• autonomic neuropathy;
  • cardiovascular autonomic tests;
  • diabetes;
  • oesophageal motility disorders


  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

Abstract  The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficient lower oesophageal sphincter (LOS) relaxation and a higher percentage of simultaneous waves (P < 0.01). Patients with CVAN (n = 22) showed a higher prevalence of pathological simultaneous contractions (>10%), and the prevalence of simultaneous waves related to the degree of autonomic neuropathy was: 9% of patients without CVAN, 7% of those suspected to have it and 50% of patients with CVAN (P < 0.001). Factors associated with the presence of pathological simultaneous waves (>10%) were the presence of CVAN and duration of diabetes (P < 0.05, logistic regression analysis). Increase in simultaneous waves and impaired relaxation of LOS are more frequent in diabetic patients with CVAN.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

As simple non-invasive cardiovascular tests have become routine, many reports have demonstrated that autonomic neuropathy is a common complication of diabetes mellitus (DM), and a predictive factor of mortality.1,2 Symptoms related to cardiovascular autonomic neuropathy (CVAN) appear progressively as diabetes evolves.1 Although symptoms are frequently not recognized for long periods of time, autonomic impairment can be detected using routine cardiovascular tests. Autonomic neuropathy can involve any segment of the gastrointestinal tract.1–7 Mandelstam and Lieber first described a relationship between oesophageal motility disorders and DM in 1967.8 Later studies reported oesophageal alterations in more than 60% of diabetic patients with symptoms related to peripheral or autonomic neuropathy, but oesophageal symptoms were often absent,9 probably due to other mechanisms.10,11 Different degrees of oesophageal dilatation, delayed transit, decrease in number, amplitude and velocity of peristaltic waves, and increased number of simultaneous and multi-peaked contractions have been described in DM,8,12–19 as well as a higher prevalence of pathological gastro-oesophageal reflux due to functional impairment of the lower oesophageal sphincter (LOS).19–21

Correlation between peripheral or CVAN and oesophageal dysfunction has not yet been clarified, because of contradictory results from studies that differ in inclusion criteria and methods of oesophageal function assessment. Some studies documented a higher percentage of oesophageal motility abnormalities, detected by manometry, such as the decrease in velocity of peristaltic waves in diabetic neuropathy,12 or a higher prevalence of multi-peaked waves in patients with both peripheral and autonomic neuropathy.13 Other functional alterations, such as delayed oesophageal transit detected by scintigraphic studies, have been reported as more prevalent in diabetic patients with autonomic neuropathy.22,23 Clinical implications based on the results obtained from these studies are difficult to establish because most included symptomatic patients, and it is well known that oesophageal symptoms could be due to other mechanisms different from motility disturbances, i.e. psychological alterations.24 In contrast to the results from these reports, a poor correlation between autonomic neuropathy and oesophageal dysfunction, assessed by radioisotope studies25 and manometry26 has been described. In a recent well-documented study that used long-term ambulatory oesophageal motility monitoring, Kinekawa et al. demonstrated a significant correlation between oesophageal dysmotility (decreased amplitude and velocity of peristaltic waves, and a lower percentage of effective peristalsis) and the presence of diabetic peripheral motor neuropathy in a group of diabetic patients, but no correlation was found between the presence of autonomic neuropathy and oesophageal dysmotility.19

Data about the relationship between oesophageal motility impairment and autonomic neuropathy in diabetic patients are needed because these results could have prognostic implications in clinical practice. Our hypothesis was that oesophageal motility impairment is related to the presence and severity of autonomic neuropathy in diabetic patients. The aim of our study was to identify both oesophageal and autonomic disorders, as well as the correlation between them, in a group of type 1 diabetic patients without gastrointestinal and autonomic symptoms.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

Inclusion criteria

This study was prospectively conducted in the Endocrinology and Gastroenterology Departments of the Clinic University Hospital of Valencia. The diabetic group (DG) was made up of 46 type 1 diabetic patients (insulin-dependent; 31 men and 15 women, mean age: 33.1 ± 7.5 years). Inclusion criteria were: duration of DM ≥5 years; age <65 years; absence of symptoms related to both oesophageal affection and dysautonomy; absence of structural gastric lesions and gastroparesis (rejected by means of the clinical evaluation and oesophageal-gastric barium transit study); absence of previous oesophageal or gastric surgery.

Patients underwent a clinical protocol including a clinical history, physical examination, blood and urinary analyses (glycaemia, glycosylated haemoglobin, abnormal elements in urine), determination of body mass index (BMI), detection of chronic diabetic complications, particularly in the retina (background examination), kidneys (assessment of creatinine clearance and microalbuminuria), and peripheral nervous system (clinical examination and electrophysiological study).

Patients who showed alterations in the above-mentioned parameters were excluded from the study: (i) associated diseases which could affect the results of CVAN tests (hypertension; heart failure, dysrhythmia or valve disease, ischaemic heart disease, chronic respiratory disease, thyroid dysfunction, ischaemic cerebrovascular events, renal failure; anaemia); (ii) gastroduodenal/systemic diseases which could be associated with gastro-oesophageal reflux; (iii) consumption of more than 30 g of alcohol per day; (iv) ingestion of drugs that could modify CVAN responses and/or oesophageal motility (diuretics, nitrites, β-blocker agents, calcium channel antagonists or anticholinergic agents); (v) state of acute ketoacidosis imbalance; (vi) detection of ketonuria and/or glycaemia levels more than 12 mmol L−1 at the time of the examination; (vii) severe chronic diabetic complications such as albuminuria >300 mg/24 h and/or serum creatinine >105 μmol L−1, blood pressure (BP) >140/90 mmHg; presence of pre- or proliferate retinopathy; painful or disability peripheral neuropathy.

Patients were paired with 34 BMI and age-matched healthy volunteers, which included the control group (CG) (18 men and 16 women, mean age 33.3 ± 8.3 yearrs.). Both diabetic patients and healthy volunteers gave their written consent to participate in the study, which was conducted following the ethical guidelines of the Declaration of Helsinki.


All subjects included in the study (diabetic patients who fulfilled the inclusion criteria and healthy volunteers) underwent CVAN tests, performed by the same doctor, who did not know the diagnosis of the subjects, as well as an oesophageal manometry and pH-metry, performed by a second doctor, who did not know the results of the CVAN study.

CVAN study

Cardiovascular autonomic neuropathy was evaluated according to a standardized protocol including cardiovascular tests that assessed heart rate (HR) and arterial BP changes that depend on cardiovascular reflexes induced by different tests.27 An electrocardiograph with three channels (Siemens Cardiostat 31, Tokyo, Japan) and a sphyngomanometer (Dr Von Recklinghausen Oscillometer model) were used to assess the HR and BP variations respectively. Cardiovascular tests were always performed at 8:00 am and before insulin administration in the case of patients. Parameters obtained were: (i) Valsalva ratio (maximum R-R interval after the Valsalva manoeuvre divided into the minimum R-R during the effort); (ii) expiration/inspiration ratio (E/I ratio), calculated as the quotient between the maximum expiratory R-R and the minimum inspiratory R-R, obtained after a cycle of six deep breaths per minute; (iii) 30/15 ratio, obtained as the longest R-R interval near beat 30 divided into the shortest R-R near beat 15, after standing up; (iv) decrease in systolic BP as a result of in response to standing; (v) increase in diastolic BP during isometric muscle exercise (30% maintenance of the maximum contraction by means of a Bruck pressure dynamometer) with respect to baseline conditions (Handgrip test).27,28

All cardiovascular tests were carried out at least twice, leaving a 2-min recovery period before repeating the manoeuvre or beginning a new one. The recorded result of each test was obtained as the mean of the two manoeuvres. Normal values of these tests were obtained from a sample of healthy volunteers studied in our department,29 and were similar to those proposed by Ewing et al.27

The diagnosis of CVAN was established by determining the total score that included the results of the five tests. Each test received a score from 0 to 2 points (0: normal; 1: borderline; 2: abnormal). In accordance with the results, the patients were divided into three groups: group A, without neuropathy (a total of 0 points); group B, with suspicion of neuropathy (1 point); group C: incipient or established neuropathy (2 or more points).30

Oesophageal manometry

Oesophageal manometry was performed in all subjects, using a multi-lumen catheter with four distal orifices placed at 90° in the same sagittal plane, and four proximal orifices spaced 5, 10, 15 and 20 cm from the former (9012P2271; Medtronic Functional Diagnostics A/S, Medtronic, Skovlunde, Denmark). Each lumen was perfused with distilled water (0.5 mL min−1) by a low compliance hydraulic system (Mui Scientitic, Mississauga, Ont, Canada). Pressures were recorded by means of a pressure transducer (9022K0122; Medtronic Dantec, Skovlunde, Denmark) connected via amplifiers to a chart recorder (PC Polygraf HR, Synectics Medical) and were analysed by the Poligram Windows 2.04 computer program. The most proximal orifice of the catheter, located at the pharynx, was used as the marker for swallowing. A station pull-through technique was used to assess the LOS function on three pull-throughs. Resting and swallowing pressures, as well as LOS relaxation, were recorded every 0.5 cm as the catheter was withdrawn through the gastro-oesophageal junction. The LOS parameters measured were: basal pressure (mmHg), obtained as the difference between the fundic expiratory pressure and the maximum expiratory pressure at the gastro-oesophageal junction, length of LOS (cm), both total and intra-abdominal segment, relaxation of LOS (%) in response to wet swallows. Body oesophageal pressures were recorded at intervals of 5 cm in the lower portion of the oesophageal body, during a minimum of 10 wet swallows. Presence, percentage and amplitude of peristaltic waves, simultaneous waves (simultaneous register of the onset of the contraction in, at least, two different points along the oesophageal body), and other swallowing waves such as double-peak waves, were analysed.31,32 The LOS parameters measured were: basal pressure (mmHg), obtained as the difference between the fundic expiratory pressure and the maximum expiratory pressure at the gastro-oesophageal junction, length of LOS (cm), both total and intra-abdominal segment, relaxation of LOS (%) in response to wet swallows.31,32

24-h oesophageal pH monitoring

Antisecretory drugs were withdrawn 10 days before this study. After a 12-h period of fasting, an antimony electrode was inserted approximately 5 cm above the LOS, which had been identified previously by manometry. Continuous recording for 24 h was performed by means of a Holter recorder (Digitraper III; Synectics Medical, Stockholm, Sweden). Patients were instructed to maintain their usual diet and lifestyle, and to register the appearance and duration of symptoms related to acid reflux on a questionnaire. Data obtained from the 24-h pH monitoring were analysed by the Polygram Windows 2.04 computer program. A total percentage higher than 3.5% of oesophageal pH lower than 4 was considered pathological gastro-oesophageal reflux.20

Statistical analysis

Differences between the groups studied regarding cardiovascular and oesophageal parameters were statistically analysed. Values were expressed as the mean ± standard deviation and percentages. Comparison among groups was established by analysis of variance (anova), and the differences among independent variables by the Student's t-test. The degree of association between two variables was analysed by Pearson correlation coefficient. Comparison of qualitative parameters was performed by the chi-square and Fisher exact tests. Non-parametric variables, detected by the Kolmogorov–Smirnov test, were analysed by the Kruskal–Wallis H-test and the Mann–Whitney U-test. The impact factor of the variables on the presence of oesophageal abnormalities was quantified by logistic regression analysis. P < 0.05 was considered to be significant. The data were analysed using SPSS version 11 (SPSS, Chicago, IL, USA).


  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

Clinical features, results of cardiovascular tests and manometric findings of both groups are shown in Table 1. No statistically significant differences between groups were found when age and BMI were analysed. The following systemic complications were detected in the DG: mild exudative retinopathy in 17 patients (30%), presence of microalbuminuria in 26 (46%) and peripheral neuropathy in 28 (50%). Except for the 30/15 ratio, all cardiovascular parameters were statistically different between groups. With respect to manometric features, LOS relaxation was significantly lower in the DG, compared with the CG. The DG showed a lower mean percentage of peristaltic waves, as well as a higher percentage of simultaneous contractions. Distribution of the percentage of simultaneous contractions and LOS relaxation in both groups of study is shown in Fig. 1; distribution of points suggest a relationship between these two variables, confirmed by the Pearson correlation coefficient (r = −0.561, P = 0.01). No differences between groups were found when basal pressure of LOS and amplitude of peristaltic waves were analysed.

Table 1.   Clinical, cardiovascular and manometric features of the studied groups
 Diabetic groupControl groupStatistical significance
  1. Values are mean ± SD, and n (%) unless otherwise specified. M, male; f, female; DM, diabetes mellitus; BMI, body mass index; HbA1c, glycosylated haemoglobin; E/I ratio: expiration/inspiration ratio; BPS standing up: variation in systolic pressure after standing up; Handgrip test: variation in diastolic pressure during isometric muscle contraction; ns, not significant.

n (gender, m/f)46 (31/15)34 (18/16) 
Age (years)33.1 ± 7.533.3 ± 8.3ns
BMI (kg m−2)23.3 ± 2.723.9 ± 1.2ns
Duration of DM (years)12.1 ± 5.4  
HbA1c (%)7.8 ± 1.34.8 ± 0.3P < 0.001
Cardiovascular tests
 Valsalva ratio1.33 ± 0.221.55 ± 0.21P < 0.001
 E/I ratio1.21 ± 0.121.29 ± 0.10P < 0.001
 30/15 ratio1.31 ± 0.161.30 ± 0.10ns
 BPS standing up9.47 ± 4.868.0 ± 4.4P < 0.001
 Handgrip test20.3 ± 6.2725.6 ± 5.6P < 0.001
Oesophageal parameters
Lower oesophageal sphincter
 Length (cm)3.1 ± 0.83.0 ± 0.5ns
 Basal pressure (mmHg)21.8 ± 8.220.4 ± 7.0ns
 Relaxation (%)78.5 ± 3.795.7 ± 6.9P < 0.001
Oesophageal body
 Simultaneous contractions (%)4.90 ± 0.750.98 ± 2.83P < 0.004
 Peristalsis (%)94.8 ± 6.099.4 ± 2.35P < 0.001
 Amplitude of peristaltic waves (mmHg)75.8 ± 25.778.0 ± 17.7ns

Figure 1.  Distribution of percentage of simultaneous contractions and lower oesophageal sphincter relaxation in control group (A) and diabetic group [B, without cardiovascular autonomic neuropathy (CVAN); C, with suspected CVAN; D, with CVAN]. All subjects are included in the figure; in those cases that one point represent more than one subject, the number of subjects are shown.

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According to the degree of autonomic lesion, diabetic patients were divided into three groups: 11 patients (eight men and three women) without CVAN; 13 patients (eight men and five women) with suspicion of CVAN; 22 patients (15 men and seven women) with incipient or established neuropathy. Differences in the results of CVAN tests between these groups with respect to those obtained from CG are shown in Table 2. Compared with patients with CVAN, patients in group A presented significant differences in all cardiovascular parameters, except for the response of systolic BP to standing up. Moreover, the E/I ratio, 30/15 ratio and the increase in diastolic BP during the Handgrip test, obtained from the group of patients without CVAN, were different from CG (P < 0.02).

Table 2.   Relationship between the degree of CVAN and clinical/cardiovascular parameters
 Diabetic groupControls
Group A: non-CVANGroup B: suspected CVANGroup C: diabetic CVAN
  1. Values are mean ± SD, and n (%) unless otherwise specified. CVAN, cardiovascular autonomic neuropathy; m, male; f, female; DM, diabetes mellitus; BMI, body mass index; HbA1c, glycosylated haemoglobin; E/I ratio: expiration/inspiration ratio; BPS standing up: variation in systolic pressure after standing up; Handgrip test: variation in diastolic pressure during isometric muscle contraction. *P < 0.01, anova test. †P < 0.02 with respect to the control group. ‡P < 0.02 with respect to group C difference with control (P < 0.02).

n (gender, m/f)11 (8/3)13 (8/5)22 (15/7)34 (18/16)
Mean age (years)27.4 ± 4.832.3 ± 6.435.8 ± 8.133.3 ± 8.3
Duration of DM (years)11.4 ± 4.812.3 ± 4.814.0 ± 5.2 
HbA1c (%)7.6 ± 1.27.3 ± 0.88.2 ± 1.35.0 ± 0.2
Valsalva ratio*1.53 ± 0.18‡1.35 ± 0.18†1.24 ± 0.20†1.55 ± 0.21
E/I ratio*1.37 ± 0.09†‡1.21 ± 0.08†‡1.15 ± 0.08†1.29 ± 0.10
30/15 ratio*1.46 ± 0.13†‡1.31 ± 0.141.24 ± 0.151.30 ± 0.10
BPS standing up*10.6 ± 6.2†8.9 ± 3.39.0 ± 4.98.0 ± 4.4
Handgrip test*24.8 ± 7.6‡21.6 ± 4.217.7 ± 7.3†25.6 ± 5.6

Regarding this classification depending on degrees of CVAN, manometric differences between groups of patients and controls were analysed (Table 3). Compared with the CG, patients with CVAN showed a higher mean percentage of simultaneous waves, and a lower percentage of both peristaltic waves and LOS relaxation (P < 0.01). These differences in LOS relaxation were also found in patients without CVAN or those suspected to have it.

Table 3.   Relationship between the degree of CVAN and oesophageal parameters
 Diabetic groupControls
Group A: non-CVANGroup B: suspected CVANGroup C: CVAN
  1. Values are mean ± SD, and n (%) unless otherwise specified. CVAN, cardiovascular autonomic neuropathy. *P < 0.001, †P < 0.01 with respect to the control group. ‡P < 0.01 with group C.

n (gender, m/f)11 (8/3)13 (8/5)22 (15/7)34 (18/16)
Lower oesophageal sphincter
 Length (cm)3.27 ± 0.643.65 ± 0.643.20 ± 0.993.02 ± 0.48
 Basal pressure (mmHg)22.6 ± 6.2821.6 ± 9.4021.5 ± 8.6020.4 ± 7.0
 Relaxation (%)*80.5 ± 1.5†‡80.7 ± 2.7†‡76.8 ± 4.8†95.7 ± 6.9
Oesophageal body
 Simultaneous contractions (%)*1.1 ± 3.6‡3.5 ± 5.27.6 ± 9.0†0.9 ± 2.8
 Peristalsis (%)*97.4 ± 6.296.8 ± 5.291.7 ± 9.3†99.4 ± 2.35
 Amplitude of peristaltic waves (mmHg)83.0 ± 22.476.0 ± 20.271.8 ± 29.578.0 ± 17.7

A pathological prevalence of simultaneous contractions (simultaneous contractions in more than 10% of wet swallows),32 was compared between groups. As shown in Table 4, there were statistically significant differences between diabetic patients and the CG: 1 of 11 patients without CVAN, 1 of 13 with suspected CVAN and 11 of 22 with CVAN (P < 0.001, chi-square test). With respect to results from the ambulatory oesophageal pH monitoring, pathological gastro-oesophageal reflux was detected in 11 patients (seven with CVAN, four suspected CVAN and none in the group without CVAN) and in one subject of the CG. No relationship between pathological reflux and the presence of simultaneous contractions was found, as only one of four patients with suspected CVAN presented non-pathological simultaneous contractions (<10% of wet swallows), and only three of seven patients with CVAN and pathological reflux showed simultaneous contractions (two patients with pathological simultaneous contractions and the other one with simultaneous contractions in less than 10% of swallowing).

Table 4.   Prevalence of oesophageal simultaneous contractions ≥10% in type 1 diabetic subjects (with and without CVAN) and controls
 Diabetic groupControls
Group A: non-CVANGroup B: suspected CVANGroup C: CVAN
  1. Values are n (%) unless otherwise specified. CVAN, cardiovascular autonomic neuropathy. P < 0.001, chi-square test; A vs B: ns; A vs C: P = 0.04; B vs C: P = 0.03.

n (gender, m/f)11 (8/3)13 (8/5)22 (15/7)34 (18/16)
Simultaneous contractions <10%0 (0)3 (23)1 (5)4 (14)
Simultaneous contractions ≥10%1 (9)1 (11)11 (50)0 (0)

Finally, a significant correlation between the presence of pathological simultaneous contractions and the presence of CVAN, and the duration of the diabetes was found by means of logistic regression analysis (P < 0.05). No relationship was detected when age and glycosylated haemoglobin levels were analysed (Table 5).

Table 5.   Factors associated with a pathological percentage of simultaneous contractions (>10%) (logistic regression analysis, Wald method)
 OR95% CIP
  1. Independent variable: simultaneous contractions >10%. Category variables: glycosylated haemoglobin (HbA1c), age, duration of diabetes (years), cardiovascular autonomic neuropathy (CVAN), peripheral neuropathy (PN), pathological gastro-oesophageal reflux (GOR). OR, odds ratio; CI, confidence interval.

Duration of diabetes0.100.01–0.860.036
Pathological GOR0.170.02–1.590.123


  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

It is well known that the prevalence of gastrointestinal disturbances in diabetic patients is higher than in the non-diabetic population. Diabetic complications (peripheral and autonomic neuropathy),33–39 psychological disturbances,40,41and other mechanisms such as physiological variations in glycaemia levels which could affect oesophageal motility, especially the peristaltic velocity,42 have been implicated in its pathogenesis. Gastrointestinal evaluation in DM is important because these disorders have a negative impact on health-related quality of life.1 Taking into account that oesophageal symptoms could be due to mechanisms different from motility disturbances, in order to assess oesophageal function, we included only asymptomatic diabetic patients with good glycaemic control.

In our study, a higher prevalence of simultaneous contractions associated with damage in peristaltic function was detected in diabetic patients, but no differences in the amplitude of peristaltic waves were found between diabetics and controls. Insufficient relaxation of LOS was observed in patients, but statistically significant differences in LOS basal pressure were not found. In agreement with this finding, we have previously reported a similar LOS basal pressure in a group of diabetics (with and without autonomic neuropathy) and controls.20 However, gastro-oesophageal reflux is common in DM, probably due to other mechanisms, i.e. episodes of spontaneous relaxation of LOS. In our group of patients, gastro-oesophageal reflux is not related to the presence of simultaneous contractions. Our results regarding the prevalence of oesophageal dysfunction in DM differ from others that showed a higher percentage; up to 80% in a group of diabetic patients with peripheral neuropathy studied by Hollis et al.,12 and up to 85% of diabetics with cardiovascular damage reported by Espíet al.43 These discrepancies might have resulted from differences in inclusion criteria, as the other studies included older symptomatic patients, and these factors could influence the presence of autonomic dysfunction.

Some studies show that signs of impaired oesophageal peristalsis are common in diabetics with CVAN. In our group of patients, without severe systemic complications or symptoms related to autonomic/oesophageal dysfunction, significant differences were found when oesophageal parameters were analysed depending on different degrees of CVAN. We observed that in patients with more severe CVAN, the pathological percentage of simultaneous contractions was higher (9% in diabetics without CVAN, 11% in those with suspected CVAN and up to a half of diabetics with CVAN). Taking into account that patients included in our study were asymptomatic, we think that this finding is of clinical importance because it could be considered an early sign of damage of oesophageal peristaltic function in DM. Other motility abnormalities, such as double-peak waves, have been reported to be more frequent in a group of asymptomatic diabetic patients with neuropathy (up to 85.7%).13 As other studies did not show these alterations,26 which can also be detected in healthy volunteers (up to 10%), they should not be considered a sign of oesophageal damage.32

The correlation between oesophageal and cardiovascular dysfunction in DM is not yet clear, as contradictory results have been obtained in different studies. Jermendy et al.,25 in a study that included diabetic patients without gastrointestinal symptoms, reported that only 54% of patients with CVAN presented oesophageal abnormalities. The authors hypothesized that both cardiovascular and oesophageal alterations are common but not equally distributed in DM, as vagal denervation of different systems (cardiovascular vs gastrointestinal) could be related to different degrees of nerve damage, and therefore, different underlying physiological mechanisms would explain the lack of correlation.25 In agreement with these observations, a poor correlation between gastrointestinal and cardiovascular abnormalities was reported by Werth et al.44 in a well-documented study that included 26 type 1 diabetics without autonomic symptoms who underwent a motility study of the whole gastrointestinal tract. These authors considered that gastrointestinal involvement would only be considered as a part of diabetic neuropathy affecting in a few patients. A relationship between oesophageal alterations, regarding amplitude and percentage of peristaltic waves, and the presence of motor neuropathy, was reported by Kinekawa et al. in a group of type 2 diabetics, but no relationship was found with the presence of signs of cardiovascular neuropathy.19 In agreement with these results, Annese et al. concluded that the detection of autonomic neuropathy has a poor predictive value on the presence of digestive motor disorders, as only 51.4% of diabetics studied presented manometric oesophageal alterations, and 45.7% of them showed abnormal oesophageal transit, detected by isotopic studies.45 In contrast to these results, our study showed oesophageal motility alterations in diabetic patients, especially regarding a pathological prevalence of simultaneous contractions. Moreover, according to different degrees of CVAN, we detected the most frequent oesophageal abnormalities in the group of diabetics with CVAN. Our results are not in agreement with those obtained by other studies and could be explained by differences in inclusion criteria of our group of patients, as none of them showed autonomic or oesophageal symptoms. We think that the high pathological percentage of simultaneous contractions, detected in up to 50% of diabetics with CVAN, could be considered an early sign of oesophageal peristaltic function damage. We conclude that cardiovascular affection correlates with early oesophageal dysfunction, especially the increase in simultaneous contractions. The presence of CVAN and the duration of diabetes are the most important predictive parameters to detect oesophageal motility disturbances in diabetic patients. More studies are needed to determine the underlying physiological mechanisms of cardiovascular and/or gastrointestinal neuropathy involvement in DM.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References

Supported in part by a grant from the Instituto de Salud Carlos III (03/02).


  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgment
  8. References
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