1. Crimea State Medical University
The department of Propedeutics of Internal Medicine
The department of Human Physiology
Heart rate variability and autonomic status in patients with diabetes mellitus type 2
Kateryna Zavgorodnya
Scientific Adviser:
Ass.prof. Tymchenko S.

2. 90% 45 %* Peripheral nerves damage
Diabetes mellitus – 2nd chronic disease in the world
90%
Autonomic nervous system damage
Peripheral nerves damage
45 %*
* The Rochester Diabetic Study //Dyck PJ, Kratz KM, Karnes JL. The prevalance by staged severity of various types of diabetic neuropathy, and nephropathy, in population based cohort. Neurology 1993;43:817–24.

3. Social and economic impact
1. According to WHO almost 50% of diabetes affected patients have the same degree of neuropathy;
2. In USA 17% of costs for treating diabetic complications (approx $300 per patient per year) goes for diabetic neuropathy;
4. Diabetic neuropathy is associated with a 20% increase in the number of patients visiting hospitals.
Carls GS, Gibson TB, Driver VR, et al. The economic value of specialized lower-extremity medical care by podiatric physicians in the treatment of diabetic foot ulcers. J Amer Podiatr Med Assoc. 2011;101(2): )
Mehra M, Merchant S, Gupta S, Potluri RC (2014) Diabetic peripheral neuropathy: resource utilization and burden of illness. J Med Econ 17: 1-9

5. Diabetic neuropathy – is a micro vascular injury of small blood vessels that supply nerves (vasa nervorum) in addition to direct influence of hyperglycemia on myelin and axonal transport in nerve fibers.
damaged by neuropathy

6. What do we handle with?
Mortality after 5–8 years in diabetic patients with CAN was 29%, while it was 6% in those without CAN. *
Cardiac autonomic neuropathy - is the damage of sympathetic and parasympathetic cardiac and vascular nerve fibers, resulting in abnormalities in heart rate control and vascular dynamics.
Сlinical manifestations:
resting tachycardia,
orthostatic hypotension, syncope,
asymptomatic myocardial infarction,
LV diastolic and systolic dysfunction
stroke, and sudden cardiac death.
*Ziegler D. Diabetic cardiovascular autonomic neuropathy: Prognosis, diagnosis and treatment. Diabetes Metab Rev 1994

7. Cardiac autonomic neuropathy stages

8. The aim: to investigate the changes of HRV and autonomic status in patients with type 2 DM.
Objectives:
Analyze the patient’s autonomic status based on Vein’s Autonomic Symptoms Scale (VASS);
Estimate autonomic functional tests and heart rate variability (HRV);
Establish the connection between autonomic status and heart rate variability in patients with type 2 DM.

9. Materials and methods 62 Diabetic patients aged 42-63
17 – insulinotherapy
45 – oral hypoglycemics 62
Diabetic patients
aged 42-63
25 males
37 females
DM duration 11,2 years±4,5
HbA1C≤9

10. Methods Vein’s Autonomic Symptoms Scale Valsalva Maneuver (VM)
Sympathetic-Parasympathetic
nervous system prevalence
Valsalva Maneuver (VM)
Lying-to-standing (LST)
Deep breathing test (DBT)
Isometric exercise (IET)
Ewing tests
Time-domain
parameters:
RRNN, SDNN, rMSSD,
pNN50
Heart rate
variability
24-hour
Holter ECG
monitoring
Frequency-domain:
HF, LF, TP, LF/HF
Kolmogorov-Smirnov and Lilliefors, Mann-Whitney U-test and Spearman correlation tests
Statistics (STATISTICA 8.0,
Stat-Soft, 2009)
Methods

11. Vein’s Autonomic Symptoms Scale (VASS) * includes:
21 sub-scales (233 items) for
organs and systems as:
cardiovascular and respiratory
gastrointestinal and urinary tract
thermoregulation and perspiration
personal traits and capacity for
work
blood analysis and ECG findings
skin and eyes examination
include questions, clinical and
laboratory findings
* Vein A.M. Autonomic disorders: symptoms, diagnostics and treatment. – 2003, 752 p.

12. Autonomic nervous regulation based on VASS (n=62)**
reference units ** * * **
* – p<0,05; ** – р<0,01

13. Ewing’s* autonomic tests
Valsalva maneuver Parasympathetic and sympathetic activity
After forcible exhales into the mouthpiece of a manometer to 40 mmHg for 15 s during EKG monitoring.
Isometric exercise response test Sympathetic activity
A dynamometer handgrip is squeezed to maximum, and then squeezed at 30% maximum for 5 min.
Lying-to-standing Sympathetic activity
fall in BP >20 mmHg for systolic or >10 mmHg for diastolic BP in
response to postural change, from supine to standing
Deep breathing test - Parasympathetic activity
EKG performed during deep breathing within 5 sec each and obtaining the maximum heart rate (inspiration) divided by the minimum heart rate (expiration), or longest RR
*Ewing DJ, Clarke BF, Diagnosis and management of diabetic autonomic neuropathy, Br Med J, 1982;285:916–8.

14. Autonomic tests results (n=62)
Parameter
Diabetic patients
our data
Normal values*
Deep breathing test
maximum–minimum heart/E/I ratio
0,83±0,85
1,33±0,49
Valsalva Maneuver
Valsalva ratio
0,87±0,21
1,38 ±0, 28
Lying-to-standing
Fall in systolic pressure (mmHg)
26± 2,3
8,8± 1,7
Isometric exercise
Rise in diastolic pressure (mmHg)
6,28 ±2,85
20,3 ±2,28
* Peter Kempler. Autonomic neuropathy: a marker of cardiovascular risk. //British Journal of Diabetes & Vascular Disease : 84

15. Assessment of heart rate variability
the intervals between
successive heartbeats
Heart rate variability (HRV) is traditionally derived from RR interval time series of electrocardiography (ECG).

16. HRV Sympathetic Parasympathetic parameters: parameters: LF rМSSD pNN50HF
Parasympathetic- sympathetic balance:
SDANNi
SDNN
HF/LF ratio
Note: *SDNN - is a standard deviation of the NN intervals. This is one of the most representative parameters of HRV.
Thus low SDNN is low HRV, which primarily indicates autonomic system damage.
* Heart rate variability: Standards of measurement, physiological interpretation, and clinical use//Task Force of The European Society of Cardiology and The North American Society of Pacing and Electrophysiology. European Heart Journal (1996) 17, 354–381

17. Time-domain and frequency-domain HRV parameters in patients (n=62)
Diabetic patients
our data
D. Ramaekers, H. Ector, 1998*
D. F. Dietrich
SAPALDIA study,
2006**
RRNN, ms
754,3 ± 9,4
795,2 ± 9,8
788 ± 0,18
SDNN, ms
1068,5 ± 4,4
2748,5 ± 5,4
3538,2 ± 0, 25
rMSSD, ms
33,1 ± 3,8
42 ± 11,3
48 ± 0,25
pNN50, %
7,9 ± 2,5
8,8 ± 2,2
11± 2
TP, ms2
1712, 3± 13,7
2810 ± 13,4
2925,2 ± 0, 25
LF, ms2
1017,0 ± 9,8
1086 ± 28,5
1318,1 ± 0,18
HF, ms2
126,4 ± 15,1
233 ± 12,1
187,8 ± 0,3
LF/HF
2,7 ± 0,8
4,5 ± 3
7,1 ± 0, 20
*D. Ramaekers. Heart rate variability and heart rate in healthy volunteers European Heart Journal (1998).
** D.F. Dietrich. Heart rate variability in an ageing population and its association with lifestyle and cardiovascular
Risk factors: results of the SAPALDIA study Europace (2006) 8, 521–529

18. Age differences in HRV parameters (n=62)
Time-domain parameters ** ms
Frequency-domain
parameters ** **
ms2 **
***
*** - p<0,001; * – p<0,05; ** – р<0,01

19. HRV: insulinotherapy vs. oral hypoglycemics (n=62)**
ms2 * ** % ms
* – p<0,05; ** – р<0,01

20. Correlation between autonomic status and HRV
correlation coefficient **
correlation coefficient **
* – p<0,05; ** – р<0,01

21. Correlation between DM duration and autonomic tests (n=62)
correlation coefficient
* – p<0,05; ** – р<0,01

22. Conclusions
Sympathetic nervous system prevailed over the parasympathetic one based on total VASS score with the prevalence in most organs and systems that is indicative of parasympathetic denervation (p<0,05).
Both time-domain and frequency-domain HRV parameters were decreased compared to average normal values in 100% of patients at rest.
The values of all Ewing tests revealed to be decreased in all patients.
HRV parameters appeared to be lower in patients, undergoing insulinotherapy compared to those, taking oral hypoglycemic medicines (p<0,05).
Sympathetic VASS score was associated with lower pNN50, HF and TP indices, while SDNN showed significant relation to SNS scores of VASS for cardiovascular, endocrine, and nervous systems (p<0,05).

23. The results of HRV analysis, cardiovascular tests and VASS scores were indicative of the autonomic nervous system impairment in diabetic patients.
CAN as an independent risk factor for poor prognosis of cardiac events in DM, so must be diagnosed on the early stages.
VASS could be suggested a valuable tool for early detection and prediction of complications in DM patients

24. Thank you for your attention!
Before it doesn’t stop us
Thank you for your attention!

25. HRV: time-domain parameters
Parasympathetic and sympathetic characteristics:
SDANNi -standard deviation of the average normal RR interval (of all filtered RR intervals for all segments of all recording )
SDNN - standard deviation of the normal RR interval
Parasympathetic characteristics: 
rМSSD - the square root of the mean squared differences of successive NN interval
pNN50 - percentage of differences between adjacent normal RR intervals exceeding 50 ms over

26. HRV: frequency-domain parameters
VLF = very low-frequency waves ( Hz) is related to fluctuations in the vasomotor tonus linked to thermoregulation, humoral system.
LF= low-frequency ( Hz) associated with the baroreflex – mainly sympathetic control, but with vagal (parasympathetic) modulation;
HF = high-frequency ( Hz) is related to parasympathetic control.
LF/HF ratio – sympathetic-parasympathetic balance