Search PubMed⌕ Search

Biomedical subjects

D Ziegler

Publications and source records attributed to D Ziegler.

At least 37 records · Page 2Linked to original sources
PubMed2001

Sildenafil citrate for the treatment of erectile dysfunction in men with Type II diabetes mellitus.

AIMS/HYPOTHESIS: Ninety percent of all men with diabetes have Type II (non-insulin-dependent) diabetes mellitus, and erectile dysfunction (ED) is common in this patient group. This study evaluated the effects of sildenafil on men with erectile dysfunction and Type II diabetes and compared the results with glycated haemoglobin concentrations and chronic diabetic complications. METHODS: Patients (mean age, 59 years) in this double-blind, placebo-controlled trial were randomised to sildenafil (25-100 mg; n = 110) or matching placebo (n = 109) for 12 weeks. Primary criteria for efficacy included questions 3 (achieving an erection) and 4 (maintaining an erection) from the International Index of Erectile Function (IIEF, score range, 0-5). Secondary outcome measures included a global efficacy question (GEQ), patient event logs, a life satisfaction checklist, and the remaining IIEF questions. RESULTS: After 12 weeks, the mean scores for questions 3 and 4 had improved significantly in patients receiving sildenafil (3.42 +/- 0.23 and 3.35 +/- 0.24) compared with placebo (1.86 +/- 0.22 and 1.84 +/- 0.23; p < 0.0001). Similarly, the GEQ score was higher in the sildenafil (64.6 %) than the placebo group (10.5 %). Even when correlating efficacy with glycated haemoglobin concentrations ( < or = 8.3 % or > 8.3 %, the median concentration found in this study) or the number of diabetic complications (0 or > or = 1), the mean scores for the GEQ and questions 3 and 4 from the IIEF remained higher for all the sildenafil groups compared with the placebo groups (p < 0.0001). CONCLUSION/INTERPRETATION: Sildenafil was well-tolerated and effective in improving erectile dysfunction in men with Type II diabetes, even in patients with poor glycaemic control and chronic complications.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2001

Diagnosis and treatment of diabetic autonomic neuropathy.

Diabetic autonomic neuropathy (DAN) is associated with a markedly reduced quality of life and poor prognosis. The manifestations of DAN cause multiple symptoms and involve the 1) cardiovascular system: resting tachycardia, reduced heart rate variability and circadian rhythm of heart rate and blood pressure, painless myocardial ischemia/infarction, orthostatic hypotension, exercise intolerance, perioperative instability, sudden death; 2) respiratory system: reduced ventilatory drive to hypercapnia/hypoxemia, sleep apnea; 3) gastrointestinal tract: esophageal motor dysfunction, diabetic gastroparesis, gallbladder atony, diabetic enteropathy, colonic hypomotility, anorectal dysfunction; and 4) genitourinary tract: diabetic cystopathy, erectile dysfunction. Treatment is based on four cornerstones: 1) causal treatment aimed at near-normoglycemia; 2) treatment based on pathogenetic mechanisms; 3) symptomatic treatment; and 4) avoidance of risk factors and complications. Pharmacologic treatment of symptomatic DAN may be difficult, due to limited efficacy and frequent adverse reactions. First-line treatments include midodrine for orthostatic hypotension, prokinetic drugs for gastroparesis, broad-spectrum antibiotics for diabetic diarrhea, and sildenafil for erectile dysfunction. Prior to an adequate symptomatic treatment a thorough risk-benefit estimate, aimed at maintaining the patient's quality of life, is required.

Autonomic Nervous System Diseases↗
PubMed2001

Diversity of polyamine patterns in soft rot pathogens and other plant-associated members of the Enterobacteriaceae.

Polyamine profiles of 91 pectolytic and other plant-associated strains from 30 taxa of the Enterobacteriaceae were obtained by gradient high performance liquid chromatography (HPLC). Pectobacterium carotovorum, basonym Erwinia carotovora, contained a high amount of putrescine and less diaminopropane. Diaminopropane was absent in Pectobacterium chrysanthemi, basonym E. chrysanthemi, whereas cadaverine was present in addition to the major compound putrescine. This chemotaxonomic difference reflects the deepest phylogenetic branching point within the recently emended genus Pectobacterium which lies between the two species P. carotovorum and P. chrysanthemi. Both important soft rot pathogens are easily distinguishable from each other and from the type species of the genus Erwinia as diaminopropane is the only major polyamine compound in E. amylovora. Chemotaxonomic heterogeneity is also emerging with respect to DYE's Amylovora group proposed in an early phytopathological concept.

Bacterial Typing Techniques↗
PubMed1999

The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones.

The antihypertensive agent moxonidine, an imidazoline Ii-receptor agonist, also induces hypophagia and lowers body weight in the obese spontaneously hypertensive rat, but the central mediation of this action and the neuronal pathways that moxonidine may interact with are not known. We studied whether moxonidine has anti-obesity effects in the genetically-obese and insulin-resistant fa/fa Zucker rat, and whether these are mediated through inhibition of the hypothalamic neuropeptide Y (NPY) neurones. Lean and obese Zucker rats were given moxonidine (3 mg kg(-1) day(-1)) or saline by gavage for 21 days. Moxonidine decreased food intake throughout by 20% in obese rats (P<0.001) and by 8% in lean rats (P<0.001), and reduced weight gain that final body weight was 15% lower in obese (P<0.001) and 7% lower in lean (P<0.01) rats than their untreated controls. Plasma insulin and leptin levels were decreased in moxonidine-treated obese rats (P<0.01 and P<0.05), but unchanged in treated lean rats. Uncoupling protein-1 gene expression in brown adipose tissue was stimulated by 40-50% (P< or =0.05) in both obese and lean animals given moxonidine. Obese animals given moxonidine showed a 37% reduction in hypothalamic NPY mRNA levels (P = 0.01), together with significantly increased NPY concentrations in the paraventricular nucleus (P<0.05), but no changes in the arcuate nucleus or other nuclei; this is consistent with reduced NPY synthesis in the arcuate nucleus and blocked release of NPY in the paraventricular nucleus. In lean animals, moxonidine did not affect NPY levels or NPY mRNA. The hypophagic, thermogenic and anti-obesity effects of moxonidine in obese Zucker rats may be partly due to inhibition of the NPY neurones, whose inappropriate overactivity may underlie obesity in this model.

Adipose Tissue↗
PubMed1999

Platelet activation in diabetic cardiovascular autonomic neuropathy.

AIMS: Platelet activation is known to be associated with arrhythmic effects in myocardial ischaemia. The present study attempts to clarify whether diabetic cardiovascular autonomic neuropathy (CAN) is associated with intravascular platelet activation. METHODS: Platelet activation was assessed by flow cytometry analysis in 30 patients with Type 1 diabetes mellitus screened for diabetic complications. Fifteen patients showed evidence of CAN as assessed by a battery of standard cardiovascular autonomic reflex tests. Fifteen patients without CAN were then selected as a matched control group. Platelet activation was assessed by flow cytometric detection of activation-dependent platelet membrane antigens (P-selectin (CD62), thrombospondin, lysosomal GP53 (CD63) and ligand-induced binding site-1 of GPIIb/IIIa (LIBS-1)). RESULTS: Significantly more activated platelets were detected in the patients with CAN showing 20.9% (coefficient of variation (CV) 44%) CD63+ (vs. 17.2% (CV 19%) in controls, P < or = 0.05), 6.4% (CV 87%) CD62+ (vs. 4.1% (CV 37%), P < or = 0.05), and 6.7% (CV 55%) thrombospondin+ (vs. 4.6% (CV 39%), P < or = 0.01) platelets, respectively. LIBS-1 on platelets was not significantly different between patients with and without CAN. No correlation was found between glucose metabolism and platelet activation. CONCLUSIONS: Cardiovascular autonomic neuropathy is associated with platelet activation in Type 1 diabetes mellitus. The high platelet activation may reflect an increased prothrombotic state in diabetic cardiovascular autonomic dysfunction.

Adult↗
PubMed1999

Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy.

AIMS: To evaluate the efficacy and safety of short-term oral treatment with the antioxidant thioctic acid (TA) on neuropathic symptoms and deficits in patients with Type 2 diabetes mellitus with symptomatic polyneuropathy. METHODS: Patients were randomly assigned to oral treatment with 600 mg of TA t.i.d. (n = 12) or placebo (n = 12) for 3 weeks. Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) in the feet were scored at weekly intervals and summarized as a Total Symptom Score (TSS). The Hamburg Pain Adjective List (HPAL) and the Neuropathy Disability Score (NDS) were assessed at baseline and day 19. RESULTS: At baseline the TSS, HPAL, and NDS were not significantly different between the groups. The TSS in the foot decreased from baseline to day 19 by -3.75 +/- 1.88 points (-47%) in the TA group and by -1.94 +/- 1.50 points (-24%) in the placebo group (P= 0.021 for TA vs. placebo). The total HPAL score decreased from baseline to day 19 by -2.20 +/- 1.65 points (-60%) in the TA group and by -0.96 +/- 1.32 points (-29%) in the placebo group (P = 0.072 for TA vs. placebo). The NDS decreased by -0.27 +/- 0.47 points in the TA group, whereas it slightly increased by +0.18 +/- 0.4 points in the placebo group (P = 0.025 for TA vs. placebo). No differences between the groups were noted regarding the rates of adverse events. CONCLUSIONS: These preliminary findings indicate that oral treatment with 600 mg of TA t.i.d. for 3 weeks may improve symptoms and deficits resulting from polyneuropathy in Type 2 diabetic patients, without causing significant adverse reactions.

Aged↗
PubMed1999

Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials.

Diabetic neuropathy represents a major health problem, as it is responsible for substantial morbidity, increased mortality, and impaired quality of life. Near-normoglycaemia is now generally accepted as the primary approach to prevention of diabetic neuropathy, but is not achievable in a considerable number of patients. In the past two decades several medical treatments that exert their effects despite hyperglycaemia have been derived from the experimental pathogenetic concepts of diabetic neuropathy. Such compounds have been designed to improve or slow the progression of the neuropathic process and are being evaluated in clinical trials, but with the exception of alpha-lipoic acid (thioctic acid) which is available in Germany, none of these drugs is currently available in clinical practice. Here we review the current evidence from the clinical trials that assessed the therapeutic efficacy and safety of thioctic acid in diabetic polyneuropathy. Thus far, 15 clinical trials have been completed using different study designs, durations of treatment, doses, sample sizes, and patient populations. Within this variety of clinical trials, those with beneficial effects of thioctic acid on either neuropathic symptoms and deficits due to polyneuropathy or reduced heart rate variability resulting from cardiac autonomic neuropathy used doses of at least 600 mg per day. The following conclusions can be drawn from the recent controlled clinical trials. 1.) Short-term treatment for 3 weeks using 600 mg of thioctic acid i.v. per day appears to reduce the chief symptoms of diabetic polyneuropathy. A 3-week pilot study of 1800 mg per day given orally indicates that the therapeutic effect may be independent of the route of administration, but this needs to be confirmed in a larger sample size. 2.) The effect on symptoms is accompanied by an improvement of neuropathic deficits. 3.) Oral treatment for 4-7 months tends to reduce neuropathic deficits and improves cardiac autonomic neuropathy. 4.) Preliminary data over 2 years indicate possible long-term improvement in motor and sensory nerve conduction in the lower limbs. 5.) Clinical and postmarketing surveillance studies have revealed a highly favourable safety profile of the drug. Based on these findings, a pivotal long-term multicenter trial of oral treatment with thioctic acid (NATHAN I Study) is being conducted in North America and Europe aimed at slowing the progression of diabetic polyneuropathy using a clinically meaningful and reliable primary outcome measure that combines clinical and neurophysiological assessment.

Clinical Trials as Topic↗
PubMed1999

Normal ranges and reproducibility of statistical, geometric, frequency domain, and non-linear measures of 24-hour heart rate variability.

Diabetic cardiovascular autonomic neuropathy (CAN) carries an increased risk of mortality. The early detection and characterization of CAN has traditionally been based on the results of autonomic reflex tests (AFTs). A variety of different measures to quantify 24-hour heart rate variability (HRV) have recently been introduced, but their normal ranges, reliability, and validity in patients with CAN have not been adequately studied. We established the normal ranges of statistical (SDNN index, CV, SNN50, RMSSD), geometric (triangular index (TI), triangular interpolation (TINN), top angle index [TAI]), frequency domain (spectral power in the VLF, LF, and HF bands, LF/HF ratio, LF in normalized units [NU]), and non-linear measures (CV1 and CV2 of the Poincaré plot) of 24-hour HRV in 94 healthy control subjects. Day-to-day reproducibility was evaluated on two occasions in 17 healthy subjects and 9 diabetic patients. The parameters of HRV were computed over time periods representing the day (6:00-24:00 hours), night (00:00-6:00 hours), and 24 hours in total. The results of all indexes, except for the LF/HF ratio and LF-NU, declined significantly with increasing age (p<0.05), but were independent of sex and BMI. The statistical, geometric, and non-linear measures (p<0.05), but not the frequency-domain parameters decreased significantly with increasing heart rate. Since the HRV data showed log normal distribution, log transformation was used to define the age-related lower limits of normal at the 2.5th centile. Intraindividual reproducibility was highest for the geometric measures. The nonlinear and statistical parameters also showed high reliability, except for the SNN50. The repeatability of the frequency domain measures was somewhat lower but still satisfactory. Reproducibility was lower in the diabetic than in the control group, higher during the day than during the night, and better than that reported previously for the AFTs. In conclusion, in healthy subjects the measures of 24-h HRV are not related to sex or BMI, but strongly dependent on age and heart rate, the latter except for the frequency domain measures. The majority of the HRV measures, in particular the geometric parameters, show a relatively high intraindividual reproducibility which underlines their suitability for the use in prospective studies.

Adult↗
PubMed1999

Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy.

OBJECTIVE: To evaluate the efficacy and safety of alpha-lipoic acid given intravenously, followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy. RESEARCH DESIGN AND METHODS: In a multicenter randomized double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy [ALADIN] III Study), 509 outpatients were randomly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by 600 mg alpha-lipoic acid three times a day orally for 6 months (A-A; n = 167); 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (A-P; n = 174); and placebo once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (P-P; n = 168). Outcome measures included the Total Symptom Score (TSS) for neuropathic symptoms (pain, burning, paresthesias, and numbness) in the feet, and the Neuropathy Impairment Score (NIS). Data analysis was based on the intention to treat. RESULTS: No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline. The TSS in the feet decreased from baseline to day 19 (median [range]) by -3.7 (-12.6 to 5.0) points in the group given alpha-lipoic acid intravenously and by -3.0 (-12.3 to 8.0) points in the placebo group (P = 0.447), but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group (85.6 [0-219] vs. 95.9 [5.5-220]); P = 0.033). After 7 months, the changes in the TSS from baseline were not significantly different between the three groups studied, which could be due to increasing intercenter variability in the TSS during the trial. The NIS decreased after 19 days by -4.34+/-0.35 points (mean +/- SEM) in A-A and A-P and -3.49+/-0.58 points in P-P (P = 0.02 for alpha-lipoic acid versus placebo) and after 7 months by -5.82+/-0.73 points in A-A, -5.76+/-0.69 points in A-P, and -4.37+/-0.83 points in P-P (P = 0.09 for A-A vs. P-P). The rates of adverse events were not different between the groups throughout the study. CONCLUSIONS: These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid, followed by a 6-month oral treatment, had no effect on neuropathic symptoms distinguishable from placebo to a clinically meaningful degree, possibly due to increasing intercenter variability in symptom scoring during the study. However, this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions. Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy.

Administration, Oral↗
PubMed1998

Effect of glycaemic control on myocardial sympathetic innervation assessed by [123I]metaiodobenzylguanidine scintigraphy: a 4-year prospective study in IDDM patients.

Diabetic cardiovascular autonomic neuropathy (CAN) has been directly characterized by reduced or absent myocardial [123I]metaiodobenzylguanidine (MIBG) uptake, but there is no information available on the relationship between the myocardial adrenergic innervation defects and long-term glycaemic control. In a prospective study over a mean of 4 years we examined myocardial sympathetic innervation in 12 Type 1 (insulin-dependent) diabetic patients using MIBG scintigraphy (absolute and relative global MIBG uptake at 2 h p.i.) in conjunction with cardiovascular autonomic function tests, QTc interval, and QT dispersion. Six healthy non-diabetic subjects served as controls for the MIBG scintigraphy at baseline. HbA1c was measured twice a year. One patient, in whom MIBG accumulation was reduced maximally, died during follow up. Among the remaining patients 5 had good or borderline glycaemic control (mean HbA1c < 7.6%; Group 1), whereas 6 patients were poorly controlled (mean HbA1c > or = 7.6%; Group 2). Absolute global MIBG uptake increased from baseline to follow-up by 260 (-190-540) [median (range)] cpm/g in Group 1 and decreased by -150 (-450-224) cpm/g in Group 2 (p < 0.05 vs Group 1). Relative global MIBG uptake decreased by -1.7 (-3.4-9.4) % in Group 1 and by -4.7 (-17.4-1.3) % in Group 2 (p < 0.05 vs Group 1). No differences between the groups were noted for the changes in the automatic function tests, QTc interval, and QT dispersion. In conclusion, long-term poor glycaemic control constitutes an essential determinant in the progression of left ventricular adrenergic dysinnervation which may be prevented by near-normoglycaemia. Evaluation of susceptibility to metabolic intervention may be superior when CAN is characterized directly by MIBG scintigraphy rather than by indirect autonomic function testing.

3-Iodobenzylguanidine↗
PubMed1998

Significance of diagnostic parameters in [13C]octanoic acid gastric emptying breath tests.

Two novel characteristic parameters, the latency time (t(lat)) and the ascension time (t(asc)), are proposed for evaluation of non-invasive [13C]octanoic acid breath tests for assessment of the gastric emptying of solids. In breath tests performed in control subjects (n = 30) and diabetic patients (n = 100), the usefulness of these parameters was compared to conventional parameters, i.e., gastric half emptying-time (t1/2,b) and lag phase (t(lag),b). The proposed parameters were only loosely correlated (controls, r = 0.199; diabetics, 0.616). A strong correlation was found between the conventional parameters (controls, r = 0.891; diabetics, r = 0.962). Based on the conventional method, 36 patients were suspicious of delayed gastric emptying including 24 patients which exhibited a simultaneous delay in both parameters. Using the new parameters, a total of 46 patients were suspicious of delayed gastric emptying with 15 and 20 having isolated delay in t(lat) and t(asc), respectively. We conclude that the novel parameters may be more appropriate for examination of the different phases of gastric emptying and for evaluation of gastric emptying disturbances in diabetic patients than the parameters conventionally used for this purpose.

Adult↗
PubMed1997

Evaluation of QT interval length, QT dispersion and myocardial m-iodobenzylguanidine uptake in insulin-dependent diabetic patients with and without autonomic neuropathy.

1. An association has been reported between QT interval abnormalities and cardiovascular autonomic neuropathy in diabetic patients. The QT interval abnormalities reflect local inhomogeneities of ventricular recovery time and may be related to an imbalance in cardiac sympathetic innervation. Sympathetic innervation of the heart can be visualized and quantified by single-photon emission-computed tomography with m-[123I]iodobenzylguanidine. In this study we evaluated cardiac sympathetic integrity by m-[123I]iodobenzylguanidine imaging and the relationship between both QT interval prolongation and QT dispersion from standard 12-lead ECG variables and m-[123I]iodobenzylguanidine uptake in insulin-dependent diabetic patients. 2. Three patient groups were studied, comprising six healthy control subjects, nine diabetic patients without cardiovascular autonomic neuropathy (CAN-) and 12 diabetic patients with cardiovascular neuropathy (CAN+). Resting 12-lead ECG was recorded for measurement of maximal QT interval and QT dispersion. The QT interval was heart rate corrected using Bazett's formula (QTc) and the Karjalainen approach (QTk). Quantitative measurement (in counts/min per g) and visual defect pattern of m-[123I]iodobenzylguanidine uptake were performed using m-[123I]iodobenzylguanidine single-photo emission-computed tomography. 3. Global myocardial m-[123I]iodobenzylguanidine uptake was significantly reduced in both diabetic patient groups compared with control subjects. The visual defect score of m-[123I]iodobenzylguanidine uptake was significantly higher in CAN+ diabetic patients than in control subjects and in CAN- patients. This score was not significantly different between control subjects and CAN- patients. QTc interval and QT dispersion were significantly increased in CAN+ diabetic patients as compared with control subjects (QTc: 432 +/- 15 ms versus 404 +/- 19 ms, P < 0.05; QT dispersion: 42 +/- 10 versus 28 +/- 8 ms, P < 0.05). QT dispersion was also significantly longer in CAN- diabetic patients than in control subjects (41 +/- 9 ms versus 28 +/- 8 ms, P < 0.05). QTc interval was significantly related to global myocardial m-[123I]iodobenzylguanidine uptake and defect score in diabetic patients (r = -0.648, P < 0.01, and r = 0.527, P < 0.05, respectively). There was no correlation between QT dispersion and both m-[123I]iodobenzylguanidine uptake measures. 4. In conclusion, these findings suggest that m-[123I]iodobenzylguanidine imaging is a valuable tool for the detection of early alterations in myocardial sympathetic innervation in long-term diabetic patients without cardiovascular autonomic neuropathy. Insulin-dependent diabetic patients with cardiovascular autonomic neuropathy have a delayed cardiac repolarization and increased variability of ventricular refractoriness. The cardiac sympathetic nervous system seems to be one of the determinants of QT interval lengthening, but does not appear to be involved in dispersion of ventricular recovery time. It is assumed that QT dispersion is based on more complex electrophysiological mechanisms which remain to be elucidated.

3-Iodobenzylguanidine↗
PubMed1997

Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy.

Antioxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes, providing a rationale for a potential therapeutic value in diabetic patients. The effects of the antioxidant alpha-lipoic acid (thioctic acid) were studied in two multicenter, randomized, double-blind placebo-controlled trials. In the Alpha-Lipoic Acid in Diabetic Neuropathy Study, 328 patients with NIDDM and symptomatic peripheral neuropathy were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (ALA 1,200 mg; 600 mg; 100 mg) or placebo (PLAC) over 3 weeks. The total symptom score (TSS) (pain, burning, paresthesia, and numbness) in the feet decreased significantly from baseline to day 19 in ALA 1,200 and ALA 600 vs. PLAC. Each of the four individual symptom scores was significantly lower in ALA 600 than in PLAC after 19 days (all P < 0.05). The total scale of the Hamburg Pain Adjective List (HPAL) was significantly reduced in ALA 1,200 and ALA 600 compared with PLAC after 19 days (both P < 0.05). In the Deutsche Kardiale Autonome Neuropathie Studie, patients with NIDDM and cardiac autonomic neuropathy diagnosed by reduced heart rate variability were randomly assigned to treatment with a daily oral dose of 800 mg alpha-lipoic acid (ALA) (n = 39) or placebo (n = 34) for 4 months. Two out of four parameters of heart rate variability at rest were significantly improved in ALA compared with placebo. A trend toward a favorable effect of ALA was noted for the remaining two indexes. In both studies, no significant adverse events were observed. In conclusion, intravenous treatment with alpha-lipoic acid (600 mg/day) over 3 weeks is safe and effective in reducing symptoms of diabetic peripheral neuropathy, and oral treatment with 800 mg/day for 4 months may improve cardiac autonomic dysfunction in NIDDM.

Antioxidants↗
PubMed1997

Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie.

OBJECTIVE: To evaluate the efficacy and safety of oral treatment with the antioxidant alpha-lipoic acid (ALA) in NIDDM patients with cardiac autonomic neuropathy (CAN), assessed by heart rate variability (HRV). RESEARCH DESIGN AND METHODS: In a randomized, double-blind placebo-controlled multicenter trial (Deutsche Kardiale Autonome Neuropathie [DEKAN] Study), NIDDM patients with reduced HRV were randomly assigned to treatment with daily oral dose of 800 mg ALA (n = 39) or placebo (n = 34) for 4 months. Parameters of HRV at rest included the coefficient of variation (CV), root mean square successive difference (RMSSD), and spectral power in the low-frequency (LF; 0.05-0.15 Hz) and high-frequency (HF; 0.15-0.5 Hz) bands. In addition, cardiovascular autonomic symptoms were assessed. RESULTS: Seventeen patients dropped out of the study (ALA n = 10; placebo n = 7). Mean blood pressure and HbA1 levels did not differ between the groups at baseline and during the study, but heart rate at baseline was higher in the group treated with ALA (P < 0.05). RMSSD increased from baseline to 4 months by 1.5 ms (-37.6 to 77.1) [median (minimum-maximum)] in the group given ALA and decreased by -0.1 ms (-19.2 to 32.8) in the placebo group (P < 0.05 for ALA vs. placebo). Power spectrum in the LF band increased by 0.06 bpm2 (-0. 09 to 0.62) in ALA, whereas it declined by -0.01 bpm2 (-0.48 to 1.86) in placebo (P < 0.05 for ALA vs. placebo). Furthermore, there was a trend toward a favorable effect of ALA versus placebo for the CV and HF band power spectrum (P = 0.097 and P = 0.094 for ALA vs. placebo). The changes in cardiovascular autonomic symptoms did not differ significantly between the groups during the period studied. No differences between the groups were noted regarding the rates of adverse events. CONCLUSIONS: These findings suggest that treatment with ALA using a well-tolerated oral dose of 800 mg/day for 4 months may slightly improve CAN in NIDDM patients.

Autonomic Nervous System Diseases↗
PubMed1997

Application of isotope-selective nondispersive infrared spectrometry (IRIS) for evaluation of [13C]octanoic acid gastric-emptying breath tests: comparison with isotope ratio-mass spectrometry (IRMS).

Suitability of isotope-selective nondispersive infrared spectrometry (IRIS) for evaluation of [13C]octanoic acid gastric-emptying breath test was assessed and compared with standard isotope ratio-mass spectrometry (IRMS). The estimated bias of IRMS and IRIS measurements of baseline-corrected 13CO2 exhalation amounted to +/-0.1 and +/-0.6 delta delta values (n = 360), respectively. In breath tests performed on 60 diabetic patients, the gastric emptying parameters were calculated by nonlinear regression analysis of the time course of 13CO2 exhalation: half-emptying time (t1/2,breath, 90 +/- 39 min), lag phase (tlag,breath, 34 +/- 27 min), and gastric emptying coefficient (GEC, 2.9 +/- 0.5). A reasonable linear correlation was found between the two methods (y = IRIS, x = IRMS) with respect to delta delta values (y = 0.35 + 0.92x, r = 0.985, Sy[symbol: see text]x = +/-0.6, n = 1116) and a rather good agreement of the computed gastric emptying parameters was obtained (t1/2,breath: y = 0.99x + 4.06, Sy[symbol: see text]x = +/- 6.3; tlag, breath: y = 0.97x + 0.96, Sy[symbol: see text]x = +/-3.4; GEC: y = 0.97x - 0.01, Sy[symbol: see text]x = +/-0.09).

Adult↗
PubMed1996

Sympathoadrenergic overactivity and lipid metabolism.

Epidemiological studies have identified high heart rates as a risk factor for coronary heart disease mortality, and heart rate was found to correlate with the severity of coronary atherosclerosis. Heart rate was positively correlated with serum concentrations of total cholesterol, triglycerides, and non-HDL cholesterol. Since heart rate responds sensitively to sympathoadrenergic activity, it was hypothesized that catecholamines play a crucial role in the unfavorable lipid alterations. In addition to influences on circulating lipids, the question arose whether catecholamines have more specific effects on molecular species of structural lipids. Of particular importance is the question of the involvement of catecholamines in the recently suggested correlation between arachidonic acid and stroke mortality. It is therefore attempted to delineate the possible effects of catecholamines on the fatty acid composition of the phospholipids of heart muscle and vasculature. This was achieved in rats by either catecholamine injection or by swimming, a condition known to be associated with marked sympatho-adrenergic stimulation. In swimming rats, linoleic acid was decreased by up to 40% in heart phospholipids, whereas stearic acid and arachidonic acid were increased. Similarly, chronic norepinephrine treatment in rats resulted in a net decrease in linoleic acid and an increase in arachidonic acid and docosahexaenoic acid, which was particularly pronounced when rats were fed an n-3 polyunsaturated fatty acid (PUFA)-rich oil diet. Thus, catecholamines do affect the PUFA composition of heart membranes, mainly through an increase in arachidonic acid content. To further define the action of catecholamines on structural lipids, isolated rat ventricular myocytes in culture were subjected four times to 30 minutes of isoproterenol (10(-6) M) stimulation over 48 hours. No changes in membrane lipid parameters were observed, although the beating rate was increased by 30% during the stimulation. When the cell membranes were enriched in n-3 PUFAs (in association with a decrease in arachidonic acid), the positive chronotropic effect elicited by isoproterenol was raised to + 50%, indicating the modulation of adrenergic function by membrane PUFAs. However, isoproterenol treatment again had no effect on the phospholipid fatty acid composition. Thus, the effect of catecholamines on membrane lipids observed in intact organism appears to be indirect and to involve most probably organs such as the liver and adipose tissue. Catecholamines are expected to induce a lipolysis-linked quantitative and qualitative alteration in circulating fatty acids, which in turn alter the heart membrane composition, similar to the composition changes elicited by diet lipid alterations. Since there is increasing evidence that such fatty acid changes affect the activity of membrane proteins, the possibility emerges that this mechanism may contribute to the catecholamine-linked cardiovascular mortality.

Animals↗