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Biomedical subjects

T Haak

Publications and source records attributed to T Haak.

At least 19 recordsLinked to original sources
PubMed2007

Insulin glargine benefits patients with type 2 diabetes inadequately controlled on oral antidiabetic treatment: an observational study of everyday practice in 12,216 patients.

AIMS: This observational study aimed to investigate the long-term efficacy and safety of adding insulin glargine (LANTUS((R))) to support oral antidiabetic (OAD) treatment in patients with type 2 diabetes in everyday practice. METHODS: A 9-month, open-label, multicentre, observational study, with an optional 20-month extension phase, in which add-on insulin glargine therapy was initiated in 12,216 patients with type 2 diabetes inadequately controlled on OADs. The insulin glargine dose was adjusted at the physician's discretion, reflecting everyday practice. The main outcome measures were changes in HbA(1c), fasting blood glucose (FBG), insulin dose and body mass index (BMI). RESULTS: At baseline, mean (+/- s.d.) age was 63.9 +/- 11.3 years; disease duration was >5 years in 47% of patients, 1-5 years in 39% of patients and <1 year in 10% of patients, while 4% of patients were newly diagnosed. Addition of insulin glargine to OAD therapy led to reductions in mean HbA(1c) (-1.5% from 8.7%) and FBG (-69 mg/dl from 202 mg/dl) levels after 3 months, which were maintained after 9 months [HbA(1c): -1.7%; FBG: -71 mg/dl (-3.9 mmol/l)] without an increase in BMI. Similar glycaemic control was observed after 20 months in the 2721 patients in the extension study. Adverse drug reactions were documented in 26 patients (0.2%). Of 47 adverse events documented, 19 were due to hypoglycaemia. CONCLUSIONS: In everyday practice, patients with type 2 diabetes who are inadequately controlled on OADs benefit from add-on basal insulin treatment with insulin glargine as they demonstrate improved glycaemic control without weight gain.

Administration, Oral↗
PubMed2006

How to screen for depression and emotional problems in patients with diabetes: comparison of screening characteristics of depression questionnaires, measurement of diabetes-specific emotional problems and standard clinical assessment.

AIMS/HYPOTHESIS: We compared the screening performance of different measures of depression: the standard clinical assessment (SCA); the Beck Depression Inventory (BDI); the Center of Epidemiological Studies-Depression Scale (CES-D); and the Problem Areas in Diabetes (PAID) questionnaire, which assesses diabetes-specific distress. We also studied the ability of these measures to detect diabetes-related distress. MATERIALS AND METHODS: A total of 376 diabetic patients (37.2% type 1; 23.9% type 2 without insulin treatment, 38.8% type 2 with insulin) completed the BDI and CES-D; patients who screened positive participated in a diagnostic interview, the Composite International Diagnostic Interview (CIDI). Also, all patients completed the PAID questionnaire. Results of the SCA that related to depression diagnosis were reviewed to correct for false negative screening results. RESULTS: The prevalence of clinical depression was 14.1%, with an additional 18.9% of patients receiving a diagnosis of subclinical depression. Sensitivity for clinical depression in SCA (56%) was moderate, whereas BDI, CES-D and the PAID questionnaire showed satisfactory sensitivity (87, 79 and 81%, respectively). For subclinical depression, the sensitivity of the PAID questionnaire (79%) was sufficient, whereas that of SCA (25%) was poor. All methods showed low sensitivity for the detection of diabetes-specific emotional problems (SCA 19%, CIDI 34%, BDI 60%, CES-D 49%). CONCLUSIONS/INTERPRETATION: The screening performance of SCA for clinical and subclinical depression was modest. Additional screening for depression using the PAID or another depression questionnaire seems reasonable. The ability of depression screening measures to identify diabetes-related distress is modest, suggesting that the PAID questionnaire could be useful when screening diabetic patients for both depression and emotional problems.

Depression↗
PubMed2006

Microdialysis-based 48-hour continuous glucose monitoring with GlucoDay: clinical performance and patients' acceptance.

BACKGROUND: This study was designed to assess clinical performance and patients' acceptance of the minimally invasive microdialysis-based continuous glucose monitoring system Gluco- Day() (Menarini Diagnostics, Florence, Italy) with a targeted monitoring time of 48 h. METHODS: An inpatient sample of 28 patients with diabetes was studied. The analysis of clinical performance was performed using mean absolute differences (MAD) (in percent), Pearson correlations, the Bland-Altman analysis, and Clarke Error Grid Analysis (EGA). GlucoDay glucose values were compared with laboratory standard blood glucose measurements (glucohexokinase assay). The patients' acceptance of the monitoring device was assessed via two self-report scales (pain during application and discomfort while wearing device). RESULTS: A mean (+/- SD) monitoring time of 45.7 +/- 3.3 h with a total of 484 paired readings could be achieved. A correlation of r (average) = 0.91 and a MAD of 19.9% indicated satisfactory to good clinical performance. Of the paired readings, 95.5% fell into the acceptable A and B zones of the EGA. Rather wide 95% limits of agreement were revealed in the Bland-Altman analysis. Whereas virtually no pain was experienced during sensor application, discomfort associated with wearing the device was rather high. All of the participants, however, stated that they would wear the device again. CONCLUSIONS: Satisfactory to good performance of the GlucoDay monitor was observed, indicating the device to be suitable for routine clinical use. In particular, however, the discomfort experienced during wearing requires further improvements in its usability.

Adult↗
PubMed2006

Effect of ACE and AT-2 inhibitors on mortality and progression to microalbuminuria in a nested case-control study of diabetic nephropathy in diabetes mellitus type 2: results from the GENDIAN study.

INTRODUCTION: There is an established role of clinical risk factors such as arterial hypertension and smoking in causing cardiovascular morbidity and diabetic nephropathy (DNP). Genetic factors increase the risk for DNP. To examine the genetic risk, we initiated a case-control study with predefined follow-up examinations. We describe the study design and baseline characteristics under special consideration of comedication, and give preliminary results of the 4-year follow-up. METHODS: We enrolled all 477 patients with DNP receiving maintenance hemodialysis in 30 centers in Southern Germany between August 1999 and January 2000. As controls, we enrolled all 482 diabetes mellitus type 2 patients without urinary microalbuminuria in two examinations on consecutive days and without other signs of renal disease in a large diabetes clinic from September 2000 to September 2001. Follow-up examinations are performed 4 and 6 years after inclusion by questionnaire and telephone interview to determine mortality and new morbidity. Controls progressing to novel DNP at follow-up, as defined by semiquantitative dipstick urinary albumin/creatinine ratio > 30 mg/g, are defined as cases in the study's nested case control component. RESULTS: At study inclusion in cases and controls, respectively, mean age was 67.3 +/- 8.2 and 58.1 +/- 11.2 years and duration of diabetes mellitus was 15.6 +/- 9.6 (at dialysis initiation) and 11.0 +/- 8.6 years. 328 controls (of which 25 had died and 14 did not perform urinalysis) were subjected to follow-up at 4 years, at a mean of 3.5 +/- 0.8 years after inclusion. 51.2% (n = 148) of living controls remained normalbuminuric, 33.9% (n = 98) had microor macroalbuminuria, and in 14.9% (n = 43) the dipstick test was inconclusive. There was no significant difference in progression to micro- or macroalbuminuria between controls treated with ACE or AT-2 inhibitors at baseline or not. Renal function as estimated by the abbreviated MDRD formula declined from 86.8 +/- 21.0 to 82.5 +/- 22.3 ml/min/1.73 m2 (p < 0.001). The decline was significant in patients on ACE or AT-2 inhibitors at baseline and not in patients without such medication at baseline. DISCUSSION: GENDIAN is a large case-control study designed to evaluate clinical and genetic determinants of DNP and other complications of long-standing diabetes mellitus type 2. We observed an association of ACE or AT-2 inhibitor therapy with cardiovascular comorbidity and a significant decline in renal function after a 4-year follow-up.

Age Factors↗
PubMed2005

Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes.

AIM: The aim of this study was to compare the efficacy and safety of a basal-bolus insulin regimen comprising either insulin detemir or neural protamine hagedorn (NPH) insulin in combination with mealtime insulin aspart in patients with type 2 diabetes. METHODS: This was a 26-week, multinational, open-label, parallel group trial with 505 patients with type 2 diabetes (mean age, 60.4 +/- 8.6 years; mean BMI, 30.4 +/- 5.3 kg/m(2); mean HbA(1c), 7.9 +/- 1.3%). Patients, randomized 2:1 to insulin detemir or NPH insulin, received basal insulin either once or twice daily according to their pretrial insulin treatment and insulin aspart at mealtimes. RESULTS: After 26 weeks of treatment, significant reductions in HbA(1c) were observed for insulin detemir (0.2%-points, p = 0.004) and NPH insulin (0.4%-points; p = 0.0001); HbA(1c) levels were comparable at study end (insulin detemir, 7.6%; NPH insulin, 7.5%). The number of basal insulin injections administered per day had no effect on HbA(1c) levels (p = 0.50). Nine-point self-measured blood glucose (SMBG) profiles were similar for the two treatment groups (p = 0.58), as were reductions in fasting plasma glucose (FPG) (insulin detemir, 0.5 mmol/l; NPH insulin, 0.6 mmol/l). At study end, FPG concentrations were similar for the two treatment groups (p = 0.66). By contrast, within-subject day-to-day variation in fasting SMBG was significantly lower with insulin detemir (p = 0.021). Moreover, patients receiving insulin detemir gained significantly less body weight than those who were administered NPH insulin (1.0 and 1.8 kg, respectively, p = 0.017). The frequency of adverse events and the risk of hypoglycaemia were comparable for the two treatment groups. CONCLUSIONS: Patients with type 2 diabetes, treated for 26 weeks with insulin detemir plus insulin aspart at mealtimes, experienced comparable glycaemic control but significantly lower within-subject variability and less weight gain compared to patients treated with NPH insulin and insulin aspart. Insulin detemir was well tolerated and had a similar safety profile to NPH insulin.

Aged↗
PubMed2005

Affective and anxiety disorders in a German sample of diabetic patients: prevalence, comorbidity and risk factors.

AIMS: The aims of this study were to examine (1) the prevalence of clinical and subclinical anxiety and affective disorders in a sample of diabetic patients attending a secondary care clinic in Germany and (2) risk factors associated with the occurrence of these disorders. METHODS: Four hundred and twenty diabetic patients (36.9% Type 1; 24.7% Type 2; 38.4% Type 2 with insulin) participated in a questionnaire-based screening survey. Those who screened positive received a diagnostic interview. RESULTS: Prevalence of clinical affective disorders was 12.6%, with an additional 18.8% of patients reporting depressive symptoms without fulfilling all criteria for a clinical affective disorder. The prevalence of anxiety disorders was 5.9%, with an additional 19.3% of patients reporting some anxiety symptoms. The comorbidity rate of affective and anxiety disorders was 1.8%, whereas 21.4% of the diabetic patients reported elevated affective as well as anxiety symptomatology. Logistic regression established demographic variables such as age, female gender and living alone as well as diabetes-specific parameters such as insulin treatment in Type 2 diabetes, hypoglycaemia problems and poor glycaemic control as risk factors for affective disorders. For anxiety symptoms female gender, younger age and Type 2 diabetes were significant independent variables. CONCLUSION: The prevalence of affective disorders in diabetic patients was twofold higher than in the non-diabetic population, whereas prevalence for anxiety disorders was not increased. Analysis of risk factors can facilitate the identification of patients who are at a greater risk for these disorders.

Adolescent↗
PubMed2004

Prevalence of fungal foot infections in patients with diabetes mellitus type 1 - underestimation of moccasin-type tinea.

In diabetic patients, mycotic infections may increase the risk of developing diabetic foot syndrome. However, few data are available on the prevalence of fungal foot infections in patients with diabetes. During a conference attended by patients with long-term diabetes, 95 individuals with type 1 diabetes mellitus (52 men, 43 women, mean disease duration 35.8 years) were examined for fungal infections of the feet. As well as frequency of infection and risk profiles, the level of patient awareness and preventive measures taken were assessed by means of a questionnaire. Clinically, 78 patients (82.1 %) showed probable pedal fungal infections, of which 84.6 % (66/78) were mycologically confirmed by direct microscopy and/or culture. Skin mycoses were found in 9 patients (toe webs 5, soles 4), onychomycosis in 29 patients and simultaneous infection of nails and skin in 28 patients (toe webs 8, soles 20). Thirty-seven (47.4 %) of these patients had positive cultures, particularly for the dermatophyte Trichophyton rubrum (69.2 % of isolates). A significant correlation was found between infection and gender (men more frequently affected) and the age of the patients. The actual frequency of mycoses was underestimated by the patients. This correlated with the assessment of their own knowledge level concerning fungal infections: 83.2 % of patients with skin mycoses and 88.4 % of those with onychomycosis of the feet felt that they needed more information about their disease. Marked mycoses on the soles were often considered to be dry skin by the patients. The high number of infections detected is especially remarkable in that this group of patients were highly motivated. It therefore appears that diabetics require more diagnostic, therapeutic and preventive care in terms of mycotic diseases than has been previously thought.

Dermatomycoses↗
PubMed2004

The addition of acarbose to insulin lispro reduces acute glycaemic responses in patients with type-2 diabetes.

This double-blind, placebo-controlled single-centre cross-over study assessed the efficacy of acarbose as adjunct to insulin lispro therapy in avoiding postprandial blood glucose rise. A total of 30 type 2 diabetic patients currently treated with insulin were included. On two consecutive days subjects received a standardised breakfast (covered by insulin lispro) and were randomly assigned study medication of either 100 mg acarbose or matching placebo. Basal and prandial insulin doses were maintained during the study period. A total of nine blood samples (for parameter assessment) were taken at 30-minute intervals. Primary efficacy variables were the difference in blood glucose rise from fasting to 90 min after breakfast between acarbose/lispro and lispro monotherapy and the difference in the postprandial glucose profile (area under the curve, 0 - 240 min). Secondary parameters consisted of differences in postprandial C-peptide, insulin and triglyceride time profiles between the two treatments. Acarbose treatment significantly reduced the rise in 90 min postprandial blood glucose (1.95 +/- 1.85 mmol/l) by more than half the increase observed under lispro monotherapy (4.37 +/- 2.13 mmol/l; p = 0.000). Postprandial blood glucose, C-peptide and serum insulin levels (AUC (0 - 240 min)) all significantly improved under acarbose treatment. Triglyceride levels were not affected by the combination therapy. Rapid-acting insulin lispro was efficiently complemented by the different mechanism of action of acarbose resulting in significant improvements of postprandial hyperglycaemia and the insulin profile.

Acarbose↗
PubMed2004

Reversible cognitive deterioration after a single episode of severe hypoglycaemia: a case report.

A case of a male 34-year-old Type 1 diabetic patient who experienced a prolonged severe hypoglycaemic episode is presented. After the hypoglycaemic event, the patient suffered from moderate to severe neuropsychological impairments. On the basis of neuropsychological assessment results, diabetes therapy was modified (less complex insulin regimen, fixed insulin doses and fixed carbohydrate distribution). At a follow-up examination (3 months), presumable complete recovery of cognitive function was observed. This case demonstrates the possible detrimental neuropsychological effects of severe hypoglycaemia, that, in this case, turned out to be reversible. It highlights the clinical implications of impaired cognitive function on self-care and self-management abilities and the usefulness of neuropsychological testing in clinical diabetes care.

Acute Disease↗
PubMed2004

Assessment of hypoglycaemia awareness using continuous glucose monitoring.

AIMS: To investigate the possibility of assessing hypoglycaemia awareness in patients with Type 1 diabetes using continuous glucose monitoring. METHODS: Twenty patients with Type 1 diabetes were investigated. Ten patients with Type 1 diabetes and strongly impaired hypoglycaemia awareness were compared with 10 patients with intact hypoglycaemia awareness regarding quality of hypoglycaemia perception (number of undetected hypoglycaemic episodes per 24 h, glucose level < 3.3 mmol/l). Hypoglycaemia detection was assessed using the event function of the Continuous Glucose Monitoring System (CGMS; Medtronic MiniMed, Northridge, CA, USA). Patients were instructed to enter an event upon suspecting being hypoglycaemic. RESULTS: Satisfactory CGMS performance could be achieved [mean r = 0.893 between calibration measurements and CGMS data, mean absolute difference (MAD) = 20.6%], although artefacts were observable and had to be controlled. Hypoglycaemia unaware patients showed a significantly higher total number of hypoglycaemic episodes (P < 0.05), number of undetected hypoglycaemic episodes (P < 0.01), and mean glucose levels (P < 0.05). Even in aware patients, undetected hypoglycaemia was observable. No significant differences regarding occurrence of nocturnal hypoglycaemia were observable. CONCLUSIONS: The possibility of direct assessment of hypoglycaemia awareness using continuous glucose monitoring was demonstrated. Its application in clinical practice could be of use for assessing hypoglycaemia perception and evaluating the impact of treatment changes on hypoglycaemia awareness.

Adult↗
PubMed2003

Emotional changes during experimentally induced hypoglycaemia in type 1 diabetes.

Emotional changes during experimentally induced hypoglycaemia in type 1 diabetic patients were investigated using a hyperinsulinaemic glucose clamp. In the experimental group (n=11), blood glucose was stabilised at euglycaemia (5.6 mmol/l, phase 1), then lowered to 2.5 mmol/l (phase 2) and raised to 5.6 mmol/l (phase 3). In the control group (n=11), euglycaemia was maintained during all phases. Hypoglycaemia elicited the expected endocrine, symptomatic and neuroglycopenic effects. During hypoglycaemia negative mood states increased significantly, whereas positive mood states decreased. Hypoglycaemia prolonged rating time of emotional stimuli (drawn from IAPS) significantly. The arousal ratings of the slides were higher during hypoglycaemia. Valence and dominance ratings were not affected. Epinephrine and norepinephrine release correlated with a higher arousal rating and a decrease in positive mood states. Deterioration in neuropsychological tasks correlated with an increase in negative mood states. Experimental induction of hypoglycaemia can offer a new research model to study emotional processes.

Adult↗
PubMed2001

Fluvastatin therapy improves microcirculation in patients with hyperlipidaemia.

The purpose of this study was to investigate the effect of fluvastatin on the microcirculation of patients with hyperlipidaemia (low-density lipoprotein cholesterol > 160 mg/dL, triglycerides < 350 mg/dl) inadequately controlled by diet. After a dietary run-in of 4 weeks, patients were randomised in a double-blind study to receive fluvastatin 40 mg twice daily (n = 24) or placebo (n = 24) for 12 weeks. The effect on microcirculation was assessed using capillary microscopy and laser Doppler fluxmetry at the nailfold at baseline and at 6 and 12 weeks after initiation of therapy. Capillaroscopy showed that fluvastatin improved microcirculation, i.e. time to peak flow during postocclusive reactive hyperaemia dropped from 19.7 +/- 7.2 s at baseline to 12.3 +/- 9.5 s at week 6 (P < 0.01) and 10.6 +/- 6.5 s at week 12 (P < 0.0001). These results were confirmed using laser Doppler fluxmetry to study microcirculation in thermoregulatory capillaries at the same site. A significant decrease in total and LDL-cholesterol was achieved during fluvastatin therapy. In conclusion, fluvastatin therapy improves microcirculation in nutritive as well as thermoregulatory capillaries in hypercholesterolaemic patients within 6 weeks.

Anticholesteremic Agents↗
PubMed2001

Pharmacokinetic profile and in vitro selective cyclooxygenase-2 inhibition by nimesulide in the dog.

The pharmacokinetic properties and in vitro potency of nimesulide, a nonsteroidal anti-inflammatory drug (NSAID) were investigated in 8 or 10 dogs after intravenous (i.v.), intramuscular (i.m.) and oral (single and multiple dose) administrations at the nominal dose of 5 mg/kg. After i.v. administration, the plasma clearance was 15.3 +/- 4.2 mL/kg/h, the steady-state volume of distribution was low (0.18 +/- 0.011 L/kg) and the elimination half-life was 8.5 +/- 2.1 h. After i.m. administration, the terminal half-life was 14.0 +/- 5.3 h indicating a slow process of absorption with a maximum plasma concentration (6.1 +/- 1.5 microg/mL) at 10.9 +/- 2.1 h postadministration and the systemic bioavailability was 69 +/- 22%. After oral administration in fasted dogs, the maximal plasma concentration (10.1 +/- 2.7 microg/mL) was observed 6.1 +/- 1.6 h after drug administration, the plasma half-life was 6.2 +/- 1.9 h and the mean bioavailability was 47 +/- 12%. After daily oral administrations for 5 days, the average plasma concentration during the fifth dosage interval was 8.1 +/- 2.9 microg/mL and the overall bioavailability was 58 +/- 16%. The mean accumulation ratio was 1.27 +/- 0.4. In vitro nimesulide inhibitory potencies for cyclooxygenase (COX)-1 and COX-2 isoenzymes were determined using a whole blood assay. Canine clotting blood was used to test for inhibition of COX-1 activity and whole blood stimulated by lipopolysaccharide (LPS) was used to test for inhibition of COX-2 activity. The inhibitory concentration (IC50) for inhibition of COX-2 and COX-1 were 1.6 +/- 0.4 microM (0.49 +/- 0.12 microg/mL) and 20.3 +/- 2.8 microM (6.3 +/- 0.86 microg/mL) giving a nimesulide COX-1/COX-2 ratio of 12.99 +/- 3.41. It was concluded that at the currently recommended dosage regimen (5 mg/kg), the plasma concentration totally inhibits COX-2 and partly inhibits COX-1 isoenzyme.

Administration, Oral↗
PubMed2001

A pharmacokinetic/pharmacodynamic approach vs. a dose titration for the determination of a dosage regimen: the case of nimesulide, a Cox-2 selective nonsteroidal anti-inflammatory drug in the dog.

The present experiment was designed to determine a dosage regimen (dose, interval of administration) in the dog for nimesulide, a nonsteroidal anti-inflammatory drug with in vitro selectivity for the inhibition of cyclo-oxygenase 2 (Cox-2), using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The PK/PD results were compared with those obtained using a classical dose titration study. In the PK/PD experiment, 11 dogs were subjected to Freund's adjuvant arthritis characterized by permanent hyperthermia. Nimesulide (5 mg/kg, oral route) was tested during the secondary phase of the inflammatory response. In the dose titration study, nimesulide (0, 3, 6 and 9 mg/kg, oral route) was tested in eight other dogs using a reversible urate crystal arthritis in a 4-period crossover design. Different PD endpoints (including lameness assessed by force plate and hyperthermia) were regularly measured during the PK/PD experiment, and plasma samples were obtained to determine the plasma nimesulide concentration. The data were modeled using an indirect effect model. The IC50 of nimesulide for lameness was 6.26 +/- 3.01 microg/mL, which was significantly higher than the EC50 value obtained for antipyretic effect (2.72 +/- 1.29 microg/mL). The ED50 estimated from the classical dose titration study were 1.34 mg/kg (lameness) and 3.0 mg/kg (skin temperature). The PK/PD parameters were used to simulate different dosage regimens (dose, interval of administration). The antipyretic and anti-inflammatory effects were calculated from the model for the recommended dosage regimen (5 mg/kg/24 h). It was apparent from this approach, that this dosage regimen enabled 76% of the theoretical maximal drug efficacy to be obtained for pyresis and 43% for lameness. It was concluded from the comparison of in vivo and in vitro IC50, that nimesulide is a potent NSAID for which some Cox-1 inhibition is required to obtain clinically relevant efficacy.

Administration, Oral↗
PubMed2000

Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy.

Diabetic polyneuropathy is a serious complication in patients with diabetes mellitus. In addition to the maintenance of a sufficient metabolic control, alpha-lipoic acid (ALA) (Thioctacid, Asta Medica) is known to have beneficial effects on diabetic polyneuropathy although the exact mechanism by which ALA exerts its effect is unknown. In order to study the effect of ALA on microcirculation in patients with diabetes mellitus and peripheral neuropathy one group of patients (4 female, 4 male, age 60+/-3 years, diabetes duration 19+/-4 years, BMI 24.8+/-1.3 kg/m2) received 1200 mg ALA orally per day over 6 weeks (trial 1). A second group of patients (5 female, 4 male, age 65+/-3 years, diabetes duration 14+/-4 years, BMI 23.6+/-0.7 kg/m2) was studied before and after they had received 600 mg ALA or placebo intravenously over 15 minutes in order to investigate whether ALA has an acute effect on microcirculation (trial 2). Patients were investigated by nailfold video-capillaroscopy. Capillary blood cell velocity was examined at rest and during postreactive hyperemia (occlusion of the wrist for 2 minutes, 200 mmHg) which is a parameter of the perfusion reserve on demand. The oral therapy with ALA resulted in a significant decrease in the time to peak capillary blood cell velocity (tpCBV) during postocclusive hyperemia (trial 1: 12.6+/-3.1 vs 35.4+/-10.9 s, p<0.05). The infusion of ALA also decreased the tpCBV in patients with diabetic neuropathy (trial 2: before: 20.8+/-4,5, ALA: 11.74+/-4.4, placebo: 21.9-5.0 s, p<0.05 ALA vs both placebo and before infusions) indicating that ALA has an acute effect on microcirculation. Capillary blood cell velocity at rest (rCBV), hemodynamic parameters, hemoglobinA1c and local skin temperature remained unchanged in both studies. These results demonstrate that in patients with diabetic polyneuropathy ALA improves microcirculation as indicated by an increased perfusion reserve on demand. The observed effects are apparently acute effects. With the restriction of the pilot character of this investigation the findings support the assumption that ALA might exert its beneficial effects at least partially by improving microcirculation which is likely to occur also at the level of the vasa nervorum.

Antioxidants↗
PubMed2000

Effect of angiotensin II infusion with and without angiotensin II type 1 receptor blockade on nitric oxide metabolism and endothelin in human beings: a placebo-controlled study in healthy volunteers.

BACKGROUND: Angiotensin II has been shown to induce the synthesis of endothelium-derived relaxing factor nitric oxide (NO) and endothelin in vitro. In human beings, to our knowledge, no data on NO release in response to angiotensin II and on the influence of angiotensin II type 1 receptor blockade have been published. METHODS: In a placebo-controlled study in nine healthy volunteers, angiotensin II was administered intravenously for 6 hours with and without pretreatment with valsartan, a specific angiotensin II type 1 receptor antagonist. NO (NO2 + NO3) and endothelin plasma concentrations, clearance values for inulin and paraaminohippuric acid and NO (NO2 + NO3) excretion in urine were determined. RESULTS: During angiotensin II infusion NO plasma concentrations remained unaltered compared with placebo after 3 hours: 6.66 +/- 5.49 versus 5.56 +/- 3.09 micromol/L (P = ns) but increased after 6 hours: 18.36 +/- 20.02 versus 7.13 +/- 3.87 micromol/L (P < .04). The same was noted after pretreatment with valsartan: 7.61 +/- 5.69 versus 5.56 +/- 3.09 micromol/L (P= ns) after 3 hours, and 21.70 +/- 11.51 versus 7.13 +/- 3.87 micromol/L (P = .02) after 6 hours. In urine fractional NO excretion decreased after angiotensin II infusion: 0.87 +/- 0.72 versus 0.95 +/- 0.71 (P = .5) during the first 3 hours, and 0.44 +/- 0.39 versus 0.78 +/- 0.43 (P = .01) during the following 3 hours. After valsartan pretreatment the decrease in fractional urinary NO excretion began earlier: 0.40 +/- 0.15 versus 0.95 +/- 0.71 (P = .04) during the first 3 hours, and 0.17 +/- 0.11 versus 0.78 +/- 0.43 (P = .01) during the following 3 hours. Endothelin plasma concentrations showed no difference after angiotensin II infusion with or without valsartan. CONCLUSIONS: Our observations demonstrate for the first time that angiotensin II increases NO plasma concentrations in human beings and that this response is not mediated by angiotensin II type 1 receptor. In spite of increased NO plasma levels, urinary NO excretion decreased. Endothelin plasma levels remained unchanged during angiotensin II infusion.

Adult↗
PubMed1999

The effect of alpha-lipoic acid on the neurovascular reflex arc in patients with diabetic neuropathy assessed by capillary microscopy.

Patients with diabetic polyneuropathy are known to have an impaired neurovascular reflex arc compared to healthy controls. This is seen in a delayed decrease in microcirculation of the ipsilateral hand after cooling of the contralateral hand. The aim of this pilot study was to investigate whether intravenous alpha-lipoic acid (ALA) (Thioctacid, Asta Medica) therapy might be able to improve this impaired neurovascular reflex arc in patients with diabetic neuropathy. In addition, clinical effects were evaluated with the aid of the neuropathy symptom score (NSS) and the neuropathy disability score (NDS). Ten patients with diabetes mellitus and polyneuropathy (5 females, 5 males, 2 smokers, 5 IDDM, 5 NIDDM, body mass index 26.1 +/- 1.0 kg/m2, age 58.3 +/- 9.5 years, diabetes duration 15.7 +/- 11.2 years, Hb A1c 6.8 +/- 0.3%) were investigated by nail-fold capillaroscopy after contralateral cooling before and after intravenous therapy with 600 mg alpha-lipoic acid per day over 3 weeks. Cardiac autonomic neuropathy was excluded by beat-to-beat variation analysis. Symptoms of diabetic neuropathy were evaluated before and after therapy with the aid of the NSS and NDS. Capillary blood cell velocity (CBV) of the hand was determined before, during, and for the following 30 min after cooling (3 min at 15 degrees C) of the contralateral hand. Blood pressure, heart rate, and local skin temperature were monitored at 2-min intervals. ALA therapy resulted in a significant improvement of the microcirculatory response to cooling, as seen by an immediate decrease in CBV of 12. 3% (P < 0.02 vs before treatment), which was absent before therapy. Blood pressure, heart rate, and local skin temperature were not different between investigations. There was a significant improvement of the NSS after therapy (5.4 +/- 1.1 vs 8.6 +/- 1.1 points, P < 0.01). These results demonstrate that intravenous therapy with ALA has a positive influence on the impaired neurovascular reflex arc in patients with diabetic neuropathy.

Adult↗