Computerized generation of circadian sensor modal days with continuous glucose monitoring for comparison of various insulin regimens based on insulin glargine in type 1 diabetes.

AIM: Our aims were (1) to design and standardize a statistical approach for data reduction in continuous glucose monitoring, allowing comparison of circadian glycemic patterns in therapeutic subcohorts of patients with type 1 diabetes, and (2) to investigate the applicability of this approach for CGMS assessment in clinical study of basal insulin replacement quality with various timings of basal injections (pre-breakfast, dinner, bedtime) of a new insulin analog. METHODS: Prospective randomized three-arm parallel study with switch over after 6 months for another 3 months of free choice injection time point (options pre-breakfast, pre-dinner and bedtime) of the new insulin analog in 16 type 1 diabetic subjects on functional insulin treatment (FIT: basal, prandial and correctional dosages). CGMS was used at the end of each follow up period of a clinical study. Representative daily profiles were off-line computed as "circadian sensor modal days" for each insulin regimen consisting of consecutive means of hourly glucose values. RESULTS: Although the overall quality of glycemic control (HbAIC) for different regimens did not reach statistical differences, CGMS displayed slightly divergent maximal swings in the course of glycemia (p=0.04-0.08) and allowed--with delineated data reduction procedure--a reliable between treatment comparison. CONCLUSION: Off-line computation of "hourly circadian sensor modal days" for data reduction can be effectively used with CGMS for description of circadian glycemic patterns in type 1 diabetes.

Normalization of pregnancy outcome in pregestational diabetes through functional insulin treatment and modular out-patient education adapted for pregnancy.

AIM: To investigate whether modular out-patient group education for flexible, Functional Insulin Treatment (FIT) adapted for pregnancy can eliminate diabetes-associated neonatal complications in pregestational diabetes. RESEARCH DESIGN AND METHODS: Outcome analysis of the modular out-patient group education and FIT based on separate insulin dosages for fasting, eating or correcting hyperglycaemia in 76 consecutive pregnancies (in 20 cases first after conception) of 59 patients with pregestational diabetes (Type 1 diabetes, n = 54). CONTROLS: (a) diabetic pregnancies: historical controls; (b) non-diabetic pregnancies: retrospective case-controlled study; (c) population-based data of all Austrian newborns registered within the respective time period. RESULTS: HbA1c of 113 +/- 18% of mean value (= 100%) of non-diabetic, non-pregnant population (103 +/- 14% during the last pregnancy trimester), and self-monitored blood glucose of 5.6 +/- 0.7 mmol/l (5.3 +/- 0.7 mmol/l during the last trimester) was achieved throughout all FIT pregnancies. Severe hypoglycaemia occurred in 14 pregnancies. The gestational age at delivery was 39.2 +/- 1.5 weeks (four cases (5.4%) < 37 weeks) with a birth weight of 3305 +/- 496 g. Four newborns (5.3%) were above the 90th, and nine (11.8%) below the 10th percentile for weight of reference population-based data. Hypoglycaemia was recorded in six newborns (8%). Malformations were found in two infants whose mothers booked for diabetes FIT education only after conception. The caesarean delivery rate was 25%. In comparison with historical diabetic pregnancy controls we demonstrated a reduction in major complications, and compared with non-diabetic women, a lowering of diabetes-related neonatal complication rates to general population levels. CONCLUSIONS: Structured, comprehensive, modular out-patient group education promoting self-choice of insulin dose for flexible, normal eating prior to conception normalizes pregnancy outcome in diabetes.

[Parameters of power spectral analysis of heart rate variability for use in clinical evaluation of various stages of diabetic cardiovascular autonomic neuropathy]. / Návrh parametru spektrální analýzy variability srdecní frekvence vhodných pro klinické hodnocení ruzných stadií diabetické kardiovaskulární autonomní neuropatie.

UNLABELLED: The aim of the study was to select parameters of power spectral analysis appropriate for clinical evaluation of various degrees of diabetic cardiovascular autonomic neuropathy. The diagnosis of autonomic neuropathy was based on Ewing's battery of cardiovascular autonomic function tests and on short-term power spectral analysis of heart rate variability during a modified orthostatic load (in positions supine-standing-supine). 52 diabetic patients and 24 age-matched controls were included. Diabetic patients were divided into two groups according to the total Ewing score. Groups of 14 subjects with early autonomic neuropathy and 38 subjects with severe AN were comparable in age and diabetes duration. RESULTS: Cumulative spectral power of the total frequency band in all three positions (Total Power LFHF 1 + 2 + 3) proved to be the most selective and discriminating parameter of power spectral analysis between the control group and diabetic patients with severe autonomic neuropathy in stepwise discriminant analysis. Spectral power of low-frequency band in positions 1 + 2 + 3 (Power LF 1 + 2 + 3) proved to be the most selective and discriminating parameter between diabetic groups with early and severe autonomic neuropathy. CONCLUSION: The most discriminating parameters of power spectral analysis of heart rate variability for the determination of autonomic function seem to be Total Power LFHF 1 + 2 + 3 and Power LF 1 + 2 + 3.

Cardiac autonomic function in patients suffering from primary focal hyperhidrosis.

Cardiac autonomic function in patients (n = 63) with primary focal hyperhidrosis and healthy controls (n = 28) was investigated by short-term frequency domain power spectral analysis of heart rate variability. The power of the very-low-frequency band (0.01-0.05 Hz) was significantly lower in patients with axillary hyperhidrosis than in controls. No differences between groups could be observed at investigation of the low-frequency band (0.05-0.15 Hz), which was a surprising finding because this band represents also sympathetic cardiac innervation. At the high-frequency band (0.15-0.5 Hz), which represents parasympathetic cardiac innervation, an interaction of type and position influencing spectral power was detected. Our highly interesting findings indicate that primary focal hyperhidrosis is based on a much more complex autonomic dysfunction than generalised sympathetic overactivity and seems to involve the parasympathetic nervous system as well.

Empowering diabetes out-patients with structured education: short-term and long-term effects of functional insulin treatment on perceived control over diabetes.

OBJECTIVE: To investigate short-term and long-term effects of structured outpatient education for Functional Insulin Treatment (FIT: selective insulin dosages for eating, fasting or correcting hyperglycaemia) on perceived control over diabetes and related health beliefs. FIT was thought to influence the perception of self-efficacy in diabetes, in contrast to conventional treatment, based on scheduled, rigid food intake and insulin delivery--it allows flexible eating, provided independent control of glycemia. METHODS: Structured, comprehensive, outpatient group training in FIT for selective use of insulin either for eating, fasting or correction included practical "insulin games." The FIT program focused on everyday criteria for choices of insulin dosages and thus on the patient's ability to execute his/her newly gained flexible treatment to his/her everyday life while preventing acute and late complications. To evaluate effects of FIT on "Perceived Control over Diabetes" and related "Health Beliefs Concerning Diabetes" (Bradley's questionnaires, 1984), a fully randomized short-term controlled Study 1 (four weeks, 32 patients), and long-term uncontrolled pilot Study 2 (three years, 68 patients) were performed. RESULTS: The short-term study revealed that FIT induced the feeling of independence from situational control while self-managing diabetes. In the long-term study, the patients were increasingly freed from the feeling of being under the control of physician and treatment-related restrictions, which--together with higher perceived self-efficacy--contributed to the feeling of "empowerment." This was associated with high treatment satisfaction and significant improvement of glycemic control. CONCLUSION: Structured out-patient group training for FIT results in measurable improvement of patients' perceived control over diabetes and self-efficacy.

Decrease of vigilance assessed by EEG-mapping in type I diabetic patients with history of recurrent severe hypoglycaemia.

In Type I diabetic patients with history of recurrent severe hypoglycaemia, a more rapid decrease in vigilance (slowing of brain function) during hypoglycaemia in comparison to patients without history of such events was found. Our aims were: (1) to study EEG parameters of vigilance in non-hypoglycaemic state in representative groups of Type I diabetic patients with and without previous recurrent severe hypoglycaemia; and (2) to compare them with non-diabetic controls. A vigilance-controlled EEG mapping (10-20 system, significance probability maps) was performed in a non-hypoglycaemic state (blood glucose 4.0-10.0 mmol/l) in a group of 13 Type I diabetic patients with a history of recurrent severe hypoglycaemia and compared to that of 14 Type I diabetic patients without history of severe hypoglycaemia, matched for HbA1c, age and gender, and to age- and gender-matched non-diabetic controls. When compared to non-diabetic controls, hypoglycaemia patients demonstrated a reduction in absolute power in beta band (13-35 Hz) and slowing of centroid frequencies of beta and total frequency bands (1.3-35 Hz) (up to P < 0.01), whereas patients without history of severe hypoglycaemia showed only a borderline reduction of absolute power in delta (1.3-3.5 Hz) band. Deceleration in hypoglycaemia patients versus those without recurrent hypoglycaemia was most remarkable (P < .01) in centroid frequency of total frequency band. Patients with history of recurrent severe hypoglycaemia demonstrated in non-hypoglycaemic state significantly reduced vigilance when compared to the group without hypoglycaemia history and to the controls, as well. Lower vigilance may be at least in part responsible for impaired hypoglycaemia perception in these patients, but, as it resembles EEG patterns seen in pathologic ageing, it might also represent a consequence of recurrent episodes of severe hypoglycaemia.

Dealing with ceiling baseline treatment satisfaction level in patients with diabetes under flexible, functional insulin treatment: assessment of improvements in treatment satisfaction with a new insulin analogue.

Even a small improvement in satisfaction with treatment for a chronic disease can be valuable. However, sensitive measurements instruments are needed to assess the effects of treatment changes in patients already well satisfied with baseline treatment. Such instruments were thought to be necessary to deal with ceiling effects in scores of satisfaction with functional insulin treatment (FIT) accommodating full flexibility of food intake and lifestyle in diabetes by manipulation of insulin (FIT; Howorka et al. 2000). The Status(S) version of the Diabetes Treatment Satisfaction Questionnaire (DTSQ, Bradley 1994) was extended with items measuring specific components of FIT and its psychometric properties investigated in a validation study with 171 FIT patients with diabetes. A new Change(C) version of DTSQ extended for FIT was used together with the DTSQ(S) by 52 participants in a subsequent randomised cross-over study involving new fast-acting lispro vs. regular insulin, where treatment satisfaction was the primary outcome variable. Insulin lispro use improved satisfaction (p < or = 0.001) both, on classical and extended versions of DTSQ(S) and (C), despite high baseline levels of satisfaction. However, the DTSQ(C) augmented the effects of lispro (p = 0.0001) apparent on DTSQ(S) scores and revealed significant treatment effects (p < or = 0.01) not significant with DTSQ(S). In parallel, glycaemic control improved with lispro (e.g., HbA1c, p = 0.023). Improved satisfaction with treatment was more apparent with DTSQ(C) than DTSQ(S) in patients who at baseline were at or near ceiling for treatment satisfaction.

[The Ewing test for autonomic neuropathy and spectral analysis of heartrate variability aid in the diagnosis of Charcot's osteoarthropathy]. / Vysetrení autonomní neuropatie Ewingovými testy i spektrální analýzou variability srdecní frekvence pomáhá diagnostikovat Charcotovu osteoartropatii.

UNLABELLED: The objective of the work was to evaluate the contribution of examining autonomic neuropathy in diabetic patients to early diagnosis of Charcot's osteoarthropathy by classical Ewing's tests, as well as the more recent method--spectral analysis of heart rate variability. The authors examined 18 diabetic patients in the early stage of Charcot's osteoarthropathy and the results were compared with a group of 30 subjects matched for age and sex. The results of examination by Ewing's test (heart rate variability during deep breathing, in orthostasis and during Valsalva's manoeuvre and blood pressure changes during orthostasis) revealed autonomic neuropathy in all examined patients, in one subject incipient neuropathy and in 17 of 18 patients manifest or severe neuropathy. The patients differed from controls highly significantly in all parameters of Ewing's tests with the exception of parameter 30:15 in orthostasis. The greatest sensitivity was recorded in the examination of the I-E difference during deep respiration. RRmax/RRmin and the brake index in orthostasis and Valsalva's ratio. The lowest sensitivity was recorded in the examination of the orthostatic fall of blood pressure. On spectral analysis the patients differed highly significantly from controls in all investigated parameters, the highest discriminating value was found in parameters of the total spectral power in the standing position (2) and the power in the low-frequency area in position 2, the first parameter alone was correctly discriminated in 94%. SUMMARY: Examination of autonomic neuropathy significantly improves the diagnosis of Charcot's osteoarthropathy. In addition to the classical Ewing tests spectral analysis of heart rate variability proved also a suitable method for its evaluation.

Optimal parameters of short-term heart rate spectrogram for routine evaluation of diabetic cardiovascular autonomic neuropathy.

Our aim was to select those parameters of heart rate variability (HRV) within its short-term power spectral analysis (PSA), which have a capability similar to that of the standard Ewing battery of cardiovascular function tests in determining different degrees of cardiovascular autonomic neuropathy (CAN) in diabetes and to compare the usefulness of both methods for diagnostic purposes in the everyday routine. Commonly used standard battery of cardiovascular autonomic function tests evaluated as total Ewing score as well as short-term PSA of HRV were used in 119 diabetic patients (age: 52.7 +/- 9.8, diabetes duration: 22.2 +/- 12.7 years). From this cohort, patients were selected according to the total Ewing score by matching for age, gender, BMI and diabetes type for 3 groups, each of 17 patients, with no CAN (total Ewing score 0-0.5), with early involvement (score 1.0-2.5) and with definite or severe CAN (score 3.0-5.0). Short-term PSA of HRV performed in three positions (supine1-standing-supine2) included frequency-domain and time-domain parameters of HRV. Cumulative spectral power of total frequency band (0.06-0.50 Hz) and spectral power of low-frequency band (0.06-0.15 Hz) during both supine positions proved to be the most selective and discriminating among all patient groups in inter-group comparison and in analysis of discriminance. The correlation between the total Ewing score and the cumulative spectral power of total frequency band was r = -0.87 (P < 0.001). About 83.2% of cases classified by short-term PSA of HRV using the variables selected by analysis of discriminance was congruent with the classification by the total Ewing score alone. Time expenditure for the performance of each examination was 31 +/- 10 min for Ewing test battery vs. 14 +/- 2 min for short-term PSA of HRV (P < 0.001). In summary, the latter method showed similar diagnostic value concerning the CAN as the classical Ewing standard battery of cardiovascular function tests, although its application proved to be shorter, less stressful and more independent from patient cooperation. Cumulative spectral power of total frequency band (LFHF cumpower) can be used for overall description of the degree of cardiac denervation in diabetes while using short-term PSA of HRV.

Weak relationship between symptom perception and objective hypoglycaemia-induced changes of autonomic function in hypoglycaemia unawareness in diabetes.

To assess the relationship between symptom perception and neurophysiological characteristics in hypoglycaemia unawareness, we investigated the awareness of symptoms, objective changes of autonomic function and counter-regulatory neuroendocrine responses to hypoglycaemia in intensively treated type I (insulin-dependent) diabetic patients with different degrees of hypoglycaemia unawareness. Hypoglycaemia (venous plasma glucose below 2.2 mmol/l) was induced with an intravenous insulin bolus in subjects with a history of repeated severe hypoglycaemia and hypoglycaemia unawareness (n = 10) and in a comparable group with good awareness of hypoglycaemia (n = 8). Autonomic symptoms, selected parameters of autonomic function and counter-regulatory hormones were assessed serially. Although hypoglycaemia was more pronounced in unaware patients (1.6 vs 2.0 mmol/l, P = 0.05), their induced adrenaline response was markedly impaired (delta adrenaline: 1.25+/-1.10 vs 2.55+/-1.46 nmol/l, P = 0.05). Astonishingly, differences between both patient groups in the course of autonomic function changes did not reach the level of significance (P = 0.35-0.92), although the unaware group reported markedly fewer autonomic symptoms, both neurogenic (P = 0.001) and neuroglycopenic (P = 0.04) than the aware group. This study indicates that in hypoglycaemia unawareness even extensive changes in autonomic function are not sufficient for the perception of hypoglycaemia and confirms that the central nervous system plays an important role in the awareness of hypoglycaemia.

[ISO 9001 conformity in research, teaching and rehabilitation]. / ISO 9001-Konformität in Forschung, Lehre und Rehabilitation.

Quality assurance, in particular in the areas of development and production of medical devices, is one of the tasks of biomedical engineering. The interdisciplinary working group "Functional Rehabilitation and Group Education, Vienna" is committed to the development and implementation of group education models on three levels: (1) direct education/instruction of patients with chronic diseases, (2) university research and teaching, and (3) development of technical aids for rehabilitation and the means for disseminating group education models in rehabilitation and therapy. Major aims were, by generating conformity with ISO 9001 standards, to achieve greater transparency and process optimization with very small resources in university (teaching, research, technical aids) and extra-university (rehabilitation) areas. A secondary aim was the establishment of interdisciplinary (clinical and biomedical) cooperation at university level. In all main areas (research, teaching and group education/instruction), ISO 9001-conformity was achieved by our activities on three methodological levels: (1) description and analysis of processes, (2) use of ISO 9001 standards for evaluating internal processes, and (3) optimization measures. The following article contains relevant elements of the quality manual and quality assurance system, and offers a typical example of innovative cooperation between medicine and medical engineering.

Effects of physical training on heart rate variability in diabetic patients with various degrees of cardiovascular autonomic neuropathy.

OBJECTIVE: To investigate the effects of regularly performed endurance training on heart rate variability in diabetic patients with different degrees of cardiovascular autonomic neuropathy (CAN). METHODS: Bicycle ergometer training (12 weeks, 2 x 30 min/week, with 65% of maximal performance) was performed by 22 insulin-requiring diabetic patients (age 49.5 +/- 8.7 years; diabetes duration 18.6 +/- 10.6 years; BMI 25.1 +/- 3.4 kg/m2): i.e., by 8 subjects with no CAN, 8 with early CAN and by 6 patients with definite/severe CAN. A standard battery of cardiovascular reflex tests was used for grading of CAN, a short-term spectral analysis of heart rate variability for follow-up monitoring of training-induced effects. RESULTS: While the training-free interval induced no changes in spectral indices, the 12-week training period increased the cumulative spectral power of the total frequency band (P = 0.04) but to a different extent (P = 0.039) in different degrees of neuropathy. In patients with no CAN the spectral power in the high-frequency (HF) band (0.15-0.50 Hz) increased from 6.2 +/- 0.3 to 6.6 +/- 0.4 In [ms2]; P = 0.016, and in the low-frequency (LF) band (0.06-0.13 Hz) from 7.1 +/- 0.1 to 7.6 +/- 0.3 in [ms2]; P = 0.08 which resulted in an increase of total spectral power (0.06-0.50 Hz) from 7.5 +/- 0.1 to 8.0 +/- 0.3 in [ms2] (P = 0.05). Patients with the early form of CAN showed an increase of spectral power in HF (5.1 +/- 0.2 to 5.8 +/- 0.1 in [ms2], P = 0.05) and LF bands (5.6 +/- 0.1 to 6.3 +/- 0.1 in [ms2], P = 0.008), resulting in an increase of total power from 6.1 +/- 0.1 to 6.6 +/- 0.1 in [ms2] (P = 0.04), whereas those with definite/severe CAN showed no changes after the training period. Training improved fitness in the whole patient cohort. The increased autonomic tone as assessed by spectral indices disappeared after a training withdrawal period of 6 weeks. CONCLUSIONS: In diabetic patients with no or early CAN, regularly performed endurance training increased heart rate variability due to improved sympathetic and parasympathetic supply, whereas in subjects with definite/severe CAN no effect on heart rate variability could be demonstrated after this kind of training.

[Modular education in diabetes and pregnancy: analysis of results of 58 pregnancies in diabetic patients with functional insulin treatment]. / Modulare Schulung bei Diabetes und Schwangerschaft: Ergebnis-Analyse in 58 Schwangerschaften von Diabetikerinnen unter funktioneller Insulinbehandlung.

Functional insulin treatment based on the patient's education for selective use of insulin for fasting, eating or correction of hyperglycaemia was used between 1985 and 1994 prospectively in 58 pregnancies (in 18 cases after conception) in 47 pregnant diabetic patients. We hypothesised that near-normalisation of glycaemia is possible throughout pregnancy by modular outpatient group education, individual counselling and functional insulin treatment. We wanted to investigate to which degree it might eliminate classical diabetes-associated neonatal complications. To avoid hospitalisation if possible and premature induction of labour, patients were taught both the primary adjustment (immediate correction of hyperglycaemia) and the secondary adjustment of the insulin dosages: correction of individual algorithms for insulin use according to daily insulin consumption and mean blood glucose MBG. A target metabolic control (HbA1c levels in the normal range, MBG < 100 and < 90 mg/dl after the 28th week of gestation respectively) was achieved in the majority of the 58 pregnancies. Severe hypoglycaemia occurred in 12 patients (21%). The gestational age at delivery was 39.0 +/- 1.6 (34-41; in 3 cases only [5%] < 37) weeks with an average birth weight of 3335 +/- 521 (1950-4450) g. The birth weight of only 5 newborn (9%) was above the 90th percentile and no one below the 10th percentile for weight of a comparable population. No cases of respiratory distress were observed. Hypoglycaemia was recorded in only 4 newborn (7%) and was comparable also to that of offsprings in non-diabetic women. Malformations were found in two offsprings whose mothers had presented first for diabetes education after conception, pregnancy being terminated in one case of meningomyelocele. Caesarean section (n = 15; 26%) was primarily due to maternal reasons. Functional insulin treatment prior to conception, modular diabetes group education, specific patient motivation for a near-normal glycaemia throughout pregnancy as well as interdisciplinary care allow pregnancy outcome in diabetic patients similar to that in non-diabetic women and thus the realisation of the 5-year targets of the WHO Declaration of St. Vincent 1989.

Secondary Hodgkin's disease in polymyositis and type 1 diabetes mellitus after a long-term immunosuppressive treatment.

Immunological disorders can play an important role in the etiopathogenesis of malignant lymphogranuloma. The authors demonstrate a patient with autoimmune polymorbidity (polymyositis and type 1 diabetes mellitus) which underwent a long-term immunosuppressive and cytostatic therapy. After 7 years of that treatment, Hodgkin's disease of mixed cellularity type developed. The clinical findings of the case are described and the clinical particularities along with possible mutual links among these diseases are stressed.

Radionuclide hepatic perfusion index and ultrasonography: assessment of portal hypertension in clinical practice.

The final value of portal blood flow pressure depends on the degree of vascular obstruction, then on the resistance in collateral vessels and, last, on splanchnic blood flow. The iniciating cause of portal hypertension most often lies in advancing anatomical damage leading to increased resistance and, consequently, to a reduction of portal blood flow, and simultaneous reciprocal development of extrahepatic collaterals. The determination of a true portal flow is a necessity particularly when deciding about a shunt surgery and its type, but it also supplies valuable information on the degree of portal flow restriction and, in this way, on the progress of pathophysiological changes, their extent and advance. The technique of radionuclide angiography and determination of the hepatic perfusion index (HPI) proposed by Sarper appears to be a profitable noninvasive method supplying well reproducible information on portal blood flow. Sarper proved it to be correlated with the degree of portal hypertension established by angiography. Ultrasonographic criteria of portal hypertension include dilatation of the portal vein in the region of the hilus hepatis exceeding 15 mm, and a more than 10 mm dilatation of the splenic vein above the spine. The mean HPI value obtained from the examination of 19 subjects without liver involvement was 0.6956 +/- 0.0583. The group of chronic hepatopathies included 19 patients with bioptically verified chronic hepatitis without reconstruction and/or steatosis, and 32 patients with liver cirrhosis likewise confirmed by biopsy: portosystemic shunts could be demonstrated in 14 of the latter. (ABSTRACT TRUNCATED AT 250 WORDS)