Enabling guidelines for computer-based decision support--process and tools.

Many guideline only implicitly or vaguely define the process of health care delivery. However, an explicit model of the medical tasks comprising this process is needed before active decision support at the patient encounter can take place. We propose to use a structured, but semi-formal representation as intermediate step in the process of enacting a guideline. This allows for the application independent representation of the content of a guideline enabled for decision support. The process and the tools of the methodology have been applied to enable guidelines from the field of Diabetes mellitus.

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

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

Classical conditioning of insulin effects in healthy humans.

OBJECTIVE: Classical conditioning of insulin effects was examined in healthy humans using a placebo-controlled design. This study examined whether subjects who experienced a conditioned stimulus (CS) paired with insulin in the acquisition phase of a conditioning protocol would show a conditioned decrease of blood glucose when receiving the CS with a placebo injection in the test phase. METHODS: Twenty healthy male students were assigned either to group 1, which received insulin (0.035 IU/kg i.v.), or to group 2, which received i.v. saline on 4 consecutive days (acquisition). On day 5 (test), both groups were injected with saline. The CS was an olfactory stimulus. Blood glucose, serum insulin, plasma glucagon, plasma catecholamines, serum cortisol, and symptoms were repeatedly measured during each session. RESULTS: In the test phase, group 1 reacted with a significantly larger decrease of blood glucose after presentation of the CS than group 2. Within group 1, a larger conditioned blood glucose decrease was associated with features that enhance classical conditioning (ie, intensity of the unconditioned response and intensity of the CS). Furthermore, in group 1, there was an increase of baseline insulin from day 1 to day 5 and a tendency for insulin reduction after CS presentation. Groups also tended to differ in cortisol and neuroglycopenic symptoms after CS presentation. CONCLUSIONS: Conditioned effects in blood glucose are in accordance with the predictions. As a result of the exploratory analyses, our data also provide hints about conditioned changes in insulin, counterregulatory hormones, and symptoms.

Guidelines for the diagnosis and outpatient management of diabetic peripheral neuropathy.

Guidelines on the out-patient management of diabetic peripheral neuropathy have been developed from an international consensus meeting attended by diabetologists, neurologists, primary care physicians, podiatrists and diabetes specialist nurses. A copy of the full document follows this summary (Appendix 1). The document arose out of suggestions from Neurodiab, a subgroup of the European Association for the Study of Diabetes, that there was a need for guidelines developed by consensus, for the outpatient management of patients with diabetic neuropathy. An international consensus group was created, chaired by two of the authors. A pilot working party met in 1995, followed by a full working party of 39 experts, neurologists and diabetes physicians (Appendix 2). This compiled a draft guideline document which was circulated to a number of international bodies. After consultation with its members, the final guidelines were approved by Neurodiab (chairman F.A. Gries) towards the end of 1997.

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

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

Prescription drug use and costs among diabetic patients in primary health care practices in Germany.

OBJECTIVE: To evaluate drug prescriptions and costs among diabetic patients in primary care practices in Germany. RESEARCH DESIGN AND METHODS: Computerized data on prescriptions and costs (drug company sales prices) were analyzed in 30,604 diabetic and 17,723 (5% random sample) nondiabetic patients from 362 primary care practices during 1994. Relative use ratios for drug groups were obtained from logistic regression models (odds ratio [OR] for diabetes) controlling for age, sex, and other covariates. Relative costs (diabetic:nondiabetic) were estimated by direct age and sex standardization. RESULTS: Diabetic patients had an increased prescription use for most drugs. A substantial increased use (OR > or = 1.4) was found for cardiovascular drugs, fibrates, gout medication, laxatives, and wound care products. Diabetic subjects (7.9% of all patients) accounted for 21% of total annual prescription costs in the practices. Total costs (U.S. dollars) per patient-year were threefold higher (diabetic patients $384; control subjects $123). After excluding antidiabetic agents and age- and sex-standardization, relative costs were still 1.5 times higher (P < 0.05). Diabetes treatment accounted for 24% of total costs in diabetic patients (insulin 12%; oral antidiabetics 6%). The most important cost factor was cardiovascular drugs (CVDs) (39%). Three CVD groups accounted for about 50% of total CVD costs in diabetic patients (ACE inhibitors 25%; Ca-antagonists 16%; nitrates 10%). CONCLUSIONS: Prescription use among diabetic patients in primary health care practices was predominantly increased for cardiovascular drugs and for treatment of diabetes-associated disorders. Diabetic patients accounted for over one-fifth of the total pharmacy costs in primary practices, indicating that diabetes is a major economic factor in drug use.

Long-term effects of a sustained-release preparation of acipimox on dyslipidemia and glucose metabolism in non-insulin-dependent diabetes mellitus.

Elevated circulating plasma nonesterified fatty acids (NEFA) may contribute to the insulin resistance and hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM), and decreasing plasma NEFA could provide a therapeutic benefit. A sustained-release preparation of acipimox, a lipolysis inhibitor, was used in an attempt to decrease circulating plasma NEFA levels long-term, and the effects on glycemic control, insulin resistance, and serum lipids were measured. Sixty NIDDM patients (43 males and 17 females) took part in a randomized controlled trial of acipimox or placebo for 12 weeks. Fasting plasma NEFA levels did not change in acipimox-treated patients (baseline v 12 weeks, 0.84 +/- 0.35 v 0.88 +/- 0.55 mmol x L(-1), mean +/- SD). Fasting blood glucose was unchanged (mean difference v placebo, -0.5 mmol x L(-1); 95% confidence interval [CI], -1.4 to 0.3 mmol x L[-1]), but serum fructosamine decreased (mean difference v placebo, -26 micromol x L(-1); 95% CI, -51 to 0 mmol x L[-1]), as did the standardized hemoglobin A1 ([HbA1] mean difference v placebo, -1.4%; 95% CI, -3.0% to -0.1%). Insulin resistance measured as steady-state plasma glucose during an insulin-dextrose infusion test was unchanged (mean difference v placebo, -1.4 mmol x L(-1); 95% CI, -3.2 to 0.5 mmol x L[-1]). Serum total cholesterol (mean difference v placebo, -0.4 mmol x L(-1); 95% CI, -0.6 to -0.1 mmol x L[-1]), serum apolipoprotein B ([apo B] mean difference v placebo, -0.19 g x L(-1); 95% CI, -0.3 to -0.1 g x L[-1]), and serum triglycerides (mean difference v placebo for pretreatment v posttreatment ratio, 0.59; 95% CI, 0.40 to 0.88) were all lower with acipimox. Serum high-density lipoprotein (HDL) cholesterol (mean difference v placebo, 0.10 mmol x L(-1); 95% CI, -0.05 to 0.3 mmol x L[-1]), serum apo A1 (mean difference v placebo, 0.03 g x L(-1); 95% CI, -0.04 to 0.1 g x L[-1]), and serum lipoprotein(a) ([Lp(a)] acipimox v placebo, 154 (0 to 1,574) v 71 (0 to 1,009), median and range) were unchanged. Despite the lack of change in fasting plasma NEFA levels, acipimox caused a modest beneficial improvement in overall glycemic control and plasma lipids in NIDDM patients and could be a useful agent in the treatment of dyslipidemic NIDDM patients.

Postmarketing surveillance of adverse drug reactions: a correlational study approach using multiple data sources.

The authors performed a correlational study on nationwide spontaneous adverse drug reaction (ADR) reports related to the antioxidant thioctic acid (Thioctacid; ASTA Medica) in Germany from April 1992 to March 1995. Thioctacid was predominantly utilized by general practitioners and internists for treatment of diabetic neuropathy. The total number of treated patients was estimated using a nationwide drug prescription database (MediPlus, IMS: 362 general practitioners and internists) and pharmacy drug sales data. All Thioctacid prescriptions in MediPlus were assessed and the mean cumulative dosage/patient/year was calculated. Then, the total number of Thioctacid patients in Germany was estimated: N=nationwide pharmacy sales (kg)/mean cumulative dosage/patient (kg). From April 1992 to March 1995, 78 patients with 112 ADRs were notified on spontaneous reports. There was a decreasing number of ADR reports per year (32 to 21 patients/year). In parallel, the estimated total numbers of treated patients/year also decreased from 426,658 to 304,155 (p<0.05). Poisson regression models were fitted including incident cases with ADR and the number of patients per year for each of the 3 years. No significant secular trend of ADR (p=0.91) and no impact of mean cumulative dosages was observed in the models. There were also no changes in the pattern of ADR (e.g. skin reactions, gastrointestinal complaints). This study suggests that a combination of spontaneous reporting systems with prescription drug databases and pharmacy sales data may be a useful tool to perform rapid postmarketing monitoring of ADR.

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

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

Effects of the carnitine-acyltransferase inhibitor etomoxir on insulin sensitivity, energy expenditure and substrate oxidation in NIDDM.

We studied the influence of Etomoxir on fat and carbohydrate oxidation, and the influence of these changes on insulin sensitivity in type 2 diabetic patients. Etomoxir is an oxirane carboxylic acid derivative that specifically inactivates carnitine-acyltransferase I (CAT I, EC: 2.3.1.21), the key enzyme for the transport of long-chain acyl-CoA compounds into the mitochondria. Thus, oxidation of fatty acids should be reduced by this drug and glucose utilisation be increased according to the Randle mechanism. In order to test this hypothesis, we measured oxidative and non-oxidative glucose utilisation using the euglycaemic hyperinsulinaemic clamp technique, the isotope dilution mass spectrometry (IDMS) method with stable isotopes (6,6-D2-glucose) and indirect calorimetry. The clamps lasted 5 hours, indirect calorimetry was performed during the last hour and calculations of glucose disposal were based on steady state conditions during the last 30 minutes. Twelve type 2 diabetic patients were treated with 100 mg etomoxir/per day for 3 days in this placebo-controlled, randomized, double-blind study. Treatment resulted in a significant increase in carbohydrate oxidation (from 72 to 113 g/24 h, p = 0.039), decrease in fat oxidation (from 139 to 114 g/24 h, p = 0.037), and decrease of the glucose appearance rate (RA) in the basal state (from 1.85 to 1.70 mg/kg min., p = 0.014). During the euglycaemic clamp neither RA (3.30 and 3.20 mg/kg min., p = 0.471) nor the glucose infusion rate (4.28 and 4.53 mg/kg min., p = 0.125) showed significant changes. In addition, no significant changes in glucose and fat oxidation were detected during the hyperinsulinaemic clamp. Under basal conditions non-oxidative glucose utilisation was decreased by etomoxir (1.26 and 0.80 mg/ kg x min). Thus, we could demonstrate a decrease in fat and increase in glucose oxidation by etomoxir, but non-oxidative glucose utilisation was decreased. No significant changes could be demonstrated under clamp conditions.

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

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

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

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

Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease.

Disturbed immune regulation has been postulated to be crucial in the pathogenesis of IDDM and other autoimmune or allergic diseases. We therefore tested the hypothesis of a general bias in the peripheral immune system in patients with recent-onset IDDM or Graves' disease in comparison to healthy control subjects by studying whole blood cultures stimulated with phytohemagglutinin. Cells from IDDM patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma-interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels (interleukin [IL]-4, IL-10) were similar. Low levels of islet cell antibodies (ICAs) in IDDM patients were associated with high levels of Th1 and Th2 cytokines. Antibodies to GAD, ICA512, or insulin did not correlate with individual cytokine profiles. Also, HLA-DQ types did not significantly correlate with either Th1 or Th2 cytokine production. Conversely, whole blood cultures from patients with Graves' disease (n = 18) produced significantly less TNF-alpha and IL-4 than normal subjects (P = 0.001-0.006). However, when the balance between Th1 and Th2 cytokine production was analyzed in individuals, the ratio between IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production was seen in Graves' disease (P = 0.0001). The ratio of counterregulatory cytokines appeared to be the most reliable marker of the individual disease process. This study provides first evidence of a systemic bias in the immune regulation of humans, which might be either toward cell-mediated immunity (Th1) in IDDM or humoral immunity (Th2) in Graves' disease.

Repeatability of three-day dietary records in the EURODIAB IDDM Complications Study.

OBJECTIVES: Repeatability of a dietary method is important in determining the quality of nutritional data. It should be assessed in the population of interest. This study evaluated the repeatability of nutritional data from standardized three-day dietary records, from the clinic-based, cross-sectional multi-centre EURODIAB IDDM Complications Study. DESIGN AND SUBJECTS: 15% of the total EURODIAB cohort was randomly selected to test the repeatability of nutritional intake data. Two three-day records, completed three weeks apart, were available for 216 diabetic patients (7.5%) representative of the total cohort. All records were analysed centrally, for intakes of protein (animal and vegetable), fat (saturated fat and cholesterol), carbohydrate, fibre, alcohol and energy. Repeatability was measured comparing mean intakes, determining the proportion of patients classified into the same/opposite quartile by the two three-day records and assessing mean differences with standard deviations (s.d.d). RESULTS: There were no significant differences in mean energy and nutrient intakes between the first and second records. Classification of individuals into the opposite quartile occurred only in 0-4% of patients and overall about 50% (range 44-74%) of the subjects were classified into the same quartiles of intakes. Only small mean differences were found for energy intake (-156 (1633) kJ; 95% confidence limits -375, 63 kJ) and nutrients with s.d.ds comparable to intra-individual variations in the general population. The differences in energy intake were randomly distributed over the range of intakes. CONCLUSIONS: The present study demonstrates that standardized three day dietary records show a high degree of repeatability within a short period of time in a sample of European IDDM patients. The good repeatability strengthens the conclusions drawn from the nutritional data in the EURODIAB IDDM Complications Study.

Protein intake and urinary albumin excretion rates in the EURODIAB IDDM Complications Study.

For people with insulin-dependent diabetes mellitus (IDDM) renal disease represents a life-threatening and costly complication. The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to determine the prevalence of renal complications and putative risk factors in stratified samples of European individuals with IDDM. The present study examined the relationship between dietary protein intake and urinary albumin excretion rate (AER). Food intake was assessed centrally by a standardized 3-day dietary record. Urinary AER was determined in a central laboratory from a timed 24-h urine collection. Complete data were available from 2696 persons with IDDM from 30 centres in 16 European countries. In individuals who reported protein consumption less than 20% of total food energy intake, mean AER was below 20 microg/min. In those in whom protein intake constituted more than 20%, mean AER increased, a trend particularly pronounced in individuals with hypertension and/or poor metabolic control. Trends reached statistical significance for intakes of total protein (% of energy, p = 0.01) and animal protein (% of energy, p = 0.02), while no association was seen for vegetable protein (p = 0.83). These findings support the current recommendation for people with diabetes not to exceed a protein intake of 20% of total energy. Monitoring and adjustment of dietary protein appears particularly desirable for individuals with AER exceeding 20 microg/min (approximately 30 mg/24h), especially when arterial pressure is raised and/or diabetic control is poor.

Nutritional intake of 2868 IDDM patients from 30 centres in Europe. EURODIAB IDDM Complications Study Group.

The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to measure the prevalence of diabetic complications in stratified samples of European insulin-dependent diabetic (IDDM) patients. As diet may be related to diabetic complications, nutritional intake was analysed in the study population. The aims of this first nutritional paper are to describe the nutrient intake in 2868 IDDM patients from 30 centres in 16 countries throughout Europe, to investigate the degree of regional differences in nutrient intake and to compare current intakes with recommended levels. Nutritional intake from 1458 male and 1410 female IDDM patients was assessed by a validated 3-day record (two weekdays, Sunday) and centrally analysed. Mean energy intake for all patients was 2390 +/- 707 kcal/day. Mean protein intake was 1.5 +/- 0.5 g/kg body weight. Carbohydrate intake was 43% and fibre intake 18 g/day. Alcohol intake for the total cohort was 2% of energy. Total fat contributed 38% of energy, with 14% from saturated fat. The Italian centres reported lower total and saturated fat intakes compared with other centres. Recommendations from the Diabetes and Nutrition Study Group of the EASD for total fat, saturated fatty acids and carbohydrate were only achieved by 14%, 14% and 15% of patients, respectively. The data of the present study clearly indicate current problems in the nutritional intake of European IDDM patients. These findings contribute to the definition of future targets in the nutritional management of IDDM patients, to be achieved as part of the initiatives taken by the St. Vincent Declaration action programme.

PTCA: periprocedural platelet activation. Part II of the Duesseldorf PTCA platelet study (DPPS)

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) with its various manipulations could create a dangerous, sudden haemostatic response. This study was performed to investigate PTCA-induced periprocedural changes in platelet activation and its consequences. METHODS: Twenty-five consecutive patients admitted for elective PTCA were preclassified as having or not having circulating activated platelets. Blood samples were taken for platelet activation marker analysis before, six times during and 2 h after PTCA. Intravascular platelet activation was analysed by flow cytometry to measure activation-dependent surface markers thrombospondin, P-selectin (CD62) and lysosomal GP53 (CD63). RESULTS: PTCA was associated with a significant reduction of peripheral platelet count. The initiation of the PTCA procedure led to a significant loss of more than 50% of the degranulated, activated platelets. After PTCA, the number of degranulated, activated platelets uniformly increased. CONCLUSIONS: We conclude that PTCA can induce consumption, particularly of preactivated platelets, and lead to sustained platelet activation after the procedure. This might explain why preactivated patients are at increased risk of suffering periprocedural ischaemic events and why increased thrombogenicity favours acute flow disruption and the progression of coronary stenosis at the lesion site.

[13C]octanoic acid breath test for non-invasive assessment of gastric emptying in diabetic patients: validation and relationship to gastric symptoms and cardiovascular autonomic function.

Since there is a need for a widely applicable non-invasive test to assess gastric emptying in diabetic patients, we evaluated the sensitivity, specificity, and reproducibility of the [13C]octanoic acid breath test as compared with scintigraphy. Moreover, we examined the relationship between the breath test indices and gastric symptoms, cardiovascular autonomic function, and metabolic parameters. Forty healthy control subjects and 34 diabetic patients were studied. Three indices of gastric emptying, assessed by the breath test, were computed: half-emptying time (t1/2breath), gastric emptying coefficient (GEC), and lag phase. Furthermore, the half-emptying time, measured by scintigraphy (t1/2scint), was calculated and gastric symptoms and cardiovascular autonomic neuropathy (CAN) were scored. The coefficients of variation of day-to-day reproducibility in 10 healthy subjects were 29.6% for t1/2breath, 7.4% for GEC, and 46.5% for lag phase. An abnormal delay for t1/2scint (> 100 min) or t1/2breath (> 200 min) was noted in 12 patients. Based on the results for t1/2scint, the sensitivity of t1/2breath and GEC was 75% and the specificity was 86%. Both t1/2breath (rs = 0.523; p < 0.05) and GEC (r2 = -0.594; p < 0.05) were significantly associated with the gastric symptom score. A significant relationship to the CAN score was demonstrated for t1/2breath (rs = 0.448; p < 0.05), GEC (rs = -0.467; p < 0.05), and t1/2scint (rs = 0.602; p < 0.05). There were no significant associations of the breath test indices with the blood glucose levels during the test, HbA1c, age, and duration of diabetes. In patients with abnormal t1/2scint (n = 12) not only was t1/2breath significantly prolonged and GEC reduced, but also the scores of CAN and gastric symptoms were significantly increased as compared with those who had a normal t1/2scint (n = 22). We conclude that the [13C]octanoic acid breath test represents a suitable measure of delayed gastric emptying in diabetic patients which is associated with the severity of gastric symptoms and CAN but not affected by the blood glucose level.