Nonlinear PD2i heart rate complexity algorithm detects autonomic neuropathy in patients with type 1 diabetes mellitus.

OBJECTIVE: The aim of this study was to test whether a new heart rate variability (HRV) complexity measure, the Point Correlation Dimension (PD2i), provides diagnostic information regarding early subclinical autonomic dysfunction in diabetes mellitus (DM). We tested the ability of PD2i to detect diabetic autonomic neuropathy (DAN) in asymptomatic young DM patients without overt neuropathy and compared them to age- and gender-matched controls. METHODS: HRV in DM type 1 patients (n=17, 10 female, 7 male) aged 12.9-31.5 years (duration of DM 12.4±1.2 years) was compared to that in a control group of 17 healthy matched probands. The R-R intervals were measured over 1h using a telemetric ECG system. RESULTS: PD2i was able to detect ANS dysfunction with p=0.0006, similar to the best discriminating MSE scale, with p=0.0002. CONCLUSIONS: The performance of PD2i to detect DAN in asymptomatic DM patients is similar to the best discriminative power of previously published complexity measures. SIGNIFICANCE: The PD2i algorithm may prove to be an easy to perform and clinically useful tool for the early detection of autonomic neuropathy in DM type 1 patients, especially given its minimal data requirements.

Recurrences in heart rate dynamics are changed in patients with diabetes mellitus.

Detection of subclinical autonomic dysfunction in patients with diabetes mellitus (DM) is of vital importance for risk stratification and subsequent management. Heart rate variability (HRV) analysis is a sensitive tool for assessment of cardiovascular autonomic dysfunction. As the heart is controlled by non-linear deterministic system, the non-linear dynamics measures should be preferred. Recurrence plot (RP) is able to analyse recurrences within system dynamics. The aim of the study was to detect heart rate dysregulation in DM by RP and to ascertain which of the recurrence quantification analysis (RQA) measures are changed in patients with DM compared to control group. We analysed HRV recordings from 17 young patients with type 1 DM and 17 healthy matched control subjects. RQA was performed on RPs with a fixed value of recurrence points percentage. From RQA measures based on diagonal lines, we have found higher percentage of determinism in DM group (P=0.038). Trapping time measure was also higher in DM (P=0.022). RQA revealed changes in dynamics recurrences with reduced complexity of heart rate control in young diabetic patients. As RQA parameters are independent of overall HRV, parameters of RP should be used together with linear HRV parameters for better description of heart rate dysregulation in patients with diabetics.

Short-term heart rate complexity is reduced in patients with type 1 diabetes mellitus.

OBJECTIVE: The aim of this study was to test whether new heart rate variability (HRV) complexity measures provide diagnostic information regarding early subclinical autonomic dysfunction in diabetes mellitus (DM). METHODS: HRV in DM type 1 patients (n=17, 10f, 7m) aged 12.9-31.5 years (duration of DM 12.4+/-1.2 years) was compared to a control group of 17 healthy matched probands. The length of R-R intervals was measured over 1h using a telemetric ECG system. In addition to linear measures, we assessed HRV complexity measures, including multiscale entropy (MSE), compression entropy and various symbolic dynamic measures (Shannon and Renyi entropies, normalized complexity index (NCI), and pattern classification). RESULTS: HRV magnitude was significantly reduced in patients with DM. Several HRV complexity parameters (MSE at scales 2-4, Renyi entropy, NCI) were also significantly reduced in diabetics. MSE indices and compression entropy did not correlate with linear measures. CONCLUSIONS: The magnitude and complexity of HRV are reduced in young patients with DM, indicating vagal dysfunction. SIGNIFICANCE: The quantification of HRV complexity in combination with its magnitude may provide an improved diagnostic tool for cardiovascular autonomic neuropathy in DM.

Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers.

CONTEXT: Mutations in the KCNJ11 and ABCC8 genes encoding the pancreatic beta-cell K(ATP) channel have recently been shown to be the most common cause of permanent neonatal diabetes mellitus (PNDM). Information regarding the frequency of PNDM has been based mainly on nonpopulation or short-term collections only. Thus, the aim of this study was to identify the incidence of PNDM in Slovakia and to switch patients to sulfonylurea (SU) where applicable. DESIGN: We searched for PNDM patients in the Slovak Children Diabetes Registry. In insulin-treated patients who matched the clinical criteria for PNDM, the KCNJ11 or ABCC8 genes were sequenced, and mutation carriers were invited for replacement of insulin with SU. RESULTS: Eight patients with diabetes onset before the sixth month of life without remission were identified since 1981, which corresponds to the PNDM incidence in Slovakia of one case in 215,417 live births. In four patients, three different KCNJ11 mutations were found (R201H, H46Y, and L164P). Three patients with the KCNJ11 mutations (R201H and H46Y) were switched from insulin to SU, decreasing their glycosylated hemoglobin from 9.3-11.0% on insulin to 5.7-6.6% on SU treatment. One patient has a novel V86A mutation in the ABCC8 gene and was also substituted with SU. CONCLUSIONS: PNDM frequency in Slovakia is much higher (one in 215,417 live births) than previously suggested from international estimates (about one in 800,000). We identified one ABCC8 and four KCNJ11 mutation carriers, of whom four were successfully transferred to SU, dramatically improving their diabetes control and quality of life.

Parasympathetic versus sympathetic control of the cardiovascular system in young patients with type 1 diabetes mellitus.

Autonomic neuropathy and cardiovascular dysregulation are common complications of the diabetes mellitus (DM). The aim of the study was to test the hypothesis that cardiovascular regulation is abnormal in young patients with type 1 DM. Patients with type 1 DM (17, 10 females, 7 males) aged 12.9-31.5 years (mean+/-SEM: 22.4+/-1.0 years) were investigated. The mean duration of DM was 12.4+/-1.2 years. The control group consisted of 17 healthy probands matched for sex and age. The length of R-R intervals was measured using telemetric system (VariaCardio TF4; Sima Media) where ECG signal (sampling frequency 1000 Hz) from thoracic belt was transferred into PC for further analysis. Systolic blood pressure (SBP) was monitored beat-to-beat using volume-clamp method by Finapres 2300 (Ohmeda). Spectral power in HF band of HRV (HRV-HF) was taken as an index of parasympathetic control and spectral power in LF band of systolic BPV (BPV-LF) as an index of sympathetic control. In young patients with type 1 DM significant reduction of spectral power in HF band of the heart rate variability was found, whereas no significant difference between DM group and control group was observed in spectral power in LF band of blood pressure variability. In conclusion, we found impaired parasympathetic control of heart rate in young patients with type 1 DM. No differences in blood vessels sympathetic control were detected using spectral analysis of BPV. We suggest that abnormalities in cardiac parasympathetic regulation precede impairment of blood vessels sympathetic control in young diabetics.

Heart rate variability in young patients with diabetes mellitus and healthy subjects explored by Poincaré and sequence plots.

Autonomic neuropathy is a common complication of the diabetes mellitus (DM). The significance of its early diagnosis is very high because the mortality of the patients with this complication is elevated. Considering the effort to apply new mathematical methods to cardiac dysregulation diagnosis, the major aim of the study was to ascertain which of the new heart rate variability (HRV) parameters are different in young patients with DM type 1 compared with control group. The next aim was to assess the HRV changes during prolonged (40 min) supine rest. The heart rate was continuously recorded during supine rest in 17 young patients with DM type 1 (10 women, 7 men) aged 22.4 +/- 1.0 years (mean +/- SEM). The control group consisted of 17 healthy matched probands. The HRV (time/frequency domains, Poincare and sequence plots, sample entropy) was analysed in two intervals - T1 starting at fifth minute and T2 starting at 30th minute of supine rest. The major results of our study are: the reduced Poincare plot pattern measures in the young DM group; the lower percentage of points in the third quadrant of sequence plot (this parameter was not correlated with the mean heart rate) and significant changes in HRV during supine rest in DM group (in contrast to control subjects). In conclusion, HRV parameters based on nonlinear dynamics were able to distinguish cardiac dysregulation in young patients with DM from the control group. The percentage of points in the third quadrant of sequence plot provides information that is not dependent on mean heart rate. Poincare and sequence plots, together with the rate of HRV changes during supine rest, can provide clinically relevant information usable in diagnosis of the cardiac dysregulation.