Bioavailability of insulin detemir and human insulin at the level of peripheral interstitial fluid in humans, assessed by open-flow microperfusion.

AIMS: To find an explanation for the lower potency of insulin detemir observed in humans compared with unmodified human insulin by investigating insulin detemir and human insulin concentrations directly at the level of peripheral insulin-sensitive tissues in humans in vivo. METHODS: Euglycaemic-hyperinsulinaemic clamp experiments were performed in healthy volunteers. Human insulin was administered i.v. at 6 pmol/kg/min and insulin detemir at 60 pmol/kg/min, achieving a comparable steady-state pharmacodynamic action. In addition, insulin detemir was doubled to 120 pmol/kg/min. Minimally invasive open-flow microperfusion (OFM) sampling methodology was combined with inulin calibration to quantify human insulin and insulin detemir in the interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissue. RESULTS: The human insulin concentration in the ISF was ∼115 pmol/l or ∼30% of the serum concentration, whereas the insulin detemir concentration in the ISF was ∼680 pmol/l or ∼2% of the serum concentration. The molar insulin detemir interstitial concentration was five to six times higher than the human insulin interstitial concentration and metabolic clearance of insulin detemir from serum was substantially reduced compared with human insulin. CONCLUSIONS: OFM proved useful for target tissue measurements of human insulin and the analogue insulin detemir. Our tissue data confirm a highly effective retention of insulin detemir in the vascular compartment. The higher insulin detemir relative to human insulin tissue concentrations at comparable pharmacodynamics, however, indicate that the lower potency of insulin detemir in humans is attributable to a reduced effect in peripheral insulin-sensitive tissues and is consistent with the reduced in vitro receptor affinity.

Dose-response relation of liquid aerosol inhaled insulin in type I diabetic patients.

AIMS/HYPOTHESIS: The AERx insulin Diabetes Management system (AERx iDMS) is a liquid aerosol device that enables insulin to be administered to the peripheral parts of the lung. This study aimed to compare the pharmacokinetic and pharmacodynamic properties of insulin which is inhaled using AERx iDMS with insulin which is subcutaneously administered. METHODS: In total, 18 C-peptide negative patients with Type I (insulin-dependent) diabetes mellitus participated in this randomised, open-label, 5-period crossover trial. Human regular insulin was administered subcutaneously (0.12 U/kg body weight) or inhaled by means of the AERx iDMS (dosages 0.3, 0.6, 1.2, and 1.8 U/kg body weight). Thereafter plasma glucose was kept constant at 7.2 mmol/l for a 10-h period (glucose clamp technique). RESULTS: Inhaled insulin provided a dose-response relation that was close to linear for both pharmacokinetic (AUC-Ins(0-10 h); Cmax-Ins) and pharmacodynamic (AUC-GIR(0-10 h); GIRmax) parameters. Time to maximum insulin concentration (Tmax-Ins) and time to maximum glucose infusion rate (TGIRmax) were shorter with inhaled insulin than with subcutaneous administration. The pharmacodynamic system efficiency of inhaled insulin (AUC-GIR(0-6 h) was 12.7% (95% C.I.: 10.2-15.6). CONCLUSION/INTERPRETATION: The inhalation of soluble human insulin using the AERx iDMS is feasible and provides a clear dose response. Further long-term studies are required to investigate safety aspects, HbA1c values, incidence of hypoglycaemic events and the quality of life.

Post-prandial administration of the insulin analogue insulin aspart in patients with Type 1 diabetes mellitus.

AIMS: In intensified insulin therapy, the recent development of short-acting insulin analogues with a very rapid onset of action forces a new discussion in terms of the optimal injection-meal interval. This study evaluated prandial glycaemia in patients with Type 1 diabetes following the subcutaneous injection of soluble human insulin (HI) and the insulin analogue insulin aspart (IAsp) at different injection-meal intervals and investigated whether administration of IAsp after the meal might provide satisfactory metabolic control. METHODS: In a randomized, double-blind, double-dummy, four-period crossover study, 20 Type 1 diabetic patients were investigated. Prandial insulin was administered 15 min before the start of the meal (HI(-15min)), immediately before the meal (HI(0min); IAsp(0min)) and 15 min after the start of the meal (IAsp(+15min)). RESULTS: Plasma glucose excursions from baseline levels during the 4 h (PGexc) were highest with HI(0min) (17.9 mmol.l(-1).h; P < 0.05 vs. other treatments) and were not statistically different for HI(-15min), IAsp(0min) and IAsp(15min) (13.6, 11.9 and 14.2 mmol.l(-1).h, respectively). Maximum concentration of plasma glucose (PGmax) was lowest with IAsp(0min) (11.2 mmol/l; P < 0.05 vs. other treatments). PGmax was comparable with HI(-15min), HI(0min) and IAsp(+15min) (13.3, 14.1 and 13.2 mmol/l, respectively). CONCLUSIONS: With regard to prandial glycaemia IAsp(+15min) is as effective as HI(-5min) and superior to HI(0min). Thus, post-prandial dosing of the insulin analogue IAsp offers an attractive and feasible therapeutic option for well-controlled patients with Type 1 diabetes mellitus.

Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans.

NN304 is a long-acting insulin analogue that is acylated with a 14-C-fatty acid chain. Protraction of action of this novel insulin analogue is due not to slow absorption after subcutaneous administration but to reversible binding to albumin. We investigated the pharmacokinetic and pharmacodynamic properties of insulin analogue NN304 (0.3 and 0.6 U/kg) in comparison to NPH insulin (0.3 and 0.6 IU/kg) in 10 healthy volunteers performing a randomised, double-blind, cross-over, placebo-controlled glucose clamp study. During the observation period of 24 hours the areas under the insulin curve for NPH[0.3 IU/kg] vs. NPH[0.6 IU/kg] were 60 vs. 102 nmol min l(-1) (p<0.01) and for insulin analogue NN304[0.3 U/kg] vs. NN304[0.6 U/kg] 490 vs. 932 nmol min l(-1) (p <0.001), suggesting a clear dose-response relationship for both NPH insulin and NN304. The amount of disposed glucose (area under the curve of glucose infusion) differed with statistical significance between the five treatments and was highest with NPH[0.6 IU/kg] (2671 mg/kg) and lowest with placebo (265 mg/kg). However, area under the curve of glucose infusion after treatment with NN304 was only 36% (dose of 0.3 U/kg) and 24% (dose of 0.6 U/kg) of that observed with corresponding doses of NPH insulin. Moreover, increasing dosages of NN304 failed to demonstrate a significant dose-response with regard to the area under the curve of glucose infusion. This study demonstrates that the principle of protracted insulin action of NN304 by reversible binding to albumin is effective in humans albeit at a much lower rate of glucose utilisation when compared to NPH insulin. Thus, in contrast to animal studies NN304 and NPH insulin can not be considered equipotent in humans.

Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion.

The absolute concentration of albumin was measured in the interstitial fluid of subcutaneous adipose tissue and skeletal muscle in six healthy volunteers by combining the method of open-flow microperfusion and the no-net-flux calibration technique. By use of open-flow microperfusion, four macroscopically perforated double lumen catheters were inserted into the tissue regions of interest and constantly perfused. Across the macroscopic perforations of the catheters interstitial fluid was partially recovered in the perfusion fluid. Catheters were perfused with five solutions, each containing different concentrations of albumin. Absolute interstitial albumin concentrations were calculated by applying linear regression analysis to perfusate vs. sampled albumin concentration (no-net-flux calibration technique). Interstitial albumin concentrations were significantly lower (P < 0.0001) in adipose tissue (7.36 g/l; r = 0.99, P < 0.0003; range: 4.3-10.7 g/l) and in skeletal muscle (13.25 g/l; r = 0.99, P < 0.0012; range: 9.7 to 15.7 g/l) compared with the serum concentration (48.9 +/- 0.7 g/l, mean +/- SE, n = 6; range: 46.4-50.4 g/l). Furthermore, interstitial albumin concentrations were significantly higher in skeletal muscle compared with adipose tissue (P < 0.01). The study indicates that open-flow microperfusion allows stable sampling of macromolecules from the interstitial space of peripheral tissue compartments. Moreover, the present data report for the first time in healthy humans in vivo the true albumin concentrations of interstitial fluid of adipose tissue and skeletal muscle.

Relation of serial measurements of plasma-soluble intercellular adhesion molecule-1 to severity of acute pancreatitis.

OBJECTIVE: Acute pancreatitis remains a clinical challenge because it is difficult to predict whether, in a given patient, the disease will be mild or will run a severe course with a possibly fatal outcome. The aim of this study was to investigate whether circulating soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of leukocyte activation is related to the severity of the disease. METHODS: The study included 29 consecutive adults admitted with acute pancreatitis. Plasma sICAM-1 levels were measured serially over a period of 6 days, and values and time courses were correlated with clinical severity. RESULTS: Our patients fell into four groups on the basis of the following measurements: 1) Decreasing sICAM- levels with maximal values of 446 +/- 90 ng/ml (mean +/- SEM) slightly above the upper limit of normal were associated with uncomplicated mild disease in seven patients. 2) In nine patients with sICAM-1 concentrations reaching a peak of 743 +/- 121 ng/ml after 3 days, severe pancreatitis was present in 11% and pancreatic necrosis occurred in 33%. 3) A second increase of sICAM-1 (maximal level: 993 +/- 169 ng/ml) after an initial decrease (relapsing pattern, 7 patients) was associated with a severe course of disease in 71% including pancreatic necrosis in 43% and nosocomial pneumonia in 42%. 4) A rapid increase of sICAM-1 reaching highest maximal values of 1738 +/- 104 ng/ml (p < 0.0001) indicated fulminant pancreatic necrosis and a fatal outcome in six patients. CONCLUSIONS: Serial plasma sICAM-1 levels in patients with acute pancreatitis within the first 6 days after admission fall into four different groups of severity according to the shape of the curves. This suggests that the time course of elevated plasma sICAM-1 concentrations reflects the risk of developing necrosis and clinical complications in acute pancreatitis.

Plasma and interstitial glucose dynamics after intravenous glucose injection: evaluation of the single-compartment glucose distribution assumption in the minimal models.

Recent experimental evidence suggests that estimates of glucose effectiveness (S(G)) from the minimal model of unlabeled glucose disappearance (Cold-MM) are in error. The single-compartment glucose distribution assumption embedded in the model has been indicated as a possible source of error. In this study, to directly examine the single-compartment assumption, we measured plasma and interstitial glucose concentrations after intravenous glucose injection. Additionally, we compared the accuracy of the estimates of glucose effectiveness from the Cold-MM and the single-compartment tracer minimal model (Hot-MM). Paired labeled intravenous glucose tolerance tests (IVGTTs) were performed in each of six C-peptide-negative type 1 diabetic subjects. Two different insulin infusion protocols were used: an infusion at constant basal rates and an infusion at variable rates to mimic a normal insulin response. During the labeled IVGTT with basal insulin infusion, the microperfusion technique was employed to sample adipose tissue interstitial fluid. Marked differences between the plasma and interstitial dynamics of (cold) glucose were observed during the first 22 min after glucose injection. These results suggest that the requirements for a single-compartment representation of glucose kinetics are not satisfied during at least the first 22 min of an IVGTT. Data from the labeled IVGTT with normal insulin response were used to identify the minimal-model parameters. The measure of S(G) derived using the Cold-MM was 3.44-fold higher than the direct measure obtained from the labeled IVGTT with basal insulin infusion (0.0179+/-0.0027 vs. 0.0052+/-0.0010 min(-1), P<0.01). The measure of glucose effectiveness (S(G)*) derived by the Hot-MM was 1.36-fold higher than the direct measure available from the labeled IVGTT with basal insulin infusion (0.0079+/-0.0013 vs. 0.0058+/-0.0004 min(-1), P>0.26). These results suggest that the Hot-MM is more appropriate for the evaluation of glucose effectiveness than the Cold-MM.

Direct access to interstitial fluid in adipose tissue in humans by use of open-flow microperfusion.

To gain direct access to the interstitial fluid (ISF), a new technique called open-flow microperfusion has been evaluated. This method is based on a double-lumen catheter with macroscopic (0.3-0.5 mm diameter) perforations that is inserted into the subcutaneous adipose tissue and constantly perfused. Thus partial equilibration between the ISF and the perfusion fluid occurs. The glucose concentration of the ISF was determined by established (zero flow rate, no net flux, and recirculation procedures) and new (ionic reference and suction technique) calibration methods by use of open-flow microperfusion. The data show that 1) the glucose concentration in the ISF is significantly lower than the corresponding arterialized venous plasma values during basal steady-state conditions (adipose tissue 3.2 +/- 0.10 mM, plasma 5.27 +/- 0.12 mM) as well as during hyperglycemic clamp experiments (adipose tissue 7.3 +/- 0.13 mM, plasma 9.91 +/- 0.16 mM), and 2) it is possible to determine the recovery continuously by using the ion concentration of the ISF as an internal standard (ionic reference).

Lactate metabolism of subcutaneous adipose tissue studied by open flow microperfusion.

Open flow microperfusion and a novel calibration technique (ionic reference technique) were evaluated for the frequent measurement of the absolute lactate concentration in sc adipose tissue. Furthermore, the influence of the plasma insulin concentration on the lactate concentration of sc adipose tissue was investigated during hyperglycemia. Sixteen lean healthy young men participated in the studies. In the postabsorbtive state the mean sc lactate concentrations were 1.29 and 1.36 mmol/L for the ionic reference technique and the no net flux protocol, respectively (not significant, P > 0.05). The simultaneously measured arterialized plasma lactate concentration was significantly lower at 0.77 mmol/L (P < 0.05). Both the sc lactate concentration (1.8+/-0.33 mmol/L) and the plasma lactate concentration (0.96+/-0.03 mmol/L) were significantly elevated during a hyperinsulinemic euglycemic clamp experiment. During a hyperglycemic clamp experiment the sc lactate concentration reached a significantly elevated plateau (2.15+/-0.27 mmol/L) that was not influenced by the increasing plasma insulin concentration. It is concluded that 1) open flow microperfusion combined with the ionic reference technique enables frequent measurement of the sc lactate concentration; 2) sc adipose tissue is a significant source of lactate release in the postabsorbtive state as well as during hyperinsulinemic clamp conditions; and 3) insulin concentrations greater than 180 pmol/L have no further influence on adipocyte stimulation of sc adipose tissue with respect to lactate release.

Near fatal anticholinergic intoxication after routine fundoscopy.

We describe a case of severe anticholinergic intoxication following the topical instillation of tropicamide-containing eyedrops. Tropicamide is a short-acting atropine-like derivative and has been regarded as an effective and safe mydriatic. Half an hour after routine fundoscopy, a 62-year-old man experienced two generalized seizures with respiratory arrest and required intubation and mechanical ventilation. The patient was treated with physostigmine and made a full recovery.

Validation of home blood glucose meters with respect to clinical and analytical approaches.

OBJECTIVE: To evaluate the clinical and analytical accuracy of home blood glucose meters. RESEARCH DESIGN AND METHODS: Six blood glucose meters--Reflolux S (Boehringer Mannheim, Mannheim, Germany), One Touch II (LifeScan, Milpitas, CA), Glucocard Memory (Menarini, Florence, Italy), Precision QID (Medisense, Cambridge, U.K.), HaemoCue (HaemoCue, Angelholm, Sweden), and Accutrend alpha (Boehringer Mannheim, Mannheim, Germany)--were compared with a reference method (Beckman Glucose Analyzer II) under controlled conditions (glucose clamp technique). Validation of the blood glucose meters was accomplished by clinically oriented approaches (error grid analysis), statistical approaches (variance components analysis), and by the criteria of the American Diabetes Association (ADA), which recommend a target variability of < 5%. RESULTS: A total of 1,794 blood glucose monitor readings and 299 reference values ranging from 2.2 to 18.2 mmol/l were analyzed (705 readings < 3.89 mmol/l, 839 readings between 3.89 and 9.99 mmol/l, and 250 readings > 9.99 mmol/l). According to error grid analysis, only Reflolux S and Glucocard M had 100% of estimations within the clinically acceptable zones A and B. Assessment of analytical accuracy revealed substantial differences between the glucose meters after separation of the data into defined glycemic ranges. None of the devices met the ADA criteria. CONCLUSIONS: To evaluate accuracy of blood glucose meters, error grid analysis, as well as statistical models, are helpful means and should be performed together. Analytical performance of currently available home blood glucose meters differs substantially within defined glycemic ranges.

Novel system for real-time ex vivo lactate monitoring in human whole blood.

The objective of the study was to evaluate the performance of an amperometric enzyme based lactate sensor and to investigate the possibility of replacing a double lumen catheter based blood withdrawal system with a heparin coated single lumen system. The inner lumen of a double lumen catheter which was placed in a peripheral vein was perfused with heparin solution. The outer lumen was used to collect heparinized blood samples at a defined flow rate. The single lumen system was attached to a heparinized catheter which was also placed in a peripheral vein. The undiluted blood samples were collected at a specified flow rate. A sensor flow chamber incorporating an amperometric thin-film lactate microbiosensor was placed in the sampling line for real-time lactate monitoring. Plasma lactate concentrations were measured during frequently performed hyperlactatemia bicycle ergometer experiments in six healthy volunteers (age 25.8 +/- 2.8 years, BMI 22.7 +/- 1 kg/m2). Additionally, plasma lactate was measured in real-time using the lactate sensors. The first three experiments were performed with a double lumen based catheter system whereas the following three experiments were performed with a heparin coated catheter system. The correlation coefficients of sensor readings and laboratory analyzer results in all six experiments were between 0.93 and 0.99, respectively (P < 0.001). The miniaturized lactate sensors showed a linear range up to 25 mmol/l lactate concentration and 95% response times < 30 s in undiluted serum. During the experiments maximum lactate concentrations of 14 mmol/l were achieved. Improvements of system performance using heparin coated catheter systems could be shown. The overall SD of the sensor readings compared to laboratory results using three double lumen catheter based systems was 0.91 mmol/l whereas the SD using three heparin coated systems was 0.65 mmol/l. In summary, real-time monitoring of lactate in human whole blood is feasible with such a device and can be improved by using heparin coated catheter systems.

Open-flow microperfusion of subcutaneous adipose tissue for on-line continuous ex vivo measurement of glucose concentration.

OBJECTIVE: To evaluate a novel technique for on-line continuous glucose measurement in subcutaneous adipose tissue, and to investigate its accuracy for detection of hypoglycemia. RESEARCH DESIGN AND METHODS: The method combined an open-flow microperfusion of subcutaneous adipose tissue using a double lumen catheter and an extracorporeal sensor cell. An isotonic ion-free solution was perfused through the inner lumen of the catheter, equilibrated with the subcutaneous tissue fluid, and sampled through the outer lumen. The recovery was continuously monitored as the ratio between the measured sampled fluid conductivity and the subcutaneous tissue fluid conductivity (assumed to have a constant value of 1.28 S/m at 25 degrees C). Glucose concentration was calculated on-line from the measured glucose in the sampled fluid and the measured recovery in healthy volunteers during hyperglycemic glucose loads (n = 8), hypoglycemic hyperinsulinemic clamp (n = 6), and a 24-h monitoring period (n = 7). RESULTS: Subcutaneous glucose concentrations in the fasting state were 94% of the plasma glucose concentrations in arterialized venous samples. According to the error grid analysis, 96.9% of the on-line measured subcutaneous glucose concentrations during hyperglycemia and 96.3% during hypoglycemia were in accurate or acceptable zones. The mean differences between the measured subcutaneous glucose and the actual plasma glucose concentration were -0.06-3.3 mmol/l (hyperglycemia), and -0.6-1.1 mmol/l (hypoglycemia). CONCLUSIONS: By combining open-flow microperfusion, glucose sensor, and conductivity measurement, glucose concentration in the subcutaneous adipose tissue can be monitored on-line, extracorporeally, and continuously without any in vivo calibration, and gives accurate measurements during hyper- and hypoglycemia.

Accuracy of home blood glucose meters during hypoglycemia.

OBJECTIVE: To evaluate the accuracy of home blood glucose meters during hypoglycemia. METHODS: Six blood glucose meters-One Touch II (LifeScan, Milpitas, CA), Companion II (Medisense, Cambridge, U.K.), Reflolux (Boehringer Mannheim, Mannheim, Germany), Accutrend (Boehringer Mannheim), Elite (Bayer, Munich, Germany), and HemoCue (HemoCue, Angelholm, Sweden)-were compared with a reference method (Beckman Glucose Analyzer 2). Glucose concentrations from arterialized venous blood samples were measured using all glucose meters (whole blood) and the reference method (plasma) during hypoglycemic-hyperinsulinemic clamps in 15 subjects. RESULTS: In total, 663 blood glucose monitor readings and 119 reference values ranging from 2.28 to 3.89 mmol/l were analyzed. The correlation coefficients and the percentage of measurements within 20% and outside 40% of the reference values for each glucose meter were as follows: One Touch II: 0.91, 99.2% and 0%; Companion II: 0.81, 88.2% and 2.5%; Reflolux: 0.78, 85.0% and 0.9%; Accutrend: 0.88, 46.0% and 6.6%; Elite: 0.78, 75.6% and 4.2%; and HemoCue: 0.93, 96.6% and 0% (P < 0.001). CONCLUSIONS: There were substantial differences between the blood glucose meters during hypoglycemia, and none of the devices met the latest criteria recommended by the American Diabetes Association.

[Driver's license, driving habits and traffic safety of patients with diabetes mellitus]. / Führerschein, Fahrgewohnheit und Verkehrssicherheit bei Patienten mit Diabetes mellitus.

Motoring practices of diabetic drivers are similar to those of the average driving population. Due to the sudden onset of disabling hypoglycemia and the long-term complications of the disease, particularly retinopathy, one might assume that diabetic drivers are more prone to road traffic accidents than the average driver; however, the risk is not increased. The Council of the European Union recently laid down guidelines for dealing with this problem, which will lead to the introduction of a new law in Austria governing driving licensing. This legislation is currently under consideration. We recommend that discrimination between patients requiring therapeutic regimens with potential hypoglycemic side effects (insulin and/or sulphonylureas) and those who are not at risk of hypoglycemia (controlled by diet only or oral antidiabetic drugs other than sulphonylureas) should be legally defined by the licensing authorities. Furthermore, the legal enforcement of participation by diabetic drivers in a structured teaching programme, with the special aim of informing on traffic attitudes and avoidance of hypoglycemia while driving, might be of great importance for safety on the road.

Evaluation of a structured outpatient group education program for intensive insulin therapy.

OBJECTIVE: To determine the efficacy and safety of a structured diabetes teaching and treatment program (DTTP) in patients with insulin-dependent diabetes mellitus (IDDM) in an outpatient setting. RESEARCH DESIGN AND METHODS: All patients with IDDM who completed a structured 5-day outpatient DTTP were reevaluated after a mean follow-up of 3 years. A standardized interview was used to assess frequency of severe hypoglycemia, type of insulin treatment, self-monitoring, and other diabetes-related parameters. HbA1c was measured by high-performance liquid chromatography. RESULTS: Of 205 patients, 4 (2%) died during the observation period. HbA1c in the 201 surviving patients decreased significantly from 8.7 +/- 2.0 to 7.5 +/- 1.2% at follow-up (P < 0.001); frequency of severe hypoglycemia decreased from a mean of 0.46 to 0.13 per patient per year (P < 0.001). Hospital admission due to acute metabolic disturbances decreased from 4.5 +/- 11.1 to 1.4 +/- 6.7 days/patient-year (P < 0.001). At follow-up, intensive insulin therapy was carried out by 98% of the patients, and 80% of the patients reported three or more measurements of blood glucose per day. Diabetes-related knowledge had a positive (P < 0.01) and body mass index a negative (P < 0.02) influence on improving HbA1c assessed by multiple regression analysis. Severe hypoglycemia after DTTP was associated with a history of severe hypoglycemia before DTTP (P < 0.001) and the existence of overt diabetic nephropathy (P < 0.05). CONCLUSIONS: A structured outpatient DTTP as used in this study is able to improve overall metabolic control and decrease the frequency of severe hypoglycemia in patients with IDDM.

Evaluation of a structured teaching and treatment programme for type 2 diabetes in general practice in a rural area of Austria.

The efficacy of a treatment and teaching programme for non-insulin-treated Type 2 diabetic patients in general practice was evaluated in a prospective, controlled study. In a rural area in southern Austria, 53 patients from seven general practices participated in a structured programme (intervention group) and 55 patients from seven general practices without the programme served as the control group. After 6 months the weight reduction in the intervention group was 2.6 kg (1.6-3.7 kg, p < 0.001) and the difference in HbA1c between the groups was 0.92% (0.23-1.61%, p < 0.01) at follow-up. Systolic (-16.6 mmHg) and diastolic (-11.1 mmHg) blood pressure, serum triglycerides (-0.63 mmol I-1), and serum cholesterol (-0.40 mmol I-1) were reduced significantly in the intervention group (p < 0.006). The number of patients with callus formation and poor nail care decreased significantly after participating in the teaching programme (p < 0.001). In the control group no reduction in body weight, metabolic control or in risk factors for diabetic foot complications were observed. Calculated health care costs per patient and year decreased in the intervention group (-33 pounds) and increased in the control group (+ 30 pounds) mainly due to changes in prescription of oral hypoglycaemic agents in both groups. This programme may be an efficient and helpful model to increase overall quality of diabetes care according to the St Vincent Declaration.

[Management of diabetes in Austria 5 years after the St. Vincent Declaration]. / Diabetesbetreuung in Osterreich 5 Jahre nach der St. Vincent-Erklärung.

In 1989 representatives of all European governments agreed on the "St. Vincent Declaration". In this statement of intent and recommendations all governments, including that of Austria, pledged to implement policies on preventive measures geared to reduce morbidity and mortality of all diabetic patients in Europe. Structured patient education has been shown to improve the overall quality of care in Type 1 diabetic patients. Reduction of acute metabolic disturbances after participation in the patient education programme reduces hospitalizations and allows significant savings in health care costs, which can help to make safe and effective therapy available to all patients with Type 1 diabetes without additional costs. A teaching and treatment programme for Type 2 diabetics by general practitioners has proven to be effective, feasible and inexpensive. Nationwide implementation of such an evaluated patient education programme shifts diabetes care to "primary health care" level, and increases long-term quality of diabetes care without generating new expenses. Patient education is considered not only the basis for successful management of diabetes, but also, as laid down in the St. Vincent Declaration, a basic human right of all patients, which still needs to be put into practice.