Long-term outcome of persons with diabetic and non-diabetic neuro-osteoarthropathy after foot correction using external fixation.

AIM: Diabetic neuro-osteoarthropathy (Charcot foot) is a serious form of diabetic foot syndrome, often leading to severe deformity of the foot and subsequently to ulcers and osteomyelitis. The aim of this retrospective study was to determine the success rate and long-term outcomes for a Charcot foot operation using external fixation in 115 individuals who underwent surgery between July 2008 and December 2012. METHODS: Some 115 consecutive persons, 78 (68%) men and 37 (32%) women, were enrolled in this study. The eligibility criterion for this retrospective study was reconstructive foot surgery using a Hoffmann II external fixator in diabetic and non-diabetic neuro-osteoarthropathy. The main examination parameters in the follow-up were walking ability, amputation and mortality. Average follow-up was 5.7 (± 3.2) years. RESULTS: Ninety-seven per cent of people were able to walk after the operation with bespoke shoes or an orthosis. At follow-up, 77% were able to walk and 51% were fully mobile even outside the home. Subsequent amputations were performed in 29 individuals (26%), with 17 (15%) minor and 12 (11%) major amputations. Forty-seven individuals died before follow-up, the majority (53%) from cardiovascular events. Average survival time post surgery was 4.5 (± 2.9) years. CONCLUSION: Reconstruction surgery using external fixation is a very useful method for maintaining walking ability in the case of conservatively non-treatable diabetic and non-diabetic neuro-osteoarthropathy. Individuals with severe Charcot foot disease had a low rate of major amputations. Osteomyelitis was the main reason for major amputations.

HbA1c and Age in Non-Diabetic Subjects: An Ignored Association?

Objective: Target HbA1c values given in the most National Therapeutic Guidelines for patients with diabetes and cut-off HbA1c values for diabetes diagnosis are usually not taking the age of the respective patients into account; despite the fact that an increase in HbA1c in subjects without diabetes with age is known for some time. In order to further quantify the association between age and HbA1c in non-diabetic subjects an analysis of one German register was performed. Methods: In this cross-sectional study we analyzed data from 7 699 visits of 2 921 patients without diabetes (age 46.6 y [range 18-93 y]; 69.1% women; BMI 27.6±6.4 kg/m²) who had at least one HbA1c and blood glucose measurement. Data were drawn from an electronic patient record system (EMIL™) in which data were collected between 01/1992 and 01/2014. The patients were divided in 6 age groups (< 30 years [n=1 057];>30-40 years [n=1 160];>40-50 years [n=1 693];>50-60 years [n=1 523];>60-70 years [n=1 310];>70 years [n=956]) and the HbA1c values of these groups were compared. Patients with: gestational diabetes, use of systemic glucocorticoids, malignant neoplasm, age<18 y at time of first visit and IGT were excluded. HbA1c measurements were DCCT adjusted. Results: Patients with age>70 years have a 0.47% [5.14 mmol/mol] higher HbA1c compared to those<30 years. The mean HbA1c of the age groups was:<30 4.98% [30.96 mmol/mol],>30-40 5.07% [31.99 mmol/mol],>40-50 5.17% [33.10 mmol/mol],>50-60 5.33% [34.79 mmol/mol],>60-70 5.42% [35.79 mmol/mol] and>70 years 5.45% [36.10 mmol/mol]. In a multiple linear model the regression coefficient for each year of age increase was ß=0.0074 (p<0.001); thus age results in an increase of 0.074% in HbA1c per decade. Conclusion: HbA1c increases significantly with ageing in people without diabetes. The use of different cut-off values for every age range for diagnosis of diabetes should be discussed.

Complete evaluation of adrenal tumours in a tertiary care institution in Thuringia, Germany.

INTRODUCTION AND OBJECTIVE: Adrenal tumours, mainly incidentalomas, are an increasingly common clinical and diagnostic challenge. The aim of the present study was the retrospective evaluation of all patients with adrenal tumours treated in our university department from 1.1.1999-31.12.2013 PATIENTS AND METHODS: 187 patients (108 females: 79 males, mean age 57.7 years) were found to have adrenal tumours in our institution during the study period. All patients underwent basic and, when indicated, advanced analytical testing for hormonal activity. Tumours were classified according to patients' gender, age at diagnosis, tumour localization and size, as well as benignity and malignancy when postinterventional histopathological examination was conducted. RESULTS: 134 (71.7%) patients had non-hormone secreting tumours, 17 (9.1%) pheochromocytoma, 13 (7.0%) Conn-syndrome, 13 (7.0%) adrenal Cushing's disease, 1 congenital adrenal hyperplasia and 2 sexual hormone-secreting tumours. 7 (3.7%) tumours could not be definitively classified due to unclear or marginal test-results. Cushing's disease was more prevalent in females (11 females: 2 males). 163 (87.2% of the total cohort) tumours were unilateral [95 (50.8%) left; 68 (36.4%) right] and 24 (12.8%) were bilateral. Tumour size was <3 cm in 109 (58.3%), 3-6 cm in 63 (33.7%) and >6 cm in 15 (8.0%) patients. 60 (32.1%) patients underwent adrenalectomy, thereof 88.9% of the patients with hormonally active tumours, while 8 (4.3%) were evaluated with ultrasound-guided biopsy. Malignancy was confirmed in 10 individuals (5.3%; 3 non-functioning tumours, 3 pheochromocytomas, 2 Cushing's patients and 2 sexual-hormone secreting tumours), while 2 surgical specimens with histopathological diagnosis of pheochromocytoma showed signs of malignant changes. Benignity was histopathologically confirmed in 55 patients. CONCLUSIONS: The prevalence of detected adrenal tumours is rising due to widely available and applied abdominal imaging procedures. The vast majority of them are benign, of small size (<3 cm) and hormonally inactive. Adrenalectomy is the therapeutic method of choice in big and/or confirmed hormone-secreting tumours.

High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control.

UNLABELLED: Fracture risk in type 1 diabetes (T1D) is supposed to be underestimated by bone mineral density (BMD). Individuals with T1D had more prevalent fractures in a cross-sectional study. Serum levels of pentosidine, an advanced glycation end product, and poor glycaemic control were associated with prevalent fractures independent of BMD. INTRODUCTION: Type 1 diabetes (T1D) is associated with increased fracture risk. Bone mineral density (BMD) underestimates the risk of fractures in some individuals. The accumulation of advanced glycation end products (AGEs) impairs bone matrix and reduces bone strength. METHODS: In a cross-sectional study, 128 men and premenopausal women with T1D were evaluated. We compared traditional risk factors for fractures, BMD, parameters of bone metabolism and AGEs in individuals with and without prevalent fractures. An independent association of serum AGE levels with prevalent fractures was investigated. RESULTS: Individuals with prevalent fractures exhibited a longer duration of T1D, higher HbA1c and more diabetic-related complications. BMD at the femoral neck (z-score -0.76 ± 0.94 vs. -0.23 ± 1.02; p = 0.031) and total hip (z-score -0.54 ± 0.93 vs. 0.11 ± 1.11; p = 0.017) was lower in those with prevalent fractures. Individuals with fractures had higher pentosidine levels (164.1 ± 53.6 vs. 133.2 ± 40.4; p = 0.002). The levels of N-ε-(carboxymethyl)-lysine (CML) and endogenous secretory receptor for AGEs (esRAGE) did not significantly differ. Multivariate logistic regression analysis adjusted for age, BMI, family history of fractures, smoking, vitamin D deficiency, BMD at lumbar spine, femoral neck and total hip identified pentosidine levels and HbA1c as independent factors associated with prevalent fractures (odds ratio 1.02, 95% CI 1.00-1.03/pmol/ml increase of pentosidine; p = 0.008 and odds ratio 1.93, 95% CI 1.16-3.20 per percentage increase of HbA1c; p = 0.011). CONCLUSIONS: The pentosidine levels but not BMD are independently associated with prevalent fractures. Impaired bone quality in T1D may result from increased AGE formation.

Diabetic nephropathy but not HbA1c is predictive for frequent complications of Charcot feet - long-term follow-up of 164 consecutive patients with 195 acute Charcot feet.

AIMS: To investigate the clinical characteristics, treatment and long-term outcome of patients with acute Charcot feet (CF). METHODS: Single-center retrospective analysis. Treatment of CF: stage-dependent immobilization/weight-off therapy, orthopaedic/adjusted shoes, foot surgery. 164 consecutive participants (type 1 vs. type 2 diabetes): 12 vs. 150, non-diabetic peripheral neuropathy: n=2, presented with 195 (17 vs. 176) CF. Mean follow-up: 4.7 ± 2.5 (range 2.2-9.8) vs. 5.4 ± 2.9 (range 0.8-18.8) years, vital at follow-up: 100 vs. 88%. RESULTS: Baseline characteristics: age: 43.7 ± 10.9 vs. 57.9 ± 8.9 years (p<0.001), male gender: 66.7 vs. 77.3%, diabetes duration: 19.2 ± 9.1 vs. 13 ± 8.6 years (p=0.018), GHb: 8.1 ± 2.4 vs. 7.6 ± 1.6%, BMI: 24 ± 5.3 vs. 33.7 ± 6.5 kg/m2 (p<0.001), Levine 1: 18.2 vs. 7.4%, Levine 2: 45.5 vs. 65.9%, Sanders 2: 58.3 vs. 68.5%, Sanders 3: 33.3 vs. 45%. THERAPY: immobilization for 6 ± 4.2 vs. 5.4 ± 4.5 months, orthopaedic/adjusted shoes: 27.3 vs. 20.5%, foot surgery: 11.8 vs. 18.2%. Major complications: 50 vs. 56% (rocker bottom deformities: 23.5 vs. 46.3%, foot ulcerations: 17.6 vs. 24.6%, CF amputations: 0 vs. 6%), not CF amputations: 16.7 vs. 15.3%, second episodes of CF: 41.6 vs. 18.3% after 5-132 months. Diabetic nephropathy was associated with an increase, intensive antihypertensive therapy with a decrease of complications. CONCLUSIONS: Patients with CF are middle-aged, overweight males with type 2 diabetes above 10 years. Patients with type 1 diabetes are younger, have normal BMI and longer diabetes duration. Major complications and second episodes of CF are frequent. Diabetic nephropathy could be a risk factor for CF related complications. The awareness for CF must be improved.The study was conducted due to the Declaration of Helsinki.

[Rare differential diagnosis in a 40-year old patient with sleep apnea syndrome]. / Seltene Differenzialdiagnose bei einem 40-jährigen Patienten mit Schlafapnoe-Syndrom.

Respiratory disorders are common and important complications in acromegaly. The prevalence of sleep apnea syndrome (SAS) in this group of patients is high (20%-50%). Consequences of SAS are serious and associated with increased morbidity and mortality, mainly as a result of cardiovascular complications. The symptoms of sleep apnea are often reversible with treatment. We report on an acromegaly patient presenting with excessive snoring and severe headaches caused by sleep apnea.

[Diagnostic pitfalls with Cushing's syndrome]. / Diagnostische Fallstricke beim Cushing-Syndrom.

Adrenal cortical carcinoma is a rare diagnosis and may present with hormone secretion. A histological differentiation between an adrenal cortical adenoma and carcinoma can be very difficult. However, a fast diagnosis including staging and complete surgical resection is pivotal for the prognosis of an adrenal cortical carcinoma. Metastasing adrenal cortical carcinoma should be treated with a mitotane based chemotherapy, and inclusion in the "firm-act study" is highly recommended. The present case report demonstrates the diagnostic pitfalls in a female patients with Cushing's syndrome who suffered from metastasing adrenal cortical carcinoma.

[HbA1c-mapping--evaluation of a new method for population-based monitoring of metabolic control in patients with diabetes mellitus]. / HbA1c-Kartografierung--Evaluation eines neuartigen versorgungs-epidemiologischen Verfahrens zum Monitoring der Stoffwechselkontrolle von Patienten mit Diabetes mellitus.

AIM: The purpose of this study was to analyse metabolic control in patients with diabetes mellitus in primary care in Thuringia and to evaluate HbA1c mapping as a newly proposed method for population-based continuous monitoring of metabolic control in primary care. METHODS: A cross-sectional study (2nd quarter 2005) using the electronic data bases of Thuringian medical laboratories (HbA1c, postal code of GP) was undertaken. The study population comprised all Thuringian patients with diabetes mellitus who were treated in ambulatory care. A comparison was made between data from HbA1c mapping and data collected by GPs (general practitioner) of two selected areas. RESULTS: We collected 89,407 HbA1c tests by HbA1c mapping: the following values were obtained - mean HbA1c: 6.73+/-1.27%; HbA1c >/=7%: 32.6%; HbA1c >/=10%: 2.4% of all HbA1c tests. The mean HbA1c was 0.2% lower in HbA1c mapping compared to data collection in GPs (HbA1c 6.8+/-1.32% vs. 7.02+/-1.26%, p<0.001). The percentage of HbA1c tests below 7% was higher, HbA1c test results between 7% and 9% were less frequent in HbA1c mapping. Patient data were as follows: type 2 diabetes 98.7%, female gender: 57%, age 69.8+/-11.6 years, insulin therapy 28.8%. CONCLUSIONS: The Thuringian cross-sectional study 2005 showed acceptable results for metabolic control in ambulatory care. The results of HbA1c mapping were comparable to the data on glycaemic control of patients with diabetes mellitus in ambulatory care.

Prevalence of the diabetic foot syndrome at the primary care level in Germany: a cross-sectional study.

AIMS: The diabetic foot syndrome (DFS) is an important complication of diabetes mellitus resulting in amputations, disability and reduced quality of life. DFS is preventable. The aim was to investigate the prevalence of the DFS at the primary care level in Germany. METHODS: This was a cross-sectional study of the prevalence of DFS, associated factors and glycaemic control at the primary care level in Germany. We examined an unselected sample of participants with known diabetes who were insured by Deutsche BKK, a large healthcare insurer. RESULTS: Three hundred and forty-one general practitioners examined 4778 participants with diabetes mellitus: 366 (7.7%) participants (mean age 49 +/- 16 years) had Type 1 and 4412 participants (mean age 66 +/- 10 years) had Type 2 diabetes. DFS was diagnosed in 138 patients, resulting in a prevalence of 3.6%[95% confidence interval (CI) 1.9, 6.0] in Type 1 and 2.8% (95% CI 2.3, 3.4) in Type 2 diabetes. DFS was independently associated with age, duration of diabetes, height, current smoking and insulin therapy. There was no significant effect of glycaemic control on the risk of DFS. The prevalence of other abnormal foot findings was: peripheral neuropathy 9.7%, peripheral arterial disease 14.8% (absent dorsalis pedis), 12.4% (absent tibialis posterior), acute diabetic foot ulcer 0.8%, amputations of lower extremities 1.5%, and amputations limited to toes 0.5%. CONCLUSIONS: The prevalence of the DFS at the primary care level in Germany is 2.9%. Almost 50% of patients with DFS had major or minor amputations. Common risk factors such as hyperkeratosis and poor glycaemic control can be modified. Effective therapeutic approaches in addition to methods for primary and secondary prevention of DFS should be used more widely.

Association of diabetic retinopathy and renal function in patients with types 1 and 2 diabetes mellitus.

AIMS: It takes years for microvascular complications in diabetes mellitus such as diabetic retinopathy (RP) and nephropathy (NP) to develop. Since retinal and renal vessels are exposed to the diabetic milieu, it is often assumed that progression of diabetic RP and NP occurs at the same time. However, smaller studies have demonstrated that this may not always be the case. The present study was undertaken to correlate diabetic retinopathy with parameters of renal function in a large ambulatory collective of patients with Types 1 and 2 diabetes. METHODS: The study design was cross-sectional. Ambulatory patients from a large university out-patient clinic were studied (323 patients with Type 1, 906 patients with Type 2 diabetes). RP status was obtained through retinal photography by an experienced ophthalmologist and was grouped into no RP, RP Stages 1-3, or blind. Retinal pathology was correlated with clinical parameters of renal function (proteinuria, estimated glomerular filtration rate according to the MDRD formula, presence of urinary sediment abnormalities, hypertension). RESULTS: No patient showed urinary sediment abnormalities (e.g. presence of hematuria or acanthocytes) or increased urinary excretion of immunoglobulin light chains suggesting the absence of other nondiabetic renal diseases. The majority of Type 1 diabetes patients with macroalbuminuria (> or = 200 mg/l) had some signs of RP independent of the presence of hypertension. There was a correlation between RP and microalbuminuria (r = 0.164, p < 0.01). In contrast, up to 47.5% of the hypertensive patients with Type 2 diabetes and overt proteinuria had no signs of RP. There was also discordance of microalbuminuria and RP in patients with Type 2 diabetes. Stratification according to K/DOQI States 2-5 (MDRD formula) showed that the majority of patients with Type 1 diabetes in States 3-5 had signs of RP, albeit the absolute number of patients in these K/DOQI stages was very small. In contrast, up to 40% of dialysis-dependent Type 2 diabetics (K/DOQI State 5) showed no evidence of RP. CONCLUSIONS: This study revealed that many patients with Type 2 diabetes and renal abnormalities (proteinuria and/or renal insufficiency) showed, in contrast to Type 1 diabetics, no signs of RP. Our study was, however, limited by the lack of renal biopsies. Although urinary sediment analysis was normal in these patients, other causes for renal insufficiency (e.g. vascular nephropathy), especially in Type 2 diabetics, cannot be excluded. Nevertheless, we believe that absence of RP in patients with Type 2 diabetes does not imply that renal abnormalities including diabetic nephropathy, are also absent. It is recommended that these patients undergo renal biopsy.

[A 64-year-old female patient with recurring hypoglycaemia. Difficult aspects of diagnosis]. / 64-jährige Patientin mit rezidivierenden Hypoglykämien. Schwierige Diagnosestellung.

Insulinomas are the most common pancreatic islet cell tumours and are characterised by uncontrolled insulin secretion even in the presence of hypoglycaemia. Diagnosis is usually made by the detection of endogenous hyperinsulinism over a period of fasting. We report the case of a patient with insulinoma without hyperinsulinaemia. A secretion and overexpression of split insulin has to be discussed. The diagnosis was made by endoscopic ultrasound-guided fine-needle aspiration and the immunohistochemical detection of chromogranine. In conclusion, the present report demonstrates that insulinomas should be considered and searched for in every case of hypoglycaemia, even when associated with normal insulin levels. It also confirms the essential role of endoscopic ultrasonography in the diagnosis of insulin-secreting tumors.

[Prevalence of diabetic retinopathy. Check-up program of a public health insurance company in Germany 2002-2004]. / Prävalenz der diabetischen Retinopathie. Studie bei Versicherten der Deutschen Betriebskrankenkasse 2002-2004.

OBJECTIVES: Population based studies have reported a prevalence of diabetic retinopathy (DR) at the time of diagnosis in up to 30% of the patients. In the context of a general diabetes check-up program (so called "Diabetes-TUV"), the prevalence of diabetic retinopathy in Germany was examined in all diabetes patients insured in a public health insurance company. METHODS: Patients were screened in the offices of 181 ophthalmologists according to a standardized protocol formulated by Prof. Kroll, Marburg. A total of 6,500 sheets were analysed out of which 14.5% were multiply documented. The latest protocols of 5,596 patients were evaluated; the mean age was 64.7 years with an average duration of diabetes of 10.2 years. RESULTS: Some 86.3% of the eyes examined had no DR, in 3.1% no evaluation was possible. Of the patients checked, 10.6% had DR. Mild/moderate DR was reported in 8.3%, severe non-proliferative DR in 1.7% and proliferative DR in 0.5%. Macular edema was reported in 0.85% of cases, vitreous hemorrhage in 0.2%. There was 0.1% iris neovascularisation and 0.1% retinal detachment. Visual impairment due to cataract or secondary cataract was found in 25.2% of patients with an 8.3% pseudophakia rate. CONCLUSION: Documentation of the eye examination in the diabetes check-up program was good. The 10.6% prevalence of DR in Germany, even after long standing diabetes, seems to be lower than in earlier population based studies in the US or UK. The data reported here could be an indication of better diabetes care in Germany. However, not all patients were examined with dilated pupils, and in the case of severe changes, the ophthalmologist might have decided not to fill in the report form and to have chosen another form of communication.

Risk of malignancies in patients with insulin-treated diabetes mellitus: results of a population-based trial with 10-year follow-up (JEVIN).

BACKGROUND: Studies involving diabetes mellitus and malignancies show contradictory results: Many of them have found incidences of malignancies that are comparable or lower, other studies have found higher rates than those of non-diabetic subjects. Hence, the goal of the present trial was to study the possible association between diabetes mellitus and the incidence of malignancies and its outcome in a selection-free population over a longer period of time. - PATIENTS AND METHODS: All the patients (n=291) who participated in the JEVIN (Jena's St. Vincent)- trial (a prospective, 10 year follow-up, population-based intervention 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 [about 100,000 inhabitants], Thuringia, Germany) were assessed. The baseline examination took place in 1989/90, follow-up examinations were performed in 1994/95 and 1999/2000. - RESULTS: Up to 1999/2000, 2 patients with type 1 and 5 patients with insulin-treated type 2 diabetes mellitus developed a malignancy (incidence 0.0241). The most frequent malignancies were cancer of the colon and rectum (3 of 291 patients, incidence 0.0103). Comparing these data with the incidence of carcinoma of the colon and rectum reported by the Robert-Koch-Institute of Germany (incidence 0.0012) diabetic patients showed a 9.9-fold increased risk (p=0.042). There were no significant differences regarding incidence of total malignancies or carcinoma of the breast, the lung, renal cells or gonads. Correlation and multivariate analyses revealed no associations between the development of malignancies and patients' outcome and diabetes duration, the duration of insulin therapy, insulin dosage, the quality of diabetes control or the presence of diabetes-related long-term complications. - CONCLUSIONS: Conclusive to other data derived from selected cohorts, population-based the JEVIN-trial demonstrate an increased incidence of malignancies of the colon and rectum in insulin-treated patients with diabetes mellitus. However, for further confirmation of these interesting results more studies in larger populations over longer periods of time are necessary to explain the heterogeneous findings in patients with diabetes mellitus of an increased incidence for some cancer entities, but not for others. Knowledge of these mechanisms should have important implications for the direction of strategies to prevent the development of malignancies, or to enhance ability to make an earlier diagnosis and more effective therapies.

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.

[Paraneoplastic pityriasis rubra pilaris in metastatic adenocarcinoma without diagnosable primary]. / Paraneoplastische Pityriasis rubra pilaris bei metastasiertem Adenokarzinom ohne lokalisierbares Primum.

HISTORY AND ADMISSION FINDINGS: A 75-year-old woman, without a history of severe illness, developed an erythematosquamous skin disease on hands and forearms. After continued spreading of these cutaneous lesions, she was admitted to hospital, presenting with a generalised desquamating erythrodermia and marked pruritus. INVESTIGATIONS: Skin biopsy showed cornocutaneous signs with alternating ortho- and parakeratosis, typical for pityriasis rubra pilaris. Laboratory findings showed a chronic to acute inflammation with leukocytosis, granulocytosis in the differential blood count, raised C-reactive protein in a range from 54.7 to a maximum of 157.2 mg/l and a protein electrophoresis with elevated alpha1- and alpha2-fraction. TREATMENT AND COURSE: The erythrodermia only temporarily receded under systemic therapy with acitretin and prednisolone. The patient developed intermittent septic fever accompanied by reduction or loss of consciousness. The general condition of the patient worsened considerably. Out of a rapidly progressing pleural effusion malignant cells similar to adenocarcinoma were isolated. Because CA15-3 was elevated we conducted an extended search especially for a breast carcinoma, but found only pathologically enlarged axillary, mediastinal and abdominal lymph nodes in conventional X-ray, CT, ultrasound and endoscopic procedures. The patient died from paraneoplastic pulmonary embolism. At autopsy, the widespread metastatic dissemination from poorly differentiated adenocarcinoma was confirmed. A necrosis in the right breast containing tumour cell remnants could probably be regarded as the primary neoplasm. Immunohistochemically no definite proof of breast nor gastro-intestinal carcinoma could be found. CONCLUSIONS: This case presents a rare paraneoplastic cutaneous manifestation as pityriasis rubra pilaris triggered by a poorly differentiated adenocarcinoma. The primary neoplasm could not definitely be identified, neither pre nor post mortem.

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.

Malignancies in patients with insulin-treated diabetes mellitus.

In patients with diabetes mellitus, contradictory results have been reported indicating both increased and reduced risks of malignancies. In the present trial all insulin-treated diabetic patients (n = 2720) attending our centre since 1995 were studied. Of these patients, 28 (type 1/type 2: n = 1/27, 23 women) developed malignancies during insulin therapy: 11 patients developed cancer of the breast, 4 patients cancer of the pancreas, 3 patients cancer of the kidneys and 10 patients developed other malignancies. The characteristics of these patients [mean +/- SD (range)] were as follows: age 68.8 +/- 8.6 (52.0 87.0) years, diabetes duration 13.1 +/- 8.1 (0.5-29.0) years, duration of insulin therapy at the time of the diagnosis of malignancy 4.3 +/- 5.7 (0.5 24.0) years, insulin dosage 0.67 +/- 0.43 (0.11-1.72) IU/kg body weight, mean HbAlc 9.6 +/- 1.9 (6.8-14.9)% (HPLC, Diamat, normal range 4.4%-5.9%). The prevalences of nephropathy, retinopathy (non-proliferative: n = 7) and peripheral neuropathy were 35.7%, 25.0% and 46.4% respectively. When the features of the 27 patients with type 2 diabetes were compared with the characteristics of the type 2 diabetic patients (n = 117, 63 women) studied in a population-based survey of insulin-treated diabetic patients, also performed in the area of Jena [JEVIN; Schiel R et al. (1997a)] there were no significant differences in the duration of insulin therapy (JEVIN: 4.7 +/- 4.3 years, P = 0.64), insulin dosage (JEVIN: 0.55 +/- 0.27 IU/kg body weight, P = 0.08), mean HbAlc (JEVIN: 9.0 +/- 2.1%, P = 0.16) and the prevalences of long-term complications of diabetes. The quality of diabetes control in insulin-treated patients suffering from malignancies is comparable to that of a selection-free population of diabetic patients. Furthermore, in comparison to non-diabetic subjects our diabetic patients showed no altered risk for malignancies as a function of insulin dosage, the duration of diabetes or insulin therapy, the quality of diabetes control or the prevalence of long-term complications of the disease.

Intensified treatment and education of type 1 diabetes as clinical routine. A nationwide quality-circle experience in Germany. ASD (the Working Group on Structured Diabetes Therapy of the German Diabetes Association).

This contribution describes the nationwide implementation of an intensive treatment and education program for type 1 diabetic patients in the clinical routine of the German health care system. Based on the formation of a working group (Arbeitsgemeinschaft Strukturierte Diabetestherapie [ASD]) of presently 57 general internal medicine departments, mainly from secondary and tertiary care levels in city and country hospitals throughout the country, a peer-review quality circle was formed as an official working group of the German Diabetes Association. The participating institutions performed a structured program of intensive treatment and education in all type 1 diabetic patients referred to them on a routine basis. The program includes multiple daily insulin injections or continuous subcutaneous insulin infusion, several times daily blood glucose self-monitoring and self-adaptation of insulin dosages and other aspects of treatment by the patients, and a far-reaching liberalization of the nutrition regimen. The group has attempted to document and to improve the quality of the structure and process of type 1 diabetes care in its participating institutions by a system of peer supervision. Furthermore, all member institutions volunteered to collect outcome data based on systematic 1-1.3 years' follow-up examinations of consecutive type 1 diabetic patients. For the 1997 evaluation of 1,103 type 1 diabetic patients, significant decreases of GHb levels and of incidence rates of severe hypoglycemia (from 0.35 to 0.16 cases per patient-year) and ketoacidosis (from 0.08 to 0.02 cases per patient-year) are presented. The ASD quality circle represents a model to improve principal aspects of type 1 diabetes care on a nationwide basis.