Improvement of Cardiovascular Autonomic Reflexes after Amelioration of Metabolic Control in Insulin-Dependent Diabetic Subjects with Severe Autonomic Neuropathy

Fedele, Domenico; Bellavere, F.; Cardone, C.; Ferri, M; Crepaldi, G.

doi:10.1055/s-2007-1013560

Cited by 19 publications

(11 citation statements)

References 11 publications

(11 reference statements)

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“…Diabetic autonomic neuropathy is usually considered to be an irreversible disorder.24 However, slight improvement in cardiovascular tests has been observed after amelioration of metabolic control. 25 Our data do not confirm this. The significantly decreased thermal discrimination thresholds seen in the present study are consistent with the report of Strian et al 26 These authors demonstrated marked improvement of thermal cutaneous sensation during improved glycaemic control in a diabetic patient with painful neuropathy.…”

Section: Resultscontrasting

confidence: 77%

Peripheral nerve function in patients with painful diabetic neuropathy treated with continuous subcutaneous insulin infusion.

Bertelsmann

Heimans

Rooy

et al. 1987

Journal of Neurology, Neurosurgery & Psychiatry

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SUMMARY In order to study the effects of improved metabolic control on painful diabetic polyneuropathy, 15 patients were treated with continuous subcutaneous insulin infusion over a 12 month period. Polyneuropathy was assessed by pain score, neurological examinations, nerve conduction studies and determination of sensory thresholds and cardiovascular reflexes. Improved metabolic control was confirmed by significantly improved levels of glycosylated haemoglobin (1 1l7 + 0O3% at entry to the study, to 8-7 + 0O3% after 12 months; mean + SEM). Symptomatic relief was confirmed by significantly improved pain scores. Thresholds for thermal cutaneous sensation improved significantly from 6-0 + 08°C at entry to the study to 2-7 + 07°C after 12 months (mean + SEM). These findings suggest a selective improvement of peripheral small nerve fibre function after continuous subcutaneous insulin infusion. The importance of quantitating thermal cutaneous sensation in longitudinal studies of patients with diabetic neuropathy was confirmed.Although the pathogenesis of diabetic neuropathy is still poorly understood, several observations suggest that hyperglycaemia is a major cause of abnormal nerve function and painful neuropathy.`3 This has led to efforts to improve glycaemic control in the management of diabetic patients with neuropathy.4 s It has been shown that the use of an insulin infusion pump is a valuable method for achieving a near normoglycaemia in a diabetic patient.67Several reports have described the effects of continuous subcutaneous insulin infusion therapy on nerve function.8 -12 However, diabetic patients with painful neuropathy have only been examined in a few trials.'3-15 Moreover, in these studies, only the function of the largest and fast conducting nerve fibres was monitored.In the present study we treated a group of 15 diabetic patients suffering from painful polyneuropathy with continuous subcutaneous insulin infusion.

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Section: Resultscontrasting

confidence: 77%

Peripheral nerve function in patients with painful diabetic neuropathy treated with continuous subcutaneous insulin infusion.

Bertelsmann

Heimans

Rooy

et al. 1987

Journal of Neurology, Neurosurgery & Psychiatry

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“…glucose control) changes. Quite a few of these changes are potentially reversible (Fedele et al, 1985), pointing to the importance of good metabolic control of glycaemia in patients with DM. Improvement has also been found when patients with and without DM exercised regularly (Williamson et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…This would be of special interest because of an unclear relationship between metabolic control, ANS damage and mortality, as described elsewhere (Hasslacher & Baessler, 1983). However, the hypothesis (Fedele et al, 1985;Sundkvist & Liljia, 1985) that in a stable metabolic state patients with DM might not suffer from excess mortality has yet to be con®rmed in the group with and without clinically manifest involvement of the peripheral nervous system. The comparison of patients in a prospective setting using spectral analysis to determine the morbidity and mortality rate in this population is urgently needed.…”

Section: Discussionmentioning

confidence: 99%

“…However, with a mean duration of the disease of 7á3 years, our population is not entirely comparable with these studies. Quite a few of these changes are potentially reversible (Fedele et al, 1985), pointing to the importance of good metabolic control of glycaemia in patients with DM. The answer to this question would provide new insight into the pathophysiology of DM.…”

Section: Rest Stress Rest Stressmentioning

confidence: 99%

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Early autonomic dysfunction in patients with diabetes mellitus assessed by spectral analysis of heart rate and blood pressure variability

Laederach‐Hofmann

Mussgay

Winter

et al. 1999

Clinical Physiology

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Patients with diabetes mellitus (DM) often have alterations of the autonomic nervous system (ANS), even early in their disease course. Previous research has not evaluated whether these changes may have consequences on adaptation mechanisms in DM, e.g. to mental stress. We therefore evaluated whether patients with DM who already had early alterations of the ANS reacted with an abnormal regulatory pattern to mental stress. We used the spectral analysis technique, known to be valuable and reliable in the investigation of disturbances of the ANS. We investigated 34 patients with DM without clinical evidence of ANS dysfunction (e.g. orthostatic hypotension) and 44 normal control subjects (NC group). No patients on medication known to alter ANS responses were accepted. The investigation consisted of a resting state evaluation and a mental stress task (BonnDet). In basal values, only the 21 patients with type 2 DM were different in respect to body mass index and systolic blood pressure. In the study parameters we found significantly lower values in resting and mental stress spectral power of mid-frequency band (known to represent predominantly sympathetic influences) and of high-frequency and respiration bands (known to represent parasympathetic influences) in patients with DM (types 1 and 2) compared with NC group (5.3 +/- 1.2 ms2 vs. 6.1 +/- 1.3 ms2, and 5.5 +/- 1.6 ms2 vs. 6.2 +/- 1.5 ms2, and 4.6 +/- 1.7 ms2 vs. 6.2 +/- 1.5 ms2, for resting values respectively; 4.7 +/- 1.4 ms2 vs. 5.9 +/- 1.2 ms2, and 4.6 +/- 1.9 ms2 vs. 5.6 +/- 1.7 ms2, and 3.7 +/- 2.1 ms2 vs. 5.6 +/- 1.7 ms2, for stress values respectively; M/F ratio 6/26 vs. 30/14). These differences remained significant even when controlled for age, sex, and body weight. However, patients with DM type 2 (and significantly higher body weight) showed only significant values in mental stress modulus values. There were no specific group effects in the patients with DM in adaptation mechanisms to mental stress compared with the NC group. These findings demonstrate that power spectral examinations at rest are sufficiently reliable to diagnose early alterations in ANS in patients with DM. The spectral analysis technique is sensitive and reliable in investigation of ANS in patients with DM without clinically symptomatic autonomic dysfunction.

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“…As both autonomic neuropathy (43) and cellular insulin resistance (44,45) appear to be causally linked to chronic hyperglycemia, improvement of glycemic control might reverse both problems. These include blunted changes in heart rate and blood pressure and an excessive fall in forearm vascular resistance.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Altered Hemodynamic and Metabolic Responses to Insulin in Patients with Insulin-Dependent Diabetes Mellitus and Autonomic Dysfunction¹

Mäkimattila

Mäntysaari

Schlenzka

et al. 1998

The Journal of Clinical Endocrinology & Metabolism

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Patients with autonomic neuropathy are more susceptible to insulin-induced hypotension than normal subjects, but the mechanisms are unclear. We quantitated the hemodynamic and metabolic effects of two doses of i.v. insulin (1 and 5 mU/kg.min, 120 min each) and several aspects of autonomic function in 28 patients with insulin-dependent diabetes mellitus (IDDM) and in 7 matched normal subjects under standardized normoglycemic conditions. The autonomic function tests included those predominantly assessing the integrity of vagal heart rate control (the expiration inspiration ratio during deep breathing and high frequency power of heart rate variability) and tests measuring sympathetic nervous function (reflex vasoconstriction to cold and blood pressure responses to standing and handgrip). During hyperinsulinemia, heart rate increased less (2 +/- 1 vs. 6 +/- 2 beats/min; P < 0.04) and diastolic blood pressure fell more (-3.1 +/- 1.2 vs. 0.9 +/- 2.1; P = NS) in the patients with IDDM than in the normal subjects. Forearm vascular resistance decreased significantly in the patients with IDDM [by -7.1 +/- 1.4 mm Hg/(mL/dL.min); P < 0.001 for high vs. low dose insulin], but not in the normal subjects (-0.1 +/- 2.5 mm Hg/(mL/dL.min; P = NS). Reflex vasoconstriction to cold was inversely correlated with the decreases in diastolic (r = -0.51; P < 0.005) and systolic (r = -0.59; P < 0.001) blood pressure and forearm vascular resistance (r = -0.53; P < 0.005), but not with the change in heart rate. The expiration inspiration ratio was, however, directly correlated with the insulin-induced change in heart rate (r = 0.63; P < 0.001), but not with diastolic or systolic blood pressure or forearm vascular resistance. Whole body (48 +/- 2 vs. 67 +/- 5 mumol/kg.min; P < 0.005) and forearm (44 +/- 4 vs. 67 +/- 8 mumol/kg.min; P < 0.05) glucose uptake were significantly lower in the IDDM patients than in the normal subjects. The latter could be attributed to a defect in the forearm glucose arterio-venous difference (1.5 +/- 0.1 vs. 2.2 +/- 0.2 mmol/L, respectively; P < 0.01), but not in blood flow. We conclude that both impaired vagal heart rate control and sympathetic nervous dysfunction exaggerate the hemodynamic effects of insulin in patients with IDDM and could contribute to insulin-induced hypotension.

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Improvement of Cardiovascular Autonomic Reflexes after Amelioration of Metabolic Control in Insulin-Dependent Diabetic Subjects with Severe Autonomic Neuropathy

Cited by 19 publications

References 11 publications

Peripheral nerve function in patients with painful diabetic neuropathy treated with continuous subcutaneous insulin infusion.

Peripheral nerve function in patients with painful diabetic neuropathy treated with continuous subcutaneous insulin infusion.

Early autonomic dysfunction in patients with diabetes mellitus assessed by spectral analysis of heart rate and blood pressure variability

Mechanisms of Altered Hemodynamic and Metabolic Responses to Insulin in Patients with Insulin-Dependent Diabetes Mellitus and Autonomic Dysfunction¹

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Improvement of Cardiovascular Autonomic Reflexes after Amelioration of Metabolic Control in Insulin-Dependent Diabetic Subjects with Severe Autonomic Neuropathy

Cited by 19 publications

References 11 publications

Peripheral nerve function in patients with painful diabetic neuropathy treated with continuous subcutaneous insulin infusion.

Peripheral nerve function in patients with painful diabetic neuropathy treated with continuous subcutaneous insulin infusion.

Early autonomic dysfunction in patients with diabetes mellitus assessed by spectral analysis of heart rate and blood pressure variability

Mechanisms of Altered Hemodynamic and Metabolic Responses to Insulin in Patients with Insulin-Dependent Diabetes Mellitus and Autonomic Dysfunction1

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Mechanisms of Altered Hemodynamic and Metabolic Responses to Insulin in Patients with Insulin-Dependent Diabetes Mellitus and Autonomic Dysfunction¹