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

https://doi.org/10.1016/j.diabres.2015.05.021Get rights and content

Highlights

  • Glycemic variability by continuous (glucose) monitoring was evaluated in type 1 diabetes.

  • CVR-R showed a significant negative correlation with glycemic variability.

  • CVR-R was also closely correlated with nighttime glycemic variability.

  • Nighttime SD was significantly higher in patients with diabetic polyneuropathy.

  • CVR-R was significantly lower in patients with polyneuropathy.

Abstract

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.

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)

  • J.K. Snell-Bergeon 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

    Diabet Med

    (2010)
  • M. Fukuda et al.

    Correlation between minimal secretory capacity of pancreatic beta-cells and stability of diabetic control

    Diabetes

    (1988)
  • S. Shibasaki et al.

    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

    (2010)
  • M. Parillo et al.

    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

    (2011)
  • C. Manohar et al.

    The effect of walking on postprandial glycemic excurision in patients with type 1 diabetes and healthy people

    Diabetes Care

    (2012)
  • R.D. Hoeldtke et al.

    Reduced epinephrine secretion and hypoglycemia unawareness in diabetic autonomic neuropathy

    Ann Intern Med

    (1982)
  • O. Awoniyi et al.

    Hypoglycemia in patients with type 1 diabetes: epidemiology, pathogenesis, and prevention

    Curr Diab Rep

    (2013)
  • Z. Ramzan et al.

    Continuous glucose monitoring in gastroparesis

    Dig Dis Sci

    (2011)
  • I.J. Cicmir et al.

    Studies of heart rate oscillations in diabetics at rest

    Horm Metab Res

    (1980)
  • Y. Seino et al.

    Report of the committee on the classification and diagnostic criteria of diabetes mellitus

    J Diabetes Investig

    (2010)
  • H. Yasuda et al.

    Rationale and usefulness of newly devised abbreviated diagnostic creiteria and staging for diabetic polyneuropathy

    Diabetes Res Clin Pract

    (2007)
  • View full text