Usefulness of cardiovascular tests of autonomic function in asymptomatic diabetic patients

A group of five cardiovascular tests of autonomic neural function was studied in 115 asymptomatic insulin-dependent diabetic patients and nine patients with symptoms of diabetic autonomic neuropathy. In the asymptomatic group, 34 patients had one or more abnormal test. R-R variation during deep breathing was most frequently abnormal, but reliance on this test alone to examine parasympathetic function would have missed 12 of the 34 abnormal patients. The two abnormal responses to isometric exercise in this group were probably false-positive results caused by poor patient effort. In the symptomatic patients, R-R variation during deep breathing was abnormal in all nine, the blood pressure response to standing was abnormal in seven, and the response to isometric exercise was abnormal in three. The blood pressure response to isometric exercise is uncomfortable, requires special equipment, and should probably be confined to the assessment of symptomatic patients in a specialist setting.     

Autonomic nerve antibodies and autonomic nerve function in type 1 and type 2 diabetic patients

Complement-fixing adrenal medulla (CF-ADM), sympathetic ganglion (CF-SG), and vagal (CF-V) nerve antibodies were determined in diabetic patients. Among 74 patients with Type 1 diabetes, CF-ADM was detected in 7 (10%) cases, CF-SG in 14 (19%) cases, and CF-V in 8 (11%) cases. Among 38 patients with Type 2 diabetes, CF-ADM was detected in 5 (13%) cases, CF-SG in 4 (11%) cases, and CF-V in 6 (16%) cases. There were associations between autonomic nerve antibodies and autonomic nerve function. CF-ADM and/or CF-SG were significantly (P less than 0.002) less prevalent in Type 1 diabetic patients with autonomic neuropathy than in those without [5/44 (11%) vs. 14/30 (47%)] and, in agreement with this, the brake index, a sign of parasympathetic and sympathetic autonomic nerve function, was significantly (P less than 0.005) higher (more normal) in these patients (-0.56 +/- 0.13 vs. -1.04 +/- 0.12). In Type 2 diabetic patients, the E/I ratio, an index of parasympathetic nerve function, was significantly (P less than 0.03) lower (more abnormal) in those with CF-V than in those without (-1.81 +/- 0.17 vs. -1.20 +/- 0.11). In conclusion, the frequency of sympathetic nerve antibodies was decreased in Type 1 diabetic patients with autonomic neuropathy, while in Type 2 diabetic patients parasympathetic nerve antibodies were related to severe parasympathetic neuropathy.     

Dissociated sensory loss in diabetic autonomic neuropathy.

Aims: Clinical observation has led to the idea that there might be a distinctive form of selective sensory and autonomic neuropathy affecting patients with Type 1 diabetic mellitus with severe symptomatic autonomic neuropathy (Type 1-DAN) and this study was conducted to evaluate the presence of such a neuropathy in Type 1-DAN. METHODS: Nineteen Type 1 diabetic patients presenting for treatment of severe symptomatic autonomic neuropathy were examined (all had > or = 2 autonomic symptoms; age 39.3 +/- 10.2 years; duration of disease 25.6 +/- 10.5 years). For comparison, 19 Type 1 diabetic patients with neuropathic foot ulcers (age 44.5 +/- 6.6 years; duration of disease 26.7 +/- 9.2 years), 14 clinically uncomplicated Type 1 diabetic patients (age 39.9 +/- 5.6 years; duration of disease 22.9 +/- 9.3 years) and 16 non-diabetic healthy people as controls (age 39.3 +/- 10.7 years) were also examined. Results The large fibre modalities (light touch and vibration perception) were better preserved in the Type 1-DAN group than in the foot ulcer group. Thus, light touch sensation was normal in 11 out of 19 Type 1-DAN patients compared to only three out of 19 foot ulcer patients (P < 0.01), and vibration perception was 24.9 +/- 15.0 V and 40.5 +/- 7.9 V, respectively (P < 0.002) with some of the Type 1-DAN patients in the normal range. In contrast, the small fibre modalities, thermal perception and autonomic function, were grossly abnormal in both groups (hot thermal perception 14.1 +/- 2.5 degrees C and 12.6 +/- 3.7 degrees C; cold thermal perception 13.8 +/- 2.7 degrees C and 10.9 +/- 4. 7 degrees C; heart rate variation 2.9 +/- 1.5 beats/min and 4.8 +/- 4.0 beats/min, respectively). CONCLUSIONS: There is indeed a subgroup of Type 1 diabetic neuropathy patients who suffer from severe autonomic symptoms associated with a selective small fibre sensory and autonomic loss with relatively preserved large fibre sensory modalities.     

C-peptide improves autonomic nerve function in IDDM patients

Summary In order to determine the possible influence of C-peptide on nerve function, 12 insulin-dependent diabetic (IDDM) patients with symptoms of diabetic polyneuropathy were studied twice under euglycaemic conditions. Tests of autonomic nerve function (respiratory heart rate variability, acceleration and brake index during tilting), quantitative sensory threshold determinations, nerve conduction studies and clinical neurological examination were carried out before and during a 3-h i. v. infusion of either C-peptide (6 pmol · kg^–1 · min^–1) or physiological saline solution in a double-blind study. Plasma C-peptide concentrations increased from 0.11±0.02 to 1.73±0.04 nmol/l during C-peptide infusion. Clinical neurological examination quantitative sensory threshold evaluations and nerve conduction measurements failed to detect significant changes between C-peptide and saline study periods. Respiratory heart rate variability increased significantly from 13±1 to 20±2% during C-peptide infusion (p<0.001), reaching normal values in five of the subjects; control studies with saline infusion did not alter the heart rate variability (basal, 14±2; saline, 15±2%). A reduced brake index value was found in seven patients and increased significantly during the C-peptide infusion period (4.6±1.0 to 10.3±2.2%, p<0.05) but not during saline infusion (5.9±2 to 4.1±1.1%, NS). It is concluded that short-term (3-h) infusion of C-peptide in physiological amounts may improve autonomic nerve function in patients with IDDM.Abbreviations IDDM Insulin-dependent diabetes mellitus - VT vibration perception threshold - CV conduction velocity - DL distal latency - CMAP compound action potential - S sensory amplitude - E/I ratio expiration/inspiration ratio     

Glutamic acid decarboxylase antibodies,autonomic nerve antibodies and autonomic neuropathy in diabetic patients

Summary To clarify whether GAD-ab are associated with diabetic autonomic neuropathy and/or complement fixing antibodies against sympathetic ganglia, adrenal medulla, and vagus nerve, we examined 133 diabetic patients (95 with IDDM). GAD-ab were determined by a radioligand binding assay using in vitro expression of recombinant GAD-65 whereas sympathetic ganglia antibodies, adrenal medulla antibodies, vagus nerve, and ICA were evaluated by indirect immunofluorescence assays. Autonomic nerve function was evaluated by objective tests (heart rate reactions to deep breathing and to tilt). In the total material of 133 patients, GAD-ab were detected in 36 patients, all of whom had IDDM. The frequency of GADab was similar (38%) in IDDM patients with and without signs of autonomic neuropathy (21 of 55 vs 15 of 40). In addition, there were no significant associations between GAD-ab and autonomic nerve antibodies; GAD-ab were detected in 9 of 21 (43%) of patients with and in 27 of 112 (24%) of patients without sympathetic ganglia antibodies, in 5 of 15 (33%) of patients with and 31 of 118 (26%) without adrenal medulla antibodies, and in 5 of 15 (33%) with and 31 of 118 (26%) of patients without vagus nerve antibodies. The frequency of ICA, however, was significantly increased in patients with sympathetic ganglia antibodies compared with those without sympathetic ganglia antibodies (10 of 21 [48%] vs 21 of 112 [19%]; p<0.01). In conclusion, GAD-ab were neither associated with disturbed autonomic nerve function nor with antibodies against autonomic nerve structures.Abbreviations GAD Glutamic acid decarboxylase - ab antibodies - ICA islet cell antibodies - CF-ADM complement-fixing adrenal medulla antibodies - CF-SG complement-fixing sympathetic ganglia antibodies - CF-V complement-fixing vagal nerve antibodies - IDDM insulin-dependent diabetes mellitus - NIDDM non-insulin-dependent diabetes mellitus - JDF Juvenile Diabetes Foundation     

Assessment of gastric neuropathy using electrogastrography in asymptomatic diabetic patients. Correlation with cardiac autonomic neuropathy.

This study assessed gastric neuropathy in type 1 diabetes mellitus and its relationships with cardiac autonomic neuropathy. Fifty-four asymptomatic type 1 patients (43 +/- 12 years) and 15 healthy subjects participated in the study. Cutaneous electrogastrography (EGG) was recorded for 4 h before, during, and 4 h after the ingestion of a standard meal. EGG frequency was divided into three bands: bradygastria [< 2 cpm), normal (2-4 cpm) and tachygastria (4-10 cpm)]. Assessment of diabetic autonomic neuropathy was based on Ewing tests and time and frequency domain indexes, which were analyzed from 24-h continuous ECG recordings. Tachygastria was significantly more common in diabetic patients than in controls throughout the recording period (38 +/- 5 vs 23 +/- 11.8%, p < 0.001), before (37 +/- 6 vs 26.5 +/- 8.9%, p < 0.001), during (41 +/- 7.8 vs 23 +/- 10.5%, p < 0.001) and after the meal (37 +/- 6.9 vs 29 +/- 9.8%, p < 0.001). The percentage of dominant frequency in the normal range was significantly lower in diabetic patients than controls (49 +/- 6 vs 63.3 +/- 11.1%, p < 0.001). Tachygastria was correlated with duration of diabetes (r = 0.234, p < 0.05), but not with glycaemic control. Abnormalities in gastric myoelectrical activity were not correlated with Ewing tests or time and frequency domain indexes.     

A 14-year prospective study of autonomic nerve function in Type 1 diabetic patients: association with nephropathy.

AIMS: Prospective studies of autonomic nerve function are rare. We have followed the progression of autonomic dysfunction in relation to nephropathy over 14 years in Type 1 diabetic patients. METHODS: Autonomic nerve function was assessed by heart-rate responses to deep breathing (E/I ratio) and tilting (acceleration and brake indices) and by the postural blood pressure reaction in 58 patients, 43 of whom were reassessed after 14 years. Nephropathy was evaluated by the degree of albuminuria (albuminuria > 20 micro g/min or > 0.03 g/24 h) and glomerular filtration rate ((51)Cr-EDTA plasma clearance). The acceleration index had deteriorated after 7 years (P = 0.0155), whereas the E/I ratio (P = 0.0070) and the diastolic postural blood pressure reaction (P = 0.0054) had deteriorated 14 years after the baseline examination (age-corrected values). All those with albuminuria at the third examination showed signs of autonomic neuropathy at baseline (10 of 10) compared with only nine of 22 without (P = 0.0016). Multiple regression analysis showed that the association between autonomic dysfunction and future albuminuria was due to the E/I ratio. In addition, individuals with an abnormal postural diastolic blood pressure fall (n = 7) at baseline showed a greater fall in glomerular filtration rate more than others 7-14 years later [29 (16.5) ml/min/1.72 m(2) vs. 11 (9) ml/min/1.72 m(2); P = 0.0074]. CONCLUSION: Autonomic nerve function had deteriorated after 14 years. Autonomic neuropathy and abnormal postural diastolic blood pressure falls at baseline were associated with future renal complications.     

Disturbed autonomic nerve function in patients with Crohn's disease

Autonomic nerve function was evaluated in 33 patients with Crohn's disease (age range, 19-66 years; mean, 36 years) by three established non-invasive tests based on the heart reactions to deep breathing (E/I ratio) and to tilt (acceleration and brake indices). Peripheral nerve function was evaluated neurographically and by measuring thresholds to vibration and temperature changes. None of the patients were diabetic, and all had normal thyroid function. In spite of normal peripheral nerve function, almost half of the patients, 48% (16/33), showed signs of autonomic neuropathy (AN). The occurrence of AN was not related to duration or severity of Crohn's disease or to biochemical evidence of inflammation or malabsorption of vitamins and trace elements. We conclude that autonomic nerve dysfunction is a feature of Crohn's disease which may be relevant with regard to the frequent disturbance in bowel function in patients with this disorder.     

Acute effects of sildenafil on flow mediated dilatation and cardiovascular autonomic nerve function in type 2 diabetic patients

Background Sildenafil, frequently used as on demand medication for the treatment of erectile dysfunction (ED), has been suggested to improve endothelial function but also to alter blood pressure (BP) and induce sympathetic activation. In people with type 2 diabetes mellitus (T2DM), a high‐risk population, the safety profile and the effects on endothelial function of a maximal sildenafil dose (100 mg) have not been investigated and therefore constituted the aim of our study. Methods A double‐blind, placebo‐controlled, cross‐over trial using a single dose of 100 mg sildenafil or placebo has been conducted in 40 subjects with T2DM without known CVD. Haemodynamic parameters, flow mediated dilatation (FMD) in brachial artery, cardiovascular autonomic function tests and spontaneous baroreflex sensitivity (BRS) were measured. Results Sixty minutes after administration of sildenafil but not placebo, a fall of supine systolic blood pressure (SBP) (?5.41 ± 1.87 vs. + 0.54 ± 1.71 mmHg) and diastolic blood pressure (DBP) (?4.46 ± 1.13 vs. + 0.89 ± 0.94 mmHg), as well as orthostatic SBP (?7.41 ± 2.35 vs. + 0.94 ± 2.06 mmHg) and DBP (?5.65 ± 1.45 vs. + 1.76 ± 1.00 mmHg) during standing occurred, accompanied by an increase in heart rate (+1.98 ± 0.69 vs. ? 2.42 ± 0.59 beats/min) (all p < 0.01 vs. placebo). Changes in BP to standing up, FMD, time domain and frequency domain indices of heart rate variability (HRV) and BRS were comparable between sildenafil and placebo. Conclusions Sildenafil administered at a maximum single dose to T2DM men results in a mild increase in heart rate and decrease in BP, but it induces neither an acute improvement of FMD nor any adverse effects on orthostatic BP regulation, HRV and BRS. Copyright © 2008 John Wiley & Sons, Ltd.     

Differences in autonomic nerve function in patients with silent and symptomatic myocardial ischaemia.

BACKGROUND--Autonomic neuropathy provides a mechanism for the absence of symptoms in silent myocardial ischaemia, but characterisation of the type of neuropathy is lacking. AIM--To characterise and compare autonomic nerve function in patients with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS--The Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and standing, lower body negative pressure, isometric handgrip, and the cold pressor test were performed by patients with silent (n = 25) and symptomatic (n = 25) ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic efferent function between patients with silent and symptomatic ischaemia was recorded, but both had significantly less HRV in response to standing than the controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with silent ischaemia showed an increased propensity for peripheral vasodilatation compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired sympathetic function was found in patients with pure silent ischaemia (n = 4) compared with the remaining patients with silent ischaemia whose pain pathways were presumed to be intact. CONCLUSIONS--Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction.     

Morphometry of endoneurial capillaries in diabetic sensory and autonomic neuropathy

Summary Nerve biopsies were obtained from 27 patients with diabetic neuropathy. All had a symmetric distal sensory and autonomic neuropathy or a purely sensory neuropathy. Mean age was 39.8 years (range 23–57 years). Two patients had Type 2 (non-insulin-dependent) diabetes mellitus and the remainder Type 1 (insulin-dependent) diabetes. Morphometric observations on endoneurial capillaries were compared with results from organ donor control cases and from patients with type 1 hereditary motor and sensory neuropathy. The area of the lumen of the capillaries did not differ between the three groups. The area occupied by the capillary endothelial cells in transverse section and the number of endothelial cell nuclei were increased both in the patients with diabetic neuropathy and hereditary motor and sensory neuropathy, as was the thickness of the surrounding basal laminal zone. Closure of endoneurial capillaries in diabetic neuropathy, reported in another study, was not confirmed. Capillary density and nearest-neighbour distances were similar in the diabetic and organ donor control cases. Capillary density was reduced in the patients with hereditary motor and sensory neuropathy, this being related to increased fascicular area consequent upon the presence of hypertrophic changes. The presence of thickening of the pericapillary basal laminal zone and endothelial cell hyperplasia both in diabetic and hereditary motor and sensory neuropathy, the latter being a neuropathy in which a vascular basis can be discounted, makes it difficult to use such changes as an argument favouring a vascular cause for diabetic neuropathy. There were differences in the basal laminal zone between the diabetic and hereditary motor and sensory neuropathy cases suggesting that the reduplicated basal lamina was more persistent in the diabetic patients.     

甲状腺功能亢进症与甲状腺功能减退症患者的自主神经功能状况分析

目的 通过对甲状腺功能亢进症(简称甲亢)和甲状腺功能减退症(简称甲减)患者心率变异性的分析,探讨两种疾病的自主神经功能状况.方法 对49例甲亢患者、25例甲减患者和40例健康者(对照)进行12导联同步24 h动态监测,计算机回放后采用人机对话方式剔除干扰,常规分析24 h心电图,计算24 h心率变异性,包括时域指标[全部RR间期的标准差(SDNN)、相邻RR间期差值的均方根(RMSSD)]和频域指标[极低频段功率(VLF)、低频段功率(LF)、高频段功率(HF)、低频段功率与高频段功率比值(LF/HF)].结果 甲亢组的时域指标SDNN[(69.65±13.55)ms]、RMSSD[(12.98±3.20)ms]明显低于对照组[(136.07±11.95)、(29.70±5.85)ms],两组比较差异均有统计学意义(P＜0.01);频域指标HF[(53.31±15.84)ms2]低于对照组[(223.38±50.09)ms2],而VLF[(1823.55±238.13)ms2]、LF[(501.88±92.47)ms2]、LF/HF(5.89±1.15)均高于对照组[(325.68±60.47)ms2、(405.60±51.41)ms2、2.14±0.56],两组比较差异均有统计学意义(P＜0.01).甲减组的时域指标SDNN[(77.00±15.48)ms]、RMSSD[(14.80±2.58)ms]也明显低于对照组(P＜0.01);频域指标HF[(57.88±12.20)ms2]、VLF[(251.48±24.67)ms2]、LF[(128.68±43.78)ms2]均低于对照组(P＜0.01);LF/HF为1.83±0.63,与对照组比较,差异无统计学意义(P＞0.05).结论 甲亢患者表现为交感神经功能亢进,迷走神经功能低下;甲减患者表现为迷走神经、交感神经功能均减低.     

Cardiovascular autonomic nerve function in patients with hypoxaemic chronic obstructive pulmonary disease.

Intraneural hypoxaemia is recognized as a pathogenic mechanism in diabetic neuropathy. A similar pathophysiological process may occur in chronic obstructive pulmonary disease (COPD). Autonomic neuropathy is not recognized in COPD. We compared 96 patients with hypoxaemic COPD to 22 age-matched control subjects to see whether autonomic dysfunction occurs in COPD and whether there was any correlation with the severity of hypoxaemia. The cardiovascular autonomic tests consisted of heart rate responses (mainly parasympathetic function) to a Valsalva manoeuvre, deep breathing and postural change and blood pressure responses (mainly of sympathetic origin) to postural change and sustained handgrip. Early autonomic neuropathy is defined as one abnormal test and definite autonomic neuropathy as two abnormal tests according to the normal range. These autonomic tests were reproducible in our study population. Although the symptoms and signs of autonomic neuropathy were rare, definite autonomic dysfunction was found in 35%, and early autonomic neuropathy in a further 47%, of patients whose arterial oxygen tension (PaO2) was less than 8 kPa (60 mmHg). Only 18% of the control group had evidence of an age-related early autonomic dysfunction. Parasympathetic autonomic dysfunction was significantly correlated with PaO2 whilst the sympathetic tests were relatively normal. Correction of hypoxaemia for one hour or administration of ipratropium bromide or terbutaline had no effect on autonomic function. Subclinical autonomic neuropathy is a feature of hypoxaemic COPD. Its importance in the disease process and its role in prognosis needs evaluation.     

Inhomogeneous derangement of cardiac autonomic nerve control in diabetic rats.

The present study compared autonomic nervous function in Kob [Spontaneously Diabetic, Bio-Breeding (BB)] rats with control Wistar rats to determine the development of cardiac neuropathy in diabetic rats. Telemetric ECG signals were obtained from an ECG radio-transmitter placed in a dorsal subcutaneous pouch of male Kob and Wistar rats for 30min every 6h at a sample rate of 5kHz. Heart rate (HR) and HR variability (HRV) were analyzed in each group by power spectrograms obtained by a fast Fourier transform algorithm. RR interval, total power (TP), low frequency (LF) power (0.04-0.67 Hz), high frequency (HF) power (0.79-1.48 Hz) and LF/HF ratio were also measured. The Kob rats had lower HRV than the control Wistar rats; HR, TP, and HF power, but not the LF/HF ratio, in the Kob rats were significantly lower than those of the control rats (p<0.001). However, in the Kob rats the response of these parameters to a muscarinic antagonist (atropine: 2mg/kg) was left intact, but their response to a beta-adrenergic antagonist (propranolol: 4mg/kg) was impeded. Autonomic nervous control of HR in spontaneously diabetic rats was inhomogeneously deranged in terms of the balance in sympathetic and parasympathetic tone, not only in the baseline condition, but also in the regulatory systems, including postsynaptic receptor function.     

Normal perivascular sensory dilator nerve function in arteries of Zucker diabetic fatty rats

BackgroundType II diabetes in humans is associated with pathology of both the cardiovascular and peripheral sensory nervous systems. Because abnormal vasodilator responses have been reported in animals of type II diabetes and perivascular sensory nerves are a source of vasodilator substances, we tested the hypothesis that sensory nerve-dependent relaxation is abnormal in arteries of the Zucker diabetic fatty (ZDF) rat model of type II diabetes.MethodsThe ZDF rats and genetic controls were studied at 26 weeks of age. Tail-cuff systolic blood pressure (BP) was measured, serum was obtained for chemical determinations, and mesenteric branch arteries were isolated for wire myograph analysis and confocal-based measurement of calcitonin gene-related peptide (CGRP) positive nerve density.ResultsNo differences in BP were detected. Serum glucose, triglycerides, and cholesterol were significantly elevated in ZDF. Sensory nerve-dependent vasodilation was assessed by measuring relaxation of phenylephrine preconstricted arterial segments to cumulative addition of divalent calcium ion (Ca²⁺) or capsaicin. Neither Ca²⁺- nor capsaicin-induced relaxation were different in ZDF versus control (maximal ZDF response to Ca²⁺ = 64% ± 2% v 59% ± 4%; ED₅₀ for Ca²⁺ = 3.7 ± 0.5 mmol/L v 3.2 ± 0.5 mmol/L; n = 5, P = not significant [NS]; maximal ZDF response to capsaicin = 68% ± 9% v 74% ± 4%; ZDF ED₅₀ = 3.8 ± 0.5 nmol/L v 9.8 ± 7 nmol/L; n = 5, P = NS). In contrast, the maximal relaxation response to acetylcholine was impaired in ZDF (maximal ZDF response = 83% ± 5% v 94% ± 2%, n = 4, P = .039; ED₅₀ for acetylcholine = 8.1 ± 2.9 nmol/L for ZDF v 33.5 ± 18.2; n = 4 per group, P = .086). The CGRP positive nerve density was not different between groups.ConclusionsBlood pressure, perivascular sensory nerve CGRP content, and dilator function is normal in the ZDF model of type II diabetes, whereas endothelium-dependent relaxation is impaired.     

Effect of essential hypertension on cardiac autonomic function in type 2 diabetic patients.

OBJECTIVES: The aim of this study was to examine the effects of essential hypertension on cardiac autonomic function in type 2 diabetic patients. BACKGROUND: Hypertension is common in type 2 diabetic patients and is associated with a high mortality. However, the combined effects of type 2 diabetes and essential hypertension on cardiac autonomic function have not been fully elucidated. METHODS: Thirty-three patients with type 2 diabetes were assigned to a hypertensive diabetic group (n = 15; age: 56 +/- 8 years, mean +/- SD) or an age-matched normotensive diabetic group (n = 18, 56 +/- 6 years). Cardiac autonomic function was assessed by baroreflex sensitivity (BRS), heart rate variability (HRV), plasma norepinephrine concentration and cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphic findings. RESULTS: Baroreflex sensitivity was lower in the hypertensive diabetic group than it was in the normotensive diabetic group (p < 0.05). The early and delayed myocardial uptake of 123I-MIBG was lower (p < 0.01 and p < 0.05, respectively), and the percent washout rate of 123I-MIBG was higher (p < 0.05) in the hypertensive diabetic group. However, the high frequency (HF) power and the ratio of low frequency (LF) power to HF power (LF/HF) of HRV and plasma norepinephrine concentration were not significantly different. The homeostasis model assessment index was higher in the hypertensive diabetic group than it was in the normotensive diabetic group (p < 0.01). CONCLUSIONS: Our results indicate that essential hypertension acts synergistically with type 2 diabetes to depress cardiac reflex vagal and sympathetic function, and the results also suggest that insulin resistance may play a pathogenic role in these processes.     

Exercise testing in young asymptomatic diabetic patients.

The cardiovascular response to submaximal bicycle exercise was studied in a group of 19 asymptomatic diabetic patients aged 18 to 39, including 11 males and 8 females and 18 control subjects (9 males and 9 females, aged 20 to 34 years). The maximum heart rate achieved by the control subjects (group I), 175.9 +/- 8.9 beats/min, was greater than that achieved by the diabetic patients (group II), 159.4 +/- 17.8 beats/min, (P less than 0.01). The work load at which the maximum heart rate was reached was lower in diabetic males, 681 +/- 155.4 kg m/min, than in healthy males, 866.7 +/- 139.9 kg m/min, (P less than 0.02). Although systolic blood pressure elevations were comparable during exercise and the postexercise period, the increase in diastolic blood pressure during exercise in the diabetic patients was greater than in control subjects (P less than 0.001). This difference, however, was only observed in the males and not in the females. The difference in diastolic blood pressure was again noted between the groups in the postexercise period; that of group II was higher than that of group I (P less than 0.01). This was particularly notable in the older diabetics (aged 31 to 40 years). One patient in group II developed ischemic ST segment changes, and 1 subject in each group was found to have J junction depression of 1.0 mm or more. The implications of these findings are discussed in relation to the possible pathophysiology of the diabetic patients.     

Brain natriuretic peptide and cardiac autonomic function in type 2 diabetic patients

The present study tested the hypothesis that increased plasma brain natriuretic peptide (BNP) levels are related to cardiac autonomic dysfunction in type 2 diabetic patients. A total of 32 consecutive Japanese patients with type 2 diabetes were assigned to either a high-BNP (>or=18 pg/ml) group (n=12; age 57+/-13 years, mean+/-S.D.) or a normal-BNP (<18 pg/ml) group (n=20; 59+/-10 years). No patient had any overt structural heart disease. Cardiac autonomic function was assessed by measurements of baroreflex sensitivity (BRS), heart rate variability (HRV) and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings. BRS was lower (p<0.005) in the high-BNP group than in the normal-BNP group. However, the components of HRV, and the early and delayed myocardial uptake of (123)I-MIBG and percentage washout rate of (123)I-MIBG were not significantly different between the groups. The plasma level of BNP negatively correlated with BRS (r=0.35, p=0.049). These findings suggest that increased plasma BNP levels were related to cardiac reflex parasympathetic dysfunction in our Japanese type 2 diabetic patients.