Increased levels of inflammatory factors are associated with severity of polyneuropathy in type 1 diabetes

Okdahl, Tina; Brock, Christina; Fløyel, Tina; Wegeberg, Anne-Marie; Jakobsen, Poul Erik; Ejskjær, Niels; Pociot, Flemming; Brock, Birgitte; Størling, Joachim

doi:10.1111/cen.14261

Cited by 20 publications

(19 citation statements)

References 28 publications

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“…Participants were on stable hyperglycemic medication, including long-acting and fast-acting insulin or insulin pumps with dose adjustment according to the regimens minimum 1 month prior to study entry. Exclusion criteria have previously been described in detail [ 16 ]. The study was conducted in accordance with the Declaration of Helsinki, local regulations, and International Conference on Harmonization Good Clinical Practice guidelines.…”

Section: Methodsmentioning

confidence: 99%

“…If a sample exceeded three standard deviations from the group-mean, it was considered an outlier and subsequently removed before analysis. In addition, if a sample was below the detection level, the sample value was transformed by dividing the detection level value with the square root of 2 [ 16 ]. Readings with a value of zero or with a coefficient of variation (CV) above 20% between duplicates were excluded from the dataset.…”

Section: Methodsmentioning

confidence: 99%

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Circulating Inflammatory Markers Are Inversely Associated with Heart Rate Variability Measures in Type 1 Diabetes

Wegeberg

Okdahl

Fløyel

et al. 2020

Mediators of Inflammation

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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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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Circulating Inflammatory Markers Are Inversely Associated with Heart Rate Variability Measures in Type 1 Diabetes

Wegeberg

Okdahl

Fløyel

et al. 2020

Mediators of Inflammation

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“…The anti-inflammatory effects of plant-based diets deserve special mentioning in this discussion, [89][90][91] given the central role of inflammation in pathologic changes of DPN. 92,93 Finally, it is important to note that Bunner and colleagues used a vitamin B12 supplement in their study, which could also have had real effects. 3 On the other hand, a recent review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy.…”

Section: Discussionmentioning

confidence: 99%

“…In light of these findings, it might actually be legitimate to recommend a noncalorie‐restricted, plant‐based diet that induces weight loss while being high in fiber, important micronutrients, and nitric oxide‐rich components that were also shown to favorably affect DPN. The anti‐inflammatory effects of plant‐based diets deserve special mentioning in this discussion, 89–91 given the central role of inflammation in pathologic changes of DPN 92,93 …”

Section: Discussionmentioning

confidence: 99%

Plant‐based diets and diabetic neuropathy: A systematic review

Storz

Küster

2020

Lifestyle Medicine

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Introduction: Diabetic polyneuropathy (DPN) is a debilitating condition and associated with significant morbidity, including gait disturbances, reduced quality of life, and pain, that is often resistant to conventional treatments. Treatment of DPN is based on several major approaches, including risk factor management, intensive glycemic control, and symptomatic pain management. Although some authors argue that none of the existing treatment options are satisfactory, an alternative strategy is frequently overlooked: the use of a whole-food, plant-based diet. The aim of this review was to systematically investigate whether a whole-food, plant-based diet could beneficially affect patients suffering from type 2 diabetes and DPN. Methods: The electronic databases of PubMed and Google Scholar were searched using the keywords "plant-based," "vegetarian," "vegan," "diet," and "diabetic neuropathy." Results: Only a handful of studies investigated the effects of a plant-based diet on diabetic neuropathy. These studies suggest that a plant-based diet may alleviate pain in affected patients while significantly improving glycemic control, overweight, and serum lipids at the same time. Moreover, a plant-based diet appears to reduce the medication burden in affected patients. However, the results must be interpreted with caution, because the number of clinical trials is limited and all studies have important limitations with regard to their methodology. The dietary intervention was often combined with exercise and other supplemental factors, complicating the interpretation of results. Several potential mechanisms of action including improved blood flow and optimized intake of important nutrients were identified. These factors might complementarily contribute to improved perfusion in the endoneurial microvasculature, thus reducing local hypoxia and improving pain. Conclusion: Physicians should consider recommending a plant-based diet to patients suffering from DPN, as current studies show favorable effects in terms of pain management, glycemic control, and reduced medication needs. Further well-designed studies are required to confirm the results of this review. K E Y W O R D S diabetes, diabetic neuropathy, hemorheology, pain, plant-based diet, risk factor management, vegan, vegetarian This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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“…If a sample exceeded three standard deviations from the group-mean it was considered an outlier, and subsequently removed before analysis. In addition, if a sample was below detection level, the sample value was transformed by dividing the detection level value with the square root of 2 (16). Readings with a value of zero or with a coe cient of variation (CV) above 20% between duplicates were excluded from the dataset.…”

Section: Cardiac Vagal Tonementioning

confidence: 99%

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

Wegeberg

Okdahl

Fløyel

et al. 2020

Preprint

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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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Increased levels of inflammatory factors are associated with severity of polyneuropathy in type 1 diabetes

Cited by 20 publications

References 28 publications

Circulating Inflammatory Markers Are Inversely Associated with Heart Rate Variability Measures in Type 1 Diabetes

Circulating Inflammatory Markers Are Inversely Associated with Heart Rate Variability Measures in Type 1 Diabetes

Plant‐based diets and diabetic neuropathy: A systematic review

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

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