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

OBJECTIVE: Distal symmetrical polyneuropathy (DSPN) is a severe common long-term complication of type 1 diabetes caused by impaired sensory-motor nerve function. As chronic low-grade inflammation may be involved in the pathogenesis of DSPN, we investigated the circulating levels of inflammatory markers in individuals with type 1 diabetes with and without DSPN. Furthermore, we determined to what extent these factors correlated with different peripheral sensory nerve functions. DESIGN: Cross-sectional study. PATIENTS: The study included 103 individuals with type 1 diabetes with (n = 50) and without DSPN (n = 53) as well as a cohort of healthy controls (n = 21). MEASUREMENTS: Circulating levels of various inflammatory markers (cytokines, chemokines and soluble adhesion molecules) were determined in serum samples by Luminex multiplexing technology. Peripheral sensory nerve testing, for example vibration, tactile and thermal perception, was assessed by standardized procedures. RESULTS: The cytokines IL-1α, IL-4, IL-12p70, IL-13, IL-17A and TNF-α; the chemokine MCP-1; and the adhesion molecule E-selectin were significantly increased in individuals with type 1 diabetes with DSPN compared to those without DSPN (P < .001). These observations were independent of age, sex, BMI, disease duration and blood pressure. Additionally, higher serum concentrations of cytokines and chemokines were associated with higher vibration and tactile perception thresholds, but not with heat tolerance threshold. CONCLUSIONS: Individuals with type 1 diabetes and concomitant DSPN display higher serum levels of several inflammatory markers. These findings support that systemic low-grade inflammation may play a role in the pathogenesis of DSPN.

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

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.

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

BACKGROUND: Although gastrointestinal (GI) symptoms are common in diabetes, they frequently do not correlate with measurable sensorimotor abnormalities. The wireless motility capsule (WMC) measures pressure, temperature, and pH as it traverses the GI tract wherefrom transit times and motility indices are derived. The aim was to investigate whether GI symptoms correlate with changes in (a) segmental transit times, (b) segmental motility index, (c) cardiac vagal tone, or (d) presence/absence of peripheral neuropathy in type 1 diabetes. METHODS: Gastrointestinal symptoms in 104 participants with type 1 diabetes were measured using Gastroparesis Cardinal Symptoms Index and Gastrointestinal Symptom Rating Scale. All underwent standardized WMC investigation measuring segmental transit time and motility. Cardiac vagal tone and presence of peripheral neuropathy were measured using electrocardiographic and nerve conduction velocity testing. KEY RESULTS: Colonic transit time was correlated with postprandial fullness (P = .01) and constipation (P = .03), while decreased colonic motility index was correlated with diarrhea (P = .01) and decreased bloating (P < .05). Symptoms were not correlated with gastric or small bowel transit time or motility index. In participants with low cardiac vagal tone, gastric motility index (P < .01) and colonic transit time (P < .05) were increased, but not in those with peripheral neuropathy. Abdominal pain was decreased with both peripheral neuropathy (P = .04) and decreased cardiac vagal tone (P = .02). CONCLUSIONS AND INFERENCES: This study supports the rationale for whole gut investigation, using not only transit times but incorporating contractility indices as well. Furthermore, a decreased parasympathetic modulation and an increased hyposensate state appear to be present in type 1 diabetes.

The day-night pattern of colonic contractility is not impaired in type 1 diabetes and distal symmetric polyneuropathy.

Colonic contractility normally shows circadian variability regulated by sleep and especially food intake. However, individuals with type 1 diabetes have a reduced or even absent gastrocolic response to a meal, indicating that colonic contractility may be affected by the disease. We hypothesized that individuals with type 1 diabetes and distal symmetric polyneuropathy (DSPN) have decreased motility (expressed as the motility index) and contractility of the colon and a reduced increase in motility index from night to morning compared to healthy controls and individuals with type 1 diabetes without DSPN. Cohorts of 35 individuals with type 1 diabetes and DSPN, 40 individuals with type 1 diabetes without DSPN, and 28 healthy controls were included in this post-hoc, cross-sectional analysis. We investigated, using a wireless motility capsule that measures pH, temperature, and pressure throughout the gastrointestinal tract, whether individuals with type 1 diabetes with and without DSPN, compared to healthy controls, exhibit altered colonic contractility in the evening, night, and morning. Max amplitude, mean peak amplitude, mean contraction, and motility index of the colon were calculated at the afore-designated times. Motility index of the colon tended to be higher in individuals with type 1 diabetes and DSPN compared to controls in the evening (P = .064), but the effect size was small (1.74%). There was no difference in motility index between the groups in the morning or evening. Furthermore, there was no difference in max amplitude, mean peak amplitude, or mean contraction between groups in the morning, evening, and night. As expected, overall contractility increased from night to morning in all groups, but there was no difference between groups in the increase in contractility from night to morning. Colonic contractility generally peaked in the morning, decreased in the evening, and was almost absent at night. Type 1 diabetes and/or DSPN did not impair contractility of the colon at any time point. Contractility and motility increased from morning to night unaffected by type 1 diabetes and/or DSPN.

Quantities of comorbidities affects physical, but not mental health related quality of life in type 1 diabetes with confirmed polyneuropathy.

BACKGROUND: A large number of adults with long-term type 1 diabetes are affected by symmetrical peripheral neuropathy. These complications increase socioeconomic expenses and diminish the individual quality of life. The 36-Item Short Form Health Survey (SF-36) is a generic patient reported questionnaire, measuring mental and physical health related quality of life. We hypothesized that diabetic neuropathy would decrease physical and mental quality of life measured with SF-36, and that clinical appearance may be associated with the decline. AIM: To investigate if diabetic neuropathy would decrease physical and mental quality of life measured with SF-36, and if clinical appearance may be associated with the decline. METHODS: Forty-eight adults [age 50 ± 9 years, 10 females, disease duration 32 (14-51) years] with verified diabetic symmetrical peripheral neuropathy and 21 healthy participants (age 51 ± 6 years, 6 females) underwent standardised nerve conduction testing and completed the SF-36 questionnaire. Furthermore, disease duration, number of comorbidities, both diabetes related and nondiabetes related, vibration perception threshold, number of hypoglycaemic events, HbA1c and administration way of insulin was notified. RESULTS: In comparison to healthy subjects, patients' mental composite score was not significantly diminished (51.9 ± 8.9 vs 53.1 ± 5.5, P = 0.558), while the physical composite score was (46.3 ± 11.7 vs 54.6 ± 3.3, P = 0.002). As expected, the overall physical health related symptoms in patients were associated to total number of comorbidities (P < 0.0001), comorbidities relation to diabetes (P = 0.0002) and HbA1c (P = 0.005) as well as comorbidities not related to diabetes (P = 0.0006). CONCLUSION: The finding of this study emphasises the importance of focusing on quality of life in adults with diabetes and especially in those with multiple comorbidities as well as the possibility of HbA1c as a biomarker for severe complication.