnic differences and mortality associated with lower-extremity gangrene and amputation in diabetes. The WHO multinational study of vascular disease in diabetes , 2001, Diabetologia.

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

[65]  Mathijs Vogelzang,et al.  Hyperglycaemic index as a tool to assess glucose control: a retrospective study , 2004, Critical care.

[66]  A. Taket,et al.  How far does screening women for domestic (partner) violence in different health-care settings meet criteria for a screening programme? Systematic reviews of nine UK National Screening Committee criteria. , 2009, Health technology assessment.

[67]  P. O'Brien,et al.  The relation of glycaemia to the risk of development and progression of retinopathy in the Diabetic Control and Complications Trial , 2001, Diabetologia.

[68]  J. Levy,et al.  A method for assessing quality of control from glucose profiles , 2007, Diabetic medicine : a journal of the British Diabetic Association.

[69]  J. Neaton,et al.  Diabetes, Other Risk Factors, and 12-Yr Cardiovascular Mortality for Men Screened in the Multiple Risk Factor Intervention Trial , 1993, Diabetes Care.

[70]  Y. Terauchi,et al.  The rationale for paired pre- and postprandial self-monitoring of blood glucose: the role of glycemic variability in micro- and macrovascular risk , 2007, Current medical research and opinion.

[71]  Michael Brownlee,et al.  Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. , 2006, JAMA.

[72]  R. Holman,et al.  Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study , 2000, BMJ : British Medical Journal.

[73]  P. Libby,et al.  The effect of hypoglycemia on myocardial ischemic injury during acute experimental coronary artery occlusion. , 1975, Circulation.

[74]  S. Saydah,et al.  Postchallenge hyperglycemia and mortality in a national sample of U.S. adults. , 2001, Diabetes care.

[75]  A. Dyer,et al.  Diabetes, Asymptomatic Hyperglycemia, and 22-Year Mortality in Black and White Men: The Chicago Heart Association Detection Project in Industry Study , 1997, Diabetes Care.

[76]  Rinaldo Bellomo,et al.  Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients , 2006, Anesthesiology.

[77]  Wójcicki Jm,et al.  J"-index. A new proposition of the assessment of current glucose control in diabetic patients. , 1995 .

[78]  K. Yano,et al.  Glucose intolerance and 23-year risk of coronary heart disease and total mortality: the Honolulu Heart Program. , 1999, Diabetes care.

[79]  Ralph B D'Agostino,et al.  Fasting and postchallenge glycemia and cardiovascular disease risk: the Framingham Offspring Study. , 2002, Diabetes care.

[80]  D. Cox,et al.  Symmetrization of the Blood Glucose Measurement Scale and Its Applications , 1997, Diabetes Care.

[81]  M. Hanefeld,et al.  Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. , 2000, Diabetes care.

[82]  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.

[83]  J. Krinsley,et al.  Glycemic variability: A strong independent predictor of mortality in critically ill patients* , 2008, Critical care medicine.

[84]  W. F. Taylor,et al.  Day-to-day variation of continuously monitored glycaemia: A further measure of diabetic instability , 1972, Diabetologia.

[85]  Beverley Balkau,et al.  High Blood Glucose Concentration Is a Risk Factor for Mortality in Middle-Aged Nondiabetic Men: 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study , 1998, Diabetes Care.

[86]  R. Holman,et al.  10-year follow-up of intensive glucose control in type 2 diabetes. , 2008, The New England journal of medicine.

[87]  Bruce Buckingham,et al.  Association of Hypoglycemia, Hyperglycemia, and Glucose Variability With Morbidity and Death in the Pediatric Intensive Care Unit , 2006, Pediatrics.

[88]  T. Shoji,et al.  Glycemic control is a predictor of survival for diabetic patients on hemodialysis. , 2001, Diabetes care.

[89]  O. Pedersen,et al.  Effect of a multifactorial intervention on mortality in type 2 diabetes. , 2008, The New England journal of medicine.