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.

AIMS In type 1 diabetic patients, insulin secretory capacity, meals and physical activity correlate with glycemic variability. Autonomic function associated with gastrointestinal motility and counterregulatory hormone secretion is another candidate which correlates with glucose variability. The aim of this study is to clarify a new clinical parameter associated with glycemic variability in insulin-depleted patients with type 1 diabetes. METHODS We studied 31 inpatients with type 1 diabetes. We evaluated glycemic variability calculated by continuous glucose monitoring, clinical parameters and the coefficient of variation of R-R interval (CVR-R). Glycemic variability was also assessed during the daytime and nighttime. RESULTS The CVR-R showed a significant negative correlation with the whole-day standard deviation (SD) (r = -0.50, p = 0.007), mean amplitude of glycemic excursions (MAGE) (r = -0.47, p=0.011), M-value (r = -0.38, p = 0.048) and mean of daily differences (MODD) (r = -0.59, p = 0.001). The CVR-R also showed a significant negative correlation with the nighttime SD (r = -0.59, p = 0.001), MAGE (r = -0.47, p=0.011), M-value (r = -0.53, p = 0.004) and MODD (r = -0.65, p = 0.0003). And furthermore, the CVR-R also showed a significant negative correlation with the daytime SD (r = -0.44, p = 0.019) and MAGE (r = -0.50, p = 0.006), but not with the daytime M-value or MODD. The nighttime SD was significantly higher in patients with diabetic polyneuropathy than in patients without it (p = 0.016), while the CVR-R was significantly lower in patients with polyneuropathy than in patients without it (p = 0.009). CONCLUSIONS CVR-R is closely correlated with glycemic variability, especially during nighttime, in insulin-depleted patients with type 1 diabetes. Measuring CVR-R may help us to presume the degree of glycemic variability in those patients.

[1]  M. Irigoyen,et al.  Low-dose Enalapril Reduces Angiotensin II and Attenuates Diabetic-induced Cardiac and Autonomic Dysfunctions , 2012, Journal of cardiovascular pharmacology.

[2]  S. Watanabe,et al.  Spectral analyses of R-R interval and systolic blood pressure in diabetic autonomic neuropathy. , 1995, Journal of the autonomic nervous system.

[3]  G. Heger,et al.  Weak relationship between symptom perception and objective hypoglycaemia-induced changes of autonomic function in hypoglycaemia unawareness in diabetes , 1998, Acta Diabetologica.

[4]  Jacqueline Ryder,et al.  Influence of caffeine on heart rate variability in patients with long-standing type 1 diabetes. , 2004, Diabetes care.

[5]  Hiroyuki Sano,et al.  Erratum to: Glycated albumin as a useful clinical biomarker for glycemic variability in type 1 diabetes assessed by continuous glucose monitoring , 2013, Diabetology International.

[6]  B. Capaldo,et al.  Effects of meals with different glycaemic index on postprandial blood glucose response in patients with Type 1 diabetes treated with continuous subcutaneous insulin infusion , 2011, Diabetic medicine : a journal of the British Diabetic Association.

[7]  R. Rizza,et al.  Measurements of Glucose Control , 1987, Diabetes Care.

[8]  A. Kashiwagi,et al.  Rationale and usefulness of newly devised abbreviated diagnostic criteria and staging for diabetic polyneuropathy. , 2007, Diabetes research and clinical practice.

[9]  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.

[10]  S. Dagogo-Jack,et al.  Hypoglycemia in Patients with Type 1 Diabetes: Epidemiology, Pathogenesis, and Prevention , 2013, Current Diabetes Reports.

[11]  D. Schoenfeld,et al.  Does Glucose Variability Influence the Relationship Between Mean Plasma Glucose and HbA1c Levels in Type 1 and Type 2 Diabetic Patients? , 2011, Diabetes Care.

[12]  Kiang Liu,et al.  Electron-Beam Tomography Coronary Artery Calcium and Cardiac Events: A 37-Month Follow-Up of 5635 Initially Asymptomatic Low- to Intermediate-Risk Adults , 2003, Circulation.

[13]  R. Fisher,et al.  Continuous Glucose Monitoring in Gastroparesis , 2011, Digestive Diseases and Sciences.

[14]  Kohjiro Ueki,et al.  Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus , 2010, Journal of diabetes investigation.

[15]  M. Rewers,et al.  Glycaemic variability is associated with coronary artery calcium in men with Type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes study , 2010, Diabetic medicine : a journal of the British Diabetic Association.

[16]  A. Brazeau,et al.  Carbohydrate counting accuracy and blood glucose variability in adults with type 1 diabetes. , 2013, Diabetes research and clinical practice.

[17]  Claudio Cobelli,et al.  The Effect of Walking on Postprandial Glycemic Excursion in Patients With Type 1 Diabetes and Healthy People , 2012, Diabetes Care.

[18]  G. Targher,et al.  Relationship Between Abnormal Microvolt T‐Wave Alternans and Poor Glycemic Control in Type 2 Diabetic Patients , 2007, Pacing and clinical electrophysiology : PACE.

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

[20]  M. Hanefeld,et al.  Relationship Between Hypoglycemic Episodes and Ventricular Arrhythmias in Patients With Type 2 Diabetes and Cardiovascular Diseases: Silent Hypoglycemias and Silent Arrhythmias , 2014, Diabetes Care.

[21]  P. Nilsson,et al.  Delayed gastric emptying rate in Type 1 diabetics with cardiac autonomic neuropathy. , 2001, Journal of diabetes and its complications.

[22]  H. Middlekauff,et al.  Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: mechanisms and implications for cardiovascular risk. , 2014, Journal of the American College of Cardiology.

[23]  L. Eberly,et al.  Hypoglycemia-associated autonomic failure in healthy humans: comparison of two vs three periods of hypoglycemia on hypoglycemia-induced counterregulatory and symptom response 5 days later. , 2014, The Journal of clinical endocrinology and metabolism.

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

[25]  J. Terasaki,et al.  Endogenous insulin secretion even at a very low level contributes to the stability of blood glucose control in fulminant type 1 diabetes , 2010, Journal of diabetes investigation.

[26]  D G Schlundt,et al.  Frequency of severe hypoglycemia in insulin-dependent diabetes mellitus can be predicted from self-monitoring blood glucose data. , 1994, The Journal of clinical endocrinology and metabolism.

[27]  D. Lucini,et al.  Exercise might improve cardiovascular autonomic regulation in adolescents with type 1 diabetes , 2013, Acta Diabetologica.

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

[29]  T. Miura,et al.  Does glycemic control reverse dispersion of ventricular repolarization in type 2 diabetes? , 2014, Cardiovascular Diabetology.

[30]  R. Witkamp,et al.  The Biphasic Effects of Moderate Alcohol Consumption with a Meal on Ambiance-Induced Mood and Autonomic Nervous System Balance: A Randomized Crossover Trial , 2014, PloS one.

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

[32]  D. Aronson Pharmacologic modulation of autonomic tone: implications for the diabetic patient , 1997, Diabetologia.

[33]  P. Cryer,et al.  Lactate and the Mechanism of Hypoglycemia-Associated Autonomic Failure in Diabetes , 2013, Diabetes.

[34]  H. Lapinski,et al.  Short and Long Term Effects of Radioiodine and Antithyroid Drugs on T4 Binding Proteins, Free T4 and T3, during Graves' Disease Therapy , 1977, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[35]  P. Cryer,et al.  Mechanisms of hypoglycemia-associated autonomic failure in diabetes. , 2013, The New England journal of medicine.

[36]  R. Hoeldtke,et al.  Reduced epinephrine secretion and hypoglycemia unawareness in diabetic autonomic neuropathy. , 1982, Annals of internal medicine.

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

[38]  Kohjiro Ueki,et al.  Report of the Committee on the Classification and Diagnostic Criteria of Diabetes Mellitus , 2010, Journal of diabetes investigation.

[39]  D. Shannon,et al.  Aging of modulation of heart rate. , 1987, The American journal of physiology.

[40]  H. Ikegami,et al.  Correlation Between Minimal Secretory Capacity of Pancreatic β-Cells and Stability of Diabetic Control , 1988, Diabetes.

[41]  W. Lehmacher,et al.  Studies of heart rate oscillations in diabetics at rest. , 1980, Hormone and metabolic research. Supplement series.

[42]  Hiroshi Ito,et al.  International clinical harmonization of glycated hemoglobin in Japan: From Japan Diabetes Society to National Glycohemoglobin Standardization Program values , 2012, Journal of diabetes investigation.