Effects of hyperglycemia on variability of RR, QT and corrected QT intervals in Type 1 diabetic patients

In this study, we evaluated the effects of hyperglycemia on the variability of RR (HRV), QT interval variability (QTV) and corrected QT interval variability (QTcV) during hyperglycemic and non-hyperglycemic conditions in six Type 1 diabetic patients at nights. The aim of this study was to investigate the association of high blood glucose levels with autonomic modulation of heart rate and variation in ventricular repolarization. Blood glucose level (BGL) threshold for defining hyperglycemia state was set at 8.33 mmol/l. Variability of RR, QT and corrected QT intervals during hyperglycemic and non-hyperglycemic were quantified using time and frequency domain measures. Hypomon® device was used to monitor ECG signals and acquire RR and QT intervals in Type 1 diabetic patients overnight. The results indicated that time and frequency domain HRV variables were significantly decreased under hyperglycemic condition and inversely correlated with BGL. QTV parameters also reduced when BGL increased and time domain measures of QTV were inversely associated with BGL. Variability in QTc interval was much less than in the QT interval and demonstrated a lower SDNN and LF power. We concluded that certain components of HRV, time-domain measures of QTV and QTc but not QTcV are strongly correlated to high blood glucose levels and can be good markers to identify hyperglycemic events in T1DM. © 2013 IEEE

Associations Between Heart Rate Variability and Metabolic Syndrome Risk Factors

Metabolic syndrome (MetS) is a clustering of risk factors for cardiovascular disease (CVD) and type 2 diabetes (T2D) – two major causes of morbidity and mortality worldwide. Heart rate variability (HRV) is a non-invasive measure of cardiac autonomic regulation that predicts mortality and morbidity. Additionally, HRV is reduced in CVD, T2D and MetS. As such, HRV has potential to be a novel cardiometabolic risk factor to be included in clinical risk assessment. Therefore, the purpose of this thesis was to examine the relationships between MetS and HRV. A systematic review of cross-sectional studies examining relationships between HRV and MetS was completed to consolidate existing evidence and to guide future studies. This was followed by a cross-sectional investigation of time and frequency domain and nonlinear HRV in a population with MetS risk factors to determine which MetS risk factors were associated with HRV parameters. A pilot study was then conducted to study the feasibility of conducting a mobile health (mHealth) and exercise intervention in a rural population, which was followed by a 24-week randomized clinical trial to examine the effects of the interactive mHealth exercise intervention compared to standard of care exercise in participants with MetS risk factors. Overall, HRV was reduced in women with MetS compared to those without, though there were no differences in men. Waist circumference and lipid profiles were most commonly related to HRV parameters when studied cross-sectionally. The changes in waist circumference and fasting plasma glucose were associated with the change in HRV parameters when studied longitudinally. Following the intervention period, waist circumference and blood pressure were improved with no other changes in MetS risk factors. HRV parameters indicative of vagal activity were reduced over the intervention period, but there were no changes in other HRV parameters. There were no differences in changes between the intervention and control groups. In conclusion, MetS and HRV are associated in women but not men. However, there were no clear associations between MetS and HRV to suggest that HRV would be a valuable clinical risk factor

The Effect of a Square-Stepping Exercise Intervention on Heart Rate Variability in Older Individuals with Type 2 Diabetes and Subjective Cognitive Complaints

Aging is associated with increased onset of diseases such as type 2 diabetes (T2D) and cognitive impairment. Heart rate variability (HRV), a measure of autonomic function, is reduced in T2D and may have the potential to indicate cognitive decline in this population. Square-stepping exercise (SSE) is a novel cognitive exercise recently implemented in cognitive research, which may have the potential to improve global cognitive function in T2D individuals. Participants with T2D (N=25, aged ≥ 50y) and self-reported cognitive complaints were randomized into either an SSE intervention or a wait-list (WL) control group for 24-weeks. HRV parameters (time and frequency domain) and GCF domains were assessed at baseline and 24-weeks. No significant differences were found in HRV parameters between groups at baseline and 24-weeks. However, heart rate was significantly reduced from baseline to 24-weeks in the SSE group, p = 0.046. Additionally, low and high frequency power were significantly decreased from baseline to 24-weeks in the WL group, p = 0.05 and p = 0.043 respectively. This study elucidates the impact of cognitive exercise training on HRV, however, it is inconclusive as to why a shift towards vagal modulation was observed in both the SSE and WL groups

Heart rate variability in young adults - Reference values and associations with cardiometabolic risk factors and vascular properties. The Cardiovascular Risk in Young Finns Study.

Background: The function of the autonomic nervous system (ANS) can be evaluated with heart rate variability (HRV). Decreased HRV is associated with aging, the male sex, increased heart rate, and overall increased cardiometabolic risk. It has been hypothesized that early atherosclerotic vascular changes and ANS function are related. Aims: The aims were to assess reference values on HRV in young adults, and examine associations with HRV and cardiometabolic risk factors and metabolic syndrome (MetS) and to study relations between HRV and ultrasonographically measured vascular properties. Participants and methods: The present thesis is part of the Cardiovascular Risk in Young Finns Study. The thesis is based on the follow-up study in 2001, when the study individuals were 24-39 years of age. HRV data were available on 1 956 individuals. Results: HRV was inversely associated with age and heart rate (for all p<0.001). Highfrequency HRV (HF) was higher, and low-frequency HRV (LF) lower in women than men (p<0.0001 for both). MetS was associated with 11% decreased HF and 12% increased LF/HF-ratio in women, and 8% decreased HF and 4% increased LF/HF-ratio in men. Carotid artery distensibility was independently associated with HF and total HRV (for both p<0.05). Conclusions: The reference values in young adults were generated. Decreased HRV was associated with age, the male sex and increased heart rate. Women had higher HF and lower LF variability than men. MetS was related to decrease in HRV. The observed associations between carotid elasticity and HRV, supports the hypothesis that reduction in carotid elasticity may lead to decrease in autonomic cardiac control.Sydämen sykevaihtelu nuorilla aikuisilla – viitearvot ja yhteys sydän- ja verisuonitautien riskitekijöihin sekä varhaisiin valtimomuutoksiin Tausta: Autonomisen hermoston toimintaa voidaan arvioida mittaamalla sydämen syketaajuudessa tapahtuvaa jaksoittaista vaihtelua, sydämen sykevaihtelua. Vähentynyt sydämen sykevaihtelu on sydän- ja verisuonitautien itsenäinen riskitekijä. Sykevaihtelun väheneminen liittyy ikääntymiseen, miessukupuoleen ja kiihtyneeseen sydämen syketaajuuteen sekä useisiin valtimotaudin riskitekijöihin. Varhaisten valtimotautimuutosten sekä autonomisen hermoston toiminnan välillä on aiemmin esitetty olevan yhteys, jota voidaan tutkia sykevaihtelun ja ultraäänellä mitattujen varhaisten valtimomuuttujien avulla. Tavoite: Tutkimuksen tavoitteena oli luoda sykevaihtelun viitearvot nuorille aikuisille sekä tutkia sykevaihtelun yhteyttä sydän- ja verisuonitautien riskitekijöihin ja metaboliseen oireyhtymään sekä selvittää onko varhaisilla valtimomuutoksilla yhteyttä sydämen autonomiseen säätelyyn. Menetelmät: Väitöskirjatutkimus on osa Lasten Sepelvaltimotaudin Riskitekijät – tutkimusta ja perustuu vuonna 2001 toteutettuun seurantatutkimukseen, jolloin tutkittavat olivat iältään 24–39 vuotta. Tutkimukseen oli käytettävissä 1 956 tutkimushenkilön sykevaihtelumittaukset. Tulokset: Kaikki sykevaihtelun muuttujat olivat yhteydessä tutkittavien ikään ja syketaajuuteen (molemmilla p<0.001). Naisilla korkeataajuuksinen sykevaihtelu oli miehiä runsaampaa (p<0.0001) ja matalataajuuksinen sykevaihtelu vähäisempää (p<0.0001). Metaboliseen oireyhtymään liittyi vähentynyt matalataajuuksinen sykevaihtelu (-11% naisilla ja -8% miehillä). Kaulavaltimon elastisuus oli itsenäisesti yhteydessä sydämen sykevaihteluun (p<0.05). Johtopäätökset: Tutkimuksessa luotiin sykevaihtelun viitearvot terveille aikuisille. Sykevaihteluun vaikuttivat voimakkaimmin ikä, sukupuoli sekä syketaajuus. Metaboliseen oireyhtymään liittyi merkittävästi vähentynyt sykevaihtelu. Valtimoiden seinämän jäykistyminen saattaa olla yksi mekanismi sydämen autonomisen säätelyn muutosten taustalla.Siirretty Doriast

Effects of sport-specific, intermittent high-intensity exercise on nocturnal heart rate variability and glycemia in elite athletes with type 1 diabetes

Type 1 diabetes (T1D) is associated with hypoglycemia and premature autonomic disturbance (using heart rate variability [HRV]) - both which have been implicated in sudden death. This study examined the effect of a single bout of intermittent high-intensity exercise (IHE) on nocturnal HRV in ten hockey players with T1D and ten teammates without T1D. HRV and BG were analyzed from 12am-6am following hockey activity and low activity days. Hockey-type IHE on a cycle ergometer decreased BG by -1.9 ± 2.8 mmol/L, while an actual hockey game increased BG by 1.0 ± 3.2 mmol/L. One participant experienced nocturnal hypoglycemia after a hockey game (lasting 230 min). A significantly better nocturnal HRV profile (QTc, SDNN, pNN50, RMSSD) was observed following the low activity day compared to the days where IHE took place (p<0.05). There was no difference in HRV between T1D and non-T1D participants. This study documented the unique ability of a hockey game to increase BG in youth with T1D. Furthermore, given that decreased HRV is commonly noted in youth with T1D, this study suggests that the onset of autonomic hindrances can be delayed in highly-active individuals

Measurement of Autonomic Function in Renal Disease and Diabetes

Renal disease and diabetes lead to dysautonomia resulting in consequences ranging from gastroparesis to sudden death. New technologies to detect dysautonomia, such as 24-hr heart rate variability, are being evaluated and compared to traditional evoked tests. These advances have, however, lead to a lack of standardization in testing batteries, procedures, and reporting formats. This series of 3 studies psychometrically assessed measures of autonomic function (AF) and explored relationships among objective and subjective measures in healthy adults and uremic patients. Participants underwent evoked tests that included change in heart rate with deep breathing and Valsalva. In addition, measures of 24-hr HRV (time-domain: SDNN, SDANN, RMSSD; frequency-domain: total power, low and high frequency) and symptomatology were obtained. Study 1 examined the development and psychometric testing of the Autonomic Symptom Checklist (ASC), an instrument designed to assess autonomic symptomatology, with uremic patients (n=244) and healthy adults (n=34). Findings showed the ASC was able to differentiate among healthy and uremic patients with and without diabetes. Test-retest reliability was moderate to high for most categories. Study 2 established normal, borderline, and abnormal AF values and determined if these values could distinguish healthy (n=158) from uremic adults (n=363). Abnormal values were established at the 2.3 quantile of healthy adults. Uremic patients, especially those with diabetes, had much poorer values than healthy adults. The influence of age and gender on AF measures was attenuated in uremic as compared to healthy adults. Study 3 examined relationships among and the clinical utility of evoked tests, 24- hr HRV, and the ASC. Data were obtained from pre (n=130) and post (n=55) kidney and kidney-pancreas transplant recipients (n=130), and healthy adults (n=22). The frequency of abnormal values was used to identify the most sensitive measure. Measures of 24-hr HRV were more sensitive than evoked measures, with frequency measures being most sensitive. In conclusion, this series of studies established reliability and validity for the ASC, referent values for AF tests, devised a scoring system for AF tests, and found 24-hr HRV measures more sensitive than evoked measures

Alternative Therapy and Treatment of Type 2 Diabetes

The rise in prevalence and incidence of type 2 diabetes mellitus (T2D) in the developing world continues unabated. Current treatment strategies, however, fall short of achieving optimal glycemic control. The aim of project I was to investigate the effect of an acute bout of a yogic breathing exercise on heart rate variability (HRV) in individuals with T2D. Project II was designed to assess the effectiveness of the neurohormone melatonin in lowering short- and long-term glucose levels, lipids and oxidative stress in T2D. Project III investigated the differential effects of two different styles of aerobic exercise on postprandial glycemia, mood and HRV in T2D. Project I investigated the effect of short-term breathing exercises and demonstrated significant differences between the T2D group and an age-matched normoglycemic group (CON) in resting measures of HRV. Standard deviation of consecutive heart beats (SDNN), the square root of the mean squared differences (RMSSD) and total spectral power (TP) were almost uniformly lower in the T2D group than the CON group. A within-group analysis revealed no significant effect of breathing exercise upon HRV in the CON group. However, a 10-minute breathing protocol involving selective breathing through only the left nostril demonstrated a significant reduction in resting heart rate in the T2D group (-1.2 beats per minute, or bpm) compared to the heart rate average during the entire breathing protocol, indicating a possible acute improvement in vagal tone. Project II, which investigated the effect of six weeks of melatonin supplementation on short-and long-term glycemic control, lipids, and oxidative stress in T2D, yielded impressive results. There was a significant reduction in malondialdehyde, a marker of oxidative stress (-6.3 vs. 0.7nmol/ml), as well as a significant drop in glycated hemoglobin (-0.24%±0.23) in the melatonin group vs. the placebo group. Project III examined the impact of a more recreational style of exercise (table tennis) following a dinner meal vs. a more traditional exercise (walking). Our results indicated that self-paced walking generated a significantly higher heart rate than table tennis, which translated into a significant drop in blood glucose levels following a 30-minute bout of exercise. We did not, however, note any difference in mood between the two groups

Relationship between autonomic function and parameters of beta cell secretion across the entire spectrum of glucose homeostasis

Background: type 2 diabetes is determined by a reduction of β cell mass and function besides a defect in insulin sensitivity. It was demonstrated that pancreatic islets are innervated by sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) fibers and autonomic function contributes to the regulation of glucose homeostasis. An alteration in neuronal control of β cell function could be involved in the pathogenesis of the type 2 diabetes. Aim: we focused on finding a possible association between autonomic function and the different parameters that describe β cell function in The Maastricht Study, a population-based cohort. We sought this association also in the population of Verona Newly Diagnosed Type 2 Diabetes Study (VNDS), a study of patients with newly diagnosed type 2 diabetes. Research design and Methods: in the Maastricht study population from 24-h electrocardiogram we derived Heart Rate Variability (HRV) time and frequency domains (individual z-scores, based upon seven and six variables, respectively). From a standard 2-hour 75 g OGTT we estimated different aspects of β cell function, i.e. C-peptidogenic index t0-30, overall insulin secretion, β cell glucose sensitivity, β cell potentiation factor, and β cell rate sensitivity, using formula-based methods and mathematical modeling. In the VNDS study cardiovascular autonomic function was assessed by a computerized system which analyzed heart rate and blood pressure variations during lying to standing (LS), deep breathing (DB), and Valsalva maneuver (VM), following the criteria presented by Ewing and Clarke. From a 5-hour 75g OGTT we estimated through mathematical modelling two main parameters of beta cell glucose sensitivity: derivative (first phase) and proportional control (second phase) of insulin secretion. Results: in the Maastricht study we analyzed 2007 individuals with a mean standard deviation (SD) age of 59.8 8.2 years, of whom 52% were men and 24% with type 2 diabetes (oversampled by design). After adjustment for age, sex, educational level and Matsuda index, time and frequency domain HRV were significantly and directly associated with C-peptidogenic index, β cell glucose sensitivity and β cell potentiation factor, but not with overall insulin secretion. Then, further adjustment for cardiovascular risk factors (model 4) did not materially alter these associations, though only the association of HRV with C-peptidogenic remained statistically significant (standardized β [95%CI] per 1-SD increment in HRV TIME domain, for respectively C-peptidogenic index, overall insulin secretion, β cell glucose sensitivity, and β cell potentiation, 0.05 [0.00; 0.09]; 0.04 [-0.00; 0.08]; 0.04 [0.00; 0.08] ; and 0.04 [-0.00; 0.08]; standardized β [95%CI] per 1-SD increment in HRV FREQUENCY domain, for respectively C-peptidogenic index, overall insulin secretion, β cell glucose sensitivity, and β cell potentiation, 0.05 [0.00; 0.09]; 0.04 [-0.00; 0.08]; 0.04 [0.00; 0.08] ; and 0.04 [-0.00; 0.08]). HRV time and frequency domain weren’t significantly associated with rate sensitivity. Furthermore, we evaluated data of 537 patients with newly diagnosed type 2 diabetes with a mean ± SD age of 58.3 ± 9.6 of whom 66.3% were male. 91 subjects (16.9%) showed at least one abnormal test used to evaluate cardiovascular autonomic function (CAN). We found a worse derivative control of beta cell function in people with signs of cardio autonomic neuropathy as compared to the other group. This difference however did not reach statistical significance (p=0.063). Conclusion: In summary, in the present research we analyzed a possible association between autonomic function and β cell secretion, estimated from OGTT. We found that autonomic dysregulation could contribute to β-cell dysfunction, in particular affecting the first phase of insulin secretion. This mechanism could add to the other factors that lead to the impairment of glucose homeostasis