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M Pfohl

Publications and source records attributed to M Pfohl.

At least 19 recordsLinked to original sources

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial.

AIMS: The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes. METHODS: The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively. The quality of glycaemic control was assessed by HbA(1c), blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self-report questionnaires have been assessed. RESULTS: CSII treatment resulted in lower HbA(1c) (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI (+/- 3.9 vs. +/- 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08-1.17] and 2.61 (95% CI: 1.59-4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII (P < 0.001), and an improvement in pump users' perception of mental health was detected when using the SF-12 questionnaire (P < 0.05). CONCLUSION: CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients' quality of life. Additional studies are needed to compare CSII with glargine- and detemir-based MDI.

Adult↗

Healing times and prediction of wound healing in neuropathic diabetic foot ulcers: a prospective study.

Time line of wound healing and prediction of healing times in diabetic foot ulcers is an important issue. Usually, the percentage of wounds healed within a defined period is used for characterization of wound healing. R=sqrtA/pi (R, radius; A, planimetric wound area; pi, constant 3.14), and the wound radius reduction was 0.39 mm/week which was previously established. The initial average wound area was 96.9+/-13.1 mm2 (mean+/-SEM), and 3.61+/-1.6 mm 2 after ten weeks with an average healing time of 75.9 (95 %-CI 71-81) days. Using the equation mentioned above and the calculated weekly wound radius reduction, the predicted healing time in the test group was 86.9 (95 %-CI 73-101) days. The predicted and the observed healing times were significantly correlated with each other (r=0.55, p=0.0002). Providing standard care, the time needed for wound healing can reliably be predicted in neuropathic diabetic foot ulcers. This may be a useful tool in daily clinical practice to predict wound healing and recognize ulcers who do not respond adequately to the treatment.

Diabetes Mellitus, Type 1↗

A 63bp deletion in the promoter of rage correlates with a decreased risk for nephropathy in patients with type 2 diabetes.

Several polymorphisms have been identified in the RAGE-promoter region that might modulate the outcome of disease. Here we analyse the association of a 63bp deletion (delta63) spanning from bp - 407 to bp - 345 with diabetic nephropathy. The deletion was determined using the polymerase chain reaction (PCR) in a cross-sectional study with 1087 patients with type 1 diabetes (n = 559) and type 2 diabetes (n = 528). 475 patients with osteoporosis served as disease independent control. The prevalence of the heterozygous genotype did not significantly differ between the three groups (type 1: 2.15 %, type 2: 2.27 %, controls: 1.47 %), indicating that heterozygous delta63 is not related to the manifestation of diabetes. Homozygous carriers were not identified in this study. The heterozygous delta63 genotype, was associated with a reduced prevalence of diabetic nephropathy in patients with type 2 diabetes (OR = 0.06; 95 % CI: [0.05, 0.07]), but not in patients with type 1 (OR = 1.49; 95 % CI: [1.14, 1.94]). We conclude, that patients with type 2 diabetes and the 63bp deletion in the promoter of RAGE seem to be protected from diabetic nephropathy. The observed difference between type 1 and type 2 diabetes might point to diverse pathomechanisms of nephropathy in both types of diabetes.

Diabetes Mellitus, Type 1↗

The effects of ulcer size on the wound radius reductions and healing times in neuropathic diabetic foot ulcers.

The main problems in the treatment of diabetic foot ulcers are prolonged wound healing and not necessary amputations, which may sometimes be caused by the impression that the results of conservative treatment are somewhat unpredictable. The aim of this study was to determine the effects of ulcer size on the wound radius reduction and healing times using a previously established equation for wound healing in neuropathic diabetic foot ulcers. This prospective study evaluates wound healing in 120 diabetic patients with neuropathic foot ulcers who were grouped according to four different ulcer areas (A 100 150 200 mm (2)). Ulcer healing was assessed by planimetric measurement of the wound area every second week until wound healing. The time course of wound healing in the different groups was compared by the weekly wound radius reduction using the equation R = sqrt A/pi. The average healing time in group A was 70 (95 %-CI 64 - 77) days with a wound radius reduction of 0.42 mm/week (95 %-CI 0.28 - 0.56). In group B the average healing time was 79 (95 %-CI 75 - 82) days and the weekly wound radius reduction was 0.47 mm (95 %-CI 0.45 - 0.49). The average healing time in group C was 85 (95 %-CI 80 - 89) days with a wound radius reduction of 0.53 mm/week (95 %-CI 0.42 - 0.56). In group D the average healing time was 97 (95 %-CI 91 - 103) days. The weekly wound radius reduction was 0.57 mm (95 %-CI 0.49 - 0.81). Wound radius reductions and the time needed for healing are affected by the ulcer area, a measure of ulcer size, in neuropathic diabetic foot ulcers. The calculation of the weekly wound radius reduction for different ulcer areas may be a useful tool in daily clinical practice to identify ulcers who do not respond adequately to the treatment.

Aged↗

Impaired 0.1-Hz vasomotion assessed by laser Doppler anemometry as an early index of peripheral sympathetic neuropathy in diabetes.

Impairment of 0.1-Hz vasomotion, which was found in diabetic patients, was suggested to be an early index of sympathetic dysfunction. We studied the relationships between alterations in vasomotion and both cardiac autonomic and sensory neuropathy. Twenty type 1 and 22 type 2 diabetic patients were investigated. Vasomotion was recorded in single capillaries at the dorsal middle phalangeal area of the left ring finger by means of laser Doppler anemometry. Cardiac autonomic neuropathy was assessed by spectral analysis of heart rate variation during rest and recording heart rate responses to deep breathing and Valsalva manoeuvre. Sensory neuropathy was investigated by measuring heat pain, vibration, and thermal sensory thresholds. Impaired vasomotion was more often (82.4%) found in diabetic patients with at least one altered cardiac autonomic test, but also in 47.1% of those with all of these tests being normal (P = 0.035). Both heart rate variation coefficient during rest (r = 0.40, P = 0.045) and Valsalva ratio (r = 0.41, P = 0.037) correlated positively with amplitudes of vasomotion in type 1 diabetic patients. The prevalence of impaired vasomotion was not higher in patients with sensory neuropathy compared to those with normal sensory functions. A disturbed warm sensation was only found in 2 patients and none had an abnormal heat pain threshold. Our data indicate that impairment of 0.1-Hz vasomotion precedes parasympathetic neuropathy, assessed by heart rate variation tests, and abnormalities in warm and heat pain sensation. Reduction of arteriolar vasomotion, detected by laser Doppler anemometry, might be an early index of sympathetic dysfunction, because it correlates with disturbances in those cardiac autonomic tests, which are at least in part under sympathetic control.

Adult↗

Endothelial nitric oxide synthase (ecNOS) 4 a/b gene polymorphism and carotid artery intima-media thickness in type-1 diabetic patients.

AIM: To study putative associations of the ecNOS 4 a/b polymorphism with carotid artery intima-media thickness (IMT) and diabetic complications in young type-1 diabetic patients. METHODS: Study participants were 147 type-1 diabetic patients (56 men and 91 women), mean age 30.1 +/- 6.6 years (range 14 - 44), with a diabetes duration of 13.1 +/- 8.1 years. HbA1c, albuminuria, and lipid status were assessed by standard laboratory techniques, the ecNOS 4 a/b genotype was determined by polymerase chain reaction with subsequent polyacrylamide gel electrophoresis. The patients were categorized according to the presence or absence of hypertension, nephropathy and retinopathy. The IMT, which can be used to estimate early stages of arteriosclerosis, was measured by high-resolution ultrasonography. RESULTS: The ecNOS genotypes were distributed as follows: 7.5 % a/a, 30.6 % a/b, and 61.9 % b/b. The IMT values did not differ between the patients with various ecNOS genotypes (a/a: 0.62 +/- 0.13; a/b: 0.63 +/- 0.21; b/b: 0.63 +/- 0.13; all: 0.63 +/- 0.15 mm). The prevalence of retinopathy was significantly higher in patients with the b/b genotype (odds ratio: 2.4 vs. a/a+a/b; 95 % CI, 1.1 - 5.3). CONCLUSIONS: Our results do not support the hypothesis that the ecNOS 4 a/b polymorphism interacts with the development of early carotid arteriosclerosis in young type-1 diabetic patients, but they give grounds to assume that in these patients it could influence the occurence of diabetic retinopathy.

Adolescent↗

Impairment of cutaneous arteriolar 0.1 Hz vasomotion in diabetes.

Arteriolar vasomotion, the cyclic contraction/dilation of terminal arterioles, is disordered in diabetes. The aim of the present study was to characterize the impairment of cutaneous vasomotion in type 1 and type 2 diabetes, especially with regard to the influence of metabolic control and to the response to shear stress. Twenty type 1 and 23 type 2 diabetic patients were investigated. Vasomotion waves were recorded in single capillaries at the dorsal middle phalangeal area of the left ring finger during rest, after warming the skin temperature to 33 degrees C, and after 3-min arterial occlusion by means of laser Doppler anemometry. Suprasystolic occlusion caused an increase in amplitudes of vasomotion only in type 1 diabetic patients (0.12 +/- 0.04 mm/s vs. 0.36 +/- 0.06 mm/s, p = 0.001). In type 1 but not in type 2 diabetic patients, both systolic and diastolic blood pressure correlated positively with amplitudes of resting vasomotion (r = 0.62, p = 0.002 and r = 0.65, p = 0.001, respectively). Amplitudes of vasomotion after warming up at frequencies of 5 - 8 cycles per minute (0.08 - 0.13 Hz) correlated inversely with the levels of glycated hemoglobin (HbA 1c ) (r = - 0.56, p = 0.005) only in type 1 diabetic patients. In conclusion, we found suprasystolic occlusion and increasing blood pressure to provoke vasomotion with a concomitant decrease in effective vascular resistance only in type 1 diabetic patients. The impaired vasomotion response to shear stress in type 2 diabetes might favour the development of skin lesions and arterial hypertension. Insufficient glycemic control seems to be an important factor in the pathogenesis of impaired vasomotion in type 1 diabetes.

Adult↗

Applied felted foam for plantar pressure relief is an efficient therapy in neuropathic diabetic foot ulcers.

The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of neuropathic diabetic foot ulcers, but the knowledge of its impact on the wound healing and healing times in foot ulcers compared to conventional methods of pressure relief is sparse. The aim of this study was to assess the effects on the wound healing of felted foam dressings for plantar pressure reduction in the therapy of neuropathic foot ulcers. This prospective cohort study evaluates healing times and wound healing in 61 diabetic patients with neuropathic foot ulcerations. Ulcer healing was assessed by planimetric measurement of the wound area at beginning of the study and after 10 weeks and at least until wound healing. The patients were consecutively enrolled in the study, 27 patients were randomized to the felted foam therapy, and 34 patients were randomized to conventional therapy. In the felted foam group, the initial average wound area was 110.8 +/- 14.4 mm 2 (mean +/- SE), and 2.1 +/- 0.5 mm 2 after ten weeks (p < 0.0001), with an average healing time of 79.6 (95%-CI 75-84) days. In the conventional therapy group, the initial average wound area was 119.2 +/- 13.8 mm 2, and 3.4 +/- 0.7 mm 2 after ten weeks (p < 0.0001). The average healing times was 83.2 (95%-CI 77-90) days. Both with respect to the wound healing process and the healing times, the felted foam technique appears to be as effective as conventional plantar ulcer treatment. We conclude that the felted foam technique is an useful alternative in the therapy of the neuropathic diabetic foot syndrome, especially in patients who are not able to avoid weight-bearing reliably.

Cohort Studies↗

[Clinical value of urinary pyridinium crosslinks as osteoporosis markers: evaluation of a population survey of vertebral osteoporosis].

BACKGROUND: The diagnostic value of biochemical parameters of bone turnover for the diagnosis of osteoporosis is open to discussion. We investigated whether the determination of crosslinks, bone type I collagen degradation products, correctly identifies osteoporotic subjects. PATIENTS AND METHOD: In a sample of 370 individuals recruited at random within a population survey of vertebral osteoporosis, urinary concentration of total pyridinoline and desoxypyridinoline were determined by HPLC. Standardized lateral X-rays of the thoracic and lumbar spine were taken and evaluated morphometrically using the method described by Eastell-Melton. RESULTS: Crosslink excretion was significantly higher in female but not in male individuals with vertebral deformities as defined by Eastell. The specificity of these biochemical parameters with regard to radiological osteoporotic alterations was 76-81%, but the sensitivity was 32.4-42.9% only. CONCLUSION: Pyridinoline and desoxypyridinoline reflect the process of bone degradation which leads to vertebral deformity. Crosslinks are specific markers of bone resorption and provide a valid parameter in the diagnosis of osteoporosis. The low sensitivity indicates that the measurement of pyridinoline and desoxypyridinoline is less suitable for screening purposes, but may be useful in confirming presence or extent of osteoporosis.

Aged↗

[Assessment of diabetic alterations of microcirculation by means of capillaroscopy and laser-Doppler anemometry].

BACKGROUND: Only minor changes of skin capillary morphology have been described in diabetic patients by means of capillaroscopy, whereas cutaneous microvascular dysfunction is well known. We examined correlations between functional and morphological abnormalities of the capillaries in Type 1 and 2 diabetic patients and the influence of diabetes duration on capillary morphology. PATIENTS AND METHODS: Density, diameters and morphology of nailfold capillaries were investigated in diabetic patients, 16 Type 1 and 19 Type 2, and compared to age- and sex-matched control groups. Capillary blood cell velocities (CBV) during rest and after 3-minute arterial occlusion were measured in the dorsal middle phalangeal area of the left ring finger by means of laser Doppler anemometry. RESULTS: Capillary density, width and arterial limb diameter were similar in Type 1 and 2 diabetic patients compared to their controls. Capillary diameters of the apical part and the venous limb were enlarged in the combined analysis of Type 1 and 2 diabetic patients compared to the control group (apex: 19.2 +/- 0.6 microns vs 17.4 +/- 0.6 microns, p = 0.0243; venous limb: 17.3 +/- 0.5 microns vs 15.9 +/- 0.4 microns, p = 0.0238). Tortuous capillaries were more often observed in Type 1 (n = 13 vs n = 7, p = 0.028) and 2 diabetic patients (n = 16 vs n = 9, p = 0.019) than in controls. In Type 1 diabetic patients an inverse correlation (r = -0.52; p = 0.019) was found between capillary density and resting CBV. In Type 2 diabetic patients capillary apex diameter correlated positively with peak CBV (r = 0.49; p = 0.017). Disease duration correlated inversely with arterial limb diameter (r = -0.48; p = 0.020) and width of the capillaries (r = -0.48; p = 0.018) in Type 2 diabetic patients. CONCLUSION: Tortuous and dilated capillaries, indicating microangiopathy, were found in the skin of diabetic patients by means of capillaroscopy. Using laser Doppler anemometry it is possible to assess impairment of postocclusive reactive hyperemia, due to diabetic microvascular dysfunction, in single capillaries. Correlations between morphological and functional microcirculatory alterations in diabetes may be explained by hemodynamic changes, depending on diabetes duration.

Adult↗

Anti-MPO-ANCA-positive microscopic polyangiitis following subacute bacterial endocarditis.

Although infectious agents such as Staphylococcus aureus have been implicated in the pathogenesis of Wegener's granulomatosis, the role of bacterial infections in the pathogenesis of other types of small-vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) is less clear. We describe a patient who developed a non-granulomatous necrotising small vessel vasculitis and perinuclear ANCA (p-ANCA) directed against myeloperoxidase (MPO) after recurrent episodes of bacterial endocarditis due to Staph. aureus. Although cytoplasmic ANCA (c-ANCA) directed against proteinase 3 have been reported in single patients with bacterial endocarditis, to our knowledge this patient is the first reported case of an anti-MPO-ANCA positive systemic vasculitis following bacterial endocarditis.

Antibodies, Antineutrophil Cytoplasmic↗

Paraoxonase 1 192 Gln/Arg gene polymorphism and cerebrovascular disease: interaction with type 2 diabetes.

Paraoxonase 1 (PON1) is an HDL-associated enzyme which protects HDL and LDL particles from lipid peroxidation. Its enzymatic serum activity varies 10-40-fold between individuals, and its biallelic gene polymorphism at codon 192 (glutamine-->arginine, Gln/Arg) has been associated with coronary artery disease in diabetic patients. To evaluate the role of this PON1 gene polymorphism in cerebrovascular disease, we determined the PON1 192 genotype in 149 patients with hemodynamically relevant extracranial artery stenosis and in 241 controls. The PON1 192 Gln/Arg genotype was determined using polymerase chain reaction followed by Alw I digestion and polyacrylamide gel electrophoresis. Among all subjects, there was no association between the PON1 192 Gln/Arg genotype and cerebrovascular disease (Odds ratio for Arg/Arg and Gln/Arg vs Gln/Gln 0.99, 95%-CI 0.70-1.39). In contrast, in the subgroup of type 2 diabetic patients the PON1 192 Arg allele conferred about twice the risk of cerebrovascular stenosis compared to those homozygous for the Gln allele (Odds ratio 2.00, 95%-CI 0.92-4.38). Our data indicate that in the general population the PON1 192 Gln/Arg gene polymorphism cannot be regarded as a major risk marker for cerebrovascular disease. The observed interaction with type 2 diabetes, however, is supporting the hypothesis that the effect of the PON1 192 Arg allele on atherosclerosis is modulated by other risk factors like diabetes.

Aged↗

Strategies for the prevention of type 2 diabetes.

Type 2 diabetes is a common chronic disease affecting more than 100 millions of people world-wide, and is a major cause of premature morbidity and mortality. Macrovascular disease and its risk factors are often already present in individuals at risk for type 2 diabetes, and some of the risk factors for the development of type 2 diabetes, such as obesity, physical inactivity, and high-fat diet, can potentially be modified. Because some of the metabolic abnormalities, such as insulin resistance or impaired glucose tolerance, that indicate a risk for diabetes can be improved by lifestyle modification and drug treatment, strategies for the prevention of type 2 diabetes appear to be necessary for affected individuals. Several clinical trials have addressed the hypothesis that type 2 diabetes can be prevented by dietary modification, physical activity, or drug treatment. Although some of these studies indicate a protective effect of these measures against the development of type 2 diabetes in people at risk, many of their conclusions are limited with respect to randomisation, sample size, or intensity of the intervention. In the large prospective Da Qing study (1997), both dietary and physical activity interventions reduced the incidence of type 2 diabetes considerably in a Chinese population. Whether this is also achievable in other ethnic populations at high risk for developing type 2 diabetes, and whether additional pharmacological measures are useful, is currently under investigation.

Diabetes Mellitus, Type 2↗

Early detection of microcirculatory impairment in diabetic patients with foot at risk.

OBJECTIVE: To assess microcirculatory impairment and alterations of the skin oxygen supply in diabetic patients with foot at risk. RESEARCH DESIGN AND METHODS: This study evaluated skin blood flow in 21 type 2 diabetic patients with a foot at risk (defined as a foot with neuropathy but without ulceration or previous ulcerations), 20 type 2 diabetic patients without foot lesions or neuropathy, and 21 normal subjects as a control group. The skin blood flow was determined by measuring the transcutaneous oxygen pressure (TcPO(2)) at the dorsum of the foot in supine and sitting position. The clinical assessment included standard measures of peripheral and autonomic neuropathy, but peripheral vascular disease was excluded by Doppler ultrasound. RESULTS: In supine position, TcPO(2) was significantly reduced (means +/- SE) in diabetic patients with foot at risk (6.04 +/- 0.52 kPa) compared with diabetic (7.14 +/- 0.43 kPa, P = 0.035) and nondiabetic (8.10 +/- 0.44 kPa, P = 0.01) control subjects. The sitting/supine TcPO(2) difference was higher in diabetic subjects with foot at risk (3.13 +/- 0.27 kPa) compared with both diabetic (2.00 +/- 0.18, P = 0.004) and nondiabetic (1.77 +/- 0.15 kPa, P = 0.0003) control subjects. The mean sitting/supine ratio was 1.70 +/- 0.12 in diabetic patients with foot at risk, 1.32 +/- 0.04 in diabetic control subjects, and 1.25 +/- 0.03 in nondiabetic control subjects (P = 0.007). The sitting/supine TcPO(2) ratio was negatively correlated with the heart rate variation coefficient at rest (r = -0.32, P = 0.044) and at deep respiration (r = -0.31, P = 0.046). CONCLUSIONS: Our data indicate that skin oxygen supply is reduced in type 2 diabetic patients with foot at risk. This is probably due to an impaired neurogenic blood flow regulation and may contribute to capillary hypertension, followed by disturbed endothelial function leading to edema and skin damage of the foot. The determination of TcPO(2) appears to be a useful tool in screening type 2 diabetic patients for foot at risk.

Adult↗