Evaluation of glycemic variability in well-controlled type 2 diabetes mellitus.

AIMS It is necessary to evaluate glucose variability and postprandial hyperglycemia in patients with well-controlled type 2 diabetes mellitus because of the limitations associated with hemoglobin A1c (HbA1c) measurements. We evaluated parameters reflecting postprandial hyperglycemia and glycemic variability in patients with optimal HbA1c. PATIENTS AND METHODS Thirty-nine patients with HbA1c levels below 7% were recruited to the study. A continuous glucose monitoring system (CGMS) was applied for two 72-h periods. 1,5-Anhydroglucitol (1,5-AG) and fructosamine (FA) were measured as parameters for postprandial hyperglycemia and glucose variability. Using CGMS data, the following postprandial hyperglycemia parameters were calculated: mean postprandial maximum glucose (MPMG) and area under the curve for glucose above 180 mg/dL (AUC-180). To measure glycemic variability, we calculated mean amplitude of glucose excursion (MAGE) using a classical (MAGEc) and new method (MAGE group of sign [MAGEgos]). RESULTS The baseline HbA1c level was 6.3±0.3%. The mean MPMG was 10.34±1.84 mmol/L, and the mean AUC-180 was 0.17±0.23 mmol/L/day. The mean MAGEgos was 3.27±1.29 mmol/L, and MAGEc was 4.30±1.43 mmol/L, indicating glycemic variability in our patients. The mean levels of 1,5-AG and FA were 16.7±7.4 μg/mL and 273.0±22.5 μmol/L, respectively. In a correlation analysis, FA was significantly correlated with MPMG, AUC-180, MAGEgos, and MAGEc. In contrast, 1,5-AG was only correlated with AUC-180. CONCLUSIONS This study demonstrated postprandial hyperglycemia and glycemic variability in subjects with well-controlled diabetes. FA may reflect postprandial hyperglycemia and glycemic variability, but 1,5-AG may be of limited value for assessing glucose variability in patients with well-controlled type 2 diabetes mellitus.

[1]  Helen Brown,et al.  Applied Mixed Models in Medicine , 2000, Technometrics.

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

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

[4]  H. Tian,et al.  Glucose fluctuations in subjects with normal glucose tolerance, impaired glucose regulation and newly diagnosed type 2 diabetes mellitus , 2012, Clinical endocrinology.

[5]  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.

[6]  Boyd,et al.  Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. , 2002, Clinical chemistry.

[7]  K. Dungan.  1,5-anhydroglucitol (GlycoMark™) as a marker of short-term glycemic control and glycemic excursions , 2008, Expert review of molecular diagnostics.

[8]  T. Yamanouchi,et al.  Estimation of plasma glucose fluctuation with a combination test of hemoglobin A1c and 1,5-anhydroglucitol. , 1992, Metabolism: clinical and experimental.

[9]  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.

[10]  Yasushi Tanaka,et al.  Relationship between clinical markers of glycemia and glucose excursion evaluated by continuous glucose monitoring (CGM). , 2010, Endocrine journal.

[11]  N. Mittman,et al.  Serum fructosamine versus glycosylated hemoglobin as an index of glycemic control, hospitalization, and infection in diabetic hemodialysis patients. , 2010, Kidney international. Supplement.

[12]  S. Yamamoto,et al.  Fully enzymatic method for determining 1,5-anhydro-D-glucitol in serum. , 1994, Clinical chemistry.

[13]  Baldev M Singh,et al.  Clinical impact of variability in HbA1c as assessed by simultaneously measuring fructosamine and use of error grid analysis , 2008, Annals of clinical biochemistry.

[14]  Y. Akanuma,et al.  Plasma 1,5-Anhydro-D-Glucitol as New Clinical Marker of Glycemic Control in NIDDM Patients , 1989, Diabetes.

[15]  A. Ceriello.  Postprandial hyperglycemia and diabetes complications: is it time to treat? , 2005, Diabetes.

[16]  David Rodbard,et al.  Interpretation of continuous glucose monitoring data: glycemic variability and quality of glycemic control. , 2009, Diabetes technology & therapeutics.

[17]  Peter A Baghurst,et al.  Calculating the mean amplitude of glycemic excursion from continuous glucose monitoring data: an automated algorithm. , 2011, Diabetes technology & therapeutics.

[18]  A. Peiris,et al.  Fructosamine--an underutilized tool in diabetes management: case report and literature review. , 2008, Tennessee medicine : journal of the Tennessee Medical Association.

[19]  E. Shultz,et al.  Glycosylated serum proteins and glycosylated hemoglobin in the assessment of glycemic control in insulin-dependent and non-insulin-dependent diabetes mellitus. , 1993, Metabolism: clinical and experimental.

[20]  H. Kaneto,et al.  Glycated albumin is a better indicator for glucose excursion than glycated hemoglobin in type 1 and type 2 diabetes. , 2008, Endocrine journal.

[21]  Sun Wook Cho,et al.  Evaluation of 1,5-anhydroglucitol as a marker for glycemic variability in patients with type 2 diabetes mellitus , 2013, Acta Diabetologica.

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

[23]  H. Funato,et al.  Clinical usefulness of serum 1,5-anhydroglucitol in monitoring glycaemic control , 1996, The Lancet.

[24]  Darrell M. Wilson,et al.  The interrelationships of glycemic control measures: HbA1c, glycated albumin, fructosamine, 1,5‐anhydroglucitrol, and continuous glucose monitoring , 2011, Pediatric diabetes.

[25]  A. Ohnishi,et al.  Structural and glycation site changes of albumin in diabetic patient with very high glycated albumin. , 2007, Clinica chimica acta; international journal of clinical chemistry.

[26]  J. Baynes,et al.  Nonenzymatic glucosylation of rat albumin. Studies in vitro and in vivo. , 1979, The Journal of biological chemistry.

[27]  M. True.  Circulating Biomarkers of Glycemia in Diabetes Management and Implications for Personalized Medicine , 2009, Journal of diabetes science and technology.

[28]  Marco Orsini Federici,et al.  Group of Signs: A New Method to Evaluate Glycemic Variability , 2008, Journal of diabetes science and technology.

[29]  J. McGill,et al.  Serum 1,5-anhydroglucitol (GlycoMark ): a short-term glycemic marker. , 2003, Diabetes technology & therapeutics.

[30]  M. Shichiri,et al.  New Indices for Predicting Glycaemic Variability , 2012, PloS one.

[31]  C. Ludvigsen,et al.  Fructosamine Clinical Usefulness and Determination of Reference Ranges , 1989 .

[32]  Hiroyuki Sano,et al.  Glycated albumin to glycated hemoglobin ratio is a sensitive indicator of blood glucose variability in patients with fulminant type 1 diabetes. , 2012, Internal medicine.

[33]  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.

[34]  R. Littell.  SAS System for Mixed Models , 1996 .

[35]  H. Winiarska,et al.  The Application of Plasma 1,5-Anhydro-D-glucitol for Monitoring Type 2 Diabetic Patients , 2005, Disease markers.