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
Introduction
Type 1 diabetes is characterized by insulin deficiency due to the loss of pancreatic beta-cells [1]. This type of diabetes is also characterized by high variability in blood glucose [2], [3]. Patients with variable blood glucose readings during routine self-monitoring are at a high risk for severe hypoglycemia [4]. Patients with diabetic microvascular complications also have high glucose variability [5]. Coronary artery calcification, a predictor of coronary events [6], is associated with glucose variability in men with type 1 diabetes [7]. Thus, it is important to clarify clinical parameters that predict glycemic variability.
Insulin secretory capacity, meals and physical activity are associated with glycemic variability [8], [9], [10], [11], [12]. The increment of serum C-peptide (CPR) by an intravenous glucagon stimulation test negatively correlates with the standard deviation (SD) of fasting plasma glucose levels [8]. Patients with low endogenous insulin secretion have a lower M-value of glucose levels compared with insulin-depleted patients [9]. Blood glucose levels after a low-glycemic-index meal were significantly lower than after a high-glycemic-index meal [10]. The quantity of carbohydrate in a meal positively correlates with glycemic variability, including the mean amplitude of glycemic excursions (MAGE) and the SD, as assessed by continuous blood glucose monitoring (CGM) [11]. Post-meal physical activity decreases postprandial glucose levels and improves postprandial glycemic variability compared with post-meal inactivity [12]. All of these factors correlate with glycemic variability in insulin-depleted patients with established type 1 diabetes [1].
Autonomic dysfunction is also a candidate for predicting glycemic variability because it is associated with gastrointestinal motility [12] and counterregulatory hormone secretion [13], both of which correlate with glucose variability [14], [15], [16]. The coefficient of variation of the R-R interval (CVR-R) calculated from electrocardiographs is one of the clinical parameters representing autonomic function that are easily and quantitatively evaluated [17]. CVR-R is associated with both parasympathetic and sympathetic nervous system functions [18]. Based on these facts, we aimed to identify any additional clinical parameters associated with glycemic variability, paying particular attention to autonomic function in insulin-depleted patients with established type 1 diabetes.
Section snippets
Subjects
We studied 31 inpatients (13 males and 18 females) with type 1 diabetes at Osaka University hospital between April 2010 and November 2013. Type 1 diabetes was diagnosed according to the criteria of the Japan Diabetes Society [19].
The patients displayed the following characteristics (mean ± SD): 47.2 ± 16.4 years of age, 18.6 ± 12.8 years duration of the disease, 22.4 ± 3.7 kg/m2 body mass index (BMI), and 8.0 ± 1.5% (63 ± 17 mmol/mol) hemoglobin A1c (HbA1c). The fasting CPR levels, evaluated by CLEIA, were
Glycemic variability evaluated by CGM
CGM was performed 12.4 ± 8.9 days after hospitalization, and the monitoring period lasted for 56.5 ± 15.3 h. The parameters representing glycemic variability for the whole day, daytime and nighttime were as follows, each in corresponding order: SD, 55.9 ± 19.5, 51.8 ± 18.5 and 43.6 ± 21.1 mg/dl; MAGE, 116.4 ± 36.4, 102.3 ± 29.3 and 89.6 ± 44.9 mg/dl; M-value, 20.7 ± 14.6, 24.1 ± 18.7 and 15.7 ± 13.8 mg/dl; and MODD, 55.1 ± 25.1, 55.6 ± 30.5 and 56.4 ± 34.1 mg/dl. Representative data from 24 h CGM of two patients is shown in
Discussion
In this study, we newly demonstrated that CVR-R is a useful clinical parameter for predicting glycemic variability, especially during the nighttime, in insulin-depleted patients with type 1 diabetes. We also showed that nighttime glycemic variability represented by the SD is associated with diabetic polyneuropathy. The insulin-secretory capacity, the content of meals and physical activity, factors that affect glucose variability, were similar in our insulin-depleted patients in a hospital
Conflict of interest statement
The authors declare that they have no conflict of interest in regard to this study.
Financial support
None.
Acknowledgements
S.I. gathered the data, contributed to discussions and wrote the manuscript. J.K., K.J, H.I., A.I., and I.S. contributed to discussions and edited the manuscript.
References (43)
- et al.
Carbohydrate counting accuracy and blood glucose variability in adults with type 1 diabetes
Diabetes Res Clin Pract
(2013) - et al.
Delayed gastric emptying rate in type 1 diabetics with cardiac autonomic neuropathy
J Diabetes Complicat
(2001) - et al.
Spectral analyses of R-R interval and systolic blood pressure in diabetic autonomic neuropathy
J Auton Nerv Syst
(1995) - et al.
Adverse effects of cigarette and noncigarette smoke exposure on the autonomic nervous system: mechanisms and implications for cardiovascular risk
J Am Coll Cardiol
(2014) Diagnosis and classification of diabetes mellitus
Diabetes Care
(2013)- et al.
The importance of HbA1c and glucose variability in patients with type 1 and type 2 diabetes: outcome of continuous glucose monitoring (CGM)
Acta Diabetol
(2012) - et al.
Does glucose variability influence the relationship between mean plasma glucose and HbA1c levels in type 1 and type 2 diabetic patients?
Diabetes Care
(2011) - et al.
Frequency of severe hypoglycemia in insulin-dependent diabtes mellitus can be predicted from self-monitoring blood glucose data
J Clin Endocrinol Metab
(1994) - et al.
Glycemic variability is higher in type 1 diabetes patients with microvascular complications irrespective of glycemic control
Diabetes Technol Ther
(2014) - 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
Circulation
(2003)
Glycaemic variability is associated with coronary artery calcium in men with Type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes study
Diabet Med
Correlation between minimal secretory capacity of pancreatic beta-cells and stability of diabetic control
Diabetes
Endogenous insulin secretion even at a very low level contributes to the stability of blood glucose control in fulminant type 1 diabetes
J Diabetes Investig
Effects of meals with different glycaemic index on postprandial blood glucose response in patients with type 1 diabetes treated with continuos subcutaneous insulin in infusion
Diabet Med
The effect of walking on postprandial glycemic excurision in patients with type 1 diabetes and healthy people
Diabetes Care
Reduced epinephrine secretion and hypoglycemia unawareness in diabetic autonomic neuropathy
Ann Intern Med
Hypoglycemia in patients with type 1 diabetes: epidemiology, pathogenesis, and prevention
Curr Diab Rep
Continuous glucose monitoring in gastroparesis
Dig Dis Sci
Studies of heart rate oscillations in diabetics at rest
Horm Metab Res
Report of the committee on the classification and diagnostic criteria of diabetes mellitus
J Diabetes Investig
Rationale and usefulness of newly devised abbreviated diagnostic creiteria and staging for diabetic polyneuropathy
Diabetes Res Clin Pract
Cited by (16)
Heart rate variability in fetuses of type 1 diabetes pregnancies
2019, Diabetes and MetabolismAssociations of age-adjusted coefficient of variation of R-R intervals with autonomic and peripheral nerve function in non-elderly persons with diabetes
2024, Journal of Diabetes InvestigationThe First Electrophysiological Abnormality in New-onset DM: Autonomic Tests
2022, Noropsikiyatri ArsiviLong-term complications of type 1 diabetes: what do we know and what do we need to understand?
2021, Minerva Pediatrics