Gastrointestinal symptoms and cardiac vagal tone in type 1 diabetes correlates with gut transit times and motility index

Introduction. A neuroimmune communication exists, and compelling evidence suggests that diabetic neuropathy and systemic inflammation are linked. Our aims were (1) to investigate biomarkers of the ongoing inflammation processes including cytokines, adhesion molecules, and chemokines and (2) to associate the findings with cardiovascular autonomic neuropathy in type 1 diabetes by measuring heart rate variability and cardiac vagal tone. Materials and Methods. We included 104 adults with type 1 diabetes. Heart rate variability, time domain, and frequency domains were calculated from a 24-hour Holter electrocardiogram, while cardiac vagal tone was determined from a 5-minute electrocardiogram. Cytokines (interleukin- (IL-) 1α, IL-4, IL-12p70, IL-13, IL-17, and tumor necrosis factor- (TNF-) α), adhesion molecules (E-selectin, P-selectin, and intercellular adhesion molecule- (ICAM-) 1), and chemokines (chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4, and C-X-C motif chemokine (CXCL)10) were assessed using a Luminex multiplexing technology. Associations between concentrations of inflammatory biomarkers and continuous variables of heart rate variability and cardiac vagal tone were estimated using multivariable linear regression adjusting for age, sex, disease duration, and smoking. Results. Participants with the presence of cardiovascular autonomic neuropathy had higher systemic levels of IL-1α, IL-4, CCL2, and E-selectin than those without cardiovascular autonomic neuropathy. IL-1α, IL-4, IL-12, TNF-α, and E-selectin were inversely associated with both sympathetic and parasympathetic heart rate variability measures (p>0.01). Discussion. Our results show that several pro- and anti-inflammatory factors, believed to be involved in the progression of diabetic polyneuropathy, are associated with cardiovascular autonomic neuropathy, suggesting that these factors may also contribute to the pathogenesis of cardiovascular autonomic neuropathy. Our findings emphasize the importance of the neuroimmune regulatory system in the pathogenesis of neuropathy in type 1 diabetes.

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Cardiac vagal tone as a novel screening tool to recognize asymptomatic cardiovascular autonomic neuropathy: Aspects of utility in type 1 diabetes

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2020.108517 ◽

2020 ◽

Vol 170 ◽

pp. 108517

Author(s):

Anne-Marie Wegeberg ◽

Elin D Lunde ◽

Sam Riahi ◽

Niels Ejskjaer ◽

Asbjørn M Drewes ◽

...

Keyword(s):

Type 1 Diabetes ◽

Autonomic Neuropathy ◽

Screening Tool ◽

Vagal Tone ◽

Cardiovascular Autonomic Neuropathy ◽

Cardiac Vagal Tone

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Cardiac vagal tone, a non-invasive measure of parasympathetic tone, is a clinically relevant tool in Type 1 diabetes mellitus

Diabetic Medicine ◽

10.1111/dme.13421 ◽

2017 ◽

Vol 34 (10) ◽

pp. 1428-1434 ◽

Cited By ~ 14

Author(s):

C. Brock ◽

N. Jessen ◽

B. Brock ◽

P. E. Jakobsen ◽

T. K. Hansen ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Vagal Tone ◽

Cardiac Vagal Tone ◽

Non Invasive ◽

Parasympathetic Tone

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Circulating Inflammatory Markers are Inversely Associated with Heart Rate Variability Measures in type 1 Diabetes

10.21203/rs.3.rs-29588/v1 ◽

2020 ◽

Author(s):

Anne-Marie Langmach Wegeberg ◽

Tina Okdahl ◽

Tina Fløyel ◽

Christina Brock ◽

Niels Ejskjaer ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Type 1 Diabetes ◽

Adhesion Molecules ◽

Autonomic Neuropathy ◽

Vagal Tone ◽

Cardiovascular Autonomic Neuropathy ◽

Cardiac Vagal Tone ◽

Tnf Α

Abstract Background A neuro-immune communication exists, and compiling evidence suggests that diabetic neuropathy and systemic inflammation are linked. Our aims were 1) to investigate biomarkers of the ongoing inflammation processes including cytokines, adhesion molecules and chemokines, and 2) to associate the findings with cardiovascular autonomic neuropathy in type 1 diabetes by measuring heart rate variability and cardiac vagal tone.Methods We included 104 adults with type 1 diabetes. Heart rate variability, time- and frequency domains, were calculated from a 24-hour Holter electrocardiogram, while cardiac vagal tone was determined from a 5-minute electrocardiogram. Cytokines (interleukin (IL)-1α, IL-4, IL-12p70, IL-13, IL-17 and tumor necrosis factor (TNF)-α), adhesion molecules (E-selectin, P-selectin and intercellular adhesion molecule (ICAM)-1) and chemokines (chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4 and C-X-C motif chemokine (CXCL)10) were assessed using a Luminex multiplexing technology. Associations between concentrations of inflammatory biomarkers and continuous variables of heart rate variability and cardiac vagal tone were estimated using multivariable linear regression adjusting for age, sex, disease duration and smoking.Results Participants with the presence of cardiovascular autonomic neuropathy had higher systemic levels of IL-1α, IL-4, CCL2 and E-selectin, than those without cardiovascular autonomic neuropathy. IL-1α, IL-4, IL-12, TNF-α and E-selectin were inversely associated with both sympathetic and parasympathetic heart rate variability measures (p>0.01).Conclusion Our results show that several pro- and anti-inflammatory factors, believed to be involved in the progression of diabetic polyneuropathy are associated with cardiovascular autonomic neuropathy, suggesting that these factors may also contribute to the pathogenesis of cardiovascular autonomic neuropathy. Our findings emphasize the importance of the neuro-immune regulatory system in the pathogenesis of neuropathy in type 1 diabetes.Trial registration: The study was approved by the North Denmark Regional Committee on Health Research Ethics (N2013-0077 and N2017-0045) and registered in public databases (Eudra CT 2013-004375-12 and clinicaltrials.gov NCT02138045.

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Gastric emptying is rapid in adolescents with type 1 diabetes and relates to gastrointestinal symptoms

International Journal of Pediatric Endocrinology ◽

10.1186/1687-9856-2015-s1-o46 ◽

2015 ◽

Vol 2015 (S1) ◽

Author(s):

Shiree Perano ◽

Christopher Rayner ◽

Stamatiki Kritas ◽

Christine Mpundu-Kaambwa ◽

Kim Donaghue ◽

...

Keyword(s):

Type 1 Diabetes ◽

Gastric Emptying ◽

Gastrointestinal Symptoms

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Extraintestinal Manifestations of Celiac Disease

Digestive Diseases ◽

10.1159/000369541 ◽

2015 ◽

Vol 33 (2) ◽

pp. 147-154 ◽

Cited By ~ 23

Author(s):

María Inés Pinto-Sánchez ◽

Premysl Bercik ◽

Elena F. Verdu ◽

Julio C. Bai

Keyword(s):

Type 1 Diabetes ◽

Celiac Disease ◽

High Risk ◽

Dermatitis Herpetiformis ◽

Gastrointestinal Symptoms ◽

Iga Deficiency ◽

Case Finding ◽

Aggressive Approach ◽

Wide Range

Case finding for celiac disease (CD) is becoming increasingly common practice and is conducted in a wide range of clinical situations ranging from the presence of gastrointestinal symptoms to failure to thrive in children, prolonged fatigue, unexpected weight loss and anemia. Case finding is also performed in associated conditions, such as autoimmune thyroid disease, dermatitis herpetiformis and type 1 diabetes, as well as in patients with irritable bowel syndrome, unexplained neuropsychiatric disorders and first-degree relatives of patients with diagnosed CD. This aggressive active case finding has dramatically changed the clinical characteristics of newly diagnosed patients. For instance, higher numbers of patients who present with extraintestinal symptoms are now being diagnosed with CD. Current recommendations state that due to a high risk for complications if the disease remains undiagnosed, patients with extraintestinal symptoms due to CD require appropriate diagnosis and treatment. Despite criticism regarding the cost-effectiveness of case finding in CD, such an aggressive approach has been considered cost-effective for high-risk patients. The diagnosis of CD among patients with extraintestinal symptoms requires a high degree of awareness of the clinical conditions that carry a high risk for underlying CD. Also, understanding the correct use of specific serology and duodenal histology is key for an appropriate diagnostic approach. Both procedures combined are able to confirm diagnosis in the vast majority of cases. However, in certain circumstances, serology and even duodenal histology cannot confirm or rule out CD. A common cause of negative IgA serology is IgA deficiency. For such eventuality, IgG-based serological tests can help confirm the diagnosis. Importantly, some histologically diagnosed cases still remain seronegative despite exclusion of IgA deficiency. On the other hand, duodenal histology may be normal despite the presence of CD-specific antibodies and active CD. This has been clearly demonstrated in some cases of untreated dermatitis herpetiformis, but may also be due to the patchy condition of CD or lesions that are not adequately recognized by nonexpert endoscopists and/or pathologists. The effectiveness of agluten-free diet depends on the clinical end point addressed. A good example is the outcome of bone loss. While risk for fracture normalizes after the first year of dietary treatment, bone parameters measured by densitometry may not be normalized in the long-term follow-up. Moreover, it is still unclear how far an early gluten-free diet will positively affect associated autoimmune diseases like type 1 diabetes and autoimmune thyroiditis.

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