Differential associations of lower cardiac vagal tone with insulin resistance and insulin secretion in recently diagnosed type 1 and type 2 diabetes

Ziegler, Dan; Strom, Alexander; Bönhof, Gidon J.; Püttgen, Sonja; Bódis, Kálmán; Burkart, Volker; Müssig, Karsten; Szendroedi, Julia; Markgraf, Daniel F.; Roden, Michael

doi:10.1016/j.metabol.2017.10.013

Cited by 24 publications

(14 citation statements)

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“…Likewise, Razainskaite-Virbichiene et al (36) demonstrated that in patients with T1DM, the parameters of time domain in supine position have a coefficient of variation <1.65, reflecting a sensitivity of 94.3% and specificity of 91.5% for the diagnosis of CAN. Additionally HRV variables were independent predictors for developing cardiovascular disease (CVD) in patients with T2DM (28,30,34,36). These findings are in agreement with our results that showed improvement in rest HRV parameters in response to short interventional treatment, as opposed to dynamic tests that remained unchanged.…”

Section: Discussionsupporting

confidence: 90%

“…Besides that, it is easier to be performed than dynamic tests and does not need patient collaboration (28)(29)(30)(31)(32)(33)(34)(35). Takase et al (28) found that a cut-off point <30ms in SDNN parameter has a sensitivity of 72% and specificity of 92% for CAN diagnosis in patients with type 2 diabetes, while Ziegler et al (30) showed that HF index was more sensitive than functional tests to detect precocious autonomic disorder in patients with diabetes, using 0,892 as a cut-off. Likewise, Razainskaite-Virbichiene et al (36) demonstrated that in patients with T1DM, the parameters of time domain in supine position have a coefficient of variation <1.65, reflecting a sensitivity of 94.3% and specificity of 91.5% for the diagnosis of CAN.…”

Section: Discussionmentioning

confidence: 99%

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Improvement in Cardiovascular Autonomic Neuropathy After High-Dose Vitamin D Supplementation in Patients With Type 1 Diabetes

et al. 2020

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BackgroundCardiovascular autonomic neuropathy (CAN) is associated with diabetes mellitus, increasing morbidity and mortality. Some cross-sectional studies associated CAN with low 25-hydroxyvitamin D levels. The aim of our study was to evaluate the effect of high-dose vitamin D (VD) supplementation on CAN in Type 1 Diabetes Mellitus (T1DM) patients.MethodsWe performed a prospective study with 23 patients diagnosed with T1DM and CAN. Subjects with VD levels <30 ng/ml received 10,000 IU/day; the ones with VD levels between 30–60 ng/ml were given 4,000 IU/day for 12 weeks.ResultsThere was an improvement in CAN parameters related to resting heart rate variability, such as time domain parameters [Maximum RR interval (0.77 ± 0.11 vs 0.94 ± 0.51 s, p <0.05), Mean length of regular RR intervals (0.71 ± 0.10 vs 0.76 ± 0.09 s, p <0.05) and Standard deviation of all NN intervals (0.02 ± 0.01 vs 0.03 ± 0.02 s; p <0.01)] and frequency domain parameters [Low Frequency (1.9 ± 0.5 vs 2.5 ± 0.9 s, p < 0.001), Total Power (2.5 ± 0.4 vs 2.8 ± 0.6 s, p <0.05)]. In addition, there was a correlation between absolute VD level variation and posttreatment High Frequency (%), as well as among percent variation in VD level and end-of-study Low Frequency/High Frequency ratio (r=0.6, p<0.01; r= -0.5, p<0.05, respectively).ConclusionOur pilot study is the first to suggest a strong association between high-dose vitamin D supplementation and improved cardiovascular autonomic neuropathy in T1DM patients. It occurred without any variation in HbA1C, blood pressure levels, lipids, and insulin dose.Clinical Trial Registrationhttp://www.isrctn.com/ISRCTN32601947, identifier ISRCTN32601947.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Improvement in Cardiovascular Autonomic Neuropathy After High-Dose Vitamin D Supplementation in Patients With Type 1 Diabetes

et al. 2020

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“…In addition to established cardiometabolic risk factors, CAN is an independent determinant of cardiovascular morbidity, progression of diabetic nephropathy and overall mortality (4)(5)(6). Autonomic imbalance has been associated with reduced insulin sensitivity and β-cell function in individuals with recent onset of type 1 and type 2 diabetes and have been suggested to be mediated by changes in the innervation of the endocrine pancreas (7) where pancreatic islets are innervated by both parasympathetic and sympathetic nerves and are involved in pancreatic hormone secretion (8). In addition, peripheral insulin sensitivity may be associated with autonomic function as hyperinsulinemic euglycemic clamp studies have demonstrated that insulin sensitivity can be affected by autonomic blockade in obese insulin-resistant individuals (9).…”

Section: Discussionmentioning

confidence: 99%

Heart Rate, Autonomic Function, and Future Changes in Glucose Metabolism in Individuals Without Diabetes: The Whitehall II Cohort Study

et al. 2019

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Short running title: Autonomic function and glucose metabolism in non-diabetic individuals Word count: Main text: 3296, Abstract: 247 Number of Figures and Tables: 2 tables (2 supplementary tables). 1 figure (1 supplementary figure). Abbreviations CAN: cardiovascular autonomic neuropathy HF power: high-frequency power HR: heart rate HRV: heart rate variability HsCRP: high-sensitivity C-reactive protein LF power: low-frequency power LH/HF ratio: low frequency / high frequency power ratio IL-6: Interleukin 6 IL-1Ra: interleukin 1 receptor antagonist RMSSD: the root mean square of the sum of the squares of differences between consecutive normal-tonormal R-R intervals SDNN: the standard deviation of all normal-to-normal R-R intervals 3 ABSTRACT Objective Autonomic nervous system dysfunction is associated with impaired glucose metabolism, but the temporality of this association remains unclear in non-diabetic individuals. We investigated the association of autonomic function (AF) with 5-year changes in glucose metabolism in individuals without diabetes. Research Design and MethodsAnalyses were based on 9.000 person-examinations for 3,631 non-diabetic participants in the Whitehall II cohort. Measures of AF included 5-minute resting heart rate and six heart rate variability (HRV) indices.Associations between baseline AF measures and 5-year changes in fasting and 2-hour plasma glucose, serum insulin concentrations, insulin sensitivity (ISI 0-120 and HOMA-IS) and beta-cell function (HOMA-β) were estimated in models adjusting for age, sex, ethnicity, metabolic factors and medication. ResultsA ten beats per minute higher in resting heart rate was associated with 5-year changes in fasting and 2-hour insulin and ISI0-120 of (% change (95%CI)) 3.3(1.8;4.8)%,p<0.001, 3.3(1.3;5.3)%,p=0.001 and -1.4(-2.4;-

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“…HRV R-R intervals were measured in the supine position during a hyperinsulinaemic-euglycaemic clamp over 3 h using a digital Spider View Holter recorder with seven electrodes to record three-channel ECGs (Sorin Group, Munich, Germany) as previously described [16]. Time-domain HRV measures included the SD of differences between adjacent normal-to-normal (NN) intervals, SD of all NN intervals (SDNN), the number of pairs of adjacent NN intervals differing by >50 ms in the entire recording divided by the total number of NN intervals (pNN50), and the root mean square of successive differences (RMSSD).…”

Section: Methodsmentioning

confidence: 99%

Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes

et al. 2020

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Aims/hypothesis Emerging evidence suggests that in addition to hyperglycaemia, dyslipidaemia could represent a contributing pathogenetic factor to diabetic neuropathy, while obesity and insulin resistance play a role in the development of diabetic cardiac autonomic neuropathy (CAN) characterised by reduced heart rate variability (HRV), particularly in type 2 diabetes. We hypothesised that distinct lipid metabolites are associated with diminished HRV in recent-onset type 2 diabetes rather than type 1 diabetes. Methods We analysed 127 plasma lipid metabolites (11 acylcarnitines, 39 NEFA, 12 sphingomyelins (SMs), 56 phosphatidylcholines and nine lysophosphatidylcholines) using MS in participants from the German Diabetes Study baseline cohort recently diagnosed with type 1 (n = 100) and type 2 diabetes (n = 206). Four time-domain HRV indices (number of normal-to-normal (NN) intervals >50 ms divided by the number of all NN intervals [pNN50]; root mean square of successive differences [RMSSD]; SD of NN intervals [SDNN]; and SD of differences between adjacent NN intervals) and three frequency-domain HRV indices (very-low-frequency [VLF], low-frequency [LF] and high-frequency [HF] power spectrum) were computed from NN intervals recorded during a 3 h hyperinsulinaemic–euglycaemic clamp at baseline and in subsets of participants with type 1 (n = 60) and type 2 diabetes (n = 95) after 5 years. Results In participants with type 2 diabetes, after Bonferroni correction and rigorous adjustment, SDNN was inversely associated with higher levels of diacyl-phosphatidylcholine (PCaa) C32:0, PCaa C34:1, acyl-alkyl-phosphatidylcholine (PCae) C36:0, SM C16:0 and SM C16:1. SD of differences between NN intervals was inversely associated with PCaa C32:0, PCaa C34:1, PCaa C34:2, PCae C36:0 and SM C16:1, and RMSSD with PCae C36:0. For VLF power, inverse associations were found with PCaa C30:0, PCaa C32:0, PCaa C32:1, PCaa C34:2 and SM C16:1, and for LF power inverse associations were found with PCaa C32:0 and SM C16:1 (r = −0.242 to r = −0.349; p ≤ 0.0005 for all correlations). In contrast, no associations of lipid metabolites with measures of cardiac autonomic function were noted in participants recently diagnosed with type 1 diabetes. After 5 years, HRV declined due to ageing rather than diabetes, whereby prediction analyses for lipid metabolites were hampered. Conclusions/interpretation Higher plasma levels of specific lipid metabolites are closely linked to cardiac autonomic dysfunction in recent-onset type 2 diabetes but not type 1 diabetes, suggesting a role for perturbed lipid metabolism in the early development of CAN in type 2 diabetes.

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Differential associations of lower cardiac vagal tone with insulin resistance and insulin secretion in recently diagnosed type 1 and type 2 diabetes

Cited by 24 publications

References 43 publications

Improvement in Cardiovascular Autonomic Neuropathy After High-Dose Vitamin D Supplementation in Patients With Type 1 Diabetes

Improvement in Cardiovascular Autonomic Neuropathy After High-Dose Vitamin D Supplementation in Patients With Type 1 Diabetes

Heart Rate, Autonomic Function, and Future Changes in Glucose Metabolism in Individuals Without Diabetes: The Whitehall II Cohort Study

Association of cardiac autonomic dysfunction with higher levels of plasma lipid metabolites in recent-onset type 2 diabetes

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