Changes in Quality of Diabetes Care and Morbidity over 20 Years in People with Type 1 Diabetes and Long Diabetes Duration: The JEVIN Trial.

Background: The JEVIN trial started as a cross-sectional study in 1989/90 in Jena, a city of the former German Democratic Republic. At that time, the centralized diabetes care system was broken down and restarted 10 years later; structured treatment and teaching programs were implemented, blood glucose self-monitoring, insulin pump-systems and analogue insulin were introduced. We surveyed people with type-1-diabetes of the baseline JEVIN trial in a 20-year follow-up. Methods: 131 patients with type-1-diabetes were analyzed in 1989/90. Of the living population in 2009/10 (n=104), 83 persons were identified and 75 persons with a mean diabetes duration of 35 years were reexamined regarding HbA1c, self-monitoring, diabetes therapy, severe hypoglycemia, diabetic late complications and compared with the results of the same persons in 1989/90. Results: HbA1c decreased from 57.1 mmol/mol in 1989/90 to 52.7 mmol/mol in 2009/10 (7.4 -7.0%; p=0.049). Self-monitoring of blood glucose increased from 2 to 35 tests/week (p<0.001). 100%-use of animal insulin changed to human and analogue insulin therapy. The incidence of severe hypoglycemia increased from 0.1 to 0.16/patient-year. Retinopathy increased from 29 to 69% (p<0.001), nephropathy from 5 to 27% (p<0.001) and neuropathy from 13 to 43% (p<0.001). 17% had no diabetic late complications. Conclusions: The JEVIN trial shows a significant improve in HbA1c in the past 20 years. Severe hypoglycemia occurred rarely and 17% were still free of any diabetic late complication after 35 years of diabetes. This indicates a good quality of diabetes care in a German setting.

Use and Effectiveness of Continuous Subcutaneous Insulin Infusion (CSII) and Multiple Daily Insulin Injection Therapy (MIT) in Children, Adolescents and Young Adults with Type 1 Diabetes Mellitus.

UNLABELLED: Today continuous subcutaneous insulin infusion (CSII) is frequently used in children and adolescents with type 1 diabetes mellitus. The present cross-sectional trial aimed to document current practice, quality of diabetes control and incidence of acute complications in different age-groups under CSII vs. multiple daily insulin injection therapy (MIT). Moreover the survey analyzed socio-demographic backgrounds of the patients. PATIENTS AND METHODS: A total of 901 patients (age 11.5±4.0, diabetes duration 4.0±3.6 years) was entered in the database. Clinical data, laboratory parameters and, using a standardized questionnaire, socio-demographic data were assessed. For age-related analyses patients were allocated to 4 groups: pre-school children (< 6 years), pre-adolescents (≥ 6 and<11 years), adolescents (≥ 11 and<16 years) and young adults (≥ 16 and<22 years). RESULTS: Of the cohort n=194 had a CSII, n=707 had a MIT. Patients with CSII vs. MIT had a longer diabetes duration, they used more frequently insulin analogues, performed more frequently blood-glucose self-tests and had a lower insulin dosage per kilogram body weight. In respect of HbA1c, the mean amplitude of blood-glucose excursions, but also of lipids, creatinine, microalbuminuria and blood pressure, there were no differences in neither age-group between patients with CSII and MIT. In patients with CSII and MIT, there was a tendency (p<0.05) towards an increase in HbA1c in adolescents and young adults and there was a decrease (p<0.05 for tendency) in the frequency of hypoglycaemia from the age group of young adults to pre-school children. Adolescents and young adults with CSII had a higher educational level. Pre-adolescents, adolescents and young adults with CSII have also better diabetes-related knowledge. Moreover, in all age-groups, the parents of patients with CSII had mostly a lower unemployment rate and higher educational levels. CONCLUSIONS: The present analyses demonstrate that in all age-groups CSII provides convenient and flexible insulin delivery during routine treatment of type 1 diabetes. There is reasonable quality of diabetes control accompanied by a low incidence of hypoglycaemia and ketoacidosis. However, under CSII and MIT there is an increase of HbA1c towards adolescence. It must also highlighted that CSII seems to be expansive and that CSII is more frequently used in patients with better educational levels and deriving from higher social classes.

[Multidisciplinary health care needs of psychologically distressed cancer patients in a Comprehensive Cancer Center]. / Multidisziplinärer Versorgungsbedarf psychisch belasteter Tumorpatienten an einem Comprehensive Cancer Center.

BACKGROUND AND OBJECTIVE: Considering the prolonged life-expectancies and the resulting demands that are placed on cancer patients and their relatives, the importance of specific counseling and support services including psycho-oncology, social services, nutritional, and exercise counseling has profoundly increased. The main focus of the current study was to evaluate the multidisciplinary health care needs of emotionally distressed cancer patients whoe were treated in a Comprehensive Cancer Center. METHODS AND STUDYGROUP: 831 out-patients were evaluated with regard to their psychological distress level and their multidisciplinary health care needs for specialist services of psycho-oncology, social services, nutritional, and exercise counseling using a tablet-PC assisted screening questionnaire. Separate analyses were completed for patients with and without psychological distress. RESULTS: One third of the screened patients showed clinically relevant psychological distress. Health care needs for all specialist services were significantly greater among these patients compared to patients without psychological distress (all p-values < 0.005). The higher needs were foremost presented by the number of needed specialist services (p < 0.001): two thirds of the psychologically distressed patients demonstrated, besides the need for a psycho-oncological service, a need for two or three further specialist services, whereas among patients without psychological distress more than 70% showed a need for at most one specialist service. CONCLUSION: Multidisciplinary health care needs of psychologically distressed cancer patients should be systematically addressed in a Comprehensive Cancer Center, and patients should be offered a coordinated and integrated health care program.

[Effect of systematic information about psychosocial support services during outpatient radiotherapy. A controlled trial]. / Effekte systematischer Informationen über psychosoziale Angebote während der ambulanten Strahlentherapie. Eine kontrollierte Studie.

BACKGROUND: Up to 50 % of all cancer patients require psychosocial support during the course of their disease. However, only a proportion of these patients make use of the existing services. This is partly because patients are unaware that psychosocial support services are available to them. We investigated whether systematically providing printed information concerning psychosocial support can increase the knowledge and usage of these services, as well as health-related self-efficacy. MATERIALS AND METHODS: In a controlled trial, 108 breast cancer patients were assigned alternately to either an intervention- or a control group. At two predefined time points before and during radiotherapy, patients in the intervention group received correspondence informing them about psychosocial services (psycho-oncology, clinical social work and the Cancer Information Service).The control group received no systematic information. Using a standardized questionnaire, all patients were subsequently questioned about their knowledge of psychosocial support services, their perceived self-efficacy and their use of psychosocial support services. RESULTS: We found that systematic provision of information had a positive effect on the knowledge of psychosocial support services (p = 0.042; d = 0.45) and self-efficacy (p = 0.047; d = 0.42). However, no increase in the actual usage of these services was observed (p = 0.661; d = 0.10). CONCLUSION: The systematic provision of information in the form of written correspondence can easily be implemented into clinical routine and is an effective way to increase cancer patients' knowledge of psychosocial support services. Furthermore, providing information about the services had a positive impact on patients' perceived self-efficacy. However, simply making this information available did not increase the usage of psychosocial support services.

An innovative telemedical support system to measure physical activity in children and adolescents with type 1 diabetes mellitus.

UNLABELLED: To assess physical activity in patients with type 1 diabetes an innovative telemedical support system has been developed. The aim of the feasibility trial was to prove its use in a clinical setting. PATIENTS/METHODS: 16 children/adolescents with type 1 diabetes mellitus aged 14.5 ± 2.2 years (diabetes duration 6.5 ± 3.6 years, HbA1c 8.8 ± 1.0%) were included in the study. During a period of 1-3 days all the patients received a telemedical assessment system. It consists of a sensor for physical activity integrated into a mobile phone (DiaTrace). Additionally it is combined with a system for continuous blood glucose monitoring (CGM). RESULTS: The technical system was highly accepted by all the 16 children and adolescents. Physical activity measured was 13.3 ± 5.5 AU/d, mean duration of total physical activity was 204.9 ± 66.5 min/d (walking 102.5 ± 62.5, running 7.4 ± 5.8, cycling 39.2 ± 32.7, driving 36.0 ± 18.6, non-specific physical activity 57.0 ± 29.7 min/d). Periods without activity lasted for 386.5 ± 187.2 min/d. Daily energy expenditure was 1,964.1 ± 185.5 kcal/d. Correlations between physical activity (measured with DiaTrace) and blood glucose profiles (measured with CGM) were calculated. Pearson's correlation coefficients ranged between 0.59 and 0.99 (median 0.91). Hence, these good correlation coefficients show the high and direct association between blood glucose values and activity units. The wide ranges in correlation coefficients demonstrate a huge variability of individualized reactions. CONCLUSIONS: Use of innovative electronic health technology is highly accepted by patients. It reveals an accurate, real-time assessment of an individual's physical activity. These information can use for insulin dose-adjustment.

Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with Type 2 diabetes previously on long-term conventional insulin therapy: the SWITCH Pilot Study.

BACKGROUND: Addition of the long-acting basal human insulin analogue insulin glargine (LANTUS) to the treatment regimen of patients with inadequate glycaemic control on oral antidiabetic drugs (OADs) alone has previously been evaluated as effective, safe and convenient. This pilot study aimed to establish whether insulin glargine plus OADs is effective in Type 2 diabetes patients previously poorly controlled on premixed insulin therapy. METHODS: In an open, controlled, randomized, parallel-group, single-centre, 16-week pilot study, 52 patients (age 65.6+/-9.2 years; diabetes duration 15.3+/-7.6 years; insulin therapy duration 4.2+/-1.7 years, body mass index 31.4+/-2.9 kg/m(2)) with Type 2 diabetes (HbA (1c)> or =8.0%) on premixed human insulin (75/25 or 70/30) were randomized to once-daily morning insulin glargine plus glimepiride (Group A; n=17), insulin glargine plus glimepiride and metformin (Group B; n=18) or premixed insulin (Group C; n=17). Glycaemic control and incidence of hypoglycaemia were evaluated. RESULTS: HbA (1c) decreased significantly from baseline in Groups A and B, but not in Group C; (Group A: 7.87+/-0.66%, -0.35%, p=0.013; Group B: 7.44+/-0.92%, -0.69%, p=0.0057; Group C: 7.83+/-1.13%, -0.25%, p=0.32). There were no between-treatment differences at endpoint in HbA (1c), fasting blood glucose, mean daily blood glucose or symptomatic hypoglycaemia (mean events/patient: Group A, 2.2; Group B, 2.3; Group C, 2.0). At endpoint, 88% of patients in Group A, 81% in Group B and 94% in Group C opted to continue with their assigned regimen. CONCLUSIONS: This pilot study is the first prospective study to show that switching from premixed insulin to insulin glargine plus OAD treatment resulted in similar glycaemic control and treatment satisfaction. The results support the need for prospective examination in a larger-scale clinical study in patients with long-standing Type 2 diabetes and sub-optimal glycaemic control previously using a conventional premixed insulin regimen.

Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with type 2 diabetes previously on long-term conventional insulin therapy: the Switch pilot study.

BACKGROUND: Addition of the long-acting basal human insulin analogue insulin glargine (LANTUS) to the treatment regimen of patients with inadequate glycaemic control on oral antidiabetic drugs (OADs) alone has previously been evaluated as effective, safe and convenient. This pilot study aimed to establish whether insulin glargine plus OADs is effective in Type 2 diabetes patients previously poorly controlled on premixed insulin therapy. METHODS: In an open, controlled, randomized, parallel-group, single-centre, 16-week pilot study, 52 patients (age 65.6+/-9.2 years; diabetes duration 15.3+/-7.6 years; insulin therapy duration 4.2+/-1.7 years, body mass index 31.4+/-2.9 kg/m2) with Type 2 diabetes (HbA1c>or=8.0%) on premixed human insulin (75/25 or 70/30) were randomized to once-daily morning insulin glargine plus glimepiride (Group A; n=17), insulin glargine plus glimepiride and metformin (Group B; n=18) or premixed insulin (Group C; n=17). Glycaemic control and incidence of hypoglycaemia were evaluated. RESULTS: HbA1c decreased significantly from baseline in Groups A and B, but not in Group C; (Group A: 7.87+/-0.66%, -0.35%, p=0.013; Group B: 7.44+/-0.92%, -0.69%, p=0.0057; Group C: 7.83+/-1.13%, -0.25%, p=0.32). There were no between-treatment differences at endpoint in HbA1c, fasting blood glucose, mean daily blood glucose or symptomatic hypoglycaemia (mean events/patient: Group A, 2.2; Group B, 2.3; Group C, 2.0). At endpoint, 88% of patients in Group A, 81% in Group B and 94% in Group C opted to continue with their assigned regimen. CONCLUSIONS: This pilot study is the first prospective study to show that switching from premixed insulin to insulin glargine plus OAD treatment resulted in similar glycaemic control and treatment satisfaction. The results support the need for prospective examination in a larger-scale clinical study in patients with long-standing Type 2 diabetes and sub-optimal glycaemic control previously using a conventional premixed insulin regimen.

Diabetes, insulin, and risk of cancer.

Up to now, the studies involving diabetes mellitus and malignancies show controversial results: Many of them have found incidences of malignancies that were comparable or even lower than those in nondiabetic subjects; others conclude that diabetes mellitus is linked to a higher incidence of malignancies and/or a predictor of mortality from cancer. Insulin and its precursors, pro- and pre-proinsulin, have been shown to have some homology to the insulin-like growth factors, but, moreover they have some affinity to bind at receptors of the tumor growth factor and some hybrids too. Hence, an association between diabetes mellitus, insulin, hyperinsulinaemia, and carcinogenesis appears plausible. On the other hand, diabetes mellitus can influence different hormone levels. In some tumor entities, such as prostate carcinoma, this effect can somewhat counterbalance the direct mitogene effect of insulin and its precursors. All in all, as a result of the complexity of these mechanisms and the differences between the tumor entities, the question whether diabetes mellitus is associated with an increased or a reduced risk for the development and in respect of the prognosis of cancer cannot be answered. The only way to give some answer is to focus on specific tumor entities: It seems that diabetes mellitus and/or hyperglycaemia are independent risk factors and/or predictors at least in respect of cancer of the colon, pancreas, female breast, endometrium, and, in men, of the liver and bladder. However, most of these data were assessed in patients with type 2 diabetes mellitus. This makes it highly questionable whether the data can easily be transferred to patients with type 1 diabetes. Moreover, additional potential limitations are that most of the studies do not focus on the treatment modality or the race of participants. In conclusion, up to the present, we have an increased risk for some and a reduced risk for other tumor entities, but still, we cannot give the general answer.

Overweight, obesity and elevated blood pressure in children and adolescents.

OBJECTIVE: Since many years in adults associations between dyslipidaemia, increased insulin resistance, arterial hypertension and the risk for cardiovascular diseases have been recognized. It was the aim of the present trial to investigate these associations and interactions between height, weight, body-mass index and blood pressure values in overweight/obese and normal weight children and adolescents. PATIENTS AND METHODS: 172 children and adolescents (n = 86 with overweight and obesity, n = 86 controls) were studied. In all the subjects anthropometrical data and blood pressure values were assessed. RESULTS: Overweight and obese children had significantly higher blood pressure values (systolic 117.9 +/- 9.7, diastolic 75.6 +/- 8.8 mmHg) than control subjects (systolic 111.4 +/- 11.0, diastolic 69.5 +/- 8.8 mmHg, p<0.001/0.001). Additionally in overweight and obese subjects the number of patients with blood pressure values below the 50th percentile was lower, but the numbers of children and adolescents with values >or=50th age-, height- and gender-specific percentiles were significantly higher. In multivariate analysis of overweight/obese children and adolescents only patients' BMI (R-square = 0.26, beta = 0.52, p<0.001), but not sex, age, height or weight revealed any association with systolic blood pressure values. Diastolic blood pressure revealed an association with childrens' and adolescents' weight (R-square = 0.22, beta = 0.48, p<0.001), but there were no associations with body-mass index, sex, age or height. In normal weight control subjects age (beta = 0.32, p = 0.01) and height (beta = 0.28, p = 0.03) showed associations with the systolic blood pressure values (R-square = 0.15), but only childrens' and adolescents' height (beta = 0.39, p<0.001) was associated with diastolic blood pressure (R-square = 0.28). CONCLUSIONS: Overweight and obesity in childhood are highly associated with multiple comorbidities, elevated blood pressure values, dyslipidaemia, reduced insulin sensitivity and alterations of large and minor vessels. Overweight and obesity in children and adolescents should not longer be regarded as variations of normality, but as diseases with an extremely high risk for the development of atherosclerosis and cardiovascular complications in adulthood. Knowledge of these complex associations implicate even in young age the need for intervention.

Structured diabetes therapy and education improves the outcome of patients with insulin treated diabetes mellitus. The 10 year follow-up of a prospective, population-based survey on the quality of diabetes care (the JEVIN Trial).

AIMS/HYPOTHESIS: JEVIN (Jena's St. Vincent Trial) is a prospective, 10 year follow-up, population-based survey of all insulin treated patients with type 1 and type 2 diabetes mellitus aged 16 to 60 years and living in the city of Jena (100,000 inhabitants), Thuringia, Germany. It aims to show the effects of implementation of the St. Vincent Declaration and to evaluate the effect of recent changes in the health care system and new treatment strategies. PATIENTS AND METHODS: 190 patients (83% of the target population), 244 patients (90%) and 261 patients (90%) were studied in 1989/90, 1994/95 and 1999/2000, respectively. RESULTS: Up to 1994/95, the HbA1c of patients with type 1 diabetes mellitus increased (1994/95: 8.50+/-1.80% versus 1989/90: 7.83+/-1.60%, p=0.002). For patients with type 2 diabetes mellitus, it remained constant (9.01+/-2.06% versus 9.17+/-1.60%, n. s.). During the period from 1994/95 to 1999/2000, there was a substantial improvement in the relative HbA1c of both, patients with type 1 (7.62+/-1.55%, p<0.0001), and with type 2 diabetes (7.57+/-1.29%, p<0.0001). Up to 1999/2000, 87.7% of the patients with type 1 (1989/90: 0%, 1994/95: 73.2%) and 96.6% of the patients with type 2 diabetes (1989/90: 0%, 1994/95: 89.7%) participated in TTP's. The incidence of acute and the prevalence of long-term complications remained constant. CONCLUSIONS: Results of the population-based, prospective trial to optimise patients' quality of diabetic control suggest: For patients with insulin treated type 2 diabetes mellitus, excellent treatment can be available by primary care physicians interested, educated and highly engaged in diabetes therapy. Moreover, structured diabetes therapy consisting of treatment and teaching programmes, regular self-monitoring, patients' insulin dose adjustment and patients' empowerment, should be offered to all patients with diabetes mellitus.

Population-based measurement of quality of diabetes care using HbA1c values in the state of Thuringia/Germany.

INTRODUCTION/HYPOTHESIS: There remains insufficient knowledge about the quality of diabetes therapy regarding structure, process and outcome given by primary care in Thuringia, and elsewhere in Germany. The project assesses a means of determining the quality of diabetes therapy in primary care by analysis of HbA1c values within a broad territory. METHODS: HbA1c tests of Thuringian patients were analysed by 20 participating medical laboratories between January 1 and March 31, 2002; each HbA1c test was identified by the postal code of the Thuringian General Practitioner (GP) who ordered the test and adjusted by a standardisation procedure (mean normal of healthy subjects 5 %). The German state of Thuringia (population of 2,421,871) consists of 23 urban and rural districts. This format was also used in the present study. RESULTS: Twenty participating laboratories contributed 59,702 HbA1c tests from diabetic patients in Thuringia. Adjusted mean HbA1c of entire Thuringia: 6.75 %, 36.4 % of all HbA1c tests were above 7.0 % and 3,0 % of all HbA1c values above 10.0 %. Regional percentage of HbA1c tests above 7.0 % ranged between 28.2 % and 47.3 %. Regional percentage of HbA1c tests above 10.0 % ranged between 1.8 % and 4.8 %. Subgroup analyses comparing urban vs. rural districts showed significantly lower mean HbA1c (6.72 % vs. 6.75 %, CI 0.01 - 0.06, p < 0.01) and percentage of HbA1c tests above 7 % (8.19 % vs. 8.24 %, CI 0.01 - 0.08, p < 0.01) in urban areas. CONCLUSIONS: Mean HbA1c as an indicator of glycaemic control of diabetes patients in primary care in Thuringia was good. The percentage of patients who need immediate medical intervention to prevent acute complications varied between districts, which is indicative for differences in quality of diabetes care in Thuringia. However, the proposed method is still experimental and has not yet been evaluated. Consequently, considerable bias might influence the results.

Diabetes mellitus and dialysis.

Diabetes mellitus is increasing, and in some countries is the single most important cause, for end-stage renal disease. In general, primarily elderly patients on renal replacement therapy, are not only affected by diabetes-related long-term complications, but also frequently with a wide range of co-morbidities. Apart from cardiac complications, the patients are subject to a wide range of vascular (i.e. peripheral vascular disease, stroke) and infectious complications. In the past this has been reflected by a relatively poor survival rate on dialysis, and minimized chances to obtain renal transplantation. Today, several renal replacement strategies are available, including the main 3: hemodialysis, peritoneal dialysis or kidney transplantation. For patients with diabetes mellitus, hemodialysis is the most commonly used therapy. Each dialysis unit should achieve an optimal dialysis adequacy represented by a single pool Kt/V of at least 1.2. The most important independent predictor of patient survival with hemodialysis treatment is age. Other factors related to complications are left ventricular hypertrophy, arterial hypertension, hypervolaemia and chronic anemia. Moreover, medial arterial calcification, malnutrition, gastrointestinal disorders and dialysis against low potassium dialysate are related to increased morbidity and mortality as well. An integral part of treatment is the availability of good vascular access. The survival rates of fistulas show a nearly twofold higher rate of failure for synthetic grafts compared with arteriovenous fistulas. The role of peritoneal dialysis in renal replacement therapy in patients with diabetic nephropathy is well established and used world-wide. Most patients with residual renal function start with continuous ambulatory peritoneal dialysis (CAPD), but automated peritoneal dialysis can also be used. An unresolved problem associated with CAPD is the glucose absorption and caloric intake. The optimum adjustment of blood glucose values is made more difficult. Death rates of diabetic patients on peritoneal dialysis remain higher than in non-diabetics. The changes in peritoneal membrane thickness and vascular alterations in relationship to the duration of dialysis are caused mainly by glucose and glucose degradation products, such as advanced glycation endproduct (AGEs). Therefore, new peritoneal dialysis solutions are needed to reduce the complications and to delay a long-time function of the peritoneal membrane. Peritonitis remains still the major cause of discontinuation of dialysis but there is no increased risk in diabetic patients. Nevertheless, an integrative care of end-stage renal disease patients with diabetic nephropathy should be offered to the patient, starting on peritoneal dialysis and switch to hemodialysis if problems arise. During the whole time patients should be kept on the renal transplantation waiting list.

Structured treatment and teaching of patients with Type 2 diabetes mellitus and impaired cognitive function--the DICOF trial.

BACKGROUND: Patient education is integral part of any diabetes therapy in Germany, but elderly patients are not able to follow the variety of topics comprising standard treatment and teaching programmes (TTP), primarily due to impaired neuropsychological function. This leads to deficits in diabetes knowledge and hindered ability for diabetes self-management. AIM: To evaluate structured TTP for geriatric patients with impaired cognitive function. PATIENTS AND METHODS: A neuropsychological examination was performed on all patients over 54 years [n=102, age 68.6 +/- 8.7 years, diabetes duration 10.3 (0.03-35.4) years, HbA1c 10.3 +/- 1.7% (HPLC, Diamat, NR 4.5-6.3%), cognitive function 87.7 +/- 12.3 IQ points] who took part in TTP for insulin therapy. Patients with impaired cognitive function participated either in the standard TTP of Berger [n = 35, age 67.6 +/- 8.9 years, diabetes duration 9.9 (0.04-35.4) years, HbA1c 10.3 +/- 2.0%] or in the specialized structured geriatric DICOF-TTP [n=33, age 70.4 +/- 8.2 years, diabetes duration 10.4 (0.03-24.9) years, HbA1c 10.7 +/- 1.8%]. RESULTS: After TTP there were no differences in knowledge and ability for diabetes self-management (standard/DICOF: knowledge 11.0 +/- 2.6 vs. 12.2 +/- 2.7 points, P = 0.11; handling 14.9 +/- 3.3 vs. 15.9 +/- 2.5 points, P = 0.18). However, patients who took part in the DICOF programme showed better scores in satisfaction with the education programme [standard/DICOF 44.7 (31-57) vs. 52.5 (45-59) points, P < 0.001]. Six months later the DICOF participants showed better results regarding diabetes self-management (standard/DICOF: handling 12.5 +/- 4.1 vs. 15.9 +/- 3.1 points, P = 0.001). Both groups showed HbA1c decrease (8.3 +/- 1.4 vs. 8.5 +/- 1.3%, P=0.62) and similar incidence of acute complications. CONCLUSIONS: Elderly patients with impaired cognitive function should take part in specialized structured TTP. This leads to both better satisfaction with the education programme and an improved ability for diabetes self-management.

Insulin pump therapy in patients with Type 1 diabetes mellitus: results of the Nationwide Quality Circle in Germany (ASD) 1999-2000.

BACKGROUND AND AIMS: Only a few specialised centres in Germany initiated insulin pump therapy before 1990. Initiation of pump therapy involves the participation in a structured treatment and teaching programme (TTP). During the last decade insulin pump therapy has been widely used. The impact of this decentralisation on the quality of care is still unknown. The aim of this trial was both to evaluate the outcome of insulin pump therapy outside specialised centres and to identify features that might be associated with persistently increased HbA1 c levels. PATIENTS AND METHODS: 250 patients with type 1 diabetes mellitus (age 36.0 +/- 13.1 years; diabetes duration 16.1 +/- 9.9 years), who were on continuous subcutaneous insulin infusion (CSII) therapy during 1999 - 2000, were individually included in the study. Second examination was performed one year after participation in the in-patient TTP for insulin pump therapy. Patients were recruited from 21 member institutions of the Working Group for Structured Diabetes Therapy of the German Diabetes Association. Further details were sought by questionnaire on those patients with persistently increased HbA1c (> 1.7 fold of mean normal range.) RESULTS: One year after participation in the TTP for CSII relative HbA1c (original value/mean normal of the local method [Müller et al., 1999]) decreased from 1.51 (0.9 - 3.2) to 1.44 (0.9 - 3.6) (p < 0.0001), severe hypoglycaemia from 0.46 to 0.12/patient/year (p < 0.001), severe ketoacidosis from 0.08 to 0.05/patients/year (p = 0.003) and hospitalisation from 5.2 to 3.1 days/patient/year (p = 0.002). In 43/207 (17%) the incidence of severe hypoglycaemia was unchanged (before 0.12 and after TTP 0.14/patients/year), there was slight increase in severe ketoacidosis (before 0.15; after TTP 0.23/patients/year) and hospitalisation days were unchanged (before 4.5; after TTP 4.4 days/patients/year). The following factors were associated with adverse outcomes: psychological problems including eating disorders and alcohol abuse (28%), lack of interest in self-management (28%) and social problems (11%). In 28% there was no follow-up treatment by diabetologists specialised in pump therapy. CONCLUSION: The benefits of insulin pump therapy are improvement of HbA1c, reduction of hypoglycaemia, ketoacidosis and hospitalisation days as well as improved flexibility. It is possible to draw up a list of clinical criteria and service requirements, which are likely to reduce failures.

Effect of smoking on risk factors for cardiovascular disease in patients with diabetes mellitus and renal insufficiency.

BACKGROUND: Many studies have been published demonstrating a strong correlation between smoking, renal lesions and cardiovascular morbidity and mortality. Possible contributing factors are elevated blood pressure values, changes in vascular reactivity, concentrations of lipids, fibrinogen and carboxyhemoglobin, in patients with diabetes mellitus, the quality of diabetes control and insulin resistance. Other possible risk factors may include advanced glycation end (AGE)-products, total plasma homocysteine and metabolites as well as symmetrical (SDMA) and asymmetrical (ADMA) dimethylarginine. It was the goal of the present trial to investigate the serum concentrations of these >new<, possible risk factors in a selection free population of patients with type 1 and insulin-treated type 2 diabetes mellitus, in patients with chronic renal insufficiency and in renal transplant recipients. The second aim was to analyse the effect of cigarette smoking on the levels of these laboratory parameters. PATIENTS AND METHODS: A total of 544 subjects (n = 98 patients with chronic renal insufficiency without hemodialysis, n = 84 patients with hemodialysis, n = 50 renal transplant recipients, n = 114 patients with type 1 and n = 147 patients with insulin treated type 2 diabetes mellitus, n = 51 healthy controls) participated in the trial. RESULTS: Patients with renal insufficiency had significantly higher concentrations of the AGE-products N-epsilon-Carboxymethyllysine (CML) and pentosidine compared with both groups of patients with insulin-treated diabetes mellitus and the healthy controls. In patients with type 1 diabetes there was a positive correlation between HbA1c and the concentration of CML (r = 0.405, p = 0.017) and between the pentosidine-concentration and the serum creatinine-level (r = 0.482, p = 0.001). In type 2 diabetes there was a correlation between CML and diastolic blood pressure (r = 0.239, p = 0.039). In comparison to the healthy controls, patients with renal diseases and patients after kidney transplantation had higher concentrations of total plasma homocysteine and its metabolites. Similar results were found for SDMA and ADMA: Patients with chronic renal insufficiency both with and without hemodialysis had significantly higher values than the renal transplant recipients and healthy controls. A clear influence of cigarette smoking on the levels of the laboratory parameters measured could not be determined in any group; neither in the patients with diabetes mellitus, nor in the patients with renal diseases, nor in the healthy controls. CONCLUSIONS: The present trial demonstrates an increase in the parameters linked to the development of cardiovascular diseases including total plasma homocysteine, its metabolites, the dimethylarginines SDMA and ADMA and advanced glycation end-products depending on the degree of renal insufficiency. Moreover, in patients with insulin-treated diabetes mellitus, the concentrations of the AGE-products CML and pentosidine seem to be strongly influenced by the quality of diabetes control and blood pressure levels. There was no influence of cigarette smoking on the levels of the laboratory parameters measured.

Current topics on low-density lipoprotein apheresis.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.

Occupational hand dermatitis in food industry apprentices: results of a 3-year follow-up cohort study.

OBJECTIVE: The aim of this prospective follow-up study was to quantify the impact of hand dermatitis (HD) in bakers, confectioners and bakery shop assistants, and to investigate related risk factors. METHOD: Bakers', confectioners' and bakery-shop assistants were included in a prospective follow-up study in the region of East Thuringia starting in August 1996. At the beginning of their vocational training 91 apprentices were interviewed and examined in a standardised way. Follow-up examinations and interviews were done after 6 months (n = 79), 12 months (n = 63) and at the end of the training (n = 69) after 36 months. RESULTS: In their case histories 3.3% (n = 3) of the apprentices reported previous HD in childhood and adolescence. The first assessment after 2 to 4 weeks of vocational training revealed HD in 17.5% (n = 16) of the individuals. At the follow-up examination after 6 months, point prevalence of HD was 29.1% (n = 23), after 12 months 27.0% (n = 17) and after 36 months 27.5% (n = 19). Mild to moderate irritant contact dermatitis was the most frequent finding. Finally, an atopic skin diathesis (> 10 points, "atopy score") (OR = 4.89; CI 95% 1.15-20.79), previous HD (OR = 41.1; CI 95% 4.99-339.13) as well as flexural dermatitis (OR = 6.8; CI 95% 1.72-27.22) proved to be predictive factors for the development of HD. No association was found to respiratory atopy (OR = 1.29; CI 95% 0.35-4.7) and metal sensitisation (OR = 1.1; CI 95% 0.29-4.35). Exogenous irritant factors did not show a strong association towards a risk increase. Wet work in general, as well as distinct occupational tasks showed only a tendency for being a risk factor for HD. However, leisure time activities, especially house building and rebuilding (OR = 5.4; CI 95% 1.05-27.81), were associated with an elevated risk. CONCLUSIONS: Endogenous and exogenous factors contribute to the development of HD in bakers' and confectioners' apprentices.

Screening for people with diabetes mellitus for poor blood glucose control in an ophthalmological laser clinic.

PURPOSE: The study was performed to test the effect of a structured intervention in diabetic patients with poor glycaemic control in an ophthalmological department. PATIENTS AND METHODS: All the patients attending the ophthalmological out-patient department with the need for laser therapy due to diabetic retinopathy were investigated from January to March 1998 (Type 1: n=20, Type 2: n=144). If an HbA(1c)-level higher than 9.0% was found the patient was informed within 1 week and a standardised letter was sent to the primary care physician and the local ophthalmologist. Over the first 3 months of 1999 the effect was evaluated. RESULTS: HbA(1c) values higher than 9.0% were found in eight/20 of the patients (40%) with Type 1 diabetes and in 61/144 of the patients (54%) with Type 2 diabetes. In 55% this new information in the context of the need for laser therapy resulted in the acceptance of a structured intervention by the patient. This led to an improvement of the HbA(1c) in the people with Type 1 diabetes. CONCLUSION: Patients with poor blood glucose control can be identified in an ophthalmological department. The need for laser therapy can be used to motivate the patients for a significant improvement of the quality of blood glucose control.

Large bore catheters with surface treatments versus untreated catheters for blood access.

Infection, thrombosis, and stenosis are among the most frequent complications associated with blood contacting catheters. Because these problems are usually related to surface properties of the base catheter material, surface treatment processes, such as ion implantation and ion beam assisted deposition (IBAD) (silver based coatings), can be used to mitigate such complications. Because these ion beam based processes affect only the near-surface region (approximately the outer 1 microm), there is little effect on bulk material properties. This study evaluated silver coated and implanted large bore catheters used for extracorporeal detoxification. In a 186 patient prospective study, 225 large bore catheters were inserted into the internal jugular or subclavian veins. 85 surface treated catheters (Spi-Argent, Spire Corporation, Bedford, MA-USA; n=39 acute catheters, n= 46 long-term catheters) and 28 catheters with surface treatment (Spi-Silicone, Spire Corporation, Bedford, MA-USA) were inserted in 90 patients. 112 untreated catheters placed in 96 patients served as controls (n = 62 acute catheters, n = 58 long-term catheters). After removal, the catheters were cultured for bacterial colonization using standard microbiologic assays. They also were examined using a scanning electron microscope (SEM). Bacterial colonization was observed in 8% of the treated catheters compared with 46.4% of untreated catheters. The SEM investigations showed all treated catheters to possess low thrombogenicity. Results of the study indicate that ion beam based processes can be used to improve thrombus and infection resistance of blood contacting catheters.

Cyclosporin A and therapeutic plasma exchange in the treatment of severe systemic lupus erythematosus.

Despite treatment with intensive immunosuppressive drug regimens, often the prognosis of patients suffering from systemic lupus erythematosus (SLE) is poor. Side effects such as infections and malignancies often occur. It was the aim of this trial to assess the effect of immunosuppression, in particular with cyclosporin, and the efficacy, safety, and clinical utility of intermittent treatment with therapeutic plasma exchange (TPE) in comparison to previous intensive therapy strategies using corticosteroids, azathioprine, and/or cyclophosphamide. In this prospective trial, 28 patients (24 women, 4 men, aged 36.3 +/- 11.8 years at the diagnosis of SLE) were treated for up to 10 years with drug regimens out of corticosteroids, azathioprine, and/or cyclophosphamide. Then, over a period of up to 8 years, in addition to conventional therapies, especially in active stages of the disease with extremely high concentrations of anti-DNA, anti-nuclear antibodies, and circulating immunocomplexes, TPE sessions were carried out depending on symptomatology. In addition, the patients received cyclosporin. Compared with previous treatment modalities, clinical symptoms improved more quickly and more effectively. During the study period of a mean of 5 years, corticosteroids, azathioprine, and cyclophosphamide were reduced by 40 to 100%. No severe side effects were seen. In acute stages of SLE and in forms with persistently high antibody levels, the addition of TPE sessions and cyclosporin as the basic immunosuppressive drug is mostly very effective with regard to improving clinical symptomatology.