Diabetes care in rural area: clinical and metabolic evaluation.

To evaluate the efficacy of conventional diabetes care in a rural area, metabolic control and the presence of late complications were studied in 622 diabetic patients treated by general practitioners beyond the reach of diabetic centers. Seventy-three (12%) of the patients were classified as type I diabetics (age, 38.0 +/- 16.1 yr; duration of diabetes, 12.8 +/- 9.3 yr) and 549 as type II diabetics (age, 67.0 +/- 10.8 yr; duration of diabetes, 7.3 +/- 5.8 yr). Fifty-eight percent of type I diabetic patients administered insulin once daily and 42% twice daily, whereas most (83%) type II diabetics on insulin received only one insulin injection per day. Treatment of type II diabetic patients consisted of sulfonylureas (58%), diet alone (22%), insulin (18%), and biguanides or a combination of sulfonylurea with biguanides (2%). Poor therapeutic efficacy was observed in all patients, and postprandial hyperglycemia (blood glucose greater than 160 mg/dl) was predominant both in type I diabetics (86%) and in type II diabetics on insulin (80%) as well as off insulin (55%). HbA1c above normal (greater than 5.8%) was seen in 96% of type I and in 90 and 73% of type II diabetics with or without insulin therapy, respectively. Accompanying glucosuria was present in type I (73%) and in type II diabetics (on insulin, 71%; off insulin, 33%). Mean prevalence of late diabetic complications was greatest for insulin-treated patients (type I, type II with, and type II without insulin treatment: retinopathy, 41, 56, 22%; proteinuria, 13, 14, 3%; peripheral neuropathy, 21, 51, 12%), whereas macroangiopathy (16, 53, 31%) predominated in type II diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Severe hypoglycaemia unawareness is associated with an early decrease in vigilance during hypoglycaemia.

To elucidate neurophysiological characteristics in hypoglycaemia unawareness, we investigated the relationship between electroencephalography (EEG) parameters of vigilance and awareness of various symptom categories early in response to hypoglycaemia in intensively treated diabetic patients with different degrees of hypoglycaemia unawareness. Hypoglycaemia (venous plasma glucose below 2.2 mmol/1) was induced with an intravenous insulin bolus in seven patients with insulin-dependent diabetes mellitus (IDDM) with a history of hypoglycaemia unawareness and repeated severe hypoglycaemia, as well as in a group of seven IDDM patients with good awareness of hypoglycaemia. Both groups were comparable in age, treatment strategy, glycaemic control and level of late complications. Basic cognitive performance and other symptom categories were estimated serially during a period of 2 h following the insulin bolus. A vigilance-controlled EEG was recorded continuously; its automatic analysis included the evaluation of vigilance indices. In the baseline prehypoglycaemic state, hypoglycaemia unaware patients showed higher initial vigilance (p = .05) than the aware group. Unaware patients reported fewer neurogenic (p = .002, mainly cholinergic, p = .009) hypoglycaemia symptoms during hypoglycaemia, and developed an impairment in cognitive performance over time (p = .002). EEG analysis indicated a more rapid decrease in vigilance after the hypoglycaemic stimulus for unaware patients than for aware patients. The lowering of plasma glucose to 3.06-3.89 mmol/l already induced a significant increase in delta and theta, as well as a decrease in alpha relative power only in the unaware group. Differences between groups with regards to the degree of deceleration were most pronounced early, during only slight hypoglycaemia, and topographically spread over central and parietal brain regions. Further lowering of plasma glucose induced an even more pronounced, abrupt increase in slow waves in unaware patients at higher plasma glucose levels than in hypoglycaemia aware subjects (for delta waves at 2.41 +/- 0.16 vs. 1.96 +/- 0.1 mmol/l, p = .04). This preceded the worsening of cognitive performance during hypoglycaemia in unaware patients by 19 +/- 3 min. Hypoglycaemia unawareness associated with previous unconsciousness is associated with- and may be the result of-an early hypoglycaemia-induced reduction in vigilance and an early EEG deceleration, which seems to be a teleologically effective measure for delaying eventual cerebral energy failure in hypoglycaemia.

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.

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.

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.

Monitoring set-up for selection of parameters for detection of hypoglycaemia in diabetic patients.

Recurrent severe hypoglycaemia is often an unsolved problem in diabetic patients under intensified insulin treatment. As no reliable long-term stable blood glucose sensor has yet been developed, registration of other body function changes could help to detect severe hypoglycaemia. A measuring system is described, capable on the one hand of recording EEG, heart rate, peripheral pulse, skin temperature, respiratory movements, skin impedance and arterial blood pressure, and capable of registering plasma glucose, counter-regulatory hormones, symptoms and cognitive performance under experimental conditions during hypoglycaemia, on the other. In a clinical study involving both insulin-induced hypoglycaemia in healthy subjects and insulin-dependent diabetic patients, the practical value and the character of changes of the recorded parameters are investigated. Currently insensitivity to hypoglycaemia, impracticability, complexity or susceptibility to artefacts make use of most parameters unsuitable for hypoglycaemia prevention. It is believed, however, that future efforts could result in indirect registration of hypoglycaemia, including a qualified combination of different parameters, individual adaptation in accordance with particular responses of individual patients, together with new measuring and sensor techniques.

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.

[Conventional or functional insulin therapy?]. / Konventionelle oder funktionelle Insulintherapie?

The main difference between "conventional" and "functional" insulin replacement is that the former requires meals to be taken at set times throughout the day to avoid hypoglycaemic insulin reactions, while the latter separates insulin replacement in the basal ("fasting") state from that required with food intake. Such strategy reverses conventional insulin treatment (namely balancing the action of administered insulin by a fixed dietary intake), by substitution with a functional control of hyperglycaemia on the basis of tailored insulin doses. To this end blood glucose self control and systemic blood glucose correction are a must during functional insulin substitution, but not necessarily so during conventional insulin therapy. From this it is apparent that "conventional" and "functional" insulin therapy refer to different strategies, both of which may be intensified by more strict rules, although the term "intensified" remains without any conceptional meaning per se. However, whatever the therapeutic recommendation, the attending physician has to be aware that he must appropriately inform and train the insulin-deficient patient (a) on how to deal with a proposed treatment schedule, and (b) to the point that he fully understands the available therapeutic possibilities and the difference in their quality. Experience has shown that a majority of informed patients opt for functional therapy.

[Type I diabetes mellitus and pregnancy: an interdisciplinary management program]. / Diabetes mellitus Typ I und Schwangerschaft: Ein interdisziplinäres Betreuungsprogramm.

The obstetrical management of pregnant women with pregestational diabetes has been significantly improved throughout recent years. In the past, efforts to maintain euglycaemia during pregnancy in the presence of a labile maternal metabolism led to repeated, long-term hospitalization. In an interdisciplinary joint effort a protocol was delineated to obtain euglycemia throughout pregnancy by functional insulin therapy aiming at "near-normoglycemic insulin substitution (NIS)". In order to achieve this goal, home glucose monitoring and, depending on the glucose levels, self-made adjustments to the insulin therapy (according to individual algorithm) are the essential parts of this protocol. Of our study group of 18 pregnant diabetic women, already eight of them (2 class B, 1 class C, 1 class D, 2 class R and 2 class RF) have been delivered. The mean maternal age was 27 years (21-39). All metabolic variables of consequence for a diabetic woman were within the normal limits. The mothers' mean weight gain was 16 kg (12-20), and the mean gestational age at delivery was 37.8 weeks (35-40). The mean birth weight was 3293 grams (2700-3700) and all newborns were within the 50th percentile. Five fetuses were delivered by caesarian section (indications: proliferative retinopathy 3, breech presentation 1, previous caesarian section 1). No congenital malformations were found, nor macrosomia, respiratory distress syndrome or postpartum hyperglycaemia in the newborn. These preliminary results are encouraging. We feel that functional insulin therapy aiming at "near-normoglycaemic insulin substitution" promises to be very effective for women who are able and willing to follow the instructions received in the special education program.

Phases of functional, near-normoglycaemic insulin substitution: what are computers good for in the rehabilitation process in type I (insulin-dependent) diabetes mellitus?

We have divided the rehabilitation process in patients with insulin-dependent diabetes mellitus into the following four phases. The basic phase, the so-called 'phase 0', provides information about literature, different strategies of treatment and introduces the use of regular insulin as well as blood sugar self-monitoring. During 'phase 1' (i.e. 'diabetes education common sense') all the initial information from 'phase 0' will be used practically and discussed in depth. After the patient's actual insulin need (U/24 h) has been estimated, initial algorithms for functional insulin use can be defined. And this is the turning point to 'phase 2' of the group rehabilitation process, the so-called education in functional insulin use. Initial algorithms should be understood as a preliminary answer to the patient's questions, 'What is my basal insulin need?', 'How much insulin do I need for a particular amount of carbohydrates?', and 'What is the hypothetical response of my blood glucose to a particular amount of insulin?'. These algorithms are going to be used and optimised now by the patient (under the supervision of the physician) during the so-called 'insulin games' (fasting or 24 h, experimental violation of traditional dietary rules, etc.) to demonstrate (1) how to influence actual glycaemia through immediate correction of blood sugar off blood sugar target (primary adjustment of insulin dosing), and (2) how to optimise algorithms for insulin use (secondary insulin adjustment) in future conditions of different insulin sensitivity. The 'phase 3' of individual teaching is an ongoing process of updating the patient's knowledge and practical skills.(ABSTRACT TRUNCATED AT 250 WORDS)

[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.

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.

EEG topography during insulin-induced hypoglycemia in patients with insulin-dependent diabetes mellitus.

A group of young patients with insulin-dependent diabetes mellitus (n = 14; 8 men, 6 women; 33.1 +/- 8.9 years) were examined by topographic EEG mapping under normoglycemic and hypoglycemic conditions (glucose levels after intravenous insulin injection down to 32.6 +/- 7.6 mg/dl). From the clinical aspect, 7 of them had a good and 7 had a poor awareness of hypoglycemia. During hypoglycemia, a decrease in alpha activity (p < 0.05), an increase in delta (p < 0.05), and especially in theta activity (p < 0.05) were found. The most sensitive parameter was the alpha/theta ratio. In the range of slight hypoglycemia (50-60 mg/dl) the increase in delta and theta activity showed a topographic maximum in lateral frontal regions. During deep hypoglycemia there was a topographic maximum of slow frequencies in posterior parts of the brain (centrotemporal to parieto-occipital regions). The differences between the group with good and with poor awareness of hypoglycemia were most pronounced during slight hypoglycemia in C3, C4, and Pz (p < 0.05). At lower glucose levels group distinction was no longer possible. These EEG changes correspond to a temporary organic brain syndrome.

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.