Poul Erik Jakobsen

The Degree of Autonomic Modulation Is Associated With the Severity of Microvascular Complications in Patients With Type 1 Diabetes

Objective: The objective of this study was to elucidate whether the degree of autonomic modulation is associated with the degree of microvascular complications in patients with type 1 diabetes. Methods: A total of 290 type 1 individuals with diabetes were randomly recruited during normal visits to outpatient clinics at 4 Danish hospitals. The degree of autonomic modulations was quantified by measuring heart rate variability (HRV) during passive spectral analysis and active tests (valsalva ratio [VT], response to standing [RT], and deep breathing [E:I]). To describe possible associations between severity of microvascular complications and measures of autonomic modulation, multivariate analysis was performed. Results: After adjusting for diabetes duration, sex, age, pulse pressure, heart rate, and smoking, autonomic dysfunction remained significantly correlated with severity of retinopathy, nephropathy, and peripheral neuropathy in individuals with type 1 diabetes patients. Conclusions: Autonomic dysfunction is present in early stages of retinopathy, nephropathy, and peripheral neuropathy in patients with type 1 diabetes.

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

To compare a novel index of parasympathetic tone, cardiac vagal tone, with established autonomic variables and to test the hypotheses that (1) cardiac vagal tone would be associated with established time and frequency domain measures of heart rate and (2) cardiac vagal tone would be lower in people with Type 1 diabetes than in a matched healthy cohort and lower still in people with established neuropathy.

Cardiovascular Autonomic Neuropathy Is Associated With Macrovascular Risk Factors in Type 2 Diabetes: New Technology Used for Routine Large-Scale Screening Adds New Insight

Background: The objective was to identify the presence of cardiovascular autonomic neuropathy (CAN) in a cohort of individuals with diabetes in outpatient clinics from 4 different parts of Denmark and to explore the difference between type 1 and type 2 diabetes in relation to CAN. Methods: The DAN-Study is a Danish multicenter study focusing on diabetic autonomic neuropathy. Over a period of 12 months, 382 type 1 and 271 type 2 individuals with diabetes were tested for CAN. Patients were randomly recruited and tested during normal visits to outpatient clinics at 4 Danish hospitals. The presence of CAN was quantified by performing 3 cardiovascular reflex tests (response to standing, deep breathing, and valsalva). To describe possible associations, multivariate analysis with CAN as the dependent variable was performed. Results: The prevalence of CAN was higher among patients with type 2 diabetes (35%) compared to patients with type 1 diabetes (25%). Multivariate analysis revealed significant associations between CAN and different risk markers in the 2 populations. In type 1 diabetes patients CAN was associated with microalbuminuria (P < .001), macroalbuminuria (P = .011), simplex retinopathy (P < .001), proliferative retinopathy (P < .001), and peripheral neuropathy (P = .041). Among type 2 diabetes patients CAN was independently associated with high pulse pressure (P < .01), BMI (P = .006), and smoking (P = .025). Conclusion: In this cross-sectional observational study CAN was independently associated with microvascular complication in type 1, whereas in type 2 CAN was associated with macrovascular risk factors.

Gastrointestinal motility in people with type 1 diabetes and peripheral neuropathy. Reply to Marathe CS, Rayner CK, Jones KL, et al [letter]

To the Editor:Wewould like to thank Marathe and colleagues for their interest in our recent paper concerning the pan-enteric prolongation of gastrointestinal transit times and an altered caecal pH profile in people with type 1 diabetes and peripheral neuropathy [1, 2]. In their letter, they raise a number of salient and important issues regarding the interpretation of our data. As Marathe et al point out, our study is subject to a number of limitations [2]. The major limitation is that the study is an observational secondary analysis of an ongoing clinical trial and, thus, not designed to address causality between exposure and outcome. However, emerging evidence from other studies provides a plausible potential causal link between pan-enteric prolongation of transit times and diabetic sensory peripheral neuropathy, owing to a shared pathogenesis [3, 4]. For instance, chronic hyperglycaemia directly leads to neuronal impairment, with subsequent indirect consequences that include atherosclerosis compromising neuronal blood flow, neuro-inflammation, heightened oxidative stress and immunological activation of e.g. glia cells. In conjunction, these systemic alterations may result in pathological alterations in, not only peripheral sensorimotor nerves, but also the autonomic nervous system, a branch of which is the enteric nervous system [5]. We readily acknowledge that future research should focus on the characterisation of these aspects in those individuals with co-existing diabetic sensorimotor and autonomic neuropathy. We agree that it would be desirable to compare transit times in people with diabetes, encompassing those with and without a peripheral neuropathy, and in both type 1 and type 2 diabetes.We are currently undertaking a study to address these outstanding questions. However, we would still argue that our data supports the conclusions that gastrointestinal dysmotility is present in a proportion of people with type 1 diabetes with neuropathy, as demonstrated using the wireless motility capsule (WMC). We would concur that previous studies examining gastric emptying demonstrate a wide variety of results in people with diabetes and, furthermore, that comparison between studies is challenging because of differences in demographics, clinical factors and methodology. We agree that the WMC has not been validated in people with type 1 diabetes and peripheral neuropathy per se but, likewise, a similar argument could be * Christina Brock christina.brock@rn.dk